Assembly of the primary cilium (Homo sapiens)

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The primary cilium is one of two main types of cilia present on the surface of many eukaryotic cells (reviewed in Flieghauf et al, 2007). Unlike the motile cilia, which are generally present in large numbers on epithelial cells and are responsible for sensory function as well as wave-like beating motions, the primary cilium is a non-motile sensory organelle with roles in signaling and development and is present in a single copy at the apical surface of most quiescent cells (reviewed in Hsiao et al, 2012). Cilium biogenesis involves the anchoring of the basal body, a centriole-derived organelle, near the plasma membrane and the subsequent polymerization of the microtubule-based axoneme and extension of the plasma membrane (reviewed in Ishikawa and Marshall, 2011; Reiter et al, 2012). Although the ciliary membrane is continuous with the plasma membrane, the protein and lipid content of the cilium and the ciliary membrane are distinct from those of the bulk cytoplasm and plasma membrane (reviewed in Emmer et al, 2010; Rohatgi and Snell, 2010). This specialized compartment is established and maintained during cilium biogenesis by the formation of a ciliary transition zone, a proteinaceous structure that, with the transition fibres, anchors the basal body to the plasma membrane and acts as a ciliary pore to limit free diffusion from the cytosol to the cilium (reviewed in Nachury et al, 2010; Reiter et al, 2012). Ciliary components are targeted from the secretory system to the ciliary base and subsequently transported to the ciliary tip, where extension of the axoneme occurs, by a motor-driven process called intraflagellar transport (IFT). Anterograde transport of cargo from the ciliary base to the tip of the cilium requires kinesin-2 type motors, while the dynein-2 motor is required for retrograde transport back to the ciliary base. In addition, both anterograde and retrograde transport depend on the IFT complex, a multiprotein assembly consisting of two subcomplexes, IFT A and IFT B. The primary cilium is a dynamic structure that undergoes continuous steady-state turnover of tubulin at the tip; as a consequence, the IFT machinery is required for cilium maintenance as well as biogenesis (reviewed in Bhogaraju et al, 2013; Hsiao et al, 2012; Li et al, 2012; Taschner et al, 2012; Sung and Leroux, 2013). The importance of the primary cilium in signaling and cell biology is highlighted by the wide range of defects and disorders, collectively known as ciliopathies, that arise as the result of mutations in genes encoding components of the ciliary machinery (reviewed in Goetz and Anderson, 2010; Madhivanan and Aguilar, 2014). View original pathway at:Reactome.

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Li C, Inglis PN, Leitch CC, Efimenko E, Zaghloul NA, Mok CA, Davis EE, Bialas NJ, Healey MP, Héon E, Zhen M, Swoboda P, Katsanis N, Leroux MR.; ''An essential role for DYF-11/MIP-T3 in assembling functional intraflagellar transport complexes.''; PubMed Europe PMC Scholia
Heider MR, Munson M.; ''Exorcising the exocyst complex.''; PubMed Europe PMC Scholia
Schwarz N, Hardcastle AJ, Cheetham ME.; ''Arl3 and RP2 mediated assembly and traffic of membrane associated cilia proteins.''; PubMed Europe PMC Scholia
Wang J, Morita Y, Mazelova J, Deretic D.; ''The Arf GAP ASAP1 provides a platform to regulate Arf4- and Rab11-Rab8-mediated ciliary receptor targeting.''; PubMed Europe PMC Scholia
Buisson J, Chenouard N, Lagache T, Blisnick T, Olivo-Marin JC, Bastin P.; ''Intraflagellar transport proteins cycle between the flagellum and its base.''; PubMed Europe PMC Scholia
Li Y, Wei Q, Zhang Y, Ling K, Hu J.; ''The small GTPases ARL-13 and ARL-3 coordinate intraflagellar transport and ciliogenesis.''; PubMed Europe PMC Scholia
Hubbert C, Guardiola A, Shao R, Kawaguchi Y, Ito A, Nixon A, Yoshida M, Wang XF, Yao TP.; ''HDAC6 is a microtubule-associated deacetylase.''; PubMed Europe PMC Scholia
Pigino G, Geimer S, Lanzavecchia S, Paccagnini E, Cantele F, Diener DR, Rosenbaum JL, Lupetti P.; ''Electron-tomographic analysis of intraflagellar transport particle trains in situ.''; PubMed Europe PMC Scholia
Che MM, Boja ES, Yoon HY, Gruschus J, Jaffe H, Stauffer S, Schuck P, Fales HM, Randazzo PA.; ''Regulation of ASAP1 by phospholipids is dependent on the interface between the PH and Arf GAP domains.''; PubMed Europe PMC Scholia
Tobin JL, Beales PL.; ''The nonmotile ciliopathies.''; PubMed Europe PMC Scholia
Porter ME, Bower R, Knott JA, Byrd P, Dentler W.; ''Cytoplasmic dynein heavy chain 1b is required for flagellar assembly in Chlamydomonas.''; PubMed Europe PMC Scholia
Akella JS, Wloga D, Kim J, Starostina NG, Lyons-Abbott S, Morrissette NS, Dougan ST, Kipreos ET, Gaertig J.; ''MEC-17 is an alpha-tubulin acetyltransferase.''; PubMed Europe PMC Scholia
Lucker BF, Miller MS, Dziedzic SA, Blackmarr PT, Cole DG.; ''Direct interactions of intraflagellar transport complex B proteins IFT88, IFT52, and IFT46.''; PubMed Europe PMC Scholia
Masuda M, Mochizuki N.; ''Structural characteristics of BAR domain superfamily to sculpt the membrane.''; PubMed Europe PMC Scholia
Tao B, Bu S, Yang Z, Siroky B, Kappes JC, Kispert A, Guay-Woodford LM.; ''Cystin localizes to primary cilia via membrane microdomains and a targeting motif.''; PubMed Europe PMC Scholia
Wei Q, Zhang Y, Li Y, Zhang Q, Ling K, Hu J.; ''The BBSome controls IFT assembly and turnaround in cilia.''; PubMed Europe PMC Scholia
Fan Y, Esmail MA, Ansley SJ, Blacque OE, Boroevich K, Ross AJ, Moore SJ, Badano JL, May-Simera H, Compton DS, Green JS, Lewis RA, van Haelst MM, Parfrey PS, Baillie DL, Beales PL, Katsanis N, Davidson WS, Leroux MR.; ''Mutations in a member of the Ras superfamily of small GTP-binding proteins causes Bardet-Biedl syndrome.''; PubMed Europe PMC Scholia
Zuo X, Guo W, Lipschutz JH.; ''The exocyst protein Sec10 is necessary for primary ciliogenesis and cystogenesis in vitro.''; PubMed Europe PMC Scholia
Follit JA, San Agustin JT, Xu F, Jonassen JA, Samtani R, Lo CW, Pazour GJ.; ''The Golgin GMAP210/TRIP11 anchors IFT20 to the Golgi complex.''; PubMed Europe PMC Scholia
Čajánek L, Nigg EA.; ''Cep164 triggers ciliogenesis by recruiting Tau tubulin kinase 2 to the mother centriole.''; PubMed Europe PMC Scholia
Liew GM, Ye F, Nager AR, Murphy JP, Lee JS, Aguiar M, Breslow DK, Gygi SP, Nachury MV.; ''The intraflagellar transport protein IFT27 promotes BBSome exit from cilia through the GTPase ARL6/BBS3.''; PubMed Europe PMC Scholia
Joo K, Kim CG, Lee MS, Moon HY, Lee SH, Kim MJ, Kweon HS, Park WY, Kim CH, Gleeson JG, Kim J.; ''CCDC41 is required for ciliary vesicle docking to the mother centriole.''; PubMed Europe PMC Scholia
Jékely G, Arendt D.; ''Evolution of intraflagellar transport from coated vesicles and autogenous origin of the eukaryotic cilium.''; PubMed Europe PMC Scholia
Dishinger JF, Kee HL, Jenkins PM, Fan S, Hurd TW, Hammond JW, Truong YN, Margolis B, Martens JR, Verhey KJ.; ''Ciliary entry of the kinesin-2 motor KIF17 is regulated by importin-beta2 and RanGTP.''; PubMed Europe PMC Scholia
Bhogaraju S, Weber K, Engel BD, Lechtreck KF, Lorentzen E.; ''Getting tubulin to the tip of the cilium: one IFT train, many different tubulin cargo-binding sites?''; PubMed Europe PMC Scholia
Kühnel K, Veltel S, Schlichting I, Wittinghofer A.; ''Crystal structure of the human retinitis pigmentosa 2 protein and its interaction with Arl3.''; PubMed Europe PMC Scholia
Sang L, Miller JJ, Corbit KC, Giles RH, Brauer MJ, Otto EA, Baye LM, Wen X, Scales SJ, Kwong M, Huntzicker EG, Sfakianos MK, Sandoval W, Bazan JF, Kulkarni P, Garcia-Gonzalo FR, Seol AD, O'Toole JF, Held S, Reutter HM, Lane WS, Rafiq MA, Noor A, Ansar M, Devi AR, Sheffield VC, Slusarski DC, Vincent JB, Doherty DA, Hildebrandt F, Reiter JF, Jackson PK.; ''Mapping the NPHP-JBTS-MKS protein network reveals ciliopathy disease genes and pathways.''; PubMed Europe PMC Scholia
Seo S, Baye LM, Schulz NP, Beck JS, Zhang Q, Slusarski DC, Sheffield VC.; ''BBS6, BBS10, and BBS12 form a complex with CCT/TRiC family chaperonins and mediate BBSome assembly.''; PubMed Europe PMC Scholia
Follit JA, Tuft RA, Fogarty KE, Pazour GJ.; ''The intraflagellar transport protein IFT20 is associated with the Golgi complex and is required for cilia assembly.''; PubMed Europe PMC Scholia
Nachury MV, Seeley ES, Jin H.; ''Trafficking to the ciliary membrane: how to get across the periciliary diffusion barrier?''; PubMed Europe PMC Scholia
Jian X, Brown P, Schuck P, Gruschus JM, Balbo A, Hinshaw JE, Randazzo PA.; ''Autoinhibition of Arf GTPase-activating protein activity by the BAR domain in ASAP1.''; PubMed Europe PMC Scholia

History

Revision	Action	Time	User	Comment
86366	view	09:16, 11 July 2016	ReactomeTeam	reactome version 56
83327	view	10:47, 18 November 2015	ReactomeTeam	Version54
82435	view	13:12, 29 September 2015	ReactomeTeam	New pathway

External references

DataNodes

View all...

