PA1B3_HUMAN
ID PA1B3_HUMAN Reviewed; 231 AA.
AC Q15102; Q53X88;
DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 191.
DE RecName: Full=Platelet-activating factor acetylhydrolase IB subunit alpha1 {ECO:0000305};
DE EC=3.1.1.47 {ECO:0000250|UniProtKB:Q29460};
DE AltName: Full=PAF acetylhydrolase 29 kDa subunit;
DE Short=PAF-AH 29 kDa subunit;
DE AltName: Full=PAF-AH subunit gamma;
DE Short=PAFAH subunit gamma;
GN Name=PAFAH1B3 {ECO:0000312|HGNC:HGNC:8576}; Synonyms=PAFAHG;
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 [MRNA].
RC TISSUE=Fetal liver;
RX PubMed=7669037; DOI=10.1006/bbrc.1995.2272;
RA Adachi H., Tsujimoto M., Hattori M., Arai H., Inoue K.;
RT "cDNA cloning of human cytosolic platelet-activating factor acetylhydrolase
RT gamma-subunit and its mRNA expression in human tissues.";
RL Biochem. Biophys. Res. Commun. 214:180-187(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (MAY-2004) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15057824; DOI=10.1038/nature02399;
RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E.,
RA Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A.,
RA Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S.,
RA Carrano A.V., Caoile C., Chan Y.M., Christensen M., Cleland C.A.,
RA Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J.,
RA Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M.,
RA Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W.,
RA Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V.,
RA Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D.,
RA McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I.,
RA Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L.,
RA Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A.,
RA She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M.,
RA Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J.,
RA Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E.,
RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M.,
RA Rubin E.M., Lucas S.M.;
RT "The DNA sequence and biology of human chromosome 19.";
RL Nature 428:529-535(2004).
RN [4]
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 (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Lung, and Uterus;
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 [6]
RP PROTEIN SEQUENCE OF 84-127; 133-141 AND 199-231, AND IDENTIFICATION BY MASS
RP SPECTROMETRY.
RC TISSUE=Fetal brain cortex;
RA Lubec G., Chen W.-Q., Sun Y.;
RL Submitted (DEC-2008) to UniProtKB.
RN [7]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [8]
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 [9]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=22223895; DOI=10.1074/mcp.m111.015131;
RA Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T.,
RA Giglione C.;
RT "Comparative large-scale characterisation of plant vs. mammal proteins
RT reveals similar and idiosyncratic N-alpha acetylation features.";
RL Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012).
RN [10]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-2, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [12]
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).
CC -!- FUNCTION: Alpha1 catalytic subunit of the cytosolic type I platelet-
CC activating factor (PAF) acetylhydrolase (PAF-AH (I)) heterotetrameric
CC enzyme that catalyzes the hydrolyze of the acetyl group at the sn-2
CC position of PAF and its analogs and modulates the action of PAF. The
CC activity and substrate specificity of PAF-AH (I) are affected by its
CC subunit composition. Both alpha1/alpha1 homodimer (PAFAH1B3/PAFAH1B3
CC homodimer) and alpha1/alpha2 heterodimer(PAFAH1B3/PAFAH1B2 heterodimer)
CC hydrolyze 1-O-alkyl-2-acetyl-sn-glycero-3-phosphoric acid (AAGPA) more
CC efficiently than PAF, but they have little hydrolytic activity towards
CC 1-O-alkyl-2-acetyl-sn-glycero-3-phosphorylethanolamine (AAGPE). Plays
CC an important role during the development of brain.
CC {ECO:0000250|UniProtKB:Q29460}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine + H2O = 1-O-
CC alkyl-sn-glycero-3-phosphocholine + acetate + H(+);
CC Xref=Rhea:RHEA:17777, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:30089, ChEBI:CHEBI:30909, ChEBI:CHEBI:36707; EC=3.1.1.47;
CC Evidence={ECO:0000250|UniProtKB:Q29460};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:17778;
CC Evidence={ECO:0000250|UniProtKB:Q29460};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-O-hexadecyl-2-acetyl-sn-glycero-3-phosphocholine + H2O = 1-
CC O-hexadecyl-sn-glycero-3-phosphocholine + acetate + H(+);
CC Xref=Rhea:RHEA:40479, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:30089, ChEBI:CHEBI:44811, ChEBI:CHEBI:64496;
CC Evidence={ECO:0000250|UniProtKB:Q29460};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40480;
CC Evidence={ECO:0000250|UniProtKB:Q29460};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1-O-hexadecyl-2-acetyl-sn-glycero-3-phosphate + H2O = 1-O-
CC hexadecyl-sn-glycero-3-phosphate + acetate + H(+);
CC Xref=Rhea:RHEA:41704, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:30089, ChEBI:CHEBI:77580, ChEBI:CHEBI:78385;
CC Evidence={ECO:0000250|UniProtKB:Q29460};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41705;
CC Evidence={ECO:0000250|UniProtKB:Q29460};
CC -!- ACTIVITY REGULATION: Beta subunit (PAFAH1B1) inhibits the
CC acetylhydrolase activity of the alpha1/alpha1 catalytic homodimer.
