Full text data of CCRL2
CCRL2
(CCR11, CCR6, CKRX, CRAM, HCR)
[Confidence: high (present in two of the MS resources)]
C-C chemokine receptor-like 2 (Chemokine receptor CCR11; Chemokine receptor X; Putative MCP-1 chemokine receptor)
C-C chemokine receptor-like 2 (Chemokine receptor CCR11; Chemokine receptor X; Putative MCP-1 chemokine receptor)
Comments
Isoform O00421-2 was detected.
Isoform O00421-2 was detected.
UniProt
O00421
ID CCRL2_HUMAN Reviewed; 344 AA.
AC O00421; B4DKQ8; O75307; Q4VBB0; Q6IPX0; Q7KYQ9; Q96KP5; Q9UPG0;
read moreDT 30-MAY-2006, integrated into UniProtKB/Swiss-Prot.
DT 30-MAY-2006, sequence version 2.
DT 22-JAN-2014, entry version 110.
DE RecName: Full=C-C chemokine receptor-like 2;
DE AltName: Full=Chemokine receptor CCR11;
DE AltName: Full=Chemokine receptor X;
DE AltName: Full=Putative MCP-1 chemokine receptor;
GN Name=CCRL2; Synonyms=CCR11, CCR6, CKRX, CRAM, HCR;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, AND
RP VARIANT TYR-167.
RX PubMed=9473515; DOI=10.1006/bbrc.1997.7981;
RA Fan P., Kyaw H., Su K., Zeng Z., Augustus M., Carter K.C., Li Y.;
RT "Cloning and characterization of a novel human chemokine receptor.";
RL Biochem. Biophys. Res. Commun. 243:264-268(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT TYR-167.
RC TISSUE=Leukocyte;
RA Ansari-Lari M.A., Liu X.-M., Gorrell J.H., Gibbs R.A.;
RT "Haplotype analysis of a gene cluster containing CCR5 and a new member
RT of chemokine receptor gene family.";
RL Submitted (JUL-1997) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), AND VARIANT VAL-243.
RC TISSUE=Monocyte;
RA Gish K., McClanahan T.K., Moore K.W.;
RT "CRAM: a novel human chemokine receptor-like gene expressed in
RT activated monocytes.";
RL Submitted (JUL-1997) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Microglia;
RA Biber K.P.H.;
RT "Cloning and characterisation of a new MCP-1 chemokine receptor
RT CCR11.";
RL Submitted (AUG-2001) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Umbilical cord blood;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT
RP TYR-167.
RC TISSUE=Lung;
RA Kopatz S.A., Aronstam R.S., Sharma S.V.;
RT "cDNA clones of human proteins involved in signal transduction
RT sequenced by the Guthrie cDNA resource center (www.cdna.org).";
RL Submitted (JUL-2003) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT TYR-167.
RX PubMed=16641997; DOI=10.1038/nature04728;
RA Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R.,
RA Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R.,
RA Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V.,
RA Hume J., Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R.,
RA Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Morgan M.B.,
RA Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Wei S.,
RA Wheeler D.A., Wright M.W., Worley K.C., Yuan Y., Zhang Z., Adams C.Q.,
RA Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z.,
RA Clendenning J., Clerc-Blankenburg K.P., Chen R., Chen Z., Davis C.,
RA Delgado O., Dinh H.H., Dong W., Draper H., Ernst S., Fu G.,
RA Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J., Hao B.,
RA Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W., Jackson L.R.,
RA Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B., Liu J.,
RA Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Palmeiri A.,
RA Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B.,
RA Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H.,
RA Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J.,
RA Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J.,
RA Zhang X., Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H.,
RA Reinhardt R., Naylor S.L., Yang H., Olson M., Weinstock G.,
RA Gibbs R.A.;
RT "The DNA sequence, annotation and analysis of human chromosome 3.";
RL Nature 440:1194-1198(2006).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANTS
RP TYR-167 AND MET-168.
RC TISSUE=Brain, Lung, Pancreas, Spleen, and Testis;
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [9]
RP TISSUE SPECIFICITY.
RX PubMed=11828366;
RX DOI=10.1002/1521-4141(200202)32:2<494::AID-IMMU494>3.0.CO;2-Y;
RA Migeotte I., Franssen J.D., Goriely S., Willems F., Parmentier M.;
RT "Distribution and regulation of expression of the putative human
RT chemokine receptor HCR in leukocyte populations.";
RL Eur. J. Immunol. 32:494-501(2002).
RN [10]
RP TISSUE SPECIFICITY, AND LACK OF RESPOND BY CCL2.
RX PubMed=15188357; DOI=10.1002/art.20275;
RA Galligan C.L., Matsuyama W., Matsukawa A., Mizuta H., Hodge D.R.,
RA Howard O.M., Yoshimura T.;
RT "Up-regulated expression and activation of the orphan chemokine
RT receptor, CCRL2, in rheumatoid arthritis.";
RL Arthritis Rheum. 50:1806-1814(2004).
RN [11]
RP TISSUE SPECIFICITY, SUBCELLULAR LOCATION, AND INDUCTION.
