RARR2_MOUSE
ID RARR2_MOUSE Reviewed; 162 AA.
AC Q9DD06; Q8CHU8;
DT 26-APR-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 03-AUG-2022, entry version 126.
DE RecName: Full=Retinoic acid receptor responder protein 2;
DE AltName: Full=Chemerin;
DE Flags: Precursor;
GN Name=Rarres2;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Kidney;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT PHE-3.
RC STRAIN=FVB/N; TISSUE=Liver;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP TISSUE SPECIFICITY.
RX PubMed=17767914; DOI=10.1016/j.bbrc.2007.08.104;
RA Roh S.G., Song S.H., Choi K.C., Katoh K., Wittamer V., Parmentier M.,
RA Sasaki S.;
RT "Chemerin--a new adipokine that modulates adipogenesis via its own
RT receptor.";
RL Biochem. Biophys. Res. Commun. 362:1013-1018(2007).
RN [4]
RP FUNCTION, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=17635925; DOI=10.1074/jbc.m700793200;
RA Goralski K.B., McCarthy T.C., Hanniman E.A., Zabel B.A., Butcher E.C.,
RA Parlee S.D., Muruganandan S., Sinal C.J.;
RT "Chemerin, a novel adipokine that regulates adipogenesis and adipocyte
RT metabolism.";
RL J. Biol. Chem. 282:28175-28188(2007).
RN [5]
RP FUNCTION, SUBCELLULAR LOCATION, INDUCTION, AND TISSUE SPECIFICITY.
RX PubMed=18242188; DOI=10.1016/j.febslet.2008.01.023;
RA Takahashi M., Takahashi Y., Takahashi K., Zolotaryov F.N., Hong K.S.,
RA Kitazawa R., Iida K., Okimura Y., Kaji H., Kitazawa S., Kasuga M.,
RA Chihara K.;
RT "Chemerin enhances insulin signaling and potentiates insulin-stimulated
RT glucose uptake in 3T3-L1 adipocytes.";
RL FEBS Lett. 582:573-578(2008).
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Kidney, Liver, and Lung;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
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.
CC {ECO:0000269|PubMed:17635925, ECO:0000269|PubMed:18242188}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:17635925,
CC ECO:0000269|PubMed:18242188}.
CC -!- TISSUE SPECIFICITY: Expressed in the differentiated adipocytes (at
CC protein level). Abundantly expressed in the liver, adipose tissue
CC including visceral, epididymal, and brown adipose tissue.
CC {ECO:0000269|PubMed:17635925, ECO:0000269|PubMed:17767914,
CC ECO:0000269|PubMed:18242188}.
CC -!- INDUCTION: Strongly induced during adipocyte differentiation.
CC {ECO:0000269|PubMed:18242188}.
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-156, which exhibits the
CC highest activity, while removal of seven amino acids results in
CC chemerin-155 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-155), elastase is able to cleave
CC six (chemerin-156), eight (chemerin-154) or eleven (chemerin-151),
CC plasmin cleaves five amino acids (chemerin-157), and tryptase cleaves
CC five (chemerin-157) or eight (chemerin-154). Multiple cleavages might
CC be required to fully activate chemerin, with an initial tryptase
CC cleavage resulting in chemerin with low activity (chemerin-157), and a
CC second cleavage by carboxypeptidase N or B producing highly active
CC chemerin (chemerin-156) (By similarity).
CC {ECO:0000250|UniProtKB:Q99969}.
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DR EMBL; AK002298; BAB21997.1; -; mRNA.
DR EMBL; BC038914; AAH38914.1; -; mRNA.
DR CCDS; CCDS20105.1; -.
DR RefSeq; NP_001334097.1; NM_001347168.1.
DR RefSeq; NP_082128.1; NM_027852.3.
DR AlphaFoldDB; Q9DD06; -.
DR SMR; Q9DD06; -.
DR STRING; 10090.ENSMUSP00000009425; -.
DR PhosphoSitePlus; Q9DD06; -.
DR CPTAC; non-CPTAC-3412; -.
DR MaxQB; Q9DD06; -.
DR PaxDb; Q9DD06; -.
DR PeptideAtlas; Q9DD06; -.
DR PRIDE; Q9DD06; -.
DR ProteomicsDB; 255103; -.
DR Antibodypedia; 32863; 365 antibodies from 23 providers.
DR DNASU; 71660; -.
DR Ensembl; ENSMUST00000204267; ENSMUSP00000144793; ENSMUSG00000009281.
DR Ensembl; ENSMUST00000204930; ENSMUSP00000144799; ENSMUSG00000009281.
