Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

C-C chemokine receptor type 6

Gene

CCR6

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

Functioni

Receptor for the C-C type chemokine CCL20 (PubMed:9169459). Binds to CCL20 and subsequently transduces a signal by increasing the intracellular calcium ion levels (PubMed:20068036). Although CCL20 is its major ligand it can also act as a receptor for non-chemokine ligands such as beta-defensins (PubMed:25585877). Binds to defensin DEFB1 leading to increase in intracellular calcium ions and cAMP levels. Its binding to DEFB1 is essential for the function of DEFB1 in regulating sperm motility and bactericidal activity (PubMed:25122636). Binds to defensins DEFB4 and DEFB4A/B and mediates their chemotactic effects (PubMed:20068036). The ligand-receptor pair CCL20-CCR6 is responsible for the chemotaxis of dendritic cells (DC), effector/ memory T-cells and B-cells and plays an important role at skin and mucosal surfaces under homeostatic and inflammatory conditions, as well as in pathology, including cancer and various autoimmune diseases. CCR6-mediated signals are essential for immune responses to microbes in the intestinal mucosa and in the modulation of inflammatory responses initiated by tissue insult and trauma (PubMed:21376174). CCR6 is essential for the recruitment of both the proinflammatory IL17 producing helper T-cells (Th17) and the regulatory T-cells (Treg) to sites of inflammation. Required for the normal migration of Th17 cells in Peyers-patches and other related tissue sites of the intestine and plays a role in regulating effector T-cell balance and distribution in inflamed intestine. Plays an important role in the coordination of early thymocyte precursor migration events important for normal subsequent thymocyte precursor development, but is not required for the formation of normal thymic natural regulatory T-cells (nTregs). Required for optimal differentiation of DN2 and DN3 thymocyte precursors. Essential for B-cell localization in the subepithelial dome of Peyers-patches and for efficient B-cell isotype switching to IgA in the Peyers-patches. Essential for appropriate anatomical distribution of memory B-cells in the spleen and for the secondary recall response of memory B-cells (By similarity). Positively regulates sperm motility and chemotaxis via its binding to CCL20 (PubMed:23765988).2 PublicationsBy similarity4 Publications

GO - Molecular functioni

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

GO - Biological processi

  • calcium-mediated signaling Source: UniProtKB
  • cell chemotaxis Source: UniProtKB
  • cellular defense response Source: ProtInc
  • chemotaxis Source: UniProtKB
  • dendritic cell chemotaxis Source: BHF-UCL
  • DN2 thymocyte differentiation Source: UniProtKB
  • DN3 thymocyte differentiation Source: UniProtKB
  • humoral immune response Source: ProtInc
  • immune response Source: ProtInc
  • isotype switching to IgA isotypes Source: UniProtKB
  • leukocyte migration involved in inflammatory response Source: UniProtKB
  • lymphocyte migration Source: UniProtKB
  • movement of cell or subcellular component Source: ProtInc
  • positive regulation of cytosolic calcium ion concentration Source: ProtInc
  • positive regulation of dendritic cell chemotaxis Source: Ensembl
  • positive regulation of epithelial cell migration Source: Ensembl
  • positive regulation of sperm motility involved in capacitation Source: UniProtKB
  • regulation of T cell migration Source: UniProtKB
  • signal transduction Source: ProtInc
  • T cell migration Source: UniProtKB
  • thymocyte migration Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

G-protein coupled receptor, Receptor, Transducer

Enzyme and pathway databases

ReactomeiR-HSA-1461957. Beta defensins.
R-HSA-380108. Chemokine receptors bind chemokines.
R-HSA-418594. G alpha (i) signalling events.

