ID PA2G5_HUMAN Reviewed; 138 AA. AC P39877; Q8N435; DT 01-FEB-1995, integrated into UniProtKB/Swiss-Prot. DT 01-FEB-1995, sequence version 1. DT 09-DEC-2015, entry version 148. DE RecName: Full=Calcium-dependent phospholipase A2; DE EC=3.1.1.4; DE AltName: Full=Group V phospholipase A2; DE AltName: Full=PLA2-10; DE AltName: Full=Phosphatidylcholine 2-acylhydrolase 5; DE Flags: Precursor; GN Name=PLA2G5; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RC TISSUE=Stomach; RX PubMed=8300559; RA Chen J., Engle S.J., Seilhamer J.J., Tischfield J.A.; RT "Cloning and recombinant expression of a novel human low molecular RT weight Ca(2+)-dependent phospholipase A2."; RL J. Biol. Chem. 269:2365-2368(1994). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RG NIEHS SNPs program; RL Submitted (JAN-2004) to the EMBL/GenBank/DDBJ databases. 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., RA Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., RA Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., RA McDonald L., Evans R., Phillips K., Atkinson A., Cooper R., Jones C., RA Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., RA Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., RA Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., RA Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., RA Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., RA Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., RA 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., RA Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., RA Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., RA Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., RA Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., RA Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., RA Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., RA Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., RA 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., RA Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., RA Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., RA Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., RA Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., RA Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., RA 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 MRNA]. RC TISSUE=Brain; 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 RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [5] RP TISSUE SPECIFICITY, AND VARIANTS FRFB CYS-45 AND SER-49. RX PubMed=22137173; DOI=10.1016/j.ajhg.2011.11.004; RA Sergouniotis P.I., Davidson A.E., Mackay D.S., Lenassi E., Li Z., RA Robson A.G., Yang X., Kam J.H., Isaacs T.W., Holder G.E., Jeffery G., RA Beck J.A., Moore A.T., Plagnol V., Webster A.R.; RT "Biallelic mutations in PLA2G5, encoding group V phospholipase A2, RT cause benign fleck retina."; RL Am. J. Hum. Genet. 89:782-791(2011). CC -!- FUNCTION: PA2 catalyzes the calcium-dependent hydrolysis of the 2- CC acyl groups in 3-sn-phosphoglycerides. This isozyme hydrolyzes CC more efficiently L-alpha-1-palmitoyl-2-oleoyl phosphatidylcholine CC than L-alpha-1-palmitoyl-2-arachidonyl phosphatidylcholine, L- CC alpha-1-palmitoyl-2-arachidonyl phosphatidylethanolamine, or L- CC alpha-1-stearoyl-2-arachidonyl phosphatidylinositol. May be CC involved in the production of lung surfactant, the remodeling or CC regulation of cardiac muscle. CC -!