RX PubMed=18397265; DOI=10.1111/j.1365-2567.2008.02836.x;
RA Hartmann T.N., Leick M., Ewers S., Diefenbacher A., Schraufstatter I.,
RA Honczarenko M., Burger M.;
RT "Human B cells express the orphan chemokine receptor CRAM-A/B in a
RT maturation-stage-dependent and CCL5-modulated manner.";
RL Immunology 125:252-262(2008).
RN [12]
RP SUBCELLULAR LOCATION, AND LIGAND-BINDING.
RX PubMed=20002784; DOI=10.1111/j.1365-2567.2009.03209.x;
RA Leick M., Catusse J., Follo M., Nibbs R.J., Hartmann T.N., Veelken H.,
RA Burger M.;
RT "CCL19 is a specific ligand of the constitutively recycling atypical
RT human chemokine receptor CRAM-B.";
RL Immunology 129:536-546(2010).
CC -!- FUNCTION: Receptor for CCL19 and chemerin/RARRES2. Does not appear
CC to be a signaling receptor, but may have a role in modulating
CC chemokine-triggered immune responses by capturing and
CC internalizing CCL19 or by presenting RARRES2 ligand to CMKLR1, a
CC functional signaling receptors. Plays a critical role for the
CC development of Th2 responses.
CC -!- SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=CRAM-B;
CC IsoId=O00421-1; Sequence=Displayed;
CC Name=2; Synonyms=CRAM-A;
CC IsoId=O00421-2; Sequence=VSP_018584;
CC -!- TISSUE SPECIFICITY: Expressed abundantly in immunal tissues such
CC as spleen, fetal liver, lymph node and bone marrow. Strong
CC expression also in lung and heart. Expressed in almost all
CC hematopoietic cells including monocytes, macrophages, PMNs, T-
CC cells (both CD4+ and CD8+), monocyte-derived iDCs, NK cells, and
CC CD34+ progenitor cells. B-cells expressed isoform 1 but not
CC isoform 2. Up-regulated on synovial neutrophils of rheumatoid
CC arthritis patients.
CC -!- INDUCTION: Up-regulated by CCL5 on the pre-B-cell lines NALM-6 and
CC G2.
CC -!- DOMAIN: Lacks the conserved DRYLAIV motif in the second
CC intracellular loop that is required for signaling of functional
CC chemokine receptors.
CC -!- MISCELLANEOUS: It was initially reported that CCRL2 responds
CC functionally to CCL2, CCL5, CCL7, and CCL8 via intracellular
CC calcium mobilization and transwell chemotaxis although no evidence
CC for a direct ligand-receptor interaction was provided in this
CC report. These results are now controversial, and other studies
CC 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:15188357).
CC -!- SIMILARITY: Belongs to the G-protein coupled receptor 1 family.
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
CC -----------------------------------------------------------------------
DR EMBL; U97123; AAC39595.1; -; mRNA.
DR EMBL; AF014958; AAB82106.1; -; mRNA.
DR EMBL; AF015524; AAC34601.1; -; mRNA.
DR EMBL; AF015525; AAC34602.1; -; mRNA.
DR EMBL; AJ344142; CAC82985.1; -; mRNA.
DR EMBL; AK296673; BAG59270.1; -; mRNA.
DR EMBL; AY337001; AAQ76789.1; -; mRNA.
DR EMBL; U95626; AAB57794.1; -; Genomic_DNA.
DR EMBL; BC025717; AAH25717.1; -; mRNA.
DR EMBL; BC071682; AAH71682.1; -; mRNA.
DR EMBL; BC096075; AAH96075.1; -; mRNA.
DR EMBL; BC096076; AAH96076.1; -; mRNA.
DR EMBL; BC099623; AAH99623.1; -; mRNA.
DR PIR; JC5942; JC5942.
DR RefSeq; NP_001124382.1; NM_001130910.1.
DR RefSeq; NP_003956.2; NM_003965.4.
DR RefSeq; XP_005265588.1; XM_005265531.1.
DR UniGene; Hs.535713; -.
DR ProteinModelPortal; O00421; -.
DR SMR; O00421; 19-307.
DR STRING; 9606.ENSP00000349967; -.
DR ChEMBL; CHEMBL2321627; -.
DR GuidetoPHARMACOLOGY; 78; -.
DR PhosphoSite; O00421; -.
DR PaxDb; O00421; -.
DR PRIDE; O00421; -.
DR DNASU; 9034; -.
DR GeneID; 9034; -.
DR KEGG; hsa:9034; -.
DR UCSC; uc003cpp.4; human.
DR CTD; 9034; -.
DR GeneCards; GC03P046448; -.
DR HGNC; HGNC:1612; CCRL2.
DR HPA; HPA043238; -.
DR MIM; 608379; gene.
DR neXtProt; NX_O00421; -.
DR PharmGKB; PA26175; -.
DR eggNOG; NOG149863; -.
DR HOVERGEN; HBG106917; -.
DR InParanoid; O00421; -.
DR KO; K08373; -.
DR OMA; FLLMWAP; -.
DR OrthoDB; EOG77HDFH; -.
