CXCR4_SHEEP
ID CXCR4_SHEEP Reviewed; 192 AA.
AC Q28553;
DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 106.
DE RecName: Full=C-X-C chemokine receptor type 4;
DE Short=CXC-R4;
DE Short=CXCR-4;
DE AltName: Full=Fusin;
DE AltName: Full=Leukocyte-derived seven transmembrane domain receptor;
DE Short=LESTR;
DE AltName: Full=Stromal cell-derived factor 1 receptor;
DE Short=SDF-1 receptor;
DE AltName: CD_antigen=CD184;
DE Flags: Fragment;
GN Name=CXCR4; Synonyms=LESTR;
OS Ovis aries (Sheep).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Caprinae; Ovis.
OX NCBI_TaxID=9940;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Hypothalamus;
RA Dyer C.J., Matteri R.L., Keisler D.H.;
RT "Development of an ovine Y3 cDNA and expression of the Y3 receptor mRNA in
RT the ovine hypothalamus and pituitary.";
RL Abstr. - Soc. Neurosci. 21:1890-1890(1995).
CC -!- FUNCTION: Receptor for the C-X-C chemokine CXCL12/SDF-1 that transduces
CC a signal by increasing intracellular calcium ion levels and enhancing
CC MAPK1/MAPK3 activation. Involved in the AKT signaling cascade (By
CC similarity). Plays a role in regulation of cell migration, e.g. during
CC wound healing. Acts as a receptor for extracellular ubiquitin; leading
CC to enhanced intracellular calcium ions and reduced cellular cAMP
CC levels. Binds bacterial lipopolysaccharide (LPS) et mediates LPS-
CC induced inflammatory response, including TNF secretion by monocytes (By
CC similarity). Involved in hematopoiesis and in cardiac ventricular
CC septum formation. Also plays an essential role in vascularization of
CC the gastrointestinal tract, probably by regulating vascular branching
CC and/or remodeling processes in endothelial cells. Involved in
CC cerebellar development. In the CNS, could mediate hippocampal-neuron
CC survival (By similarity). {ECO:0000250|UniProtKB:P61073,
CC ECO:0000250|UniProtKB:P70658}.
CC -!- SUBUNIT: Monomer. Can form homodimers. Interacts with CD164. Interacts
CC with ARRB2; the interaction is dependent on the C-terminal
CC phosphorylation of CXCR4 and allows activation of MAPK1 and MAPK3.
CC Interacts with ARR3; the interaction is dependent on the C-terminal
CC phosphorylation of CXCR4 and modulates calcium mobilization. Interacts
CC with RNF113A; the interaction, enhanced by CXCL12, promotes CXCR4
CC ubiquitination and subsequent degradation. Interacts (via the
CC cytoplasmic C-terminal) with ITCH (via the WW domains I and II); the
CC interaction, enhanced by CXCL12, promotes CXCR4 ubiquitination and
CC leads to its degradation. Interacts with extracellular ubiquitin.
CC Interacts with DBN1; this interaction is enhanced by antigenic
CC stimulation. Following LPS binding, may form a complex with GDF5,
CC HSP90AA1 and HSPA8. {ECO:0000250|UniProtKB:P61073}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:P61073};
CC Multi-pass membrane protein {ECO:0000250|UniProtKB:P61073}. Cell
CC junction {ECO:0000250}. Early endosome {ECO:0000250}. Late endosome
CC {ECO:0000250}. Lysosome {ECO:0000250}. Note=In unstimulated cells,
CC diffuse pattern on plasma membrane. On agonist stimulation, colocalizes
CC with ITCH at the plasma membrane where it becomes ubiquitinated (By
CC similarity). In the presence of antigen, distributes to the
CC immunological synapse forming at the T-cell-APC contact area, where it
CC localizes at the peripheral and distal supramolecular activation
CC cluster (SMAC) (By similarity). {ECO:0000250}.
CC -!- PTM: Phosphorylated on agonist stimulation. Rapidly phosphorylated on
CC serine and threonine residues in the C-terminal.
CC {ECO:0000250|UniProtKB:P61073}.
CC -!- PTM: Ubiquitinated after ligand binding, leading to its degradation.
CC Ubiquitinated by ITCH at the cell membrane on agonist stimulation. The
CC ubiquitin-dependent mechanism, endosomal sorting complex required for
CC transport (ESCRT), then targets CXCR4 for lysosomal degradation. This
CC process is dependent also on prior Ser-/Thr-phosphorylation in the C-
CC terminal of CXCR4. Also binding of ARRB1 to STAM negatively regulates
CC CXCR4 sorting to lysosomes though modulating ubiquitination of SFR5S.
CC {ECO:0000250|UniProtKB:P61073}.
CC -!- PTM: Sulfation is required for efficient binding of CXCL12/SDF-1alpha
CC and promotes its dimerization. {ECO:0000250|UniProtKB:P61073}.
CC -!- PTM: O- and N-glycosylated. N-glycosylation can mask coreceptor
CC function. The O-glycosylation chondroitin sulfate attachment does not
CC affect interaction with CXCL12/SDF-1alpha nor its coreceptor activity.
CC {ECO:0000250|UniProtKB:P61073}.
