ID SDF1_FELCA Reviewed; 93 AA. AC O62657; Q54AJ3; DT 15-DEC-1998, integrated into UniProtKB/Swiss-Prot. DT 01-AUG-1998, sequence version 1. DT 12-SEP-2018, entry version 107. DE RecName: Full=Stromal cell-derived factor 1; DE Short=SDF-1; DE AltName: Full=C-X-C motif chemokine 12; DE Flags: Precursor; GN Name=CXCL12; Synonyms=SDF1; OS Felis catus (Cat) (Felis silvestris catus). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Laurasiatheria; Carnivora; Feliformia; Felidae; OC Felinae; Felis. OX NCBI_TaxID=9685; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS ALPHA AND BETA). RC TISSUE=Thymus; RX PubMed=9777331; DOI=10.1046/j.1365-2370.1998.00107.x; RA Nishimura Y., Miyazawa T., Ikeda Y., Izumiya Y., Nakamura K., RA Cai J.S., Sato E., Kohmoto M., Mikami T.; RT "Molecular cloning and sequencing of feline stromal cell-derived RT factor-1 alpha and beta."; RL Eur. J. Immunogenet. 25:303-305(1998). CC -!- FUNCTION: Chemoattractant active on T-lymphocytes and monocytes CC but not neutrophils. Activates the C-X-C chemokine receptor CXCR4 CC to induce a rapid and transient rise in the level of intracellular CC calcium ions and chemotaxis. Also binds to atypical chemokine CC receptor ACKR3, which activates the beta-arrestin pathway and acts CC as a scavenger receptor for SDF-1. Acts as a positive regulator of CC monocyte migration and a negative regulator of monocyte adhesion CC via the LYN kinase. Binds to the allosteric site (site 2) of CC integrins and activates integrins ITGAV:ITGB3, ITGA4:ITGB1 and CC ITGA5:ITGB1 in a CXCR4-independent manner. Stimulates migration of CC monocytes and T-lymphocytes through its receptors, CXCR4 and CC ACKR3, and decreases monocyte adherence to surfaces coated with CC ICAM-1, a ligand for beta-2 integrins. SDF1A/CXCR4 signaling axis CC inhibits beta-2 integrin LFA-1 mediated adhesion of monocytes to CC ICAM-1 through LYN kinase. Plays a protective role after CC myocardial infarction. Has several critical functions during CC embryonic development; required for B-cell lymphopoiesis, CC myelopoiesis in bone marrow and heart ventricular septum CC formation. Stimulates the proliferation of bone marrow-derived B- CC cell progenitors in the presence of IL7 as well as growth of CC stromal cell-dependent pre-B-cells. {ECO:0000250|UniProtKB:P40224, CC ECO:0000250|UniProtKB:P48061}. CC -!- SUBUNIT: Monomer or homodimer; in equilibrium. Dimer formation is CC induced by non acidic pH and the presence of multivalent anions, CC and by binding to CXCR4 or heparin. Monomeric form is required for CC full chemotactic activity and resistance to ischemia/reperfusion CC injury, whereas the dimeric form acts as a partial agonist of CC CXCR4, stimulating Ca2+ mobilization but with no chemotactic CC activity and instead acts as a selective antagonist that blocks CC chemotaxis induced by the monomeric form. Interacts with the N- CC terminus of ACKR3. Interacts with integrin subunit ITGB3 (via the CC allosteric site (site 2)). {ECO:0000250|UniProtKB:P48061}. CC -!- SUBCELLULAR LOCATION: Secreted. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=Beta; Synonyms=SDF-1b; CC IsoId=O62657-1; Sequence=Displayed; CC Name=Alpha; Synonyms=SDF-1a; CC IsoId=O62657-2; Sequence=VSP_001055; CC -!