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Protein

HRAS-like suppressor 3

Gene

PLA2G16

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

Functioni

Lipid-modifying enzyme that acts as major regulator of adipocyte lipolysis by catalyzing the release of fatty acids from phospholipids in adipose tissue (PubMed:19615464, PubMed:19047760, PubMed:20837014, PubMed:22605381, PubMed:22923616). Shows phospholipase A1 and A2 activity, catalyzing the calcium-independent hydrolysis of acyl groups in various phosphatidylcholines (PC) and phosphatidylethanolamine (PE) (PubMed:19615464, PubMed:19047760, PubMed:20837014, PubMed:22605381, PubMed:22923616). For most substrates, phospholipase A1 activity is much higher than phospholipase A2 activity (PubMed:19047760). Phospholipase activity causes decreased intracellular levels of ether-type lipids, affecting peroxisome metabolism (By similarity). May also have acyltransferase activity: catalyzes both N-acylation of phosphatidylethanolamine to form N-acyl-phosphatidylethanolamine and O-acylation of lyso-phosphatidylcholines to form phosphatidylcholines (PubMed:22605381, PubMed:25383759). The relevance of acyltransferase activity in vivo is however unclear and would require additional evidences (PubMed:22605381, PubMed:25383759). Also has weak lysophospholipase activity (By similarity).By similarity7 Publications
(Microbial infection) Acts as a host factor for picornaviruses: required during early infection to promote viral genome release into the cytoplasm (PubMed:28077878). May act as a cellular sensor of membrane damage at sites of virus entry, which relocalizes to sites of membrane rupture upon virus unfection (PubMed:28077878). Facilitates safe passage of the RNA away from LGALS8, enabling viral genome translation by host ribosome (PubMed:28077878). May also be involved in initiating pore formation, increasing pore size or in maintaining pores for genome delivery (PubMed:28077878). The lipid-modifying enzyme activity is required for this process (PubMed:28077878).1 Publication

Catalytic activityi

Phosphatidylcholine + H2O = 1-acylglycerophosphocholine + a carboxylate.5 Publications
Phosphatidylcholine + H2O = 2-acylglycerophosphocholine + a carboxylate.5 Publications

Kineticsi

  1. KM=300 µM for dipalmitoyl-PC1 Publication
  1. Vmax=2.57 µmol/min/mg enzyme with dipalmitoyl-PC as substrate1 Publication
  2. Vmax=267 nmol/min/mg enzyme with dipalmitoyl-PE as substrate1 Publication

pH dependencei

Optimum pH is 9.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei233 Publications1
Active sitei353 Publications1
Active sitei113Acyl-thioester intermediate3 Publications1

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionHydrolase
Biological processLipid degradation, Lipid metabolism

Enzyme and pathway databases

ReactomeiR-HSA-1482788. Acyl chain remodelling of PC.
R-HSA-1482801. Acyl chain remodelling of PS.
R-HSA-1482839. Acyl chain remodelling of PE.
R-HSA-1482922. Acyl chain remodelling of PI.
SIGNORiP53816.

Chemistry databases

SwissLipidsiSLP:000001077.

Names & Taxonomyi

Protein namesi
Recommended name:
HRAS-like suppressor 31 Publication (EC:3.1.1.325 Publications, EC:3.1.1.45 Publications)
Short name:
HRSL31 Publication
Alternative name(s):
Adipose-specific phospholipase A2By similarity
Short name:
AdPLABy similarity
Group XVI phospholipase A1/A2Imported
H-rev 107 protein homolog1 Publication
Short name:
H-REV1071 Publication
Short name:
HREV107-11 Publication
HRAS-like suppressor 1
HREV107-3
Renal carcinoma antigen NY-REN-651 Publication
Gene namesi
Name:PLA2G16Imported
Synonyms:HRASLS31 Publication, HREV1071 Publication
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 11

Organism-specific databases

EuPathDBiHostDB:ENSG00000176485.10.
HGNCiHGNC:17825. PLA2G16.

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
Topological domaini1 – 132CytoplasmicSequence analysisAdd BLAST132
Transmembranei133 – 155HelicalSequence analysisAdd BLAST23
Topological domaini156 – 162LumenalSequence analysis7

Keywords - Cellular componenti

Cytoplasm, Membrane, Peroxisome

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi23H → A: No effect on PPP2R1A-binding. 1 Publication1
Mutagenesisi39 – 57PSEVA…ALTDK → DILLALTDDMGRTQKVVSNK RLILGVIVKV: Induces a major structural rearrangement accompanied by domain-swapping dimerization and changes in substrate-specificity. 1 PublicationAdd BLAST19
Mutagenesisi113C → S: No effect on PPP2R1A-binding. Impaired ability to act as a host factor for picornaviruses. 2 Publications1

Organism-specific databases

DisGeNETi11145.
OpenTargetsiENSG00000176485.
PharmGKBiPA164724584.

