Protein folding (Homo sapiens)

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Bibliography

1. Plimpton RL, Cuéllar J, Lai CW, Aoba T, Makaju A, Franklin S, Mathis AD, Prince JT, Carrascosa JL, Valpuesta JM, Willardson BM.; ''Structures of the Gβ-CCT and PhLP1-Gβ-CCT complexes reveal a mechanism for G-protein β-subunit folding and Gβγ dimer assembly.''; PubMed Europe PMC Scholia
2. Freund A, Zhong FL, Venteicher AS, Meng Z, Veenstra TD, Frydman J, Artandi SE.; ''Proteostatic control of telomerase function through TRiC-mediated folding of TCAB1.''; PubMed Europe PMC Scholia
3. Litterman N, Ikeuchi Y, Gallardo G, O'Connell BC, Sowa ME, Gygi SP, Harper JW, Bonni A.; ''An OBSL1-Cul7Fbxw8 ubiquitin ligase signaling mechanism regulates Golgi morphology and dendrite patterning.''; PubMed Europe PMC Scholia
4. Kubota H, Hynes GM, Kerr SM, Willison KR.; ''Tissue-specific subunit of the mouse cytosolic chaperonin-containing TCP-1.''; PubMed Europe PMC Scholia
5. Naletova IN, Popova KM, Eldarov MA, Kuravsky ML, Schmalhausen EV, Sevostyanova IA, Muronetz VI.; ''Chaperonin TRiC assists the refolding of sperm-specific glyceraldehyde-3-phosphate dehydrogenase.''; PubMed Europe PMC Scholia
6. Lukov GL, Baker CM, Ludtke PJ, Hu T, Carter MD, Hackett RA, Thulin CD, Willardson BM.; ''Mechanism of assembly of G protein betagamma subunits by protein kinase CK2-phosphorylated phosducin-like protein and the cytosolic chaperonin complex.''; PubMed Europe PMC Scholia
7. Bigotti MG, Clarke AR.; ''Chaperonins: The hunt for the Group II mechanism.''; PubMed Europe PMC Scholia
8. Tian G, Lewis SA, Feierbach B, Stearns T, Rommelaere H, Ampe C, Cowan NJ.; ''Tubulin subunits exist in an activated conformational state generated and maintained by protein cofactors.''; PubMed Europe PMC Scholia
9. Lu J, Chiang J, Iyer RR, Thompson E, Kaneski CR, Xu DS, Yang C, Chen M, Hodes RJ, Lonser RR, Brady RO, Zhuang Z.; ''Decreased glucocerebrosidase activity in Gaucher disease parallels quantitative enzyme loss due to abnormal interaction with TCP1 and c-Cbl.''; PubMed Europe PMC Scholia
10. Young JC, Agashe VR, Siegers K, Hartl FU.; ''Pathways of chaperone-mediated protein folding in the cytosol.''; PubMed Europe PMC Scholia
11. Yam AY, Xia Y, Lin HT, Burlingame A, Gerstein M, Frydman J.; ''Defining the TRiC/CCT interactome links chaperonin function to stabilization of newly made proteins with complex topologies.''; PubMed Europe PMC Scholia
12. Won KA, Schumacher RJ, Farr GW, Horwich AL, Reed SI.; ''Maturation of human cyclin E requires the function of eukaryotic chaperonin CCT.''; PubMed Europe PMC Scholia
13. Bhamidipati A, Lewis SA, Cowan NJ.; ''ADP ribosylation factor-like protein 2 (Arl2) regulates the interaction of tubulin-folding cofactor D with native tubulin.''; PubMed Europe PMC Scholia
14. Lai CW, Kolesnikov AV, Frederick JM, Blake DR, Jiang L, Stewart JS, Chen CK, Barrow JR, Baehr W, Kefalov VJ, Willardson BM.; ''Phosducin-like protein 1 is essential for G-protein assembly and signaling in retinal rod photoreceptors.''; PubMed Europe PMC Scholia
