HDAC6 interactions in the central nervous system (Homo sapiens)

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106115511083686568212194LegendLabelVelvet Antler Polypeptides (VAP)MYH9TUBA4ABIRC5VIMVCP26, 64, 939519, 7279410, 923795HDAC6 in complex with other proteinsRegulators of HDAC6(De)acetylation activityInhibit / reduceInteract / bind (directional interaction)Stimulate / induceDonepeziltatOligomycin AMAP1BGSK3ASevofluraneNR3C1MYD88HDAC4SHHHSPA8KALRNHSPA4miR-218-5pITIH4PTK2BMAP3K5SEPTIN7SNCAmiR-26amiR-155-5PATP13A2LINC00461 POU5F1ARID3AOPTNPARK7NR3C1MAPRE1MIIPACTR1APXNTWIST1CYBBSTUB1ATXN3HDAC6BDNFAPOEBBIP1MAPTHDAC11ERGHDAC9SQSTM1TRIM50 UBDG3BP1TPPPPRKCESMAD2PROM1RAD23BAKT1CFTRISG15EP300SOD1100884568454541850, 1148115GRK239, 49, 65GSK3B22, 109PRKCZ65EGFR49AURKA2, 30, 46MAPK338MAPK13812, 83SIRT2HDAC6HDAC6CDC20HDAC11HSP90AA1HSF1HDAC6CTNNB1PROM118HDAC6ELP1MAPK8HDAC6926106EP400KAT5HDAC685SMAD2PCDC2079APCCDC20RAC1DLG4DLG2SNCAIPHTTELP3PPP1CAHDAC6SGK3SGK1MAP1LC3ANEDD9Aggresome-autophagy61, 76, 80, 88, 101...HDAC6HDAC6CSNK2B62PhosphorylationDCTN1GRIA2GRIA1TARDBPFUSDYNC1I2Interact/Bind (non-directional interaction)Functional interactions: regulate, modulatecontrol, associate, mediate, co-localize 783259Phosphorylation of HDAC6HDAC69987115914848HDAC6HSPA4MAPTCSNK2A2MDH1NDUFV1MIFRHOT1CNOT6HSPA8SP1FOXP3CCDC141HIF1APRKNGARS1HSPB1CTTNCTNNB1XRCC6PRDX1PRDX2DNAJA1HSP90AA1TUBBTUBB3TUBA1CTUBA3CSMAD7tat108336, 16672143, 44822131, 35479023, 116131119, 7021, 9515, 9669, 1022810, 9266, 97, 9894757526, 7724, 80732764205103106, 1177, 177110734, 4274, 104, 105557711111112413511011710652636014, 291845, 534536258955841089640, 865857Chemical compoundRNATUBA4AmiR-613HDAC6PRKCZMAPTHDAC6PRKNHSP90AA1HSF1HDAC6HDAC6PHDAC6HDAC6HDAC6HDAC6LabelAPCXRCC6BAX47115VHLHDAC6VHL49KALRNSQSTM14960BCL2BAXMethylmercury (MeHg)


Description

HDAC6 stands out as a distinctive member within the histone deacetylase family due to its predominant presence in the cytosol, facilitating its interaction with a wide array of non-histone proteins. Its dysregulation has been linked to various outcomes, encompassing diverse cancer types, immune-related disorders, and neurological conditions, including Alzheimer's, Parkinson's, ALS, Huntington's, Charcot-Marie-Tooth disease, and Rett syndrome. The current network represents the known HDAC6 interactions in the central nervous system (CNS).

