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Protein

Calcium-independent phospholipase A2-gamma

Gene

PNPLA8

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

Functioni

Calcium-independent phospholipase A2, which catalyzes the hydrolysis of the sn-2 position of glycerophospholipids, PtdSer and to a lower extent PtdCho. Cleaves membrane phospholipids.2 Publications

Catalytic activityi

2-lysophosphatidylcholine + H2O = glycerophosphocholine + a carboxylate.

Enzyme regulationi

Inhibited by E-6-bromomethylene-3-1-naphthalenyl-2H-tetrahydropyran-2-one (BEL).

pH dependencei

Optimum pH is 8.0.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei483NucleophilePROSITE-ProRule annotation1
Active sitei627Proton acceptorPROSITE-ProRule annotation1

GO - Molecular functioni

  • ATP binding Source: UniProtKB
  • calcium-independent phospholipase A2 activity Source: UniProtKB
  • lysophospholipase activity Source: UniProtKB-EC
  • phospholipase A2 activity Source: Reactome

GO - Biological processi

  • arachidonic acid metabolic process Source: UniProtKB
  • arachidonic acid secretion Source: UniProtKB
  • cell death Source: UniProtKB
  • fatty acid metabolic process Source: UniProtKB
  • linoleic acid metabolic process Source: UniProtKB
  • phosphatidylcholine acyl-chain remodeling Source: Reactome
  • phosphatidylcholine catabolic process Source: UniProtKB
  • phosphatidylethanolamine acyl-chain remodeling Source: Reactome
  • phosphatidylethanolamine catabolic process Source: UniProtKB
  • prostaglandin biosynthetic process Source: UniProtKB

Keywordsi

Molecular functionHydrolase
Biological processLipid degradation, Lipid metabolism

Enzyme and pathway databases

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

Chemistry databases

SwissLipidsiSLP:000000564.
SLP:000000607.

Names & Taxonomyi

Protein namesi
Recommended name:
Calcium-independent phospholipase A2-gamma (EC:3.1.1.5)
Alternative name(s):
Intracellular membrane-associated calcium-independent phospholipase A2 gamma
Short name:
iPLA2-gamma
PNPLA-gamma
Patatin-like phospholipase domain-containing protein 8
iPLA2-2
Gene namesi
Name:PNPLA8
Synonyms:IPLA22, IPLA2G
ORF Names:BM-043
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 7

Organism-specific databases

EuPathDBiHostDB:ENSG00000135241.16.
HGNCiHGNC:28900. PNPLA8.

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Transmembranei475 – 495HelicalSequence analysisAdd BLAST21

Keywords - Cellular componenti

Cytoplasm, Endoplasmic reticulum, Golgi apparatus, Membrane

Pathology & Biotechi

Involvement in diseasei

Mitochondrial myopathy with lactic acidosis (MMLA)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn autosomal recessive disorder characterized by progressive muscle weakness, hypotonia, seizures, poor weight gain, lactic acidosis, and elevated serum pyruvate concentration. Some patients manifest growth failure and moderate neural deafness.
See also OMIM:251950

Organism-specific databases

DisGeNETi50640.
MalaCardsiPNPLA8.
MIMi251950. phenotype.
OpenTargetsiENSG00000135241.
PharmGKBiPA145148236.

Chemistry databases

ChEMBLiCHEMBL2189126.

Polymorphism and mutation databases

BioMutaiPNPLA8.
DMDMi74734299.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00003032141 – 782Calcium-independent phospholipase A2-gammaAdd BLAST782

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi4N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi361N-linked (GlcNAc...) asparagineSequence analysis1
Modified residuei736N6-succinyllysineBy similarity1

Keywords - PTMi

Glycoprotein

Proteomic databases

EPDiQ9NP80.
MaxQBiQ9NP80.
PaxDbiQ9NP80.
PeptideAtlasiQ9NP80.
PRIDEiQ9NP80.

PTM databases

iPTMnetiQ9NP80.
PhosphoSitePlusiQ9NP80.