CC {ECO:0000250|UniProtKB:Q29460}.
CC -!- SUBUNIT: Forms a catalytic dimer which is either homodimer
CC (alpha1/alpha1 homodimer) or heterodimer with PAFAH1B2 (alpha1/alpha2
CC heterodimer). Component of the cytosolic (PAF-AH (I)) heterotetrameric
CC enzyme, which is composed of PAFAH1B1 (beta), PAFAH1B2 (alpha2) and
CC PAFAH1B3 (alpha1) subunits. The catalytic activity of the enzyme
CC resides in the alpha1 (PAFAH1B3) and alpha2 (PAFAH1B2) subunits,
CC whereas the beta subunit (PAFAH1B1) has regulatory activity. Trimer
CC formation is not essential for the catalytic activity (By similarity).
CC Interacts with VLDLR; this interaction may modulate the Reelin pathway
CC (By similarity). {ECO:0000250|UniProtKB:Q29460,
CC ECO:0000250|UniProtKB:Q61205}.
CC -!- INTERACTION:
CC Q15102; Q8TBB1: LNX1; NbExp=9; IntAct=EBI-711522, EBI-739832;
CC Q15102; A8MW99: MEI4; NbExp=3; IntAct=EBI-711522, EBI-19944212;
CC Q15102; Q9GZT8: NIF3L1; NbExp=3; IntAct=EBI-711522, EBI-740897;
CC Q15102; P68402: PAFAH1B2; NbExp=4; IntAct=EBI-711522, EBI-713724;
CC Q15102; Q15102: PAFAH1B3; NbExp=8; IntAct=EBI-711522, EBI-711522;
CC Q15102; Q9NRD5: PICK1; NbExp=3; IntAct=EBI-711522, EBI-79165;
CC Q15102; Q9H190: SDCBP2; NbExp=5; IntAct=EBI-711522, EBI-742426;
CC -!- SUBCELLULAR LOCATION: Cytoplasm.
CC -!- TISSUE SPECIFICITY: In the adult, expressed in brain, skeletal muscle,
CC kidney, thymus, spleen, colon, testis, ovary and peripheral blood
CC leukocytes. In the fetus, highest expression occurs in brain.
CC -!- MISCELLANEOUS: Originally the subunits of the type I platelet-
CC activating factor (PAF) acetylhydrolase was named alpha (PAFAH1B1),
CC beta (PAFAH1B2) and gamma (PAFAH1B3) (PubMed:7669037) (By similarity).
CC Now these subunits have been renamed beta (PAFAH1B1), alpha2 (PAFAH1B2)
CC and alpha1 (PAFAH1B3) respectively (By similarity).
CC {ECO:0000250|UniProtKB:P43034, ECO:0000250|UniProtKB:P68402,
CC ECO:0000250|UniProtKB:Q29460, ECO:0000303|PubMed:7669037}.
CC -!- SIMILARITY: Belongs to the 'GDSL' lipolytic enzyme family. Platelet-
CC activating factor acetylhydrolase IB beta/gamma subunits subfamily.
CC {ECO:0000305}.
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DR EMBL; D63391; BAA09706.1; -; mRNA.
DR EMBL; CR407626; CAG28554.1; -; mRNA.
DR EMBL; AC006486; AAD11989.1; -; Genomic_DNA.
DR EMBL; CH471126; EAW57122.1; -; Genomic_DNA.
DR EMBL; BC003016; AAH03016.1; -; mRNA.
DR EMBL; BC007863; AAH07863.1; -; mRNA.
DR CCDS; CCDS12602.1; -.
DR PIR; JC4246; JC4246.
DR RefSeq; NP_001139411.1; NM_001145939.1.
DR RefSeq; NP_001139412.1; NM_001145940.1.
DR RefSeq; NP_002564.1; NM_002573.3.
DR AlphaFoldDB; Q15102; -.
DR SMR; Q15102; -.
DR BioGRID; 111087; 59.
DR IntAct; Q15102; 44.
DR MINT; Q15102; -.
DR STRING; 9606.ENSP00000444935; -.
DR ChEMBL; CHEMBL5108; -.
DR DrugBank; DB07821; (1R)-1,2,2-trimethylpropyl (R)-methylphosphinate.
DR iPTMnet; Q15102; -.
DR PhosphoSitePlus; Q15102; -.
DR SwissPalm; Q15102; -.
DR BioMuta; PAFAH1B3; -.
DR DMDM; 3024344; -.
DR REPRODUCTION-2DPAGE; IPI00014808; -.
DR CPTAC; CPTAC-246; -.
DR CPTAC; CPTAC-247; -.
DR EPD; Q15102; -.
DR jPOST; Q15102; -.
DR MassIVE; Q15102; -.
DR MaxQB; Q15102; -.
DR PaxDb; Q15102; -.
DR PeptideAtlas; Q15102; -.
DR PRIDE; Q15102; -.
DR ProteomicsDB; 60435; -.
DR Antibodypedia; 30926; 286 antibodies from 26 providers.
DR DNASU; 5050; -.
DR Ensembl; ENST00000262890.8; ENSP00000262890.2; ENSG00000079462.8.
DR Ensembl; ENST00000538771.5; ENSP00000444935.1; ENSG00000079462.8.
DR GeneID; 5050; -.
DR KEGG; hsa:5050; -.
DR MANE-Select; ENST00000262890.8; ENSP00000262890.2; NM_002573.4; NP_002564.1.
DR UCSC; uc002otg.3; human.
DR CTD; 5050; -.
DR DisGeNET; 5050; -.
DR GeneCards; PAFAH1B3; -.
DR HGNC; HGNC:8576; PAFAH1B3.
DR HPA; ENSG00000079462; Low tissue specificity.
DR MIM; 603074; gene.
DR neXtProt; NX_Q15102; -.
DR OpenTargets; ENSG00000079462; -.
DR PharmGKB; PA32907; -.
DR VEuPathDB; HostDB:ENSG00000079462; -.
DR eggNOG; KOG1388; Eukaryota.
DR GeneTree; ENSGT00950000183199; -.
DR InParanoid; Q15102; -.
DR OMA; LMHQCEV; -.
DR OrthoDB; 1604899at2759; -.
DR PhylomeDB; Q15102; -.
DR TreeFam; TF323955; -.
DR PathwayCommons; Q15102; -.
DR Reactome; R-HSA-6811436; COPI-independent Golgi-to-ER retrograde traffic.
DR SignaLink; Q15102; -.
DR BioGRID-ORCS; 5050; 10 hits in 1076 CRISPR screens.
DR ChiTaRS; PAFAH1B3; human.
DR GeneWiki; PAFAH1B3; -.
DR GenomeRNAi; 5050; -.
DR Pharos; Q15102; Tbio.
DR PRO; PR:Q15102; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; Q15102; protein.
DR Bgee; ENSG00000079462; Expressed in cortical plate and 141 other tissues.
DR ExpressionAtlas; Q15102; baseline and differential.
DR Genevisible; Q15102; HS.
DR GO; GO:0008247; C:1-alkyl-2-acetylglycerophosphocholine esterase complex; ISS:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0003847; F:1-alkyl-2-acetylglycerophosphocholine esterase activity; ISS:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0047179; F:platelet-activating factor acetyltransferase activity; IBA:GO_Central.
DR GO; GO:0046982; F:protein heterodimerization activity; IDA:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB.
DR GO; GO:0044877; F:protein-containing complex binding; IEA:Ensembl.
DR GO; GO:0007420; P:brain development; IBA:GO_Central.
DR GO; GO:0016042; P:lipid catabolic process; IEA:UniProtKB-KW.
DR GO; GO:0006629; P:lipid metabolic process; TAS:ProtInc.
DR GO; GO:0007399; P:nervous system development; TAS:ProtInc.
DR GO; GO:0007283; P:spermatogenesis; IEA:Ensembl.
DR Gene3D; 3.40.50.1110; -; 1.
DR InterPro; IPR013830; SGNH_hydro.
DR InterPro; IPR036514; SGNH_hydro_sf.
DR Pfam; PF13472; Lipase_GDSL_2; 1.
PE 1: Evidence at protein level;
KW Acetylation; Cytoplasm; Direct protein sequencing; Hydrolase;
KW Lipid degradation; Lipid metabolism; Phosphoprotein; Reference proteome.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0007744|PubMed:19413330,
FT ECO:0007744|PubMed:22223895, ECO:0007744|PubMed:22814378"
FT CHAIN 2..231
FT /note="Platelet-activating factor acetylhydrolase IB
FT subunit alpha1"
FT /id="PRO_0000058155"
FT ACT_SITE 47
FT /evidence="ECO:0000250|UniProtKB:Q29460"
FT ACT_SITE 192
FT /evidence="ECO:0000250|UniProtKB:Q29460"
FT ACT_SITE 195
FT /evidence="ECO:0000250|UniProtKB:Q29460"
FT MOD_RES 2
FT /note="N-acetylserine"
FT /evidence="ECO:0007744|PubMed:19413330,
FT ECO:0007744|PubMed:22223895, ECO:0007744|PubMed:22814378"
FT MOD_RES 2
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT VARIANT 214
FT /note="R -> G (in dbSNP:rs1043818)"
FT /id="VAR_051261"
SQ SEQUENCE 231 AA; 25734 MW; 58A4CB8E7076AE23 CRC64;
MSGEENPASK PTPVQDVQGD GRWMSLHHRF VADSKDKEPE VVFIGDSLVQ LMHQCEIWRE
LFSPLHALNF GIGGDGTQHV LWRLENGELE HIRPKIVVVW VGTNNHGHTA EQVTGGIKAI
VQLVNERQPQ ARVVVLGLLP RGQHPNPLRE KNRQVNELVR AALAGHPRAH FLDADPGFVH
SDGTISHHDM YDYLHLSRLG YTPVCRALHS LLLRLLAQDQ GQGAPLLEPA P