Name	Type	Database reference
ACTR1A	Protein	P61163 (Uniprot-TrEMBL)
AKAP9	Protein	Q99996 (Uniprot-TrEMBL)
ALMS1	Protein	Q8TCU4 (Uniprot-TrEMBL)
ARF4	Protein	P18085 (Uniprot-TrEMBL)
ARF4:GDP	Complex	R-HSA-5623424 (Reactome)
ARF4:GTP:VxPx-containing ciliary membrane proteins	Complex	R-HSA-5620917 (Reactome)
ARF4:GTP	Complex	R-HSA-5623423 (Reactome)
ARL13B	Protein	Q3SXY8 (Uniprot-TrEMBL)
ARL13B:INPP5E:PDE6D	Complex	R-HSA-5637977 (Reactome)
ARL13B:INPP5E	Complex	R-HSA-5624905 (Reactome)
ARL13B	Protein	Q3SXY8 (Uniprot-TrEMBL)
ARL3	Protein	P36405 (Uniprot-TrEMBL)
ARL3:GDP	Complex	R-HSA-5624072 (Reactome)
ARL3:GTP:UNC119B:myristoylated ciliary cargo	Complex	R-HSA-5624104 (Reactome)
ARL3:GTP:UNC119B	Complex	R-HSA-5624076 (Reactome)
ARL3:GTP	Complex	R-HSA-5624073 (Reactome)
ARL6	Protein	Q9H0F7 (Uniprot-TrEMBL)
ARL6:GTP:BBSome:ciliary cargo	Complex	R-HSA-5624112 (Reactome)
ARL6:GTP:BBSome:ciliary cargo	Complex	R-HSA-5624114 (Reactome)
ARL6:GTP	Complex	R-HSA-5624106 (Reactome)
ASAP1 dimer: ARF4:GTP:VxPx-containing ciliary membrane proteins	Complex	R-HSA-5623429 (Reactome)
ASAP1	Protein	Q9ULH1 (Uniprot-TrEMBL)
ASAP1 dimer	Complex	R-HSA-5623427 (Reactome)
ATAT	Protein	Q5SQI0 (Uniprot-TrEMBL)
AZI1	Protein	Q9UPN4 (Uniprot-TrEMBL)
Ac-CoA	Metabolite	CHEBI:15351 (ChEBI)
B9D1	Protein	Q9UPM9 (Uniprot-TrEMBL)
B9D2	Protein	Q9BPU9 (Uniprot-TrEMBL)
BBIP1	Protein	A8MTZ0 (Uniprot-TrEMBL)
BBIP1	Protein	A8MTZ0 (Uniprot-TrEMBL)
BBS/CCT complex	Complex	R-HSA-5624117 (Reactome)
BBS1	Protein	Q8NFJ9 (Uniprot-TrEMBL)
BBS10	Protein	Q8TAM1 (Uniprot-TrEMBL)
BBS12	Protein	Q6ZW61 (Uniprot-TrEMBL)
BBS1	Protein	Q8NFJ9 (Uniprot-TrEMBL)
BBS2	Protein	Q9BXC9 (Uniprot-TrEMBL)
BBS2	Protein	Q9BXC9 (Uniprot-TrEMBL)
BBS4	Protein	Q96RK4 (Uniprot-TrEMBL)
BBS4	Protein	Q96RK4 (Uniprot-TrEMBL)
BBS5	Protein	Q8N3I7 (Uniprot-TrEMBL)
BBS5	Protein	Q8N3I7 (Uniprot-TrEMBL)
BBS7	Protein	Q8IWZ6 (Uniprot-TrEMBL)
BBS7	Protein	Q8IWZ6 (Uniprot-TrEMBL)
BBS9	Protein	Q3SYG4 (Uniprot-TrEMBL)
BBS9	Protein	Q3SYG4 (Uniprot-TrEMBL)
BBSome ciliary cargo	Complex	R-HSA-5624113 (Reactome)
BBSome	Complex	R-HSA-5617794 (Reactome)
C2CD3	Protein	Q4AC94 (Uniprot-TrEMBL)
C2CD3	Protein	Q4AC94 (Uniprot-TrEMBL)
CC2D2A	Protein	Q9P2K1 (Uniprot-TrEMBL)
CCP110	Protein	O43303 (Uniprot-TrEMBL)
CCP110	Protein	O43303 (Uniprot-TrEMBL)
CCT2	Protein	P78371 (Uniprot-TrEMBL)
CCT3	Protein	P49368 (Uniprot-TrEMBL)
CCT4	Protein	P50991 (Uniprot-TrEMBL)
CCT5	Protein	P48643 (Uniprot-TrEMBL)
CCT8	Protein	P50990 (Uniprot-TrEMBL)
CDK1	Protein	P06493 (Uniprot-TrEMBL)
CDK5RAP2	Protein	Q96SN8 (Uniprot-TrEMBL)
CENPJ	Protein	Q9HC77 (Uniprot-TrEMBL)
CEP135	Protein	Q66GS9 (Uniprot-TrEMBL)
CEP152	Protein	O94986 (Uniprot-TrEMBL)
CEP162	Protein	Q5TB80 (Uniprot-TrEMBL)
CEP164	Protein	Q9UPV0 (Uniprot-TrEMBL)
CEP164	Protein	Q9UPV0 (Uniprot-TrEMBL)
CEP192	Protein	Q8TEP8 (Uniprot-TrEMBL)
CEP250	Protein	Q9BV73 (Uniprot-TrEMBL)
CEP290	Protein	O15078 (Uniprot-TrEMBL)
CEP41	Protein	Q9BYV8 (Uniprot-TrEMBL)
CEP57	Protein	Q86XR8 (Uniprot-TrEMBL)
CEP63	Protein	Q96MT8 (Uniprot-TrEMBL)
CEP70	Protein	Q8NHQ1 (Uniprot-TrEMBL)
CEP72	Protein	Q9P209 (Uniprot-TrEMBL)
CEP76	Protein	Q8TAP6 (Uniprot-TrEMBL)
CEP78	Protein	Q5JTW2 (Uniprot-TrEMBL)
CEP83	Protein	Q9Y592 (Uniprot-TrEMBL)
CEP83	Protein	Q9Y592 (Uniprot-TrEMBL)
CEP89	Protein	Q96ST8 (Uniprot-TrEMBL)
CEP89	Protein	Q96ST8 (Uniprot-TrEMBL)
CEP97	Protein	Q8IW35 (Uniprot-TrEMBL)
CEP97	Protein	Q8IW35 (Uniprot-TrEMBL)
CETN2	Protein	P41208 (Uniprot-TrEMBL)
CKAP5	Protein	Q14008 (Uniprot-TrEMBL)
CLASP1	Protein	Q7Z460 (Uniprot-TrEMBL)
CLUAP	Protein	Q96AJ1 (Uniprot-TrEMBL)
CLUAP	Protein	Q96AJ1 (Uniprot-TrEMBL)
CNGA2	Protein	Q16280 (Uniprot-TrEMBL)
CNGA4	Protein	Q8IV77 (Uniprot-TrEMBL)
CNGB1	Protein	Q14028 (Uniprot-TrEMBL)
CNTRL	Protein	Q7Z7A1 (Uniprot-TrEMBL)
CSNK1D	Protein	P48730 (Uniprot-TrEMBL)
CSNK1E	Protein	P49674 (Uniprot-TrEMBL)
Centrosome:C2CD3:distal appendage proteins:TTBK2	Complex	R-HSA-5626178 (Reactome)
Centrosome:C2CD3:distal appendage proteins	Complex	R-HSA-5626176 (Reactome)
CoA-SH	Metabolite	CHEBI:15346 (ChEBI)
DCTN1-2	Protein	Q14203-2 (Uniprot-TrEMBL)
DCTN2	Protein	Q13561 (Uniprot-TrEMBL)
DCTN3	Protein	O75935 (Uniprot-TrEMBL)
DYNC1H1	Protein	Q14204 (Uniprot-TrEMBL)
DYNC1I2	Protein	Q13409 (Uniprot-TrEMBL)
DYNC2H1	Protein	Q8NCM8 (Uniprot-TrEMBL)
DYNC2LI1	Protein	Q8TCX1 (Uniprot-TrEMBL)
DYNLL1	Protein	P63167 (Uniprot-TrEMBL)
DYNLL2	Protein	Q96FJ2 (Uniprot-TrEMBL)
DYNLRB1	Protein	Q9NP97 (Uniprot-TrEMBL)
DYNLRB2	Protein	Q8TF09 (Uniprot-TrEMBL)
EXOC1	Protein	Q9NV70 (Uniprot-TrEMBL)
EXOC2	Protein	Q96KP1 (Uniprot-TrEMBL)
EXOC3	Protein	O60645 (Uniprot-TrEMBL)
EXOC4	Protein	Q96A65 (Uniprot-TrEMBL)
EXOC5	Protein	O00471 (Uniprot-TrEMBL)
EXOC6	Protein	Q8TAG9 (Uniprot-TrEMBL)
EXOC7	Protein	Q9UPT5 (Uniprot-TrEMBL)
EXOC8	Protein	Q8IYI6 (Uniprot-TrEMBL)
FBF1	Protein	Q8TES7 (Uniprot-TrEMBL)
FBF1	Protein	Q8TES7 (Uniprot-TrEMBL)
FGFR1OP	Protein	O95684 (Uniprot-TrEMBL)
GBF1	Protein	Q92538 (Uniprot-TrEMBL)
GDP	Metabolite	CHEBI:17552 (ChEBI)
GDP	Metabolite	CHEBI:17552 (ChEBI)
GTP	Metabolite	CHEBI:15996 (ChEBI)
GTP	Metabolite	CHEBI:15996 (ChEBI)
Golgi-derived vesicle		R-NUL-5637956 (Reactome)
H2O	Metabolite	CHEBI:15377 (ChEBI)
HAUS2	Protein	Q9NVX0 (Uniprot-TrEMBL)
HDAC6	Protein	Q9UBN7 (Uniprot-TrEMBL)
HSP90AA1	Protein	P07900 (Uniprot-TrEMBL)
HSPB11	Protein	Q9Y547 (Uniprot-TrEMBL)
HSPB11	Protein	Q9Y547 (Uniprot-TrEMBL)
IFT A	Complex	R-HSA-5617795 (Reactome)
IFT A	Complex	R-HSA-5625350 (Reactome)
IFT B*	Complex	R-HSA-5617798 (Reactome)
IFT B	Complex	R-HSA-5617799 (Reactome)
IFT B	Complex	R-HSA-5625418 (Reactome)
IFT122	Protein	Q9HBG6 (Uniprot-TrEMBL)
IFT122	Protein	Q9HBG6 (Uniprot-TrEMBL)
IFT140	Protein	Q96RY7 (Uniprot-TrEMBL)
IFT140	Protein	Q96RY7 (Uniprot-TrEMBL)
IFT172	Protein	Q9UG01 (Uniprot-TrEMBL)
IFT172	Protein	Q9UG01 (Uniprot-TrEMBL)
IFT20	Protein	Q8IY31 (Uniprot-TrEMBL)
IFT20:TRIP11	Complex	R-HSA-5617801 (Reactome)
IFT20	Protein	Q8IY31 (Uniprot-TrEMBL)
IFT27	Protein	Q9BW83 (Uniprot-TrEMBL)
IFT27	Protein	Q9BW83 (Uniprot-TrEMBL)
IFT43	Protein	Q96FT9 (Uniprot-TrEMBL)
IFT43	Protein	Q96FT9 (Uniprot-TrEMBL)
IFT46	Protein	Q9NQC8 (Uniprot-TrEMBL)
IFT46	Protein	Q9NQC8 (Uniprot-TrEMBL)
IFT52	Protein	Q9Y366 (Uniprot-TrEMBL)
IFT52	Protein	Q9Y366 (Uniprot-TrEMBL)
IFT57	Protein	Q9NWB7 (Uniprot-TrEMBL)
IFT57	Protein	Q9NWB7 (Uniprot-TrEMBL)
IFT74	Protein	Q96LB3 (Uniprot-TrEMBL)
IFT74	Protein	Q96LB3 (Uniprot-TrEMBL)
IFT80	Protein	Q9P2H3 (Uniprot-TrEMBL)
IFT80	Protein	Q9P2H3 (Uniprot-TrEMBL)
IFT81	Protein	Q8WYA0 (Uniprot-TrEMBL)
IFT81	Protein	Q8WYA0 (Uniprot-TrEMBL)
IFT88	Protein	Q13099 (Uniprot-TrEMBL)
IFT88	Protein	Q13099 (Uniprot-TrEMBL)
INPP5E	Protein	Q9NRR6 (Uniprot-TrEMBL)
INPP5E	Protein	Q9NRR6 (Uniprot-TrEMBL)
IQCB1	Protein	Q15051 (Uniprot-TrEMBL)
KIF17	Protein	Q9P2E2 (Uniprot-TrEMBL)
KIF17 dimer:TNPO1	Complex	R-HSA-5624928 (Reactome)
KIF17 dimer:TNPO1	Complex	R-HSA-5624930 (Reactome)
KIF17 dimer	Complex	R-HSA-5624926 (Reactome)
KIF24	Protein	Q5T7B8 (Uniprot-TrEMBL)
