ABHDA_HUMAN
ID ABHDA_HUMAN Reviewed; 306 AA.
AC Q9NUJ1; B7Z6A8; C9IZX5; D3DN63; Q8TCF9;
DT 20-MAR-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 03-AUG-2022, entry version 164.
DE RecName: Full=Palmitoyl-protein thioesterase ABHD10, mitochondrial {ECO:0000303|PubMed:31740833};
DE EC=3.1.2.22 {ECO:0000269|PubMed:31740833};
DE AltName: Full=Acyl-protein thioesterase ABHD10 {ECO:0000303|PubMed:31740833};
DE AltName: Full=Alpha/beta hydrolase domain-containing protein 10 {ECO:0000303|PubMed:22294686};
DE Short=Abhydrolase domain-containing protein 10 {ECO:0000303|PubMed:22294686};
DE AltName: Full=Mycophenolic acid acyl-glucuronide esterase, mitochondrial {ECO:0000303|PubMed:22294686};
DE EC=3.1.1.93 {ECO:0000269|PubMed:22294686};
DE Flags: Precursor;
GN Name=ABHD10 {ECO:0000312|HGNC:HGNC:25656};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Placenta;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16641997; DOI=10.1038/nature04728;
RA Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J.,
RA Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P.,
RA Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A.,
RA Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L.,
RA Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G.,
RA Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W.,
RA Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M.,
RA Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P.,
RA Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H.,
RA Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J.,
RA Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W.,
RA Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B.,
RA Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O.,
RA Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B.,
RA Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H.,
RA Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J.,
RA Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X.,
RA Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R.,
RA Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A.;
RT "The DNA sequence, annotation and analysis of human chromosome 3.";
RL Nature 440:1194-1198(2006).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Ovary;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 73-306 (ISOFORM 1).
RC TISSUE=Melanoma;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [7]
RP FUNCTION, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES.
RC TISSUE=Liver;
RX PubMed=22294686; DOI=10.1074/jbc.m111.271288;
RA Iwamura A., Fukami T., Higuchi R., Nakajima M., Yokoi T.;
RT "Human alpha/beta hydrolase domain containing 10 (ABHD10) is responsible
RT enzyme for deglucuronidation of mycophenolic acid acyl-glucuronide in
RT liver.";
RL J. Biol. Chem. 287:9240-9249(2012).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [10]
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, SUBCELLULAR LOCATION,
RP MUTAGENESIS OF SER-152, AND ACTIVE SITE.
RX PubMed=31740833; DOI=10.1038/s41589-019-0399-y;
RA Cao Y., Qiu T., Kathayat R.S., Azizi S.A., Thorne A.K., Ahn D., Fukata Y.,
RA Fukata M., Rice P.A., Dickinson B.C.;
RT "ABHD10 is an S-depalmitoylase affecting redox homeostasis through
RT peroxiredoxin-5.";
RL Nat. Chem. Biol. 15:1232-1240(2019).
CC -!- FUNCTION: Acts as an acyl-protein thioesterase that hydrolyzes fatty
CC acids from acylated residues in proteins (PubMed:31740833). Regulates
CC the mitochondrial S-depalmitoylation of the nucleophilic active site
CC residue of peroxiredoxin-5/PRDX5, a key antioxidant protein, therefore
CC modulating mitochondrial antioxidant ability (PubMed:31740833). Also
CC catalyzes the deglucuronidation of mycophenolic acid acyl-glucuronide,
CC an active metabolite of the immunosuppressant drug mycophenolate
CC (PubMed:22294686). {ECO:0000269|PubMed:22294686,
CC ECO:0000269|PubMed:31740833}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + S-hexadecanoyl-L-cysteinyl-[protein] = H(+) +
CC hexadecanoate + L-cysteinyl-[protein]; Xref=Rhea:RHEA:19233,
CC Rhea:RHEA-COMP:10131, Rhea:RHEA-COMP:11032, ChEBI:CHEBI:7896,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:29950,
CC ChEBI:CHEBI:74151; EC=3.1.2.22;
CC Evidence={ECO:0000269|PubMed:31740833};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:19234;
CC Evidence={ECO:0000269|PubMed:31740833};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + mycophenolic acid O-acyl-beta-D-glucuronide = D-
CC glucuronate + H(+) + mycophenolate; Xref=Rhea:RHEA:34179,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:58720,
CC ChEBI:CHEBI:62932, ChEBI:CHEBI:66982; EC=3.1.1.93;
CC Evidence={ECO:0000269|PubMed:22294686};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:34180;
CC Evidence={ECO:0000305|PubMed:22294686};
CC -!- ACTIVITY REGULATION: Inhibited by palmostatin-B.
