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Protein

Group 3 secretory phospholipase A2

Gene

PLA2G3

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.2 Publications

Catalytic activityi

Phosphatidylcholine + H2O = 1-acylglycerophosphocholine + a carboxylate.PROSITE-ProRule annotation

Cofactori

Ca2+Note: Binds 1 Ca2+ ion per subunit.

Enzyme regulationi

Arachidonic acid release is markedly increased by glypican, a glycosylphosphatidylinositol-anchored heparan sulfate proteoglycan.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi158 – 1581Calcium; via carbonyl oxygenBy similarity
Metal bindingi160 – 1601Calcium; via carbonyl oxygenBy similarity
Metal bindingi162 – 1621Calcium; via carbonyl oxygenBy similarity
Active sitei184 – 1841
Metal bindingi185 – 1851CalciumBy similarity
Active sitei214 – 2141PROSITE-ProRule annotation

GO - Molecular functioni

  • calcium-dependent phospholipase A2 activity Source: ProtInc
  • metal ion binding Source: UniProtKB-KW

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Hydrolase

Keywords - Biological processi

Cilium biogenesis/degradation, Lipid degradation, Lipid metabolism

Keywords - Ligandi

Calcium, Metal-binding

Enzyme and pathway databases

ReactomeiR-HSA-1482788. Acyl chain remodelling of PC.
R-HSA-1482839. Acyl chain remodelling of PE.
R-HSA-1482925. Acyl chain remodelling of PG.

Chemistry

SwissLipidsiSLP:000001086.

Names & Taxonomyi

Protein namesi
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 namesi
Name:PLA2G3
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 22

Organism-specific databases

HGNCiHGNC:17934. PLA2G3.

Subcellular locationi

GO - Cellular componenti

  • centriole Source: UniProtKB
  • extracellular region Source: Reactome
  • extracellular space Source: ProtInc
  • mast cell granule Source: Ensembl
  • plasma membrane Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Cytoskeleton, Membrane, Secreted

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi167 – 1671N → S: Loss of glycosylation. 1 Publication
Mutagenesisi184 – 1841H → Q: Loss of PGE2 synthesis. 2 Publications
Mutagenesisi280 – 2801N → S: Loss of glycosylation. 1 Publication

Organism-specific databases

PharmGKBiPA38267.

Chemistry

ChEMBLiCHEMBL4667.

Polymorphism and mutation databases

BioMutaiPLA2G3.
DMDMi317373314.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 1919Sequence analysisAdd
BLAST
Chaini20 – 509490Group 3 secretory phospholipase A2PRO_0000022992Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi159 ↔ 181By similarity
Glycosylationi167 – 1671N-linked (GlcNAc...)1 Publication
Disulfide bondi180 ↔ 220By similarity
Disulfide bondi187 ↔ 213By similarity
Disulfide bondi211 ↔ 244By similarity
Glycosylationi280 – 2801N-linked (GlcNAc...)1 Publication
Glycosylationi325 – 3251N-linked (GlcNAc...)Sequence analysis
Glycosylationi396 – 3961N-linked (GlcNAc...)Sequence analysis
Glycosylationi439 – 4391N-linked (GlcNAc...)Sequence analysis

Post-translational modificationi

N-glycosylation does not affect the catalytic activity, but is required for proper secretion. A nonglycosylated form was observed in several cell types.1 Publication
In several cell types, the N- and C-termini are cleaved off.

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiQ9NZ20.
PRIDEiQ9NZ20.

PTM databases

iPTMnetiQ9NZ20.
PhosphoSiteiQ9NZ20.

Expressioni

Tissue specificityi

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).1 Publication

Inductioni

By IL1B/interleukin-1 beta and TNF in microvascular endothelial cells (at protein level).1 Publication

Gene expression databases

BgeeiQ9NZ20.
CleanExiHS_PLA2G3.
GenevisibleiQ9NZ20. HS.

Organism-specific databases

HPAiHPA021016.

