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Protein

Retinoic acid receptor responder protein 2

Gene

RARRES2

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

Functioni

Adipocyte-secreted protein (adipokine) that regulates adipogenesis, metabolism and inflammation through activation of the chemokine-like receptor 1 (CMKLR1). Its other ligands include G protein-coupled receptor 1 (GPR1) and chemokine receptor-like 2 (CCRL2). Positively regulates adipocyte differentiation, modulates the expression of adipocyte genes involved in lipid and glucose metabolism and might play a role in angiogenesis, a process essential for the expansion of white adipose tissue. Also acts as a proinflammatory adipokine, causing an increase in secretion of proinflammatory and prodiabetic adipokines, which further impair adipose tissue metabolic function and have negative systemic effects including impaired insulin sensitivity, altered glucose and lipid metabolism, and a decrease in vascular function in other tissues. Can have both pro- and anti-inflammatory properties depending on the modality of enzymatic cleavage by different classes of proteases. Acts as a chemotactic factor for leukocyte populations expressing CMKLR1, particularly immature plasmacytoid dendritic cells, but also immature myeloid DCs, macrophages and natural killer cells. Exerts an anti-inflammatory role by preventing TNF/TNFA-induced VCAM1 expression and monocytes adhesion in vascular endothelial cells. The effect is mediated via inhibiting activation of NF-kappa-B and CRK/p38 through stimulation of AKT1/NOS3 signaling and nitric oxide production. Its dual role in inflammation and metabolism might provide a link between chronic inflammation and obesity, as well as obesity-related disorders such as type 2 diabetes and cardiovascular disease. Exhibits an antimicrobial function in the skin.7 Publications

GO - Molecular functioni

  • signaling receptor binding Source: UniProtKB

GO - Biological processi

Keywordsi

Biological processChemotaxis, Differentiation, Inflammatory response

Enzyme and pathway databases

ReactomeiR-HSA-114608 Platelet degranulation

Names & Taxonomyi

Protein namesi
Recommended name:
Retinoic acid receptor responder protein 2
Alternative name(s):
Chemerin
RAR-responsive protein TIG2
Tazarotene-induced gene 2 protein
Gene namesi
Name:RARRES2
Synonyms:TIG2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 7

Organism-specific databases

EuPathDBiHostDB:ENSG00000106538.9
HGNCiHGNC:9868 RARRES2
MIMi601973 gene
neXtProtiNX_Q99969

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

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Organism-specific databases

DisGeNETi5919
OpenTargetsiENSG00000106538
PharmGKBiPA34229

Polymorphism and mutation databases

BioMutaiRARRES2

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 201 PublicationAdd BLAST20
ChainiPRO_000002252921 – 157Retinoic acid receptor responder protein 2Add BLAST137
PropeptideiPRO_0000424870158 – 1636

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi77 ↔ 87By similarity
Disulfide bondi98 ↔ 117By similarity
Disulfide bondi101 ↔ 135Sequence analysis

Post-translational modificationi

Secreted in an inactive precursor form, prochemerin, which is proteolytically processed by a variety of extracellular proteases to generate forms with differing levels of bioactivity. For example, the removal of six amino acids results in chemerin-157, which exhibits the highest activity, while removal of seven amino acids results in chemerin-156 which has slightly less activity. Some proteases are able to cleave at more than one site and chemerin forms may be sequentially processed by different enzymes to modulate activity levels. The coordinated expression and activity of chemerin-modifying enzymes is essential for regulating its bioactivation, inactivation and, consequently, biological function. Cathepsin G cleaves seven C-terminal amino acids from prochemerin (chemerin-156), elastase is able to cleave six (chemerin-157), eight (chemerin-155) or eleven (chemerin-152), plasmin cleaves five amino acids (chemerin-158), and tryptase cleaves five (chemerin-158) or eight (chemerin-155). Multiple cleavages might be required to fully activate chemerin, with an initial tryptase cleavage resulting in chemerin with low activity (chemerin-158), and a second cleavage by carboxypeptidase N or B producing highly active chemerin (chemerin-157).2 Publications

Keywords - PTMi

Disulfide bond

Proteomic databases

EPDiQ99969
MaxQBiQ99969
PaxDbiQ99969
PeptideAtlasiQ99969
PRIDEiQ99969
ProteomicsDBi78557