CC {ECO:0000269|PubMed:31740833}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=100.7 uM for mycophenolic acid O-acyl-beta-D-glucuronide
CC {ECO:0000269|PubMed:22294686};
CC Vmax=47.6 nmol/min/mg enzyme with mycophenolic acid O-acyl-beta-D-
CC glucuronide as substrate {ECO:0000269|PubMed:22294686};
CC -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000269|PubMed:31740833}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q9NUJ1-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9NUJ1-2; Sequence=VSP_056093;
CC Name=3;
CC IsoId=Q9NUJ1-3; Sequence=VSP_056742, VSP_056743;
CC -!- SIMILARITY: Belongs to the AB hydrolase superfamily. {ECO:0000305}.
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DR EMBL; AK002204; BAA92133.1; -; mRNA.
DR EMBL; AK300018; BAH13194.1; -; mRNA.
DR EMBL; AC060225; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471052; EAW79688.1; -; Genomic_DNA.
DR EMBL; CH471052; EAW79689.1; -; Genomic_DNA.
DR EMBL; BC014516; AAH14516.1; -; mRNA.
DR EMBL; AL713726; CAD28516.2; -; mRNA.
DR CCDS; CCDS2963.1; -. [Q9NUJ1-1]
DR CCDS; CCDS63718.1; -. [Q9NUJ1-3]
DR RefSeq; NP_001258998.1; NM_001272069.1. [Q9NUJ1-3]
DR RefSeq; NP_060864.1; NM_018394.3. [Q9NUJ1-1]
DR RefSeq; XP_011511262.1; XM_011512960.2. [Q9NUJ1-3]
DR AlphaFoldDB; Q9NUJ1; -.
DR SMR; Q9NUJ1; -.
DR BioGRID; 120628; 79.
DR DIP; DIP-56934N; -.
DR IntAct; Q9NUJ1; 26.
DR MINT; Q9NUJ1; -.
DR STRING; 9606.ENSP00000273359; -.
DR ESTHER; human-ABHD10; ABHD10.
DR MEROPS; S09.062; -.
DR GlyGen; Q9NUJ1; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q9NUJ1; -.
DR PhosphoSitePlus; Q9NUJ1; -.
DR SwissPalm; Q9NUJ1; -.
DR BioMuta; ABHD10; -.
DR DMDM; 74734347; -.
DR EPD; Q9NUJ1; -.
DR jPOST; Q9NUJ1; -.
DR MassIVE; Q9NUJ1; -.
DR MaxQB; Q9NUJ1; -.
DR PaxDb; Q9NUJ1; -.
DR PeptideAtlas; Q9NUJ1; -.
DR PRIDE; Q9NUJ1; -.
DR ProteomicsDB; 6765; -.
DR ProteomicsDB; 7863; -.
DR ProteomicsDB; 82676; -. [Q9NUJ1-1]
DR Antibodypedia; 32454; 76 antibodies from 21 providers.
DR DNASU; 55347; -.
DR Ensembl; ENST00000273359.8; ENSP00000273359.3; ENSG00000144827.9. [Q9NUJ1-1]
DR Ensembl; ENST00000494817.1; ENSP00000418973.1; ENSG00000144827.9. [Q9NUJ1-3]
DR GeneID; 55347; -.
DR KEGG; hsa:55347; -.
DR MANE-Select; ENST00000273359.8; ENSP00000273359.3; NM_018394.4; NP_060864.1.
DR UCSC; uc003dyk.6; human. [Q9NUJ1-1]
DR CTD; 55347; -.
DR DisGeNET; 55347; -.
DR GeneCards; ABHD10; -.
DR HGNC; HGNC:25656; ABHD10.
DR HPA; ENSG00000144827; Low tissue specificity.
DR MIM; 618756; gene.
DR neXtProt; NX_Q9NUJ1; -.
DR OpenTargets; ENSG00000144827; -.
DR PharmGKB; PA134978569; -.
DR VEuPathDB; HostDB:ENSG00000144827; -.
DR eggNOG; ENOG502QT21; Eukaryota.
DR GeneTree; ENSGT00390000017765; -.
DR HOGENOM; CLU_066961_0_0_1; -.
DR InParanoid; Q9NUJ1; -.
DR OMA; TISRWLE; -.
DR OrthoDB; 1106156at2759; -.
DR PhylomeDB; Q9NUJ1; -.
