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Q924I3

- ACKR4_MOUSE

UniProt

Q924I3 - ACKR4_MOUSE

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Protein

Atypical chemokine receptor 4

Gene

Ackr4

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 4 out of 5- Experimental evidence at protein leveli

Functioni

Atypical chemokine receptor that controls chemokine levels and localization via high-affinity chemokine binding that is uncoupled from classic ligand-driven signal transduction cascades, resulting instead in chemokine sequestration, degradation, or transcytosis. Also known as interceptor (internalizing receptor) or chemokine-scavenging receptor or chemokine decoy receptor. Acts as a receptor for chemokines CCL2, CCL8, CCL13, CCL19, CCL21 and CCL25. Chemokine-binding does not activate G-protein-mediated signal transduction but instead induces beta-arrestin recruitment, leading to ligand internalization. Plays an important role in controlling the migration of immune and cancer cells that express chemokine receptors CCR7 and CCR9, by reducing the availability of CCL19, CCL21, and CCL25 through internalization. Negatively regulates CXCR3-induced chemotaxis. Regulates T-cell development in the thymus and inhibits spontaneous autoimmunity.2 Publications

GO - Molecular functioni

  1. chemokine receptor activity Source: UniProtKB
  2. scavenger receptor activity Source: InterPro

GO - Biological processi

  1. chemokine-mediated signaling pathway Source: GOC
  2. chemotaxis Source: InterPro
Complete GO annotation...

Keywords - Molecular functioni

G-protein coupled receptor, Receptor, Transducer

Enzyme and pathway databases

ReactomeiREACT_230248. Chemokine receptors bind chemokines.

Names & Taxonomyi

Protein namesi
Recommended name:
Atypical chemokine receptor 4
Alternative name(s):
C-C chemokine receptor type 11
Short name:
C-C CKR-11
Short name:
CC-CKR-11
Short name:
CCR-11
CC chemokine receptor-like 1
Short name:
CCRL1
CCX CKR
Gene namesi
Name:Ackr4
Synonyms:Ccr11, Ccrl1
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589: Chromosome 9

Organism-specific databases

MGIiMGI:2181676. Ackr4.

Subcellular locationi

Early endosome By similarity. Recycling endosome By similarity. Cell membrane By similarity; Multi-pass membrane protein By similarity
Note: Predominantly localizes to endocytic vesicles, and upon stimulation by the ligand is internalized via caveolae. Once internalized, the ligand dissociates from the receptor, and is targeted to degradation while the receptor is recycled back to the cell membrane (By similarity).By similarity

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 4141ExtracellularSequence AnalysisAdd
BLAST
Transmembranei42 – 6221Helical; Name=1Sequence AnalysisAdd
BLAST
Topological domaini63 – 7715CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei78 – 9922Helical; Name=2Sequence AnalysisAdd
BLAST
Topological domaini100 – 11415ExtracellularSequence AnalysisAdd
BLAST
Transmembranei115 – 13521Helical; Name=3Sequence AnalysisAdd
BLAST
Topological domaini136 – 15419CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei155 – 17521Helical; Name=4Sequence AnalysisAdd
BLAST
Topological domaini176 – 19924ExtracellularSequence AnalysisAdd
BLAST
Transmembranei200 – 22021Helical; Name=5Sequence AnalysisAdd
BLAST
Topological domaini221 – 24020CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei241 – 26121Helical; Name=6Sequence AnalysisAdd
BLAST
Topological domaini262 – 28928ExtracellularSequence AnalysisAdd
BLAST
Transmembranei290 – 31021Helical; Name=7Sequence AnalysisAdd
BLAST
Topological domaini311 – 35040CytoplasmicSequence AnalysisAdd
BLAST

GO - Cellular componenti

  1. endosome Source: UniProtKB-KW
  2. integral component of membrane Source: UniProtKB-KW
  3. plasma membrane Source: UniProtKB-KW
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Endosome, Membrane

Pathology & Biotechi

Disruption phenotypei

Mice have a larger thymus with relatively fewer cortical thymic epithelial cells and this is associated with severe reductions in cortical CCL25 distribution and accumulation of DN2 thymocyte precursor cells in the medulla. The downstream effects materialize in reduced proportions of DN3 cells and significantly reduced numbers of cortical DN3 cells. Aberrant thymocyte development culminates in increased prevalence of spontaneous autoimmune-like disease, characterized by lymphocytic infiltration of peripheral organs.1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 350350Atypical chemokine receptor 4PRO_0000069297Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi6 – 61N-linked (GlcNAc...)Sequence Analysis
Glycosylationi19 – 191N-linked (GlcNAc...)Sequence Analysis

Post-translational modificationi

The Ser/Thr residues in the C-terminal cytoplasmic tail may be phosphorylated.By similarity

Keywords - PTMi

Glycoprotein, Phosphoprotein

Proteomic databases

PRIDEiQ924I3.

