P14555 (PA2GA_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Phospholipase A2, membrane associated
EC=3.1.1.4

Alternative name(s):
GIIC sPLA2
Group IIA phospholipase A2
Non-pancreatic secretory phospholipase A2
Short name=NPS-PLA2
Phosphatidylcholine 2-acylhydrolase 2A

Gene names

Name:	PLA2G2A
Synonyms:	PLA2B, PLA2L, RASF-A

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	144 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	Thought to participate in the regulation of the phospholipid metabolism in biomembranes including eicosanoid biosynthesis. Catalyzes the calcium-dependent hydrolysis of the 2-acyl groups in 3-sn-phosphoglycerides.
Catalytic activity	Phosphatidylcholine + H2O = 1-acylglycerophosphocholine + a carboxylate.
Cofactor	Binds 1 calcium ion per subunit.
Subcellular location	Membrane; Peripheral membrane protein.
Miscellaneous	Group II phospholipase A2 is found in many cells and also extracellularly. The membrane-bound and secreted forms are identical and are encoded by a single gene.
Sequence similarities	Belongs to the phospholipase A2 family.

Ontologies

Keywords
Biological process	Lipid degradation Lipid metabolism
Cellular component	Membrane
Coding sequence diversity	Polymorphism
Domain	Signal
Ligand	Calcium Metal-binding
Molecular function	Hydrolase
PTM	Disulfide bond
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	defense response to Gram-positive bacterium Traceable author statement PubMed 18827909. Source: BHF-UCL lipid catabolic process Inferred from electronic annotation. Source: UniProtKB-KW low-density lipoprotein particle remodeling Traceable author statement PubMed 18827909. Source: BHF-UCL phosphatidic acid biosynthetic process Traceable author statement. Source: Reactome phosphatidylcholine acyl-chain remodeling Traceable author statement. Source: Reactome phosphatidylethanolamine acyl-chain remodeling Traceable author statement. Source: Reactome phosphatidylglycerol acyl-chain remodeling Traceable author statement. Source: Reactome phosphatidylinositol acyl-chain remodeling Traceable author statement. Source: Reactome phosphatidylserine acyl-chain remodeling Traceable author statement. Source: Reactome positive regulation of inflammatory response Traceable author statement PubMed 18827909. Source: BHF-UCL positive regulation of macrophage derived foam cell differentiation Traceable author statement PubMed 18827909. Source: BHF-UCL
Cellular_component	endoplasmic reticulum membrane Traceable author statement. Source: Reactome extracellular space Inferred from direct assay PubMed 17069818. Source: BHF-UCL secretory granule Inferred from electronic annotation. Source: Compara
Molecular_function	calcium ion binding Inferred from electronic annotation. Source: InterPro calcium-dependent phospholipase A2 activity Traceable author statement PubMed 9272153. Source: UniProtKB phospholipid binding Inferred from direct assay PubMed 9032461. Source: BHF-UCL
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 20

20

Ref.11 Ref.12 Ref.13 Ref.14

Chain

21 – 144

124

Phospholipase A2, membrane associated

PRO_0000022750

Sites

Active site

67

1

By similarity

Active site

111

1

By similarity

Metal binding

47

1

Calcium; via carbonyl oxygen

Metal binding

49

1

Calcium; via carbonyl oxygen

Metal binding

51

1

Calcium; via carbonyl oxygen

Metal binding

68

1

Calcium

Amino acid modifications

Disulfide bond

46 ↔ 137

Disulfide bond

48 ↔ 64

Disulfide bond

63 ↔ 117

Disulfide bond

69 ↔ 144

Disulfide bond

70 ↔ 110

Disulfide bond

79 ↔ 103

Disulfide bond

97 ↔ 108

Natural variations

Natural variant

19

1

H → Y. Ref.6
Corresponds to variant rs11573162 [ dbSNP | Ensembl ].

VAR_018953

Experimental info

Sequence conflict

12

1

I → Y in AAT73043. Ref.4

Secondary structure

1

.

.

.

.

.

.

.

.

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.

.

.

.

.

.

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.

.

.

.

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.

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144

Helix Strand Turn

Details...