PTM databases

iPTMnetiQ99969
PhosphoSitePlusiQ99969

Expressioni

Tissue specificityi

Expressed at the highest levels in placenta, liver, and white adipose tissue (WAT), and to a lesser extent in many other tissues such as lung, brown adipose tissue, heart, ovary, kidney, skeletal muscle and pancreas. Within WAT, expression is enriched in adipocytes as compared to the stromal vascular fraction. Expression and secretion increases dramatically with adipogenesis. Highly expressed in skin (basal and suprabasal layers of the epidermis, hair follicles and endothelial cells). Expression is elevated in numerous metabolic and inflammatory diseases including psoriasis, obesity, type 2 diabetes, metabolic syndrome and cardiovascular disease.3 Publications

Inductioni

Inhibited in psoriatic lesions. Activated by tazarotene in skin rafts and in the epidermis of psoriatic lesions.1 Publication

Gene expression databases

BgeeiENSG00000106538 Expressed in 223 organ(s), highest expression level in left adrenal gland
CleanExiHS_RARRES2
ExpressionAtlasiQ99969 baseline and differential
GenevisibleiQ99969 HS

Organism-specific databases

HPAiHPA049359

Interactioni

GO - Molecular functioni

Protein-protein interaction databases

BioGridi111854, 4 interactors
STRINGi9606.ENSP00000223271

Structurei

3D structure databases

ProteinModelPortaliQ99969
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiENOG410IY1C Eukaryota
ENOG410ZEJF LUCA
GeneTreeiENSGT00390000016226
HOGENOMiHOG000093205
HOVERGENiHBG000698
InParanoidiQ99969
KOiK10044
OMAiYYFPGQF
OrthoDBiEOG091G0OJ5
PhylomeDBiQ99969
TreeFamiTF330938

Family and domain databases

InterProiView protein in InterPro
IPR029562 Chemerin
PANTHERiPTHR15106 PTHR15106, 1 hit

Sequence (1+)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry has 1 described isoform and 1 potential isoform that is computationally mapped.iShow all

Q99969-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MRRLLIPLAL WLGAVGVGVA ELTEAQRRGL QVALEEFHKH PPVQWAFQET
60 70 80 90 100
SVESAVDTPF PAGIFVRLEF KLQQTSCRKR DWKKPECKVR PNGRKRKCLA
110 120 130 140 150
CIKLGSEDKV LGRLVHCPIE TQVLREAEEH QETQCLRVQR AGEDPHSFYF
160
PGQFAFSKAL PRS
Length:163
Mass (Da):18,618
Last modified:May 1, 1997 - v1
Checksum:iA96EB7D0999EC3DB
GO

Computationally mapped potential isoform sequencesi

There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
C9J8S2C9J8S2_HUMAN
Retinoic acid receptor responder pr...
RARRES2
159Annotation score:

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U77594 mRNA Translation: AAB47975.1
AB015632 mRNA Translation: BAA76499.1
AK312197 mRNA Translation: BAG35130.1
CR541992 mRNA Translation: CAG46789.1
CR542026 mRNA Translation: CAG46823.1
AC005586 Genomic DNA Translation: AAS00384.1
CH471173 Genomic DNA Translation: EAW54120.1
CH471173 Genomic DNA Translation: EAW54121.1
BC000069 mRNA Translation: AAH00069.1
CCDSiCCDS5902.1
RefSeqiNP_002880.1, NM_002889.3
UniGeneiHs.647064

Genome annotation databases

EnsembliENST00000223271; ENSP00000223271; ENSG00000106538
ENST00000466675; ENSP00000418009; ENSG00000106538
ENST00000482669; ENSP00000418483; ENSG00000106538
GeneIDi5919
KEGGihsa:5919
UCSCiuc003wha.4 human

Similar proteinsi

Entry informationi

Entry nameiRARR2_HUMAN
AccessioniPrimary (citable) accession number: Q99969
Secondary accession number(s): Q7LE02
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: May 1, 1997
Last modified: September 12, 2018
This is version 142 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, Direct protein sequencing, Reference proteome
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

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