Reviewed, UniProtKB/Swiss-Prot Q9NZ20 (PA2G3_HUMAN)

Names and origin

Protein names

Recommended name:
    Group 3 secretory phospholipase A2
    EC=3.1.1.4
Alternative name(s):
    Group III secretory phospholipase A2
      Short name=GIII sPLA2
    Phosphatidylcholine 2-acylhydrolase GIII
    sPLA2-III

Gene names

Name:

PLA2G3

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	509 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	PA2 catalyzes the calcium-dependent hydrolysis of the 2-acyl groups in 3-sn-phosphoglycerides. Shows an 11-fold preference for phosphatidylglycerol over phosphatidylcholine (PC). Preferential cleavage: 1-palmitoyl-2-linoleoyl-phosphatidylethanolamine (PE) > 1-palmitoyl-2-linoleoyl-PC > 1-palmitoyl-2-arachidonoyl-PC > 1-palmitoyl-2-arachidonoyl-PE. Ref.4
Catalytic activity	Phosphatidylcholine + H2O = 1-acylglycerophosphocholine + a carboxylate.
Cofactor	Binds 1 calcium ion per subunit.
Enzyme regulation	Arachidonic acid release is markedly increased by glypican, a glycosylphosphatidylinositol-anchored heparan sulfate proteoglycan.
Subcellular location	Secreted. Cell membrane. Ref.4
Tissue specificity	Expressed in kidney, heart, liver, and skeletal muscle. Also present in placenta and peripheral blood leukocytes. Not detected in brain, colon, thymus, spleen and small intestine. In lung, expressed in bronchial epithelial cells and alveolar macrophages, but scarcely detected in alveolar epithelium, arterial walls and interstitial fibroblasts (at protein level). In joints of osteoarthritis and rheumatoid arthritis, expressed in endothelial cells (at protein level). In normal heart, detected in some vessels. In myocardial tissues with acute infarction, expressed in vascular endothelial cells adjacent to cardiomyocytes and those in lesions with granulation. Expression in cardiomyocytes is scarce (at protein level). In uterus, breast and colon cancers, detected in tumor cells and neighboring microvascular endothelium, but not in normal glandular tissues (at protein level). Ref.5
Induction	By IL1B and TNF in microvascular endothelial cells (at protein level). Ref.5
Post-translational modification	N-glycosylation does not affect the catalytical activity, but is required for proper secretion. A nonglycosylated form was observed in several cell types. Ref.5 In several cell types, the N- and C-termini are cleaved off.
Sequence similarities	Belongs to the phospholipase A2 family.

Ontologies

Keywords
Biological process	Lipid degradation
Cellular component	Cell membrane Membrane Secreted
Coding sequence diversity	Polymorphism
Domain	Signal
Ligand	Calcium Metal-binding
Molecular function	Hydrolase
PTM	Disulfide bond Glycoprotein Phosphoprotein
Gene Ontology (GO)
Biological process	lipid catabolic process Inferred from electronic annotation. Source: UniProtKB-KW phospholipid metabolic process Ref.1 Traceable author statement. Source: ProtInc
Cellular component	extracellular space Ref.1 Traceable author statement. Source: ProtInc plasma membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	calcium ion binding Inferred from electronic annotation. Source: UniProtKB-KW calcium-dependent phospholipase A2 activity Ref.1 Traceable author statement. Source: ProtInc
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 19	19	Potential
	Chain	20 – 509	490	Group 3 secretory phospholipase A2		PRO_0000022992
Regions
	Region	150 – 291	142	Phospholipase A2-like
Sites
	Active site	184	1
	Active site	214	1	By similarity
	Metal binding	158	1	Calcium; via carbonyl oxygen By similarity
	Metal binding	160	1	Calcium; via carbonyl oxygen By similarity
	Metal binding	162	1	Calcium; via carbonyl oxygen By similarity
	Metal binding	185	1	Calcium By similarity
Amino acid modifications
	Modified residue	326	1	Phosphothreonine Ref.6
	Modified residue	327	1	Phosphothreonine Ref.6
	Modified residue	335	1	Phosphoserine Ref.6
	Glycosylation	167	1	N-linked (GlcNAc...) Ref.5
	Glycosylation	280	1	N-linked (GlcNAc...) Ref.5
	Glycosylation	325	1	N-linked (GlcNAc...) Potential
	Glycosylation	396	1	N-linked (GlcNAc...) Potential
	Glycosylation	439	1	N-linked (GlcNAc...) Potential
	Disulfide bond	159 ↔ 181		By similarity
	Disulfide bond	180 ↔ 220		By similarity
	Disulfide bond	187 ↔ 213		By similarity
	Disulfide bond	211 ↔ 244		By similarity
Natural variations
	Natural variant	70	1	A → S: dbSNP rs2232176.		VAR_024555
	Natural variant	116	1	E → Q: dbSNP rs2074734.		VAR_024556
	Natural variant	157	1	L → V: dbSNP rs2074735.		VAR_020288
	Natural variant	307	1	H → Y: dbSNP rs2232180.		VAR_056581
	Natural variant	322	1	S → R: dbSNP rs2072193.		VAR_024557
	Natural variant	378	1	R → Q: dbSNP rs2232183.		VAR_034366
Experimental info
	Mutagenesis	167	1	N → S: Loss of glycosylation. Ref.5
	Mutagenesis	184	1	H → Q: Loss of PGE2 synthesis. Ref.4 Ref.5
	Mutagenesis	280	1	N → S: Loss of glycosylation. Ref.5