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  102. Mo Z, Zhao X, Liu H, Hu Q, Chen XQ, Pham J, Wei N, Liu Z, Zhou J, Burgess RW, Pfaff SL, Caskey CT, Wu C, Bai G, Yang XL; ''Aberrant GlyRS-HDAC6 interaction linked to axonal transport deficits in Charcot-Marie-Tooth neuropathy.''; Nat Commun, 2018 PubMed Europe PMC Scholia
  103. Nakashima H, Nguyen T, Goins WF, Chiocca EA; ''Interferon-stimulated gene 15 (ISG15) and ISG15-linked proteins can associate with members of the selective autophagic process, histone deacetylase 6 (HDAC6) and SQSTM1/p62.''; J Biol Chem, 2015 PubMed Europe PMC Scholia
  104. Dhanyamraju PK, Holz PS, Finkernagel F, Fendrich V, Lauth M; ''Histone deacetylase 6 represents a novel drug target in the oncogenic Hedgehog signaling pathway.''; Mol Cancer Ther, 2015 PubMed Europe PMC Scholia
  105. Yang W, Liu Y, Gao R, Yu H, Sun T; ''HDAC6 inhibition induces glioma stem cells differentiation and enhances cellular radiation sensitivity through the SHH/Gli1 signaling pathway.''; Cancer Lett, 2018 PubMed Europe PMC Scholia
  106. Tsai YC, Riess O, Soehn AS, Nguyen HP; ''The Guanine nucleotide exchange factor kalirin-7 is a novel synphilin-1 interacting protein and modifies synphilin-1 aggregate transport and formation.''; PLoS One, 2012 PubMed Europe PMC Scholia
  107. Roca-Agujetas V, Barbero-Camps E, de Dios C, Podlesniy P, Abadin X, Morales A, Marí M, Trullàs R, Colell A; ''Cholesterol alters mitophagy by impairing optineurin recruitment and lysosomal clearance in Alzheimer's disease.''; Mol Neurodegener, 2021 PubMed Europe PMC Scholia
  108. Wu AC, Yang WB, Chang KY, Lee JS, Liou JP, Su RY, Cheng SM, Hwang DY, Kikkawa U, Hsu TI, Wang CY, Chang WC, Chen PY, Chuang JY; ''HDAC6 involves in regulating the lncRNA-microRNA-mRNA network to promote the proliferation of glioblastoma cells.''; J Exp Clin Cancer Res, 2022 PubMed Europe PMC Scholia
  109. Chen S, Owens GC, Makarenkova H, Edelman DB; ''HDAC6 regulates mitochondrial transport in hippocampal neurons.''; PLoS One, 2010 PubMed Europe PMC Scholia
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  111. Kalveram B, Schmidtke G, Groettrup M; ''The ubiquitin-like modifier FAT10 interacts with HDAC6 and localizes to aggresomes under proteasome inhibition.''; J Cell Sci, 2008 PubMed Europe PMC Scholia
  112. Gao YS, Hubbert CC, Lu J, Lee YS, Lee JY, Yao TP; ''Histone deacetylase 6 regulates growth factor-induced actin remodeling and endocytosis.''; Mol Cell Biol, 2007 PubMed Europe PMC Scholia
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History

View all...
CompareRevisionActionTimeUserComment
135049view11:00, 2 August 2024EweitzEconomize layout
134414view21:02, 21 July 2024EweitzRefine legend
134413view20:56, 21 July 2024EweitzFix typos, copyedit, standardize case
134412view20:53, 21 July 2024EweitzEconomize layout
134178view05:48, 16 July 2024EgonwRemoved duplicate and template comments
128236view18:47, 29 January 2024Khanspersconnected one interaction
127801view13:48, 16 December 2023EgonwUsed the Uniprot -TrEMBL data source (to make the link out work)
127721view18:14, 28 November 2023KhanspersOntology Term : 'PW:0001338' removed !
127717view18:44, 27 November 2023KhanspersOntology Term : 'regulatory pathway pertinent to the brain' added !
127716view18:41, 27 November 2023KhanspersOntology Term : 'histone modification pathway' added !
127662view19:44, 14 November 2023AlexanderPicoModified title
127612view14:45, 7 November 2023NasimBahramSanganiModified description
127611view14:40, 7 November 2023NasimBahramSanganiNew pathway

