AB17A_HUMAN
ID AB17A_HUMAN Reviewed; 310 AA.
AC Q96GS6; A8K0G8; D6W5Z9; Q6PJU2; Q8WUH9; Q9BWL0; Q9H7Q9;
DT 24-JUL-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2001, sequence version 1.
DT 03-AUG-2022, entry version 163.
DE RecName: Full=Alpha/beta hydrolase domain-containing protein 17A {ECO:0000305};
DE Short=Abhydrolase domain-containing protein 17A {ECO:0000312|HGNC:HGNC:28756};
DE EC=3.1.2.22 {ECO:0000269|PubMed:26701913};
GN Name=ABHD17A {ECO:0000312|HGNC:HGNC:28756}; Synonyms=C19orf27, FAM108A1;
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] (ISOFORM 4).
RC TISSUE=Cerebellum, and Spleen;
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 MRNA] (ISOFORM 1).
RC TISSUE=Embryo;
RX PubMed=16303743; DOI=10.1093/dnares/12.2.117;
RA Otsuki T., Ota T., Nishikawa T., Hayashi K., Suzuki Y., Yamamoto J.,
RA Wakamatsu A., Kimura K., Sakamoto K., Hatano N., Kawai Y., Ishii S.,
RA Saito K., Kojima S., Sugiyama T., Ono T., Okano K., Yoshikawa Y.,
RA Aotsuka S., Sasaki N., Hattori A., Okumura K., Nagai K., Sugano S.,
RA Isogai T.;
RT "Signal sequence and keyword trap in silico for selection of full-length
RT human cDNAs encoding secretion or membrane proteins from oligo-capped cDNA
RT libraries.";
RL DNA Res. 12:117-126(2005).
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] (ISOFORMS 1; 2 AND 3).
RC TISSUE=Brain, Cervix, Colon, Muscle, Ovary, Prostate, and Skin;
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 PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-307, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [6]
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, SUBCELLULAR LOCATION,
RP MOTIF, PALMITOYLATION, ACTIVE SITE, AND MUTAGENESIS OF 1-MET--PRO-19 AND
RP SER-190.
RX PubMed=26701913; DOI=10.7554/elife.11306;
RA Lin D.T., Conibear E.;
RT "ABHD17 proteins are novel protein depalmitoylases that regulate N-Ras
RT palmitate turnover and subcellular localization.";
RL Elife 4:E11306-E11306(2015).
CC -!- FUNCTION: Hydrolyzes fatty acids from S-acylated cysteine residues in
CC proteins (PubMed:26701913). Has depalmitoylating activity towards NRAS
CC (PubMed:26701913). Has depalmitoylating activity towards DLG4/PSD95
CC (PubMed:26701913). May have depalmitoylating activity towards MAP6 (By
CC similarity). {ECO:0000250|UniProtKB:Q5XIJ5,
CC ECO:0000269|PubMed:26701913}.
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:26701913};
CC -!- ACTIVITY REGULATION: Inhibited by palmostatin-B.
CC {ECO:0000269|PubMed:26701913}.
CC -!- INTERACTION:
CC Q96GS6; O60760: HPGDS; NbExp=4; IntAct=EBI-2870273, EBI-10187349;
CC Q96GS6; P09022: Hoxa1; Xeno; NbExp=3; IntAct=EBI-2870273, EBI-3957603;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:26701913};
CC Lipid-anchor {ECO:0000269|PubMed:26701913}; Cytoplasmic side
CC {ECO:0000269|PubMed:26701913}. Endosome membrane
CC {ECO:0000269|PubMed:26701913}; Lipid-anchor
CC {ECO:0000269|PubMed:26701913}; Cytoplasmic side
CC {ECO:0000269|PubMed:26701913}. Cell projection, dendritic spine
CC {ECO:0000250|UniProtKB:Q5XIJ5}. Postsynaptic density membrane
CC {ECO:0000250|UniProtKB:Q5XIJ5}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1;
CC IsoId=Q96GS6-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q96GS6-2; Sequence=VSP_027268;
CC Name=3;
CC IsoId=Q96GS6-3; Sequence=VSP_027269, VSP_027270;
CC Name=4;
CC IsoId=Q96GS6-4; Sequence=VSP_027271;
CC -!- PTM: Palmitoylated on cysteine residues located in a cysteine cluster
CC at the N-terminus which promotes membrane localization
CC (PubMed:26701913). Palmitoylation is required for post-synaptic
CC localization and for depalmitoylating activity towards DLG4/PSD95 (By
CC similarity). {ECO:0000250|UniProtKB:Q7M759,
CC ECO:0000305|PubMed:26701913}.
CC -!- SIMILARITY: Belongs to the AB hydrolase superfamily. ABHD17 family.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAB15709.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC Sequence=BAB84869.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC Sequence=BAC03419.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AK024419; BAB15709.1; ALT_INIT; mRNA.