Interactioni

Protein-protein interaction databases

BioGridi119074. 2 interactions.
IntActiQ9NZ20. 2 interactions.
STRINGi9606.ENSP00000215885.

Structurei

3D structure databases

ProteinModelPortaliQ9NZ20.
SMRiQ9NZ20. Positions 154-248.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni150 – 291142Phospholipase A2-likeAdd
BLAST

Sequence similaritiesi

Belongs to the phospholipase A2 family.Curated

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiENOG410IF4P. Eukaryota.
ENOG4111S6V. LUCA.
GeneTreeiENSGT00530000063569.
HOGENOMiHOG000147808.
HOVERGENiHBG053481.
InParanoidiQ9NZ20.
KOiK01047.
OMAiLAPPLDC.
OrthoDBiEOG7DFXBZ.
PhylomeDBiQ9NZ20.
TreeFamiTF324679.

Family and domain databases

Gene3Di1.20.90.10. 2 hits.
InterProiIPR016090. PLipase_A2_dom.
IPR033113. PLipase_A2_His_AS.
[Graphical view]
PfamiPF05826. Phospholip_A2_2. 2 hits.
[Graphical view]
SUPFAMiSSF48619. SSF48619. 2 hits.
PROSITEiPS00118. PA2_HIS. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q9NZ20-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MGVQAGLFGM LGFLGVALGG SPALRWYRTS CHLTKAVPGN PLGYLSFLAK
60 70 80 90 100
DAQGLALIHA RWDAHRRLQS CSWEDEPELT AAYGALCAHE TAWGSFIHTP
110 120 130 140 150
GPELQRALAT LQSQWEACRA LEESPAGARK KRAAGQSGVP GGGHQREKRG
160 170 180 190 200
WTMPGTLWCG VGDSAGNSSE LGVFQGPDLC CREHDRCPQN ISPLQYNYGI
210 220 230 240 250
RNYRFHTISH CDCDTRFQQC LQNQHDSISD IVGVAFFNVL EIPCFVLEEQ
260 270 280 290 300
EACVAWYWWG GCRMYGTVPL ARLQPRTFYN ASWSSRATSP TPSSRSPAPP
310 320 330 340 350
KPRQKQHLRK GPPHQKGSKR PSKANTTALQ DPMVSPRLDV APTGLQGPQG
360 370 380 390 400
GLKPQGARWV CRSFRRHLDQ CEHQIGPREI EFQLLNSAQE PLFHCNCTRR
410 420 430 440 450
LARFLRLHSP PEVTNMLWEL LGTTCFKLAP PLDCVEGKNC SRDPRAIRVS
460 470 480 490 500
ARHLRRLQQR RHQLQDKGTD ERQPWPSEPL RGPMSFYNQC LQLTQAARRP

DRQQKSWSQ
Length:509
Mass (Da):57,167
Last modified:January 11, 2011 - v2
Checksum:iED03BED129B0BC9F
GO

Sequence cautioni

The sequence AAD15617.1 differs from that shown. Reason: Erroneous gene model prediction. Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti70 – 701S → A.2 Publications
Corresponds to variant rs2232176 [ dbSNP | Ensembl ].
VAR_024555
Natural varianti116 – 1161E → Q.
Corresponds to variant rs2074734 [ dbSNP | Ensembl ].
VAR_024556
Natural varianti157 – 1571L → V.
Corresponds to variant rs2074735 [ dbSNP | Ensembl ].
VAR_020288
Natural varianti307 – 3071H → Y.
Corresponds to variant rs2232180 [ dbSNP | Ensembl ].
VAR_056581
Natural varianti322 – 3221S → R.
Corresponds to variant rs2072193 [ dbSNP | Ensembl ].
VAR_024557
Natural varianti378 – 3781R → Q.
Corresponds to variant rs2232183 [ dbSNP | Ensembl ].
VAR_034366

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF220490 mRNA. Translation: AAF44746.1.
AC005005 Genomic DNA. Translation: AAD15617.1. Sequence problems.
BC025316 mRNA. Translation: AAH25316.1.
CCDSiCCDS13889.1.
RefSeqiNP_056530.2. NM_015715.4.
UniGeneiHs.149623.

