SDF1_HUMAN
ID SDF1_HUMAN Reviewed; 93 AA.
AC P48061; B2R4G0; E7EVL0; H7BYN8; Q2L985; Q2L986; Q2L988; Q5IT36; Q6ICW0;
AC Q9H554;
DT 01-FEB-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1996, sequence version 1.
DT 03-AUG-2022, entry version 217.
DE RecName: Full=Stromal cell-derived factor 1;
DE Short=SDF-1;
DE Short=hSDF-1;
DE AltName: Full=C-X-C motif chemokine 12;
DE AltName: Full=Intercrine reduced in hepatomas;
DE Short=IRH;
DE Short=hIRH;
DE AltName: Full=Pre-B cell growth-stimulating factor;
DE Short=PBSF;
DE Contains:
DE RecName: Full=SDF-1-beta(3-72);
DE Contains:
DE RecName: Full=SDF-1-alpha(3-67);
DE Flags: Precursor;
GN Name=CXCL12; Synonyms=SDF1, SDF1A, SDF1B;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS ALPHA AND BETA).
RX PubMed=7490086; DOI=10.1006/geno.1995.1180;
RA Shirozu M., Nakano T., Inazawa J., Tashiro K., Tada H., Shinohara T.,
RA Honjo T.;
RT "Structure and chromosomal localization of the human stromal cell-derived
RT factor 1 (SDF1) gene.";
RL Genomics 28:495-500(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS GAMMA; DELTA; EPSILON AND THETA),
RP TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, AND ALTERNATIVE SPLICING.
RC TISSUE=Fetal brain, Fetal heart, and Heart;
RX PubMed=16626895; DOI=10.1016/j.gene.2006.02.001;
RA Yu L., Cecil J., Peng S.B., Schrementi J., Kovacevic S., Paul D., Su E.W.,
RA Wang J.;
RT "Identification and expression of novel isoforms of human stromal cell-
RT derived factor 1.";
RL Gene 374:174-179(2006).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM BETA).
RC TISSUE=Fibroblast;
RA Spotila L.D.;
RL Submitted (OCT-1994) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM ALPHA).
RC TISSUE=Liver;
RA Begum N.A., Barnard G.F.;
RT "Nucleotide sequence of hIRH, human intercrine reduced in hepatomas.";
RL Submitted (JAN-1995) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM GAMMA).
RA Callebaut C., Verdin E.;
RT "Inhibition of X4 and R5 HIV-1 by human SDF-1g, a novel chemokine that
RT interferes with HIV transcription.";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM ALPHA).
RA Zhao X., Zhang H., Lee S., Wong K., Zheng B.;
RT "Polymorphism study of cell-derived factor 1 (SDF1) gene and their
RT correlation with HIV infection in a Chinese cohort.";
RL Submitted (DEC-2004) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM ALPHA).
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (MAY-2004) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS ALPHA AND BETA).
RC TISSUE=Thymus, and Uterus;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 7).
RX PubMed=16344560; DOI=10.1101/gr.4039406;
RA Kimura K., Wakamatsu A., Suzuki Y., Ota T., Nishikawa T., Yamashita R.,
RA Yamamoto J., Sekine M., Tsuritani K., Wakaguri H., Ishii S., Sugiyama T.,
RA Saito K., Isono Y., Irie R., Kushida N., Yoneyama T., Otsuka R., Kanda K.,
RA Yokoi T., Kondo H., Wagatsuma M., Murakawa K., Ishida S., Ishibashi T.,
RA Takahashi-Fujii A., Tanase T., Nagai K., Kikuchi H., Nakai K., Isogai T.,
RA Sugano S.;
RT "Diversification of transcriptional modulation: large-scale identification
RT and characterization of putative alternative promoters of human genes.";
RL Genome Res. 16:55-65(2006).
RN [10]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RG SeattleSNPs variation discovery resource;
RL Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases.
RN [11]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164054; DOI=10.1038/nature02462;
RA Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L.,
RA Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K.,
RA Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L.,
RA Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P.,
RA Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N.,
RA Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A.,
RA Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C.,
RA Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D.,
RA Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C.,
RA Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K.,
RA Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A.,
RA Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S.,
RA McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S.,
RA Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V.,
RA Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A.,
RA Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M.,
RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A.,
RA Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P.,
RA Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y.,
RA Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D.,
RA Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 10.";
RL Nature 429:375-381(2004).