Names & Taxonomyi

Protein namesi
Recommended name:
C-C chemokine receptor type 6
Short name:
C-C CKR-6
Short name:
CC-CKR-6
Short name:
CCR-6
Alternative name(s):
Chemokine receptor-like 3
Short name:
CKR-L3
DRY6
G-protein coupled receptor 29
GPR-CY4
Short name:
GPRCY4
LARC receptor
CD_antigen: CD196
Gene namesi
Name:CCR6
Synonyms:CKRL3, CMKBR6, GPR29, STRL22
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 6

Organism-specific databases

HGNCiHGNC:1607. CCR6.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 4747ExtracellularSequence analysisAdd
BLAST
Transmembranei48 – 7427Helical; Name=1Sequence analysisAdd
BLAST
Topological domaini75 – 839CytoplasmicSequence analysis
Transmembranei84 – 10421Helical; Name=2Sequence analysisAdd
BLAST
Topological domaini105 – 11915ExtracellularSequence analysisAdd
BLAST
Transmembranei120 – 14122Helical; Name=3Sequence analysisAdd
BLAST
Topological domaini142 – 15918CytoplasmicSequence analysisAdd
BLAST
Transmembranei160 – 18021Helical; Name=4Sequence analysisAdd
BLAST
Topological domaini181 – 21131ExtracellularSequence analysisAdd
BLAST
Transmembranei212 – 23827Helical; Name=5Sequence analysisAdd
BLAST
Topological domaini239 – 25416CytoplasmicSequence analysisAdd
BLAST
Transmembranei255 – 27925Helical; Name=6Sequence analysisAdd
BLAST
Topological domaini280 – 30324ExtracellularSequence analysisAdd
BLAST
Transmembranei304 – 32118Helical; Name=7Sequence analysisAdd
BLAST
Topological domaini322 – 37453CytoplasmicSequence analysisAdd
BLAST

GO - Cellular componenti

  • cell surface Source: UniProtKB
  • cytosol Source: Ensembl
  • integral component of plasma membrane Source: ProtInc
  • plasma membrane Source: Reactome
  • sperm flagellum Source: UniProtKB
  • sperm midpiece Source: UniProtKB
  • sperm plasma membrane Source: UniProtKB
  • sperm principal piece Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi36 – 361C → A: No loss of calcium flux but loss of chemotaxis in response to CCL20 stimulation. No effect on cell surface expression. 1 Publication
Mutagenesisi36 – 361C → D or G: Loss of calcium flux and chemotaxis in response to CCL20 stimulation. No effect on cell surface expression. 1 Publication
Mutagenesisi36 – 361C → S: No loss of calcium flux but loss of chemotaxis in response to CCL20 stimulation, impaired CCL20-binding and no effect on cell surface expression; when associated with or without S-288. Loss of calcium flux in response to CCL20 stimulation and significant reduction in cell surface expression; when associated with S-118; S-197 and S-288. 1 Publication
Mutagenesisi57 – 571C → S: No effect on calcium flux and chemotaxis in response to CCL20 stimulation. No effect on cell surface expression. 1 Publication
Mutagenesisi118 – 1181C → S: Loss of calcium flux and chemotaxis in response to CCL20 stimulation, impaired CCL20-binding and significant reduction in cell surface expression; when associated with or without S-197. Loss of calcium flux in response to CCL20 stimulation and significant reduction in cell surface expression; when associated with S-36; S-197 and S-288. 1 Publication
Mutagenesisi131 – 1311C → S: No effect on calcium flux and chemotaxis in response to CCL20 stimulation. No effect on cell surface expression. 1 Publication
Mutagenesisi138 – 1381C → S: No effect on calcium flux and chemotaxis in response to CCL20 stimulation. No effect on cell surface expression. 1 Publication
Mutagenesisi168 – 1681C → S: No effect on calcium flux and chemotaxis in response to CCL20 stimulation. No effect on cell surface expression. 1 Publication
Mutagenesisi197 – 1971C → S: Loss of calcium flux and chemotaxis in response to CCL20 stimulation, impaired CCL20-binding and significant reduction in cell surface expression; when associated with or without S-118. Loss of calcium flux in response to CCL20 stimulation and significant reduction in cell surface expression; when associated with S-36; S-118 and S-288. 1 Publication
Mutagenesisi233 – 2331C → S: No effect on calcium flux and chemotaxis in response to CCL20 stimulation. No effect on cell surface expression. 1 Publication
Mutagenesisi266 – 2661C → S: No effect on calcium flux and chemotaxis in response to CCL20 stimulation. No effect on cell surface expression. 1 Publication
Mutagenesisi288 – 2881C → A, G or R: No loss of calcium flux but loss of chemotaxis in response to CCL20 stimulation. No effect on cell surface expression. 1 Publication
Mutagenesisi288 – 2881C → S: No loss of calcium flux but loss of chemotaxis in response to CCL20 stimulation, impaired CCL20-binding and no effect on cell surface expression; when associated with or without S-36. Loss of calcium flux in response to CCL20 stimulation and significant reduction in cell surface expression; when associated with S-36; S-118 and S-197. 1 Publication
Mutagenesisi309 – 3091C → S: No effect on calcium flux and chemotaxis in response to CCL20 stimulation. No effect on cell surface expression. 1 Publication
Mutagenesisi310 – 3101C → S: No effect on calcium flux and chemotaxis in response to CCL20 stimulation. No effect on cell surface expression. 1 Publication
Mutagenesisi336 – 3361C → S: Reduced calcium flux and chemotaxis in response to CCL20 stimulation, and reduced CCL20-binding. No effect on cell surface expression. 1 Publication
Mutagenesisi348 – 3481C → S: No effect on calcium flux and chemotaxis in response to CCL20 stimulation. No effect on CCL20-binding and cell surface expression. 1 Publication

