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P40224

- SDF1_MOUSE

UniProt

P40224 - SDF1_MOUSE

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Protein
Stromal cell-derived factor 1
Gene
Cxcl12, Sdf1
Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5 - Experimental evidence at transcript leveli

Functioni

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.2 Publications
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.2 Publications

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei46 – 461Important for dimer formation By similarity
Binding sitei62 – 621Heparin By similarity
Binding sitei69 – 691Heparin By similarity
Binding sitei85 – 851Heparin By similarity

GO - Molecular functioni

  1. chemokine activity Source: MGI
  2. chemokine receptor binding Source: UniProtKB

GO - Biological processi

  1. T cell proliferation Source: MGI
  2. ameboidal cell migration Source: MGI
  3. brain development Source: MGI
  4. cell chemotaxis Source: GOC
  5. germ cell development Source: MGI
  6. germ cell migration Source: MGI
  7. immune response Source: InterPro
  8. induction of positive chemotaxis Source: MGI
  9. motor neuron axon guidance Source: MGI
  10. patterning of blood vessels Source: MGI
  11. positive regulation of T cell migration Source: MGI
  12. positive regulation of cell adhesion Source: MGI
  13. positive regulation of cell migration Source: MGI
  14. regulation of cell migration Source: MGI
Complete GO annotation...

Keywords - Molecular functioni

Cytokine, Growth factor

Keywords - Biological processi

Chemotaxis

Enzyme and pathway databases

ReactomeiREACT_198574. Nuclear signaling by ERBB4.

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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589: Chromosome 6

Organism-specific databases

MGIiMGI:103556. Cxcl12.

Subcellular locationi

GO - Cellular componenti

  1. external side of plasma membrane Source: MGI
  2. extracellular space Source: UniProtKB-KW
Complete GO annotation...

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)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2121 Reviewed prediction
Add
BLAST
Chaini22 – 9372Stromal cell-derived factor 1
PRO_0000005112Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi30 ↔ 55 By similarity
Disulfide bondi32 ↔ 71 By similarity

Keywords - PTMi

Disulfide bond

Proteomic databases

PRIDEiP40224.

PTM databases

PhosphoSiteiP40224.

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

ArrayExpressiP40224.
BgeeiP40224.
CleanExiMM_CXCL12.
GenevestigatoriP40224.

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 By similarity.

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000072800.

Structurei

3D structure databases

ProteinModelPortaliP40224.
SMRiP40224. Positions 26-87.

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni29 – 335Receptor and heparin binding By similarity
Regioni39 – 413Receptor binding By similarity
Regioni41 – 5111Heparin binding By similarity
Add
BLAST
Regioni48 – 503Receptor binding By similarity
Regioni60 – 7011Receptor binding By similarity
Add
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi22 – 232Receptor activation motif By similarity

Sequence similaritiesi

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiNOG26489.
GeneTreeiENSGT00390000014056.
HOGENOMiHOG000220915.
HOVERGENiHBG107437.
InParanoidiP40224.
KOiK10031.
OrthoDBiEOG7C5MBS.
PhylomeDBiP40224.

Family and domain databases

InterProiIPR001811. Chemokine_IL8-like_dom.
[Graphical view]
PfamiPF00048. IL8. 1 hit.
[Graphical view]
SMARTiSM00199. SCY. 1 hit.
[Graphical view]
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. Align

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

MDAKVVAVLA LVLAALCISD GKPVSLSYRC PCRFFESHIA RANVKHLKIL   50
NTPNCALQIV ARLKNNNRQV CIDPKLKWIQ EYLEKALNKR LKM 93
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)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei90 – 934Missing in isoform Alpha.
VSP_037607

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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 .
CCDSi CCDS39605.1. [P40224-2 ]
CCDS39606.1. [P40224-1 ]
PIRi A53497.
I81182.
RefSeqi NP_038683.1. NM_013655.4. [P40224-2 ]
NP_068350.1. NM_021704.3. [P40224-1 ]
UniGenei Mm.303231.

3D structure databases

ProteinModelPortali P40224.
SMRi P40224. Positions 26-87.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

STRINGi 10090.ENSMUSP00000072800.

PTM databases

PhosphoSitei P40224.

Proteomic databases

PRIDEi P40224.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSMUST00000112866 ; ENSMUSP00000108487 ; ENSMUSG00000061353 . [P40224-1 ]
ENSMUST00000112871 ; ENSMUSP00000108492 ; ENSMUSG00000061353 . [P40224-2 ]
GeneIDi 20315.
KEGGi mmu:20315.
UCSCi uc009dks.2. mouse. [P40224-2 ]

Organism-specific databases

CTDi 6387.
MGIi MGI:103556. Cxcl12.

Phylogenomic databases

eggNOGi NOG26489.
GeneTreei ENSGT00390000014056.
HOGENOMi HOG000220915.
HOVERGENi HBG107437.
InParanoidi P40224.
KOi K10031.
OrthoDBi EOG7C5MBS.
PhylomeDBi P40224.

Enzyme and pathway databases

Reactomei REACT_198574. Nuclear signaling by ERBB4.

Miscellaneous databases

ChiTaRSi CXCL12. mouse.
NextBioi 298091.
PROi P40224.
SOURCEi Search...

Gene expression databases

ArrayExpressi P40224.
Bgeei P40224.
CleanExi MM_CXCL12.
Genevestigatori P40224.

Family and domain databases

InterProi IPR001811. Chemokine_IL8-like_dom.
[Graphical view ]
Pfami PF00048. IL8. 1 hit.
[Graphical view ]
SMARTi SM00199. SCY. 1 hit.
[Graphical view ]
SUPFAMi SSF54117. SSF54117. 1 hit.
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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.
    , 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.

Entry informationi

Entry nameiSDF1_MOUSE
AccessioniPrimary (citable) accession number: P40224
Secondary accession number(s): Q4FJL5, Q543V6
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 1, 1995
Last sequence update: July 7, 2009
Last modified: September 3, 2014
This is version 128 of the entry and version 2 of the sequence. [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

External Data

Dasty 3

Similar proteinsi