15. Lukov GL, Hu T, McLaughlin JN, Hamm HE, Willardson BM.; ''Phosducin-like protein acts as a molecular chaperone for G protein betagamma dimer assembly.''; PubMed Europe PMC Scholia
16. Tracy CM, Kolesnikov AV, Blake DR, Chen CK, Baehr W, Kefalov VJ, Willardson BM.; ''Retinal cone photoreceptors require phosducin-like protein 1 for G protein complex assembly and signaling.''; PubMed Europe PMC Scholia
17. Guenther MG, Yu J, Kao GD, Yen TJ, Lazar MA.; ''Assembly of the SMRT-histone deacetylase 3 repression complex requires the TCP-1 ring complex.''; PubMed Europe PMC Scholia
18. Howlett AC, Gray AJ, Hunter JM, Willardson BM.; ''Role of molecular chaperones in G protein beta5/regulator of G protein signaling dimer assembly and G protein betagamma dimer specificity.''; PubMed Europe PMC Scholia
19. Wells CA, Dingus J, Hildebrandt JD.; ''Role of the chaperonin CCT/TRiC complex in G protein betagamma-dimer assembly.''; PubMed Europe PMC Scholia
20. Melki R, Batelier G, Soulié S, Williams RC.; ''Cytoplasmic chaperonin containing TCP-1: structural and functional characterization.''; PubMed Europe PMC Scholia
21. Miyata Y, Shibata T, Aoshima M, Tsubata T, Nishida E.; ''The molecular chaperone TRiC/CCT binds to the Trp-Asp 40 (WD40) repeat protein WDR68 and promotes its folding, protein kinase DYRK1A binding, and nuclear accumulation.''; PubMed Europe PMC Scholia
22. Tian G, Thomas S, Cowan NJ.; ''Effect of TBCD and its regulatory interactor Arl2 on tubulin and microtubule integrity.''; PubMed Europe PMC Scholia
23. Zebol JR, Hewitt NM, Moretti PA, Lynn HE, Lake JA, Li P, Vadas MA, Wattenberg BW, Pitson SM.; ''The CCT/TRiC chaperonin is required for maturation of sphingosine kinase 1.''; PubMed Europe PMC Scholia
24. Spiess C, Meyer AS, Reissmann S, Frydman J.; ''Mechanism of the eukaryotic chaperonin: protein folding in the chamber of secrets.''; PubMed Europe PMC Scholia
25. Trinidad AG, Muller PA, Cuellar J, Klejnot M, Nobis M, Valpuesta JM, Vousden KH.; ''Interaction of p53 with the CCT complex promotes protein folding and wild-type p53 activity.''; PubMed Europe PMC Scholia
26. Kasembeli M, Lau WC, Roh SH, Eckols TK, Frydman J, Chiu W, Tweardy DJ.; ''Modulation of STAT3 folding and function by TRiC/CCT chaperonin.''; PubMed Europe PMC Scholia

History

External references

DataNodes

Name	Type	Database reference	Comment
ACTB(1-375)	Protein	P60709 (Uniprot-TrEMBL)
ADP [cytosol]	Metabolite	CHEBI:16761 (ChEBI)
ADP	Metabolite	CHEBI:16761 (ChEBI)
ATP [cytosol]	Metabolite	CHEBI:15422 (ChEBI)
ATP	Metabolite	CHEBI:15422 (ChEBI)
CCT/TriC (ADP) associated actin	Complex	REACT_17090 (Reactome)
CCT/TriC substrate proteins with unknown chaperones		REACT_17376 (Reactome)
CCT/TriC(ADP)-associated non-native tubulin	Complex	REACT_17102 (Reactome)
CCT/TriC(ADP):Sphingosine kinase 1	Complex	REACT_18085 (Reactome)
CCT/TriC(ADP)	Complex	REACT_17874 (Reactome)
CCT/TriC(ATP)-associated actin	Complex	REACT_17160 (Reactome)
CCT/TriC(ATP):unfolded tubulin complex	Complex	REACT_17889 (Reactome)
