UniProtKB - Q969S8 (HDA10_HUMAN)
Protein
Polyamine deacetylase HDAC10
Gene
HDAC10
Organism
Homo sapiens (Human)
Status
Functioni
Polyamine deacetylase (PDAC), which acts preferentially on N8-acetylspermidine, and also on acetylcadaverine and acetylputrescine (PubMed:28516954). Exhibits attenuated catalytic activity toward N1,N8-diacetylspermidine and very low activity, if any, toward N1-acetylspermidine (PubMed:28516954). Histone deacetylase activity has been observed in vitro (PubMed:11861901, PubMed:11726666, PubMed:11677242, PubMed:11739383). Has also been shown to be involved in MSH2 deacetylation (PubMed:26221039). The physiological relevance of protein/histone deacetylase activity is unclear and could be very weak (PubMed:28516954). May play a role in the promotion of late stages of autophagy, possibly autophagosome-lysosome fusion and/or lysosomal exocytosis in neuroblastoma cells (PubMed:23801752, PubMed:29968769). May play a role in homologous recombination (PubMed:21247901). May promote DNA mismatch repair (PubMed:26221039).9 Publications
Miscellaneous
Like some other members of the HD type 2 subfamily, such as HDAC4, inhibited by the antitumor drug trichostatin A (TSA).1 Publication
Caution
Protein/histone deacetylase activity in vivo is uncertain. The 3D structure analysis of the zebrafish ortholog shows that a glutamate gatekeeper and a sterically constricted active site confer specificity for N8-acetylspermidine hydrolysis and disfavour acetyllysine hydrolysis. Supporting this observation, has been shown to exhibit only very low activity, if any, towards acetyl-lysine peptide substrates (PubMed:28516954). However, histone deacetylase activity has been observed in vitro (PubMed:28516954, PubMed:11861901, PubMed:11726666, PubMed:11677242, PubMed:11739383). Has also been shown to be involved in MSH2 deacetylation (PubMed:26221039).6 Publications
Catalytic activityi
Kineticsi
- KM=110 µM for acetylcadaverine1 Publication
- KM=170 µM for acetylputrescine1 Publication
- KM=100 µM for N8-acetylspermidine1 Publication
- KM=180 µM for N1-acetylspermine1 Publication
- KM=150 µM for N1,N8-diacetylspermidine1 Publication
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Binding sitei | 20 | SubstrateBy similarity | 1 | |
Active sitei | 135 | Proton donor/acceptorBy similarity | 1 | |
Metal bindingi | 172 | ZincBy similarity | 1 | |
Metal bindingi | 174 | Zinc; via pros nitrogenBy similarity | 1 | |
Metal bindingi | 265 | ZincBy similarity | 1 | |
Sitei | 272 | Substrate specificityBy similarity | 1 | |
Binding sitei | 305 | SubstrateBy similarity | 1 |
GO - Molecular functioni
- acetylputrescine deacetylase activity Source: UniProtKB-EC
- acetylspermidine deacetylase activity Source: UniProtKB-EC
- deacetylase activity Source: UniProtKB
- enzyme binding Source: UniProtKB
- histone deacetylase activity Source: UniProtKB
- histone deacetylase binding Source: UniProtKB
- protein deacetylase activity Source: UniProtKB
- zinc ion binding Source: UniProtKB
GO - Biological processi
- chromatin organization Source: UniProtKB
- DNA repair Source: UniProtKB-KW
- histone deacetylation Source: UniProtKB
- homologous recombination Source: UniProtKB
- macroautophagy Source: UniProtKB
- negative regulation of transcription, DNA-templated Source: UniProtKB