PTM databases

PhosphoSiteiQ924I3.

Expressioni

Tissue specificityi

Expressed in lung, heart, spleen, skeletal muscle, testis, astrocytes and microglia. Expressed by cortical thymic epithelial cells.3 Publications

Gene expression databases

BgeeiQ924I3.
CleanExiMM_CCRL1.
GenevestigatoriQ924I3.

Interactioni

Subunit structurei

Forms heteromers with CXCR3. Interacts with ARRB1 and ARRB2 (By similarity).By similarity

Structurei

3D structure databases

ProteinModelPortaliQ924I3.
SMRiQ924I3. Positions 39-322.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

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

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiNOG148788.
GeneTreeiENSGT00760000118785.
HOGENOMiHOG000234122.
HOVERGENiHBG106917.
InParanoidiQ924I3.
KOiK04186.
OMAiLEICIGF.
OrthoDBiEOG7GJ6DG.
PhylomeDBiQ924I3.
TreeFamiTF330966.

Family and domain databases

Gene3Di1.20.1070.10. 1 hit.
InterProiIPR005383. Chemokine_CCRL1.
IPR000355. Chemokine_rcpt.
IPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
[Graphical view]
PANTHERiPTHR24227. PTHR24227. 1 hit.
PTHR24227:SF35. PTHR24227:SF35. 1 hit.
PfamiPF00001. 7tm_1. 1 hit.
[Graphical view]
PRINTSiPR00657. CCCHEMOKINER.
PR01558. CHEMOKINER11.
PR00237. GPCRRHODOPSN.
PROSITEiPS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q924I3-1 [UniParc]FASTAAdd to Basket

« Hide

        10         20         30         40         50
MALELNQSAE YYYEENEMNY THDYSQYEVI CIKEEVRQFA KVFLPAFFTV
60 70 80 90 100
AFVTGLAGNS VVVAIYAYYK KQRTKTDVYI LNLAVADLLL LITLPFWAVN
110 120 130 140 150
AVHGWILGKM MCKVTSALYT VNFVSGMQFL ACISIDRYWA ITKAPSQSGA
160 170 180 190 200
GRPCWIICCC VWMAAILLSI PQLVFYTVNQ NARCTPIFPH HLGTSLKASI
210 220 230 240 250
QMLEIGIGFV VPFLIMGVCY ASTARALIKM PNIKKSRPLR VLLAVVVVFI
260 270 280 290 300
VTQLPYNVVK FCQAIDAIYL LITSCDMSKR MDVAIQVTES IALFHSCLNP
310 320 330 340 350
ILYVFMGASF KNYIMKVAKK YGSWRRQRQN VEEIPFDSEG PTEPTSSFTI
Length:350
Mass (Da):39,531
Last modified:December 1, 2001 - v1
Checksum:iC5F7D9DC949CECCF
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti50 – 501V → M in BAC27061. (PubMed:16141072)Curated
Sequence conflicti287 – 2871V → L in AAL68400. (PubMed:11981810)Curated
Sequence conflicti287 – 2871V → L in AAL68962. (PubMed:11981810)Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF306532 mRNA. Translation: AAK81712.1.
AY072796 mRNA. Translation: AAL68400.1.
AY072938 mRNA. Translation: AAL68962.1.
AK030643 mRNA. Translation: BAC27061.1.
AK042430 mRNA. Translation: BAC31258.1.
CCDSiCCDS23459.1.
RefSeqiNP_663746.2. NM_145700.2.
XP_006511797.1. XM_006511734.1.
XP_006511798.1. XM_006511735.1.
UniGeneiMm.269254.