Helix

22 – 33

12

Helix

37 – 40

4

Turn

41 – 43

3

Turn

45 – 47

3

Beta strand

48 – 50

3

Helix

59 – 76

18

Beta strand

81 – 83

3

Beta strand

88 – 91

4

Beta strand

94 – 97

4

Helix

102 – 120

19

Helix

122 – 124

3

Helix

127 – 129

3

Helix

134 – 136

3

Sequences

	Sequence		Length	Mass (Da)
	P14555 [UniParc]. Last modified April 1, 1990. Version 2. Checksum: 923C5FA0C6979CDA	FASTA	144	16,083
	10 20 30 40 50 60 MKTLLLLAVI MIFGLLQAHG NLVNFHRMIK LTTGKEAALS YGFYGCHCGV GGRGSPKDAT 70 80 90 100 110 120 DRCCVTHDCC YKRLEKRGCG TKFLSYKFSN SGSRITCAKQ DSCRSQLCEC DKAAATCFAR 130 140 NKTTYNKKYQ YYSNKHCRGS TPRC

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning and recombinant expression of phospholipase A2 present in rheumatoid arthritic synovial fluid." Seilhamer J.J., Pruzanski W., Vadas P., Plant S., Miller J.A., Kloss J., Johnson L.K. J. Biol. Chem. 264:5335-5338(1989) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Rheumatoid arthritic synovial fluid.
[2]	"Structure and properties of a human non-pancreatic phospholipase A2." Kramer R.M., Hession C., Johansen B., Hayes G., McGray P., Chow E.P., Tizard R., Pepinsky R.B. J. Biol. Chem. 264:5768-5775(1989) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]	"Structure and properties of a secretable phospholipase A2 from human platelets." Kramer R.M., Johansen B., Hession C., Pepinsky R.B. Adv. Exp. Med. Biol. 275:35-53(1990) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]	"Cloning and sequence determination of human platelet phospholipase A2 from liver tissues." Liang N.S., Fang Z.W., Li Y., Yang F., Lu Y., Xie Y.A. Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Liver.
[5]	"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)." Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B. Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[6]	NIEHS SNPs program Submitted (NOV-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT TYR-19.
[7]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Tongue.
[8]	"The DNA sequence and biological annotation of human chromosome 1." Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R. Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[9]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[10]	"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]. Tissue: Prostate.
[11]	"The primary structure of a membrane-associated phospholipase A2 from human spleen." Kanda A., Ono T., Yoshida N., Tojo H., Okamoto M. Biochem. Biophys. Res. Commun. 163:42-48(1989) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 21-144. Tissue: Spleen.
[12]	"Amino acid composition and NH2-terminal amino acid sequence of human phospholipase A2 purified from rheumatoid synovial fluid." Hara S., Kudo I., Matsuta K., Miyamoto T., Inoue K. J. Biochem. 104:326-328(1988) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 21-54. Tissue: Synovial fluid.
[13]	"Phospholipase A2 from human synovial fluid: purification and structural homology to the placental enzyme." Lai C.Y., Wada K. Biochem. Biophys. Res. Commun. 157:488-493(1988) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 21-33. Tissue: Synovial fluid.
[14]	"Purification and characterization of a phospholipase A2 from human ileal mucosa." Minami T., Tojo H., Shinomura Y., Matsuzawa Y., Okamoto M. Biochim. Biophys. Acta 1170:125-130(1993) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 21-75. Tissue: Ileal mucosa.
[15]	"Structure of recombinant human rheumatoid arthritic synovial fluid phospholipase A2 at 2.2-A resolution." Wery J.-P., Schevitz R.W., Clawson D.K., Bobbitt J.L., Dow E.R., Gamboa G., Goodson T. Jr., Hermann R.B., Kramer R.M., McClure D.B., Mihelich E.D., Putnam J.E., Sharp J.D., Stark D.H., Teater C., Warrick M.W., Jones N.D. Nature 352:79-82(1991) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS).
[16]	"Structures of free and inhibited human secretory phospholipase A2 from inflammatory exudate." Scott D.L., White S.P., Browning J.L., Rosa J.J., Gelb M.H., Sigler P.B. Science 254:1007-1010(1991) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS).
[17]	"Structure-based design of the first potent and selective inhibitor of human non-pancreatic secretory phospholipase A2." Schevitz R.W., Bach N.J., Carlson D.G., Chirgadze N.Y., Clawson D.K., Dillard R.D., Draheim S.E., Hartley L.W., Jones N.D., Mihelich E.D., Olkowski J.L., Snyder D.W., Dand S.C., Wery J.-P. Nat. Struct. Biol. 2:458-465(1995) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS).
[18]	"Crystal structure of human secretory phospholipase A2-IIA complex with the potent indolizine inhibitor 120-1032." Kitadokoro K., Hagishita S., Sato T., Ohtan M., Miki K. J. Biochem. 123:619-623(1998) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS).
+	Additional computationally mapped references.