DR Reactome; REACT_111102; Signal Transduction.
DR GeneWiki; CCRL2; -.
DR GenomeRNAi; 9034; -.
DR NextBio; 33847; -.
DR PRO; PR:O00421; -.
DR ArrayExpress; O00421; -.
DR Bgee; O00421; -.
DR CleanEx; HS_CCR6; -.
DR CleanEx; HS_CCRL2; -.
DR Genevestigator; O00421; -.
DR GO; GO:0005887; C:integral to plasma membrane; IDA:UniProtKB.
DR GO; GO:0004950; F:chemokine receptor activity; TAS:ProtInc.
DR GO; GO:0006935; P:chemotaxis; TAS:ProtInc.
DR GO; GO:0006954; P:inflammatory response; ISS:UniProtKB.
DR InterPro; IPR000355; Chemokine_rcpt.
DR InterPro; IPR000276; GPCR_Rhodpsn.
DR InterPro; IPR017452; GPCR_Rhodpsn_7TM.
DR PANTHER; PTHR24227; PTHR24227; 1.
DR Pfam; PF00001; 7tm_1; 1.
DR PRINTS; PR00657; CCCHEMOKINER.
DR PRINTS; PR00237; GPCRRHODOPSN.
DR PROSITE; PS00237; G_PROTEIN_RECEP_F1_1; FALSE_NEG.
DR PROSITE; PS50262; G_PROTEIN_RECEP_F1_2; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell membrane; Complete proteome;
KW Disulfide bond; G-protein coupled receptor; Glycoprotein; Membrane;
KW Polymorphism; Receptor; Reference proteome; Transducer; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1 344 C-C chemokine receptor-like 2.
FT /FTId=PRO_0000236798.
FT TOPO_DOM 1 43 Extracellular (Potential).
FT TRANSMEM 44 64 Helical; Name=1; (Potential).
FT TOPO_DOM 65 74 Cytoplasmic (Potential).
FT TRANSMEM 75 95 Helical; Name=2; (Potential).
FT TOPO_DOM 96 104 Extracellular (Potential).
FT TRANSMEM 105 125 Helical; Name=3; (Potential).
FT TOPO_DOM 126 144 Cytoplasmic (Potential).
FT TRANSMEM 145 165 Helical; Name=4; (Potential).
FT TOPO_DOM 166 198 Extracellular (Potential).
FT TRANSMEM 199 219 Helical; Name=5; (Potential).
FT TOPO_DOM 220 238 Cytoplasmic (Potential).
FT TRANSMEM 239 259 Helical; Name=6; (Potential).
FT TOPO_DOM 260 286 Extracellular (Potential).
FT TRANSMEM 287 307 Helical; Name=7; (Potential).
FT TOPO_DOM 308 344 Cytoplasmic (Potential).
FT CARBOHYD 3 3 N-linked (GlcNAc...) (Potential).
FT DISULFID 103 181 By similarity.
FT VAR_SEQ 1 1 M -> MIYTRFLKGSLKM (in isoform 2).
FT /FTId=VSP_018584.
FT VARIANT 4 4 Y -> C (in dbSNP:rs11574443).
FT /FTId=VAR_049385.
FT VARIANT 167 167 F -> Y (in dbSNP:rs3204849).
FT /FTId=VAR_026488.
FT VARIANT 168 168 V -> M (in dbSNP:rs6441977).
FT /FTId=VAR_026489.
FT VARIANT 243 243 I -> V (in dbSNP:rs3204850).
FT /FTId=VAR_026490.
FT CONFLICT 45 45 C -> S (in Ref. 5; BAG59270).
FT CONFLICT 135 135 K -> R (in Ref. 5; BAG59270).
FT CONFLICT 158 158 T -> Q (in Ref. 4; CAC82985).
FT CONFLICT 334 334 S -> P (in Ref. 5; BAG59270).
SQ SEQUENCE 344 AA; 39513 MW; D8BBF3A0EE5BB14C CRC64;
MANYTLAPED EYDVLIEGEL ESDEAEQCDK YDAQALSAQL VPSLCSAVFV IGVLDNLLVV
LILVKYKGLK RVENIYLLNL AVSNLCFLLT LPFWAHAGGD PMCKILIGLY FVGLYSETFF
NCLLTVQRYL VFLHKGNFFS ARRRVPCGII TSVLAWVTAI LATLPEFVVY KPQMEDQKYK
CAFSRTPFLP ADETFWKHFL TLKMNISVLV LPLFIFTFLY VQMRKTLRFR EQRYSLFKLV
FAIMVVFLLM WAPYNIAFFL STFKEHFSLS DCKSSYNLDK SVHITKLIAT THCCINPLLY
AFLDGTFSKY LCRCFHLRSN TPLQPRGQSA QGTSREEPDH STEV
//
ID CCRL2_HUMAN Reviewed; 344 AA.
AC O00421; B4DKQ8; O75307; Q4VBB0; Q6IPX0; Q7KYQ9; Q96KP5; Q9UPG0;
read moreDT 30-MAY-2006, integrated into UniProtKB/Swiss-Prot.