Genome annotation databases

EnsembliENSMUST00000076147; ENSMUSP00000075507; ENSMUSG00000079355.
ENSMUST00000188000; ENSMUSP00000140792; ENSMUSG00000079355.
GeneIDi252837.
KEGGimmu:252837.
UCSCiuc009rhh.2. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF306532 mRNA. Translation: AAK81712.1 .
AY072796 mRNA. Translation: AAL68400.1 .
AY072938 mRNA. Translation: AAL68962.1 .
AK030643 mRNA. Translation: BAC27061.1 .
AK042430 mRNA. Translation: BAC31258.1 .
CCDSi CCDS23459.1.
RefSeqi NP_663746.2. NM_145700.2.
XP_006511797.1. XM_006511734.1.
XP_006511798.1. XM_006511735.1.
UniGenei Mm.269254.

3D structure databases

ProteinModelPortali Q924I3.
SMRi Q924I3. Positions 39-322.
ModBasei Search...
MobiDBi Search...

Protein family/group databases

GPCRDBi Search...

PTM databases

PhosphoSitei Q924I3.

Proteomic databases

PRIDEi Q924I3.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSMUST00000076147 ; ENSMUSP00000075507 ; ENSMUSG00000079355 .
ENSMUST00000188000 ; ENSMUSP00000140792 ; ENSMUSG00000079355 .
GeneIDi 252837.
KEGGi mmu:252837.
UCSCi uc009rhh.2. mouse.

Organism-specific databases

CTDi 51554.
MGIi MGI:2181676. Ackr4.

Phylogenomic databases

eggNOGi NOG148788.
GeneTreei ENSGT00760000118785.
HOGENOMi HOG000234122.
HOVERGENi HBG106917.
InParanoidi Q924I3.
KOi K04186.
OMAi LEICIGF.
OrthoDBi EOG7GJ6DG.
PhylomeDBi Q924I3.
TreeFami TF330966.

Enzyme and pathway databases

Reactomei REACT_230248. Chemokine receptors bind chemokines.

Miscellaneous databases

NextBioi 387341.
PROi Q924I3.
SOURCEi Search...

Gene expression databases

Bgeei Q924I3.
CleanExi MM_CCRL1.
Genevestigatori Q924I3.

Family and domain databases

Gene3Di 1.20.1070.10. 1 hit.
InterProi IPR005383. Chemokine_CCRL1.
IPR000355. Chemokine_rcpt.
IPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
[Graphical view ]
PANTHERi PTHR24227. PTHR24227. 1 hit.
PTHR24227:SF35. PTHR24227:SF35. 1 hit.
Pfami PF00001. 7tm_1. 1 hit.
[Graphical view ]
PRINTSi PR00657. CCCHEMOKINER.
PR01558. CHEMOKINER11.
PR00237. GPCRRHODOPSN.
PROSITEi PS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  1. "Astrocytes express functional chemokine receptors."
    Dorf M.E., Berman M.A., Tanabe S., Heesen M., Luo Y.
    J. Neuroimmunol. 111:109-121(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY.
    Strain: BALB/c.
  2. "Characterization of mouse CCX-CKR, a receptor for the lymphocyte-attracting chemokines TECK/mCCL25, SLC/mCCL21 and MIP-3beta/mCCL19: comparison to human CCX-CKR."
    Townson J.R., Nibbs R.J.
    Eur. J. Immunol. 32:1230-1241(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION IN CHEMOKINES BINDING, TISSUE SPECIFICITY.
  3. "RANTES and eotaxin stimulate chemotaxis, chemokine/cytokine synthesis, and receptor modulation in murine astrocytes."
    Luo Y., Berman M.A., Fischer F.R., Abromson-Leeman S.R., Kuziel W.A., Gerard C., Dorf M.E.
    Submitted (SEP-2000) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Strain: BALB/c.
  4. "The transcriptional landscape of the mammalian genome."
    Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.
    , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
    Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Strain: C57BL/6J.
    Tissue: Head and Thymus.
  5. "CCX-CKR deficiency alters thymic stroma impairing thymocyte development and promoting autoimmunity."
    Bunting M.D., Comerford I., Seach N., Hammett M.V., Asquith D.L., Koerner H., Boyd R.L., Nibbs R.J., McColl S.R.
    Blood 121:118-128(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, DISRUPTION PHENOTYPE, TISSUE SPECIFICITY.

Entry informationi

Entry nameiACKR4_MOUSE
AccessioniPrimary (citable) accession number: Q924I3
Secondary accession number(s): Q8C0M1, Q8QZW9
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 5, 2005
Last sequence update: December 1, 2001
Last modified: November 26, 2014
This is version 99 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. 7-transmembrane G-linked receptors
    List of 7-transmembrane G-linked receptor entries
  2. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  3. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3