Organism-specific databases

MalaCardsiCCR6.
Orphaneti220393. Diffuse cutaneous systemic sclerosis.
220402. Limited cutaneous systemic sclerosis.
PharmGKBiPA26171.

Chemistry

ChEMBLiCHEMBL4423.
GuidetoPHARMACOLOGYi63.

Polymorphism and mutation databases

BioMutaiCCR6.
DMDMi2851567.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 374374C-C chemokine receptor type 6PRO_0000069286Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi7 – 71N-linked (GlcNAc...)Sequence analysis
Glycosylationi23 – 231N-linked (GlcNAc...)Sequence analysis
Disulfide bondi118 ↔ 1971 Publication

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiP51684.
PeptideAtlasiP51684.
PRIDEiP51684.

PTM databases

iPTMnetiP51684.
PhosphoSiteiP51684.

Expressioni

Tissue specificityi

Sperm. Mainly localized in the tail and in the postacrosomal region but is also found in the midpiece and basal region in a small percentage of sperm cells. Reduced levels found in the sperms of asthenozoospermia and leukocytospermia patients (at protein level). Spleen, lymph nodes, appendix, and fetal liver. Expressed in lymphocytes, T-cells and B-cells but not in natural killer cells, monocytes or granulocytes.3 Publications

Inductioni

By IL2/interleukin-2.

Gene expression databases

BgeeiENSG00000112486.
CleanExiHS_CCR6.
GenevisibleiP51684. HS.

Organism-specific databases

HPAiCAB006820.
HPA014488.

Interactioni

GO - Molecular functioni

  • C-C chemokine binding Source: UniProtKB

Protein-protein interaction databases

BioGridi107640. 2 interactions.
DIPiDIP-5865N.
MINTiMINT-1525119.
STRINGi9606.ENSP00000339393.

Chemistry

BindingDBiP51684.

Structurei

3D structure databases

ProteinModelPortaliP51684.
SMRiP51684. Positions 40-331.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

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

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410IKPR. Eukaryota.
ENOG410XSP7. LUCA.
GeneTreeiENSGT00760000118785.
HOGENOMiHOG000234122.
HOVERGENiHBG106917.
InParanoidiP51684.
KOiK04181.
OMAiCYMFIVK.
OrthoDBiEOG091G08B0.
PhylomeDBiP51684.
TreeFamiTF330966.