Polymorphism and mutation databases

BioMutaiPLA2G16.
DMDMi20141767.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001524841 – 162HRAS-like suppressor 3Add BLAST162

Proteomic databases

EPDiP53816.
MaxQBiP53816.
PaxDbiP53816.
PeptideAtlasiP53816.
PRIDEiP53816.

PTM databases

iPTMnetiP53816.
PhosphoSitePlusiP53816.

Expressioni

Tissue specificityi

Widely expressed. low expression, if any, in hematopoietic cells and thymus. In testis, confined to round spermatids. Expressed in normal ovarian epithelial cells. Down-regulated in some ovarian carcinomas and testicular germ cell tumors. Highly expressed in white adipose tissue (PubMed:19136964).5 Publications

Inductioni

By IFNG and IRF1.1 Publication

Gene expression databases

BgeeiENSG00000176485.
CleanExiHS_PLA2G16.
ExpressionAtlasiP53816. baseline and differential.
GenevisibleiP53816. HS.

Organism-specific databases

HPAiHPA058997.

Interactioni

Subunit structurei

Interacts with PPP2R1A; this interaction might decrease PP2A activity.1 Publication

Binary interactionsi

Show more details

Protein-protein interaction databases

BioGridi116317. 6 interactors.
IntActiP53816. 4 interactors.
MINTiMINT-1461468.
STRINGi9606.ENSP00000320337.

Structurei

Secondary structure

1162
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi13 – 18Combined sources6
Beta strandi21 – 29Combined sources9
Beta strandi32 – 37Combined sources6
Beta strandi41 – 43Combined sources3
Beta strandi45 – 48Combined sources4
Helixi49 – 52Combined sources4
Beta strandi59 – 64Combined sources6
Helixi65 – 69Combined sources5
Beta strandi72 – 76Combined sources5
Helixi79 – 82Combined sources4
Helixi89 – 98Combined sources10
Turni99 – 101Combined sources3
Beta strandi103 – 109Combined sources7
Helixi110 – 122Combined sources13

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2KYTNMR-A1-125[»]
4DOTX-ray1.96A1-132[»]
4FA0X-ray2.65A1-134[»]
4Q95X-ray2.20A/B2-38[»]
A/B59-129[»]
ProteinModelPortaliP53816.
SMRiP53816.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the H-rev107 family.Curated

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410IW0Y. Eukaryota.
ENOG4111TDD. LUCA.
GeneTreeiENSGT00390000013327.
HOGENOMiHOG000293227.
InParanoidiP53816.
KOiK16817.
OMAiHVNNKHD.
OrthoDBiEOG091G08MK.
PhylomeDBiP53816.
TreeFamiTF330836.

Family and domain databases

InterProiView protein in InterPro
IPR007053. LRAT-like_dom.
PfamiView protein in Pfam
PF04970. LRAT. 1 hit.

Sequencei

Sequence statusi: Complete.

P53816-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MRAPIPEPKP GDLIEIFRPF YRHWAIYVGD GYVVHLAPPS EVAGAGAASV
60 70 80 90 100
MSALTDKAIV KKELLYDVAG SDKYQVNNKH DDKYSPLPCS KIIQRAEELV
110 120 130 140 150
GQEVLYKLTS ENCEHFVNEL RYGVARSDQV RDVIIAASVA GMGLAAMSLI
160
GVMFSRNKRQ KQ
Length:162
Mass (Da):17,937
Last modified:January 31, 2002 - v2
Checksum:i3565BFC756A6DA3C
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti90S → T in CAA63423 (PubMed:9771974).Curated1
Sequence conflicti90S → T in BAH08749 (PubMed:19615464).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X92814 mRNA. Translation: CAA63423.1.
AB030814 mRNA. Translation: BAB08108.1.
AF317086 mRNA. Translation: AAL26892.1.
AB439591 mRNA. Translation: BAH08749.1.
AK313075 mRNA. Translation: BAG35901.1.
CH471076 Genomic DNA. Translation: EAW74158.1.
BC001387 mRNA. Translation: AAH01387.1.
BC103807 mRNA. Translation: AAI03808.1.
CCDSiCCDS8047.1.
RefSeqiNP_001121675.1. NM_001128203.1.
NP_009000.2. NM_007069.3.
XP_006718489.1. XM_006718426.1.
UniGeneiHs.502775.

Genome annotation databases

EnsembliENST00000323646; ENSP00000320337; ENSG00000176485.
ENST00000415826; ENSP00000389124; ENSG00000176485.
GeneIDi11145.
KEGGihsa:11145.
UCSCiuc001nxh.4. human.

Similar proteinsi

Entry informationi

Entry nameiPA216_HUMAN
AccessioniPrimary (citable) accession number: P53816
Secondary accession number(s): B2R7Q4
, B7XAK5, Q3SYI3, Q9HDD1
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: January 31, 2002
Last modified: October 25, 2017
This is version 145 of the entry and version 2 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

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 11
    Human chromosome 11: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. SIMILARITY comments
    Index of protein domains and families