DT 30-MAY-2006, sequence version 2.
DT 22-JAN-2014, entry version 110.
DE RecName: Full=C-C chemokine receptor-like 2;
DE AltName: Full=Chemokine receptor CCR11;
DE AltName: Full=Chemokine receptor X;
DE AltName: Full=Putative MCP-1 chemokine receptor;
GN Name=CCRL2; Synonyms=CCR11, CCR6, CKRX, CRAM, HCR;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, AND
RP VARIANT TYR-167.
RX PubMed=9473515; DOI=10.1006/bbrc.1997.7981;
RA Fan P., Kyaw H., Su K., Zeng Z., Augustus M., Carter K.C., Li Y.;
RT "Cloning and characterization of a novel human chemokine receptor.";
RL Biochem. Biophys. Res. Commun. 243:264-268(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANT TYR-167.
RC TISSUE=Leukocyte;
RA Ansari-Lari M.A., Liu X.-M., Gorrell J.H., Gibbs R.A.;
RT "Haplotype analysis of a gene cluster containing CCR5 and a new member
RT of chemokine receptor gene family.";
RL Submitted (JUL-1997) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), AND VARIANT VAL-243.
RC TISSUE=Monocyte;
RA Gish K., McClanahan T.K., Moore K.W.;
RT "CRAM: a novel human chemokine receptor-like gene expressed in
RT activated monocytes.";
RL Submitted (JUL-1997) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Microglia;
RA Biber K.P.H.;
RT "Cloning and characterisation of a new MCP-1 chemokine receptor
RT CCR11.";
RL Submitted (AUG-2001) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Umbilical cord blood;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT
RP TYR-167.
RC TISSUE=Lung;
RA Kopatz S.A., Aronstam R.S., Sharma S.V.;
RT "cDNA clones of human proteins involved in signal transduction
RT sequenced by the Guthrie cDNA resource center (www.cdna.org).";
RL Submitted (JUL-2003) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT TYR-167.
RX PubMed=16641997; DOI=10.1038/nature04728;
RA Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R.,
RA Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R.,
RA Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V.,
RA Hume J., Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R.,
RA Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Morgan M.B.,
RA Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Wei S.,
RA Wheeler D.A., Wright M.W., Worley K.C., Yuan Y., Zhang Z., Adams C.Q.,
RA Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z.,
RA Clendenning J., Clerc-Blankenburg K.P., Chen R., Chen Z., Davis C.,
RA Delgado O., Dinh H.H., Dong W., Draper H., Ernst S., Fu G.,
RA Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J., Hao B.,
RA Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W., Jackson L.R.,
RA Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B., Liu J.,
RA Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Palmeiri A.,
RA Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B.,
RA Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H.,
RA Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J.,
RA Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J.,
RA Zhang X., Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H.,
RA Reinhardt R., Naylor S.L., Yang H., Olson M., Weinstock G.,
RA Gibbs R.A.;
RT "The DNA sequence, annotation and analysis of human chromosome 3.";
RL Nature 440:1194-1198(2006).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANTS
RP TYR-167 AND MET-168.
RC TISSUE=Brain, Lung, Pancreas, Spleen, and Testis;
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [9]
RP TISSUE SPECIFICITY.
RX PubMed=11828366;
RX DOI=10.1002/1521-4141(200202)32:2<494::AID-IMMU494>3.0.CO;2-Y;
RA Migeotte I., Franssen J.D., Goriely S., Willems F., Parmentier M.;
RT "Distribution and regulation of expression of the putative human
RT chemokine receptor HCR in leukocyte populations.";
RL Eur. J. Immunol. 32:494-501(2002).
RN [10]
RP TISSUE SPECIFICITY, AND LACK OF RESPOND BY CCL2.
RX PubMed=15188357; DOI=10.1002/art.20275;
RA Galligan C.L., Matsuyama W., Matsukawa A., Mizuta H., Hodge D.R.,
RA Howard O.M., Yoshimura T.;
RT "Up-regulated expression and activation of the orphan chemokine
RT receptor, CCRL2, in rheumatoid arthritis.";
RL Arthritis Rheum. 50:1806-1814(2004).
RN [11]
RP TISSUE SPECIFICITY, SUBCELLULAR LOCATION, AND INDUCTION.
RX PubMed=18397265; DOI=10.1111/j.1365-2567.2008.02836.x;
RA Hartmann T.N., Leick M., Ewers S., Diefenbacher A., Schraufstatter I.,
RA Honczarenko M., Burger M.;
RT "Human B cells express the orphan chemokine receptor CRAM-A/B in a
RT maturation-stage-dependent and CCL5-modulated manner.";
RL Immunology 125:252-262(2008).
RN [12]
RP SUBCELLULAR LOCATION, AND LIGAND-BINDING.
RX PubMed=20002784; DOI=10.1111/j.1365-2567.2009.03209.x;
RA Leick M., Catusse J., Follo M., Nibbs R.J., Hartmann T.N., Veelken H.,
RA Burger M.;
RT "CCL19 is a specific ligand of the constitutively recycling atypical
RT human chemokine receptor CRAM-B.";
RL Immunology 129:536-546(2010).