Family and domain databases

InterProiIPR004067. Chemokine_CCR6.
IPR000355. Chemokine_rcpt.
IPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
[Graphical view]
PfamiPF00001. 7tm_1. 1 hit.
[Graphical view]
PRINTSiPR00657. CCCHEMOKINER.
PR01529. CHEMOKINER6.
PR00237. GPCRRHODOPSN.
PROSITEiPS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

P51684-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MSGESMNFSD VFDSSEDYFV SVNTSYYSVD SEMLLCSLQE VRQFSRLFVP
60 70 80 90 100
IAYSLICVFG LLGNILVVIT FAFYKKARSM TDVYLLNMAI ADILFVLTLP
110 120 130 140 150
FWAVSHATGA WVFSNATCKL LKGIYAINFN CGMLLLTCIS MDRYIAIVQA
160 170 180 190 200
TKSFRLRSRT LPRSKIICLV VWGLSVIISS STFVFNQKYN TQGSDVCEPK
210 220 230 240 250
YQTVSEPIRW KLLMLGLELL FGFFIPLMFM IFCYTFIVKT LVQAQNSKRH
260 270 280 290 300
KAIRVIIAVV LVFLACQIPH NMVLLVTAAN LGKMNRSCQS EKLIGYTKTV
310 320 330 340 350
TEVLAFLHCC LNPVLYAFIG QKFRNYFLKI LKDLWCVRRK YKSSGFSCAG
360 370
RYSENISRQT SETADNDNAS SFTM
Length:374
Mass (Da):42,494
Last modified:July 15, 1998 - v2
Checksum:iD7F963534E990BC4
GO

Sequence cautioni

The sequence CAB02144 differs from that shown. Reason: Erroneous initiation. Curated

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti60 – 601G → A in AAB06949 (Ref. 4) Curated
Sequence conflicti74 – 741Y → N in AAB06949 (Ref. 4) Curated
Sequence conflicti86 – 861L → V in AAB06949 (Ref. 4) Curated
Sequence conflicti164 – 1641S → T in AAC51124 (PubMed:9070937).Curated
Sequence conflicti164 – 1641S → T in AAC51125 (PubMed:9070937).Curated
Sequence conflicti182 – 1821T → S in AAB06949 (Ref. 4) Curated
Sequence conflicti192 – 1921Q → L in AAB06949 (Ref. 4) Curated
Sequence conflicti206 – 2061E → V in AAB06949 (Ref. 4) Curated
Sequence conflicti225 – 2251I → F in AAB06949 (Ref. 4) Curated
Sequence conflicti370 – 3745SSFTM → VVLHYVIES in AAB06949 (Ref. 4) Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U45984 Genomic DNA. Translation: AAB62714.1.
Z79784 Genomic DNA. Translation: CAB02144.1. Different initiation.
U60000 mRNA. Translation: AAB06949.1.
U68030 mRNA. Translation: AAC51124.1.
U68032 Genomic DNA. Translation: AAC51125.1.
AY242126 mRNA. Translation: AAO92293.1.
AL121935 Genomic DNA. Translation: CAB99328.1.
CH471051 Genomic DNA. Translation: EAW47506.1.
CH471051 Genomic DNA. Translation: EAW47507.1.
BC037960 mRNA. Translation: AAH37960.1.
CCDSiCCDS5298.1.
PIRiJC5068.
RefSeqiNP_004358.2. NM_004367.5.
NP_113597.2. NM_031409.3.
UniGeneiHs.46468.

Genome annotation databases

EnsembliENST00000341935; ENSP00000343952; ENSG00000112486.
ENST00000349984; ENSP00000339393; ENSG00000112486.
ENST00000400926; ENSP00000383715; ENSG00000112486.
GeneIDi1235.
KEGGihsa:1235.
UCSCiuc003qvm.5. human.

