Search Results

Overview

Uniprot ID	Q9UBN7
Protein Name	Protein deacetylase HDAC6
Gene Name	HDAC6
Organism	Homo sapiens

Kla Sites from experimental identification

Position	Flanking peptide
1206	KNIAHQNKFGEDMPH
32	QDSSVTSKRNIKKGA
51	IPNLAEVKKKGKMKK
53	NLAEVKKKGKMKKLG
849	REGPSSSKLVTKKAP
860	KKAPQPAKPRLAERM
873	RMTTREKKVLEAGMG

Function

Deacetylates a wide range of non-histone substrates (PubMed:12024216, PubMed:18606987, PubMed:20308065, PubMed:24882211, PubMed:26246421, PubMed:30538141, PubMed:31857589, PubMed:30770470, PubMed:38534334, PubMed:39567688). Plays a central role in microtubule-dependent cell motility by mediating deacetylation of tubulin (PubMed:12024216, PubMed:20308065, PubMed:26246421). Required for cilia disassembly via deacetylation of alpha-tubulin (PubMed:17604723, PubMed:26246421). Alpha-tubulin deacetylation results in destabilization of dynamic microtubules (By similarity). Promotes deacetylation of CTTN, leading to actin polymerization, promotion of autophagosome-lysosome fusion and completion of autophagy (PubMed:30538141). Deacetylates SQSTM1 (PubMed:31857589). Deacetylates peroxiredoxins PRDX1 and PRDX2, decreasing their reducing activity (PubMed:18606987). Deacetylates antiviral protein RIGI in the presence of viral mRNAs which is required for viral RNA detection by RIGI (By similarity). Sequentially deacetylates and polyubiquitinates DNA mismatch repair protein MSH2 which leads to MSH2 degradation, reducing cellular sensitivity to DNA-damaging agents and decreasing cellular DNA mismatch repair activities (PubMed:24882211). Deacetylates DNA mismatch repair protein MLH1 which prevents recruitment of the MutL alpha complex (formed by the MLH1-PMS2 heterodimer) to the MutS alpha complex (formed by the MSH2-MSH6 heterodimer), leading to tolerance of DNA damage (PubMed:30770470). Deacetylates RHOT1/MIRO1 which blocks mitochondrial transport and mediates axon growth inhibition (By similarity). Deacetylates transcription factor SP1 which leads to increased expression of ENG, positively regulating angiogenesis (PubMed:38534334). Deacetylates KHDRBS1/SAM68 which regulates alternative splicing by inhibiting the inclusion of CD44 alternate exons (PubMed:26080397). Deacetylates PRDM16 (By similarity). Acts as a valine sensor by binding to valine through the primate-specific SE14 repeat region (PubMed:39567688). In valine deprivation conditions, translocates from the cytoplasm to the nucleus where it deacetylates TET2 which promotes TET2-dependent DNA demethylation, leading to DNA damage (PubMed:39567688). Promotes odontoblast differentiation following IPO7-mediated nuclear import and subsequent repression of RUNX2 expression (By similarity). In addition to its protein deacetylase activity, plays a key role in the degradation of misfolded proteins: when misfolded proteins are too abundant to be degraded by the chaperone refolding system and the ubiquitin-proteasome, mediates the transport of misfolded proteins to a cytoplasmic juxtanuclear structure called aggresome (PubMed:17846173). Probably acts as an adapter that recognizes polyubiquitinated misfolded proteins and targets them to the aggresome, facilitating their clearance by autophagy (PubMed:17846173). Involved in the MTA1-mediated epigenetic regulation of ESR1 expression in breast cancer (PubMed:24413532)

Protein Sequence

10 MTSTGQDSTT 20 TRQRRSRQNP 30 QSPPQDSSVT 40 SKRNIKKGAV 50 PRSIPNLAEV 60 KKKGKMKKLG 70 QAMEEDLIVG 80 LQGMDLNLEA 90 EALAGTGLVL 100 DEQLNEFHCL 110 WDDSFPEGPE 120 RLHAIKEQLI 130 QEGLLDRCVS 140 FQARFAEKEE 150 LMLVHSLEYI 160 DLMETTQYMN 170 EGELRVLADT 180 YDSVYLHPNS 190 YSCACLASGS 200 VLRLVDAVLG 210 AEIRNGMAII 220 RPPGHHAQHS 230 LMDGYCMFNH 240 VAVAARYAQQ 250 KHRIRRVLIV 260 DWDVHHGQGT 270 QFTFDQDPSV 280 LYFSIHRYEQ 290 GRFWPHLKAS 300 NWSTTGFGQG 310 QGYTINVPWN 320 QVGMRDADYI 330 AAFLHVLLPV 340 ALEFQPQLVL 350 VAAGFDALQG 360 DPKGEMAATP 370 AGFAQLTHLL 380 MGLAGGKLIL 390 SLEGGYNLRA 400 LAEGVSASLH 410 TLLGDPCPML 420 ESPGAPCRSA 430 QASVSCALEA 440 LEPFWEVLVR 450 STETVERDNM 460 EEDNVEESEE 470 EGPWEPPVLP 480 ILTWPVLQSR 490 TGLVYDQNMM 500 NHCNLWDSHH 510 PEVPQRILRI 520 MCRLEELGLA 530 GRCLTLTPRP 540 ATEAELLTCH 550 SAEYVGHLRA 560 TEKMKTRELH 570 RESSNFDSIY 580 ICPSTFACAQ 590 LATGAACRLV 600 EAVLSGEVLN 610 GAAVVRPPGH 620 HAEQDAACGF 630 CFFNSVAVAA 640 RHAQTISGHA 650 LRILIVDWDV 660 HHGNGTQHMF 670 EDDPSVLYVS 680 LHRYDHGTFF 690 PMGDEGASSQ 700 IGRAAGTGFT 710 VNVAWNGPRM 720 GDADYLAAWH 730 RLVLPIAYEF 740 NPELVLVSAG 750 FDAARGDPLG 760 GCQVSPEGYA 770 HLTHLLMGLA 780 SGRIILILEG 790 GYNLTSISES 800 MAACTRSLLG 810 DPPPLLTLPR 820 PPLSGALASI 830 TETIQVHRRY 840 WRSLRVMKVE 850 DREGPSSSKL 860 VTKKAPQPAK 870 PRLAERMTTR 880 EKKVLEAGMG 890 KVTSASFGEE 900 STPGQTNSET 910 AVVALTQDQP 920 SEAATGGATL 930 AQTISEAAIG 940 GAMLGQTTSE 950 EAVGGATPDQ 960 TTSEETVGGA 970 ILDQTTSEDA 980 VGGATLGQTT 990 SEEAVGGATL 1000 AQTTSEAAME 1010 GATLDQTTSE 1020 EAPGGTELIQ 1030 TPLASSTDHQ 1040 TPPTSPVQGT 1050 TPQISPSTLI 1060 GSLRTLELGS 1070 ESQGASESQA 1080 PGEENLLGEA 1090 AGGQDMADSM 1100 LMQGSRGLTD 1110 QAIFYAVTPL 1120 PWCPHLVAVC 1130 PIPAAGLDVT 1140 QPCGDCGTIQ 1150 ENWVCLSCYQ 1160 VYCGRYINGH 1170 MLQHHGNSGH 1180 PLVLSYIDLS 1190 AWCYYCQAYV 1200 HHQALLDVKN 1210 IAHQNKFGED MPHPH