CC -!- FUNCTION: Receptor for CCL19 and chemerin/RARRES2. Does not appear
CC to be a signaling receptor, but may have a role in modulating
CC chemokine-triggered immune responses by capturing and
CC internalizing CCL19 or by presenting RARRES2 ligand to CMKLR1, a
CC functional signaling receptors. Plays a critical role for the
CC development of Th2 responses.
CC -!- SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=CRAM-B;
CC IsoId=O00421-1; Sequence=Displayed;
CC Name=2; Synonyms=CRAM-A;
CC IsoId=O00421-2; Sequence=VSP_018584;
CC -!- TISSUE SPECIFICITY: Expressed abundantly in immunal tissues such
CC as spleen, fetal liver, lymph node and bone marrow. Strong
CC expression also in lung and heart. Expressed in almost all
CC hematopoietic cells including monocytes, macrophages, PMNs, T-
CC cells (both CD4+ and CD8+), monocyte-derived iDCs, NK cells, and
CC CD34+ progenitor cells. B-cells expressed isoform 1 but not
CC isoform 2. Up-regulated on synovial neutrophils of rheumatoid
CC arthritis patients.
CC -!- INDUCTION: Up-regulated by CCL5 on the pre-B-cell lines NALM-6 and
CC G2.
CC -!- DOMAIN: Lacks the conserved DRYLAIV motif in the second
CC intracellular loop that is required for signaling of functional
CC chemokine receptors.
CC -!- MISCELLANEOUS: It was initially reported that CCRL2 responds
CC functionally to CCL2, CCL5, CCL7, and CCL8 via intracellular
CC calcium mobilization and transwell chemotaxis although no evidence
CC for a direct ligand-receptor interaction was provided in this
CC report. These results are now controversial, and other studies
CC 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:15188357).
CC -!- SIMILARITY: Belongs to the G-protein coupled receptor 1 family.
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
CC -----------------------------------------------------------------------
DR EMBL; U97123; AAC39595.1; -; mRNA.
DR EMBL; AF014958; AAB82106.1; -; mRNA.
DR EMBL; AF015524; AAC34601.1; -; mRNA.
DR EMBL; AF015525; AAC34602.1; -; mRNA.
DR EMBL; AJ344142; CAC82985.1; -; mRNA.
DR EMBL; AK296673; BAG59270.1; -; mRNA.
DR EMBL; AY337001; AAQ76789.1; -; mRNA.
DR EMBL; U95626; AAB57794.1; -; Genomic_DNA.
DR EMBL; BC025717; AAH25717.1; -; mRNA.
DR EMBL; BC071682; AAH71682.1; -; mRNA.
DR EMBL; BC096075; AAH96075.1; -; mRNA.
DR EMBL; BC096076; AAH96076.1; -; mRNA.
DR EMBL; BC099623; AAH99623.1; -; mRNA.
DR PIR; JC5942; JC5942.
DR RefSeq; NP_001124382.1; NM_001130910.1.
DR RefSeq; NP_003956.2; NM_003965.4.
DR RefSeq; XP_005265588.1; XM_005265531.1.
DR UniGene; Hs.535713; -.
DR ProteinModelPortal; O00421; -.
DR SMR; O00421; 19-307.
DR STRING; 9606.ENSP00000349967; -.
DR ChEMBL; CHEMBL2321627; -.
DR GuidetoPHARMACOLOGY; 78; -.
DR PhosphoSite; O00421; -.
DR PaxDb; O00421; -.
DR PRIDE; O00421; -.
DR DNASU; 9034; -.
DR GeneID; 9034; -.
DR KEGG; hsa:9034; -.
DR UCSC; uc003cpp.4; human.
DR CTD; 9034; -.
DR GeneCards; GC03P046448; -.
DR HGNC; HGNC:1612; CCRL2.
DR HPA; HPA043238; -.
DR MIM; 608379; gene.
DR neXtProt; NX_O00421; -.
DR PharmGKB; PA26175; -.
DR eggNOG; NOG149863; -.
DR HOVERGEN; HBG106917; -.
DR InParanoid; O00421; -.
DR KO; K08373; -.
DR OMA; FLLMWAP; -.
DR OrthoDB; EOG77HDFH; -.
DR Reactome; REACT_111102; Signal Transduction.
DR GeneWiki; CCRL2; -.
DR GenomeRNAi; 9034; -.
DR NextBio; 33847; -.
DR PRO; PR:O00421; -.
DR ArrayExpress; O00421; -.
DR Bgee; O00421; -.
DR CleanEx; HS_CCR6; -.
DR CleanEx; HS_CCRL2; -.
DR Genevestigator; O00421; -.
DR GO; GO:0005887; C:integral to plasma membrane; IDA:UniProtKB.
DR GO; GO:0004950; F:chemokine receptor activity; TAS:ProtInc.
DR GO; GO:0006935; P:chemotaxis; TAS:ProtInc.
DR GO; GO:0006954; P:inflammatory response; ISS:UniProtKB.
DR InterPro; IPR000355; Chemokine_rcpt.