- SIMILARITY: Belongs to the intercrine alpha (chemokine CxC) CC family. {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; AB011965; BAA28601.1; -; mRNA. DR EMBL; AB011966; BAA28602.1; -; mRNA. DR RefSeq; NP_001009847.1; NM_001009847.1. [O62657-1] DR ProteinModelPortal; O62657; -. DR SMR; O62657; -. DR STRING; 9685.ENSFCAP00000007102; -. DR GeneID; 493806; -. DR KEGG; fca:493806; -. DR CTD; 6387; -. DR eggNOG; ENOG410J1S5; Eukaryota. DR eggNOG; ENOG4112BS6; LUCA. DR HOVERGEN; HBG107437; -. DR InParanoid; O62657; -. DR KO; K10031; -. DR OMA; STPNCAL; -. DR OrthoDB; EOG091G14JB; -. DR Proteomes; UP000011712; Unplaced. DR Bgee; ENSFCAG00000007670; Expressed in 3 organ(s), highest expression level in liver. DR GO; GO:0009897; C:external side of plasma membrane; IBA:GO_Central. DR GO; GO:0005615; C:extracellular space; IEA:UniProtKB-KW. DR GO; GO:0042056; F:chemoattractant activity; IBA:GO_Central. DR GO; GO:0008009; F:chemokine activity; IBA:GO_Central. DR GO; GO:0042379; F:chemokine receptor binding; ISS:UniProtKB. DR GO; GO:0045236; F:CXCR chemokine receptor binding; IBA:GO_Central. DR GO; GO:0008083; F:growth factor activity; IEA:UniProtKB-KW. DR GO; GO:0005178; F:integrin binding; ISS:UniProtKB. DR GO; GO:0007411; P:axon guidance; IBA:GO_Central. DR GO; GO:0070098; P:chemokine-mediated signaling pathway; IBA:GO_Central. DR GO; GO:0006952; P:defense response; IEA:InterPro. DR GO; GO:0006955; P:immune response; IEA:InterPro. DR GO; GO:0050930; P:induction of positive chemotaxis; IBA:GO_Central. DR GO; GO:0033622; P:integrin activation; ISS:UniProtKB. DR GO; GO:0030335; P:positive regulation of cell migration; IBA:GO_Central. DR CDD; cd00273; Chemokine_CXC; 1. DR InterPro; IPR001811; Chemokine_IL8-like_dom. DR InterPro; IPR033899; CXC_Chemokine_domain. DR InterPro; IPR036048; Interleukin_8-like_sf. DR Pfam; PF00048; IL8; 1. DR SMART; SM00199; SCY; 1. DR SUPFAM; SSF54117; SSF54117; 1. PE 3: Inferred from homology; KW Alternative splicing; Chemotaxis; Complete proteome; Cytokine; KW Disulfide bond; Growth factor; Reference proteome; Secreted; Signal. FT SIGNAL 1 21 {ECO:0000255}. FT CHAIN 22 93 Stromal cell-derived factor 1. FT /FTId=PRO_0000005108. FT REGION 29 33 Receptor and heparin binding. FT {ECO:0000250}. FT REGION 39 41 Receptor binding. {ECO:0000250}. FT REGION 41 51 Heparin binding. {ECO:0000250}. FT REGION 48 50 Receptor binding. {ECO:0000250}. FT REGION 60 70 Receptor binding. {ECO:0000250}. FT MOTIF 22 23 Receptor activation motif. {ECO:0000250}. FT BINDING 62 62 Heparin. {ECO:0000250}. FT BINDING 69 69 Heparin. {ECO:0000250}. FT BINDING 85 85 Heparin. {ECO:0000250}. FT SITE 45 45 Important for integrin interaction and FT activation. FT {ECO:0000250|UniProtKB:P48061}. FT SITE 46 46 Important for dimer formation. FT {ECO:0000250}. FT SITE 48 48 Important for integrin interaction and FT activation. FT {ECO:0000250|UniProtKB:P48061}. FT SITE 64 64 Important for integrin interaction and FT activation. FT {ECO:0000250|UniProtKB:P48061}. FT DISULFID 30 55 {ECO:0000250}. FT DISULFID 32 71 {ECO:0000250}. FT VAR_SEQ 90 93 Missing (in isoform Alpha). FT {ECO:0000303|PubMed:9777331}. FT /FTId=VSP_001055. SQ SEQUENCE 93 AA; 10581 MW; 44FC763711E9BE37 CRC64; MDAKVVAVLA LVLAALCLSD GKPVSLSYRC PCRFFESHVA RANVKHLKIL NTPNCALQIV ARLKNNNRQV CIDPKLKWIQ EYLEKALNKR FKM //