- negative regulation of transcription by RNA polymerase II Source: UniProtKB
- oligodendrocyte development Source: Ensembl
- peptidyl-lysine deacetylation Source: UniProtKB
- polyamine deacetylation Source: UniProtKB
- positive regulation of mismatch repair Source: UniProtKB
- protein deacetylation Source: UniProtKB
- regulation of transcription, DNA-templated Source: UniProtKB
- spermidine deacetylation Source: UniProtKB
Keywordsi
Molecular function | Hydrolase |
Biological process | Autophagy, DNA damage, DNA recombination, DNA repair |
Ligand | Metal-binding, Zinc |
Enzyme and pathway databases
BRENDAi | 3.5.1.98, 2681 |
PathwayCommonsi | Q969S8 |
Reactomei | R-HSA-2122947, NOTCH1 Intracellular Domain Regulates Transcription R-HSA-2644606, Constitutive Signaling by NOTCH1 PEST Domain Mutants R-HSA-2894862, Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants R-HSA-3214815, HDACs deacetylate histones R-HSA-350054, Notch-HLH transcription pathway |
SABIO-RKi | Q969S8 |
SIGNORi | Q969S8 |
Names & Taxonomyi
Protein namesi | |
Gene namesi | Name:HDAC10 |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
EuPathDBi | HostDB:ENSG00000100429.17 |
HGNCi | HGNC:18128, HDAC10 |
MIMi | 608544, gene |
neXtProti | NX_Q969S8 |
Subcellular locationi
Nucleus
- histone deacetylase complex Source: UniProtKB
- nucleoplasm Source: UniProtKB
- nucleus Source: UniProtKB
Other locations
- cytoplasm Source: UniProtKB
Keywords - Cellular componenti
Cytoplasm, NucleusPathology & Biotechi
Involvement in diseasei
In neuroblastoma cells, may promote autophagy in response to chemotherapy-induced DNA damage and efflux of chemotherapeutics via lysosomal exocytosis, hence protecting cells from cytotoxic agents (PubMed:23801752, PubMed:29968769). Expression levels may correlate with survival in neuroblastoma patients, with low levels in the tumor correlating with long-term patient survival and high expression with poor prognosis (PubMed:23801752). Therefore has been proposed as a biomarker to predict neuroblastoma chemoresistance and treatment outcome (PubMed:23801752).1 Publication2 Publications
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 135 | H → A: Abolishes deacetylase activity. Does not affect interaction with HDAC3. Loss of autophagy regulation. 3 Publications | 1 |
Organism-specific databases
DisGeNETi | 83933 |
OpenTargetsi | ENSG00000100429 |
PharmGKBi | PA38297 |
Miscellaneous databases
Pharosi | Q969S8, Tclin |
Chemistry databases
ChEMBLi | CHEMBL5103 |
DrugBanki | DB05015, Belinostat DB13346, Bufexamac DB06603, Panobinostat |
DrugCentrali | Q969S8 |
GuidetoPHARMACOLOGYi | 2614 |
Polymorphism and mutation databases
BioMutai | HDAC10 |
DMDMi | 27734403 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000114712 | 1 – 669 | Polyamine deacetylase HDAC10Add BLAST | 669 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 393 | PhosphoserineCombined sources | 1 |
Keywords - PTMi
PhosphoproteinProteomic databases
jPOSTi | Q969S8 |
MassIVEi | Q969S8 |
MaxQBi | Q969S8 |
PaxDbi | Q969S8 |
PeptideAtlasi | Q969S8 |
PRIDEi | Q969S8 |
ProteomicsDBi | 75833 [Q969S8-1] 75834 [Q969S8-2] 75835 [Q969S8-4] 75836 [Q969S8-5] |
PTM databases
iPTMneti | Q969S8 |
PhosphoSitePlusi | Q969S8 |
Expressioni
Tissue specificityi
Widely expressed with high levels in liver and kidney.3 Publications
Gene expression databases
