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 27-MAR-2024, entry version 129.
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; Mammalia;
OC Eutheria; Laurasiatheria; Carnivora; Feliformia; Felidae; 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., Cai J.S.,
RA Sato E., Kohmoto M., Mikami T.;
RT "Molecular cloning and sequencing of feline stromal cell-derived factor-1
RT alpha and beta.";
RL Eur. J. Immunogenet. 25:303-305(1998).
CC -!- FUNCTION: Chemoattractant active on T-lymphocytes and monocytes but not
CC neutrophils. Activates the C-X-C chemokine receptor CXCR4 to induce a
CC rapid and transient rise in the level of intracellular calcium ions and
CC chemotaxis. Also binds to atypical chemokine receptor ACKR3, which
CC activates the beta-arrestin pathway and acts as a scavenger receptor
CC for SDF-1. Acts as a positive regulator of monocyte migration and a
CC negative regulator of monocyte adhesion via the LYN kinase. Binds to
CC the allosteric site (site 2) of integrins and activates integrins
CC ITGAV:ITGB3, ITGA4:ITGB1 and ITGA5:ITGB1 in a CXCR4-independent manner.
CC Stimulates migration of monocytes and T-lymphocytes through its
CC receptors, CXCR4 and ACKR3, and decreases monocyte adherence to
CC surfaces coated with ICAM-1, a ligand for beta-2 integrins. SDF1A/CXCR4
CC signaling axis inhibits beta-2 integrin LFA-1 mediated adhesion of
CC monocytes to ICAM-1 through LYN kinase. Plays a protective role after
CC myocardial infarction. Has several critical functions during embryonic
CC development; required for B-cell lymphopoiesis, myelopoiesis in bone
CC marrow and heart ventricular septum formation. Stimulates the
CC proliferation of bone marrow-derived B-cell progenitors in the presence
CC of IL7 as well as growth of stromal cell-dependent pre-B-cells.
CC {ECO:0000250|UniProtKB:P40224, 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, and by
CC binding to CXCR4 or heparin. Monomeric form is required for full
CC chemotactic activity and resistance to ischemia/reperfusion injury,
CC whereas the dimeric form acts as a partial agonist of CXCR4,
CC stimulating Ca2+ mobilization but with no chemotactic activity and
CC instead acts as a selective antagonist that blocks chemotaxis induced
CC by the monomeric form. Interacts with the N-terminus of ACKR3.
CC Interacts with integrin subunit ITGB3 (via the allosteric site (site
CC 2)). Interacts with TNFAIP6 (via Link domain).
CC {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) family.
CC {ECO:0000305}.
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DR EMBL; AB011965; BAA28601.1; -; mRNA.
DR EMBL; AB011966; BAA28602.1; -; mRNA.
DR RefSeq; NP_001009847.1; NM_001009847.1. [O62657-1]
DR AlphaFoldDB; O62657; -.
DR BMRB; O62657; -.
DR SMR; O62657; -.
DR STRING; 9685.ENSFCAP00000060431; -.
DR PaxDb; 9685-ENSFCAP00000007102; -.
DR Ensembl; ENSFCAT00000058624.1; ENSFCAP00000044453.1; ENSFCAG00000036777.3. [O62657-1]
DR GeneID; 493806; -.
DR KEGG; fca:493806; -.
DR eggNOG; ENOG502S54U; Eukaryota.
DR GeneTree; ENSGT00390000014056; -.
DR HOGENOM; CLU_154284_2_0_1; -.
DR InParanoid; O62657; -.
DR OrthoDB; 5350863at2759; -.
DR Proteomes; UP000011712; Chromosome D2.
DR Bgee; ENSFCAG00000036777; Expressed in spleen and 9 other cell types or tissues.
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:0008009; F:chemokine activity; IEA:InterPro.
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:0060326; P:cell chemotaxis; 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 CDD; cd00273; Chemokine_CXC; 1.
DR Gene3D; 2.40.50.40; -; 1.
DR InterPro; IPR039809; Chemokine_b/g/d.
DR InterPro; IPR001811; Chemokine_IL8-like_dom.
DR InterPro; IPR033899; CXC_Chemokine_domain.
DR InterPro; IPR036048; Interleukin_8-like_sf.
DR PANTHER; PTHR12015; SMALL INDUCIBLE CYTOKINE A; 1.
DR PANTHER; PTHR12015:SF206; STROMAL CELL-DERIVED FACTOR 1; 1.
DR Pfam; PF00048; IL8; 1.
DR PRINTS; PR00436; INTERLEUKIN8.
DR SMART; SM00199; SCY; 1.
DR SUPFAM; SSF54117; Interleukin 8-like chemokines; 1.
PE 3: Inferred from homology;
KW Alternative splicing; Chemotaxis; Cytokine; Disulfide bond; Growth factor;
KW Reference proteome; Secreted; Signal.
FT SIGNAL 1..21
FT /evidence="ECO:0000255"
FT CHAIN 22..93
FT /note="Stromal cell-derived factor 1"
FT /id="PRO_0000005108"
FT REGION 29..33
FT /note="Receptor and heparin binding"
FT /evidence="ECO:0000250"
FT REGION 39..41
FT /note="Receptor binding"
FT /evidence="ECO:0000250"
FT REGION 48..50
FT /note="Receptor binding"
FT /evidence="ECO:0000250"
FT REGION 60..70
FT /note="Receptor binding"
FT /evidence="ECO:0000250"
FT MOTIF 22..23
FT /note="Receptor activation motif"
FT /evidence="ECO:0000250"
FT BINDING 41..51
FT /ligand="heparin"
FT /ligand_id="ChEBI:CHEBI:28304"
FT /evidence="ECO:0000250"
FT BINDING 62
FT /ligand="heparin"
FT /ligand_id="ChEBI:CHEBI:28304"
FT /evidence="ECO:0000250"
FT BINDING 69
FT /ligand="heparin"
FT /ligand_id="ChEBI:CHEBI:28304"
FT /evidence="ECO:0000250"
FT BINDING 85
FT /ligand="heparin"
FT /ligand_id="ChEBI:CHEBI:28304"
FT /evidence="ECO:0000250"
FT SITE 45
FT /note="Important for integrin interaction and activation"
FT /evidence="ECO:0000250|UniProtKB:P48061"
FT SITE 46
FT /note="Important for dimer formation"
FT /evidence="ECO:0000250"
FT SITE 48
FT /note="Important for integrin interaction and activation"
FT /evidence="ECO:0000250|UniProtKB:P48061"
FT SITE 64
FT /note="Important for integrin interaction and activation"
FT /evidence="ECO:0000250|UniProtKB:P48061"
FT DISULFID 30..55
FT /evidence="ECO:0000250"
FT DISULFID 32..71
FT /evidence="ECO:0000250"
FT VAR_SEQ 90..93
FT /note="Missing (in isoform Alpha)"
FT /evidence="ECO:0000303|PubMed:9777331"
FT /id="VSP_001055"
SQ SEQUENCE 93 AA; 10581 MW; 44FC763711E9BE37 CRC64;
MDAKVVAVLA LVLAALCLSD GKPVSLSYRC PCRFFESHVA RANVKHLKIL NTPNCALQIV
ARLKNNNRQV CIDPKLKWIQ EYLEKALNKR FKM
//