Cross-referencesi

Web resourcesi

Wikipedia

CC chemokine receptors entry

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U45984 Genomic DNA. Translation: AAB62714.1.
Z79784 Genomic DNA. Translation: CAB02144.1. Different initiation.
U60000 mRNA. Translation: AAB06949.1.
U68030 mRNA. Translation: AAC51124.1.
U68032 Genomic DNA. Translation: AAC51125.1.
AY242126 mRNA. Translation: AAO92293.1.
AL121935 Genomic DNA. Translation: CAB99328.1.
CH471051 Genomic DNA. Translation: EAW47506.1.
CH471051 Genomic DNA. Translation: EAW47507.1.
BC037960 mRNA. Translation: AAH37960.1.
CCDSiCCDS5298.1.
PIRiJC5068.
RefSeqiNP_004358.2. NM_004367.5.
NP_113597.2. NM_031409.3.
UniGeneiHs.46468.

3D structure databases

ProteinModelPortaliP51684.
SMRiP51684. Positions 40-331.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi107640. 2 interactions.
DIPiDIP-5865N.
MINTiMINT-1525119.
STRINGi9606.ENSP00000339393.

Chemistry

BindingDBiP51684.
ChEMBLiCHEMBL4423.
GuidetoPHARMACOLOGYi63.

Protein family/group databases

GPCRDBiSearch...

PTM databases

iPTMnetiP51684.
PhosphoSiteiP51684.

Polymorphism and mutation databases

BioMutaiCCR6.
DMDMi2851567.

Proteomic databases

PaxDbiP51684.
PeptideAtlasiP51684.
PRIDEiP51684.

Protocols and materials databases

DNASUi1235.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000341935; ENSP00000343952; ENSG00000112486.
ENST00000349984; ENSP00000339393; ENSG00000112486.
ENST00000400926; ENSP00000383715; ENSG00000112486.
GeneIDi1235.
KEGGihsa:1235.
UCSCiuc003qvm.5. human.

Organism-specific databases

CTDi1235.
GeneCardsiCCR6.
HGNCiHGNC:1607. CCR6.
HPAiCAB006820.
HPA014488.
MalaCardsiCCR6.
MIMi601835. gene.
neXtProtiNX_P51684.
Orphaneti220393. Diffuse cutaneous systemic sclerosis.
220402. Limited cutaneous systemic sclerosis.
PharmGKBiPA26171.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IKPR. Eukaryota.
ENOG410XSP7. LUCA.
GeneTreeiENSGT00760000118785.
HOGENOMiHOG000234122.
HOVERGENiHBG106917.
InParanoidiP51684.
KOiK04181.
OMAiCYMFIVK.
OrthoDBiEOG091G08B0.
PhylomeDBiP51684.
TreeFamiTF330966.

Enzyme and pathway databases

ReactomeiR-HSA-1461957. Beta defensins.
R-HSA-380108. Chemokine receptors bind chemokines.
R-HSA-418594. G alpha (i) signalling events.

Miscellaneous databases

ChiTaRSiCCR6. human.
GeneWikiiC-C_chemokine_receptor_type_6.
GenomeRNAii1235.
PROiP51684.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000112486.
CleanExiHS_CCR6.
GenevisibleiP51684. HS.

Family and domain databases

InterProiIPR004067. Chemokine_CCR6.
IPR000355. Chemokine_rcpt.
IPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
[Graphical view]
PfamiPF00001. 7tm_1. 1 hit.
[Graphical view]
PRINTSiPR00657. CCCHEMOKINER.
PR01529. CHEMOKINER6.
PR00237. GPCRRHODOPSN.
PROSITEiPS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiCCR6_HUMAN
AccessioniPrimary (citable) accession number: P51684
Secondary accession number(s): E1P5C6, P78553, Q92846
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: July 15, 1998
Last modified: September 7, 2016
This is version 163 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

Caution

It is uncertain whether Met-1 or Met-6 is the initiator.Curated

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. 7-transmembrane G-linked receptors
    List of 7-transmembrane G-linked receptor entries
  2. Human cell differentiation molecules
    CD nomenclature of surface proteins of human leucocytes and list of entries
  3. Human chromosome 6
    Human chromosome 6: entries, gene names and cross-references to MIM
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. 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.