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Protein

HRAS-like suppressor 3

Gene

Pla2g16

Organism
Mus musculus (Mouse)
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:18614531, PubMed:19047760, PubMed:19136964). Shows phospholipase A1 and A2 activity, catalyzing the calcium-independent hydrolysis of acyl groups in various phosphatidylcholines (PC) and phosphatidylethanolamine (PE) (PubMed:18614531, PubMed:19047760, PubMed:22134920). For most substrates, phospholipase A1 activity is much higher than phospholipase A2 activity (PubMed:18614531, PubMed:19047760). Phospholipase activity causes decreased intracellular levels of ether-type lipids, affecting peroxisome metabolism (PubMed:22134920). 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 (By similarity). The relevance of acyltransferase activity in vivo is however unclear and would require additional evidences (By similarity). Also has weak lysophospholipase activity (PubMed:18614531).By similarity4 Publications
(Microbial infection) Acts as a host factor for picornaviruses: required during early infection to promote viral genome release into the cytoplasm (PubMed:28077878).1 Publication

Catalytic activityi

Phosphatidylcholine + H2O = 1-acylglycerophosphocholine + a carboxylate.3 Publications
Phosphatidylcholine + H2O = 2-acylglycerophosphocholine + a carboxylate.2 Publications

Kineticsi

  1. KM=16 µM for 1-palmitoyl-2-linoleoyl-phosphatidylcholine (PC)1 Publication
  1. Vmax=7.8 µmol/min/mg enzyme with 1-palmitoyl-2-linoleoyl-PC as substrate (in the presence of 2 mM calcium)1 Publication

pH dependencei

Optimum pH is 8.0.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei231 Publication1
Active sitei35By similarity1
Active sitei113Acyl-thioester intermediate1 Publication1

GO - Molecular functioni

GO - Biological processi

  • ether lipid metabolic process Source: UniProtKB
  • lipid catabolic process Source: UniProtKB
  • negative regulation of cell cycle Source: Ensembl
  • peroxisome organization Source: UniProtKB
  • phospholipid biosynthetic process Source: UniProtKB
  • phospholipid metabolic process Source: MGI
  • regulation of adipose tissue development Source: UniProtKB
  • triglyceride metabolic process Source: UniProtKB

Keywordsi

Molecular functionHydrolase
Biological processLipid degradation, Lipid metabolism

Enzyme and pathway databases

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

Names & Taxonomyi

Protein namesi
Recommended name:
HRAS-like suppressor 3By similarity (EC:3.1.1.322 Publications, EC:3.1.1.43 Publications)
Short name:
HRSL3By similarity
Alternative name(s):
Adipose-specific phospholipase A2Imported
Short name:
AdPLA1 Publication
Group XVI phospholipase A2Imported
H-rev 107 protein homologBy similarity
Gene namesi
Name:Pla2g16Imported
Synonyms:H-rev107By similarity, Hrasls3By similarity, Hrev107By similarity
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 19

Organism-specific databases

MGIiMGI:2179715. Pla2g16.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 132CytoplasmicSequence analysisAdd BLAST132
Transmembranei133 – 155HelicalSequence analysisAdd BLAST23
Topological domaini156 – 162LumenalSequence analysis7

GO - Cellular componenti

  • endoplasmic reticulum Source: UniProtKB
  • integral component of membrane Source: UniProtKB-KW
  • perinuclear region of cytoplasm Source: UniProtKB
  • peroxisomal membrane Source: UniProtKB-SubCell
  • peroxisome Source: UniProtKB

Keywords - Cellular componenti

Cytoplasm, Membrane, Peroxisome

Pathology & Biotechi

Disruption phenotypei

Mice display resistance to diet-induced obesity: they show strongly reduced adipose tissue mass and triglyceride content but normal adipogenesis accompanied by higher energy expenditure and increased fatty acid oxidation in adipocytes (PubMed:19136964). Mice show resistance to infection by picornaviruses, such as coxsackievirus A10, probably due to reduced viral genome release into the host cytoplasm (PubMed:28077878).2 Publications

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi23H → A or Q: Abolishes enzyme activity. 2 Publications1
Mutagenesisi112N → A or Q: Abolishes enzyme activity. 1 Publication1
Mutagenesisi113C → A or S: Abolishes enzyme activity. 1 Publication1
Mutagenesisi129Q → A: Abolishes enzyme activity. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001524851 – 162HRAS-like suppressor 3Add BLAST162

Proteomic databases

PaxDbiQ8R3U1.
PeptideAtlasiQ8R3U1.
PRIDEiQ8R3U1.

