ID PAFA2_HUMAN Reviewed; 392 AA. AC Q99487; D3DPK1; O15458; Q5SY02; DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot. DT 01-MAY-1997, sequence version 1. DT 24-JAN-2024, entry version 178. DE RecName: Full=Platelet-activating factor acetylhydrolase 2, cytoplasmic {ECO:0000303|PubMed:8955149}; DE EC=3.1.1.47 {ECO:0000269|PubMed:9494101}; DE AltName: Full=PAF:lysophospholipid transacetylase {ECO:0000250|UniProtKB:P83006}; DE AltName: Full=PAF:sphingosine transacetylase {ECO:0000250|UniProtKB:P83006}; DE AltName: Full=Platelet-activating factor acetyltransferase PAFAH2 {ECO:0000250|UniProtKB:P83006}; DE EC=2.3.1.149 {ECO:0000250|UniProtKB:P83006}; DE AltName: Full=Serine-dependent phospholipase A2 {ECO:0000303|PubMed:9494101}; DE Short=SD-PLA2 {ECO:0000305}; DE Short=hSD-PLA2 {ECO:0000303|PubMed:9494101}; GN Name=PAFAH2 {ECO:0000312|HGNC:HGNC:8579}; 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], AND TISSUE SPECIFICITY. RC TISSUE=Brain; RX PubMed=8955149; DOI=10.1074/jbc.271.51.33032; RA Hattori K., Adachi H., Matsuzawa A., Yamamoto K., Tsujimoto M., Aoki J., RA Hattori M., Arai H., Inoue K.; RT "cDNA cloning and expression of intracellular platelet-activating factor RT (PAF) acetylhydrolase II. Its homology with plasma PAF acetylhydrolase."; RL J. Biol. Chem. 271:33032-33038(1996). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, CATALYTIC ACTIVITY, ACTIVITY RP REGULATION, BIOPHYSICOCHEMICAL PROPERTIES, SUBUNIT, SUBCELLULAR LOCATION, RP AND TISSUE SPECIFICITY. RC TISSUE=Prostate; RX PubMed=9494101; DOI=10.1042/bj3301309; RA Rice S.Q.J., Southan C., Boyd H.F., Terrett J.A., Macphee C.H., Moores K., RA Gloger I.S., Tew D.G.; RT "Expression, purification and characterization of a human serine-dependent RT phospholipase A2 with high specificity for oxidized phospholipids and RT platelet activating factor."; RL Biochem. J. 330:1309-1315(1998). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16710414; DOI=10.1038/nature04727; RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K., RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.; RT "The DNA sequence and biological annotation of human chromosome 1."; RL Nature 441:315-321(2006). 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 (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Eye; 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 REVIEW. RX PubMed=9218411; DOI=10.1074/jbc.272.29.17895; RA Stafforini D.M., McIntyre T.M., Zimmerman G.A., Prescott S.M.; RT "Platelet-activating factor acetylhydrolases."; RL J. Biol. Chem. 272:17895-17898(1997). CC -!- FUNCTION: Catalyzes the hydrolyze of the acetyl group at the sn-2 CC position of platelet-activating factor (PAF) and its analogs, leading CC to their inactivation (PubMed:9494101). Hydrolyzes propionyl and CC butyroyl moieties approximately half as effectively as PAF (By CC similarity). Also catalyzes transacetylation of the acetyl group from CC platelet-activating factor (PAF) to lysoplasmalogen and to sphingosine, CC producing plasmalogen analogs of PAF and N-acetylsphingosine (C2- CC ceramide) respectively. Has a marked selectivity for phospholipids with CC short acyl chains at the sn-2 position (By similarity). CC {ECO:0000250|UniProtKB:P79106, ECO:0000250|UniProtKB:P83006, CC ECO:0000269|PubMed:9494101}. 