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Protein

C-C chemokine receptor-like 2

Gene

CCRL2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.

GO - Molecular functioni

  • CCR chemokine receptor binding Source: UniProtKB
  • chemokine receptor activity Source: ProtInc
  • chemokine receptor binding Source: UniProtKB

GO - Biological processi

  • chemotaxis Source: ProtInc
  • G-protein coupled receptor signaling pathway Source: ProtInc
  • inflammatory response Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

G-protein coupled receptor, Receptor, Transducer

Enzyme and pathway databases

ReactomeiR-HSA-380108. Chemokine receptors bind chemokines.

Names & Taxonomyi

Protein namesi
Recommended name:
C-C chemokine receptor-like 2
Alternative name(s):
Chemokine receptor CCR11
Chemokine receptor X
Putative MCP-1 chemokine receptor
Gene namesi
Name:CCRL2
Synonyms:CCR11, CCR6, CKRX, CRAM, HCR
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 3

Organism-specific databases

HGNCiHGNC:1612. CCRL2.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 43ExtracellularSequence analysisAdd BLAST43
Transmembranei44 – 64Helical; Name=1Sequence analysisAdd BLAST21
Topological domaini65 – 74CytoplasmicSequence analysis10
Transmembranei75 – 95Helical; Name=2Sequence analysisAdd BLAST21
Topological domaini96 – 104ExtracellularSequence analysis9
Transmembranei105 – 125Helical; Name=3Sequence analysisAdd BLAST21
Topological domaini126 – 144CytoplasmicSequence analysisAdd BLAST19
Transmembranei145 – 165Helical; Name=4Sequence analysisAdd BLAST21
Topological domaini166 – 198ExtracellularSequence analysisAdd BLAST33
Transmembranei199 – 219Helical; Name=5Sequence analysisAdd BLAST21
Topological domaini220 – 238CytoplasmicSequence analysisAdd BLAST19
Transmembranei239 – 259Helical; Name=6Sequence analysisAdd BLAST21
Topological domaini260 – 286ExtracellularSequence analysisAdd BLAST27
Transmembranei287 – 307Helical; Name=7Sequence analysisAdd BLAST21
Topological domaini308 – 344CytoplasmicSequence analysisAdd BLAST37

GO - Cellular componenti

  • integral component of plasma membrane Source: UniProtKB
  • plasma membrane Source: Reactome
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Organism-specific databases

DisGeNETi9034.
OpenTargetsiENSG00000121797.
PharmGKBiPA26175.

Chemistry databases

ChEMBLiCHEMBL2321627.
GuidetoPHARMACOLOGYi78.

Polymorphism and mutation databases

BioMutaiCCRL2.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002367981 – 344C-C chemokine receptor-like 2Add BLAST344

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi3N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi103 ↔ 181PROSITE-ProRule annotation

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

MaxQBiO00421.
PaxDbiO00421.
PeptideAtlasiO00421.
PRIDEiO00421.

PTM databases

iPTMnetiO00421.
PhosphoSitePlusiO00421.

Expressioni

Tissue specificityi

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.4 Publications

Inductioni

Up-regulated by CCL5 on the pre-B-cell lines NALM-6 and G2.1 Publication

Gene expression databases

BgeeiENSG00000121797.
CleanExiHS_CCR6.
HS_CCRL2.
ExpressionAtlasiO00421. baseline and differential.
GenevisibleiO00421. HS.

Organism-specific databases

HPAiHPA043238.

Interactioni

GO - Molecular functioni

  • CCR chemokine receptor binding Source: UniProtKB
  • chemokine receptor binding Source: UniProtKB

Protein-protein interaction databases

BioGridi114500. 8 interactors.
STRINGi9606.ENSP00000349967.

Chemistry databases

BindingDBiO00421.

Structurei

3D structure databases

ProteinModelPortaliO00421.
SMRiO00421.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domaini

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

Sequence similaritiesi

Belongs to the G-protein coupled receptor 1 family.PROSITE-ProRule annotation

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410IKE4. Eukaryota.
ENOG411157E. LUCA.
GeneTreeiENSGT00760000118785.
HOVERGENiHBG106917.
InParanoidiO00421.
KOiK08373.
OMAiDETFWKH.
OrthoDBiEOG091G0FG5.
PhylomeDBiO00421.
TreeFamiTF330966.

Family and domain databases

InterProiIPR000355. Chemokine_rcpt.
IPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
[Graphical view]
PfamiPF00001. 7tm_1. 1 hit.
[Graphical view]
PRINTSiPR00657. CCCHEMOKINER.
PR00237. GPCRRHODOPSN.
PROSITEiPS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: O00421-1) [UniParc]FASTAAdd to basket
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.

« Hide

        10         20         30         40         50
MANYTLAPED EYDVLIEGEL ESDEAEQCDK YDAQALSAQL VPSLCSAVFV
60 70 80 90 100
IGVLDNLLVV LILVKYKGLK RVENIYLLNL AVSNLCFLLT LPFWAHAGGD
110 120 130 140 150
PMCKILIGLY FVGLYSETFF NCLLTVQRYL VFLHKGNFFS ARRRVPCGII
160 170 180 190 200
TSVLAWVTAI LATLPEFVVY KPQMEDQKYK CAFSRTPFLP ADETFWKHFL
210 220 230 240 250
TLKMNISVLV LPLFIFTFLY VQMRKTLRFR EQRYSLFKLV FAIMVVFLLM
260 270 280 290 300
WAPYNIAFFL STFKEHFSLS DCKSSYNLDK SVHITKLIAT THCCINPLLY
310 320 330 340
AFLDGTFSKY LCRCFHLRSN TPLQPRGQSA QGTSREEPDH STEV
Length:344
Mass (Da):39,513
Last modified:May 30, 2006 - v2
Checksum:iD8BBF3A0EE5BB14C
GO
Isoform 2 (identifier: O00421-2) [UniParc]FASTAAdd to basket
Also known as: CRAM-A

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

Show »
Length:356
Mass (Da):40,952
Checksum:i83883A727B797D00
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti45C → S in BAG59270 (PubMed:14702039).Curated1
Sequence conflicti135K → R in BAG59270 (PubMed:14702039).Curated1
Sequence conflicti158T → Q in CAC82985 (Ref. 4) Curated1
Sequence conflicti334S → P in BAG59270 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_0493854Y → C.Corresponds to variant rs11574443dbSNPEnsembl.1
Natural variantiVAR_026488167F → Y.5 PublicationsCorresponds to variant rs3204849dbSNPEnsembl.1
Natural variantiVAR_026489168V → M.1 PublicationCorresponds to variant rs6441977dbSNPEnsembl.1
Natural variantiVAR_026490243I → V.1 PublicationCorresponds to variant rs3204850dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0185841M → MIYTRFLKGSLKM in isoform 2. 2 Publications1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS43079.1. [O00421-1]
CCDS46814.1. [O00421-2]
PIRiJC5942.
RefSeqiNP_001124382.1. NM_001130910.1. [O00421-2]
NP_003956.2. NM_003965.4. [O00421-1]
XP_011532510.1. XM_011534208.1. [O00421-1]
XP_011532511.1. XM_011534209.1. [O00421-1]
XP_016862925.1. XM_017007436.1. [O00421-1]
UniGeneiHs.535713.

Genome annotation databases

EnsembliENST00000357392; ENSP00000349967; ENSG00000121797. [O00421-2]
ENST00000399036; ENSP00000381994; ENSG00000121797. [O00421-1]
ENST00000400880; ENSP00000383677; ENSG00000121797. [O00421-1]
ENST00000400882; ENSP00000383678; ENSG00000121797. [O00421-1]
GeneIDi9034.
KEGGihsa:9034.
UCSCiuc003cpp.5. human. [O00421-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS43079.1. [O00421-1]
CCDS46814.1. [O00421-2]
PIRiJC5942.
RefSeqiNP_001124382.1. NM_001130910.1. [O00421-2]
NP_003956.2. NM_003965.4. [O00421-1]
XP_011532510.1. XM_011534208.1. [O00421-1]
XP_011532511.1. XM_011534209.1. [O00421-1]
XP_016862925.1. XM_017007436.1. [O00421-1]
UniGeneiHs.535713.

3D structure databases

ProteinModelPortaliO00421.
SMRiO00421.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi114500. 8 interactors.
STRINGi9606.ENSP00000349967.

Chemistry databases

BindingDBiO00421.
ChEMBLiCHEMBL2321627.
GuidetoPHARMACOLOGYi78.

Protein family/group databases

GPCRDBiSearch...

PTM databases

iPTMnetiO00421.
PhosphoSitePlusiO00421.

Polymorphism and mutation databases

BioMutaiCCRL2.

Proteomic databases

MaxQBiO00421.
PaxDbiO00421.
PeptideAtlasiO00421.
PRIDEiO00421.

Protocols and materials databases

DNASUi9034.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000357392; ENSP00000349967; ENSG00000121797. [O00421-2]
ENST00000399036; ENSP00000381994; ENSG00000121797. [O00421-1]
ENST00000400880; ENSP00000383677; ENSG00000121797. [O00421-1]
ENST00000400882; ENSP00000383678; ENSG00000121797. [O00421-1]
GeneIDi9034.
KEGGihsa:9034.
UCSCiuc003cpp.5. human. [O00421-1]

Organism-specific databases

CTDi9034.
DisGeNETi9034.
GeneCardsiCCRL2.
HGNCiHGNC:1612. CCRL2.
HPAiHPA043238.
MIMi608379. gene.
neXtProtiNX_O00421.
OpenTargetsiENSG00000121797.
PharmGKBiPA26175.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IKE4. Eukaryota.
ENOG411157E. LUCA.
GeneTreeiENSGT00760000118785.
HOVERGENiHBG106917.
InParanoidiO00421.
KOiK08373.
OMAiDETFWKH.
OrthoDBiEOG091G0FG5.
PhylomeDBiO00421.
TreeFamiTF330966.

Enzyme and pathway databases

ReactomeiR-HSA-380108. Chemokine receptors bind chemokines.

Miscellaneous databases

GeneWikiiCCRL2.
GenomeRNAii9034.
PROiO00421.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000121797.
CleanExiHS_CCR6.
HS_CCRL2.
ExpressionAtlasiO00421. baseline and differential.
GenevisibleiO00421. HS.

Family and domain databases

InterProiIPR000355. Chemokine_rcpt.
IPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
[Graphical view]
PfamiPF00001. 7tm_1. 1 hit.
[Graphical view]
PRINTSiPR00657. CCCHEMOKINER.
PR00237. GPCRRHODOPSN.
PROSITEiPS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiCCRL2_HUMAN
AccessioniPrimary (citable) accession number: O00421
Secondary accession number(s): B4DKQ8
, O75307, Q4VBB0, Q6IPX0, Q7KYQ9, Q96KP5, Q9UPG0
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 30, 2006
Last sequence update: May 30, 2006
Last modified: November 2, 2016
This is version 134 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

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 (PubMed:15188357).1 Publication

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. 7-transmembrane G-linked receptors
    List of 7-transmembrane G-linked receptor entries
  2. Human chromosome 3
    Human chromosome 3: entries, gene names and cross-references to MIM
  3. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  6. SIMILARITY comments
    Index of protein domains and families

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.