RARR2_BOVIN
ID RARR2_BOVIN Reviewed; 162 AA.
AC Q29RS5;
DT 12-DEC-2006, integrated into UniProtKB/Swiss-Prot.
DT 04-APR-2006, sequence version 1.
DT 03-AUG-2022, entry version 92.
DE RecName: Full=Retinoic acid receptor responder protein 2;
DE AltName: Full=Chemerin;
DE Flags: Precursor;
GN Name=RARRES2;
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Hereford; TISSUE=Testis;
RG NIH - Mammalian Gene Collection (MGC) project;
RL Submitted (FEB-2006) to the EMBL/GenBank/DDBJ databases.
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 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 five amino acids results in chemerin-157, which exhibits the
CC highest activity, while removal of six amino acids results in chemerin-
CC 156 which has slightly less activity. Some proteases are able to cleave
CC at more than one site and chemerin forms may be sequentially processed
CC by different enzymes to modulate activity levels. The coordinated
CC expression and activity of chemerin-modifying enzymes is essential for
CC regulating its bioactivation, inactivation and, consequently,
CC biological function. Cathepsin G cleaves six C-terminal amino acids
CC from prochemerin (chemerin-156), elastase is able to cleave five
CC (chemerin-157), seven (chemerin-155) or ten (chemerin-152), plasmin
CC cleaves four amino acids (chemerin-158), and tryptase cleaves four
CC (chemerin-158) or seven (chemerin-155). Multiple cleavages might be
CC required to fully activate chemerin, with an initial tryptase cleavage
CC resulting in chemerin with low activity (chemerin-158), and a second
CC cleavage by carboxypeptidase N or B producing highly active chemerin
CC (chemerin-157) (By similarity). {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; BC114047; AAI14048.1; -; mRNA.
DR RefSeq; NP_001039485.1; NM_001046020.2.
DR RefSeq; XP_005205858.1; XM_005205801.3.
DR RefSeq; XP_005205859.1; XM_005205802.1.
DR RefSeq; XP_005205860.1; XM_005205803.2.
DR RefSeq; XP_015326241.1; XM_015470755.1.
DR AlphaFoldDB; Q29RS5; -.
DR SMR; Q29RS5; -.
DR STRING; 9913.ENSBTAP00000005523; -.
DR PaxDb; Q29RS5; -.
DR Ensembl; ENSBTAT00000005523; ENSBTAP00000005523; ENSBTAG00000004215.
DR Ensembl; ENSBTAT00000084323; ENSBTAP00000074117; ENSBTAG00000004215.
DR GeneID; 508990; -.
DR KEGG; bta:508990; -.
DR CTD; 5919; -.
DR VEuPathDB; HostDB:ENSBTAG00000004215; -.
DR VGNC; VGNC:33732; RARRES2.
DR eggNOG; ENOG502SE7C; Eukaryota.
DR GeneTree; ENSGT00390000016226; -.
DR HOGENOM; CLU_138029_0_0_1; -.
DR InParanoid; Q29RS5; -.
DR OMA; WAFQKTS; -.
DR OrthoDB; 1596588at2759; -.
DR TreeFam; TF330938; -.
DR Reactome; R-BTA-114608; Platelet degranulation.
DR Proteomes; UP000009136; Chromosome 4.
DR Bgee; ENSBTAG00000004215; Expressed in cortex of kidney and 104 other tissues.
DR ExpressionAtlas; Q29RS5; baseline and differential.
DR GO; GO:0062023; C:collagen-containing extracellular matrix; IEA:Ensembl.
DR GO; GO:0031012; C:extracellular matrix; IBA:GO_Central.
DR GO; GO:0005576; C:extracellular region; ISS:UniProtKB.
DR GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR GO; GO:0005102; F:signaling receptor binding; IBA:GO_Central.
DR GO; GO:0019732; P:antifungal humoral response; IEA:Ensembl.
DR GO; GO:0061760; P:antifungal innate immune response; IEA:Ensembl.
DR GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
DR GO; GO:0006935; P:chemotaxis; IEA:UniProtKB-KW.
DR GO; GO:0050829; P:defense response to Gram-negative bacterium; IEA:Ensembl.
DR GO; GO:0050830; P:defense response to Gram-positive bacterium; IEA:Ensembl.
DR GO; GO:0048566; P:embryonic digestive tract development; IEA:Ensembl.
DR GO; GO:0006954; P:inflammatory response; IEA:UniProtKB-KW.
DR GO; GO:0045087; P:innate immune response; IBA:GO_Central.
DR GO; GO:0008286; P:insulin receptor signaling pathway; IEA:Ensembl.
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:0010759; P:positive regulation of macrophage chemotaxis; IEA:Ensembl.
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 GO; GO:0001523; P:retinoid metabolic process; IEA:Ensembl.
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 Reference proteome; Secreted; Signal.
FT SIGNAL 1..20
FT /evidence="ECO:0000250|UniProtKB:Q99969"
FT CHAIN 21..155
FT /note="Retinoic acid receptor responder protein 2"
FT /id="PRO_0000267643"
FT PROPEP 156..162
FT /evidence="ECO:0000250"
FT /id="PRO_0000424868"
FT DISULFID 77..87
FT /evidence="ECO:0000250"
FT DISULFID 98..117
FT /evidence="ECO:0000250"
FT DISULFID 101..135
FT /evidence="ECO:0000255"
SQ SEQUENCE 162 AA; 18357 MW; 1F44C3D29B79D1D9 CRC64;
MWQLLLPLAL GLGTMGLGRA ELTTAQHRGL QVALEEFHKH PPVLWAFQVT SVDNAADTLF
PAGQFVRLEF KLQQTSCRKK DWRKEDCKVK PNGRKRKCLA CIKLDSKDQV LGRMVHCPIQ
TQVQRELDDA QDAQCSRVER AGEDPHSYYL PGQFAFIKAL SP