PTM databases

iPTMnetiQ8R3U1.
PhosphoSitePlusiQ8R3U1.

Expressioni

Tissue specificityi

Ubiquitously expressed in normal tissues but down-regulated in primary carcinomas or in many cell lines derived from tumors (PubMed:12055182). Highly expressed in white adipose tissue and in adipocytes (PubMed:18614531, PubMed:19136964). Expressed at lower levels in brown adipose tissue (PubMed:18614531, PubMed:19136964).3 Publications

Gene expression databases

BgeeiENSMUSG00000060675.
ExpressionAtlasiQ8R3U1. baseline and differential.
GenevisibleiQ8R3U1. MM.

Interactioni

Subunit structurei

Interacts with PPP2R1A; this interaction might decrease PP2A activity.By similarity

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000025925.

Structurei

3D structure databases

ProteinModelPortaliQ8R3U1.
SMRiQ8R3U1.
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.
InParanoidiQ8R3U1.
KOiK16817.
OMAiHVNNKHD.
OrthoDBiEOG091G08MK.
PhylomeDBiQ8R3U1.
TreeFamiTF330836.

Family and domain databases

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

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q8R3U1-1) [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
MLAPIPEPKP GDLIEIFRPM YRHWAIYVGD GYVIHLAPPS EIAGAGAASI
60 70 80 90 100
MSALTDKAIV KKELLCHVAG KDKYQVNNKH DEEYTPLPLS KIIQRAERLV
110 120 130 140 150
GQEVLYRLTS ENCEHFVNEL RYGVPRSDQV RDAVKAVGIA GVGLAALGLV
160
GVMLSRNKKQ KQ
Length:162
Mass (Da):17,872
Last modified:April 26, 2005 - v2
Checksum:iE688128CF00AADAB
GO
Isoform 2 (identifier: Q8R3U1-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     131-162: RDAVKAVGIAGVGLAALGLVGVMLSRNKKQKQ → CHRPCTLTLGVRSFSQLPVAGPECGWRQNYKQDDNSLM

Note: No experimental confirmation available.
Show »
Length:168
Mass (Da):18,932
Checksum:i73F410B77F832256
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti42I → V in AAH24581 (PubMed:15489334).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_013542131 – 162RDAVK…KKQKQ → CHRPCTLTLGVRSFSQLPVA GPECGWRQNYKQDDNSLM in isoform 2. 1 PublicationAdd BLAST32

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB298806 mRNA. Translation: BAH08635.1.
AK039703 mRNA. Translation: BAE20550.1.
AK042007 mRNA. Translation: BAE20615.1.
AK052657 mRNA. Translation: BAC35085.1.
AK163505 mRNA. Translation: BAE37375.1.
CH466612 Genomic DNA. Translation: EDL33312.1.
CH466612 Genomic DNA. Translation: EDL33314.1.
BC024581 mRNA. Translation: AAH24581.1.
CCDSiCCDS29528.1. [Q8R3U1-1]
RefSeqiNP_644675.2. NM_139269.2. [Q8R3U1-1]
XP_006526984.1. XM_006526921.2. [Q8R3U1-1]
UniGeneiMm.274810.

Genome annotation databases

EnsembliENSMUST00000025925; ENSMUSP00000025925; ENSMUSG00000060675. [Q8R3U1-1]
ENSMUST00000136465; ENSMUSP00000119403; ENSMUSG00000060675. [Q8R3U1-2]
ENSMUST00000136756; ENSMUSP00000115151; ENSMUSG00000060675. [Q8R3U1-1]
GeneIDi225845.
KEGGimmu:225845.
UCSCiuc008glh.1. mouse. [Q8R3U1-2]
uc008gli.1. mouse. [Q8R3U1-1]

Keywords - Coding sequence diversityi

Alternative splicing

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.

Entry informationi

Entry nameiPA216_MOUSE
AccessioniPrimary (citable) accession number: Q8R3U1
Secondary accession number(s): B7X6T3, Q3V3C3, Q8BWF7
Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 26, 2005
Last sequence update: April 26, 2005
Last modified: May 10, 2017
This is version 104 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families