DR InterPro; IPR000276; GPCR_Rhodpsn.
DR InterPro; IPR017452; GPCR_Rhodpsn_7TM.
DR PANTHER; PTHR24227; PTHR24227; 1.
DR Pfam; PF00001; 7tm_1; 1.
DR PRINTS; PR00657; CCCHEMOKINER.
DR PRINTS; PR00237; GPCRRHODOPSN.
DR PROSITE; PS00237; G_PROTEIN_RECEP_F1_1; FALSE_NEG.
DR PROSITE; PS50262; G_PROTEIN_RECEP_F1_2; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell membrane; Complete proteome;
KW Disulfide bond; G-protein coupled receptor; Glycoprotein; Membrane;
KW Polymorphism; Receptor; Reference proteome; Transducer; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1 344 C-C chemokine receptor-like 2.
FT /FTId=PRO_0000236798.
FT TOPO_DOM 1 43 Extracellular (Potential).
FT TRANSMEM 44 64 Helical; Name=1; (Potential).
FT TOPO_DOM 65 74 Cytoplasmic (Potential).
FT TRANSMEM 75 95 Helical; Name=2; (Potential).
FT TOPO_DOM 96 104 Extracellular (Potential).
FT TRANSMEM 105 125 Helical; Name=3; (Potential).
FT TOPO_DOM 126 144 Cytoplasmic (Potential).
FT TRANSMEM 145 165 Helical; Name=4; (Potential).
FT TOPO_DOM 166 198 Extracellular (Potential).
FT TRANSMEM 199 219 Helical; Name=5; (Potential).
FT TOPO_DOM 220 238 Cytoplasmic (Potential).
FT TRANSMEM 239 259 Helical; Name=6; (Potential).
FT TOPO_DOM 260 286 Extracellular (Potential).
FT TRANSMEM 287 307 Helical; Name=7; (Potential).
FT TOPO_DOM 308 344 Cytoplasmic (Potential).
FT CARBOHYD 3 3 N-linked (GlcNAc...) (Potential).
FT DISULFID 103 181 By similarity.
FT VAR_SEQ 1 1 M -> MIYTRFLKGSLKM (in isoform 2).
FT /FTId=VSP_018584.
FT VARIANT 4 4 Y -> C (in dbSNP:rs11574443).
FT /FTId=VAR_049385.
FT VARIANT 167 167 F -> Y (in dbSNP:rs3204849).
FT /FTId=VAR_026488.
FT VARIANT 168 168 V -> M (in dbSNP:rs6441977).
FT /FTId=VAR_026489.
FT VARIANT 243 243 I -> V (in dbSNP:rs3204850).
FT /FTId=VAR_026490.
FT CONFLICT 45 45 C -> S (in Ref. 5; BAG59270).
FT CONFLICT 135 135 K -> R (in Ref. 5; BAG59270).
FT CONFLICT 158 158 T -> Q (in Ref. 4; CAC82985).
FT CONFLICT 334 334 S -> P (in Ref. 5; BAG59270).
SQ SEQUENCE 344 AA; 39513 MW; D8BBF3A0EE5BB14C CRC64;
MANYTLAPED EYDVLIEGEL ESDEAEQCDK YDAQALSAQL VPSLCSAVFV IGVLDNLLVV
LILVKYKGLK RVENIYLLNL AVSNLCFLLT LPFWAHAGGD PMCKILIGLY FVGLYSETFF
NCLLTVQRYL VFLHKGNFFS ARRRVPCGII TSVLAWVTAI LATLPEFVVY KPQMEDQKYK
CAFSRTPFLP ADETFWKHFL TLKMNISVLV LPLFIFTFLY VQMRKTLRFR EQRYSLFKLV
FAIMVVFLLM WAPYNIAFFL STFKEHFSLS DCKSSYNLDK SVHITKLIAT THCCINPLLY
AFLDGTFSKY LCRCFHLRSN TPLQPRGQSA QGTSREEPDH STEV
//
MIM
608379
*RECORD*
*FIELD* NO
608379
*FIELD* TI
*608379 CHEMOKINE, CC MOTIF, RECEPTOR-LIKE PROTEIN 2; CCRL2
;;HCR;;
CRAM
*FIELD* TX
read more
DESCRIPTION
CCRL2 is an atypical chemokine receptor that may have a role in
modulating chemokine-triggered immune responses (Hartmann et al., 2008).
CLONING
By searching an EST database for significant homology to chemokine
receptors, followed by library screening, Fan et al. (1998) obtained a
genomic clone of CCRL2, which they designated HCR. The deduced 345-amino
acid protein has a calculated molecular mass of 39.5 kD. CCRL2 contains
a 7-transmembrane topography and 2 potential N-glycosylation sites. It
shares 43.1% amino acid identity with CKR1 (601159) and 40.5 to 42.7%
identity with several other cytokine receptors. Northern blot analysis
detected a 1.7-kb transcript expressed predominantly in spleen, fetal
liver, lymph node, bone marrow, lung, and heart. Expression was lower in
thymus and placenta, marginal in skeletal muscle, and was not detected
in several other tissues.
