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P40224 (SDF1_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 124. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:Cxcl12
Synonyms:Sdf1
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length93 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at transcript level

General annotation (Comments)

Function

Chemoattractant active on T-lymphocytes, 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. 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. Ref.3 Ref.9

Stimulates the proliferation of bone marrow-derived b progenitor cells in the presence of IL-7 as well as growth of the stromal cell-dependent B-cell clone DW34 cells. Ref.3 Ref.9

Subunit structure

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 By similarity.

Subcellular location

Secreted.

Tissue specificity

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. Ref.2

Induction

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. Ref.2

Disruption phenotype

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. Ref.9

Sequence similarities

Belongs to the intercrine alpha (chemokine CxC) family.

Ontologies

Keywords
   Biological processChemotaxis
   Cellular componentSecreted
   Coding sequence diversityAlternative splicing
   DomainSignal
   Molecular functionCytokine
Growth factor
   PTMDisulfide bond
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processT cell proliferation

Inferred from mutant phenotype PubMed 12707343. Source: MGI

ameboidal cell migration

Inferred from mutant phenotype PubMed 15626744. Source: MGI

brain development

Inferred from direct assay PubMed 12183377. Source: MGI

cell chemotaxis

Inferred from direct assay PubMed 12183377. Source: GOC

germ cell development

Inferred from direct assay PubMed 12900445. Source: MGI

germ cell migration

Inferred from direct assay PubMed 12900445. Source: MGI

immune response

Inferred from electronic annotation. Source: InterPro

induction of positive chemotaxis

Inferred from direct assay PubMed 12900445. Source: MGI

motor neuron axon guidance

Inferred from mutant phenotype PubMed 16129397. Source: MGI

patterning of blood vessels

Inferred from mutant phenotype PubMed 15626744. Source: MGI

positive regulation of cell migration

Inferred from direct assay PubMed 12900445. Source: MGI

regulation of cell migration

Inferred from direct assay PubMed 12183377. Source: MGI

   Cellular_componentexternal side of plasma membrane

Inferred from direct assay PubMed 19008373. Source: MGI

extracellular space

Inferred from electronic annotation. Source: UniProtKB-KW

   Molecular_functionchemokine activity

Inferred from direct assay PubMed 12183377. Source: MGI

chemokine receptor binding

Inferred from sequence or structural similarity. Source: UniProtKB

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform Beta (identifier: P40224-2)

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.
Isoform Alpha (identifier: P40224-1)

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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2121 Potential
Chain22 – 9372Stromal cell-derived factor 1
PRO_0000005112

Regions

Region29 – 335Receptor and heparin binding By similarity
Region39 – 413Receptor binding By similarity
Region41 – 5111Heparin binding By similarity
Region48 – 503Receptor binding By similarity
Region60 – 7011Receptor binding By similarity
Motif22 – 232Receptor activation motif By similarity

Sites

Binding site621Heparin By similarity
Binding site691Heparin By similarity
Binding site851Heparin By similarity
Site461Important for dimer formation By similarity

Amino acid modifications

Disulfide bond30 ↔ 55 By similarity
Disulfide bond32 ↔ 71 By similarity

Natural variations

Alternative sequence90 – 934Missing in isoform Alpha.
VSP_037607

Sequences

Sequence LengthMass (Da)Tools
Isoform Beta [UniParc].

Last modified July 7, 2009. Version 2.
Checksum: 625367D344B8AD69

FASTA9310,561
        10         20         30         40         50         60 
MDAKVVAVLA LVLAALCISD GKPVSLSYRC PCRFFESHIA RANVKHLKIL NTPNCALQIV 

        70         80         90 
ARLKNNNRQV CIDPKLKWIQ EYLEKALNKR LKM 

« Hide

Isoform Alpha [UniParc].

