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Protein

Retinoic acid receptor responder protein 2

Gene

Rarres2

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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. Exhibits an antimicrobial function in the skin.2 Publications

GO - Molecular functioni

GO - Biological processi

  • brown fat cell differentiation Source: MGI
  • chemotaxis Source: UniProtKB-KW
  • embryonic digestive tract development Source: MGI
  • inflammatory response Source: UniProtKB-KW
  • in utero embryonic development Source: Ensembl
  • positive regulation of chemotaxis Source: UniProtKB
  • positive regulation of fat cell differentiation Source: UniProtKB
  • positive regulation of glucose import in response to insulin stimulus Source: UniProtKB
  • positive regulation of macrophage chemotaxis Source: MGI
  • positive regulation of protein phosphorylation Source: UniProtKB
  • regulation of lipid catabolic process Source: UniProtKB
  • retinoid metabolic process Source: MGI
Complete GO annotation...

Keywords - Biological processi

Chemotaxis, Differentiation, Inflammatory response

Enzyme and pathway databases

ReactomeiR-MMU-114608. Platelet degranulation.

Names & Taxonomyi

Protein namesi
Recommended name:
Retinoic acid receptor responder protein 2
Alternative name(s):
Chemerin
Gene namesi
Name:Rarres2
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 6

Organism-specific databases

MGIiMGI:1918910. Rarres2.

Subcellular locationi

GO - Cellular componenti

  • extracellular exosome Source: MGI
  • extracellular matrix Source: MGI
  • extracellular region Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Secreted

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2020By similarityAdd
BLAST
Chaini21 – 156136Retinoic acid receptor responder protein 2PRO_0000022530Add
BLAST
Propeptidei157 – 1626By similarityPRO_0000424871

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi79 ↔ 89By similarity
Disulfide bondi100 ↔ 119By similarity
Disulfide bondi103 ↔ 134Sequence analysis

Post-translational modificationi

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-156, which exhibits the highest activity, while removal of seven amino acids results in chemerin-155 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-155), elastase is able to cleave six (chemerin-156), eight (chemerin-154) or eleven (chemerin-151), plasmin cleaves five amino acids (chemerin-157), and tryptase cleaves five (chemerin-157) or eight (chemerin-154). Multiple cleavages might be required to fully activate chemerin, with an initial tryptase cleavage resulting in chemerin with low activity (chemerin-157), and a second cleavage by carboxypeptidase N or B producing highly active chemerin (chemerin-156) (By similarity).By similarity

Keywords - PTMi

Disulfide bond

Proteomic databases

MaxQBiQ9DD06.
PaxDbiQ9DD06.
PeptideAtlasiQ9DD06.
PRIDEiQ9DD06.

Expressioni

Tissue specificityi

Expressed in the differentiated adipocytes (at protein level). Abundantly expressed in the liver, adipose tissue including visceral, epididymal, and brown adipose tissue.3 Publications

Inductioni

Strongly induced during adipocyte differentiation.1 Publication

Gene expression databases

BgeeiQ9DD06.
ExpressionAtlasiQ9DD06. baseline and differential.
GenevisibleiQ9DD06. MM.

Interactioni

GO - Molecular functioni

Protein-protein interaction databases

IntActiQ9DD06. 1 interaction.
MINTiMINT-4128770.
STRINGi10090.ENSMUSP00000009425.

Structurei

3D structure databases

ProteinModelPortaliQ9DD06.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiENOG410IY1C. Eukaryota.
ENOG410ZEJF. LUCA.
GeneTreeiENSGT00390000016226.
HOGENOMiHOG000093205.
HOVERGENiHBG000698.
InParanoidiQ9DD06.
KOiK10044.
OMAiYYFPGQF.
OrthoDBiEOG7B05FP.
PhylomeDBiQ9DD06.
TreeFamiTF330938.

Family and domain databases

InterProiIPR029562. Chemerin.
[Graphical view]
PANTHERiPTHR15106:SF2. PTHR15106:SF2. 1 hit.

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q9DD06-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MKCLLISLAL WLGTVGTRGT EPELSETQRR SLQVALEEFH KHPPVQLAFQ
60 70 80 90 100
EIGVDRAEEV LFSAGTFVRL EFKLQQTNCP KKDWKKPECT IKPNGRRRKC
110 120 130 140 150
LACIKMDPKG KILGRIVHCP ILKQGPQDPQ ELQCIKIAQA GEDPHGYFLP
160
GQFAFSRALR TK
Length:162
Mass (Da):18,350
Last modified:June 1, 2001 - v1
Checksum:i56FDE44B1BF167F3
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti3 – 31C → F in strain: FVB/N. 1 Publication

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK002298 mRNA. Translation: BAB21997.1.
BC038914 mRNA. Translation: AAH38914.1.
CCDSiCCDS20105.1.
RefSeqiNP_082128.1. NM_027852.2.
XP_006506687.1. XM_006506624.1.
UniGeneiMm.28231.