KIF3A	Protein	Q9Y496 (Uniprot-TrEMBL)
KIF3B	Protein	O15066 (Uniprot-TrEMBL)
KIF3C	Protein	O14782 (Uniprot-TrEMBL)
KIFAP3	Protein	Q92845 (Uniprot-TrEMBL)
Kinesin-2 motors	Complex	R-HSA-5624910 (Reactome)
Kinesin-2 motors	Complex	R-HSA-5625387 (Reactome)
LZTFL1 oligomer:BBSome	Complex	R-HSA-5624121 (Reactome)
LZTFL1	Protein	Q9NQ48 (Uniprot-TrEMBL)
LZTFL1 oligomer	Complex	R-HSA-5624119 (Reactome)
MAPRE1	Protein	Q15691 (Uniprot-TrEMBL)
MARK4	Protein	Q96L34 (Uniprot-TrEMBL)
MARK4	Protein	Q96L34 (Uniprot-TrEMBL)
MCHR1	Protein	Q99705 (Uniprot-TrEMBL)
MKKS	Protein	Q9NPJ1 (Uniprot-TrEMBL)
MKS1	Protein	Q9NXB0 (Uniprot-TrEMBL)
MyrG2-CYS1	Protein	Q717R9 (Uniprot-TrEMBL)
MyrG2-NPHP3	Protein	Q7Z494 (Uniprot-TrEMBL)
NDE1	Protein	Q9NXR1 (Uniprot-TrEMBL)
NEDD1	Protein	Q8NHV4 (Uniprot-TrEMBL)
NEK2	Protein	P51955 (Uniprot-TrEMBL)
NINL	Protein	Q9Y2I6 (Uniprot-TrEMBL)
NPHP complex	Complex	R-HSA-5626668 (Reactome)
NPHP1	Protein	O15259 (Uniprot-TrEMBL)
NPHP4	Protein	O75161 (Uniprot-TrEMBL)
ODF2	Protein	Q5BJF6 (Uniprot-TrEMBL)
OFD1	Protein	O75665 (Uniprot-TrEMBL)
PAFAH1B1	Protein	P43034 (Uniprot-TrEMBL)
PCM1	Protein	Q15154 (Uniprot-TrEMBL)
PCNT	Protein	O95613 (Uniprot-TrEMBL)
PDE6D	Protein	O43924 (Uniprot-TrEMBL)
PDE6D:INPP5E	Complex	R-HSA-5624934 (Reactome)
PDE6D:INPP5E	Complex	R-HSA-5624936 (Reactome)
PDE6D	Protein	O43924 (Uniprot-TrEMBL)
PKD1	Protein	P98161 (Uniprot-TrEMBL)
PKD2	Protein	Q13563 (Uniprot-TrEMBL)
PLK1	Protein	P53350 (Uniprot-TrEMBL)
PLK4	Protein	O00444 (Uniprot-TrEMBL)
PPP2R1A	Protein	P30153 (Uniprot-TrEMBL)
PRKACA	Protein	P17612 (Uniprot-TrEMBL)
PRKAR2B	Protein	P31323 (Uniprot-TrEMBL)
Pi	Metabolite	CHEBI:18367 (ChEBI)
RAB11A	Protein	P62491 (Uniprot-TrEMBL)
RAB11A:GTP:Golgi derived vesicle	Complex	R-HSA-5637979 (Reactome)
RAB11A:GTP:RAB11FIP3 dimer:ASAP1 dimer:ARF4:GTP:VxPx-containing ciliary membrane proteins	Complex	R-HSA-5623434 (Reactome)
RAB11A:GTP:RAB11FIP3 dimer:ASAP1 dimer:VxPx-containing ciliary membrane proteins	Complex	R-HSA-5623437 (Reactome)
RAB11A:GTP	Complex	R-HSA-5623431 (Reactome)
RAB11FIP3	Protein	O75154 (Uniprot-TrEMBL)
RAB11FIP3 dimer	Complex	R-HSA-5623435 (Reactome)
RAB3IP	Protein	Q96QF0 (Uniprot-TrEMBL)
RAB3IP:BBSome	Complex	R-HSA-5617806 (Reactome)
RAB3IP:RAB11A:GTP:Golgi-derived vesicle	Complex	R-HSA-5637982 (Reactome)
RAB3IP:RAB8A:GDP	Complex	R-HSA-5623440 (Reactome)
RAB3IP	Protein	Q96QF0 (Uniprot-TrEMBL)
RAB8A	Protein	P61006 (Uniprot-TrEMBL)
RAB8A:GDP:RAB3IP:RAB11A:GTP:FIP3 dimer:ASAP1 dimer:VxPx-containing ciliary membrane proteins	Complex	R-HSA-5623444 (Reactome)
RAB8A:GDP	Complex	R-HSA-5623441 (Reactome)
RAB8A:GTP:RAB3IP:RAB11A:GTP:RAB11FIP3 dimer:ASAP1 dimer:VxPx-containing ciliary membrane proteins	Complex	R-HSA-5623447 (Reactome)
RAB8A:GTP:RAB3IP:RAB11A:GTP:RAB11FIP3 dimer:ASAP1 dimer:VxPx-containing ciliary membrane proteins	Complex	R-HSA-5623450 (Reactome)
RAB8A:GTP	Complex	R-HSA-5623445 (Reactome)
RABL5	Protein	Q9H7X7 (Uniprot-TrEMBL)
RABL5	Protein	Q9H7X7 (Uniprot-TrEMBL)
RHO	Protein	P08100 (Uniprot-TrEMBL)
RP2	Protein	O75695 (Uniprot-TrEMBL)
RP2:ARL3:GDP:UNC119B	Complex	R-HSA-5637984 (Reactome)
RP2:ARL3:GTP:UNC119B(active)	Complex	R-HSA-5637988 (Reactome)
RP2:ARL3:GTP:UNC119B	Complex	R-HSA-5637985 (Reactome)
RP2	Protein	O75695 (Uniprot-TrEMBL)
RPGRIP1L	Protein	Q68CZ1 (Uniprot-TrEMBL)
SCLT1	Protein	Q96NL6 (Uniprot-TrEMBL)
SCLT1	Protein	Q96NL6 (Uniprot-TrEMBL)
SDCCAG8	Protein	Q86SQ7 (Uniprot-TrEMBL)
SEPT2	Protein	Q15019 (Uniprot-TrEMBL)
SFI1	Protein	A8K8P3 (Uniprot-TrEMBL)
SMO	Protein	Q99835 (Uniprot-TrEMBL)
SSNA1	Protein	O43805 (Uniprot-TrEMBL)
SSTR3	Protein	P32745 (Uniprot-TrEMBL)
TCP1	Protein	P17987 (Uniprot-TrEMBL)
TCTE3	Protein	Q8IZS6 (Uniprot-TrEMBL)
TCTEX1D1	Protein	Q8N7M0 (Uniprot-TrEMBL)
TCTEX1D2	Protein	Q8WW35 (Uniprot-TrEMBL)
TCTN1	Protein	Q2MV58 (Uniprot-TrEMBL)
TCTN2	Protein	Q96GX1 (Uniprot-TrEMBL)
TCTN3	Protein	Q6NUS6 (Uniprot-TrEMBL)
TMEM216	Protein	Q9P0N5 (Uniprot-TrEMBL)
TMEM67	Protein	Q5HYA8 (Uniprot-TrEMBL)
TNPO1	Protein	Q92973 (Uniprot-TrEMBL)
TNPO1	Protein	Q92973 (Uniprot-TrEMBL)
TRAF3IP1	Protein	Q8TDR0 (Uniprot-TrEMBL)
TRAF3IP1	Protein	Q8TDR0 (Uniprot-TrEMBL)
TRIP11	Protein	Q15643 (Uniprot-TrEMBL)
TRIP11	Protein	Q15643 (Uniprot-TrEMBL)
TTBK2	Protein	Q6IQ55 (Uniprot-TrEMBL)
TTBK2	Protein	Q6IQ55 (Uniprot-TrEMBL)
TTC21B	Protein	Q7Z4L5 (Uniprot-TrEMBL)
TTC21B	Protein	Q7Z4L5 (Uniprot-TrEMBL)
TTC26	Protein	A0AVF1 (Uniprot-TrEMBL)
TTC26	Protein	A0AVF1 (Uniprot-TrEMBL)
TTC30A	Protein	Q86WT1 (Uniprot-TrEMBL)
TTC30B	Protein	Q8N4P2 (Uniprot-TrEMBL)
TTC30	Complex	R-HSA-5637976 (Reactome)
TTC8	Protein	Q8TAM2 (Uniprot-TrEMBL)
TTC8	Protein	Q8TAM2 (Uniprot-TrEMBL)
TUBA1A	Protein	Q71U36 (Uniprot-TrEMBL)
TUBA4A	Protein	P68366 (Uniprot-TrEMBL)
TUBB	Protein	P07437 (Uniprot-TrEMBL)
TUBB4A	Protein	P04350 (Uniprot-TrEMBL)
TUBB4B	Protein	P68371 (Uniprot-TrEMBL)
TUBG1	Protein	P23258 (Uniprot-TrEMBL)
Tectonic-like complex	Complex	R-HSA-5626670 (Reactome)
UNC119B	Protein	A6NIH7 (Uniprot-TrEMBL)
UNC119B:myristoylated ciliary cargo	Complex	R-HSA-5624105 (Reactome)
UNC119B:myristoylated ciliary cargo	Complex	R-HSA-5624122 (Reactome)
UNC119B	Protein	A6NIH7 (Uniprot-TrEMBL)
VxPx-containing ciliary membrane proteins	Complex	R-HSA-5620919 (Reactome)
VxPx-containing ciliary membrane proteins	Complex	R-HSA-5623420 (Reactome)
WDR19	Protein	Q8NEZ3 (Uniprot-TrEMBL)
WDR19	Protein	Q8NEZ3 (Uniprot-TrEMBL)
WDR34	Protein	Q96EX3 (Uniprot-TrEMBL)
WDR35	Protein	Q9P2L0 (Uniprot-TrEMBL)
WDR35	Protein	Q9P2L0 (Uniprot-TrEMBL)
WDR60	Protein	Q8WVS4 (Uniprot-TrEMBL)
YWHAE	Protein	P62258 (Uniprot-TrEMBL)
YWHAG	Protein	P61981 (Uniprot-TrEMBL)
acetylated microtubule		R-HSA-5618327 (Reactome)
acetylated microtubule		R-HSA-5624939 (Reactome)
acetylated microtubule		R-HSA-5624939 (Reactome)
active dynein-2 motors	Complex	R-HSA-5625410 (Reactome)
active kinesin-2 motors	Complex	R-HSA-5624943 (Reactome)
anterograde IFT trains	Complex	R-HSA-5624945 (Reactome)
anterograde IFT trains	Complex	R-HSA-5625417 (Reactome)
basal body:transition zone proteins:RAB3IP:RAB11A:GTP:Golgi-derived vesicle	Complex	R-HSA-5637989 (Reactome)
basal body:transition zone proteins	Complex	R-HSA-5626673 (Reactome)
basal body	Complex	R-HSA-5626181 (Reactome)
centrosome:C2CD2:distal appendage proteins:TTBK2:MARK4	Complex	R-HSA-5626678 (Reactome)
dynein-2	Complex	R-HSA-5624940 (Reactome)
dynein-2	Complex	R-HSA-5625411 (Reactome)
exocyst complex:RAB8A:GTP:RAB3IP:RAB11:GTP:RAB11FIP3 dimer:ASAP1 dimer:VxPx-containing ciliary membrane proteins	Complex	R-HSA-5623455 (Reactome)
exocyst complex	Complex	R-HSA-5623453 (Reactome)
microtubule		R-HSA-190599 (Reactome)
mother centriole:C2CD3	Complex	R-HSA-5626175 (Reactome)
mother centriole	Complex	R-HSA-5626171 (Reactome)
myristoylated ciliary cargo	Complex	R-HSA-5624099 (Reactome)
myristoylated ciliary proteins	Complex	R-HSA-5624102 (Reactome)
retrograde IFT trains	Complex	R-HSA-5624947 (Reactome)
retrograde IFT trains	Complex	R-HSA-5625425 (Reactome)

Annotated Interactions

View all...