DR EMBL; AK074043; BAB84869.1; ALT_INIT; mRNA.
DR EMBL; AK289533; BAF82222.1; -; mRNA.
DR EMBL; AK090438; BAC03419.1; ALT_INIT; mRNA.
DR EMBL; AK074548; BAC11052.1; -; mRNA.
DR EMBL; CH471139; EAW69441.1; -; Genomic_DNA.
DR EMBL; CH471139; EAW69444.1; -; Genomic_DNA.
DR EMBL; CH471139; EAW69446.1; -; Genomic_DNA.
DR EMBL; BC000158; AAH00158.1; -; mRNA.
DR EMBL; BC009256; AAH09256.1; -; mRNA.
DR EMBL; BC011667; AAH11667.1; -; mRNA.
DR EMBL; BC020512; AAH20512.1; -; mRNA.
DR EMBL; BC033749; AAH33749.1; -; mRNA.
DR EMBL; BC035961; AAH35961.1; -; mRNA.
DR EMBL; BC071644; AAH71644.1; -; mRNA.
DR EMBL; BC071876; AAH71876.1; -; mRNA.
DR EMBL; BC094816; AAH94816.1; -; mRNA.
DR CCDS; CCDS32867.1; -. [Q96GS6-2]
DR CCDS; CCDS45902.1; -. [Q96GS6-1]
DR RefSeq; NP_001123583.1; NM_001130111.1. [Q96GS6-1]
DR RefSeq; NP_112490.3; NM_031213.3. [Q96GS6-2]
DR RefSeq; XP_011526640.1; XM_011528338.1. [Q96GS6-2]
DR RefSeq; XP_016882830.1; XM_017027341.1.
DR AlphaFoldDB; Q96GS6; -.
DR SMR; Q96GS6; -.
DR BioGRID; 123627; 45.
DR IntAct; Q96GS6; 21.
DR MINT; Q96GS6; -.
DR ESTHER; human-ABHD17A; ABHD17-depalmitoylase.
DR MEROPS; S09.052; -.
DR TCDB; 4.C.3.2.1; the acyl-coa thioesterase (acoa-t) family.
DR TCDB; 8.A.161.1.1; the acyl protein thioesterase (apte) family.
DR iPTMnet; Q96GS6; -.
DR PhosphoSitePlus; Q96GS6; -.
DR SwissPalm; Q96GS6; -.
DR BioMuta; ABHD17A; -.
DR DMDM; 74751891; -.
DR EPD; Q96GS6; -.
DR jPOST; Q96GS6; -.
DR MassIVE; Q96GS6; -.
DR MaxQB; Q96GS6; -.
DR PeptideAtlas; Q96GS6; -.
DR PRIDE; Q96GS6; -.
DR ProteomicsDB; 76661; -. [Q96GS6-1]
DR ProteomicsDB; 76662; -. [Q96GS6-2]
DR ProteomicsDB; 76663; -. [Q96GS6-3]
DR ProteomicsDB; 76664; -. [Q96GS6-4]
DR Antibodypedia; 53691; 49 antibodies from 15 providers.
DR DNASU; 81926; -.
DR Ensembl; ENST00000250974.9; ENSP00000250974.9; ENSG00000129968.17. [Q96GS6-2]
DR Ensembl; ENST00000292577.12; ENSP00000292577.6; ENSG00000129968.17. [Q96GS6-1]
DR Ensembl; ENST00000676686.1; ENSP00000504042.1; ENSG00000129968.17. [Q96GS6-1]
DR GeneID; 81926; -.
DR KEGG; hsa:81926; -.
DR MANE-Select; ENST00000292577.12; ENSP00000292577.6; NM_001130111.2; NP_001123583.1.
DR UCSC; uc002luf.4; human. [Q96GS6-1]
DR CTD; 81926; -.
DR GeneCards; ABHD17A; -.
DR HGNC; HGNC:28756; ABHD17A.
DR HPA; ENSG00000129968; Low tissue specificity.
DR MIM; 617942; gene.
DR neXtProt; NX_Q96GS6; -.
DR OpenTargets; ENSG00000129968; -.
DR PharmGKB; PA134947443; -.
DR VEuPathDB; HostDB:ENSG00000129968; -.
DR GeneTree; ENSGT00940000155854; -.
DR HOGENOM; CLU_029375_5_4_1; -.
DR InParanoid; Q96GS6; -.
DR OMA; NDIVCMY; -.
DR OrthoDB; 691954at2759; -.
DR PhylomeDB; Q96GS6; -.
DR TreeFam; TF314365; -.
DR PathwayCommons; Q96GS6; -.
DR Reactome; R-HSA-9648002; RAS processing.
