CCRL2_MOUSE
ID CCRL2_MOUSE Reviewed; 360 AA.
AC O35457; O70171; Q3UKM6; Q4FK04; Q91YD7;
DT 30-MAY-2006, integrated into UniProtKB/Swiss-Prot.
DT 30-MAY-2006, sequence version 2.
DT 03-AUG-2022, entry version 145.
DE RecName: Full=C-C chemokine receptor-like 2;
DE AltName: Full=Chemokine receptor CCR11;
DE AltName: Full=G-protein coupled beta chemokine receptor;
DE AltName: Full=Lipopolysaccharide-inducible C-C chemokine receptor;
DE Short=L-CCR;
GN Name=Ccrl2; Synonyms=Ccr11, Lccr;
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 [MRNA], AND TISSUE SPECIFICITY.
RX PubMed=9563519; DOI=10.1016/s0014-5793(98)00299-3;
RA Shimada T., Matsumoto M., Tatsumi Y., Kanamaru A., Akira S.;
RT "A novel lipopolysaccharide inducible C-C chemokine receptor related gene
RT in murine macrophages.";
RL FEBS Lett. 425:490-494(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], INDUCTION, AND TISSUE SPECIFICITY.
RC STRAIN=CD-1;
RX PubMed=12555200; DOI=10.1002/glia.10156;
RA Zuurman M.W., Heeroma J., Brouwer N., Boddeke H.W., Biber K.P.H.;
RT "LPS-induced expression of a novel chemokine receptor (L-CCR) in mouse
RT glial cells in vitro and in vivo.";
RL Glia 41:327-336(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=129/Sv, and C57BL/10;
RA Luo Y., Berman M.A., Fischer F.R., Abromson-Leeman S.R., Kuziel W.A.,
RA Gerard C., Dorf M.E.;
RT "RANTES and eotaxin stimulate chemotaxis, chemokine/cytokine synthesis, and
RT receptor modulation in murine astroctyes.";
RL Submitted (OCT-2000) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Placenta;
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Ebert L., Muenstermann E., Schatten R., Henze S., Bohn E., Mollenhauer J.,
RA Wiemann S., Schick M., Korn B.;
RT "Cloning of mouse full open reading frames in Gateway(R) system entry
RT vector (pDONR201).";
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Mammary gland;
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 [7]
RP FUNCTION.
RX PubMed=12885941; DOI=10.1189/jlb.0802415;
RA Biber K., Zuurman M.W., Homan H., Boddeke H.W.G.M.;
RT "Expression of L-CCR in HEK 293 cells reveals functional responses to CCL2,
RT CCL5, CCL7, and CCL8.";
RL J. Leukoc. Biol. 74:243-251(2003).
RN [8]
RP TISSUE SPECIFICITY.
RX PubMed=14999816; DOI=10.1002/glia.10352;
RA Brouwer N., Zuurman M.W., Wei T., Ransohoff R.M., Boddeke H.W., Biber K.;
RT "Induction of glial L-CCR mRNA expression in spinal cord and brain in
RT experimental autoimmune encephalomyelitis.";
RL Glia 46:84-94(2004).
RN [9]
RP TISSUE SPECIFICITY.
RX PubMed=14966207; DOI=10.1177/002215540405200311;
RA Oostendorp J., Hylkema M.N., Luinge M., Geerlings M., Meurs H., Timens W.,
RA Zaagsma J., Postma D.S., Boddeke H.W., Biber K.;
RT "Localization and enhanced mRNA expression of the orphan chemokine receptor
RT L-CCR in the lung in a murine model of ovalbumin-induced airway
RT inflammation.";
RL J. Histochem. Cytochem. 52:401-410(2004).
RN [10]
RP LIGAND-BINDING, DISRUPTION PHENOTYPE, FUNCTION, AND LACK OF RESPOND TO
RP CCL2; CCL5; CCL7 AND CCL8.
