RARR2_CRIGR
ID RARR2_CRIGR Reviewed; 163 AA.
AC Q8HDG8;
DT 26-APR-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 25-MAY-2022, entry version 50.
DE RecName: Full=Retinoic acid receptor responder protein 2;
DE AltName: Full=Chemerin;
DE AltName: Full=RAR-responsive protein TIG2;
DE AltName: Full=Tazarotene-induced gene 2 protein;
DE Flags: Precursor;
GN Name=RARRES2; Synonyms=TIG2;
OS Cricetulus griseus (Chinese hamster) (Cricetulus barabensis griseus).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea;
OC Cricetidae; Cricetinae; Cricetulus.
OX NCBI_TaxID=10029;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=12493756; DOI=10.1074/jbc.m210565200;
RA Satake H., Chen H.Y., Varki A.;
RT "Genes modulated by expression of GD3 synthase in Chinese hamster ovary
RT cells. Evidence that the Tis21 gene is involved in the induction of GD3 9-
RT O-acetylation.";
RL J. Biol. Chem. 278:7942-7948(2003).
CC -!- FUNCTION: Adipocyte-secreted protein (adipokine) that regulates
CC adipogenesis, metabolism and inflammation through activation of the
CC chemokine-like receptor 1 (CMKLR1). Acts also as a ligand for CMKLR2.
CC Can also bind to C-C chemokine receptor-like 2 (CCRL2), but with a
CC lower affinity than it does to CMKLR1 or CMKLR2. Positively regulates
CC adipocyte differentiation, modulates the expression of adipocyte genes
CC involved in lipid and glucose metabolism and might play a role in
CC angiogenesis, a process essential for the expansion of white adipose
CC tissue. Also acts as a pro-inflammatory adipokine, causing an increase
CC in secretion of pro-inflammatory and prodiabetic adipokines, which
CC further impair adipose tissue metabolic function and have negative
CC systemic effects including impaired insulin sensitivity, altered
CC glucose and lipid metabolism, and a decrease in vascular function in
CC other tissues. Can have both pro- and anti-inflammatory properties
CC depending on the modality of enzymatic cleavage by different classes of
CC proteases. Acts as a chemotactic factor for leukocyte populations
CC expressing CMKLR1, particularly immature plasmacytoid dendritic cells,
CC but also immature myeloid DCs, macrophages and natural killer cells.
CC Exerts an anti-inflammatory role by preventing TNF/TNFA-induced VCAM1
CC expression and monocytes adhesion in vascular endothelial cells. The
CC effect is mediated via inhibiting activation of NF-kappa-B and CRK/p38
CC through stimulation of AKT1/NOS3 signaling and nitric oxide production.
CC Its dual role in inflammation and metabolism might provide a link
CC Exhibits an antimicrobial function in the skin (By similarity).
CC {ECO:0000250|UniProtKB:Q99969}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250|UniProtKB:Q9DD06}.
CC -!- PTM: Secreted in an inactive precursor form, prochemerin, which is
CC proteolytically processed by a variety of extracellular proteases to
CC generate forms with differing levels of bioactivity. For example, the
CC removal of six amino acids results in chemerin-157, which exhibits the
CC highest activity, while removal of seven amino acids results in
CC chemerin-156 which has slightly less activity. Some proteases are able
CC to cleave at more than one site and chemerin forms may be sequentially
CC processed by different enzymes to modulate activity levels. The
CC coordinated expression and activity of chemerin-modifying enzymes is
CC essential for regulating its bioactivation, inactivation and,
CC consequently, biological function. Cathepsin G cleaves seven C-terminal
CC amino acids from prochemerin (chemerin-156), elastase is able to cleave
CC six (chemerin-157), eight (chemerin-155) or eleven (chemerin-152),
CC plasmin cleaves five amino acids (chemerin-158), and tryptase cleaves
CC five (chemerin-158) or eight (chemerin-155). Multiple cleavages might
CC be required to fully activate chemerin, with an initial tryptase
CC cleavage resulting in chemerin with low activity (chemerin-158), and a
CC second cleavage by carboxypeptidase N or B producing highly active
CC chemerin (chemerin-157). {ECO:0000250|UniProtKB:Q99969}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AB089674; BAC45229.1; -; mRNA.
DR RefSeq; NP_001231216.1; NM_001244287.1.
DR AlphaFoldDB; Q8HDG8; -.
DR SMR; Q8HDG8; -.
DR STRING; 10029.NP_001231216.1; -.
DR GeneID; 100689253; -.
DR KEGG; cge:100689253; -.
DR CTD; 5919; -.
DR eggNOG; ENOG502SE7C; Eukaryota.
DR OrthoDB; 1596588at2759; -.
DR GO; GO:0005576; C:extracellular region; ISS:UniProtKB.
DR GO; GO:0005102; F:signaling receptor binding; IEA:InterPro.
DR GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
DR GO; GO:0006935; P:chemotaxis; IEA:UniProtKB-KW.
DR GO; GO:0006954; P:inflammatory response; IEA:UniProtKB-KW.
DR GO; GO:0050921; P:positive regulation of chemotaxis; ISS:UniProtKB.
DR GO; GO:0045600; P:positive regulation of fat cell differentiation; ISS:UniProtKB.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; ISS:UniProtKB.
DR GO; GO:0046626; P:regulation of insulin receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0050994; P:regulation of lipid catabolic process; ISS:UniProtKB.
DR InterPro; IPR029562; Chemerin.
DR InterPro; IPR046350; Cystatin_sf.
DR PANTHER; PTHR15106; PTHR15106; 1.
DR SUPFAM; SSF54403; SSF54403; 1.
PE 2: Evidence at transcript level;
KW Chemotaxis; Differentiation; Disulfide bond; Inflammatory response;
KW Secreted; Signal.
FT SIGNAL 1..20
FT /evidence="ECO:0000250|UniProtKB:Q99969"
FT CHAIN 21..157
FT /note="Retinoic acid receptor responder protein 2"
FT /id="PRO_0000022528"
FT PROPEP 158..163
FT /evidence="ECO:0000250"
FT /id="PRO_0000424869"
FT DISULFID 79..89
FT /evidence="ECO:0000250"
FT DISULFID 100..119
FT /evidence="ECO:0000250"
FT DISULFID 103..135
FT /evidence="ECO:0000255"
SQ SEQUENCE 163 AA; 18707 MW; E705E0AA3447B3B8 CRC64;
MKYLLISLAL WLGMVGIHGT ELELSETQRR GLQVALEEFH KHPPVQWAFQ EIGVDNANDM
VFSAGTFVRL EFKLQQTSCF KKDWKNPECK IKANGRKRKC LACIKLDPRG KVLGRMVHCP
ILKQGLQQEL QESQCNRITQ AGEDPRSHFF PGQFAFSRAL KHK