Sequences

	Sequence		Length	Mass (Da)
	Q9NZ20-1 [UniParc]. Last modified October 1, 2000. Version 1. Checksum: 2D610DECA6EE6CF8	FASTA	509	57,151
	10 20 30 40 50 60 MGVQAGLFGM LGFLGVALGG SPALRWYRTS CHLTKAVPGN PLGYLSFLAK DAQGLALIHA 70 80 90 100 110 120 RWDAHRRLQA CSWEDEPELT AAYGALCAHE TAWGSFIHTP GPELQRALAT LQSQWEACRA 130 140 150 160 170 180 LEESPAGARK KRAAGQSGVP GGGHQREKRG WTMPGTLWCG VGDSAGNSSE LGVFQGPDLC 190 200 210 220 230 240 CREHDRCPQN ISPLQYNYGI RNYRFHTISH CDCDTRFQQC LQNQHDSISD IVGVAFFNVL 250 260 270 280 290 300 EIPCFVLEEQ EACVAWYWWG GCRMYGTVPL ARLQPRTFYN ASWSSRATSP TPSSRSPAPP 310 320 330 340 350 360 KPRQKQHLRK GPPHQKGSKR PSKANTTALQ DPMVSPRLDV APTGLQGPQG GLKPQGARWV 370 380 390 400 410 420 CRSFRRHLDQ CEHQIGPREI EFQLLNSAQE PLFHCNCTRR LARFLRLHSP PEVTNMLWEL 430 440 450 460 470 480 LGTTCFKLAP PLDCVEGKNC SRDPRAIRVS ARHLRRLQQR RHQLQDKGTD ERQPWPSEPL 490 500 RGPMSFYNQC LQLTQAARRP DRQQKSWSQ