CCT/TriC:substrate complex	Complex	REACT_17268 (Reactome)
CCT2 [cytosol]	Protein	P78371 (Uniprot-TrEMBL)
CCT3 [cytosol]	Protein	P49368 (Uniprot-TrEMBL)
CCT4 [cytosol]	Protein	P50991 (Uniprot-TrEMBL)
CCT5 [cytosol]	Protein	P48643 (Uniprot-TrEMBL)
CCT6A [cytosol]	Protein	P40227 (Uniprot-TrEMBL)
CCT7 [cytosol]	Protein	Q99832 (Uniprot-TrEMBL)
CCT8 [cytosol]	Protein	P50990 (Uniprot-TrEMBL)
Cofactor B:GTP-alpha tubulin	Complex	REACT_17838 (Reactome)
Cofactor D:GTP:beta tubulin	Complex	REACT_17888 (Reactome)
Cofactor E:GTP-alpha tubulin folding	Complex	REACT_17474 (Reactome)
GTP [cytosol]	Metabolite	CHEBI:15996 (ChEBI)
GTP-alpha-tubulin folding intermediate	Complex	REACT_17776 (Reactome)
GTP:beta-tubulin folding intermediate	Complex	REACT_18072 (Reactome)
GTP	Metabolite	CHEBI:15996 (ChEBI)
PFDN1(2-122) [cytosol]	Protein	O60925 (Uniprot-TrEMBL)
PFDN2 [cytosol]	Protein	Q9UHV9 (Uniprot-TrEMBL)
PFDN4 [cytosol]	Protein	Q9NQP4 (Uniprot-TrEMBL)
PFDN5(2-154) [cytosol]	Protein	Q99471 (Uniprot-TrEMBL)
PFDN6(2-129) [cytosol]	Protein	O15212 (Uniprot-TrEMBL)
Pi	Metabolite	CHEBI:18367 (ChEBI)
Prefoldin-associated actin/tubulin	Complex	REACT_18141 (Reactome)
Prefoldin	Complex	REACT_17255 (Reactome)
SPHK1 [cytosol]	Protein	Q9NYA1 (Uniprot-TrEMBL)
SPHK1	Protein	Q9NYA1 (Uniprot-TrEMBL)
TBCA [cytosol]	Protein	O75347 (Uniprot-TrEMBL)
TBCA	Protein	O75347 (Uniprot-TrEMBL)
TBCB [cytosol]	Protein	Q99426 (Uniprot-TrEMBL)
TBCB	Protein	Q99426 (Uniprot-TrEMBL)
TBCC [cytosol]	Protein	Q15814 (Uniprot-TrEMBL)
TBCC	Protein	Q15814 (Uniprot-TrEMBL)
TBCD [cytosol]	Protein	Q9BTW9 (Uniprot-TrEMBL)
TBCD	Protein	Q9BTW9 (Uniprot-TrEMBL)
TBCE [cytosol]	Protein	Q15813 (Uniprot-TrEMBL)
TBCE	Protein	Q15813 (Uniprot-TrEMBL)
TCP1 [cytosol]	Protein	P17987 (Uniprot-TrEMBL)
TUBA1A folding intermediate [cytosol]	Protein	Q71U36 (Uniprot-TrEMBL)
TUBA1A unfolded [cytosol]	Protein	Q71U36 (Uniprot-TrEMBL)
TUBA1B folding intermediate [cytosol]	Protein	P68363 (Uniprot-TrEMBL)
TUBA1B unfolded [cytosol]	Protein	P68363 (Uniprot-TrEMBL)
TUBA1C folding intermediate [cytosol]	Protein	Q9BQE3 (Uniprot-TrEMBL)
TUBA1C unfolded [cytosol]	Protein	Q9BQE3 (Uniprot-TrEMBL)
TUBA3C folding intermediate [cytosol]	Protein	Q13748 (Uniprot-TrEMBL)
TUBA3C unfolded [cytosol]	Protein	Q13748 (Uniprot-TrEMBL)
TUBA4A folding intermediate [cytosol]	Protein	P68366 (Uniprot-TrEMBL)
TUBA4A unfolded [cytosol]	Protein	P68366 (Uniprot-TrEMBL)
TUBB1 [cytosol]	Protein	Q9H4B7 (Uniprot-TrEMBL)
TUBB1 folding intermediate [cytosol]	Protein	Q9H4B7 (Uniprot-TrEMBL)
TUBB1 unfolded [cytosol]	Protein	Q9H4B7 (Uniprot-TrEMBL)
TUBB2A [cytosol]	Protein	Q13885 (Uniprot-TrEMBL)
TUBB2A folding intermediate [cytosol]	Protein	Q13885 (Uniprot-TrEMBL)
TUBB2A unfolded [cytosol]	Protein	Q13885 (Uniprot-TrEMBL)
TUBB2B [cytosol]	Protein	Q9BVA1 (Uniprot-TrEMBL)
TUBB2B folding intermediate [cytosol]	Protein	Q9BVA1 (Uniprot-TrEMBL)
TUBB2B unfolded [cytosol]	Protein	Q9BVA1 (Uniprot-TrEMBL)
TUBB3 [cytosol]	Protein	Q13509 (Uniprot-TrEMBL)
TUBB3 folding intermediate [cytosol]	Protein	Q13509 (Uniprot-TrEMBL)
TUBB3 unfolded [cytosol]	Protein	Q13509 (Uniprot-TrEMBL)