Expressioni

Tissue specificityi

Expressed in parenchymal tissues including heart, skeletal muscle, placenta, brain, liver and pancreas. Also expressed in bronchial epithelial cells and kidney. Highest expression is observed in skeletal muscle and heart.4 Publications

Gene expression databases

BgeeiENSG00000135241.
CleanExiHS_PNPLA8.
ExpressionAtlasiQ9NP80. baseline and differential.
GenevisibleiQ9NP80. HS.

Organism-specific databases

HPAiHPA020083.

Interactioni

Protein-protein interaction databases

BioGridi119111. 8 interactors.
IntActiQ9NP80. 9 interactors.
MINTiMINT-4725725.
STRINGi9606.ENSP00000257694.

Structurei

3D structure databases

ProteinModelPortaliQ9NP80.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini445 – 640PNPLAPROSITE-ProRule annotationAdd BLAST196

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi449 – 454GXGXXGPROSITE-ProRule annotation6
Motifi481 – 485GXSXGPROSITE-ProRule annotation5
Motifi627 – 629DGA/GPROSITE-ProRule annotation3

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG4231. Eukaryota.
ENOG410XQXJ. LUCA.
GeneTreeiENSGT00530000063645.
HOGENOMiHOG000115579.
HOVERGENiHBG102100.
InParanoidiQ9NP80.
KOiK16815.
OMAiKYDSKSQ.
OrthoDBiEOG091G05AJ.
PhylomeDBiQ9NP80.
TreeFamiTF319230.

Family and domain databases

InterProiView protein in InterPro
IPR016035. Acyl_Trfase/lysoPLipase.
IPR002641. PNPLA_dom.
PfamiView protein in Pfam
PF01734. Patatin. 1 hit.
SUPFAMiSSF52151. SSF52151. 1 hit.
PROSITEiView protein in PROSITE
PS51635. PNPLA. 1 hit.

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q9NP80-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MSINLTVDIY IYLLSNARSV CGKQRSKQLY FLFSPKHYWR ISHISLQRGF
60 70 80 90 100
HTNIIRCKWT KSEAHSCSKH CYSPSNHGLH IGILKLSTSA PKGLTKVNIC
110 120 130 140 150
MSRIKSTLNS VSKAVFGNQN EMISRLAQFK PSSQILRKVS DSGWLKQKNI
160 170 180 190 200
KQAIKSLKKY SDKSAEKSPF PEEKSHIIDK EEDIGKRSLF HYTSSITTKF
210 220 230 240 250
GDSFYFLSNH INSYFKRKEK MSQQKENEHF RDKSELEDKK VEEGKLRSPD
260 270 280 290 300
PGILAYKPGS ESVHTVDKPT SPSAIPDVLQ VSTKQSIANF LSRPTEGVQA
310 320 330 340 350
LVGGYIGGLV PKLKYDSKSQ SEEQEEPAKT DQAVSKDRNA EEKKRLSLQR
360 370 380 390 400
EKIIARVSID NRTRALVQAL RRTTDPKLCI TRVEELTFHL LEFPEGKGVA
410 420 430 440 450
VKERIIPYLL RLRQIKDETL QAAVREILAL IGYVDPVKGR GIRILSIDGG
460 470 480 490 500
GTRGVVALQT LRKLVELTQK PVHQLFDYIC GVSTGAILAF MLGLFHMPLD
510 520 530 540 550
ECEELYRKLG SDVFSQNVIV GTVKMSWSHA FYDSQTWENI LKDRMGSALM
560 570 580 590 600
IETARNPTCP KVAAVSTIVN RGITPKAFVF RNYGHFPGIN SHYLGGCQYK
610 620 630 640 650
MWQAIRASSA APGYFAEYAL GNDLHQDGGL LLNNPSALAM HECKCLWPDV
660 670 680 690 700
PLECIVSLGT GRYESDVRNT VTYTSLKTKL SNVINSATDT EEVHIMLDGL
710 720 730 740 750
LPPDTYFRFN PVMCENIPLD ESRNEKLDQL QLEGLKYIER NEQKMKKVAK
760 770 780
ILSQEKTTLQ KINDWIKLKT DMYEGLPFFS KL
Length:782
Mass (Da):88,477
Last modified:October 1, 2000 - v1
Checksum:iC66AD18A53AF649A
GO
Isoform 2 (identifier: Q9NP80-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     565-626: Missing.

