DegronMD - Q99969(RARRES2)

FUNCTION: Adipocyte-secreted protein (adipokine) that regulates adipogenesis, metabolism and inflammation through activation of the chemokine-like receptor 1 (CMKLR1). Acts also as a ligand for CMKLR2. Can also bind to C-C chemokine receptor-like 2 (CCRL2), but with a lower affinity than it does to CMKLR1 or CMKLR2 (PubMed:27716822). 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 pro-inflammatory adipokine, causing an increase in secretion of pro-inflammatory 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:0000269|PubMed:14675762, ECO:0000269|PubMed:17635925, ECO:0000269|PubMed:17767914, ECO:0000269|PubMed:18242188, ECO:0000269|PubMed:20237162, ECO:0000269|PubMed:22634313, ECO:0000269|PubMed:23527010, ECO:0000269|PubMed:27716822}. View more >>

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Mutation	Sample	Cancer	Dataset	Degron hit	Class	Location	Type	Impact score
p.R113W	TCGA-CD-8527	STAD	TCGA	KRKCLACIK	DEG_APCC_DBOX_1	95:103	Mutation rewiring degron network	0.0556
p.R113W	DO47739	STAD	ICGC	KRKCLACIK	DEG_APCC_DBOX_1	95:103	Mutation rewiring degron network	0.0556
p.C98G	TCGA-CR-6482	HNSC	TCGA	KRKCLACIK	DEG_APCC_DBOX_1	95:103	Mutation altering degron motif	0.6489
p.C98G	DO15943	HNSC	ICGC	KRKCLACIK	DEG_APCC_DBOX_1	95:103	Mutation altering degron motif	0.6489
p.R96G	TCGA-CR-7371	HNSC	TCGA	KRKCLACIK	DEG_APCC_DBOX_1	95:103	Mutation altering degron motif	0.7568
p.R96G	DO15454	HNSC	ICGC	KRKCLACIK	DEG_APCC_DBOX_1	95:103	Mutation altering degron motif	0.7568
p.E86K	TCGA-E7-A7XN	BLCA	TCGA	KRKCLACIK	DEG_APCC_DBOX_1	95:103	Mutation rewiring degron network	0.0833
p.E86K	DO51878	BLCA	ICGC	KRKCLACIK	DEG_APCC_DBOX_1	95:103	Mutation rewiring degron network	0.0833
p.E86K	SIDM01577	Plasma Cell Myeloma	GDSC	KRKCLACIK	DEG_APCC_DBOX_1	95:103	Mutation rewiring degron network	0.0833
p.E86K	ACH-000889	Myeloma	CCLE	KRKCLACIK	DEG_APCC_DBOX_1	95:103	Mutation rewiring degron network	0.0833
p.G93R	TCGA-EE-A29M	SKCM	TCGA	KRKCLACIK	DEG_APCC_DBOX_1	95:103	Mutation rewiring degron network	0.2778
p.G93R	DO37404	SKCM	ICGC	KRKCLACIK	DEG_APCC_DBOX_1	95:103	Mutation rewiring degron network	0.2778
p.A9T	TCGA-EO-A22U	UCEC	TCGA	MRRLLIPLA	DEG_APCC_DBOX_1	1:9	Mutation altering degron motif	0.6028
p.A9T	DO43755	UCEC	ICGC	MRRLLIPLA	DEG_APCC_DBOX_1	1:9	Mutation altering degron motif	0.6028
p.C101R	TCGA-FR-A8YC	SKCM	TCGA	KRKCLACIK	DEG_APCC_DBOX_1	95:103	Mutation altering degron motif	0.719
p.C101R	DO50301	SKCM	ICGC	KRKCLACIK	DEG_APCC_DBOX_1	95:103	Mutation altering degron motif	0.719
p.R113Q	TCGA-XK-AAIW	PRAD	TCGA	KRKCLACIK	DEG_APCC_DBOX_1	95:103	Mutation rewiring degron network	0.0556
p.R113Q	DO51407	PRAD	ICGC	KRKCLACIK	DEG_APCC_DBOX_1	95:103	Mutation rewiring degron network	0.0556
p.G112D	DO231987	LICA	ICGC	KRKCLACIK	DEG_APCC_DBOX_1	95:103	Mutation rewiring degron network	0.0833
p.P91T	DO228974	LICA	ICGC	KRKCLACIK	DEG_APCC_DBOX_1	95:103	Mutation rewiring degron network	0.2222
p.R2G	DO224541	LUSC	ICGC	MRRLLIPLA	DEG_APCC_DBOX_1	1:9	Mutation altering degron motif	0.7568
p.R2G	DO231003	LUSC	ICGC	MRRLLIPLA	DEG_APCC_DBOX_1	1:9	Mutation altering degron motif	0.7568
p.R96W	DO228138	PBCA	ICGC	KRKCLACIK	DEG_APCC_DBOX_1	95:103	Mutation altering degron motif	0.8634
p.A14T	SIDM01608	Endometrial Carcinoma	GDSC	MRRLLIPLA	DEG_APCC_DBOX_1	1:9	Mutation rewiring degron network	0.1944
p.A14T	ACH-000990	Endometrial/Uterine Cancer	CCLE	MRRLLIPLA	DEG_APCC_DBOX_1	1:9	Mutation rewiring degron network	0.1944

Kaplan plot for RARRES2 in

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*NOTE: the Kaplan plots were collected from OncoLnc

DegronMD: protein-targeted degradation, mutation and drug response to degrons

RARRES2

UniProt ID: Q99969

Entrez ID: 5919

Protein name: Retinoic acid receptor responder protein 2 (Chemerin) (RAR-responsive protein TIG2) (Tazarotene-induced gene 2 protein)

External links: UniprotKB HGNC RefSeq COSMIC

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Kaplan plot for RARRES2 in