Hartmann et al. (2008) noted that 2 CCLR2 splice variants exist, one
encoding a 345-amino acid protein referred to as CCRL2B, CRAMB, CKRX, or
HCR, and the other encoding a 357-amino acid protein referred to as
CCRL2A or CRAMA.
GENE FUNCTION
Using RT-PCR and flow cytometry, Hartmann et al. (2008) showed that CCL5
(187011) induced ERK1 (MAPK3; 601795)/ERK2 (MAPK1; 176948)
phosphorylation and expression of CRAMA and CRAMB, but not other
CCL5-binding molecules, in a pre-B cell line. CCL5 did not induce
calcium mobilization or migratory responses in the cell lines. Hartmann
et al. (2008) suggested that CCRL2 may be involved in immunomodulatory
functions together with CCL5.
Zabel et al. (2008) identified chemerin (RARRES2; 601973) as a protein
that interacted with, but was not internalized by, mouse and human
CCRL2. They proposed that CCRL2 focuses chemerin localization and
thereby contributes to inflammatory processes mediated by the chemerin
receptor, CMKLR1 (602351).
By screening for proteins that could bind human CCRL2, Leick et al.
(2009) identified the homeostatic chemokine CCL19 (602227) as a CCRL2
ligand. CCL19 bound to CCRL2-expressing cells with an affinity
comparable to its binding of CCR7 (600242), but binding to CCRL2 did not
result in cellular activation for calcium mobilization or migration.
Confocal microscopy showed that CCRL2 was constitutively recycled via
clathrin-coated pits and could internalize CCL19, as well as anti-CCRL2
antibodies. Leick et al. (2009) concluded that CCRL2 is a nonclassical
chemokine receptor that may be involved in modulating CCL19-mediated
lymphocyte and dendritic cell trafficking.
ANIMAL MODEL
Zabel et al. (2008) found that Ccrl2-knockout mice displayed no overt
phenotype and had normal numbers of mast cells in all tissues analyzed.
Analysis of Ccrl2-knockout mice showed that Ccrl2 was not required for
expression of IgE-mediated mast cell-dependent passive cutaneous
anaphylaxis. However, Ccrl2 was required for development of optimal
cutaneous tissue swelling and leukocyte infiltrates after sensitization
with low doses of antigen-specific IgE.
MAPPING
By FISH, Fan et al. (1998) mapped the CCRL2 gene to chromosome X.
However, Hartz (2004) mapped the CCRL2 gene to chromosome 3p21 based on
an alignment of the CCRL2 sequence (GenBank GENBANK U97123) with the
genomic sequence.
*FIELD* RF
1. Fan, P.; Kyaw, H.; Su, K.; Zeng, Z.; Augustus, M.; Carter, K. C.;
Li, Y.: Cloning and characterization of a novel human chemokine receptor. Biochem.
Biophys. Res. Commun. 243: 264-268, 1998.
2. Hartmann, T. N.; Leick, M.; Ewers, S.; Diefenbacher, A.; Schraufstatter,
I.; Honczarenko, M.; Burger, M.: Human B cells express the orphan
chemokine receptor CRAM-A/B in a maturation-stage-dependent and CCL5-modulated
manner. Immunology 125: 252-262, 2008.
3. Hartz, P. A.: Personal Communication. Baltimore, Md. 1/7/2004.
4. Leick, M.; Catusse, J.; Follo, M.; Nibbs, R. J.; Hartmann, T. N.;
Veelken, H.; Burger, M.: CCL19 is a specific ligand of the constitutively
recycling atypical human chemokine receptor CRAM-B. Immunology 129:
536-546, 2009.
5. Zabel, B. A.; Nakae, S.; Zuniga, L.; Kim, J.-Y.; Ohyama, T.; Alt,
C.; Pan, J.; Suto, H.; Soler, D.; Allen, S. J.; Handel, T. M.; Song,
C. H.; Galli, S. J.; Butcher, E. C.: Mast cell-expressed orphan receptor
CCRL2 binds chemerin and is required for optimal induction of IgE-mediated
passive cutaneous anaphylaxis. J. Exp. Med. 205: 2207-2220, 2008.
*FIELD* CN
Paul J. Converse - updated: 10/25/2010
Paul J. Converse - updated: 10/27/2009
*FIELD* CD
Patricia A. Hartz: 1/7/2004
*FIELD* ED
mgross: 10/29/2010
terry: 10/25/2010
mgross: 10/29/2009
terry: 10/27/2009
mgross: 1/7/2004
*RECORD*
*FIELD* NO
608379
*FIELD* TI
*608379 CHEMOKINE, CC MOTIF, RECEPTOR-LIKE PROTEIN 2; CCRL2
;;HCR;;
CRAM
*FIELD* TX
read more
DESCRIPTION
CCRL2 is an atypical chemokine receptor that may have a role in
modulating chemokine-triggered immune responses (Hartmann et al., 2008).