Genome annotation databases

EnsembliENSMUST00000204267; ENSMUSP00000144793; ENSMUSG00000009281.
ENSMUST00000204930; ENSMUSP00000144799; ENSMUSG00000009281.
GeneIDi71660.
KEGGimmu:71660.
UCSCiuc009but.1. mouse.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK002298 mRNA. Translation: BAB21997.1.
BC038914 mRNA. Translation: AAH38914.1.
CCDSiCCDS20105.1.
RefSeqiNP_082128.1. NM_027852.2.
XP_006506687.1. XM_006506624.1.
UniGeneiMm.28231.

3D structure databases

ProteinModelPortaliQ9DD06.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiQ9DD06. 1 interaction.
MINTiMINT-4128770.
STRINGi10090.ENSMUSP00000009425.

Proteomic databases

MaxQBiQ9DD06.
PaxDbiQ9DD06.
PeptideAtlasiQ9DD06.
PRIDEiQ9DD06.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000204267; ENSMUSP00000144793; ENSMUSG00000009281.
ENSMUST00000204930; ENSMUSP00000144799; ENSMUSG00000009281.
GeneIDi71660.
KEGGimmu:71660.
UCSCiuc009but.1. mouse.

Organism-specific databases

CTDi5919.
MGIiMGI:1918910. Rarres2.

Phylogenomic databases

eggNOGiENOG410IY1C. Eukaryota.
ENOG410ZEJF. LUCA.
GeneTreeiENSGT00390000016226.
HOGENOMiHOG000093205.
HOVERGENiHBG000698.
InParanoidiQ9DD06.
KOiK10044.
OMAiYYFPGQF.
OrthoDBiEOG7B05FP.
PhylomeDBiQ9DD06.
TreeFamiTF330938.

Enzyme and pathway databases

ReactomeiR-MMU-114608. Platelet degranulation.

Miscellaneous databases

ChiTaRSiRarres2. mouse.
PROiQ9DD06.
SOURCEiSearch...

Gene expression databases

BgeeiQ9DD06.
ExpressionAtlasiQ9DD06. baseline and differential.
GenevisibleiQ9DD06. MM.

Family and domain databases

InterProiIPR029562. Chemerin.
[Graphical view]
PANTHERiPTHR15106:SF2. PTHR15106:SF2. 1 hit.
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "The transcriptional landscape of the mammalian genome."
    Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.
    , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
    Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Strain: C57BL/6J.
    Tissue: Kidney.
  2. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT PHE-3.
    Strain: FVB/N.
    Tissue: Liver.
  3. "Chemerin--a new adipokine that modulates adipogenesis via its own receptor."
    Roh S.G., Song S.H., Choi K.C., Katoh K., Wittamer V., Parmentier M., Sasaki S.
    Biochem. Biophys. Res. Commun. 362:1013-1018(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: TISSUE SPECIFICITY.
  4. "Chemerin, a novel adipokine that regulates adipogenesis and adipocyte metabolism."
    Goralski K.B., McCarthy T.C., Hanniman E.A., Zabel B.A., Butcher E.C., Parlee S.D., Muruganandan S., Sinal C.J.
    J. Biol. Chem. 282:28175-28188(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
  5. "Chemerin enhances insulin signaling and potentiates insulin-stimulated glucose uptake in 3T3-L1 adipocytes."
    Takahashi M., Takahashi Y., Takahashi K., Zolotaryov F.N., Hong K.S., Kitazawa R., Iida K., Okimura Y., Kaji H., Kitazawa S., Kasuga M., Chihara K.
    FEBS Lett. 582:573-578(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, SUBCELLULAR LOCATION, INDUCTION, TISSUE SPECIFICITY.
  6. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Kidney, Liver and Lung.

Entry informationi

Entry nameiRARR2_MOUSE
AccessioniPrimary (citable) accession number: Q9DD06
Secondary accession number(s): Q8CHU8
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 26, 2005
Last sequence update: June 1, 2001
Last modified: July 6, 2016
This is version 94 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.