RN [12]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [13]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM ALPHA).
RC TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [14]
RP FUNCTION.
RX PubMed=8752281; DOI=10.1038/382833a0;
RA Oberlin E., Amara A., Bachelerie F., Bessia C., Virelizier J.-L.,
RA Arenzana-Seisdedos F., Schwartz O., Heard J.-M., Clark-Lewis I.,
RA Legler D.F., Loetscher M., Baggiolini M., Moser B.;
RT "The CXC chemokine SDF-1 is the ligand for LESTR/fusin and prevents
RT infection by T-cell-line-adapted HIV-1.";
RL Nature 382:833-835(1996).
RN [15]
RP INTERACTION WITH CXCR4.
RX PubMed=9427609; DOI=10.1038/nm0198-072;
RA Donzella G.A., Schols D., Lin S.W., Este J.A., Nagashima K.A., Maddon P.J.,
RA Allaway G.P., Sakmar T.P., Henson G., De Clercq E., Moore J.P.;
RT "AMD3100, a small molecule inhibitor of HIV-1 entry via the CXCR4 co-
RT receptor.";
RL Nat. Med. 4:72-77(1998).
RN [16]
RP INTERACTION WITH HEPARAN SULFATE, AND MUTAGENESIS OF 45-LYS--LYS-48.
RX PubMed=10446158; DOI=10.1074/jbc.274.34.23916;
RA Amara A., Lorthioir O., Valenzuela A., Magerus A., Thelen M., Montes M.,
RA Virelizier J.L., Delepierre M., Baleux F., Lortat-Jacob H.,
RA Arenzana-Seisdedos F.;
RT "Stromal cell-derived factor-1alpha associates with heparan sulfates
RT through the first beta-strand of the chemokine.";
RL J. Biol. Chem. 274:23916-23925(1999).
RN [17]
RP FUNCTION.
RX PubMed=11069075;
RX DOI=10.1002/1521-4141(200010)30:10<2924::aid-immu2924>3.0.co;2-y;
RA Moepps B., Braun M., Knoepfle K., Dillinger K., Knoechel W., Gierschik P.;
RT "Characterization of a Xenopus laevis CXC chemokine receptor 4:
RT implications for hematopoietic cell development in the vertebrate embryo.";
RL Eur. J. Immunol. 30:2924-2934(2000).
RN [18]
RP FUNCTION.
RX PubMed=11859124; DOI=10.4049/jimmunol.168.5.2340;
RA Braun M., Wunderlin M., Spieth K., Knoechel W., Gierschik P., Moepps B.;
RT "Xenopus laevis stromal cell-derived factor 1: conservation of structure
RT and function during vertebrate development.";
RL J. Immunol. 168:2340-2347(2002).
RN [19]
RP IDENTIFICATION OF SDF-1ALPHA(3-67) AND SDF-1BETA(3-72) BY MASS
RP SPECTROMETRY, AND PROTEOLYTIC PROCESSING OF N-TERMINUS AND C-TERMINUS.
RX PubMed=14525775; DOI=10.1182/blood-2003-08-2857;
RA De La Luz Sierra M., Yang F., Narazaki M., Salvucci O., Davis D.,
RA Yarchoan R., Zhang H.H., Fales H., Tosato G.;
RT "Differential processing of stromal-derived factor-1alpha and beta explains
RT functional diversity.";
RL Blood 103:2452-2459(2004).
RN [20]
RP FUNCTION, AND INTERACTION WITH ACKR3.
RX PubMed=16107333; DOI=10.1074/jbc.m508234200;
RA Balabanian K., Lagane B., Infantino S., Chow K.Y., Harriague J., Moepps B.,
RA Arenzana-Seisdedos F., Thelen M., Bachelerie F.;
RT "The chemokine SDF-1/CXCL12 binds to and signals through the orphan
RT receptor RDC1 in T lymphocytes.";
RL J. Biol. Chem. 280:35760-35766(2005).
RN [21]
RP DIMERIZATION, AND MUTAGENESIS OF HIS-46.
RX PubMed=15741341; DOI=10.1110/ps.041219505;
RA Veldkamp C.T., Peterson F.C., Pelzek A.J., Volkman B.F.;
RT "The monomer-dimer equilibrium of stromal cell-derived factor-1 (CXCL 12)
RT is altered by pH, phosphate, sulfate, and heparin.";
RL Protein Sci. 14:1071-1081(2005).
