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Protein

C-C chemokine receptor-like 2

Gene

CCRL2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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.

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

GO - Molecular functioni

  • C-C chemokine binding Source: GO_Central
  • C-C chemokine receptor activity Source: GO_Central
  • CCR chemokine receptor binding Source: UniProtKB
  • chemokine binding Source: GO_Central
  • chemokine receptor activity Source: ProtInc
  • chemokine receptor binding Source: UniProtKB

GO - Biological processi

Keywordsi

Molecular functionG-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

EuPathDBiHostDB:ENSG00000121797.9
HGNCiHGNC:1612 CCRL2
MIMi608379 gene
neXtProtiNX_O00421

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

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

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...) asparagineSequence analysis1
Disulfide bondi103 ↔ 181PROSITE-ProRule annotation

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

MaxQBiO00421
PaxDbiO00421
PeptideAtlasiO00421
PRIDEiO00421
ProteomicsDBi47877
47878 [O00421-2]

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 Expressed in 125 organ(s), highest expression level in visceral pleura
CleanExiHS_CCR6
HS_CCRL2
ExpressionAtlasiO00421 baseline and differential
GenevisibleiO00421 HS

Organism-specific databases

HPAiHPA043238

Interactioni

GO - Molecular functioni

Protein-protein interaction databases

BioGridi114500, 8 interactors
IntActiO00421, 2 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
GeneTreeiENSGT00930000150855
HOVERGENiHBG106917
InParanoidiO00421
KOiK08373
OMAiLLMWAPY
OrthoDBiEOG091G0FG5
PhylomeDBiO00421
TreeFamiTF330966

Family and domain databases

InterProiView protein in InterPro
IPR000355 Chemokine_rcpt
IPR000276 GPCR_Rhodpsn
IPR017452 GPCR_Rhodpsn_7TM
PfamiView protein in Pfam
PF00001 7tm_1, 1 hit
PRINTSiPR00657 CCCHEMOKINER
PR00237 GPCRRHODOPSN
PROSITEiView protein in PROSITE
PS50262 G_PROTEIN_RECEP_F1_2, 1 hit

Sequences (2+)i

Sequence statusi: Complete.

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

This entry has 2 described isoforms and 1 potential isoform that is computationally mapped.Show allAlign All

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

Computationally mapped potential isoform sequencesi

There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
C9JP23C9JP23_HUMAN
C-C chemokine receptor-like 2
CCRL2
217Annotation score:

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 dbSNP:rs11574443Ensembl.1
Natural variantiVAR_026488167F → Y5 PublicationsCorresponds to variant dbSNP:rs3204849Ensembl.1
Natural variantiVAR_026489168V → M1 PublicationCorresponds to variant dbSNP:rs6441977Ensembl.1
Natural variantiVAR_026490243I → V1 PublicationCorresponds to variant dbSNP:rs3204850Ensembl.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

Similar proteinsi

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
IntActiO00421, 2 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
ProteomicsDBi47877
47878 [O00421-2]

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
EuPathDBiHostDB:ENSG00000121797.9
GeneCardsiCCRL2
HGNCiHGNC:1612 CCRL2
HPAiHPA043238
MIMi608379 gene
neXtProtiNX_O00421
OpenTargetsiENSG00000121797
PharmGKBiPA26175
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IKE4 Eukaryota
ENOG411157E LUCA
GeneTreeiENSGT00930000150855
HOVERGENiHBG106917
InParanoidiO00421
KOiK08373
OMAiLLMWAPY
OrthoDBiEOG091G0FG5
PhylomeDBiO00421
TreeFamiTF330966

Enzyme and pathway databases

ReactomeiR-HSA-380108 Chemokine receptors bind chemokines

Miscellaneous databases

GeneWikiiCCRL2
GenomeRNAii9034
PROiPR:O00421
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000121797 Expressed in 125 organ(s), highest expression level in visceral pleura
CleanExiHS_CCR6
HS_CCRL2
ExpressionAtlasiO00421 baseline and differential
GenevisibleiO00421 HS

Family and domain databases

InterProiView protein in InterPro
IPR000355 Chemokine_rcpt
IPR000276 GPCR_Rhodpsn
IPR017452 GPCR_Rhodpsn_7TM
PfamiView protein in Pfam
PF00001 7tm_1, 1 hit
PRINTSiPR00657 CCCHEMOKINER
PR00237 GPCRRHODOPSN
PROSITEiView protein in PROSITE
PS50262 G_PROTEIN_RECEP_F1_2, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiCCRL2_HUMAN
AccessioniPrimary (citable) accession number: O00421
Secondary accession number(s): B4DKQ8
, O75307, Q4VBB0, Q6IPX0, Q7KYQ9, Q96KP5, Q9UPG0
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 30, 2006
Last sequence update: May 30, 2006
Last modified: November 7, 2018
This is version 143 of the entry and version 2 of the sequence. See 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

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  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. 7-transmembrane G-linked receptors
    List of 7-transmembrane G-linked receptor entries
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