Bgeei | ENSG00000100429, Expressed in granulocyte and 173 other tissues |
ExpressionAtlasi | Q969S8, baseline and differential |
Genevisiblei | Q969S8, HS |
Organism-specific databases
HPAi | ENSG00000100429, Low tissue specificity |
Interactioni
Subunit structurei
Binary interactionsi
Q969S8
With | #Exp. | IntAct |
---|---|---|
TRIM54 [Q9BYV2] | 2 | EBI-301762,EBI-2130429 |
GO - Molecular functioni
- enzyme binding Source: UniProtKB
- histone deacetylase binding Source: UniProtKB
Protein-protein interaction databases
BioGRIDi | 123818, 39 interactors |
CORUMi | Q969S8 |
IntActi | Q969S8, 23 interactors |
STRINGi | 9606.ENSP00000216271 |
Chemistry databases
BindingDBi | Q969S8 |
Miscellaneous databases
RNActi | Q969S8, protein |
Family & Domainsi
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 1 – 323 | Histone deacetylaseAdd BLAST | 323 |
Motif
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Motifi | 21 – 24 | Substrate specificityBy similarity | 4 |
Sequence similaritiesi
Phylogenomic databases
eggNOGi | KOG1343, Eukaryota |
GeneTreei | ENSGT00940000160061 |
HOGENOMi | CLU_007727_6_0_1 |
InParanoidi | Q969S8 |
OMAi | DDGRNLW |
OrthoDBi | 1484694at2759 |
PhylomeDBi | Q969S8 |
TreeFami | TF106173 |
Family and domain databases
Gene3Di | 3.40.800.20, 2 hits |
InterProi | View protein in InterPro IPR000286, His_deacetylse IPR023801, His_deacetylse_dom IPR037138, His_deacetylse_dom_sf IPR023696, Ureohydrolase_dom_sf |
Pfami | View protein in Pfam PF00850, Hist_deacetyl, 1 hit |
PRINTSi | PR01270, HDASUPER |
SUPFAMi | SSF52768, SSF52768, 2 hits |
s (4+)i Sequence
Sequence statusi: Complete.
This entry describes 4 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 4 described isoforms and 2 potential isoforms that are computationally mapped.Show allAlign All
Isoform 1 (identifier: Q969S8-1) [UniParc]FASTAAdd to basket
Also known as: Alpha1 Publication, HDAC10b1 Publication, HDAC10v11 Publication
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
10 20 30 40 50
MGTALVYHED MTATRLLWDD PECEIERPER LTAALDRLRQ RGLEQRCLRL
60 70 80 90 100
SAREASEEEL GLVHSPEYVS LVRETQVLGK EELQALSGQF DAIYFHPSTF
110 120 130 140 150
HCARLAAGAG LQLVDAVLTG AVQNGLALVR PPGHHGQRAA ANGFCVFNNV
160 170 180 190 200
AIAAAHAKQK HGLHRILVVD WDVHHGQGIQ YLFEDDPSVL YFSWHRYEHG
210 220 230 240 250
RFWPFLRESD ADAVGRGQGL GFTVNLPWNQ VGMGNADYVA AFLHLLLPLA
260 270 280 290 300
FEFDPELVLV SAGFDSAIGD PEGQMQATPE CFAHLTQLLQ VLAGGRVCAV
310 320 330 340 350
LEGGYHLESL AESVCMTVQT LLGDPAPPLS GPMAPCQSAL ESIQSARAAQ
360 370 380 390 400
APHWKSLQQQ DVTAVPMSPS SHSPEGRPPP LLPGGPVCKA AASAPSSLLD
410 420 430 440 450
QPCLCPAPSV RTAVALTTPD ITLVLPPDVI QQEASALREE TEAWARPHES
460 470 480 490 500
LAREEALTAL GKLLYLLDGM LDGQVNSGIA ATPASAAAAT LDVAVRRGLS
510 520 530 540 550
HGAQRLLCVA LGQLDRPPDL AHDGRSLWLN IRGKEAAALS MFHVSTPLPV
560 570 580 590 600
MTGGFLSCIL GLVLPLAYGF QPDLVLVALG PGHGLQGPHA ALLAAMLRGL
610 620 630 640 650
AGGRVLALLE ENSTPQLAGI LARVLNGEAP PSLGPSSVAS PEDVQALMYL
660
RGQLEPQWKM LQCHPHLVA
Isoform 4 (identifier: Q969S8-4) [UniParc]FASTAAdd to basket
Also known as: A, HDAC10v21 Publication
The sequence of this isoform differs from the canonical sequence as follows:
612-669: NSTPQLAGIL...MLQCHPHLVA → VSWAGWRCCG...GPGAEWRGTS
Note: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.Curated
Show »Computationally mapped potential isoform sequencesi
