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Protein

C-C chemokine receptor type 6

Gene

CCR6

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

Caution

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

GO - Molecular functioni

  • C-C chemokine binding Source: UniProtKB
  • C-C chemokine receptor activity Source: UniProtKB
  • chemokine receptor activity Source: ProtInc
  • signaling 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
  • G-protein coupled receptor signaling pathway Source: Reactome
  • 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
  • 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 flagellated 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

Keywordsi

Molecular functionG-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

EuPathDBiHostDB:ENSG00000112486.14
HGNCiHGNC:1607 CCR6
MIMi601835 gene
neXtProtiNX_P51684

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 – 47ExtracellularSequence analysisAdd BLAST47
Transmembranei48 – 74Helical; Name=1Sequence analysisAdd BLAST27
Topological domaini75 – 83CytoplasmicSequence analysis9
Transmembranei84 – 104Helical; Name=2Sequence analysisAdd BLAST21
Topological domaini105 – 119ExtracellularSequence analysisAdd BLAST15
Transmembranei120 – 141Helical; Name=3Sequence analysisAdd BLAST22
Topological domaini142 – 159CytoplasmicSequence analysisAdd BLAST18
Transmembranei160 – 180Helical; Name=4Sequence analysisAdd BLAST21
Topological domaini181 – 211ExtracellularSequence analysisAdd BLAST31
Transmembranei212 – 238Helical; Name=5Sequence analysisAdd BLAST27
Topological domaini239 – 254CytoplasmicSequence analysisAdd BLAST16
Transmembranei255 – 279Helical; Name=6Sequence analysisAdd BLAST25
Topological domaini280 – 303ExtracellularSequence analysisAdd BLAST24
Transmembranei304 – 321Helical; Name=7Sequence analysisAdd BLAST18
Topological domaini322 – 374CytoplasmicSequence analysisAdd BLAST53

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi36C → A: No loss of calcium flux but loss of chemotaxis in response to CCL20 stimulation. No effect on cell surface expression. 1 Publication1
Mutagenesisi36C → D or G: Loss of calcium flux and chemotaxis in response to CCL20 stimulation. No effect on cell surface expression. 1 Publication1
Mutagenesisi36C → 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 Publication1
Mutagenesisi57C → S: No effect on calcium flux and chemotaxis in response to CCL20 stimulation. No effect on cell surface expression. 1 Publication1
Mutagenesisi118C → 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 Publication1
Mutagenesisi131C → S: No effect on calcium flux and chemotaxis in response to CCL20 stimulation. No effect on cell surface expression. 1 Publication1
Mutagenesisi138C → S: No effect on calcium flux and chemotaxis in response to CCL20 stimulation. No effect on cell surface expression. 1 Publication1
Mutagenesisi168C → S: No effect on calcium flux and chemotaxis in response to CCL20 stimulation. No effect on cell surface expression. 1 Publication1
Mutagenesisi197C → 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 Publication1
Mutagenesisi233C → S: No effect on calcium flux and chemotaxis in response to CCL20 stimulation. No effect on cell surface expression. 1 Publication1
Mutagenesisi266C → S: No effect on calcium flux and chemotaxis in response to CCL20 stimulation. No effect on cell surface expression. 1 Publication1
Mutagenesisi288C → 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 Publication1
Mutagenesisi288C → 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 Publication1
Mutagenesisi309C → S: No effect on calcium flux and chemotaxis in response to CCL20 stimulation. No effect on cell surface expression. 1 Publication1
Mutagenesisi310C → S: No effect on calcium flux and chemotaxis in response to CCL20 stimulation. No effect on cell surface expression. 1 Publication1
Mutagenesisi336C → S: Reduced calcium flux and chemotaxis in response to CCL20 stimulation, and reduced CCL20-binding. No effect on cell surface expression. 1 Publication1
Mutagenesisi348C → S: No effect on calcium flux and chemotaxis in response to CCL20 stimulation. No effect on CCL20-binding and cell surface expression. 1 Publication1

Organism-specific databases

DisGeNETi1235
MalaCardsiCCR6
OpenTargetsiENSG00000112486
Orphaneti220393 Diffuse cutaneous systemic sclerosis
220402 Limited cutaneous systemic sclerosis
PharmGKBiPA26171

Chemistry databases

ChEMBLiCHEMBL4423
GuidetoPHARMACOLOGYi63

Polymorphism and mutation databases

BioMutaiCCR6
DMDMi2851567

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000692861 – 374C-C chemokine receptor type 6Add BLAST374

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi7N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi23N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi118 ↔ 1971 Publication

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiP51684
PeptideAtlasiP51684
PRIDEiP51684
ProteomicsDBi56368

PTM databases

iPTMnetiP51684
PhosphoSitePlusiP51684

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, 70 interactors
DIPiDIP-5865N
STRINGi9606.ENSP00000339393

Chemistry databases

BindingDBiP51684

Structurei

3D structure databases

ProteinModelPortaliP51684
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
OMAiIMKDLWC
OrthoDBiEOG091G08B0
PhylomeDBiP51684
TreeFamiTF330966

Family and domain databases

CDDicd15172 7tmA_CCR6, 1 hit
InterProiView protein in InterPro
IPR004067 Chemokine_CCR6
IPR000355 Chemokine_rcpt
IPR000276 GPCR_Rhodpsn
IPR017452 GPCR_Rhodpsn_7TM
PANTHERiPTHR10489:SF611 PTHR10489:SF611, 1 hit
PfamiView protein in Pfam
PF00001 7tm_1, 1 hit
PRINTSiPR00657 CCCHEMOKINER
PR01529 CHEMOKINER6
PR00237 GPCRRHODOPSN
PROSITEiView protein in PROSITE
PS00237 G_PROTEIN_RECEP_F1_1, 1 hit
PS50262 G_PROTEIN_RECEP_F1_2, 1 hit

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)DescriptionActionsGraphical viewLength
Sequence conflicti60G → A in AAB06949 (Ref. 4) Curated1
Sequence conflicti74Y → N in AAB06949 (Ref. 4) Curated1
Sequence conflicti86L → V in AAB06949 (Ref. 4) Curated1
Sequence conflicti164S → T in AAC51124 (PubMed:9070937).Curated1
Sequence conflicti164S → T in AAC51125 (PubMed:9070937).Curated1
Sequence conflicti182T → S in AAB06949 (Ref. 4) Curated1
Sequence conflicti192Q → L in AAB06949 (Ref. 4) Curated1
Sequence conflicti206E → V in AAB06949 (Ref. 4) Curated1
Sequence conflicti225I → F in AAB06949 (Ref. 4) Curated1
Sequence conflicti370 – 374SSFTM → VVLHYVIES in AAB06949 (Ref. 4) Curated5

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 No translation available.
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
ENST00000643861; ENSP00000493637; ENSG00000112486
GeneIDi1235
KEGGihsa:1235
UCSCiuc003qvm.5 human

Similar proteinsi

Entry informationi

Entry nameiCCR6_HUMAN
AccessioniPrimary (citable) accession number: P51684
Secondary accession number(s): E1P5C6, P78553, Q92846
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: July 15, 1998
Last modified: June 20, 2018
This is version 179 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. 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

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