RX PubMed=18794339; DOI=10.1084/jem.20080300;
RA Zabel B.A., Nakae S., Zuniga L., Kim J.Y., Ohyama T., Alt C., Pan J.,
RA Suto H., Soler D., Allen S.J., Handel T.M., Song C.H., Galli S.J.,
RA Butcher E.C.;
RT "Mast cell-expressed orphan receptor CCRL2 binds chemerin and is required
RT for optimal induction of IgE-mediated passive cutaneous anaphylaxis.";
RL J. Exp. Med. 205:2207-2220(2008).
RN [11]
RP TISSUE SPECIFICITY, DISRUPTION PHENOTYPE, AND FUNCTION.
RX PubMed=20606167; DOI=10.1182/blood-2009-12-259903;
RA Otero K., Vecchi A., Hirsch E., Kearley J., Vermi W., Del Prete A.,
RA Gonzalvo-Feo S., Garlanda C., Azzolino O., Salogni L., Lloyd C.M.,
RA Facchetti F., Mantovani A., Sozzani S.;
RT "Nonredundant role of CCRL2 in lung dendritic cell trafficking.";
RL Blood 116:2942-2949(2010).
CC -!- FUNCTION: Receptor for CCL19 and chemerin/RARRES2. Does not appear to
CC be a signaling receptor, but may have a role in modulating chemokine-
CC triggered immune responses by capturing and internalizing CCL19 or by
CC presenting RARRES2 ligand to CMKLR1, a functional signaling receptor.
CC Plays a critical role for the development of Th2 responses (By
CC similarity). {ECO:0000250, ECO:0000269|PubMed:12885941,
CC ECO:0000269|PubMed:18794339, ECO:0000269|PubMed:20606167}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250}; Multi-pass membrane
CC protein {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Expressed in macrophages, astrocytes, in glial
CC cells. Constitutively expressed by mast cells. Detected in bronchial
CC epithelium in OVA-induced airway inflammation. Up-regulated during
CC dendritic cell (DC) maturation. {ECO:0000269|PubMed:12555200,
CC ECO:0000269|PubMed:14966207, ECO:0000269|PubMed:14999816,
CC ECO:0000269|PubMed:20606167, ECO:0000269|PubMed:9563519}.
CC -!- INDUCTION: By bacterial lipopolysaccharide in astrocytes.
CC {ECO:0000269|PubMed:12555200}.
CC -!- DOMAIN: Lacks the conserved DRYLAIV motif in the second intracellular
CC loop that is required for signaling of functional chemokine receptors.
CC {ECO:0000250}.
CC -!- DISRUPTION PHENOTYPE: No visible phenotype. Deficient-mice have normal
CC numbers of mast cells in all tissues analyzed. Wild-type and deficient
CC mice develop marked local inflammation when sensitized with a high dose
CC of DNP-specific IgE, however deficient mice have significantly reduced
CC IgE-dependent passive cutaneous anaphylaxis (PCA) reactions when lower
CC sensitizing dose is used. Deficient-mice show normal recruitment of
CC circulating DC into the lung, but a defective trafficking of antigen-
CC loaded lung DC to mediastinal lymph nodes. This defect was associated
CC to a reduction in lymph node cellularity and reduced priming of T-
CC helper cell 2 response. {ECO:0000269|PubMed:18794339,
CC ECO:0000269|PubMed:20606167}.
CC -!- MISCELLANEOUS: It was initially reported that CCRL2 responds
CC functionally to CCL2, CCL5, CCL7, and CCL8 via intracellular calcium
CC mobilization and transwell chemotaxis although no evidence for a direct
CC ligand-receptor interaction was provided in this report
CC (PubMed:14999816). These results are now controversial and other
CC studies failed to confirm CCRL2 recognition and transwell chemotaxis of
CC these chemokines or a series of other CC- and CXC-chemokines using
CC CCRL2-transfected cells (PubMed:18794339).