Note: No experimental confirmation available.
Show »
Length:720
Mass (Da):81,602
Checksum:iC5FEF9D74A3E9954
GO
Isoform 3 (identifier: Q9NP80-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-100: Missing.

Note: No experimental confirmation available.
Show »
Length:682
Mass (Da):77,031
Checksum:iB42D353E75FE540D
GO

Sequence cautioni

The sequence AAF67630 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence BAA92090 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence EAL24384 differs from that shown. Reason: Erroneous gene model prediction.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti570 – 575NRGITP → IGGITH in AAF67630 (Ref. 9) Curated6
Sequence conflicti570 – 571NR → GI in BAA92090 (PubMed:14702039).Curated2
Sequence conflicti622N → S in BAA92090 (PubMed:14702039).Curated1
Sequence conflicti623D → G in BX647865 (PubMed:17974005).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0455941 – 100Missing in isoform 3. 1 PublicationAdd BLAST100
Alternative sequenceiVSP_028005565 – 626Missing in isoform 2. 1 PublicationAdd BLAST62

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB041261 mRNA. Translation: BAA94997.1.
AF263613 mRNA. Translation: AAF75269.1.
AF263947 mRNA. Translation: AAF81246.1.
AL834147 mRNA. Translation: CAD38859.1.
BX647865 mRNA. No translation available.
AC005058 Genomic DNA. Translation: AAD08847.1.
CH236947 Genomic DNA. Translation: EAL24384.1. Sequence problems.
CH236947 Genomic DNA. Translation: EAL24385.1.
CH471070 Genomic DNA. Translation: EAW83433.1.
BC032999 mRNA. Translation: AAH32999.1.
AK002115 mRNA. Translation: BAA92090.1. Different initiation.
AK024335 mRNA. Translation: BAB14890.1.
AF217519 mRNA. Translation: AAF67630.1. Different initiation.
CCDSiCCDS34733.1. [Q9NP80-1]
CCDS59075.1. [Q9NP80-3]
CCDS59508.1. [Q9NP80-2]
PIRiJC7284.
RefSeqiNP_001242936.1. NM_001256007.2. [Q9NP80-1]
NP_001242937.1. NM_001256008.2. [Q9NP80-1]
NP_001242938.1. NM_001256009.2. [Q9NP80-2]
NP_001242939.1. NM_001256010.2. [Q9NP80-3]
NP_001242940.1. NM_001256011.2. [Q9NP80-3]
NP_056538.1. NM_015723.4. [Q9NP80-1]
XP_005250453.1. XM_005250396.4. [Q9NP80-2]
XP_011514576.1. XM_011516274.2.
UniGeneiHs.617340.

Genome annotation databases

EnsembliENST00000257694; ENSP00000257694; ENSG00000135241. [Q9NP80-1]
ENST00000422087; ENSP00000410804; ENSG00000135241. [Q9NP80-1]
ENST00000426128; ENSP00000394988; ENSG00000135241. [Q9NP80-2]
ENST00000436062; ENSP00000406779; ENSG00000135241. [Q9NP80-1]
ENST00000453144; ENSP00000387789; ENSG00000135241. [Q9NP80-3]
GeneIDi50640.
KEGGihsa:50640.
UCSCiuc003vff.3. human. [Q9NP80-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiPLPL8_HUMAN
AccessioniPrimary (citable) accession number: Q9NP80
Secondary accession number(s): A4D0S1
, C9JZI4, O95035, Q8N3I3, Q9H7T5, Q9NR17, Q9NUN2, Q9NZ79
Entry historyiIntegrated into UniProtKB/Swiss-Prot: September 11, 2007
Last sequence update: October 1, 2000
Last modified: September 27, 2017
This is version 136 of the entry and version 1 of the sequence. See 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 7
    Human chromosome 7: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot