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O00421 (CCRL2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 116. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
C-C chemokine receptor-like 2
Alternative name(s):
Chemokine receptor CCR11
Chemokine receptor X
Putative MCP-1 chemokine receptor
Gene names
Name:CCRL2
Synonyms:CCR11, CCR6, CKRX, CRAM, HCR
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length344 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Receptor for CCL19 and chemerin/RARRES2. Does not appear to be a signaling receptor, but may have a role in modulating chemokine-triggered immune responses by capturing and internalizing CCL19 or by presenting RARRES2 ligand to CMKLR1, a functional signaling receptors. Plays a critical role for the development of Th2 responses.

Subcellular location

Cell membrane; Multi-pass membrane protein Ref.11 Ref.12.

Tissue specificity

Expressed abundantly in immunal tissues such as spleen, fetal liver, lymph node and bone marrow. Strong expression also in lung and heart. Expressed in almost all hematopoietic cells including monocytes, macrophages, PMNs, T-cells (both CD4+ and CD8+), monocyte-derived iDCs, NK cells, and CD34+ progenitor cells. B-cells expressed isoform 1 but not isoform 2. Up-regulated on synovial neutrophils of rheumatoid arthritis patients. Ref.1 Ref.9 Ref.10 Ref.11

Induction

Up-regulated by CCL5 on the pre-B-cell lines NALM-6 and G2. Ref.11

Domain

Lacks the conserved DRYLAIV motif in the second intracellular loop that is required for signaling of functional chemokine receptors.

Miscellaneous

It was initially reported that CCRL2 responds functionally to CCL2, CCL5, CCL7, and CCL8 via intracellular calcium mobilization and transwell chemotaxis although no evidence for a direct ligand-receptor interaction was provided in this report. These results are now controversial, and other studies failed to confirm CCRL2 recognition and transwell chemotaxis of these chemokines or a series of other CC- and CXC-chemokines using CCRL2-transfected cells (Ref.10).

Sequence similarities

Belongs to the G-protein coupled receptor 1 family.

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: O00421-1)

Also known as: CRAM-B;

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: O00421-2)

Also known as: CRAM-A;

The sequence of this isoform differs from the canonical sequence as follows:
     1-1: M → MIYTRFLKGSLKM

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 344344C-C chemokine receptor-like 2
PRO_0000236798

Regions

Topological domain1 – 4343Extracellular Potential
Transmembrane44 – 6421Helical; Name=1; Potential
Topological domain65 – 7410Cytoplasmic Potential
Transmembrane75 – 9521Helical; Name=2; Potential
Topological domain96 – 1049Extracellular Potential
Transmembrane105 – 12521Helical; Name=3; Potential
Topological domain126 – 14419Cytoplasmic Potential
Transmembrane145 – 16521Helical; Name=4; Potential
Topological domain166 – 19833Extracellular Potential
Transmembrane199 – 21921Helical; Name=5; Potential
Topological domain220 – 23819Cytoplasmic Potential
Transmembrane239 – 25921Helical; Name=6; Potential
Topological domain260 – 28627Extracellular Potential
Transmembrane287 – 30721Helical; Name=7; Potential
Topological domain308 – 34437Cytoplasmic Potential

Amino acid modifications

Glycosylation31N-linked (GlcNAc...) Potential
Disulfide bond103 ↔ 181 By similarity

Natural variations

Alternative sequence11M → MIYTRFLKGSLKM in isoform 2.
VSP_018584
Natural variant41Y → C.
Corresponds to variant rs11574443 [ dbSNP | Ensembl ].
VAR_049385
Natural variant1671F → Y. Ref.1 Ref.2 Ref.6 Ref.7 Ref.8
Corresponds to variant rs3204849 [ dbSNP | Ensembl ].
VAR_026488
Natural variant1681V → M. Ref.8
Corresponds to variant rs6441977 [ dbSNP | Ensembl ].
VAR_026489
Natural variant2431I → V. Ref.3
Corresponds to variant rs3204850 [ dbSNP | Ensembl ].
VAR_026490

Experimental info

Sequence conflict451C → S in BAG59270. Ref.5
Sequence conflict1351K → R in BAG59270. Ref.5
Sequence conflict1581T → Q in CAC82985. Ref.4
Sequence conflict3341S → P in BAG59270. Ref.5

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (CRAM-B) [UniParc].

Last modified May 30, 2006. Version 2.
Checksum: D8BBF3A0EE5BB14C

FASTA34439,513
        10         20         30         40         50         60 
MANYTLAPED EYDVLIEGEL ESDEAEQCDK YDAQALSAQL VPSLCSAVFV IGVLDNLLVV 

        70         80         90        100        110        120 
LILVKYKGLK RVENIYLLNL AVSNLCFLLT LPFWAHAGGD PMCKILIGLY FVGLYSETFF 

       130        140        150        160        170        180 
NCLLTVQRYL VFLHKGNFFS ARRRVPCGII TSVLAWVTAI LATLPEFVVY KPQMEDQKYK 

       190        200        210        220        230        240 
CAFSRTPFLP ADETFWKHFL TLKMNISVLV LPLFIFTFLY VQMRKTLRFR EQRYSLFKLV 

       250        260        270        280        290        300 
FAIMVVFLLM WAPYNIAFFL STFKEHFSLS DCKSSYNLDK SVHITKLIAT THCCINPLLY 

       310        320        330        340 
AFLDGTFSKY LCRCFHLRSN TPLQPRGQSA QGTSREEPDH STEV 

« Hide

Isoform 2 (CRAM-A) [UniParc].

Checksum: 83883A727B797D00
Show »

FASTA35640,952

References

« Hide 'large scale' references
[1]"Cloning and characterization of a novel human chemokine receptor."
Fan P., Kyaw H., Su K., Zeng Z., Augustus M., Carter K.C., Li Y.
Biochem. Biophys. Res. Commun. 243:264-268(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, VARIANT TYR-167.
[2]"Haplotype analysis of a gene cluster containing CCR5 and a new member of chemokine receptor gene family."
Ansari-Lari M.A., Liu X.-M., Gorrell J.H., Gibbs R.A.
Submitted (JUL-1997) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT TYR-167.
Tissue: Leukocyte.
[3]"CRAM: a novel human chemokine receptor-like gene expressed in activated monocytes."
Gish K., McClanahan T.K., Moore K.W.
Submitted (JUL-1997) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), VARIANT VAL-243.
Tissue: Monocyte.
[4]"Cloning and characterisation of a new MCP-1 chemokine receptor CCR11."
Biber K.P.H.
Submitted (AUG-2001) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Tissue: Microglia.
[5]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
Tissue: Umbilical cord blood.
[6]"cDNA clones of human proteins involved in signal transduction sequenced by the Guthrie cDNA resource center (www.cdna.org)."
Kopatz S.A., Aronstam R.S., Sharma S.V.
Submitted (JUL-2003) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANT TYR-167.
Tissue: Lung.
[7]"The DNA sequence, annotation and analysis of human chromosome 3."
Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J. expand/collapse author list , Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W., Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P., Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H., Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J., Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W., Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B., Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H., Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J., Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X., Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R., Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A.
Nature 440:1194-1198(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANT TYR-167.
[8]"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] (ISOFORM 1), VARIANTS TYR-167 AND MET-168.
Tissue: Brain, Lung, Pancreas, Spleen and Testis.
[9]"Distribution and regulation of expression of the putative human chemokine receptor HCR in leukocyte populations."
Migeotte I., Franssen J.D., Goriely S., Willems F., Parmentier M.
Eur. J. Immunol. 32:494-501(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY.
[10]"Up-regulated expression and activation of the orphan chemokine receptor, CCRL2, in rheumatoid arthritis."
Galligan C.L., Matsuyama W., Matsukawa A., Mizuta H., Hodge D.R., Howard O.M., Yoshimura T.
Arthritis Rheum. 50:1806-1814(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY, LACK OF RESPOND BY CCL2.
[11]"Human B cells express the orphan chemokine receptor CRAM-A/B in a maturation-stage-dependent and CCL5-modulated manner."
Hartmann T.N., Leick M., Ewers S., Diefenbacher A., Schraufstatter I., Honczarenko M., Burger M.
Immunology 125:252-262(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY, SUBCELLULAR LOCATION, INDUCTION.
[12]"CCL19 is a specific ligand of the constitutively recycling atypical human chemokine receptor CRAM-B."
Leick M., Catusse J., Follo M., Nibbs R.J., Hartmann T.N., Veelken H., Burger M.
Immunology 129:536-546(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION, LIGAND-BINDING.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U97123 mRNA. Translation: AAC39595.1.
AF014958 mRNA. Translation: AAB82106.1.
AF015524 mRNA. Translation: AAC34601.1.
AF015525 mRNA. Translation: AAC34602.1.
AJ344142 mRNA. Translation: CAC82985.1.
AK296673 mRNA. Translation: BAG59270.1.
AY337001 mRNA. Translation: AAQ76789.1.
U95626 Genomic DNA. Translation: AAB57794.1.
BC025717 mRNA. Translation: AAH25717.1.
BC071682 mRNA. Translation: AAH71682.1.
BC096075 mRNA. Translation: AAH96075.1.
BC096076 mRNA. Translation: AAH96076.1.
BC099623 mRNA. Translation: AAH99623.1.
CCDSCCDS43079.1. [O00421-1]
CCDS46814.1. [O00421-2]
PIRJC5942.
RefSeqNP_001124382.1. NM_001130910.1. [O00421-2]
NP_003956.2. NM_003965.4. [O00421-1]
UniGeneHs.535713.

3D structure databases

ProteinModelPortalO00421.
SMRO00421. Positions 28-316.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

STRING9606.ENSP00000349967.

Chemistry

ChEMBLCHEMBL2321627.
GuidetoPHARMACOLOGY78.

Protein family/group databases

GPCRDBSearch...

PTM databases

PhosphoSiteO00421.

Proteomic databases

PaxDbO00421.
PRIDEO00421.

Protocols and materials databases

DNASU9034.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000357392; ENSP00000349967; ENSG00000121797. [O00421-2]
ENST00000399036; ENSP00000381994; ENSG00000121797. [O00421-1]
ENST00000400880; ENSP00000383677; ENSG00000121797. [O00421-1]
ENST00000400882; ENSP00000383678; ENSG00000121797. [O00421-1]
GeneID9034.
KEGGhsa:9034.
UCSCuc003cpp.4. human. [O00421-1]
uc010hjg.3. human. [O00421-2]

Organism-specific databases

CTD9034.
GeneCardsGC03P046448.
HGNCHGNC:1612. CCRL2.
HPAHPA043238.
MIM608379. gene.
neXtProtNX_O00421.
PharmGKBPA26175.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG149863.
HOVERGENHBG106917.
InParanoidO00421.
KOK08373.
OMAFLLMWAP.
OrthoDBEOG77HDFH.
PhylomeDBO00421.
TreeFamTF330966.

Enzyme and pathway databases

ReactomeREACT_111102. Signal Transduction.

Gene expression databases

ArrayExpressO00421.
BgeeO00421.
CleanExHS_CCR6.
HS_CCRL2.
GenevestigatorO00421.

Family and domain databases

Gene3D1.20.1070.10. 1 hit.
InterProIPR000355. Chemokine_rcpt.
IPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
[Graphical view]
PANTHERPTHR24227. PTHR24227. 1 hit.
PfamPF00001. 7tm_1. 1 hit.
[Graphical view]
PRINTSPR00657. CCCHEMOKINER.
PR00237. GPCRRHODOPSN.
PROSITEPS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiCCRL2.
GenomeRNAi9034.
NextBio33847.
PROO00421.
SOURCESearch...

Entry information

Entry nameCCRL2_HUMAN
AccessionPrimary (citable) accession number: O00421
Secondary accession number(s): B4DKQ8 expand/collapse secondary AC list , O75307, Q4VBB0, Q6IPX0, Q7KYQ9, Q96KP5, Q9UPG0
Entry history
Integrated into UniProtKB/Swiss-Prot: May 30, 2006
Last sequence update: May 30, 2006
Last modified: July 9, 2014
This is version 116 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 3

Human chromosome 3: entries, gene names and cross-references to MIM

7-transmembrane G-linked receptors

List of 7-transmembrane G-linked receptor entries