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Novel human secreted phospholipase A2 with homology to the group III bee venom enzyme." Valentin E., Ghomashchi F., Gelb M.H., Lazdunski M., Lambeau G. J. Biol. Chem. 275:7492-7496(2000) [PubMed: 10713052] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], CHARACTERIZATION.
[2]	"The DNA sequence of human chromosome 22." Dunham I., Hunt A.R., Collins J.E., Bruskiewich R., Beare D.M., Clamp M., Smink L.J., Ainscough R., Almeida J.P., Babbage A.K., Bagguley C., Bailey J., Barlow K.F., Bates K.N., Beasley O.P., Bird C.P., Blakey S.E., Bridgeman A.M. , Buck D., Burgess J., Burrill W.D., Burton J., Carder C., Carter N.P., Chen Y., Clark G., Clegg S.M., Cobley V.E., Cole C.G., Collier R.E., Connor R., Conroy D., Corby N.R., Coville G.J., Cox A.V., Davis J., Dawson E., Dhami P.D., Dockree C., Dodsworth S.J., Durbin R.M., Ellington A.G., Evans K.L., Fey J.M., Fleming K., French L., Garner A.A., Gilbert J.G.R., Goward M.E., Grafham D.V., Griffiths M.N.D., Hall C., Hall R.E., Hall-Tamlyn G., Heathcott R.W., Ho S., Holmes S., Hunt S.E., Jones M.C., Kershaw J., Kimberley A.M., King A., Laird G.K., Langford C.F., Leversha M.A., Lloyd C., Lloyd D.M., Martyn I.D., Mashreghi-Mohammadi M., Matthews L.H., Mccann O.T., Mcclay J., Mclaren S., McMurray A.A., Milne S.A., Mortimore B.J., Odell C.N., Pavitt R., Pearce A.V., Pearson D., Phillimore B.J.C.T., Phillips S.H., Plumb R.W., Ramsay H., Ramsey Y., Rogers L., Ross M.T., Scott C.E., Sehra H.K., Skuce C.D., Smalley S., Smith M.L., Soderlund C., Spragon L., Steward C.A., Sulston J.E., Swann R.M., Vaudin M., Wall M., Wallis J.M., Whiteley M.N., Willey D.L., Williams L., Williams S.A., Williamson H., Wilmer T.E., Wilming L., Wright C.L., Hubbard T., Bentley D.R., Beck S., Rogers J., Shimizu N., Minoshima S., Kawasaki K., Sasaki T., Asakawa S., Kudoh J., Shintani A., Shibuya K., Yoshizaki Y., Aoki N., Mitsuyama S., Roe B.A., Chen F., Chu L., Crabtree J., Deschamps S., Do A., Do T., Dorman A., Fang F., Fu Y., Hu P., Hua A., Kenton S., Lai H., Lao H.I., Lewis J., Lewis S., Lin S.-P., Loh P., Malaj E., Nguyen T., Pan H., Phan S., Qi S., Qian Y., Ray L., Ren Q., Shaull S., Sloan D., Song L., Wang Q., Wang Y., Wang Z., White J., Willingham D., Wu H., Yao Z., Zhan M., Zhang G., Chissoe S., Murray J., Miller N., Minx P., Fulton R., Johnson D., Bemis G., Bentley D., Bradshaw H., Bourne S., Cordes M., Du Z., Fulton L., Goela D., Graves T., Hawkins J., Hinds K., Kemp K., Latreille P., Layman D., Ozersky P., Rohlfing T., Scheet P., Walker C., Wamsley A., Wohldmann P., Pepin K., Nelson J., Korf I., Bedell J.A., Hillier L.W., Mardis E., Waterston R., Wilson R., Emanuel B.S., Shaikh T., Kurahashi H., Saitta S., Budarf M.L., McDermid H.E., Johnson A., Wong A.C.C., Morrow B.E., Edelmann L., Kim U.J., Shizuya H., Simon M.I., Dumanski J.P., Peyrard M., Kedra D., Seroussi E., Fransson I., Tapia I., Bruder C.E., O'Brien K.P., Wilkinson P., Bodenteich A., Hartman K., Hu X., Khan A.S., Lane L., Tilahun Y., Wright H. Nature 402:489-495(1999) [PubMed: 10591208] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain.
[4]	"Cellular arachidonate-releasing function of novel classes of secretory phospholipase A2s (groups III and XII)." Murakami M., Masuda S., Shimbara S., Bezzine S., Lazdunski M., Lambeau G., Gelb M.H., Matsukura S., Kokubu F., Adachi M., Kudo I. J. Biol. Chem. 278:10657-10667(2003) [PubMed: 12522102] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, MUTAGENESIS OF HIS-184.
[5]	"Cellular distribution, post-translational modification, and tumorigenic potential of human group III secreted phospholipase A(2)." Murakami M., Masuda S., Shimbara S., Ishikawa Y., Ishii T., Kudo I. J. Biol. Chem. 280:24987-24998(2005) [PubMed: 15863501] [Abstract] Cited for: TISSUE SPECIFICITY, INDUCTION, GLYCOSYLATION AT ASN-167 AND ASN-280, MUTAGENESIS OF ASN-167; HIS-184 AND ASN-280.
[6]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-326; THR-327 AND SER-335, MASS SPECTROMETRY.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	AF220490 mRNA. Translation: AAF44746.1. AC005005 Genomic DNA. Translation: AAD15617.1. BC025316 mRNA. Translation: AAH25316.1.
IPI	IPI00024578.
RefSeq	NP_056530.2.
UniGene	Hs.149623
3D structure databases
HSSP	HSSP built from PDB template 1POC based on UniProtKB P00630.
ModBase	Search...
PTM databases
PhosphoSite	Q9NZ20.
Proteomic databases
PRIDE	Q9NZ20.
Genome annotation databases
Ensembl	ENSG00000100078. Homo sapiens. [Contig view]
GeneID	50487.
KEGG	hsa:50487.
Organism-specific databases
GeneCards	GC22M029855.
H-InvDB	HIX0016386.
HGNC	HGNC:17934. PLA2G3.
HPA	HPA018314.
MIM	611651. gene.
PharmGKB	PA38267.
GenAtlas	Search...
Phylogenomic databases
HOGENOM	Q9NZ20.
HOVERGEN	Q9NZ20.
Enzyme and pathway databases
BRENDA	3.1.1.4. 247.
Gene expression databases
Bgee	Q9NZ20.
CleanEx	HS_PLA2G3.
GermOnline	ENSG00000100078. Homo sapiens.
Family and domain databases
InterPro	IPR016090. Phospholipase_A2. IPR013090. Phospholipase_A2_AS. IPR001211. Phospholipase_A2_euk. IPR008774. Phospholipase_A2_met. [Graphical view]
Gene3D	G3DSA:1.20.90.10. Phospholipase_A2. 1 hit.
PANTHER	PTHR12253. Phospholipase_A2_met. 1 hit.
Pfam	PF05826. Phospholip_A2_2. 1 hit. [Graphical view]
SMART	SM00085. PA2c. 1 hit. [Graphical view]
PROSITE	PS00119. PA2_ASP. False negative. PS00118. PA2_HIS. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	53048.
SOURCE	Search...

Entry information

Entry name

PA2G3_HUMAN

Accession

Primary (citable) accession number: Q9NZ20
Secondary accession number(s): O95768

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 11, 2002
Last sequence update:	October 1, 2000
Last modified:	June 16, 2009
This is version 76 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)