DR TreeFam; TF329757; -.
DR BioCyc; MetaCyc:ENSG00000144827-MON; -.
DR BRENDA; 3.1.1.93; 2681.
DR PathwayCommons; Q9NUJ1; -.
DR Reactome; R-HSA-156588; Glucuronidation.
DR SignaLink; Q9NUJ1; -.
DR BioGRID-ORCS; 55347; 15 hits in 1078 CRISPR screens.
DR ChiTaRS; ABHD10; human.
DR GenomeRNAi; 55347; -.
DR Pharos; Q9NUJ1; Tbio.
DR PRO; PR:Q9NUJ1; -.
DR Proteomes; UP000005640; Chromosome 3.
DR RNAct; Q9NUJ1; protein.
DR Bgee; ENSG00000144827; Expressed in nephron tubule and 201 other tissues.
DR ExpressionAtlas; Q9NUJ1; baseline and differential.
DR Genevisible; Q9NUJ1; HS.
DR GO; GO:0005829; C:cytosol; IDA:BHF-UCL.
DR GO; GO:0005759; C:mitochondrial matrix; TAS:Reactome.
DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB.
DR GO; GO:0004553; F:hydrolase activity, hydrolyzing O-glycosyl compounds; IDA:BHF-UCL.
DR GO; GO:0102390; F:mycophenolic acid acyl-glucuronide esterase activity; IEA:UniProtKB-EC.
DR GO; GO:0008474; F:palmitoyl-(protein) hydrolase activity; IDA:UniProtKB.
DR GO; GO:0052695; P:cellular glucuronidation; TAS:Reactome.
DR GO; GO:0019391; P:glucuronoside catabolic process; IDA:BHF-UCL.
DR GO; GO:0002084; P:protein depalmitoylation; IDA:UniProtKB.
DR Gene3D; 3.40.50.1820; -; 1.
DR InterPro; IPR029058; AB_hydrolase.
DR InterPro; IPR000073; AB_hydrolase_1.
DR Pfam; PF00561; Abhydrolase_1; 1.
DR SUPFAM; SSF53474; SSF53474; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Hydrolase; Mitochondrion; Reference proteome;
KW Transit peptide.
FT TRANSIT 1..52
FT /note="Mitochondrion"
FT /evidence="ECO:0000255"
FT CHAIN 53..306
FT /note="Palmitoyl-protein thioesterase ABHD10,
FT mitochondrial"
FT /id="PRO_0000280733"
FT DOMAIN 78..178
FT /note="AB hydrolase-1"
FT /evidence="ECO:0000255"
FT ACT_SITE 152
FT /note="Charge relay system"
FT /evidence="ECO:0000305|PubMed:31740833"
FT ACT_SITE 249
FT /note="Charge relay system"
FT /evidence="ECO:0000250|UniProtKB:Q8N2K0"
FT ACT_SITE 279
FT /note="Charge relay system"
FT /evidence="ECO:0000250|UniProtKB:Q8N2K0"
FT VAR_SEQ 1..157
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_056093"
FT VAR_SEQ 193..205
FT /note="LKKEVEMKGVWSM -> DSGRKNYISLHSA (in isoform 3)"
FT /evidence="ECO:0000305"
FT /id="VSP_056742"
FT VAR_SEQ 206..306
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000305"
FT /id="VSP_056743"
FT VARIANT 251
FT /note="I -> V (in dbSNP:rs17429033)"
FT /id="VAR_031194"
FT MUTAGEN 152
FT /note="S->A: Loss of palmitoyl-(protein) hydrolase
FT activity."
FT /evidence="ECO:0000269|PubMed:31740833"
SQ SEQUENCE 306 AA; 33933 MW; E41139D5C22A83FE CRC64;
MAVARLAAVA AWVPCRSWGW AAVPFGPHRG LSVLLARIPQ RAPRWLPACR QKTSLSFLNR
PDLPNLAYKK LKGKSPGIIF IPGYLSYMNG TKALAIEEFC KSLGHACIRF DYSGVGSSDG
NSEESTLGKW RKDVLSIIDD LADGPQILVG SSLGGWLMLH AAIARPEKVV ALIGVATAAD
TLVTKFNQLP VELKKEVEMK GVWSMPSKYS EEGVYNVQYS FIKEAEHHCL LHSPIPVNCP
IRLLHGMKDD IVPWHTSMQV ADRVLSTDVD VILRKHSDHR MREKADIQLL VYTIDDLIDK
LSTIVN
