Gene/Proteome Database (LMPD)
LMPD ID
LMP002013
Gene ID
Species
Homo sapiens (Human)
Gene Name
retinoic acid receptor responder (tazarotene induced) 2
Gene Symbol
Synonyms
HP10433; TIG2
Alternate Names
retinoic acid receptor responder protein 2; chemerin; RAR-responsive protein TIG2; tazarotene-induced gene 2 protein
Chromosome
7
Map Location
7q36.1
Summary
This gene encodes a secreted chemotactic protein that initiates chemotaxis via the ChemR23 G protein-coupled seven-transmembrane domain ligand. Expression of this gene is upregulated by the synthetic retinoid tazarotene and occurs in a wide variety of tissues. The active protein has several roles, including that as an adipokine and as an antimicrobial protein with activity against bacteria and fungi. [provided by RefSeq, Nov 2014]
Orthologs
Proteins
| retinoic acid receptor responder protein 2 precursor | |
|---|---|
| Refseq ID | NP_002880 |
| Protein GI | 4506427 |
| UniProt ID | Q99969 |
| mRNA ID | NM_002889 |
| Length | 163 |
| RefSeq Status | REVIEWED |
| MRRLLIPLALWLGAVGVGVAELTEAQRRGLQVALEEFHKHPPVQWAFQETSVESAVDTPFPAGIFVRLEFKLQQTSCRKRDWKKPECKVRPNGRKRKCLACIKLGSEDKVLGRLVHCPIETQVLREAEEHQETQCLRVQRAGEDPHSFYFPGQFAFSKALPRS | |
| sig_peptide: 1..20 inference: COORDINATES: ab initio prediction:SignalP:4.0 calculated_mol_wt: 2106 peptide sequence: MRRLLIPLALWLGAVGVGVA mat_peptide: 21..157 product: retinoic acid receptor responder protein 2 experiment: DESCRIPTION:antimicrobial peptide[PMID: 24660117] calculated_mol_wt: 15877 peptide sequence: ELTEAQRRGLQVALEEFHKHPPVQWAFQETSVESAVDTPFPAGIFVRLEFKLQQTSCRKRDWKKPECKVRPNGRKRKCLACIKLGSEDKVLGRLVHCPIETQVLREAEEHQETQCLRVQRAGEDPHSFYFPGQFAFS | |
Gene Information
Entrez Gene ID
Gene Name
retinoic acid receptor responder (tazarotene induced) 2
Gene Symbol
Species
Homo sapiens
Gene Ontology (GO Annotations)
| GO ID | Source | Type | Description |
|---|---|---|---|
| GO:0031012 | IDA:DFLAT | C | extracellular matrix |
| GO:0005576 | ISS:UniProtKB | C | extracellular region |
| GO:0070062 | IDA:UniProt | C | extracellular vesicular exosome |
| GO:0005102 | IPI:UniProtKB | F | receptor binding |
| GO:0050873 | IEA:Ensembl | P | brown fat cell differentiation |
| GO:0006935 | IEA:UniProtKB-KW | P | chemotaxis |
| GO:0048566 | IMP:DFLAT | P | embryonic digestive tract development |
| GO:0001701 | IEP:DFLAT | P | in utero embryonic development |
| GO:0006954 | IEA:UniProtKB-KW | P | inflammatory response |
| GO:0050921 | ISS:UniProtKB | P | positive regulation of chemotaxis |
| GO:0045600 | ISS:UniProtKB | P | positive regulation of fat cell differentiation |
| GO:2001275 | IDA:UniProtKB | P | positive regulation of glucose import in response to insulin stimulus |
| GO:0010759 | IMP:DFLAT | P | positive regulation of macrophage chemotaxis |
| GO:0001934 | IDA:UniProtKB | P | positive regulation of protein phosphorylation |
| GO:0050994 | ISS:UniProtKB | P | regulation of lipid catabolic process |
| GO:0001523 | IDA:UniProtKB | P | retinoid metabolic process |
Domain Information
InterPro Annotations
| Accession | Description |
|---|---|
| IPR029562 | Retinoic acid receptor responder protein 2 |
UniProt Annotations
Entry Information
Gene Name
retinoic acid receptor responder (tazarotene induced) 2
Protein Entry
RARR2_HUMAN
UniProt ID
Species
Human
Comments
| Comment Type | Description |
|---|---|
| Function | 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. {ECO |
| Induction | Inhibited in psoriatic lesions. Activated by tazarotene in skin rafts and in the epidermis of psoriatic lesions. |
| Ptm | 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). |
| Subcellular Location | Secreted . |
| Tissue Specificity | 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. {ECO |
Identical and Related Proteins
Unique RefSeq proteins for LMP002013 (as displayed in Record Overview)
| Protein GI | Database | Accession | Length | Protein Name |
|---|---|---|---|---|
| 4506427 | RefSeq | NP_002880 | 163 | retinoic acid receptor responder protein 2 precursor |
Identical Sequences to LMP002013 proteins
| Reference | Database | Accession | Length | Protein Name |
|---|---|---|---|---|
| GI:4506427 | GenBank | ADF13406.1 | 163 | Sequence 8 from patent US 7666401 |
| GI:4506427 | GenBank | ADT46220.1 | 163 | Sequence 8 from patent US 7842453 |
| GI:4506427 | GenBank | AEN51744.1 | 163 | Sequence 8 from patent US 8003347 |
| GI:4506427 | GenBank | AEP61110.1 | 163 | Sequence 104 from patent US 8026065 |
| GI:4506427 | GenBank | AEQ82131.1 | 163 | Sequence 8 from patent US 8030453 |
| GI:4506427 | GenBank | AIC55019.1 | 163 | RARRES2, partial [synthetic construct] |
Related Sequences to LMP002013 proteins
| Reference | Database | Accession | Length | Protein Name |
|---|---|---|---|---|
| GI:4506427 | GenBank | AAX37088.1 | 164 | retinoic acid receptor responder 2, partial [synthetic construct] |
| GI:4506427 | GenBank | ACM85677.1 | 166 | Sequence 11175 from patent US 6812339 |
| GI:4506427 | GenBank | JAA28993.1 | 163 | retinoic acid receptor responder (tazarotene induced) 2 [Pan troglodytes] |
| GI:4506427 | GenBank | JAA35872.1 | 163 | retinoic acid receptor responder (tazarotene induced) 2 [Pan troglodytes] |
| GI:4506427 | RefSeq | XP_003815095.1 | 163 | PREDICTED: retinoic acid receptor responder protein 2 [Pan paniscus] |
| GI:4506427 | RefSeq | XP_004046507.1 | 163 | PREDICTED: retinoic acid receptor responder protein 2 [Gorilla gorilla gorilla] |