There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketC9J8B8 | C9J8B8_HUMAN | Polyamine deacetylase HDAC10 | HDAC10 | 619 | Annotation score: | ||
Q08AP5 | Q08AP5_HUMAN | HDAC10 protein | HDAC10 | 96 | Annotation score: |
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 92 | A → T in AAS48345 (Ref. 6) Curated | 1 | |
Sequence conflicti | 177 | Q → R in AAS48345 (Ref. 6) Curated | 1 | |
Sequence conflicti | 337 | Q → QRC in CAC21653 (PubMed:17974005).Curated | 1 | |
Sequence conflicti | 337 | Q → QRCEG no nucleotide entry (PubMed:11739383).Curated | 1 | |
Sequence conflicti | 594 | A → T in AAK92205 (PubMed:11677242).Curated | 1 | |
Sequence conflicti | 594 | A → T in AAK92206 (PubMed:11677242).Curated | 1 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_049356 | 429 | V → I. Corresponds to variant dbSNP:rs34402301Ensembl. | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_014698 | 252 – 301 | Missing in isoform 5. 1 PublicationAdd BLAST | 50 | |
Alternative sequenceiVSP_002089 | 252 – 271 | Missing in isoform 2. 1 PublicationAdd BLAST | 20 | |
Alternative sequenceiVSP_014699 | 447 – 669 | Missing in isoform 5. 1 PublicationAdd BLAST | 223 | |
Alternative sequenceiVSP_002090 | 612 – 669 | NSTPQ…PHLVA → VSWAGWRCCGVGRGKGPVTA SVFAPGPELHTPASRDPGPG AEWRGTS in isoform 4. 2 PublicationsAdd BLAST | 58 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AF426160 mRNA Translation: AAL30513.1 AF393962 mRNA Translation: AAK84023.1 AF407272 mRNA Translation: AAK92205.1 AF407273 mRNA Translation: AAK92206.1 CR456465 mRNA Translation: CAG30351.1 AY450395 mRNA Translation: AAS48345.1 AL022328 Genomic DNA No translation available. BC125083 mRNA Translation: AAI25084.1 AL512711 mRNA Translation: CAC21653.2 |
CCDSi | CCDS14088.1 [Q969S8-1] CCDS54545.1 [Q969S8-2] |
RefSeqi | NP_001152758.1, NM_001159286.1 [Q969S8-2] NP_114408.3, NM_032019.5 [Q969S8-1] |
Genome annotation databases
Ensembli | ENST00000216271; ENSP00000216271; ENSG00000100429 [Q969S8-1] ENST00000349505; ENSP00000343540; ENSG00000100429 [Q969S8-2] ENST00000454936; ENSP00000406150; ENSG00000100429 [Q969S8-5] |
GeneIDi | 83933 |
KEGGi | hsa:83933 |
UCSCi | uc003bkg.4, human [Q969S8-1] |
Keywords - Coding sequence diversityi
Alternative splicing, PolymorphismSimilar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AF426160 mRNA Translation: AAL30513.1 AF393962 mRNA Translation: AAK84023.1 AF407272 mRNA Translation: AAK92205.1 AF407273 mRNA Translation: AAK92206.1 CR456465 mRNA Translation: CAG30351.1 AY450395 mRNA Translation: AAS48345.1 AL022328 Genomic DNA No translation available. BC125083 mRNA Translation: AAI25084.1 AL512711 mRNA Translation: CAC21653.2 |
CCDSi | CCDS14088.1 [Q969S8-1] CCDS54545.1 [Q969S8-2] |
RefSeqi | NP_001152758.1, NM_001159286.1 [Q969S8-2] NP_114408.3, NM_032019.5 [Q969S8-1] |
3D structure databases
SMRi | Q969S8 |
ModBasei | Search... |
Protein-protein interaction databases
BioGRIDi | 123818, 39 interactors |
CORUMi | Q969S8 |
IntActi | Q969S8, 23 interactors |
STRINGi | 9606.ENSP00000216271 |
Chemistry databases
BindingDBi | Q969S8 |
ChEMBLi | CHEMBL5103 |
DrugBanki | DB05015, Belinostat DB13346, Bufexamac DB06603, Panobinostat |
DrugCentrali | Q969S8 |
GuidetoPHARMACOLOGYi | 2614 |
PTM databases
iPTMneti | Q969S8 |
PhosphoSitePlusi | Q969S8 |