Web resources

NIEHS-SNPs

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

M22430 mRNA. Translation: AAA36550.1.
M22431 Genomic DNA. Translation: AAA36549.1.
AY656695 mRNA. Translation: AAT73043.1.
CR456865 mRNA. Translation: CAG33146.1.
AY462114 Genomic DNA. Translation: AAR16084.1.
AL358253 Genomic DNA. Translation: CAH74017.1.
AK291302 mRNA. Translation: BAF83991.1.
CH471134 Genomic DNA. Translation: EAW94907.1.
BC005919 mRNA. Translation: AAH05919.1.

IPI

IPI00026962.

PIR

PSHUYF. A32862.

RefSeq

NP_000291.1. NM_000300.3.
NP_001155199.1. NM_001161727.1.
NP_001155200.1. NM_001161728.1.
NP_001155201.1. NM_001161729.1.

UniGene

Hs.466804.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1AYP	X-ray	2.57	A/B/C/D/E/F	21-144	[»]
1BBC	X-ray	2.20	A	21-144	[»]
1DB4	X-ray	2.20	A	21-144	[»]
1DB5	X-ray	2.80	A	21-144	[»]
1DCY	X-ray	2.70	A	21-144	[»]
1J1A	X-ray	2.20	A/B	21-144	[»]
1KQU	X-ray	2.10	A	21-144	[»]
1KVO	X-ray	2.00	A/B/C/D/E/F	21-144	[»]
1N28	X-ray	1.50	A/B	22-144	[»]
1N29	X-ray	2.60	A	22-144	[»]
1POD	X-ray	2.10	A	21-144	[»]
1POE	X-ray	2.10	A/B	21-144	[»]
2GNY	model	-	A	21-144	[»]
3U8B	X-ray	2.30	A	21-144	[»]
3U8D	X-ray	1.80	A/B	21-144	[»]
3U8H	X-ray	2.30	A/B	21-144	[»]
3U8I	X-ray	1.10	A/B	21-144	[»]

ProteinModelPortal

P14555.

ModBase

Search...

Protein-protein interaction databases

IntAct

P14555. 1 interaction.

MINT

MINT-1206447.

STRING

9606.ENSP00000364252.

PTM databases

PhosphoSite

P14555.

Polymorphism databases

DMDM

129483.

Proteomic databases

PaxDb

P14555.

PeptideAtlas

P14555.

PRIDE

P14555.

Protocols and materials databases

DNASU

5320.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000375111; ENSP00000364252; ENSG00000188257.
ENST00000400520; ENSP00000383364; ENSG00000188257.

GeneID

5320.

KEGG

hsa:5320.

UCSC

uc001bcu.3. human.

Organism-specific databases

CTD

5320.

GeneCards

GC01M020301.

HGNC

HGNC:9031. PLA2G2A.

HPA

HPA015236.

MIM

172411. gene.

neXtProt

NX_P14555.

PharmGKB

PA270.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG271943.

HOGENOM

HOG000231749.

HOVERGEN

HBG008137.

InParanoid

P14555.

KO

K01047.

OMA

RGCGTKF.

OrthoDB

EOG4N04G9.

PhylomeDB

P14555.

Enzyme and pathway databases

Pathway_Interaction_DB

glypican_1pathway. Glypican 1 network.

Reactome

REACT_111217. Metabolism.

Gene expression databases

Bgee

P14555.

CleanEx

HS_PLA2G2A.

Genevestigator

P14555.

GermOnline

ENSG00000188257. Homo sapiens.

Family and domain databases

Gene3D

1.20.90.10. 1 hit.

InterPro

IPR001211. PLipase_A2.
IPR013090. PLipase_A2_AS.
IPR016090. PLipase_A2_dom.
[Graphical view]

PANTHER

PTHR11716. PTHR11716. 1 hit.

Pfam

PF00068. Phospholip_A2_1. 1 hit.
[Graphical view]

PRINTS

PR00389. PHPHLIPASEA2.

SMART

SM00085. PA2c. 1 hit.
[Graphical view]

SUPFAM

SSF48619. PhospholipaseA2. 1 hit.

PROSITE

PS00119. PA2_ASP. 1 hit.
PS00118. PA2_HIS. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

P14555.

ChEMBL

CHEMBL3474.

ChiTaRS

PLA2G2A. human.

EvolutionaryTrace

P14555.

GenomeRNAi

5320.

NextBio

20582.

SOURCE

Search...

Entry information

Entry name

PA2GA_HUMAN

Accession

Primary (citable) accession number: P14555
Secondary accession number(s): A8K5I7 , Q6DN24, Q6IBD9, Q9UCD2

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 1, 1990
Last sequence update:	April 1, 1990
Last modified:	May 1, 2013
This is version 157 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.