CC -!- SIMILARITY: Belongs to the G-protein coupled receptor 1 family.
CC {ECO:0000255|PROSITE-ProRule:PRU00521}.
CC -!- CAUTION: Was originally (Ref.1) thought to be a receptor for
CC neuropeptide Y type 3 (NPY3R) (NPY3-R). {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; U38942; AAA81347.1; -; mRNA.
DR AlphaFoldDB; Q28553; -.
DR SMR; Q28553; -.
DR STRING; 9940.ENSOARP00000011227; -.
DR eggNOG; KOG3656; Eukaryota.
DR Proteomes; UP000002356; Unplaced.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-SubCell.
DR GO; GO:0005769; C:early endosome; ISS:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005770; C:late endosome; ISS:UniProtKB.
DR GO; GO:0005764; C:lysosome; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0038147; F:C-X-C motif chemokine 12 receptor activity; ISS:UniProtKB.
DR GO; GO:0019955; F:cytokine binding; IEA:InterPro.
DR GO; GO:0071345; P:cellular response to cytokine stimulus; ISS:UniProtKB.
DR GO; GO:0006935; P:chemotaxis; IEA:InterPro.
DR GO; GO:0038160; P:CXCL12-activated CXCR4 signaling pathway; ISS:UniProtKB.
DR InterPro; IPR022726; Chemokine_CXCR4_N_dom.
DR InterPro; IPR000355; Chemokine_rcpt.
DR InterPro; IPR001277; CXCR4/ACKR2.
DR InterPro; IPR000276; GPCR_Rhodpsn.
DR InterPro; IPR017452; GPCR_Rhodpsn_7TM.
DR Pfam; PF00001; 7tm_1; 1.
DR Pfam; PF12109; CXCR4_N; 1.
DR PRINTS; PR00657; CCCHEMOKINER.
DR PRINTS; PR00645; CXCCHMKINER4.
DR PRINTS; PR00237; GPCRRHODOPSN.
DR PROSITE; PS00237; G_PROTEIN_RECEP_F1_1; 1.
DR PROSITE; PS50262; G_PROTEIN_RECEP_F1_2; 1.
PE 2: Evidence at transcript level;
KW Cell junction; Cell membrane; Disulfide bond; Endosome;
KW G-protein coupled receptor; Glycoprotein; Lysosome; Membrane; Proteoglycan;
KW Receptor; Reference proteome; Sulfation; Transducer; Transmembrane;
KW Transmembrane helix; Ubl conjugation.
FT CHAIN <1..>192
FT /note="C-X-C chemokine receptor type 4"
FT /id="PRO_0000069359"
FT TOPO_DOM 1..28
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 29..53
FT /note="Helical; Name=1"
FT /evidence="ECO:0000250|UniProtKB:P61073"
FT TOPO_DOM 54..67
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 68..89
FT /note="Helical; Name=2"
FT /evidence="ECO:0000250|UniProtKB:P61073"
FT TOPO_DOM 90..100
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 101..120
FT /note="Helical; Name=3"
FT /evidence="ECO:0000250|UniProtKB:P61073"
FT TOPO_DOM 121..144
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 145..164
FT /note="Helical; Name=4"
FT /evidence="ECO:0000250|UniProtKB:P61073"
FT TOPO_DOM 165..185
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 186..>192
FT /note="Helical; Name=5"
FT /evidence="ECO:0000250|UniProtKB:P61073"
FT REGION 1..11
FT /note="Important for chemokine binding and signaling"
FT /evidence="ECO:0000250"
FT REGION 84..87
FT /note="Chemokine binding"
FT /evidence="ECO:0000250"
FT REGION 103..107
FT /note="Chemokine binding"
FT /evidence="ECO:0000250"
FT REGION 125..137
FT /note="Involved in dimerization; when bound to chemokine"
FT /evidence="ECO:0000250"
FT REGION 176..180
FT /note="Chemokine binding, important for signaling"
FT /evidence="ECO:0000250"
FT MOTIF 123..125
FT /note="Important for signaling"
FT /evidence="ECO:0000250"
FT SITE 161
FT /note="Chemokine binding"
FT /evidence="ECO:0000250"
FT MOD_RES 1
FT /note="Sulfotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P61073"
FT MOD_RES 11
FT /note="Sulfotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P61073"
FT CARBOHYD 8
FT /note="O-linked (Xyl...) (chondroitin sulfate) serine"
FT /evidence="ECO:0000250|UniProtKB:P61073"
FT DISULFID 99..176
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00521"
FT NON_TER 1
FT NON_TER 192
SQ SEQUENCE 192 AA; 22178 MW; A8BCFE303C52BD98 CRC64;
YTEDDLGSGD YDSMKEPCFR EENAHFNRIF LPTVYSIIFL TGIVGNGLVI LVMGYQKKLR
SMTDKYRLHL SVADLLFVLT LPFWAVDAVA NWYFGQFLCK AVHVIYTVNL YSSVLILAFI
SLDRYLAIVH ATNSQRPRKL LAEKVVYVGV WLPAVLLTIP DLIFADIKEA DERYICDRFY
PSDLWLVVFQ FQ
