Q86XP0 (PA24D_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Cytosolic phospholipase A2 delta
Short name=cPLA2-delta
EC=3.1.1.4

Alternative name(s):
Phospholipase A2 group IVD

Gene names

Name:

PLA2G4D

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	818 AA.
Sequence status	Complete.
Protein existence	Evidence at transcript level

General annotation (Comments)

Function	Calcium-dependent phospholipase A2 that selectively hydrolyzes glycerophospholipids in the sn-2 position. Not arachidonic acid-specific but has linoleic acid-specific activity. May play a role in inflammation in psoriatic lesions. Ref.1
Catalytic activity	Phosphatidylcholine + H2O = 1-acylglycerophosphocholine + a carboxylate.
Enzyme regulation	Stimulated by cytosolic Ca2+. Ref.1
Subcellular location	Cytoplasm › cytosol. Cytoplasmic vesicle membrane; Peripheral membrane protein; Cytoplasmic side By similarity. Note: Translocates to membrane vesicles in a calcium-dependent fashion. Translocates to perinuclear regions upon ionomycin stimulation By similarity.
Tissue specificity	Expressed in stratified squamous epithelia, such as those in skin and cervix, but not in other tissues. Strongly expressed in the upper spinous layer of the psoriatic epidermis, expressed weakly and discontinuously in atopic dermatitis and mycosis fungoides, and not detected in the epidermis of normal skin. Ref.1
Domain	The N-terminal C2 domain associates with lipid membranes upon calcium binding. It modulates enzyme activity by presenting the active site to its substrate in response to elevations of cytosolic Ca2+ By similarity.
Sequence similarities	Contains 1 C2 domain. Contains 1 PLA2c domain.
Sequence caution	The sequence AAH34571.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.

Ontologies

Keywords
Biological process	Lipid degradation Lipid metabolism
Cellular component	Cytoplasm Cytoplasmic vesicle Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Ligand	Calcium Metal-binding
Molecular function	Hydrolase
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	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 phospholipid catabolic process Inferred from electronic annotation. Source: InterPro
Cellular_component	cytoplasmic vesicle membrane Inferred from electronic annotation. Source: UniProtKB-SubCell cytosol Traceable author statement. Source: Reactome
Molecular_function	metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW phospholipase A2 activity Inferred from electronic annotation. Source: EC
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q86XP0-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: Q86XP0-2)

The sequence of this isoform differs from the canonical sequence as follows:
     682-723: ALQQTELYCR...HLFSDPACPE → VPWSPQGNPS...VPKGRRGVRP
     724-818: Missing.