- CATALYTIC ACTIVITY: Phosphatidylcholine + H(2)O = 1- CC acylglycerophosphocholine + a carboxylate. {ECO:0000255|PROSITE- CC ProRule:PRU10035, ECO:0000255|PROSITE-ProRule:PRU10036}. CC -!- COFACTOR: CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108; Evidence={ECO:0000250}; CC Note=Binds 1 Ca(2+) ion per subunit. {ECO:0000250}; CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC pH dependence: CC Optimum pH is 6.5. Activity remains high up to pH 9.0.; CC -!- SUBCELLULAR LOCATION: Secreted. CC -!- TISSUE SPECIFICITY: Heart, placenta and less abundantly, in lung. CC Detected in the outer and inner plexiform layers of the retina (at CC protein level). {ECO:0000269|PubMed:22137173}. CC -!- PTM: This enzyme lacks one of the seven disulfide bonds found in CC similar PA2 proteins. CC -!- DISEASE: Fleck retina, familial benign (FRFB) [MIM:228980]: An CC autosomal recessive condition associated with a distinctive CC retinal appearance and no apparent visual or electrophysiologic CC deficits. Affected individuals are asymptomatic, but fundus CC examination reveals a striking pattern of diffuse, yellow-white, CC fleck-like lesions extending to the far periphery of the retina CC but sparing the foveal region. {ECO:0000269|PubMed:22137173}. CC Note=The disease is caused by mutations affecting the gene CC represented in this entry. CC -!- SIMILARITY: Belongs to the phospholipase A2 family. {ECO:0000305}. CC -!- WEB RESOURCE: Name=NIEHS-SNPs; CC URL="http://egp.gs.washington.edu/data/pla2g5/"; 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; U03090; AAC28886.1; -; mRNA. DR EMBL; AY524778; AAR92480.1; -; Genomic_DNA. DR EMBL; AL158172; CAC13158.1; -; Genomic_DNA. DR EMBL; BC036792; AAH36792.2; -; mRNA. DR CCDS; CCDS202.1; -. DR PIR; A49959; A49959. DR RefSeq; NP_000920.1; NM_000929.2. DR RefSeq; XP_005245950.1; XM_005245893.3. DR RefSeq; XP_006710759.1; XM_006710696.2. DR RefSeq; XP_011539889.1; XM_011541587.1. DR RefSeq; XP_011539890.1; XM_011541588.1. DR RefSeq; XP_011539891.1; XM_011541589.1. DR RefSeq; XP_011539892.1; XM_011541590.1. DR RefSeq; XP_011539893.1; XM_011541591.1. DR RefSeq; XP_011539894.1; XM_011541592.1. DR UniGene; Hs.319438; -. DR PDB; 2GHN; Model; -; A=21-138. DR PDBsum; 2GHN; -. DR ProteinModelPortal; P39877; -. DR SMR; P39877; 22-138. DR STRING; 9606.ENSP00000364249; -. DR BindingDB; P39877; -. DR ChEMBL; CHEMBL4323; -. DR GuidetoPHARMACOLOGY; 1430; -. DR SwissLipids; SLP:000000140; -. DR BioMuta; PLA2G5; -. DR DMDM; 730258; -. DR PaxDb; P39877; -. DR PRIDE; P39877; -. DR Ensembl; ENST00000375108; ENSP00000364249; ENSG00000127472. DR GeneID; 5322; -. DR KEGG; hsa:5322; -. DR UCSC; uc001bcx.3; human. DR CTD; 5322; -. DR GeneCards; PLA2G5; -. DR HGNC; HGNC:9038; PLA2G5. DR HPA; HPA053361; -. DR MalaCards; PLA2G5; -. DR MIM; 228980; phenotype. DR MIM; 601192; gene. DR neXtProt; NX_P39877; -. DR Orphanet; 363989; Familial benign flecked retina. DR PharmGKB; PA33366; -. DR eggNOG; KOG4087; Eukaryota. DR eggNOG; ENOG411283D; LUCA. DR GeneTree; ENSGT00760000119160; -. DR HOGENOM; HOG000231749; -. DR HOVERGEN; HBG008137; -. DR InParanoid; P39877; -. DR KO; K01047; -. DR OMA; YCLKRNL; -. DR OrthoDB; EOG7N63PF; -. DR PhylomeDB; P39877; -. DR TreeFam; TF319283; -. DR Reactome; R-HSA-1482788; Acyl chain remodelling of PC. DR Reactome; R-HSA-1482801; Acyl chain remodelling of PS. DR Reactome; R-HSA-1482839; Acyl chain remodelling of PE. DR Reactome; R-HSA-1482922; Acyl chain remodelling of PI. DR Reactome; R-HSA-1482925; Acyl chain remodelling of PG. DR Reactome; R-HSA-1483166; Synthesis