TUBB4A [cytosol]	Protein	P04350 (Uniprot-TrEMBL)
TUBB4A folding intermediate [cytosol]	Protein	P04350 (Uniprot-TrEMBL)
TUBB4A unfolded [cytosol]	Protein	P04350 (Uniprot-TrEMBL)
TUBB4B [cytosol]	Protein	P68371 (Uniprot-TrEMBL)
TUBB4B folding intermediate [cytosol]	Protein	P68371 (Uniprot-TrEMBL)
TUBB4B unfolded [cytosol]	Protein	P68371 (Uniprot-TrEMBL)
TUBB6 [cytosol]	Protein	Q9BUF5 (Uniprot-TrEMBL)
TUBB6 folding intermediate [cytosol]	Protein	Q9BUF5 (Uniprot-TrEMBL)
TUBB6 unfolded [cytosol]	Protein	Q9BUF5 (Uniprot-TrEMBL)
Unfolded ACTB [cytosol]	Protein	P60709 (Uniprot-TrEMBL)
VBP1 [cytosol]	Protein	P61758 (Uniprot-TrEMBL)
actin/tubulin-bound CCT/TriC(ADP)	Complex	REACT_17195 (Reactome)
alpha-beta heterodimer	Complex	REACT_18200 (Reactome)
beta tubulin:GTP: Cofactor D:alpha tubulin:GTP:Cofactor E	Complex	REACT_17650 (Reactome)
beta-tubulin:GTP:Cofactor D:alpha-tubulin:GTP:Cofactor E : Cofactor C	Complex	REACT_17144 (Reactome)
cofactor A:GTP:beta-tubulin folding intermediate	Complex	REACT_17443 (Reactome)
tubulin-GTP folding intermediate	Complex	REACT_17885 (Reactome)
unfolded actin/tubulin	Protein	REACT_17525 (Reactome)

Annotated Interactions

Source	Target	Type	Database reference	Comment
	ACTB(1-375)	Arrow	REACT_16915 (Reactome)
	ADP	Arrow	REACT_16909 (Reactome)
	ADP	Arrow	REACT_17011 (Reactome)
ATP			REACT_16909 (Reactome)
ATP			REACT_17011 (Reactome)
CCT/TriC (ADP) associated actin			REACT_17011 (Reactome)
CCT/TriC substrate proteins with unknown chaperones			REACT_16984 (Reactome)
CCT/TriC(ADP)-associated non-native tubulin			REACT_16909 (Reactome)
	CCT/TriC(ADP):Sphingosine kinase 1	Arrow	REACT_16980 (Reactome)
	CCT/TriC(ADP)	Arrow	REACT_16915 (Reactome)
	CCT/TriC(ADP)	Arrow	REACT_17032 (Reactome)
CCT/TriC(ADP)			REACT_16961 (Reactome)
CCT/TriC(ADP)			REACT_16980 (Reactome)
CCT/TriC(ADP)			REACT_16984 (Reactome)
	CCT/TriC(ATP)-associated actin	Arrow	REACT_17011 (Reactome)
CCT/TriC(ATP)-associated actin			REACT_16915 (Reactome)
	CCT/TriC(ATP):unfolded tubulin complex	Arrow	REACT_16909 (Reactome)
CCT/TriC(ATP):unfolded tubulin complex			REACT_17032 (Reactome)
	CCT/TriC:substrate complex	Arrow	REACT_16984 (Reactome)
	Cofactor B:GTP-alpha tubulin	Arrow	REACT_16900 (Reactome)
Cofactor B:GTP-alpha tubulin			REACT_16937 (Reactome)
	Cofactor D:GTP:beta tubulin	Arrow	REACT_16986 (Reactome)
	Cofactor D:GTP:beta tubulin	Arrow	REACT_17024 (Reactome)
Cofactor D:GTP:beta tubulin			REACT_17060 (Reactome)
	Cofactor E:GTP-alpha tubulin folding	Arrow	REACT_16937 (Reactome)
	Cofactor E:GTP-alpha tubulin folding	Arrow	REACT_17027 (Reactome)
Cofactor E:GTP-alpha tubulin folding			REACT_17060 (Reactome)
GTP-alpha-tubulin folding intermediate			REACT_16900 (Reactome)
GTP-alpha-tubulin folding intermediate			REACT_17027 (Reactome)
GTP:beta-tubulin folding intermediate			REACT_16994 (Reactome)
GTP:beta-tubulin folding intermediate			REACT_17024 (Reactome)
GTP			REACT_17032 (Reactome)
	Pi	Arrow	REACT_16915 (Reactome)
	Pi	Arrow	REACT_16958 (Reactome)
	Pi	Arrow	REACT_17032 (Reactome)