Gene Ontology

Classification	GO ID	Description
Cellular Component	GO:0016235	aggresome
Cellular Component	GO:0030424	axon
Cellular Component	GO:1904115	axon cytoplasm
Cellular Component	GO:0005901	caveola
Cellular Component	GO:0031252	cell leading edge
Cellular Component	GO:0005813	centrosome
Cellular Component	GO:0036064	ciliary basal body
Cellular Component	GO:0005737	cytoplasm
Cellular Component	GO:0000153	cytoplasmic ubiquitin ligase complex
Cellular Component	GO:0005829	cytosol
Cellular Component	GO:0030425	dendrite
Cellular Component	GO:0000118	histone deacetylase complex
Cellular Component	GO:0016234	inclusion body
Cellular Component	GO:0005874	microtubule
Cellular Component	GO:0005875	microtubule associated complex
Cellular Component	GO:0005771	multivesicular body
Cellular Component	GO:0005634	nucleus
Cellular Component	GO:0043204	perikaryon
Cellular Component	GO:0048471	perinuclear region of cytoplasm
Molecular Function	GO:0003779	actin binding
Molecular Function	GO:0043014	alpha-tubulin binding
Molecular Function	GO:0042030	ATPase inhibitor activity
Molecular Function	GO:0008013	beta-catenin binding
Molecular Function	GO:0048487	beta-tubulin binding
Molecular Function	GO:0019213	deacetylase activity
Molecular Function	GO:0070840	dynein complex binding
Molecular Function	GO:0019899	enzyme binding
Molecular Function	GO:0004407	histone deacetylase activity
Molecular Function	GO:0042826	histone deacetylase binding
Molecular Function	GO:0051879	Hsp90 protein binding
Molecular Function	GO:0008017	microtubule binding
Molecular Function	GO:0051787	misfolded protein binding
Molecular Function	GO:0036479	peroxidase inhibitor activity
Molecular Function	GO:0031593	polyubiquitin modification-dependent protein binding
Molecular Function	GO:0033558	protein lysine deacetylase activity
Molecular Function	GO:0000978	RNA polymerase II cis-regulatory region sequence-specific DNA binding
Molecular Function	GO:0048156	tau protein binding
Molecular Function	GO:0001222	transcription corepressor binding
Molecular Function	GO:0042903	tubulin deacetylase activity
Molecular Function	GO:0043130	ubiquitin binding
Molecular Function	GO:0061630	ubiquitin protein ligase activity
Molecular Function	GO:0031625	ubiquitin protein ligase binding
Molecular Function	GO:0008270	zinc ion binding
Biological Process	GO:0070842	aggresome assembly
Biological Process	GO:0019896	axonal transport of mitochondrion
Biological Process	GO:0034605	cellular response to heat
Biological Process	GO:0070301	cellular response to hydrogen peroxide
Biological Process	GO:0035967	cellular response to topologically incorrect protein
Biological Process	GO:0060271	cilium assembly
Biological Process	GO:0061523	cilium disassembly
Biological Process	GO:0006351	DNA-templated transcription
Biological Process	GO:0007173	epidermal growth factor receptor signaling pathway
Biological Process	GO:0006886	intracellular protein transport
Biological Process	GO:0032418	lysosome localization
Biological Process	GO:1905336	negative regulation of aggrephagy
Biological Process	GO:0045892	negative regulation of DNA-templated transcription
Biological Process	GO:0045814	negative regulation of gene expression, epigenetic
Biological Process	GO:0010727	negative regulation of hydrogen peroxide metabolic process
Biological Process	GO:0031333	negative regulation of protein-containing complex assembly
Biological Process	GO:0043242	negative regulation of protein-containing complex disassembly
Biological Process	GO:0045861	negative regulation of proteolysis
Biological Process	GO:0070845	polyubiquitinated misfolded protein transport
Biological Process	GO:0010634	positive regulation of epithelial cell migration
Biological Process	GO:0033148	positive regulation of intracellular estrogen receptor signaling pathway
Biological Process	GO:0032461	positive regulation of protein oligomerization
Biological Process	GO:1905091	positive regulation of type 2 mitophagy
Biological Process	GO:0006476	protein deacetylation
Biological Process	GO:0031648	protein destabilization
Biological Process	GO:0006515	protein quality control for misfolded or incompletely synthesized proteins
Biological Process	GO:0060765	regulation of androgen receptor signaling pathway
Biological Process	GO:0010506	regulation of autophagy
Biological Process	GO:1903146	regulation of autophagy of mitochondrion
Biological Process	GO:0016241	regulation of macroautophagy
Biological Process	GO:0060632	regulation of microtubule-based movement
Biological Process	GO:0031647	regulation of protein stability
Biological Process	GO:0051788	response to misfolded protein
Biological Process	GO:0090042	tubulin deacetylation
Biological Process	GO:0061734	type 2 mitophagy

Reference

[1] Yang Z, Yan C, Ma J, Peng P, Ren X et al.. Lactylome analysis suggests lactylation-dependent mechanisms of metabolic adaptation in hepatocellular carcinoma.. Nat Metab 5(1):61-79. 2023 Jan. PMID: 36593272.

[2] Hong H, Chen X, Wang H, Gu X, Yuan Y et al.. Global profiling of protein lysine lactylation and potential target modified protein analysis in hepatocellular carcinoma.. Proteomics 23(9):e2200432. 2023 May. PMID: 36625413.

[3] He C, Zhang J, Bai X, Lu C, Zhang K. Lysine lactylation-based insight to understanding the characterization of cervical cancer.. Biochim Biophys Acta Mol Basis Dis 1870(7):167356. 2024 Oct. PMID: 39025375.

[4] Guo X, Ren X, Yan C, Huang H. Quantitative Proteomics Reveals the Role of Lysine Lactylation in Lenalidomide-Resistance in Multiple Myeloma Cells.. ACS Chem Biol 20(7):1728-1738. 2025 Jul 18. PMID: 40590393.

[5] He J, Lai T, Zhou Z, Yang H, Lei Z et al.. Multiomics profiling reveals the involvement of protein lactylation in nonhomologous end joining pathway conferring radioresistance in lung adenocarcinoma cell.. Sci Rep 15(1):24651. 2025 Jul 9. PMID: 40634431.

[6] Wu Q, Li Z, Gong T, Zheng X, Zhou X et al.. Porphyromonas gingivalis infection induces lysine lactylation reprogramming in human umbilical vein endothelial cells.. Front Cell Infect Microbiol 16:1706727. 2026. PMID: 41696360.