DR SignaLink; Q96GS6; -.
DR BioGRID-ORCS; 81926; 119 hits in 1065 CRISPR screens.
DR ChiTaRS; ABHD17A; human.
DR GenomeRNAi; 81926; -.
DR Pharos; Q96GS6; Tbio.
DR PRO; PR:Q96GS6; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; Q96GS6; protein.
DR Bgee; ENSG00000129968; Expressed in granulocyte and 96 other tissues.
DR ExpressionAtlas; Q96GS6; baseline and differential.
DR Genevisible; Q96GS6; HS.
DR GO; GO:0099031; C:anchored component of postsynaptic density membrane; IEA:Ensembl.
DR GO; GO:0099033; C:anchored component of postsynaptic recycling endosome membrane; IEA:Ensembl.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0043197; C:dendritic spine; IEA:UniProtKB-SubCell.
DR GO; GO:0010008; C:endosome membrane; IDA:UniProtKB.
DR GO; GO:0098978; C:glutamatergic synapse; IEA:Ensembl.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0016607; C:nuclear speck; IDA:HPA.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0055038; C:recycling endosome membrane; IEA:Ensembl.
DR GO; GO:0008474; F:palmitoyl-(protein) hydrolase activity; IMP:UniProtKB.
DR GO; GO:1902817; P:negative regulation of protein localization to microtubule; IEA:Ensembl.
DR GO; GO:1905668; P:positive regulation of protein localization to endosome; IEA:Ensembl.
DR GO; GO:0002084; P:protein depalmitoylation; IMP:UniProtKB.
DR GO; GO:0072657; P:protein localization to membrane; IMP:UniProtKB.
DR GO; GO:0099175; P:regulation of postsynapse organization; IBA:GO_Central.
DR Gene3D; 3.40.50.1820; -; 1.
DR InterPro; IPR029058; AB_hydrolase.
DR InterPro; IPR022742; Hydrolase_4.
DR Pfam; PF12146; Hydrolase_4; 1.
DR SUPFAM; SSF53474; SSF53474; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell membrane; Cell projection; Endosome; Hydrolase;
KW Lipoprotein; Membrane; Palmitate; Phosphoprotein;
KW Postsynaptic cell membrane; Reference proteome; Synapse.
FT CHAIN 1..310
FT /note="Alpha/beta hydrolase domain-containing protein 17A"
FT /id="PRO_0000297509"
FT ACT_SITE 190
FT /note="Charge relay system"
FT /evidence="ECO:0000305|PubMed:26701913"
FT ACT_SITE 255
FT /note="Charge relay system"
FT /evidence="ECO:0000250|UniProtKB:O75608"
FT ACT_SITE 284
FT /note="Charge relay system"
FT /evidence="ECO:0000250|UniProtKB:O75608"
FT MOD_RES 307
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19690332"
FT VAR_SEQ 109
FT /note="G -> GARQGHQAQGGHPQLAWVGRLGDSNNPAPGGCLLGKSWGTGAALACG
FT YIHLL (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_027268"
FT VAR_SEQ 177..310
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_027271"
FT VAR_SEQ 236
FT /note="N -> K (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_027269"
FT VAR_SEQ 237..310
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_027270"
FT MUTAGEN 1..19
FT /note="Missing: Reduces catalytic activity. Loss of
FT membrane localization. No effect on NRAS plasma membrane
FT localization."
FT /evidence="ECO:0000269|PubMed:26701913"
FT MUTAGEN 190
FT /note="S->A: Loss of catalytic activity. No effect on its
FT localization. No effect on NRAS plasma membrane
FT localization."
FT /evidence="ECO:0000269|PubMed:26701913"
FT CONFLICT 98
FT /note="R -> H (in Ref. 4; AAH00158/AAH11667)"
FT /evidence="ECO:0000305"
FT CONFLICT Q96GS6-2:144
FT /note="K -> E (in Ref. 4; AAH20512)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 310 AA; 33990 MW; 35FC521C6C245BA0 CRC64;
MNGLSLSELC CLFCCPPCPG RIAAKLAFLP PEATYSLVPE PEPGPGGAGA APLGTLRASS
GAPGRWKLHL TERADFQYSQ RELDTIEVFP TKSARGNRVS CMYVRCVPGA RYTVLFSHGN
AVDLGQMSSF YIGLGSRLHC NIFSYDYSGY GASSGRPSER NLYADIDAAW QALRTRYGIS
PDSIILYGQS IGTVPTVDLA SRYECAAVVL HSPLTSGMRV AFPDTKKTYC FDAFPNIEKV
SKITSPVLII HGTEDEVIDF SHGLALYERC PKAVEPLWVE GAGHNDIELY SQYLERLRRF
ISQELPSQRA