	Prefoldin-associated actin/tubulin	Arrow	REACT_16892 (Reactome)
Prefoldin-associated actin/tubulin			REACT_16961 (Reactome)
	Prefoldin	Arrow	REACT_16961 (Reactome)
Prefoldin			REACT_16892 (Reactome)
			REACT_16892 (Reactome)	During the synthesis of actin and tubulin, the nascent ribosome-associated chains bind to the heteromeric chaperone protein, prefoldin (PFD) (Hansen et al., 1999).
			REACT_16900 (Reactome)	Quasi-native alpha-tubulin folding intermediates generated via ATP-dependent interaction with CCT (Tian et al., 1995) are captured in a reversible reaction by cofactors B and/or E (Tian et al., 1997), forming the tubulin intermediate/cofactor complexes Factor B:alpha tubulin or Factor E:alpha tubulin.
			REACT_16909 (Reactome)	The interaction between CCT and unfolded target proteins is thought to occur when CCT is in its ADP-bound state. ADP is then exchanged for ATP in CCT.
			REACT_16915 (Reactome)	TriC/CCT-mediated beta-actin folding involves rapid ATP-independent formation of a binary complex, followed by a slower ATP-dependent release of the native product (Gao et al., 1992). Group II chaperonins enclose substrate proteins following substrate binding through the formation of a "built- in" lid over the central cavity. Upon ATP binding, lid formation is triggered by the transition state of ATP hydrolysis (Meyer, et al., 2003).
			REACT_16937 (Reactome)	The factor B:alpha tubulin complex act as a reservoir capable of accepting or delivering alpha tubulin to cofactor E (Tian et al., 1997). In the reverse reaction, cofactor B may displace cofactor E in the cofactor E:alpha tubulin complex.
			REACT_16958 (Reactome)	Beta tubulin within the active (Factor E:alpha tubulin: Factor D:beta tubulin:Factor C )-supercomplex hydrolyzes GTP. This results in the dissociation of the complex and the release of the native tubulin heterodimer (Tian et al., 1997).
			REACT_16961 (Reactome)	Unfolded actins and tubulins compete efficiently for binding to TriC/CCT and their chaperonin binding sites appear to be at least in part overlapping (Melki et al., 1993).
			REACT_16980 (Reactome)	CCT/TRiC facilitates folding of newly translated SK1 into its mature active form (Zebol et al., 2008)
			REACT_16984 (Reactome)	A combination of proteomic and bioinformatics analyses of TRiC substrates has revealed that they have complex topologies that are slow folding and aggregation prone (Yam et al., 2008). These substrates are also enriched in proteins that belong to oligomeric assemblies suggesting that TRiC plays a role in promoting complex assembly (Yam et al., 2008). Two possible mechanisms describing the role of TriC have been suggested (Yam et al., 2008). The processes of TRiC-mediated folding and assembly could be directly coupled, or TRiC could fold monomeric subunits and hold them in an assembly-competent state until they associate with the appropriate partner subunits. The complete list of TriC subsrates is not yet known. Many of its substrates that are targeted during biosynthesis are conserved between mammals and yeast (Yam et al. 2008).