CC {ECO:0000305|PubMed:14999816, ECO:0000305|PubMed:18794339}.
CC -!- SIMILARITY: Belongs to the G-protein coupled receptor 1 family.
CC {ECO:0000255|PROSITE-ProRule:PRU00521}.
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DR EMBL; AB009384; BAA25879.1; -; mRNA.
DR EMBL; AJ318863; CAC79612.1; -; mRNA.
DR EMBL; AF316576; AAG30950.1; -; mRNA.
DR EMBL; AF030185; AAB86479.1; -; mRNA.
DR EMBL; AK007808; BAB25273.1; -; mRNA.
DR EMBL; AK145946; BAE26775.1; -; mRNA.
DR EMBL; AK151856; BAE30745.1; -; mRNA.
DR EMBL; CT010248; CAJ18456.1; -; mRNA.
DR EMBL; BC038631; AAH38631.1; -; mRNA.
DR CCDS; CCDS23582.1; -.
DR RefSeq; NP_001289305.1; NM_001302376.1.
DR RefSeq; NP_001289306.1; NM_001302377.1.
DR RefSeq; NP_059494.2; NM_017466.5.
DR AlphaFoldDB; O35457; -.
DR SMR; O35457; -.
DR STRING; 10090.ENSMUSP00000107519; -.
DR GlyGen; O35457; 2 sites.
DR PhosphoSitePlus; O35457; -.
DR PaxDb; O35457; -.
DR PRIDE; O35457; -.
DR ProteomicsDB; 281346; -.
DR Antibodypedia; 6921; 453 antibodies from 34 providers.
DR DNASU; 54199; -.
DR Ensembl; ENSMUST00000111888; ENSMUSP00000107519; ENSMUSG00000043953.
DR Ensembl; ENSMUST00000199839; ENSMUSP00000143116; ENSMUSG00000043953.
DR GeneID; 54199; -.
DR KEGG; mmu:54199; -.
DR UCSC; uc009rvk.2; mouse.
DR CTD; 9034; -.
DR MGI; MGI:1920904; Ccrl2.
DR VEuPathDB; HostDB:ENSMUSG00000043953; -.
DR eggNOG; KOG3656; Eukaryota.
DR GeneTree; ENSGT01020000230359; -.
DR HOGENOM; CLU_009579_8_3_1; -.
DR InParanoid; O35457; -.
DR OMA; CKSNYNL; -.
DR OrthoDB; 1277718at2759; -.
DR PhylomeDB; O35457; -.
DR TreeFam; TF330966; -.
DR Reactome; R-MMU-380108; Chemokine receptors bind chemokines.
DR BioGRID-ORCS; 54199; 4 hits in 74 CRISPR screens.
DR ChiTaRS; Ccrl2; mouse.
DR PRO; PR:O35457; -.
DR Proteomes; UP000000589; Chromosome 9.
DR RNAct; O35457; protein.
DR Bgee; ENSMUSG00000043953; Expressed in granulocyte and 94 other tissues.
DR ExpressionAtlas; O35457; baseline and differential.
DR Genevisible; O35457; MM.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0009897; C:external side of plasma membrane; IBA:GO_Central.
DR GO; GO:0005887; C:integral component of plasma membrane; ISS:UniProtKB.
DR GO; GO:0019957; F:C-C chemokine binding; IBA:GO_Central.
DR GO; GO:0016493; F:C-C chemokine receptor activity; ISS:MGI.
DR GO; GO:0048020; F:CCR chemokine receptor binding; ISO:MGI.
DR GO; GO:0042379; F:chemokine receptor binding; IPI:UniProtKB.
DR GO; GO:0019722; P:calcium-mediated signaling; IBA:GO_Central.
DR GO; GO:0060326; P:cell chemotaxis; IBA:GO_Central.
DR GO; GO:0006955; P:immune response; IBA:GO_Central.