Genome annotation databases

EnsembliENST00000215885; ENSP00000215885; ENSG00000100078.
GeneIDi50487.
KEGGihsa:50487.
UCSCiuc003aka.4. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF220490 mRNA. Translation: AAF44746.1.
AC005005 Genomic DNA. Translation: AAD15617.1. Sequence problems.
BC025316 mRNA. Translation: AAH25316.1.
CCDSiCCDS13889.1.
RefSeqiNP_056530.2. NM_015715.4.
UniGeneiHs.149623.

3D structure databases

ProteinModelPortaliQ9NZ20.
SMRiQ9NZ20. Positions 154-248.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi119074. 2 interactions.
IntActiQ9NZ20. 2 interactions.
STRINGi9606.ENSP00000215885.

Chemistry

ChEMBLiCHEMBL4667.
SwissLipidsiSLP:000001086.

PTM databases

iPTMnetiQ9NZ20.
PhosphoSiteiQ9NZ20.

Polymorphism and mutation databases

BioMutaiPLA2G3.
DMDMi317373314.

Proteomic databases

PaxDbiQ9NZ20.
PRIDEiQ9NZ20.

Protocols and materials databases

DNASUi50487.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000215885; ENSP00000215885; ENSG00000100078.
GeneIDi50487.
KEGGihsa:50487.
UCSCiuc003aka.4. human.

Organism-specific databases

CTDi50487.
GeneCardsiPLA2G3.
H-InvDBHIX0016386.
HGNCiHGNC:17934. PLA2G3.
HPAiHPA021016.
MIMi611651. gene.
neXtProtiNX_Q9NZ20.
PharmGKBiPA38267.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IF4P. Eukaryota.
ENOG4111S6V. LUCA.
GeneTreeiENSGT00530000063569.
HOGENOMiHOG000147808.
HOVERGENiHBG053481.
InParanoidiQ9NZ20.
KOiK01047.
OMAiLAPPLDC.
OrthoDBiEOG7DFXBZ.
PhylomeDBiQ9NZ20.
TreeFamiTF324679.

Enzyme and pathway databases

ReactomeiR-HSA-1482788. Acyl chain remodelling of PC.
R-HSA-1482839. Acyl chain remodelling of PE.
R-HSA-1482925. Acyl chain remodelling of PG.

Miscellaneous databases

GenomeRNAii50487.
NextBioi53048.
PROiQ9NZ20.
SOURCEiSearch...

Gene expression databases

BgeeiQ9NZ20.
CleanExiHS_PLA2G3.
GenevisibleiQ9NZ20. HS.

Family and domain databases

Gene3Di1.20.90.10. 2 hits.
InterProiIPR016090. PLipase_A2_dom.
IPR033113. PLipase_A2_His_AS.
[Graphical view]
PfamiPF05826. Phospholip_A2_2. 2 hits.
[Graphical view]
SUPFAMiSSF48619. SSF48619. 2 hits.
PROSITEiPS00118. PA2_HIS. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [Abstract]
    Cited for: TISSUE SPECIFICITY, INDUCTION, GLYCOSYLATION AT ASN-167 AND ASN-280, MUTAGENESIS OF ASN-167; HIS-184 AND ASN-280.
  6. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    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] [Europe PMC] [Abstract]
    Cited for: FUNCTION, SUBCELLULAR LOCATION.

Entry informationi

Entry nameiPA2G3_HUMAN
AccessioniPrimary (citable) accession number: Q9NZ20
Secondary accession number(s): O95768
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 11, 2002
Last sequence update: January 11, 2011
Last modified: May 11, 2016
This is version 136 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 22
    Human chromosome 22: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.