Source	Target	Type	Database reference	Comment
	ARF4:GDP	Arrow	R-HSA-5623513 (Reactome)
ARF4:GDP			R-HSA-5623508 (Reactome)
	ARF4:GTP:VxPx-containing ciliary membrane proteins	Arrow	R-HSA-5620914 (Reactome)
ARF4:GTP:VxPx-containing ciliary membrane proteins			R-HSA-5620918 (Reactome)
	ARF4:GTP	Arrow	R-HSA-5623508 (Reactome)
ARF4:GTP			R-HSA-5620914 (Reactome)
	ARL13B:INPP5E:PDE6D	Arrow	R-HSA-5624953 (Reactome)
ARL13B:INPP5E:PDE6D			R-HSA-5638012 (Reactome)
	ARL13B:INPP5E	Arrow	R-HSA-5638012 (Reactome)
ARL13B			R-HSA-5624953 (Reactome)
	ARL3:GDP	Arrow	R-HSA-5638016 (Reactome)
	ARL3:GTP:UNC119B:myristoylated ciliary cargo	Arrow	R-HSA-5624133 (Reactome)
ARL3:GTP:UNC119B:myristoylated ciliary cargo			R-HSA-5624130 (Reactome)
	ARL3:GTP:UNC119B	Arrow	R-HSA-5624130 (Reactome)
ARL3:GTP:UNC119B			R-HSA-5638004 (Reactome)
ARL3:GTP			R-HSA-5624133 (Reactome)
	ARL6:GTP:BBSome:ciliary cargo	Arrow	R-HSA-5624126 (Reactome)
	ARL6:GTP:BBSome:ciliary cargo	Arrow	R-HSA-5624127 (Reactome)
ARL6:GTP:BBSome:ciliary cargo			R-HSA-5624127 (Reactome)
ARL6:GTP			R-HSA-5624126 (Reactome)
	ASAP1 dimer: ARF4:GTP:VxPx-containing ciliary membrane proteins	Arrow	R-HSA-5620918 (Reactome)
ASAP1 dimer: ARF4:GTP:VxPx-containing ciliary membrane proteins			R-HSA-5620921 (Reactome)
ASAP1 dimer			R-HSA-5620918 (Reactome)
ATAT		mim-catalysis	R-HSA-5618328 (Reactome)
	Ac-CoA	Arrow	R-HSA-5618331 (Reactome)
Ac-CoA			R-HSA-5618328 (Reactome)
BBIP1			R-HSA-5624125 (Reactome)
BBS/CCT complex		Arrow	R-HSA-5624125 (Reactome)
BBS1			R-HSA-5624125 (Reactome)
BBS2			R-HSA-5624125 (Reactome)
BBS4			R-HSA-5624125 (Reactome)
BBS5			R-HSA-5624125 (Reactome)
BBS7			R-HSA-5624125 (Reactome)
BBS9			R-HSA-5624125 (Reactome)
BBSome ciliary cargo			R-HSA-5624126 (Reactome)
	BBSome	Arrow	R-HSA-5624125 (Reactome)
BBSome			R-HSA-5617815 (Reactome)
BBSome			R-HSA-5624126 (Reactome)
BBSome			R-HSA-5624129 (Reactome)
C2CD3			R-HSA-5626220 (Reactome)
	CCP110	Arrow	R-HSA-5626227 (Reactome)
CEP164			R-HSA-5626223 (Reactome)
CEP83			R-HSA-5626223 (Reactome)
CEP89			R-HSA-5626223 (Reactome)
	CEP97	Arrow	R-HSA-5626227 (Reactome)
CLUAP			R-HSA-5617820 (Reactome)
	Centrosome:C2CD3:distal appendage proteins:TTBK2	Arrow	R-HSA-5626228 (Reactome)
Centrosome:C2CD3:distal appendage proteins:TTBK2			R-HSA-5626699 (Reactome)
	Centrosome:C2CD3:distal appendage proteins	Arrow	R-HSA-5626223 (Reactome)
Centrosome:C2CD3:distal appendage proteins			R-HSA-5626228 (Reactome)
	CoA-SH	Arrow	R-HSA-5618328 (Reactome)
CoA-SH			R-HSA-5618331 (Reactome)
FBF1			R-HSA-5626223 (Reactome)
GBF1		mim-catalysis	R-HSA-5623508 (Reactome)
	GDP	Arrow	R-HSA-5617816 (Reactome)
	GDP	Arrow	R-HSA-5623508 (Reactome)
	GDP	Arrow	R-HSA-5623521 (Reactome)
GTP			R-HSA-5617816 (Reactome)
GTP			R-HSA-5623508 (Reactome)
GTP			R-HSA-5623521 (Reactome)
H2O			R-HSA-5623513 (Reactome)
HDAC6		mim-catalysis	R-HSA-5618331 (Reactome)
HSPB11			R-HSA-5617820 (Reactome)
	IFT A	Arrow	R-HSA-5617829 (Reactome)
	IFT A	Arrow	R-HSA-5625421 (Reactome)
	IFT A	Arrow	R-HSA-5625424 (Reactome)
IFT A			R-HSA-5624949 (Reactome)
IFT A			R-HSA-5624952 (Reactome)
	IFT B*	Arrow	R-HSA-5617820 (Reactome)
IFT B*			R-HSA-5617825 (Reactome)
	IFT B	Arrow	R-HSA-5617825 (Reactome)
	IFT B	Arrow	R-HSA-5625421 (Reactome)
	IFT B	Arrow	R-HSA-5625424 (Reactome)
IFT B			R-HSA-5624949 (Reactome)
IFT B			R-HSA-5624952 (Reactome)
IFT122			R-HSA-5617829 (Reactome)
IFT140			R-HSA-5617829 (Reactome)
IFT172			R-HSA-5617820 (Reactome)
IFT20:TRIP11			R-HSA-5617828 (Reactome)
	IFT20	Arrow	R-HSA-5617828 (Reactome)
IFT20			R-HSA-5617825 (Reactome)
IFT27			R-HSA-5617820 (Reactome)
IFT43			R-HSA-5617829 (Reactome)
IFT46			R-HSA-5617820 (Reactome)
IFT52			R-HSA-5617820 (Reactome)
IFT57			R-HSA-5617820 (Reactome)
IFT74			R-HSA-5617820 (Reactome)
IFT80			R-HSA-5617820 (Reactome)
IFT81			R-HSA-5617820 (Reactome)
IFT88			R-HSA-5617820 (Reactome)
INPP5E			R-HSA-5624956 (Reactome)
	KIF17 dimer:TNPO1	Arrow	R-HSA-5624948 (Reactome)
	KIF17 dimer:TNPO1	Arrow	R-HSA-5624951 (Reactome)
KIF17 dimer:TNPO1			R-HSA-5624948 (Reactome)
KIF17 dimer			R-HSA-5624951 (Reactome)
	Kinesin-2 motors	Arrow	R-HSA-5625421 (Reactome)
	Kinesin-2 motors	Arrow	R-HSA-5625424 (Reactome)
Kinesin-2 motors			R-HSA-5624952 (Reactome)
	LZTFL1 oligomer:BBSome	Arrow	R-HSA-5624129 (Reactome)
LZTFL1 oligomer:BBSome		TBar	R-HSA-5624127 (Reactome)
LZTFL1 oligomer			R-HSA-5624129 (Reactome)
MARK4			R-HSA-5626699 (Reactome)
NPHP complex			R-HSA-5626681 (Reactome)
	PDE6D:INPP5E	Arrow	R-HSA-5624954 (Reactome)
	PDE6D:INPP5E	Arrow	R-HSA-5624956 (Reactome)
PDE6D:INPP5E			R-HSA-5624953 (Reactome)
PDE6D:INPP5E			R-HSA-5624954 (Reactome)
	PDE6D	Arrow	R-HSA-5638012 (Reactome)
PDE6D			R-HSA-5624956 (Reactome)
	Pi	Arrow	R-HSA-5623513 (Reactome)
			R-HSA-5617815 (Reactome)	The BBS1 component of the BBSome complex binds RAB3IP, a GEF for the small GTPase RAB8A. RAB3IP is required for RAB8A to localize to the cilium, and depletion of RAB3IP compromises cilia formation (Nachury et al, 2007; Loktev et al, 2008). GTP-bound RAB8A may promote ciliogenesis by promoting the traffic of post-Golgi vesicles to the base of the primary cilium (Nachury et al, 2007; reviewed in Zerial and McBride, 2001; Ishikawa et al, 2011; Hsiao et al, 2012; Sung and Leroux, 2013).
			R-HSA-5617816 (Reactome)	RAB3IP is a GEF for RAB8A, the only RAB GTPase localized in the cilium. GTP-bound RAB8A may play a role in recruiting vesicles from the Golgi to the ciliary base and is required for cilia formation (Nachury et al, 2007; Yoshimura et al, 2007; reviewed in Reiter et al, 2012).