RN [22]
RP DIMERIZATION, AND INTERACTION WITH CXCR4.
RX PubMed=16725153; DOI=10.1016/j.jmb.2006.04.052;
RA Veldkamp C.T., Seibert C., Peterson F.C., Sakmar T.P., Volkman B.F.;
RT "Recognition of a CXCR4 sulfotyrosine by the chemokine stromal cell-derived
RT factor-1alpha (SDF-1alpha/CXCL12).";
RL J. Mol. Biol. 359:1400-1409(2006).
RN [23]
RP FUNCTION.
RX PubMed=18802065; DOI=10.4049/jimmunol.181.7.4632;
RA Malik M., Chen Y.-Y., Kienzle M.F., Tomkowicz B.E., Collman R.G.,
RA Ptasznik A.;
RT "Monocyte migration and LFA-1-mediated attachment to brain microvascular
RT endothelia is regulated by SDF-1 alpha through Lyn kinase.";
RL J. Immunol. 181:4632-4637(2008).
RN [24]
RP FUNCTION, AND INTERACTION WITH ACKR3.
RX PubMed=19255243; DOI=10.1124/mol.108.053389;
RA Kalatskaya I., Berchiche Y.A., Gravel S., Limberg B.J., Rosenbaum J.S.,
RA Heveker N.;
RT "AMD3100 is a CXCR7 ligand with allosteric agonist properties.";
RL Mol. Pharmacol. 75:1240-1247(2009).
RN [25]
RP INTERACTION WITH MOLLUSCUM CONTAGIOSUM VIRUS PROTEIN MC148 (MICROBIAL
RP INFECTION).
RX PubMed=21802105; DOI=10.1016/j.virol.2011.07.001;
RA Jin Q., Altenburg J.D., Hossain M.M., Alkhatib G.;
RT "Role for the conserved N-terminal cysteines in the anti-chemokine
RT activities by the chemokine-like protein MC148R1 encoded by Molluscum
RT contagiosum virus.";
RL Virology 417:449-456(2011).
RN [26]
RP RECEPTOR INTERACTION.
RX PubMed=22457824; DOI=10.1371/journal.pone.0034192;
RA Canals M., Scholten D.J., de Munnik S., Han M.K., Smit M.J., Leurs R.;
RT "Ubiquitination of CXCR7 controls receptor trafficking.";
RL PLoS ONE 7:E34192-E34192(2012).
RN [27]
RP INTERACTION WITH TNFAIP6, AND MUTAGENESIS OF LYS-45; HIS-46 AND LYS-48.
RX PubMed=27044744; DOI=10.1074/jbc.m116.720953;
RA Dyer D.P., Salanga C.L., Johns S.C., Valdambrini E., Fuster M.M.,
RA Milner C.M., Day A.J., Handel T.M.;
RT "The Anti-inflammatory Protein TSG-6 Regulates Chemokine Function by
RT Inhibiting Chemokine/Glycosaminoglycan Interactions.";
RL J. Biol. Chem. 291:12627-12640(2016).
RN [28]
RP FUNCTION, INTERACTION WITH ITGB3, SITES IMPORTANT FOR INTEGRIN BINDING, AND
RP MUTAGENESIS OF LYS-45; LYS-48 AND LYS-64.
RX PubMed=29301984; DOI=10.1042/bcj20170867;
RA Fujita M., Davari P., Takada Y.K., Takada Y.;
RT "Stromal cell-derived factor-1 (CXCL12) activates integrins by direct
RT binding to an allosteric ligand-binding site (site 2) of integrins without
RT CXCR4.";
RL Biochem. J. 475:723-732(2018).
RN [29]
RP STRUCTURE BY NMR OF 22-88, DISULFIDE BONDS, AND MUTAGENESIS OF LYS-22;
RP PRO-23; 22-LYS-PRO-23; 25-SER--SER-27; TYR-28 AND ARG-29.
RX PubMed=9384579; DOI=10.1093/emboj/16.23.6996;
RA Crump M.P., Gong J.H., Loetscher P., Rajarathnam K., Amara A.,
RA Arenzana-Seisdedos F., Virelizier J.-L., Baggiolini M., Sykes B.D.,
RA Clark-Lewis I.;
RT "Solution structure and basis for functional activity of stromal cell-
RT derived factor-1; dissociation of CXCR4 activation from binding and
RT inhibition of HIV-1.";
RL EMBO J. 16:6996-7007(1997).