External references

DataNodes

View all...
NameTypeDatabase referenceComment
ACTR1A GeneProductENSG00000138107 (Ensembl)
AKT1 GeneProductENSG00000142208 (Ensembl)
APCGeneProductENSG00000134982 (Ensembl)
APOE GeneProductENSG00000130203 (Ensembl)
ARID3AProteinENSG00000116017 (Ensembl)
ATP13A2ProteinENSG00000159363 (Ensembl)
ATXN3 GeneProductENSG00000066427 (Ensembl) Burnett et al. also found that ataxin-3 interacts with HDAC6 and dynein motor
AURKA GeneProductENSG00000087586 (Ensembl) AurA phosphorylates HDAC6 to activate
BAX GeneProductENSG00000087088 (Ensembl)
BBIP1 GeneProductENSG00000214413 (Ensembl)
BCL2 GeneProductENSG00000171791 (Ensembl)
BDNFGeneProductENSG00000176697 (Ensembl)
BIRC5GeneProductENSG00000089685 (Ensembl)
CCDC141 GeneProductENSG00000163492 (Ensembl)
CDC20 GeneProductENSG00000117399 (Ensembl)
CFTR GeneProductENSG00000001626 (Ensembl)
CNOT6ProteinENSG00000113300 (Ensembl)
CSNK2A2GeneProductENSG00000070770 (Ensembl) To verify the association of HDAC6 with CK2, we performed a pull-down assay using two recombinant proteins (GST–HDAC6 and CK2 holoenzyme) and individual subunit proteins (Fig. 2C, top). Only CK2 holoenzyme was found to be associated with HDAC6, whereas CK2α and CK2β alone failed to precipitate with HDAC6, indicating that the CK2 holoenzyme associates with HDAC6
CSNK2B GeneProductENSG00000204435 (Ensembl) To verify the association of HDAC6 with CK2, we performed a pull-down assay using two recombinant proteins (GST–HDAC6 and CK2 holoenzyme) and individual subunit proteins (Fig. 2C, top). Only CK2 holoenzyme was found to be associated with HDAC6, whereas CK2α and CK2β alone failed to precipitate with HDAC6, indicating that the CK2 holoenzyme associates with HDAC6
CTNNB1 GeneProductENSG00000168036 (Ensembl)
CTTN GeneProductENSG00000085733 (Ensembl)
CYBBGeneProductENSG00000165168 (Ensembl)
DCTN1 GeneProductENSG00000204843 (Ensembl)
DLG2 GeneProductENSG00000150672 (Ensembl)
DLG4 GeneProductENSG00000132535 (Ensembl)
DNAJA1 GeneProductENSG00000086061 (Ensembl) Proteomic identification and functional characterization of MYH9, Hsc70, and DNAJA1 as novel substrates of HDAC6 deacetylase activity
DYNC1I2GeneProductENSG00000077380 (Ensembl)
DonepezilMetabolite
EGFR GeneProductENSG00000146648 (Ensembl)
ELP1GeneProductENSG00000070061 (Ensembl)
ELP3GeneProductENSG00000134014 (Ensembl)
EP300 GeneProductENSG00000100393 (Ensembl)
EP400GeneProductENSG00000183495 (Ensembl)
ERGGeneProductENSG00000157554 (Ensembl)
FOXP3GeneProductENSG00000049768 (Ensembl)
FUS GeneProductENSG00000089280 (Ensembl)
G3BP1 GeneProductENSG00000145907 (Ensembl)
GARS1 GeneProductENSG00000106105 (Ensembl) Interestingly, pulldown experiments showed that HDAC6 can co-immunoprecipitate with HSPB1 (CMT2E) (Zhang et al., 2007), but also with GlyRS (CMT2D)
GRIA1 GeneProductENSG00000155511 (Ensembl)
GRIA2 GeneProductENSG00000120251 (Ensembl)
GRK2 GeneProductENSG00000173020 (Ensembl)
GSK3AGeneProductENSG00000105723 (Ensembl)
GSK3B GeneProductENSG00000082701 (Ensembl) GSK3b was found to co-localize with HDAC6 in hippocampal neurons, and inhibition of GSK3b resulted in decreased binding of antibody to phosphoserine-22, a potential GSK3b phosphorylation site in HDAC6.. We also provide evidence that GSK3b may directly regulate HDAC6.
HDAC11 GeneProductENSG00000163517 (Ensembl)
HDAC4Protein
HDAC6GeneProductENSG00000094631 (Ensembl)
HDAC9GeneProductENSG00000048052 (Ensembl)
HIF1A GeneProductENSG00000100644 (Ensembl)