			R-HSA-5617820 (Reactome)	Based on studies done in C. reinhardtii, C. elegans and mouse, the human IFT B complex likely consists of, minimally, IFT20, RABL5/IFT22, HSPB11/IFT25, IFT27, IFT46, IFT52, TRAF3IP1/IFT54, IFT74, IFT80, IFT81, IFT88, CLUAP/QILIN, IFT70/TTC30, and TTC26/IFT56, with IFT172 being an additional candidate (Follit et al, 2009; Piperno and Mead, 1997; Cole et al, 1998; Cole, 2003; Ou, 2007; Hallbritter et al, 2013; reviewed in Taschner et al, 2012). Work in C. reinhardtii and mouse suggests that IFT B consists of a salt stable core complex of IFT88, IFT81, IFT74, IFT70, IFT52, IFT46 IFT 27, IFT25 and IFT22 with peripheral, weakly associated subunits IFT 172, IFT80, IFT57, CLUAP, TTC26 and IFT20 (Lucker et al, 2005; Lucker et al, 2010; Follit et al, 2009; Bhogaraju et al, 2011). In Chlamydomonas, core components IFT81 and IFT74 have been shown to interact directly and a stable sub-complex of IFT81/74/27/25 has been demonstrated (Lucker et al, 2005; Taschner et al, 2011). Human IFT81 and IFT74 have likewise been shown to directly interact and to form a tubulin-binding complex (Bhogaraju et al, 2013). A recent study has elucidated more detail of the protein-protein interactions that direct the assembly of the IFTB complex (Taschner et al, 2014). This reaction shows putative human IFT B proteins assembling in a single step; details of how and when this assembly occurs are not shown, nor are the specific protein-protein interactions within the complex or details of how IFT B is regulated. Moreover, this reaction shows the formation of a presumptive IFT B* complex, lacking IFT20, to allow the recruitment of IFT20 from the Golgi compartment to be depicted.
			R-HSA-5617825 (Reactome)	IFT20 is unique among IFT B components in that, in addition to being localized at the cilium and the centrosome, a pool of IFT20 exists at the Golgi in complex with the golgin protein TRIP11 (Follit et al, 2006; Follit et al, 2008; Follit et al, 2009). Independent of its interaction with TRIP11, IFT20 has been shown to interact with the IFT B complex member TRAF3IP1 at the cilium, and overexpression of TRAF3IP1 displaces IFT20 from the Golgi (Follit et al, 2009). Partial depletion of IFT20 disrupts the traffic of membrane proteins to the cilium (Follit et al, 2006; Follit et al, 2009). Taken together, these data suggest a model where TRAF3IP1 mediates recruitment of IFT20-carrying vesicles from the Golgi to the site of cilium assembly, thus completing assembly of the IFT B complex and delivering both lipid and protein cargo for cilium biogenesis (Follit et al, 2008; Follit et al, 2009; reviewed in Ishikawa et al, 2011).
			R-HSA-5617828 (Reactome)	IFT20 is a member of the IFT B anterograde complex that is required for cilia formation and that, uniquely among IFT proteins, is found at the Golgi in addition to the centrosome and the cilium. Fluorescently-labelled IFT20 shuttles between the Golgi complex and the cilium and the ciliary microtubules (Follit et al, 2006; Follit et al, 2009). Golgi-association of IFT20 depends on interaction with the peripheral membrane protein TRIP11 and this interaction occurs independently of the IFT B complex (Follit et al, 2008). Golgi-localization of IFT20 is abolished in cells lacking TRIP11, and cilia in these cells are short and have a depleted complement of polycystin-2, a ciliary-localized membrane protein (Follit et al, 2008). RNAi-depletion of IFT20 in mammalian cells similarly compromises the traffic of polycystin-2 to the cilium (Follit et al, 2006). These data suggest that IFT20 may have a role at the Golgi complex in sorting and transporting membrane proteins that are destined for the cilium (Follit et al, 2006; Follit et al, 2008; Follit et al, 2009). IFT54, another IFT B component that is localized at the cilia, interacts with IFT20 but not with TRIP11, and overexpression of IFT54 displaces IFT20 from the Golgi. This supports a model where, after dissociation of the TRIP11:IFT20 complex, IFT54 docks IFT20 at the primary cilium, possibly on the surface of Golgi-derived vesicles, thus completing assembly of the IFT B complex and delivering ciliary membrane and membrane proteins to the site of cilium assembly (Follit et al, 2009; Omori et al, 2008; Li et al, 2008).
			R-HSA-5617829 (Reactome)	The IFT A complex is believed to be composed of six components: WDR19/IFT144, IFT140, IFT122, TTC21B/IFT139, WDR35/IFT121 and IFT43 (Piperno et al, 1998; Cole and Snell, 2009; reviewed in Taschner et al, 2012). Each of these proteins was identified as a TULP3-interacting protein in human cells, supporting the notion established in other organisms that they are all components of the IFT A complex (Mukhopadhyay et al, 2010; reviewed in Taschner et al, 2012). The IFT A proteins are large and generally have similar domain organization, consisting of N-terminal WD motifs and C-terminal TPR repeats. These protein interaction domains may help the IFT A complex scaffold recruitment of the IFT B complex, as well as recruit ciliary cargo and motor proteins. Intriguingly, the domain structure of IFT A proteins is similar to that of nucleoporins and coat proteins and it has been suggested that they evolved from a coat protein precursor, consistent with a role in vesicle trafficking (Devos et al, 2004; Jekely and Arendt, 2006). Details of protein-protein interactions within the IFT A complex are not known, nor are the details of how and where the complex assembles in a human cell.
			R-HSA-5618328 (Reactome)	Cilia are enriched in acetylated tubulin, a marker that is associated with stability, and the kinesin motor preferentially travels on acetylated microtubules (Johnson et al, 1998; Reed et al, 2006; Cai et al, 2009). Alpha tubulin acetyltransferase (ATAT), also known as MEC17, has been shown to catalyze the acetylation of alpha tubulin at K40 (Akella et al, 2010; Shida et al, 2010; Montagnac et al, 2013). ATAT preferentially acetylates polymerized alpha tubulin and may access the luminal K40 residue through 'breathing' of the microtubules protofilaments (Shida et al, 2010). ATAT was identified as an interacting protein with components of the BBSome, and siRNA knockdown of ATAT delays assembly of the primary cilium (Jin et al, 2010; Shida et al, 2010). BBIP1 is another component of the BBSome that has been shown to affect tubulin acetylation and stability, potentially through its interaction with HDAC6. BBIP1 exerts its effect on microtubule acetylation independently of its role as a component of the BBSome; it may exert its indirect effect by promoting ATAT-mediated acceleration, by counteracting HDAC6-mediated deacetylation, or by another mechanism (Loktev et al, 2008)
			R-HSA-5618331 (Reactome)	HDAC6 is a microtubule-associated deacetylase that targets the K40 acetyl groups of alpha tubulin (Hubbert et al, 2002; Loktev et al, 2008; Zhang et al, 2008). HDAC6 also interacts with BBIP1, a component of the BBSome that is required for BBSome assembly, and additionally (and independently of its role in the BBSome) plays a role in microtubule polymerization and acetylation (Loktev et al, 2008). Depletion of BBIP1 causes a marked reduction in cytoplasmic microtubule acetylation, and this defect is partially overcome by inhibition of HDAC6. These data suggest that BBIP1 may exert its effect on microtubule acetylation by negatively regulating HDAC6, although other mechanisms are also possible (Loktev et al, 2008).
			R-HSA-5620914 (Reactome)	ARF4 is a small GTPase that faciliates the targeting of some membrane proteins destined for the cilium. ARF4-mediated targeting of these cargo may depend in part on a VxPx-like motif in the C-terminal tails (Deretic et al, 2005; Geng et al, 2006; Jenkins et al, 2006; Mazelova et al, 2009; Ward et al, 2011; Wang et al, 2012; reviewed in Li et al, 2012). ARF4 is the only ARF protein with a role in ciliogenesis, and its localization at the TGN positions it to act as primary sorting mechanism for membrane proteins destined for the cilium (reviewed in Deretic, 2013; Li et al, 2012). ARF4 is myristoylated at the N-terminus and is membrane-associated in its GTP-bound form (reviewed in Li et al, 2012).
			R-HSA-5620918 (Reactome)	ASAP1 is a dimeric ARF GTPase activating protein (GAP) and scaffolding protein that is recruited to the trans-Golgi network (TGN) through interactions with activated ARF4, PI(4,5)P2 and acidic phospholipids (Brown et al, 1998; Che et al, 2005; Nie et al, 2006). Once at the TGN, ASAP1 forms a tripartite complex with ARF4 and ciliary cargo, possibly by interacting with a putative C-terminal FR targeting motif present in a number of membrane proteins destined for the cilium, although this remains to be conclusively demonstrated (Corbit et al, 2005; Wang et al, 2012; reviewed in Bhogaraju et al, 2013). In addition to its role as an ARF GAP, ASAP1 also scaffolds the recruitment of a number of other proteins required for ciliary targeting, including RAB11 and the RAB11 effector FIP3 (Mazelova et al, 2009; Inoue et al, 2008; reviewed in Deretic 2013).
			R-HSA-5620921 (Reactome)	Recruitment of ASAP1 to the TGN facilitates the subsequent recruitment of both RAB11A and the RAB11 effector protein FIP3 to the ciliary targeting complex. RAB11FIP3 functions as a homodimer and can bind simultaneously to RAB11 and ARF4 through its C-terminal region (Inoue et al, 2008; Mazelova et al, 2009; Wang et al, 2012; Shiba et al, 2006; Eathiraj et al, 2006; Schonteich et al, 2007). RAB11FIP3 also interacts with the BAR domain of ASAP1 and in this way may play a role in stimulating the ARF GAP activity of ASAP1, promoting the inactivation ARF4 and its subsequent dissociation from the TGN (Inoue et al, 2008; reviewed in Deretic, 2013).
			R-HSA-5623508 (Reactome)	GBF1 promotes guanine nucleotide exchange on ARF4 at the Golgi membrane, activating the small GTPase and promoting its association with the Golgi membrane (Szul et al, 2007; reviewed in Deretic, 2013). Activated ARF4 at the trans-Golgi network may represent the initial sorting point for membrane proteins destined for the primary cilium (reviewed in Li et al, 2012).
			R-HSA-5623513 (Reactome)	Recruitment of RAB11FIP3 to the trans-Golgi network (TGN) simulates ASAP1 to activate the ARF4 GTPase activity, causing the hydrolysis of GTP and the release of ARF4:GDP from the Golgi membrane (Mazelova et al, 2009; Inoue et al, 2008; reviewed in Deretic, 2013).
			R-HSA-5623519 (Reactome)	RAB8A is another small GTPase that is required for ciliogenesis. RAB8A is recruited to the ciliary targeting complex at the trans-Golgi network (TGN) through interactions of the RAB8A guanine nucleotide exchange factor (GEF) RAB3IP (also known as RABIN8) with ASAP1 and RAB11 (Wang et al, 2012; Westlake et al, 2011; Feng et al, 2012; reviewed in Deretic, 2013). RAB8A is recruited in the inactive GDP bound form, and is activated at the TGN by RAB3IP in a RAB11A-dependent fashion (Hatulla et al, 2002; Knodler et al, 2010; Westlake et al, 2012; Wang et al, 2012; Feng et al, 2012).
			R-HSA-5623521 (Reactome)	Once recruited to the ciliary targeting complex, RAB3IP/RABIN8 stimulates nucleotide exchange on RAB8A. Activated RAB8A is required for ciliogenesis and plays a role in mediating vesicle docking at the basal body, providing both lipid and protein content to the emerging cilium (Hattula et al, 2002; Knodler et al, 2010; Nachury et al, 2007; Wang et al, 2012; Westlake et al, 2011; Yoshimura et al, 2007; reviewed in Deretic, 2013; Sung and Leroux, 2013).