Checksum: C4B8AD69078E55FA
Show »

FASTA8910,032

References

« Hide 'large scale' references
[1]"Signal sequence trap: a cloning strategy for secreted proteins and type I membrane proteins."
Tashiro K., Tada H., Heilker R., Shirozu M., Nakano T., Honjo T.
Science 261:600-603(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS ALPHA AND BETA).
[2]"Molecular cloning of TPAR1, a gene whose expression is repressed by the tumor promoter 12-O-tetradecanoylphorbol 13-acetate (TPA)."
Jiang W., Zhou P., Kahn S.M., Tomita N., Johnson M.D., Weinstein I.B.
Exp. Cell Res. 215:284-293(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM ALPHA), ALTERNATIVE SPLICING, TISSUE SPECIFICITY, INDUCTION.
[3]"Molecular cloning and structure of a pre-B-cell growth-stimulating factor."
Nagasawa T., Kikutani H., Kishimoto T.
Proc. Natl. Acad. Sci. U.S.A. 91:2305-2309(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM ALPHA), FUNCTION.
[4]Nomura M., Nakata Y., Uzawa A., Nose M., Akashi M., Suzuki G.
Submitted (DEC-1994) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS ALPHA AND BETA).
Strain: AKR/J.
[5]"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. expand/collapse author list , 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] (ISOFORMS ALPHA AND BETA).
Strain: C57BL/6J and NOD.
Tissue: Embryo, Kidney and Spleen.
[6]"Cloning of mouse full open reading frames in Gateway(R) system entry vector (pDONR201)."
Ebert L., Muenstermann E., Schatten R., Henze S., Bohn E., Mollenhauer J., Wiemann S., Schick M., Korn B.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM BETA).
[7]Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM ALPHA).
Strain: C57BL/6J.
Tissue: Mammary gland.
[9]"Defects of B-cell lymphopoiesis and bone-marrow myelopoiesis in mice lacking the CXC chemokine PBSF/SDF-1."
Nagasawa T., Hirota S., Tachibana K., Takakura N., Nishikawa S., Kitamura Y., Yoshida N., Kikutani H., Kishimoto T.
Nature 382:635-638(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, DISRUPTION PHENOTYPE.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
PIRA53497.
I81182.
RefSeqNP_038683.1. NM_013655.4.
NP_068350.1. NM_021704.3.
UniGeneMm.303231.

3D structure databases

ProteinModelPortalP40224.
SMRP40224. Positions 26-87.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

STRING10090.ENSMUSP00000072800.

PTM databases

PhosphoSiteP40224.

Proteomic databases

PRIDEP40224.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000112866; ENSMUSP00000108487; ENSMUSG00000061353. [P40224-1]
ENSMUST00000112871; ENSMUSP00000108492; ENSMUSG00000061353. [P40224-2]
GeneID20315.
KEGGmmu:20315.
UCSCuc009dks.2. mouse. [P40224-2]

Organism-specific databases

CTD6387.
MGIMGI:103556. Cxcl12.

Phylogenomic databases

eggNOGNOG26489.
GeneTreeENSGT00390000014056.
HOGENOMHOG000220915.
HOVERGENHBG107437.
InParanoidP40224.
KOK10031.
OrthoDBEOG7C5MBS.
PhylomeDBP40224.

Gene expression databases

ArrayExpressP40224.
BgeeP40224.
CleanExMM_CXCL12.
GenevestigatorP40224.

Family and domain databases

InterProIPR001811. Chemokine_IL8-like_dom.
[Graphical view]
PfamPF00048. IL8. 1 hit.
[Graphical view]
SMARTSM00199. SCY. 1 hit.
[Graphical view]
SUPFAMSSF54117. SSF54117. 1 hit.
ProtoNetSearch...

Other

ChiTaRSCXCL12. mouse.
NextBio298091.
PROP40224.
SOURCESearch...

Entry information

Entry nameSDF1_MOUSE
AccessionPrimary (citable) accession number: P40224
Secondary accession number(s): Q4FJL5, Q543V6
Entry history
Integrated into UniProtKB/Swiss-Prot: February 1, 1995
Last sequence update: July 7, 2009
Last modified: April 16, 2014
This is version 124 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot