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Protein

Stromal cell-derived factor 1

Gene

Cxcl12

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -Experimental evidence at transcript leveli

Functioni

Chemoattractant active on T-lymphocytes and monocytes but not neutrophils. Activates the C-X-C chemokine receptor CXCR4 to induce a rapid and transient rise in the level of intracellular calcium ions and chemotaxis. Also binds to atypical chemokine receptor ACKR3, which activates the beta-arrestin pathway and acts as a scavenger receptor for SDF-1. Binds to the allosteric site (site 2) of integrins and activates integrins ITGAV:ITGB3, ITGA4:ITGB1 and ITGA5:ITGB1 in a CXCR4-independent manner (By similarity). Acts as a positive regulator of monocyte migration and a negative regulator of monocyte adhesion via the LYN kinase. Stimulates migration of monocytes and T-lymphocytes through its receptors, CXCR4 and ACKR3, and decreases monocyte adherence to surfaces coated with ICAM-1, a ligand for beta-2 integrins. SDF1A/CXCR4 signaling axis inhibits beta-2 integrin LFA-1 mediated adhesion of monocytes to ICAM-1 through LYN kinase. Plays a protective role after myocardial infarction. Induces down-regulation and internalization of ACKR3 expressed in various cells (By similarity). Has several critical functions during embryonic development; required for B-cell lymphopoiesis, myelopoiesis in bone marrow and heart ventricular septum formation. Stimulates the proliferation of bone marrow-derived B-cell progenitors in the presence of IL7 as well as growth of stromal cell-dependent pre-B-cells (PubMed:8134392).By similarity2 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei45Important for integrin interaction and activationBy similarity1
Sitei46Important for dimer formationBy similarity1
Sitei48Important for integrin interaction and activationBy similarity1
Binding sitei62HeparinBy similarity1
Sitei64Important for integrin interaction and activationBy similarity1
Binding sitei69HeparinBy similarity1
Binding sitei85HeparinBy similarity1

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionCytokine, Growth factor
Biological processChemotaxis

Enzyme and pathway databases

ReactomeiR-MMU-376176 Signaling by ROBO receptors
R-MMU-380108 Chemokine receptors bind chemokines
R-MMU-418594 G alpha (i) signalling events

Names & Taxonomyi

Protein namesi
Recommended name:
Stromal cell-derived factor 1
Short name:
SDF-1
Alternative name(s):
12-O-tetradecanoylphorbol 13-acetate repressed protein 1
Short name:
TPAR1
C-X-C motif chemokine 12
Pre-B cell growth-stimulating factor
Short name:
PBSF
Thymic lymphoma cell-stimulating factor
Short name:
TLSF
Gene namesi
Name:Cxcl12
Synonyms:Sdf1
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 6

Organism-specific databases

MGIiMGI:103556 Cxcl12

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

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Disruption phenotypei

Half of the embryos die by E18.5 and neonates die within an hour. Mutants display defective B-lymphopoiesis, defective myelopoiesis in the bone marrow but not in the liver, and defective formation of the heart ventricular septum.1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 21Sequence analysisAdd BLAST21
ChainiPRO_000000511222 – 93Stromal cell-derived factor 1Add BLAST72

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi30 ↔ 55By similarity
Disulfide bondi32 ↔ 71By similarity

Keywords - PTMi

Disulfide bond

Proteomic databases

PaxDbiP40224
PRIDEiP40224

PTM databases

iPTMnetiP40224
PhosphoSitePlusiP40224

Expressioni

Tissue specificityi

Highest expression levels detected in kidney, liver, spleen and muscle. Isoform Alpha is expressed ubiquitously but at varying levels, while isoform Beta displays tissue-specific expression, with expression detected in kidney, liver, heart, spleen and muscle but not in lung, colon, brain, skin and stomach.1 Publication

Inductioni

Down-regulated by 12-O-tetradecanoylphorbol 13-acetate (TPA), with 5-fold decrease in expression levels at 1 hour after TPA treatment, 12-fold decrease at 4 hours, undetectable levels after 8 hours and low-level expression returning at 24 hours after treatment. Down-regulated by serum stimulation, with expression levels reaching their minimum at 4 hours after stimulation and returning back to normal levels at 16 hours after stimulation.1 Publication

Gene expression databases

BgeeiENSMUSG00000061353
CleanExiMM_CXCL12
ExpressionAtlasiP40224 baseline and differential
GenevisibleiP40224 MM

Interactioni

Subunit structurei

Monomer or homodimer; in equilibrium. Dimer formation is induced by non acidic pH and the presence of multivalent anions, and by binding to CXCR4 or heparin. Monomeric form is required for full chemotactic activity and resistance to ischemia/reperfusion injury, whereas the dimeric form acts as a partial agonist of CXCR4, stimulating Ca2+ mobilization but with no chemotactic activity and instead acts as a selective antagonist that blocks chemotaxis induced by the monomeric form. Interacts with the N-terminus of ACKR3. Interacts with integrin subunit ITGB3 (via the allosteric site (site 2)).By similarity

GO - Molecular functioni

Protein-protein interaction databases

DIPiDIP-61153N
IntActiP40224, 3 interactors
STRINGi10090.ENSMUSP00000072800

Structurei

3D structure databases

ProteinModelPortaliP40224
SMRiP40224
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni29 – 33Receptor and heparin bindingBy similarity5
Regioni39 – 41Receptor bindingBy similarity3
Regioni41 – 51Heparin bindingBy similarityAdd BLAST11
Regioni48 – 50Receptor bindingBy similarity3
Regioni60 – 70Receptor bindingBy similarityAdd BLAST11

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi22 – 23Receptor activation motifBy similarity2

Sequence similaritiesi

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiENOG410J1S5 Eukaryota
ENOG4112BS6 LUCA
GeneTreeiENSGT00390000014056
HOGENOMiHOG000220915
HOVERGENiHBG107437
InParanoidiP40224
KOiK10031
PhylomeDBiP40224

Family and domain databases

CDDicd00273 Chemokine_CXC, 1 hit
InterProiView protein in InterPro
IPR001811 Chemokine_IL8-like_dom
IPR033899 CXC_Chemokine_domain
IPR036048 Interleukin_8-like_sf
PfamiView protein in Pfam
PF00048 IL8, 1 hit
SMARTiView protein in SMART
SM00199 SCY, 1 hit
SUPFAMiSSF54117 SSF54117, 1 hit

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform Beta (identifier: P40224-2) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MDAKVVAVLA LVLAALCISD GKPVSLSYRC PCRFFESHIA RANVKHLKIL
60 70 80 90
NTPNCALQIV ARLKNNNRQV CIDPKLKWIQ EYLEKALNKR LKM
Length:93
Mass (Da):10,561
Last modified:July 7, 2009 - v2
Checksum:i625367D344B8AD69
GO
Isoform Alpha (identifier: P40224-1) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     90-93: Missing.

Show »
Length:89
Mass (Da):10,032
Checksum:iC4B8AD69078E55FA
GO

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_03760790 – 93Missing in isoform Alpha. 6 Publications4

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L12029 mRNA Translation: AAA40100.1
L12030 mRNA Translation: AAA40101.1
S74318 mRNA Translation: AAB32650.1
D21072 mRNA Translation: BAA04648.1
D43804 mRNA Translation: BAA07862.1
D43805 mRNA Translation: BAA07863.1
AK045092 mRNA Translation: BAC32216.1
AK075596 mRNA Translation: BAC35845.1
AK157553 mRNA Translation: BAE34120.1
CT010389 mRNA Translation: CAJ18596.1
CH466523 Genomic DNA Translation: EDK99572.1
BC006640 mRNA Translation: AAH06640.1
CCDSiCCDS39605.1 [P40224-2]
CCDS39606.1 [P40224-1]
PIRiA53497
I81182
RefSeqiNP_038683.1, NM_013655.4 [P40224-2]
NP_068350.1, NM_021704.3 [P40224-1]
UniGeneiMm.303231

Genome annotation databases

EnsembliENSMUST00000112866; ENSMUSP00000108487; ENSMUSG00000061353 [P40224-1]
ENSMUST00000112871; ENSMUSP00000108492; ENSMUSG00000061353 [P40224-2]
GeneIDi20315
KEGGimmu:20315
UCSCiuc009dks.2 mouse [P40224-2]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiSDF1_MOUSE
AccessioniPrimary (citable) accession number: P40224
Secondary accession number(s): Q4FJL5, Q543V6
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 1, 1995
Last sequence update: July 7, 2009
Last modified: June 20, 2018
This is version 159 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

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