			R-HSA-5623524 (Reactome)	RAB3IP interacts directly with the EXOC6/SEC15 component of the exocyst, recruiting this membrane-targeting complex to the Golgi-derived vesicles (Feng et al, 2012; reviewed in Deretic, 2013). The exocyst is an octameric complex with roles in tethering and fusion of secretory vesicles with target membranes. A number of the exocyst components have been shown to be localized to the ciliary base and/or to be required for ciliogenesis. Consistent with this, IQCB1/NPHP5, a component of the basal body, has been shown to interact with members of the exocyst complex (Wu et al, 2005; Rogers et al, 2004; Zuo et al, 2009; Feng et al, 2012; Sang et al, 2011; reviewed in Das and Guo, 2011; Heider and Munson, 2012).
			R-HSA-5623525 (Reactome)	Membrane budding at the trans-Golgi network is promoted at least in part by the BAR domain of ASAP1, which is involved in sensing and inducing membrane curvature as well as providing the recognition site for small GTPases (Nie et al, 2006; Jian et al, 2009; Inoue et al, 2008; reviewed in Masuda et al, 2010). Oligomerization between ASAP1 and RAB11FIP3 may contribute to coat formation on vesicles budding from the TGN and destined for the plasma or ciliary membrane (Inoue et al, 2008; Mazelova et al, 2009; reviewed in Deretic, 2013).
			R-HSA-5623527 (Reactome)	Exocyst-mediated fusion of the Golgi-derived vesicle delivers the VxPx-containing membrane proteins to the ciliary membrane, although the precise mechanisms remain to be worked out (Mazelova et al, 2009; Wang et al, 2012; reviewed in Sung and Leroux, 2013). Vesicles carrying membrane proteins destined for the cilum may fuse at the periciliary membrane at the base of the cilium and deliver cargo to the IFT system. Ciliary membrane proteins may also diffuse laterally into the periciliary membrane after fusion of vesicles with the plasma membrane (reviewed in Hsiao et al, 2012; Sung and Leroux, 2013). Although not depicted in this reaction, there is evidence that some of the protein-protein interactions of the ciliary-targeting complex may persist into the periciliary or ciliary membrane region (Wang et al, 2012).
			R-HSA-5624125 (Reactome)	The BBSome is a complex of 8 conserved proteins with roles in ciliary trafficking (Nachury et al, 2007; Loktev et al, 2008; reviewed in Nachury et al, 2010; Hsiao et al, 2012). Mutations in the BBS genes leads to Bardet-Biedl syndrome, a heterogeneous ciliopathy characterized by obesity, blindness, cystic kidney disease, retinitis pigmentosa, polydactyly, mental retardation, and renal failure in some cases (reviewed in Tobin and Beales, 2009). The BBSome is the primary effector of ARL6/BBS3, a small GTPase that recruits the BBSome and associated membrane proteins destined for the primary cilium to membranes (Jin et al, 2010; Nachury et al, 2007; Zhang et al, 2011; Seo et al 2011). The BBSome also interacts with the RAB8A guanine nucleotide exchange factor RAB3IP, and in this way promotes the recruitment of RAB8A to the cilium (Nachury et al, 2007). Components of the BBSome are enriched in beta propeller and TPR domains and have been shown to form linear arrays on liposomes (Jin et al, 2010). Where these arrays form, and how they contribute to ciliary targeting remains to be elucidated (Jin et al, 2010; reviewed in Nachury et al, 2010). In mammalian cells, formation of the BBSome depends on a BBS/CCT complex that consists of MKKS/BBS6, BBS10, BBS12 and 6 members of the CCT/TRiC family of chaperonins. The BBS/CCT complex interacts with a subset of the BBSome protein and plays a role in the BBS7 stability, promoting the formation of an intermediate "BBSome core complex" (Seo et al, 2010; Jin et al, 2010; Zhang el al, 2012).
			R-HSA-5624126 (Reactome)	ARL6 is a small GTPase that was also identified as BBS3, a gene that when mutated gives rise to the ciliopathy Bardet-Biedel syndrome (Chiang et al, 2004; Fan et al, 2004). In its GTP-form, membrane-associated ARL6 recruits the BBSome along with BBSome-associated cargo such as SSTR3, MHCR1 or SMO to the cilium (Jin et al, 2010; Zhang et al, 2011; Seo et al, 2011). Binding of IFT27 to the nucleotide-free form of ARL6 may also play a role in promoting the exit of the BBSome from the cilium (Liew et al, 2014). The BBSome, a complex consisting of BBS1, BBS2, BBS4, BBS5, BBS7, BBC9, TTC8/BBS8 and BBIP10 is thought to contribute to ciliary targeting, either by promoting budding of vesicles from the secretory pathway or through lateral diffusion of BBSome-enriched 'rafts' from the plasma membrane as indicated in this reaction (Jin et al, 2010; reviewed in Li et al, 2012; Sung and Leroux, 2013; Nachury et al, 2010). The interaction between the BBSome and ARL6 is mediated by the N-terminal B-propeller domain of BBSome component BBS1 (Jin et al, 2010). BBSome function is negatively regulated by LZTFL1, which forms a complex with the BBSome in the cytosol and inhibits its traffic to the cilium (Seo et al, 2011).
			R-HSA-5624127 (Reactome)	ARL6:GTP and the BBSome complex are required for the ciliary accumulation of proteins such as SSTR3, MHRC1 and SMO (Zhang et al, 2011; Jin et al, 2010; Seo et al, 2011; reviewed in Nachury et al, 2010; Sung and Leroux, 2013). BBSome localization to the primary cilium is negatively regulated by LZTFL1, and ciliary accumulation of some BBSome cargo is increased by LZTFL1 depletion (Seo et al, 2011).
			R-HSA-5624129 (Reactome)	LZTFL1 was identified as a tumor suppressor and as a protein that interacts with components of the BBSome (Wei et al, 2010; Seo et al, 2011). LZTFL1 forms cytosolic complexes with the BBSome and negatively regulates its entry into the cilium without affecting the assembly or stability of the BBSome complex. Both the BBSome and LZTFL1 have been shown to regulate the localization of the Hh signaling protein SMO (Seo et al, 2011). A recent study suggests that LZTFL1 may additionally play a role in coordinating the interaction between the BBSome and the IFT B component IFT27 and in this way contribute to the traffic of Hh pathway proteins into and out of the cilium (Eguether et al, 2014).
			R-HSA-5624130 (Reactome)	Binding of ARL3 to UNC119B induces a conformational change that obstructs UNC119B cargo-binding and promotes the release of the myrisoylated cargo into the ciliary membrane (Wright et al, 2011; Ismail et al, 2012).
			R-HSA-5624131 (Reactome)	UNC119B is an ARL3 effector that binds directly to the myristoyl moieties at glycine 2 of NPHP3 and CYS1 (Wright et al, 2011). Myristoylation is required for the ciliary localization of these proteins (Wright et al, 2011; Tao et al, 2006), and both mutation of the glycine 2 myristoylation target in NPHP3 and siRNA knockdown of UNC119B dramatically reduce the ciliary localization of NPHP3 and CYS1 (Tao et al, 2006; Wright et al, 2011; reviewed in Schwarz et al, 2012).
			R-HSA-5624132 (Reactome)	UNC119B promotes the translocation of myristoylated NPHP3 from the ER membrane to the primary cilium by an unknown mechanism. Ciliary localization depends both on myristoylation and UNC119B, as mutation of the glycine 2 acceptor site or siRNA knockdown of UNC119B drastically reduces the amount of NPHP3 or CYS1 in the cilium (Wright et al, 2011).
			R-HSA-5624133 (Reactome)	ARL3 is an ARF-like small GTPase that is localized to the primary cilium in both the GDP- and the GTP-bound form (Zhou et al, 2006; Wright et al, 2011). ARL3 binds UNC119B in a GTP-dependent fashion and is required for the ciliary localization of NPHP3 and CYS1. Upon GTPase activation, ARL3 promotes the transfer of the myristoylated cargo into the ciliary membrane (Wright et al, 2011).
			R-HSA-5624948 (Reactome)	Ciliary localization of the alternative kinesin-2 motor KIF17 depends on TNPO1 and the RAN:GDP/RAN:GTP gradient. Once in the cilium, the TNPO1:KIF17 complex is likely dissociated by RAN:GTP binding and subsequent GTP hydrolysis, freeing KIF17 to play its role in anterograde IFT transport (Dishinger et al, 2010).
			R-HSA-5624949 (Reactome)	IFT particles were first characterized in Chlamydomonas reinhardtii, where they were observed by differential interference contrast microscopy as electron-dense granules that move along doublet microtubules of the ciliary axoneme (Kozminski et al, 1993; Kozminski et al, 1995; reviewed in Pedersen et al, 2008). More recent ultrastructural analysis of Chlamydomonas flagella confirms the presence of two distinct types of IFT trains, a longer, less electron-opaque anterograde train and shorter, more opaque retrograde trains. Both the anterograde and retrograde trains are associated with the outer microtubule doublets and with the inner surface of the flagellar membrane (Pigino et al, 2009). Isolation and characterization of IFT particles revealed that they consist of 2 biochemically distinct subcomplexes, IFT A and IFT B that are widely conserved in ciliated organisms (Piperno et al, 1997; Cole et al, 1998; reviewed in Sung and Leroux, 2013). Anterograde traffic is driven by kinesin-2 type motors in an ATP-dependent manner. Evidence from C. elegans suggests distinct and sequential roles for the canonical heterotrimeric kinesin-2 motor and the alternate homodimeric kinesin-2, OSM-3 (homologue of human KIF17) in mediating anterograde transport, but this has not been demonstrated in human cells where the canonical kinesin-2 motor predominates (Evans et al, 2006; Snow et al, 2004; Ou et al, 2005). Human KIF17 appears to be required in some cell types for cilia formation, and plays a role in the import of some ciliary cargo (Jenkins et al, 2006; Insinna et al, 2008; Insinna et al, 2009; Dishinger et al, 2010; reviewed in Verhey et al, 2011). Assembly of the anterograde IFT trains at the base of the primary cilium may be facilitated by the BBSome complex, which has also been shown to display IFT-like movement along the axoneme; however, the BBSome is highly sub-stoichiometric with respect to the IFT complex, so this notion requires more substantiation (Ou et al, 2005; Wei et al, 2012; Blacque et al, 2004; Nachury et al, 2007; Lechtreck et al, 2009; reviewed in Sung and Leroux, 2013). Studies in C. elegans also suggest a role for ARL13B and ARL3 in regulating the stability of the anterograde IFT train (Li et al, 2010).
			R-HSA-5624951 (Reactome)	KIF17 is an alternate kinesin-2 motor that is required in some cell types for anterograde IFT and for the ciliary localization of CNG (Ou et al, 2005; Jenkins et al, 2006; Insinna et al, 2008; Insinna et al, 2009; Li et al, 2010; reviewed in Scholey, 2008; Verhey et al, 2011). KIF17 contains a C-terminal ciliary localization signal that mediates its interaction with nuclear import factor TNPO1 (importin beta-2). This interaction is required for the ciliary targeting of KIF17 and is regulated by RAN GTP levels such that the interaction is promoted in the cytosol where RAN:GTP levels are low, and is destabilized in the cilium where RAN:GTP levels are high (Dishinger et al, 2010). The roles of TNPO1 and the RAN:GTP gradient in promoting ciliary localization of KIF17 are analogous to their roles in nuclear import and provide evidence for the first time of conserved mechanisms governing nuclear and ciliary localization (Dishinger et al, 2010; Devos et al, 2004; Gruss, 2010).