CLONING
By searching an EST database for significant homology to chemokine
receptors, followed by library screening, Fan et al. (1998) obtained a
genomic clone of CCRL2, which they designated HCR. The deduced 345-amino
acid protein has a calculated molecular mass of 39.5 kD. CCRL2 contains
a 7-transmembrane topography and 2 potential N-glycosylation sites. It
shares 43.1% amino acid identity with CKR1 (601159) and 40.5 to 42.7%
identity with several other cytokine receptors. Northern blot analysis
detected a 1.7-kb transcript expressed predominantly in spleen, fetal
liver, lymph node, bone marrow, lung, and heart. Expression was lower in
thymus and placenta, marginal in skeletal muscle, and was not detected
in several other tissues.
Hartmann et al. (2008) noted that 2 CCLR2 splice variants exist, one
encoding a 345-amino acid protein referred to as CCRL2B, CRAMB, CKRX, or
HCR, and the other encoding a 357-amino acid protein referred to as
CCRL2A or CRAMA.
GENE FUNCTION
Using RT-PCR and flow cytometry, Hartmann et al. (2008) showed that CCL5
(187011) induced ERK1 (MAPK3; 601795)/ERK2 (MAPK1; 176948)
phosphorylation and expression of CRAMA and CRAMB, but not other
CCL5-binding molecules, in a pre-B cell line. CCL5 did not induce
calcium mobilization or migratory responses in the cell lines. Hartmann
et al. (2008) suggested that CCRL2 may be involved in immunomodulatory
functions together with CCL5.
Zabel et al. (2008) identified chemerin (RARRES2; 601973) as a protein
that interacted with, but was not internalized by, mouse and human
CCRL2. They proposed that CCRL2 focuses chemerin localization and
thereby contributes to inflammatory processes mediated by the chemerin
receptor, CMKLR1 (602351).
By screening for proteins that could bind human CCRL2, Leick et al.
(2009) identified the homeostatic chemokine CCL19 (602227) as a CCRL2
ligand. CCL19 bound to CCRL2-expressing cells with an affinity
comparable to its binding of CCR7 (600242), but binding to CCRL2 did not
result in cellular activation for calcium mobilization or migration.
Confocal microscopy showed that CCRL2 was constitutively recycled via
clathrin-coated pits and could internalize CCL19, as well as anti-CCRL2
antibodies. Leick et al. (2009) concluded that CCRL2 is a nonclassical
chemokine receptor that may be involved in modulating CCL19-mediated
lymphocyte and dendritic cell trafficking.
ANIMAL MODEL
Zabel et al. (2008) found that Ccrl2-knockout mice displayed no overt
phenotype and had normal numbers of mast cells in all tissues analyzed.
Analysis of Ccrl2-knockout mice showed that Ccrl2 was not required for
expression of IgE-mediated mast cell-dependent passive cutaneous
anaphylaxis. However, Ccrl2 was required for development of optimal
cutaneous tissue swelling and leukocyte infiltrates after sensitization
with low doses of antigen-specific IgE.
MAPPING
By FISH, Fan et al. (1998) mapped the CCRL2 gene to chromosome X.
However, Hartz (2004) mapped the CCRL2 gene to chromosome 3p21 based on
an alignment of the CCRL2 sequence (GenBank GENBANK U97123) with the
genomic sequence.
*FIELD* RF
1. Fan, P.; Kyaw, H.; Su, K.; Zeng, Z.; Augustus, M.; Carter, K. C.;
Li, Y.: Cloning and characterization of a novel human chemokine receptor. Biochem.
Biophys. Res. Commun. 243: 264-268, 1998.
2. Hartmann, T. N.; Leick, M.; Ewers, S.; Diefenbacher, A.; Schraufstatter,
I.; Honczarenko, M.; Burger, M.: Human B cells express the orphan
chemokine receptor CRAM-A/B in a maturation-stage-dependent and CCL5-modulated
manner. Immunology 125: 252-262, 2008.
3. Hartz, P. A.: Personal Communication. Baltimore, Md. 1/7/2004.
4. Leick, M.; Catusse, J.; Follo, M.; Nibbs, R. J.; Hartmann, T. N.;
Veelken, H.; Burger, M.: CCL19 is a specific ligand of the constitutively
recycling atypical human chemokine receptor CRAM-B. Immunology 129:
536-546, 2009.
5. Zabel, B. A.; Nakae, S.; Zuniga, L.; Kim, J.-Y.; Ohyama, T.; Alt,
C.; Pan, J.; Suto, H.; Soler, D.; Allen, S. J.; Handel, T. M.; Song,
C. H.; Galli, S. J.; Butcher, E. C.: Mast cell-expressed orphan receptor
CCRL2 binds chemerin and is required for optimal induction of IgE-mediated
passive cutaneous anaphylaxis. J. Exp. Med. 205: 2207-2220, 2008.
*FIELD* CN
Paul J. Converse - updated: 10/25/2010
Paul J. Converse - updated: 10/27/2009
*FIELD* CD
Patricia A. Hartz: 1/7/2004
*FIELD* ED
mgross: 10/29/2010
terry: 10/25/2010
mgross: 10/29/2009
terry: 10/27/2009
mgross: 1/7/2004