of PA. DR GeneWiki; PLA2G5; -. DR GenomeRNAi; 5322; -. DR NextBio; 20590; -. DR PRO; PR:P39877; -. DR Proteomes; UP000005640; Chromosome 1. DR Bgee; P39877; -. DR CleanEx; HS_PLA2G5; -. DR Genevisible; P39877; HS. DR GO; GO:0009986; C:cell surface; IEA:Ensembl. DR GO; GO:0005576; C:extracellular region; TAS:Reactome. DR GO; GO:0005794; C:Golgi apparatus; IEA:Ensembl. DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:Ensembl. DR GO; GO:0005886; C:plasma membrane; IEA:Ensembl. DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro. DR GO; GO:0047498; F:calcium-dependent phospholipase A2 activity; TAS:ProtInc. DR GO; GO:0008201; F:heparin binding; IEA:Ensembl. DR GO; GO:0050482; P:arachidonic acid secretion; IEA:Ensembl. DR GO; GO:0046474; P:glycerophospholipid biosynthetic process; TAS:Reactome. DR GO; GO:0019370; P:leukotriene biosynthetic process; IEA:Ensembl. DR GO; GO:0016042; P:lipid catabolic process; IEA:UniProtKB-KW. DR GO; GO:0006654; P:phosphatidic acid biosynthetic process; TAS:Reactome. DR GO; GO:0036151; P:phosphatidylcholine acyl-chain remodeling; TAS:Reactome. DR GO; GO:0036152; P:phosphatidylethanolamine acyl-chain remodeling; TAS:Reactome. DR GO; GO:0036148; P:phosphatidylglycerol acyl-chain remodeling; TAS:Reactome. DR GO; GO:0036149; P:phosphatidylinositol acyl-chain remodeling; TAS:Reactome. DR GO; GO:0036150; P:phosphatidylserine acyl-chain remodeling; TAS:Reactome. DR GO; GO:0006644; P:phospholipid metabolic process; TAS:Reactome. DR GO; GO:0006663; P:platelet activating factor biosynthetic process; IEA:Ensembl. DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IDA:CACAO. DR GO; GO:0010518; P:positive regulation of phospholipase activity; IDA:CACAO. DR GO; GO:0051591; P:response to cAMP; IEA:Ensembl. DR GO; GO:0034097; P:response to cytokine; IEA:Ensembl. DR GO; GO:0044281; P:small molecule metabolic process; TAS:Reactome. DR Gene3D; 1.20.90.10; -; 1. DR InterPro; IPR001211; PLipase_A2. DR InterPro; IPR013090; PLipase_A2_AS. DR InterPro; IPR016090; PLipase_A2_dom. DR PANTHER; PTHR11716; PTHR11716; 1. DR Pfam; PF00068; Phospholip_A2_1; 1. DR PRINTS; PR00389; PHPHLIPASEA2. DR SMART; SM00085; PA2c; 1. DR SUPFAM; SSF48619; SSF48619; 1. DR PROSITE; PS00119; PA2_ASP; 1. DR PROSITE; PS00118; PA2_HIS; 1. PE 1: Evidence at protein level; KW 3D-structure; Calcium; Complete proteome; Disease mutation; KW Disulfide bond; Hydrolase; Lipid degradation; Lipid metabolism; KW Metal-binding; Reference proteome; Secreted; Signal. FT SIGNAL 1 20 {ECO:0000255}. FT CHAIN 21 138 Calcium-dependent phospholipase A2. FT /FTId=PRO_0000022761. FT ACT_SITE 67 67 {ECO:0000250}. FT ACT_SITE 111 111 {ECO:0000250}. FT METAL 47 47 Calcium; via carbonyl oxygen. FT {ECO:0000250}. FT METAL 49 49 Calcium; via carbonyl oxygen. FT {ECO:0000250}. FT METAL 51 51 Calcium; via carbonyl oxygen. FT {ECO:0000250}. FT METAL 68 68 Calcium. {ECO:0000250}. FT DISULFID 46 137 {ECO:0000250}. FT DISULFID 48 64 {ECO:0000250}. FT DISULFID 63 117 {ECO:0000250}. FT DISULFID 70 110 {ECO:0000250}. FT DISULFID 79 103 {ECO:0000250}. FT DISULFID 97 108 {ECO:0000250}. FT VARIANT 45 45 G -> C (in FRFB). FT {ECO:0000269|PubMed:22137173}. FT /FTId=VAR_067343. FT VARIANT 49 49 G -> S (in FRFB). FT {ECO:0000269|PubMed:22137173}. FT /FTId=VAR_067344. SQ SEQUENCE 138 AA; 15674 MW; 0D17DC76E55F42BC CRC64; MKGLLPLAWF LACSVPAVQG GLLDLKSMIE KVTGKNALTN YGFYGCYCGW GGRGTPKDGT DWCCWAHDHC YGRLEEKGCN IRTQSYKYRF AWGVVTCEPG PFCHVNLCAC DRKLVYCLKR NLRSYNPQYQ YFPNILCS //