Note: May be due to an intron retention.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 818	818	Cytosolic phospholipase A2 delta		PRO_0000247023
Regions
	Domain	9 – 120	112	C2
	Domain	273 – 818	546	PLA2c
Sites
	Active site	361	1	Nucleophile By similarity
	Active site	647	1	Proton acceptor By similarity
Natural variations
	Alternative sequence	682 – 723	42	ALQQT…PACPE → VPWSPQGNPSAQPGQAPEAS SRATEPLPHTAGVPKGRRGV RP in isoform 2.		VSP_019881
	Alternative sequence	724 – 818	95	Missing in isoform 2.		VSP_019882
	Natural variant	275	1	P → R. Corresponds to variant rs11635685 [ dbSNP | Ensembl ].		VAR_057676
	Natural variant	434	1	S → T. Corresponds to variant rs4924618 [ dbSNP | Ensembl ].		VAR_057677
	Natural variant	573	1	R → W. Corresponds to variant rs17747505 [ dbSNP | Ensembl ].		VAR_027049
	Natural variant	649	1	A → G. Corresponds to variant rs17690899 [ dbSNP | Ensembl ].		VAR_027050
	Natural variant	747	1	R → G. Ref.4 Corresponds to variant rs2459692 [ dbSNP | Ensembl ].		VAR_027051
	Natural variant	783	1	R → Q. Corresponds to variant rs750052 [ dbSNP | Ensembl ].		VAR_057678
	Natural variant	807	1	R → Q. Corresponds to variant rs750051 [ dbSNP | Ensembl ].		VAR_057679
Experimental info
	Sequence conflict	10	1	P → T in BAC67158. Ref.1
Isoform 2:
	Sequence conflict	713	1	G → R in AAH34571. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified November 24, 2009. Version 2. Checksum: 06187324748A4C21	FASTA	818	91,952
	10 20 30 40 50 60 MESLSPGGPP GHPYQGEAST CWQLTVRVLE ARNLRWADLL SEADPYVILQ LSTAPGMKFK 70 80 90 100 110 120 TKTLTDTSHP VWNEAFRFLI QSQVKNVLEL SIYDEDSVTE DDICFKVLYD ISEVLPGKLL 130 140 150 160 170 180 RKTFSQSPQG EEELDVEFLM EETSDRPENL ITNKVIVARE LSCLDVHLDS TGSTAVVADQ 190 200 210 220 230 240 DKLELELVLK GSYEDTQTSF LGTASAFRFH YMAALETELS GRLRSSRSNG WNGDNSAGYL 250 260 270 280 290 300 TVPLRPLTIG KEVTMDVPAP NAPGVRLQLK AEGCPEELAV HLGFNLCAEE QAFLSRRKQV 310 320 330 340 350 360 VAKALKQALQ LDRDLQEDEV PVVGIMATGG GARAMTSLYG HLLALQKLGL LDCVTYFSGI 370 380 390 400 410 420 SGSTWTMAHL YGDPEWSQRD LEGPIRYARE HLAKSKLEVF SPERLASYRR ELELRAEQGH 430 440 450 460 470 480 PTTFVDLWAL VLESMLHGQV MDQKLSGQRA ALERGQNPLP LYLSLNVKEN NLETLDFKEW 490 500 510 520 530 540 VEFSPYEVGF LKYGAFVPPE LFGSEFFMGR LMRRIPEPRI CFLEAIWSNI FSLNLLDAWY 550 560 570 580 590 600 DLTSSGESWK QHIKDKTRSL EKEPLTTSGT SSRLEASWLQ PGTALAQAFK GFLTGRPLHQ 610 620 630 640 650 660 RSPNFLQGLQ LHQDYCSHKD FSTWADYQLD SMPSQLTPKE PRLCLVDAAY FINTSSPSMF 670 680 690 700 710 720 RPGRRLDLIL SFDYSLSAPF EALQQTELYC RARGLPFPRV EPSPQDQHQP RECHLFSDPA 730 740 750 760 770 780 CPEAPILLHF PLVNASFKDH SAPGVQRSPA ELQGGQVDLT GATCPYTLSN MTYKEEDFER 790 800 810 LLRLSDYNVQ TSQGAILQAL RTALKHRTLE ARPPRAQT
	Isoform 2 [UniParc]. Checksum: 0C385309D4BAB085	FASTA	723	80,930
	10 20 30 40 50 60 MESLSPGGPP GHPYQGEAST CWQLTVRVLE ARNLRWADLL SEADPYVILQ LSTAPGMKFK 70 80 90 100 110 120 TKTLTDTSHP VWNEAFRFLI QSQVKNVLEL SIYDEDSVTE DDICFKVLYD ISEVLPGKLL 130 140 150 160 170 180 RKTFSQSPQG EEELDVEFLM EETSDRPENL ITNKVIVARE LSCLDVHLDS TGSTAVVADQ 190 200 210 220 230 240 DKLELELVLK GSYEDTQTSF LGTASAFRFH YMAALETELS GRLRSSRSNG WNGDNSAGYL 250 260 270 280 290 300 TVPLRPLTIG KEVTMDVPAP NAPGVRLQLK AEGCPEELAV HLGFNLCAEE QAFLSRRKQV 310 320 330 340 350 360 VAKALKQALQ LDRDLQEDEV PVVGIMATGG GARAMTSLYG HLLALQKLGL LDCVTYFSGI 370 380 390 400 410 420 SGSTWTMAHL YGDPEWSQRD LEGPIRYARE HLAKSKLEVF SPERLASYRR ELELRAEQGH 430 440 450 460 470 480 PTTFVDLWAL VLESMLHGQV MDQKLSGQRA ALERGQNPLP LYLSLNVKEN NLETLDFKEW 490 500 510 520 530 540 VEFSPYEVGF LKYGAFVPPE LFGSEFFMGR LMRRIPEPRI CFLEAIWSNI FSLNLLDAWY 550 560 570 580 590 600 DLTSSGESWK QHIKDKTRSL EKEPLTTSGT SSRLEASWLQ PGTALAQAFK GFLTGRPLHQ 610 620 630 640 650 660 RSPNFLQGLQ LHQDYCSHKD FSTWADYQLD SMPSQLTPKE PRLCLVDAAY FINTSSPSMF 670 680 690 700 710 720 RPGRRLDLIL SFDYSLSAPF EVPWSPQGNP SAQPGQAPEA SSRATEPLPH TAGVPKGRRG VRP

