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P40224

- SDF1_MOUSE

UniProt

P40224 - SDF1_MOUSE

Protein

Stromal cell-derived factor 1

Gene

Cxcl12

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at transcript leveli
  1. 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.By similarity
    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.

    Sites

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

    GO - Molecular functioni

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

    GO - Biological processi

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

    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

    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 – 2121Sequence AnalysisAdd
    BLAST
    Chaini22 – 9372Stromal cell-derived factor 1PRO_0000005112Add
    BLAST

    Amino acid modifications

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

    Protein-protein interaction databases

    STRINGi10090.ENSMUSP00000072800.

    Structurei

    3D structure databases

    ProteinModelPortaliP40224.
    SMRiP40224. Positions 26-87.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Region

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

    Motif

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Motifi22 – 232Receptor activation motifBy 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. 6 PublicationsVSP_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

    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: October 1, 2014
    This is version 129 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