RN [30]
RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 22-88 OF MUTANT ALA-54, AND
RP DISULFIDE BONDS.
RX PubMed=9618518; DOI=10.1073/pnas.95.12.6941;
RA Dealwis C., Fernandez E.J., Thompson D.A., Simon R.J., Siani M.A.,
RA Lolis E.;
RT "Crystal structure of chemically synthesized [N33A] stromal cell-derived
RT factor 1alpha, a potent ligand for the HIV-1 'fusin' coreceptor.";
RL Proc. Natl. Acad. Sci. U.S.A. 95:6941-6946(1998).
RN [31]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 22-88, DISULFIDE BONDS, AND
RP MUTAGENESIS OF ARG-33; PHE-34; PHE-35; GLU-36; SER-37; HIS-38 AND
RP 33-ARG--HIS-38.
RX PubMed=10954912; DOI=10.1089/10799900050116390;
RA Ohnishi Y., Senda T., Nandhagopal N., Sugimoto K., Shioda T., Nagal Y.,
RA Mitsui Y.;
RT "Crystal structure of recombinant native SDF-1alpha with additional
RT mutagenesis studies: an attempt at a more comprehensive interpretation of
RT accumulated structure-activity relationship data.";
RL J. Interferon Cytokine Res. 20:691-700(2000).
RN [32]
RP STRUCTURE BY NMR OF 22-89, AND DISULFIDE BONDS.
RX PubMed=15588815; DOI=10.1016/j.jmb.2004.11.003;
RA Gozansky E.K., Louis J.M., Caffrey M., Clore G.M.;
RT "Mapping the binding of the N-terminal extracellular tail of the CXCR4
RT receptor to stromal cell-derived factor-1alpha.";
RL J. Mol. Biol. 345:651-658(2005).
RN [33]
RP X-RAY CRYSTALLOGRAPHY (2.07 ANGSTROMS) OF 22-88 IN COMPLEX WITH HEPARIN
RP DISACCHARIDE I-S, DISULFIDE BONDS, AND MUTAGENESIS OF ARG-29; ARG-33;
RP 34-PHE-PHE-35; 36-GLU--HIS-38; HIS-46; LYS-48; 52-THR--ALA-56; ARG-62;
RP ARG-68 AND GLN-69.
RX PubMed=17264079; DOI=10.1074/jbc.m608796200;
RA Murphy J.W., Cho Y., Sachpatzidis A., Fan C., Hodsdon M.E., Lolis E.;
RT "Structural and functional basis of CXCL12 (stromal cell-derived factor-1
RT alpha) binding to heparin.";
RL J. Biol. Chem. 282:10018-10027(2007).
RN [34]
RP X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS) OF 22-89, DISULFIDE BONDS, AND
RP MUTAGENESIS OF LYS-22.
RX PubMed=17357154; DOI=10.1002/prot.21350;
RA Ryu E.K., Kim T.G., Kwon T.H., Jung I.D., Ryu D., Park Y.M., Kim J.,
RA Ahn K.H., Ban C.;
RT "Crystal structure of recombinant human stromal cell-derived factor-
RT 1alpha.";
RL Proteins 67:1193-1197(2007).
RN [35]
RP STRUCTURE BY NMR OF 22-89 OF MUTANT CYS-57 AND CYS-86 IN COMPLEX WITH CXCR4
RP FRAGMENT, SUBUNIT, DIMERIZATION, DISULFIDE BONDS, AND MUTAGENESIS OF
RP ARG-41; HIS-46; LYS-48; VAL-60; ARG-62; ARG-68; VAL-70; GLU-81; GLU-84 AND
RP LYS-85.
RX PubMed=18799424; DOI=10.1126/scisignal.1160755;
RA Veldkamp C.T., Seibert C., Peterson F.C., De la Cruz N.B.,
RA Haugner J.C. III, Basnet H., Sakmar T.P., Volkman B.F.;
RT "Structural basis of CXCR4 sulfotyrosine recognition by the chemokine SDF-
RT 1/CXCL12.";
RL Sci. Signal. 1:RA4-RA4(2008).