DR GO; GO:0006954; P:inflammatory response; IDA:UniProtKB.
DR GO; GO:0007204; P:positive regulation of cytosolic calcium ion concentration; IBA:GO_Central.
DR InterPro; IPR000355; Chemokine_rcpt.
DR InterPro; IPR000276; GPCR_Rhodpsn.
DR InterPro; IPR017452; GPCR_Rhodpsn_7TM.
DR Pfam; PF00001; 7tm_1; 1.
DR PRINTS; PR00657; CCCHEMOKINER.
DR PRINTS; PR00237; GPCRRHODOPSN.
DR PROSITE; PS50262; G_PROTEIN_RECEP_F1_2; 1.
PE 1: Evidence at protein level;
KW Cell membrane; Disulfide bond; G-protein coupled receptor; Glycoprotein;
KW Membrane; Receptor; Reference proteome; Transducer; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..360
FT /note="C-C chemokine receptor-like 2"
FT /id="PRO_0000236800"
FT TOPO_DOM 1..42
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 43..63
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255"
FT TOPO_DOM 64..73
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 74..94
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255"
FT TOPO_DOM 95..109
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 110..130
FT /note="Helical; Name=3"
FT /evidence="ECO:0000255"
FT TOPO_DOM 131..141
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 142..162
FT /note="Helical; Name=4"
FT /evidence="ECO:0000255"
FT TOPO_DOM 163..202
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 203..223
FT /note="Helical; Name=5"
FT /evidence="ECO:0000255"
FT TOPO_DOM 224..243
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 244..264
FT /note="Helical; Name=6"
FT /evidence="ECO:0000255"
FT TOPO_DOM 265..285
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 286..307
FT /note="Helical; Name=7"
FT /evidence="ECO:0000255"
FT TOPO_DOM 308..360
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT CARBOHYD 3
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 105
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 108..185
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00521"
FT CONFLICT 37
FT /note="P -> S (in Ref. 4; BAE26775)"
FT /evidence="ECO:0000305"
FT CONFLICT 39
FT /note="Q -> R (in Ref. 2; CAC79612)"
FT /evidence="ECO:0000305"
FT CONFLICT 157
FT /note="I -> V (in Ref. 3; AAB86479)"
FT /evidence="ECO:0000305"
FT CONFLICT 215
FT /note="F -> L (in Ref. 2; CAC79612)"
FT /evidence="ECO:0000305"
FT CONFLICT 292
FT /note="V -> A (in Ref. 2; CAC79612)"
FT /evidence="ECO:0000305"
FT CONFLICT 334
FT /note="Y -> S (in Ref. 3; AAB86479)"
FT /evidence="ECO:0000305"
FT CONFLICT 341
FT /note="E -> K (in Ref. 3; AAB86479)"
FT /evidence="ECO:0000305"
FT CONFLICT 359
FT /note="I -> K (in Ref. 5; CAJ18456)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 360 AA; 40745 MW; E0DBF990A8595E3B CRC64;
MDNYTVAPDD EYDVLILDDY LDNSGPDQVP APEFLSPQQV LQFCCAVFAV GLLDNVLAVF
ILVKYKGLKN LGNIYFLNLA LSNLCFLLPL PFWAHTAAHG ESPGNGTCKV LVGLHSSGLY
SEVFSNILLL VQGYRVFSQG RLASIFTTVS CGIVACILAW AMATALSLPE SVFYEPRMER
QKHKCAFGKP HFLPIEAPLW KYVLTSKMII LVLAFPLLVF IICCRQLRRR QSFRERQYDL
HKPALVITGV FLLMWAPYNT VLFLSAFQEH LSLQDEKSSY HLDASVQVTQ LVATTHCCVN
PLLYLLLDRK AFMRYLRSLF PRCNDIPYQS SGGYQQAPPR EGHGRPIELY SNLHQRQDII