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:0000269|PubMed:9494101}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:17778; CC Evidence={ECO:0000269|PubMed:9494101}; 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:P83006}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:40480; CC Evidence={ECO:0000250|UniProtKB:P83006}; CC -!- CATALYTIC ACTIVITY: CC Reaction=1-O-(1Z-alkenyl)-sn-glycero-3-phosphoethanolamine + 1-O- CC hexadecyl-2-acetyl-sn-glycero-3-phosphocholine = 1-O-(1Z-alkenyl)-2- CC acetyl-sn-glycero-3-phosphoethanolamine + 1-O-hexadecyl-sn-glycero-3- CC phosphocholine; Xref=Rhea:RHEA:41396, ChEBI:CHEBI:44811, CC ChEBI:CHEBI:64496, ChEBI:CHEBI:77288, ChEBI:CHEBI:78419; CC Evidence={ECO:0000250|UniProtKB:P83006}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41397; CC Evidence={ECO:0000250|UniProtKB:P83006}; CC -!- CATALYTIC ACTIVITY: CC Reaction=1-O-hexadecyl-2-acetyl-sn-glycero-3-phosphocholine + sphing-4- CC enine = 1-O-hexadecyl-sn-glycero-3-phosphocholine + H(+) + N- CC (acetyl)-sphing-4-enine; Xref=Rhea:RHEA:41408, ChEBI:CHEBI:15378, CC ChEBI:CHEBI:44811, ChEBI:CHEBI:46979, ChEBI:CHEBI:57756, CC ChEBI:CHEBI:64496; Evidence={ECO:0000250|UniProtKB:P83006}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41409; CC Evidence={ECO:0000250|UniProtKB:P83006}; CC -!- CATALYTIC ACTIVITY: CC Reaction=a 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine + a 1- CC organyl-2-lyso-sn-glycero-3-phospholipid = 1-O-alkyl-sn-glycero-3- CC phosphocholine + a 1-organyl-2-acetyl-sn-glycero-3-phospholipid; CC Xref=Rhea:RHEA:11048, ChEBI:CHEBI:685, ChEBI:CHEBI:30909, CC ChEBI:CHEBI:36707, ChEBI:CHEBI:76590; EC=2.3.1.149; CC Evidence={ECO:0000250|UniProtKB:P83006}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:11049; CC Evidence={ECO:0000250|UniProtKB:P83006}; CC -!- CATALYTIC ACTIVITY: CC Reaction=1-O-hexadecyl-2-glutaryl-sn-glycero-3-phosphocholine + H2O = CC 1-O-hexadecyl-sn-glycero-3-phosphocholine + glutarate + H(+); CC Xref=Rhea:RHEA:41700, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, CC ChEBI:CHEBI:30921, ChEBI:CHEBI:64496, ChEBI:CHEBI:78371; CC Evidence={ECO:0000250|UniProtKB:P79106}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41701; CC Evidence={ECO:0000250|UniProtKB:P79106}; CC -!- CATALYTIC ACTIVITY: CC Reaction=1-O-hexadecyl-2-succinyl-sn-glycero-3-phosphocholine + H2O = CC 1-O-hexadecyl-sn-glycero-3-phosphocholine + H(+) + succinate; CC Xref=Rhea:RHEA:41696, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, CC ChEBI:CHEBI:30031, ChEBI:CHEBI:64496, ChEBI:CHEBI:78369; CC Evidence={ECO:0000250|UniProtKB:P79106}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41697; CC Evidence={ECO:0000250|UniProtKB:P79106}; CC -!- CATALYTIC ACTIVITY: CC Reaction=1-O-hexadecyl-2-butanoyl-sn-glycero-3-phosphocholine + H2O = CC 1-O-hexadecyl-sn-glycero-3-phosphocholine + butanoate + H(+); CC Xref=Rhea:RHEA:41692, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, CC ChEBI:CHEBI:17968, ChEBI:CHEBI:64496, ChEBI:CHEBI:78368; CC Evidence={ECO:0000250|UniProtKB:P79106}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41693; CC Evidence={ECO:0000250|UniProtKB:P79106}; CC -!