			REACT_16986 (Reactome)	Factor A:beta tubulin complex act as a reservoir capable of accepting or delivering its target tubulin protein to cofactor D (Tian et al., 1997). In the reverse reaction, Cofactor A may displace cofactor D in a cofactor D:beta tubulin complex.
			REACT_16994 (Reactome)	Beta-tubulin folding intermediates generated via ATP-dependent interaction with TriC/CCT are captured by cofactors A and D (Tian et al., 1996; Tian et al., 1997) in a reversible reaction forming tubulin intermediate/cofactor complexes Factor A:beta tubulin or Factor D:beta tubulin.
			REACT_17011 (Reactome)	The interaction between CCT and unfolded target proteins is thought to occur when CCT is in its ADP-bound state. ADP is then exchanged for ATP in CCT.
			REACT_17016 (Reactome)	Entry of cofactor C to the factor E:alpha tubulin: factor D:beta tubulin complex generates the active alpha:beta-supercomplex (Tian et al., 1997).
			REACT_17024 (Reactome)	Beta-tubulin folding intermediates generated via ATP-dependent interaction with TriC/CCT are captured by cofactors A and D (Tian et al., 1996; Tian et al., 1997) in a reversible reaction forming tubulin intermediate/cofactor complexes Factor A:beta tubulin or Factor D:beta tubulin.
			REACT_17027 (Reactome)	Quasi-native alpha-tubulin folding intermediates generated via ATP-dependent interaction with CCT (Tian et al., 1995) are captured in a reversible reaction by cofactors B and/or E (Tian et al., 1997), forming the tubulin intermediate/cofactor complexes Factor B:alpha tubulin or Factor E:alpha tubulin.
			REACT_17032 (Reactome)	Group II chaperonins enclose substrate proteins following substrate binding through the formation of a "built- in" lid over the central cavity. Upon ATP binding, lid formation is triggered by the transition state of ATP hydrolysis (Meyer, et al., 2003). In the case of CCT-mediated tubulin folding, one or more rounds of ATP hydrolysis are likely required before the association of non-exchangeable GTP with chaperonin-bound alpha tubulin.
			REACT_17060 (Reactome)	Factor E:alpha tubulin and Factor D:beta tubulin interact with each other in a reversible reaction to form the complex (Factor E alpha tubulin:Factor D:beta tubulin) (Tian et al., 1997).
SPHK1			REACT_16980 (Reactome)
	TBCA	Arrow	REACT_16986 (Reactome)
TBCA			REACT_16994 (Reactome)
	TBCB	Arrow	REACT_16937 (Reactome)
TBCB			REACT_16900 (Reactome)
	TBCC	Arrow	REACT_16958 (Reactome)
TBCC			REACT_17016 (Reactome)
	TBCD	Arrow	REACT_16958 (Reactome)
TBCD			REACT_16986 (Reactome)
TBCD			REACT_17024 (Reactome)
	TBCE	Arrow	REACT_16958 (Reactome)
TBCE			REACT_16937 (Reactome)
TBCE			REACT_17027 (Reactome)
	actin/tubulin-bound CCT/TriC(ADP)	Arrow	REACT_16961 (Reactome)
	alpha-beta heterodimer	Arrow	REACT_16958 (Reactome)
	beta tubulin:GTP: Cofactor D:alpha tubulin:GTP:Cofactor E	Arrow	REACT_17060 (Reactome)
beta tubulin:GTP: Cofactor D:alpha tubulin:GTP:Cofactor E			REACT_17016 (Reactome)
	beta-tubulin:GTP:Cofactor D:alpha-tubulin:GTP:Cofactor E : Cofactor C	Arrow	REACT_17016 (Reactome)
beta-tubulin:GTP:Cofactor D:alpha-tubulin:GTP:Cofactor E : Cofactor C			REACT_16958 (Reactome)
	cofactor A:GTP:beta-tubulin folding intermediate	Arrow	REACT_16994 (Reactome)
cofactor A:GTP:beta-tubulin folding intermediate			REACT_16986 (Reactome)
	tubulin-GTP folding intermediate	Arrow	REACT_17032 (Reactome)
unfolded actin/tubulin			REACT_16892 (Reactome)