RN [36]
RP STRUCTURE BY NMR OF 22-89, ASSAY ON RAT ISCHEMIA/REPERFUSION MODEL,
RP DIMERIZATION, AND DISULFIDE BONDS.
RX PubMed=19551879; DOI=10.1002/pro.167;
RA Veldkamp C.T., Ziarek J.J., Su J., Basnet H., Lennertz R., Weiner J.J.,
RA Peterson F.C., Baker J.E., Volkman B.F.;
RT "Monomeric structure of the cardioprotective chemokine SDF-1/CXCL12.";
RL Protein Sci. 18:1359-1369(2009).
RN [37]
RP STRUCTURE BY NMR OF 22-89, AND DISULFIDE BONDS.
RA Ziarek J.J., Veldkamp C.T., Peterson F.C., Volkman B.F.;
RT "Solution structure of human SDF1-alpha H25R.";
RL Submitted (SEP-2009) to the PDB data bank.
RN [38]
RP X-RAY CRYSTALLOGRAPHY (1.60 ANGSTROMS) OF 22-88, AND DIMERIZATION.
RX PubMed=20077567; DOI=10.1002/prot.22666;
RA Murphy J.W., Yuan H., Kong Y., Xiong Y., Lolis E.J.;
RT "Heterologous quaternary structure of CXCL12 and its relationship to the CC
RT chemokine family.";
RL Proteins 78:1331-1337(2010).
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. SDF-1-beta(3-72) and SDF-1-alpha(3-67) show a reduced
CC chemotactic activity. Binding to cell surface proteoglycans seems to
CC inhibit formation of SDF-1-alpha(3-67) and thus to preserve activity on
CC local sites. Also binds to atypical chemokine receptor ACKR3, which
CC activates the beta-arrestin pathway and acts as a scavenger receptor
CC for SDF-1. Binds to the allosteric site (site 2) of integrins and
CC activates integrins ITGAV:ITGB3, ITGA4:ITGB1 and ITGA5:ITGB1 in a
CC CXCR4-independent manner (PubMed:29301984). Acts as a positive
CC regulator of monocyte migration and a negative regulator of monocyte
CC adhesion via the LYN kinase. Stimulates migration of monocytes and T-
CC lymphocytes through its receptors, CXCR4 and ACKR3, and decreases
CC monocyte adherence to surfaces coated with ICAM-1, a ligand for beta-2
CC integrins. SDF1A/CXCR4 signaling axis inhibits beta-2 integrin LFA-1
CC mediated adhesion of monocytes to ICAM-1 through LYN kinase. Inhibits
CC CXCR4-mediated infection by T-cell line-adapted HIV-1. Plays a
CC protective role after myocardial infarction. Induces down-regulation
CC and internalization of ACKR3 expressed in various cells. Has several
CC critical functions during embryonic development; required for B-cell
CC lymphopoiesis, myelopoiesis in bone marrow and heart ventricular septum
CC formation. Stimulates the proliferation of bone marrow-derived B-cell
CC progenitors in the presence of IL7 as well as growth of stromal cell-
CC dependent pre-B-cells (By similarity). {ECO:0000250|UniProtKB:P40224,
CC ECO:0000269|PubMed:11069075, ECO:0000269|PubMed:11859124,
CC ECO:0000269|PubMed:16107333, ECO:0000269|PubMed:18802065,
CC ECO:0000269|PubMed:19255243, ECO:0000269|PubMed:29301984,
CC ECO:0000269|PubMed:8752281}.
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)) (PubMed:29301984). Interacts with TNFAIP6 (via Link domain).
CC {ECO:0000269|PubMed:10446158, ECO:0000269|PubMed:16107333,
CC ECO:0000269|PubMed:16725153, ECO:0000269|PubMed:17264079,
CC ECO:0000269|PubMed:18799424, ECO:0000269|PubMed:19255243,
CC ECO:0000269|PubMed:27044744, ECO:0000269|PubMed:29301984,
CC ECO:0000269|PubMed:9427609}.
CC -!- SUBUNIT: (Microbial infection) Interacts with molluscum contagiosum
CC virus protein MC148. {ECO:0000269|PubMed:21802105}.
