Q9NZ20 (PA2G3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

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
Short name=sPLA2-III
Phosphatidylcholine 2-acylhydrolase 3

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. Plays a role in ciliogenesis. Ref.4 Ref.7
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. Cytoplasm › cytoskeleton › centrosome › centriole Ref.4 Ref.7.
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/interleukin-1 beta and TNF in microvascular endothelial cells (at protein level). Ref.5
Post-translational modification	N-glycosylation does not affect the catalytic 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.
Sequence caution	The sequence AAD15617.1 differs from that shown. Reason: Erroneous gene model prediction.

Ontologies

Keywords
Biological process	Cilium biogenesis/degradation Lipid degradation
Cellular component	Cell membrane Cytoplasm Cytoskeleton Membrane Secreted
Coding sequence diversity	Polymorphism
Domain	Signal
Ligand	Calcium Metal-binding
Molecular function	Hydrolase
PTM	Disulfide bond Glycoprotein Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	cilium morphogenesis Inferred from mutant phenotype Ref.7. Source: UniProtKB lipid catabolic process Inferred from electronic annotation. Source: UniProtKB-KW phospholipid metabolic process Traceable author statement. Source: ProtInc
Cellular component	centriole Inferred from direct assay Ref.7. Source: UniProtKB extracellular space Traceable author statement. Source: ProtInc plasma membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	calcium ion binding Inferred from electronic annotation. Source: InterPro calcium-dependent phospholipase A2 activity 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	S → A. Ref.1 Ref.3 Corresponds to variant rs2232176 [ dbSNP | Ensembl ].		VAR_024555
	Natural variant	116	1	E → Q. Corresponds to variant rs2074734 [ dbSNP | Ensembl ].		VAR_024556
	Natural variant	157	1	L → V. Corresponds to variant rs2074735 [ dbSNP | Ensembl ].		VAR_020288
	Natural variant	307	1	H → Y. Corresponds to variant rs2232180 [ dbSNP | Ensembl ].		VAR_056581
	Natural variant	322	1	S → R. Corresponds to variant rs2072193 [ dbSNP | Ensembl ].		VAR_024557
	Natural variant	378	1	R → Q. Corresponds to variant rs2232183 [ dbSNP | Ensembl ].		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 [UniParc]. Last modified January 11, 2011. Version 2. Checksum: ED03BED129B0BC9F	FASTA	509	57,167
	10 20 30 40 50 60 MGVQAGLFGM LGFLGVALGG SPALRWYRTS CHLTKAVPGN PLGYLSFLAK DAQGLALIHA 70 80 90 100 110 120 RWDAHRRLQS 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, VARIANT ALA-70.
[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], VARIANT ALA-70. 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. Tissue: Cervix carcinoma.
[7]	"Functional genomic screen for modulators of ciliogenesis and cilium length." Kim J., Lee J.E., Heynen-Genel S., Suyama E., Ono K., Lee K., Ideker T., Aza-Blanc P., Gleeson J.G. Nature 464:1048-1051(2010) [PubMed: 20393563] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF220490 mRNA. Translation: AAF44746.1. AC005005 Genomic DNA. Translation: AAD15617.1. Sequence problems. BC025316 mRNA. Translation: AAH25316.1.
IPI	IPI00024578.
RefSeq	NP_056530.2. NM_015715.3.
UniGene	Hs.149623.
3D structure databases
ProteinModelPortal	Q9NZ20.
SMR	Q9NZ20. Positions 151-268.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9NZ20. 2 interactions.
STRING	Q9NZ20.
PTM databases
PhosphoSite	Q9NZ20.
Polymorphism databases
DMDM	20139239.
Proteomic databases
PRIDE	Q9NZ20.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000215885; ENSP00000215885; ENSG00000100078.
GeneID	50487.
KEGG	hsa:50487.
UCSC	uc003aka.1. human.
Organism-specific databases
CTD	50487.
GeneCards	GC22M031530.
H-InvDB	HIX0016386.
HGNC	HGNC:17934. PLA2G3.
HPA	HPA021016.
MIM	611651. gene.
neXtProt	NX_Q9NZ20.
PharmGKB	PA38267.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG09862.
GeneTree	ENSGT00530000063569.
HOGENOM	HBG125085.
HOVERGEN	HBG053481.
InParanoid	Q9NZ20.
OMA	HTPGPEL.
OrthoDB	EOG4CC415.
PhylomeDB	Q9NZ20.
Gene expression databases
ArrayExpress	Q9NZ20.
Bgee	Q9NZ20.
CleanEx	HS_PLA2G3.
Genevestigator	Q9NZ20.
GermOnline	ENSG00000100078. Homo sapiens.
Family and domain databases
InterPro	IPR016090. PLipase_A2. IPR013090. PLipase_A2_AS. IPR001211. PLipase_A2_euk. [Graphical view]
Gene3D	G3DSA:1.20.90.10. Phospholipase_A2. 2 hits.
KO	K01047.
PANTHER	PTHR12253. Phospholipase_A2_met. 1 hit.
Pfam	PF05826. Phospholip_A2_2. 2 hits. [Graphical view]
SMART	SM00085. PA2c. 1 hit. [Graphical view]
SUPFAM	SSF48619. PhospholipaseA2. 2 hits.
PROSITE	PS00119. PA2_ASP. False negative. PS00118. PA2_HIS. 1 hit. [Graphical view]
ProtoNet	Search...
Other
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:	January 11, 2011
Last modified:	January 25, 2012
This is version 102 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.