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning of a gene for a novel epithelium-specific cytosolic phospholipase A2, cPLA2delta, induced in psoriatic skin." Chiba H., Michibata H., Wakimoto K., Seishima M., Kawasaki S., Okubo K., Mitsui H., Torii H., Imai Y. J. Biol. Chem. 279:12890-12897(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, ENZYME REGULATION, TISSUE SPECIFICITY.
[2]	"Analysis of the DNA sequence and duplication history of human chromosome 15." Zody M.C., Garber M., Sharpe T., Young S.K., Rowen L., O'Neill K., Whittaker C.A., Kamal M., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Kodira C.D., Madan A., Qin S., Yang X., Abbasi N., Abouelleil A. , Arachchi H.M., Baradarani L., Birditt B., Bloom S., Bloom T., Borowsky M.L., Burke J., Butler J., Cook A., DeArellano K., DeCaprio D., Dorris L. III, Dors M., Eichler E.E., Engels R., Fahey J., Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G., Johnson E., Jones C., Kamat A., Kaur A., Locke D.P., Madan A., Munson G., Jaffe D.B., Lui A., Macdonald P., Mauceli E., Naylor J.W., Nesbitt R., Nicol R., O'Leary S.B., Ratcliffe A., Rounsley S., She X., Sneddon K.M.B., Stewart S., Sougnez C., Stone S.M., Topham K., Vincent D., Wang S., Zimmer A.R., Birren B.W., Hood L., Lander E.S., Nusbaum C. Nature 440:671-675(2006) [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] OF 491-818 (ISOFORM 2). Tissue: Brain.
[4]	"A family based study of the genetic association between the PLA2G4D gene and schizophrenia." Tao R., Yu Y., Zhang X., Shi J., Guo Y., Wang C., Han B., Xu Q., Shang H., Zhang X., Xie L., Liu S., Ju G., Shen Y., Wei J. Prostaglandins Leukot. Essent. Fatty Acids 73:419-422(2005) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT GLY-747.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AB090876 mRNA. Translation: BAC67158.1. AC084693 Genomic DNA. No translation available. BC034571 mRNA. Translation: AAH34571.1. Different initiation.
IPI	IPI00384577. IPI00784249.
RefSeq	NP_828848.3. NM_178034.3.
UniGene	Hs.380225.
3D structure databases
ProteinModelPortal	Q86XP0.
SMR	Q86XP0. Positions 23-166, 234-807.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000290472.
PTM databases
PhosphoSite	Q86XP0.
Polymorphism databases
DMDM	269849641.
Proteomic databases
PaxDb	Q86XP0.
PRIDE	Q86XP0.
Protocols and materials databases
DNASU	283748.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000290472; ENSP00000290472; ENSG00000159337.
GeneID	283748.
KEGG	hsa:283748.
UCSC	uc001zox.3. human.
Organism-specific databases
CTD	283748.
GeneCards	GC15M042359.
H-InvDB	HIX0026772.
HGNC	HGNC:30038. PLA2G4D.
HPA	HPA039489.
MIM	612864. gene.
neXtProt	NX_Q86XP0.
PharmGKB	PA134974074.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG300348.
HOGENOM	HOG000231788.
HOVERGEN	HBG080412.
InParanoid	Q86XP0.
KO	K16342.
OMA	TYKEEDF.
OrthoDB	EOG43N7C3.
PhylomeDB	Q86XP0.
Enzyme and pathway databases
Reactome	REACT_111217. Metabolism.
Gene expression databases
Bgee	Q86XP0.
CleanEx	HS_PLA2G4D.
Genevestigator	Q86XP0.
GermOnline	ENSG00000159337. Homo sapiens.
Family and domain databases
InterPro	IPR016035. Acyl_Trfase/lysoPLipase. IPR000008. C2_Ca-dep. IPR008973. C2_Ca/lipid-bd_dom_CaLB. IPR018029. C2_membr_targeting. IPR002642. LysoPLipase_cat_dom. [Graphical view]
Pfam	PF00168. C2. 1 hit. PF01735. PLA2_B. 1 hit. [Graphical view]
SMART	SM00239. C2. 1 hit. SM00022. PLAc. 1 hit. [Graphical view]
SUPFAM	SSF52151. Acyl_Trfase/lysoPlipase. 1 hit. SSF49562. C2_CaLB. 1 hit.
PROSITE	PS50004. C2. 1 hit. PS51210. PLA2C. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChEMBL	CHEMBL2287.
GenomeRNAi	283748.
NextBio	94215.
SOURCE	Search...

Entry information

Entry name

PA24D_HUMAN

Accession

Primary (citable) accession number: Q86XP0
Secondary accession number(s): Q8N176

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 25, 2006
Last sequence update:	November 24, 2009
Last modified:	May 1, 2013
This is version 85 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.