			R-HSA-5624952 (Reactome)	Remodelling of IFT trains is thought to occur at the ciliary tip (Iomini et al, 2001; Buisson et al, 2013; reviewed in Snell and Cole, 2009). Retrograde transport is driven by the multi-subunit dynein-2 motor in an ATP-dependent fashion (Hou et al, 2004; Pazour et al, 1999; Porter et al, 1999; reviewed in Cole and Snell, 2009; Ishikawa et al, 2011). Mutations in genes encoding members of the IFT A complex or the dynein-2 motor generally result in short, swollen cilia that abnormally acccumulate IFT components (Iomini et al, 2009; Piperno et al, 1998; Pazour et al, 1999). The subunit composition of the human dynein-2 complex has recently been analyzed and preliminary characterization of the IFT A complex has begun, but detailed understanding of the molecular architecture of the retrograde IFT trains is still lacking (Assante et al, 2014; Piperno et al, 1998; Mukhopadhyay et al, 2010; reviewed in Taschner et al, 2012).
			R-HSA-5624953 (Reactome)	The small GTPase ARL13B is required for the ciliary localization of INPP5E. ARL13B binds directly to INPP5E and is thought to displace PDE6D from the complex (Humbert et al, 2012).
			R-HSA-5624954 (Reactome)	INPP5E is a ciliary peripheral membrane protein that is associated with the ciliopathy Joubert's Syndrome (Bielas et al, 2009; Jacoby et al, 2009). Ciliary localization of the full-length protein depends on a targeting sequence and interactions with PDE6D and ARL13B, although the detailed mechanism remains unresolved (Humbert et al, 2012).
			R-HSA-5624956 (Reactome)	The inositol polyphosphate phosphatase INPP5E is a ciliary localized peripheral membrane protein with a CaaX prenylation motif in its C-terminus (Jacoby et al, 2009; Bielas et al, 2009; Humbert et al, 2012). This motif is downstream of the ciliary targeting sequence and prenylation is not required for the ciliary localization of INPP5E. The CaaX motif is required for the interaction between INPP5E and the phosphodiesterase PDE6D, and PDE6D is required for the ciliary localization of full length INPP5E but not a truncated solubilized form. These data suggest that PDE6D may play a role in extracting prenylated INPP5E from a donor membrane prior to ciliary targeting (Humbert et al, 2012).
			R-HSA-5625416 (Reactome)	Anterograde trains travel along the axoneme of the primary cilium at an estimated rate of 2 micrometers per second in an ATP- and kinesin-2-dependent fashion (reviewed in Cole and Snell, 2009). Although the particulars of IFT train-cargo interactions have not been fully elaborated, recent studies in C. reinhardtii and human cells have shown that the IFT B components IFT74 and IFT81 have tubulin-binding sites, while IFT46 is required for the ciliary transport of the outer dynein arm, and more recently, TTC26 has been shown to be required for the transport of motility-related proteins into the flagella (Bhogaraju et al, 2013; Ahmed et al, 2008; Hou et al, 2007; Ishikawa et al, 2014; reviewed in Bhogarju et al, 2014).
			R-HSA-5625421 (Reactome)	Based on work done in C. reinhardtii and Trypanosoma brucei, anterograde IFT trains are believed to disassemble at the ciliary tip, releasing cargo and the IFT motors. Smaller retrograde trains are subsequently reassembled for transport back to the ciliary base (Iomini et al, 2001; Buisson et al, 2013; Pigino et al, 2009; reviewed in Ishikawa et al, 2011; Bhogaraju et al, 2013). A direct interaction between IFT27 and the nucleotide-free form of ARL6 may contribute to ARL6 activation and in this way contribute to ciliary exit of some cargo (Liew et al, 2014).
			R-HSA-5625424 (Reactome)	At the base of the cilium, retrograde trains are believed to disassemble and recycle for a subsequent round of IFT transport (Iomini et al, 2001; Buisson et al, 2013; reviewed in Ishikawa et al, 2011; Cole and Snell, 2009).
			R-HSA-5625426 (Reactome)	Retrograde trains are shorter than anterograde particles and travel along the axoneme of the primary cilium at an estimated rate of 3 micrometers per second (reviewed in Cole and Snell, 2009).
			R-HSA-5626220 (Reactome)	C2 domain-containing protein 3 (C2CD3) is basal body-localized protein that is required for ciliogenesis and Hh signaling (Hoover et al, 2008; Balestra et al, 2013). C2CD3 is recruited to the centrosome in a pericentriolar material 1 protein (PCM1)- and microtubule-dependent manner and is required for the subsequent recruitment of the distal appendage proteins to the mother centriole (Tanos et al, 2013; Sillibourne et al, 2013; Ye et al, 2014; reviewed in Winey and O'Toole, 2014). The distal appendage proteins are thought to be a component of the transition fibres that anchor the basal body to the membrane at the base of the cilium and are themselves required for the recruitment of Tau-tubulin kinase 2 (TTBK2) and for docking ciliary vesicles to the mother centriole (Tanos et al, 2013; Wei et al, 2013; Joo et al, 2013; Schmidt et al, 2012; Sillibourne et al, 2013; Burke et al, 2014).
			R-HSA-5626223 (Reactome)	C2CD3 and the centrosome component OFD1 are required for the recruitment of distal appendage proteins CEP164, CEP83/CCDC41, CEP89, FBF1 and SCLT1 to the mother centriole (Ye et al, 2014; Tang et al, 2013; Singla et al, 2010). Distal appendage proteins are believed to form part of the transition fibres that anchor the basal bodies to the actin rich cortex at the base of the emerging primary cilium, and are also required for the recruitment and binding of ciliary vesicles and intraflagellar transport (IFT) complexes (Tanos et al, 2013; Wei et al, 2013; Joo et al, 2010; Schmidt et al, 2012; Sillibourne et al, 2013; Ye et al, 2014; reviewed in Winey and O'Toole, 2014).
			R-HSA-5626227 (Reactome)	CCP110 is a negative regulator of ciliogenesis that caps the mother centriole. CCP110 may inhibit ciliogenesis in part by preventing the CEP290-dependent recruitment of RAB8A to the centrosome and cilia (Spektor et al, 2007; Tsang et al, 2008; reviewed in Tsang and Dynlacht, 2013). CCP110 and CEP97 also form a complex with the KIF24, a kinesin with centriolar microtubule depolymerizing activity that is required for the initial recruitment and/or stability of CCP110 at the centriole (Kobayashi et al, 2011). Recruitment of TTBK2 promotes the displacement of CCP110 and its binding partner CEP97. This results in the formation of a basal body and promotes recruitment of IFT complex members and allows axonemal extension to occur (Goetz et al, 2012; Ye et al, 2014; reviewed in Tsang and Dynlacht, 2013). Although the kinase activity of TTBK2 is required for cilium formation and TTBK2 has been shown to phosphorylate CEP164, the relevant physiological target during ciliogenesis has not been unambiguously identified (Cajanek et al, 2014). Similarly, the kinase activity of MARK4 is also required for ciliogenesis, and the interaction between MARK4 and ODF2, a putative substrate, is needed to promote the dissociation of the CCP110 and CEP97 proteins from the centriole (Kuhns et al, 2013; reviewed in Kim and Dynlacht, 2013).
			R-HSA-5626228 (Reactome)	C2CD3 and the distal appendage protein CEP164 are required for the recruitment of the kinase Tau tubulin kinase 2 (TTBK2) to the centriole (Ye et al, 2014; Cajanek et al, 2014). TTBK2 recruitment promotes the release of CCP110, a negative regulator of ciliogenesis that caps the mother centriole (Goetz et al, 2012; Ye et al, 2014; Tsang et al, 2008; Spektor et al, 2007). CCP110 is initially recruited and/or stabilized at the mother centriole in a KIF24-dependent manner; KIF24, a kinesin-like protein, also restricts ciliogenesis through its microtubule depolymerizing activity (Kobayashi et al, 2011). In addition to promoting the release of CCP110, TTBK2 also plays a role in the recruitment of intraflagellar transport (IFT) proteins and in this way contributes to extension of the ciliary axoneme (Goetz et al, 2012; Ye et al, 2014). Mutations in TTBK2 disrupt ciliogenesis and are associated with the development of spinocerebellar ataxia (Houlden et al, 2007; Bouskila et al, 2011; reviewed in Jackson, 2012).
			R-HSA-5626681 (Reactome)	The transition zone is a protein-rich zone at the base of the primary cilium that forms after maturation of the mother centriole and prior to or concurrent with the initiation of intraflagellar transport (IFT) (reviewed in Benzing and Schermer, 2011; Reiter et al, 2012). The transition zone consists of a growing number of proteins and protein complexes, many of whose genes are associated with ciliopathies such as nephronophthisis, Meckel-Gruber syndrome and Joubert's syndrome (Reiter et al, 2006; Hu et al, 2010; Sang et al, 2011; Williams et al, 2011; Garcia-Gonzalo et al, 2011; Chih et al, 2012; reviewed in Reiter et al, 2012). In conjunction with SEPT2, which was recently shown to form a septin ring diffusion barrier at the base of the cilium, the transition zone and its resident proteins contribute to protein sorting and ciliary membrane composition and act as a ciliary gate (Hu et al, 2010; Williams et al, 2011; Garcia-Gonzalo et al, 2011; Chih et al, 2012; reviewed in Reiter et al, 2012).
			R-HSA-5626699 (Reactome)	MARK4 (microtubule associated protein/microtubule affinity regulating kinase 4) was identified in a screen as a positive regulator of ciliogenesis (Kuhns et al, 2013). MARK4 interacts at the centriole with the subdistal appendage component ODF2 and this interaction is required to promote axonemal extension (Kuhns et al, 2013; reviewed in Kim and Dynlacht, 2013). Like Tau tubulin kinase 2 (TTBK2), MARK4 appears to have a role in promoting the dissociation of CCP110 and CEP97, uncapping the centriole and allowing axonemal extension to take place (Kuhns et al, 2013; Ye et al, 2014;; Goetz et al, 2012). Although this reaction shows that MARK4 is recruited to the centriole subsequent to TTBK2, the timing of the ODF2:MARK4 interaction is not known.