HSF1 GeneProductENSG00000185122 (Ensembl)
HSP90AA1GeneProductENSG00000080824 (Ensembl)
HSPA4ProteinENSG00000170606 (Ensembl)
HSPA8 GeneProductENSG00000109971 (Ensembl)
HSPA8GeneProductENSG00000109971 (Ensembl)
HSPB1 GeneProductENSG00000106211 (Ensembl)
HTT GeneProductENSG00000197386 (Ensembl)
ISG15GeneProductENSG00000187608 (Ensembl)
ITIH4ProteinENSG00000055955 (Ensembl)
KALRNGeneProductENSG00000160145 (Ensembl)
KAT5 GeneProductENSG00000172977 (Ensembl)
LINC00461 Rna
MAP1BProteinENSG00000131711 (Ensembl)
MAP1LC3A GeneProductENSG00000101460 (Ensembl)
MAP3K5ProteinENSG00000197442 (Ensembl)
MAPK1 GeneProductENSG00000100030 (Ensembl)
MAPK3 GeneProductENSG00000102882 (Ensembl)
MAPK8 GeneProductENSG00000107643 (Ensembl)
MAPRE1 GeneProductENSG00000101367 (Ensembl)
MAPT GeneProductENSG00000186868 (Ensembl)
MDH1ProteinENSG00000014641 (Ensembl)
MIFProteinENSG00000240972 (Ensembl)
MIIP GeneProductENSG00000116691 (Ensembl)
MYD88GeneProductENSG00000172936 (Ensembl)
MYH9GeneProductENSG00000100345 (Ensembl)
Methylmercury (MeHg)Metabolite
NDUFV1ProteinENSG00000167792 (Ensembl)
NEDD9 GeneProductENSG00000111859 (Ensembl)
NR3C1 GeneProductENSG00000113580 (Ensembl)
NR3C1GeneProductENSG00000113580 (Ensembl)
OPTNGeneProductENSG00000123240 (Ensembl)
Oligomycin AMetabolite
PARK7GeneProductENSG00000116288 (Ensembl)
POU5F1GeneProductENSG00000204531 (Ensembl)
PPP1CAGeneProductENSG00000172531 (Ensembl)
PRDX1 GeneProductENSG00000117450 (Ensembl)
PRDX2 GeneProductENSG00000167815 (Ensembl)
PRKCE GeneProductENSG00000171132 (Ensembl)
PRKCZ GeneProductENSG00000067606 (Ensembl)
PRKN GeneProductENSG00000185345 (Ensembl)
PROM1 GeneProductENSG00000007062 (Ensembl)
PROM1GeneProductENSG00000007062 (Ensembl)
PTK2BProteinENSG00000120899 (Ensembl)
PXN GeneProductENSG00000089159 (Ensembl)
RAC1GeneProductENSG00000136238 (Ensembl)
RAD23B GeneProductENSG00000119318 (Ensembl)
RHOT1ProteinENSG00000126858 (Ensembl)
SEPTIN7GeneProductENSG00000122545  (Ensembl)
SGK1 GeneProductENSG00000118515 (Ensembl)
SGK3 GeneProductENSG00000104205 (Ensembl)
SHHProteinENSG00000164690 (Ensembl)
SIRT2 GeneProductENSG00000068903 (Ensembl)
SMAD2 GeneProductENSG00000175387 (Ensembl)
SMAD7GeneProductENSG00000101665 (Ensembl) Silencing HDAC6 increased SMAD7 protein expression
SNCAProteinENSG00000145335 (Ensembl)
SNCAIP GeneProductENSG00000064692 (Ensembl)
SOD1 GeneProductENSG00000142168 (Ensembl)
SP1GeneProductENSG00000185591 (Ensembl)
SQSTM1 GeneProductENSG00000161011 (Ensembl)
STUB1 GeneProductENSG00000103266 (Ensembl)
SevofluraneMetabolite
TARDBP GeneProductENSG00000120948 (Ensembl)
TPPP GeneProductENSG00000171368 (Ensembl)
TRIM50 GeneProductENSG00000146755 (Ensembl)
TUBA1CGeneProductENSG00000167553 (Ensembl)
TUBA3CGeneProductENSG00000198033 (Ensembl)
TUBA4AGeneProductENSG00000127824 (Ensembl)
TUBB GeneProductENSG00000196230 (Ensembl)
TUBB3 GeneProductENSG00000258947 (Ensembl)
TWIST1 GeneProductENSG00000122691 (Ensembl)
UBD GeneProductENSG00000213886 (Ensembl)
VCPGeneProductENSG00000165280 (Ensembl)
VHLGeneProductENSG00000134086 (Ensembl)
VIMProteinENSG00000026025 (Ensembl)
Velvet Antler Polypeptides (VAP)Metabolite
XRCC6 GeneProductENSG00000196419 (Ensembl)
miR-155-5PRna
miR-218-5pRna
miR-26aRna
miR-613Rna
tatGeneProduct155871 (Entrez Gene)
tatGeneProduct155871 (Uniprot-TrEMBL)

Annotated Interactions

No annotated interactions

Retrieved from "https://classic.wikipathways.org/index.php/Pathway:WP5426"
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