Polymorphism and mutation databases
BioMutai | HDAC10 |
DMDMi | 27734403 |
Proteomic databases
jPOSTi | Q969S8 |
MassIVEi | Q969S8 |
MaxQBi | Q969S8 |
PaxDbi | Q969S8 |
PeptideAtlasi | Q969S8 |
PRIDEi | Q969S8 |
ProteomicsDBi | 75833 [Q969S8-1] 75834 [Q969S8-2] 75835 [Q969S8-4] 75836 [Q969S8-5] |
Protocols and materials databases
Antibodypediai | 14233, 469 antibodies |
DNASUi | 83933 |
Genome annotation databases
Ensembli | ENST00000216271; ENSP00000216271; ENSG00000100429 [Q969S8-1] ENST00000349505; ENSP00000343540; ENSG00000100429 [Q969S8-2] ENST00000454936; ENSP00000406150; ENSG00000100429 [Q969S8-5] |
GeneIDi | 83933 |
KEGGi | hsa:83933 |
UCSCi | uc003bkg.4, human [Q969S8-1] |
Organism-specific databases
CTDi | 83933 |
DisGeNETi | 83933 |
EuPathDBi | HostDB:ENSG00000100429.17 |
GeneCardsi | HDAC10 |
HGNCi | HGNC:18128, HDAC10 |
HPAi | ENSG00000100429, Low tissue specificity |
MIMi | 608544, gene |
neXtProti | NX_Q969S8 |
OpenTargetsi | ENSG00000100429 |
PharmGKBi | PA38297 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG1343, Eukaryota |
GeneTreei | ENSGT00940000160061 |
HOGENOMi | CLU_007727_6_0_1 |
InParanoidi | Q969S8 |
OMAi | DDGRNLW |
OrthoDBi | 1484694at2759 |
PhylomeDBi | Q969S8 |
TreeFami | TF106173 |
Enzyme and pathway databases
BRENDAi | 3.5.1.98, 2681 |
PathwayCommonsi | Q969S8 |
Reactomei | R-HSA-2122947, NOTCH1 Intracellular Domain Regulates Transcription R-HSA-2644606, Constitutive Signaling by NOTCH1 PEST Domain Mutants R-HSA-2894862, Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants R-HSA-3214815, HDACs deacetylate histones R-HSA-350054, Notch-HLH transcription pathway |
SABIO-RKi | Q969S8 |
SIGNORi | Q969S8 |
Miscellaneous databases
BioGRID-ORCSi | 83933, 0 hits in 847 CRISPR screens |
ChiTaRSi | HDAC10, human |
GeneWikii | HDAC10 |
GenomeRNAii | 83933 |
Pharosi | Q969S8, Tclin |
PROi | PR:Q969S8 |
RNActi | Q969S8, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000100429, Expressed in granulocyte and 173 other tissues |
ExpressionAtlasi | Q969S8, baseline and differential |
Genevisiblei | Q969S8, HS |
Family and domain databases
Gene3Di | 3.40.800.20, 2 hits |
InterProi | View protein in InterPro IPR000286, His_deacetylse IPR023801, His_deacetylse_dom IPR037138, His_deacetylse_dom_sf IPR023696, Ureohydrolase_dom_sf |
Pfami | View protein in Pfam PF00850, Hist_deacetyl, 1 hit |
PRINTSi | PR01270, HDASUPER |
SUPFAMi | SSF52768, SSF52768, 2 hits |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | HDA10_HUMAN | |
Accessioni | Q969S8Primary (citable) accession number: Q969S8 Secondary accession number(s): Q08AP4 Q9UGX2 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | January 10, 2003 |
Last sequence update: | December 1, 2001 | |
Last modified: | December 2, 2020 | |
This is version 166 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. |
Miscellaneousi
Keywords - Technical termi
Reference proteomeDocuments
- Human polymorphisms and disease mutations
Index of human polymorphisms and disease mutations - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - SIMILARITY comments
Index of protein domains and families - Human chromosome 22
Human chromosome 22: entries, gene names and cross-references to MIM - Human entries with polymorphisms or disease mutations
List of human entries with polymorphisms or disease mutations