- CATALYTIC ACTIVITY: CC Reaction=1-O-hexadecyl-2-propanoyl-sn-glycero-3-phosphocholine + H2O = CC 1-O-hexadecyl-sn-glycero-3-phosphocholine + H(+) + propanoate; CC Xref=Rhea:RHEA:41688, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, CC ChEBI:CHEBI:17272, ChEBI:CHEBI:64496, ChEBI:CHEBI:78367; CC Evidence={ECO:0000250|UniProtKB:P79106}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:41689; CC Evidence={ECO:0000250|UniProtKB:P79106}; CC -!- ACTIVITY REGULATION: Inhibited by phenylmethanesulfonyl fluoride, CC 3,4,dichloroisocoumarin, diisopropyl fluorophosphate (DFP) and diethyl CC p-nitrophenyl phosphate (DENP). {ECO:0000269|PubMed:9494101}. CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=42 uM for 2-O-acetyl-1-O-hexadecyl-sn-glycero-3-phosphocholine CC (PAF) {ECO:0000269|PubMed:9494101}; CC KM=10 uM for 1-decanoyl-2-(4-nitrophenylglutaryl) phosphate (DNGP) CC {ECO:0000269|PubMed:9494101}; CC Vmax=35 umol/min/mg enzyme with CC 2-O-acetyl-1-O-hexadecyl-sn-glycero-3-phosphocholine (PAF) as CC substrate {ECO:0000269|PubMed:9494101}; CC Vmax=1.7 umol/min/mg enzyme with 1-decanoyl-2-(4-nitrophenylglutaryl) CC phosphate (DNGP) as substrate {ECO:0000269|PubMed:9494101}; CC -!- SUBUNIT: Monomer. {ECO:0000305|PubMed:9494101}. CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:9494101}. Membrane CC {ECO:0000250|UniProtKB:P79106}; Lipid-anchor CC {ECO:0000250|UniProtKB:P79106}. Endoplasmic reticulum membrane CC {ECO:0000250|UniProtKB:P79106}; Lipid-anchor CC {ECO:0000250|UniProtKB:P79106}. Note=In resting cells, localizes to CC intracellular membranes and cytoplasm. Translocates from the cytoplasm CC to intracellular membranes upon oxidative stress. CC {ECO:0000250|UniProtKB:P79106}. CC -!- TISSUE SPECIFICITY: Broadly expressed in different tissues, but high in CC B- and T-lymphocytes. In brain, expression is restricted to amygdala CC and frontal cortex. {ECO:0000269|PubMed:8955149, CC ECO:0000269|PubMed:9494101}. CC -!- SIMILARITY: Belongs to the serine esterase family. {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; D87845; BAA13468.1; -; mRNA. DR EMBL; U89386; AAC39707.1; -; mRNA. DR EMBL; AL592064; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471059; EAX07852.1; -; Genomic_DNA. DR EMBL; CH471059; EAX07853.1; -; Genomic_DNA. DR EMBL; BC001158; AAH01158.1; -; mRNA. DR CCDS; CCDS270.1; -. DR RefSeq; NP_000428.2; NM_000437.3. DR RefSeq; XP_006710733.1; XM_006710670.3. DR AlphaFoldDB; Q99487; -. DR SMR; Q99487; -. DR BioGRID; 111088; 16. DR STRING; 9606.ENSP00000363400; -. DR ESTHER; human-PAFAH2; PAF-Acetylhydrolase. DR iPTMnet; Q99487; -. DR PhosphoSitePlus; Q99487; -. DR SwissPalm; Q99487; -. DR BioMuta; PAFAH2; -. DR DMDM; 6647691; -. DR EPD; Q99487; -. DR jPOST; Q99487; -. DR MassIVE; Q99487; -. DR MaxQB; Q99487; -. DR PaxDb; 9606-ENSP00000363400; -. DR PeptideAtlas; Q99487; -. DR ProteomicsDB; 78290; -. DR Pumba; Q99487; -. DR Antibodypedia; 622; 160 antibodies from 23 providers. DR DNASU; 5051; -. DR Ensembl; ENST00000374282.8; ENSP00000363400.3; ENSG00000158006.14. DR Ensembl; ENST00000374284.5; ENSP00000363402.1; ENSG00000158006.14. DR GeneID; 5051; -. DR KEGG; hsa:5051; -. DR MANE-Select; ENST00000374282.8; ENSP00000363400.3; NM_000437.4; NP_000428.2. DR UCSC; uc001bld.4; human. DR AGR; HGNC:8579; -. DR CTD; 5051; -. DR DisGeNET; 5051; -. DR GeneCards; PAFAH2; -. DR HGNC; HGNC:8579; PAFAH2. DR HPA; ENSG00000158006; Tissue enhanced (lymphoid). DR MIM; 602344; gene. DR neXtProt; NX_Q99487; -. DR OpenTargets; ENSG00000158006; -. DR PharmGKB; PA32910; -. DR VEuPathDB; HostDB:ENSG00000158006; -. DR eggNOG; KOG3847; Eukaryota. DR GeneTree; ENSGT00390000005233; -. DR HOGENOM; CLU_022501_0_0_1; -. DR InParanoid; Q99487; -. DR OMA; MGVNQSM; -. DR OrthoDB; 3079661at2759; -. DR PhylomeDB; Q99487; -. DR TreeFam; TF313831; -. DR BRENDA; 3.1.1.47; 2681. DR PathwayCommons; Q99487; -. DR Reactome; R-HSA-418346; Platelet homeostasis. DR BioGRID-ORCS; 5051; 18 hits in 1159 CRISPR screens. DR ChiTaRS; PAFAH2; human. DR GeneWiki; PAFAH2; -. DR GenomeRNAi; 5051; -. DR Pharos; Q99487; Tbio. DR PRO; PR:Q99487; -. DR Proteomes; UP000005640; Chromosome 1. DR RNAct; Q99487; Protein. DR Bgee; ENSG00000158006; Expressed in body of pancreas and 132 other cell types or tissues. DR ExpressionAtlas; Q99487; baseline and differential. DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB. DR GO; GO:0005789; C:endoplasmic reticulum membrane; TAS:Reactome. DR GO; GO:0003847; F:1-alkyl-2-acetylglycerophosphocholine esterase activity; ISS:UniProtKB. DR GO; GO:0005543; F:phospholipid binding; TAS:ProtInc. DR GO; GO:0047179; F:platelet-activating factor acetyltransferase activity; ISS:UniProtKB. DR GO; GO:0007596; P:blood coagulation; TAS:Reactome. DR GO; GO:0016042; P:lipid catabolic process; IEA:UniProtKB-KW. DR GO; GO:0006629; P:lipid metabolic process; TAS:ProtInc. DR Gene3D; 3.40.50.1820; alpha/beta hydrolase; 1. DR InterPro; IPR029058; AB_hydrolase. DR InterPro; IPR016715; PAF_acetylhydro_eukaryote. DR PANTHER; PTHR10272; PLATELET-ACTIVATING FACTOR ACETYLHYDROLASE; 1. DR PANTHER; PTHR10272:SF6; PLATELET-ACTIVATING FACTOR ACETYLHYDROLASE 2, CYTOPLASMIC; 1. DR Pfam; PF03403; PAF-AH_p_II; 1. DR PIRSF; PIRSF018169; PAF_acetylhydrolase; 1. DR SUPFAM; SSF53474; alpha/beta-Hydrolases; 1. DR PROSITE; PS00120; LIPASE_SER; 1. DR Genevisible; Q99487; HS. PE 1: Evidence at protein level; KW Cytoplasm; Endoplasmic reticulum; Hydrolase; Lipid degradation; KW Lipid metabolism; Lipoprotein; Membrane; Myristate; Reference proteome; KW Transferase. FT INIT_MET 1 FT /note="Removed" FT CHAIN 2..392 FT /note="Platelet-activating factor acetylhydrolase 2, FT cytoplasmic" FT /id="PRO_0000090383" FT ACT_SITE 236 FT /note="Nucleophile" FT /evidence="ECO:0000250|UniProtKB:P79106" FT ACT_SITE 259 FT /note="Charge relay system" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10037" FT ACT_SITE 314 FT /note="Charge relay system" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10037" FT LIPID 2 FT /note="N-myristoyl glycine" FT /evidence="ECO:0000250|UniProtKB:P79106" FT CONFLICT 212 FT /note="L -> F (in Ref. 2; AAC39707)" FT /evidence="ECO:0000305" SQ SEQUENCE 392 AA; 44036 MW; 690FB7E6F5B68317 CRC64; MGVNQSVGFP PVTGPHLVGC GDVMEGQNLQ GSFFRLFYPC QKAEETMEQP LWIPRYEYCT GLAEYLQFNK RCGGLLFNLA VGSCRLPVSW NGPFKTKDSG YPLIIFSHGL GAFRTLYSAF CMELASRGFV VAVPEHRDRS AATTYFCKQA PEENQPTNES LQEEWIPFRR VEEGEKEFHV RNPQVHQRVS ECLRVLKILQ EVTAGQTVFN ILPGGLDLMT LKGNIDMSRV AVMGHSFGGA TAILALAKET QFRCAVALDA WMFPLERDFY PKARGPVFFI NTEKFQTMES VNLMKKICAQ HEQSRIITVL GSVHRSQTDF AFVTGNLIGK FFSTETRGSL DPYEGQEVMV RAMLAFLQKH LDLKEDYNQW NNLIEGIGPS LTPGAPHHLS SL //