			R-HSA-5638004 (Reactome)	RP2 is an ARL3 GAP that is localized to the primary cilium and plays a role in trafficking proteins from the Golgi to the ciliary membrane (Veltel et al, 2008a; Hurd et al, 2011; Evans et al, 2010; Wright et al, 2011). RP2 forms a ternary complex with UNC119B and ARL3, activating the ARL3 GTPase activity and promoting the release of UNC119B (Veltel et al, 2008b; Wright et al, 2011; Kuhnel et al, 2006; reviewed in Schwarz et al, 2012; Li et al, 2012)
			R-HSA-5638006 (Reactome)	RP2 is an ARL3 GAP that is localized to the primary cilium and plays a role in trafficking proteins from the Golgi to the ciliary membrane (Veltel et al, 2008a; Hurd et al, 2011; Evans et al, 2010; Wright et al, 2011). RP2 forms a ternary complex with UNC119B and ARL3, activating the ARL3 GTPase activity and promoting the release of UNC119B (Veltel et al, 2008b; Wright et al, 2011; Kuhnel et al, 2006; reviewed in Schwarz et al, 2012; Li et al, 2012)
			R-HSA-5638007 (Reactome)	RP2 is an ARL3 GAP that is localized to the primary cilium and plays a role in trafficking proteins from the Golgi to the ciliary membrane (Veltel et al, 2008a; Hurd et al, 2011; Evans et al, 2010; Wright et al, 2011). RP2 forms a ternary complex with UNC119B and ARL3, activating the ARL3 GTPase activity and promoting the release of UNC119B (Veltel et al, 2008b; Wright et al, 2011; Kuhnel et al, 2006; reviewed in Schwarz et al, 2012; Li et al, 2012)
			R-HSA-5638009 (Reactome)	The distal appendage protein CEP164 interacts with RAB3IP, and in this way recruits Golgi-derived vesicles to the basal body to initiate ciliary membrane biogenesis (Schmidt et al, 2012; Westlake et al, 2011; Rohatgi and Snell, 2010). RAB3IP recruitment to the distal appendages of centrioles promotes the appropriate localization and activation of RAB8A (Nachury et al, 2007; Yoshimura et al, 2007; Westlake et al, 2011; Schmidt et al, 2012).
			R-HSA-5638012 (Reactome)	ARL13B promotes the ciliary localization of INPP5E by interacting with it directly and displacing PDE6D from the complex (Humbert et al, 2012).
			R-HSA-5638014 (Reactome)	The RAB8 guanine nucleotide exchange factor RAB3IP/RABIN8 is recruited to vesicles through interaction with membrane-tethered RAB11:GTP (Westlake et al, 2011; Knodler et al, 2010). Recruitment of RAB3IP may also depend on the TRAPPCII complex, a multiprotein complex with roles in vesicular trafficking (Westlake et al, 2011; reviewed in Sacher et al, 2008). RAB3IP is required for RAB8A to localize to the cilium, and depletion of RAB3IP compromises cilia formation (Nachury et al, 2007; Loktev et al, 2008). GTP-bound RAB8A may promote ciliogenesis by promoting the traffic of post-Golgi vesicles to the base of the primary cilium (Nachury et al, 2007; Westlake et al, 2011; Feng et al, 2012; reviewed in Reiter et al, 2012)
			R-HSA-5638016 (Reactome)	ARL3 hydrolysis of GTP promotes the release of UNC119B, dissociating the complex (Wright et al, 2011; reveiwed in Schwarz et al, 2012).
RAB11A:GTP:Golgi derived vesicle			R-HSA-5638014 (Reactome)
	RAB11A:GTP:RAB11FIP3 dimer:ASAP1 dimer:ARF4:GTP:VxPx-containing ciliary membrane proteins	Arrow	R-HSA-5620921 (Reactome)
RAB11A:GTP:RAB11FIP3 dimer:ASAP1 dimer:ARF4:GTP:VxPx-containing ciliary membrane proteins			R-HSA-5623513 (Reactome)
RAB11A:GTP:RAB11FIP3 dimer:ASAP1 dimer:ARF4:GTP:VxPx-containing ciliary membrane proteins		mim-catalysis	R-HSA-5623513 (Reactome)
	RAB11A:GTP:RAB11FIP3 dimer:ASAP1 dimer:VxPx-containing ciliary membrane proteins	Arrow	R-HSA-5623513 (Reactome)
RAB11A:GTP:RAB11FIP3 dimer:ASAP1 dimer:VxPx-containing ciliary membrane proteins			R-HSA-5623519 (Reactome)
RAB11A:GTP			R-HSA-5620921 (Reactome)
RAB11FIP3 dimer			R-HSA-5620921 (Reactome)
	RAB3IP:BBSome	Arrow	R-HSA-5617815 (Reactome)
	RAB3IP:RAB11A:GTP:Golgi-derived vesicle	Arrow	R-HSA-5638014 (Reactome)
RAB3IP:RAB11A:GTP:Golgi-derived vesicle			R-HSA-5638009 (Reactome)
RAB3IP:RAB8A:GDP			R-HSA-5623519 (Reactome)
RAB3IP			R-HSA-5617815 (Reactome)
RAB3IP			R-HSA-5638014 (Reactome)
	RAB8A:GDP:RAB3IP:RAB11A:GTP:FIP3 dimer:ASAP1 dimer:VxPx-containing ciliary membrane proteins	Arrow	R-HSA-5623519 (Reactome)
RAB8A:GDP:RAB3IP:RAB11A:GTP:FIP3 dimer:ASAP1 dimer:VxPx-containing ciliary membrane proteins			R-HSA-5623521 (Reactome)
RAB8A:GDP:RAB3IP:RAB11A:GTP:FIP3 dimer:ASAP1 dimer:VxPx-containing ciliary membrane proteins		mim-catalysis	R-HSA-5623521 (Reactome)
RAB8A:GDP			R-HSA-5617816 (Reactome)
	RAB8A:GTP:RAB3IP:RAB11A:GTP:RAB11FIP3 dimer:ASAP1 dimer:VxPx-containing ciliary membrane proteins	Arrow	R-HSA-5623521 (Reactome)
	RAB8A:GTP:RAB3IP:RAB11A:GTP:RAB11FIP3 dimer:ASAP1 dimer:VxPx-containing ciliary membrane proteins	Arrow	R-HSA-5623525 (Reactome)
RAB8A:GTP:RAB3IP:RAB11A:GTP:RAB11FIP3 dimer:ASAP1 dimer:VxPx-containing ciliary membrane proteins			R-HSA-5623524 (Reactome)
RAB8A:GTP:RAB3IP:RAB11A:GTP:RAB11FIP3 dimer:ASAP1 dimer:VxPx-containing ciliary membrane proteins			R-HSA-5623525 (Reactome)
	RAB8A:GTP	Arrow	R-HSA-5617816 (Reactome)
RABL5			R-HSA-5617820 (Reactome)
	RP2:ARL3:GDP:UNC119B	Arrow	R-HSA-5638006 (Reactome)
RP2:ARL3:GDP:UNC119B			R-HSA-5638016 (Reactome)
	RP2:ARL3:GTP:UNC119B(active)	Arrow	R-HSA-5638007 (Reactome)
RP2:ARL3:GTP:UNC119B(active)			R-HSA-5638006 (Reactome)
RP2:ARL3:GTP:UNC119B(active)		mim-catalysis	R-HSA-5638006 (Reactome)
	RP2:ARL3:GTP:UNC119B	Arrow	R-HSA-5638004 (Reactome)
RP2:ARL3:GTP:UNC119B			R-HSA-5638007 (Reactome)
	RP2	Arrow	R-HSA-5638016 (Reactome)
RP2			R-HSA-5638004 (Reactome)
RP2		mim-catalysis	R-HSA-5638007 (Reactome)
SCLT1			R-HSA-5626223 (Reactome)
SEPT2		Arrow	R-HSA-5626681 (Reactome)
TNPO1			R-HSA-5624951 (Reactome)
TRAF3IP1			R-HSA-5617820 (Reactome)
	TRIP11	Arrow	R-HSA-5617828 (Reactome)
TTBK2			R-HSA-5626228 (Reactome)
TTC21B			R-HSA-5617829 (Reactome)
TTC26			R-HSA-5617820 (Reactome)
TTC30			R-HSA-5617820 (Reactome)
TTC8			R-HSA-5624125 (Reactome)
Tectonic-like complex			R-HSA-5626681 (Reactome)
	UNC119B:myristoylated ciliary cargo	Arrow	R-HSA-5624131 (Reactome)
	UNC119B:myristoylated ciliary cargo	Arrow	R-HSA-5624132 (Reactome)
UNC119B:myristoylated ciliary cargo			R-HSA-5624132 (Reactome)
UNC119B:myristoylated ciliary cargo			R-HSA-5624133 (Reactome)
	UNC119B	Arrow	R-HSA-5638016 (Reactome)
UNC119B			R-HSA-5624131 (Reactome)
	VxPx-containing ciliary membrane proteins	Arrow	R-HSA-5623527 (Reactome)
VxPx-containing ciliary membrane proteins			R-HSA-5620914 (Reactome)
WDR19			R-HSA-5617829 (Reactome)
WDR35			R-HSA-5617829 (Reactome)
	acetylated microtubule	Arrow	R-HSA-5618328 (Reactome)
	acetylated microtubule	Arrow	R-HSA-5625421 (Reactome)
	acetylated microtubule	Arrow	R-HSA-5625424 (Reactome)
acetylated microtubule			R-HSA-5618331 (Reactome)
active dynein-2 motors			R-HSA-5624952 (Reactome)
active kinesin-2 motors			R-HSA-5624949 (Reactome)
	anterograde IFT trains	Arrow	R-HSA-5624949 (Reactome)
	anterograde IFT trains	Arrow	R-HSA-5625416 (Reactome)
anterograde IFT trains			R-HSA-5625416 (Reactome)
anterograde IFT trains			R-HSA-5625421 (Reactome)
	basal body:transition zone proteins:RAB3IP:RAB11A:GTP:Golgi-derived vesicle	Arrow	R-HSA-5638009 (Reactome)
basal body:transition zone proteins:RAB3IP:RAB11A:GTP:Golgi-derived vesicle		mim-catalysis	R-HSA-5617816 (Reactome)
	basal body:transition zone proteins	Arrow	R-HSA-5626681 (Reactome)
basal body:transition zone proteins			R-HSA-5638009 (Reactome)
	basal body	Arrow	R-HSA-5626227 (Reactome)
basal body			R-HSA-5626681 (Reactome)
	centrosome:C2CD2:distal appendage proteins:TTBK2:MARK4	Arrow	R-HSA-5626699 (Reactome)
centrosome:C2CD2:distal appendage proteins:TTBK2:MARK4			R-HSA-5626227 (Reactome)
	dynein-2	Arrow	R-HSA-5625421 (Reactome)
	dynein-2	Arrow	R-HSA-5625424 (Reactome)
dynein-2			R-HSA-5624949 (Reactome)
	exocyst complex:RAB8A:GTP:RAB3IP:RAB11:GTP:RAB11FIP3 dimer:ASAP1 dimer:VxPx-containing ciliary membrane proteins	Arrow	R-HSA-5623524 (Reactome)
exocyst complex:RAB8A:GTP:RAB3IP:RAB11:GTP:RAB11FIP3 dimer:ASAP1 dimer:VxPx-containing ciliary membrane proteins			R-HSA-5623527 (Reactome)
exocyst complex			R-HSA-5623524 (Reactome)
	microtubule	Arrow	R-HSA-5618331 (Reactome)
microtubule			R-HSA-5618328 (Reactome)
	mother centriole:C2CD3	Arrow	R-HSA-5626220 (Reactome)
mother centriole:C2CD3			R-HSA-5626223 (Reactome)
mother centriole			R-HSA-5626220 (Reactome)
myristoylated ciliary cargo			R-HSA-5624131 (Reactome)
	myristoylated ciliary proteins	Arrow	R-HSA-5624130 (Reactome)
	retrograde IFT trains	Arrow	R-HSA-5624952 (Reactome)
	retrograde IFT trains	Arrow	R-HSA-5625426 (Reactome)
retrograde IFT trains			R-HSA-5625424 (Reactome)
retrograde IFT trains			R-HSA-5625426 (Reactome)

Assembly of the primary cilium (Homo sapiens)

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