DR GeneID; 71660; -.
DR KEGG; mmu:71660; -.
DR UCSC; uc009but.1; mouse.
DR CTD; 5919; -.
DR MGI; MGI:1918910; Rarres2.
DR VEuPathDB; HostDB:ENSMUSG00000009281; -.
DR eggNOG; ENOG502SE7C; Eukaryota.
DR GeneTree; ENSGT00390000016226; -.
DR HOGENOM; CLU_138029_0_0_1; -.
DR InParanoid; Q9DD06; -.
DR PhylomeDB; Q9DD06; -.
DR TreeFam; TF330938; -.
DR Reactome; R-MMU-114608; Platelet degranulation.
DR BioGRID-ORCS; 71660; 2 hits in 75 CRISPR screens.
DR ChiTaRS; Rarres2; mouse.
DR PRO; PR:Q9DD06; -.
DR Proteomes; UP000000589; Chromosome 6.
DR RNAct; Q9DD06; protein.
DR Bgee; ENSMUSG00000009281; Expressed in placenta labyrinth and 243 other tissues.
DR ExpressionAtlas; Q9DD06; baseline and differential.
DR Genevisible; Q9DD06; MM.
DR GO; GO:0062023; C:collagen-containing extracellular matrix; ISO:MGI.
DR GO; GO:0031012; C:extracellular matrix; IBA:GO_Central.
DR GO; GO:0005576; C:extracellular region; IDA:UniProtKB.
DR GO; GO:0005615; C:extracellular space; HDA:BHF-UCL.
DR GO; GO:0005102; F:signaling receptor binding; ISO:MGI.
DR GO; GO:0019732; P:antifungal humoral response; ISO:MGI.
DR GO; GO:0061760; P:antifungal innate immune response; ISO:MGI.
DR GO; GO:0050873; P:brown fat cell differentiation; IDA:MGI.
DR GO; GO:0006935; P:chemotaxis; IEA:UniProtKB-KW.
DR GO; GO:0050829; P:defense response to Gram-negative bacterium; ISO:MGI.
DR GO; GO:0050830; P:defense response to Gram-positive bacterium; ISO:MGI.
DR GO; GO:0048566; P:embryonic digestive tract development; ISO:MGI.
DR GO; GO:0006954; P:inflammatory response; IEA:UniProtKB-KW.
DR GO; GO:0045087; P:innate immune response; ISO:MGI.
DR GO; GO:0008286; P:insulin receptor signaling pathway; ISO:MGI.
DR GO; GO:0050921; P:positive regulation of chemotaxis; IDA:UniProtKB.
DR GO; GO:0045600; P:positive regulation of fat cell differentiation; IMP:UniProtKB.
DR GO; GO:0010759; P:positive regulation of macrophage chemotaxis; ISO:MGI.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; IDA:UniProtKB.
DR GO; GO:0003084; P:positive regulation of systemic arterial blood pressure; ISO:MGI.
DR GO; GO:0046626; P:regulation of insulin receptor signaling pathway; IDA:UniProtKB.
DR GO; GO:0050994; P:regulation of lipid catabolic process; IMP:UniProtKB.
DR GO; GO:0001523; P:retinoid metabolic process; ISO:MGI.
DR InterPro; IPR029562; Chemerin.
DR InterPro; IPR046350; Cystatin_sf.
DR PANTHER; PTHR15106; PTHR15106; 1.
DR SUPFAM; SSF54403; SSF54403; 1.
PE 1: Evidence at protein 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..156
FT /note="Retinoic acid receptor responder protein 2"
FT /id="PRO_0000022530"
FT PROPEP 157..162
FT /evidence="ECO:0000250"
FT /id="PRO_0000424871"
FT DISULFID 79..89
FT /evidence="ECO:0000250"
FT DISULFID 100..119
FT /evidence="ECO:0000250"
FT DISULFID 103..134
FT /evidence="ECO:0000255"
FT VARIANT 3
FT /note="C -> F (in strain: FVB/N)"
FT /evidence="ECO:0000269|PubMed:15489334"
SQ SEQUENCE 162 AA; 18350 MW; 56FDE44B1BF167F3 CRC64;
MKCLLISLAL WLGTVGTRGT EPELSETQRR SLQVALEEFH KHPPVQLAFQ EIGVDRAEEV
LFSAGTFVRL EFKLQQTNCP KKDWKKPECT IKPNGRRRKC LACIKMDPKG KILGRIVHCP
ILKQGPQDPQ ELQCIKIAQA GEDPHGYFLP GQFAFSRALR TK