CC -!- INTERACTION:
CC P48061; P51671: CCL11; NbExp=2; IntAct=EBI-3913254, EBI-727357;
CC P48061; Q99616: CCL13; NbExp=2; IntAct=EBI-3913254, EBI-725342;
CC P48061; P78556: CCL20; NbExp=2; IntAct=EBI-3913254, EBI-3913209;
CC P48061; O00585: CCL21; NbExp=2; IntAct=EBI-3913254, EBI-953695;
CC P48061; O15444: CCL25; NbExp=2; IntAct=EBI-3913254, EBI-7783341;
CC P48061; Q9Y258: CCL26; NbExp=2; IntAct=EBI-3913254, EBI-7783416;
CC P48061; Q9NRJ3: CCL28; NbExp=2; IntAct=EBI-3913254, EBI-7783254;
CC P48061; P13501: CCL5; NbExp=5; IntAct=EBI-3913254, EBI-2848366;
CC P48061; PRO_0000005175 [P13501]: CCL5; NbExp=2; IntAct=EBI-3913254, EBI-11712923;
CC P48061; P02778: CXCL10; NbExp=2; IntAct=EBI-3913254, EBI-7815386;
CC P48061; O14625: CXCL11; NbExp=3; IntAct=EBI-3913254, EBI-2871971;
CC P48061; O95715: CXCL14; NbExp=2; IntAct=EBI-3913254, EBI-2798068;
CC P48061; Q6UXB2: CXCL17; NbExp=2; IntAct=EBI-3913254, EBI-16804198;
CC P48061; P19875: CXCL2; NbExp=2; IntAct=EBI-3913254, EBI-2114901;
CC P48061; P80162: CXCL6; NbExp=2; IntAct=EBI-3913254, EBI-9214033;
CC P48061; Q07325: CXCL9; NbExp=2; IntAct=EBI-3913254, EBI-3911467;
CC P48061; P02776: PF4; NbExp=4; IntAct=EBI-3913254, EBI-2565740;
CC P48061; P10720: PF4V1; NbExp=4; IntAct=EBI-3913254, EBI-1223944;
CC P48061; P47992: XCL1; NbExp=2; IntAct=EBI-3913254, EBI-10209901;
CC P48061; Q9UBD3: XCL2; NbExp=2; IntAct=EBI-3913254, EBI-10319095;
CC -!- SUBCELLULAR LOCATION: Secreted.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=7;
CC Name=Beta; Synonyms=SDF-1-beta(1-72), hSDF-1beta;
CC IsoId=P48061-1; Sequence=Displayed;
CC Name=Alpha; Synonyms=SDF-1-alpha(1-68), hSDF-1alpha;
CC IsoId=P48061-2; Sequence=VSP_001056;
CC Name=Gamma; Synonyms=hSDF-1gamma, SDF-1g;
CC IsoId=P48061-3; Sequence=VSP_041209;
CC Name=Delta; Synonyms=hSDF-1delta;
CC IsoId=P48061-4; Sequence=VSP_042118;
CC Name=Epsilon; Synonyms=hSDFepsilon;
CC IsoId=P48061-5; Sequence=VSP_042119;
CC Name=Theta; Synonyms=hSDFphi, hSDFtheta, Phi;
CC IsoId=P48061-6; Sequence=VSP_042120;
CC Name=7;
CC IsoId=P48061-7; Sequence=VSP_054781;
CC -!- TISSUE SPECIFICITY: Isoform Alpha and isoform Beta are ubiquitously
CC expressed, with highest levels detected in liver, pancreas and spleen.
CC Isoform Gamma is mainly expressed in heart, with weak expression
CC detected in several other tissues. Isoform Delta, isoform Epsilon and
CC isoform Theta have highest expression levels in pancreas, with lower
CC levels detected in heart, kidney, liver and spleen.
CC {ECO:0000269|PubMed:16626895}.
CC -!- DEVELOPMENTAL STAGE: Isoform Alpha is ubiquitously expressed in fetal
CC tissues. Isoform Beta and isoform Delta have more limited expression
CC patterns, with highest levels detected in fetal spleen and fetal liver,
CC respectively. Isoform Gamma and isoform Theta are weakly detected in
CC fetal kidney. {ECO:0000269|PubMed:16626895}.
CC -!- PTM: Processed forms SDF-1-beta(3-72) and SDF-1-alpha(3-67) are
CC produced after secretion by proteolytic cleavage of isoforms Beta and
CC Alpha, respectively. The N-terminal processing is probably achieved by
CC DPP4. Isoform Alpha is first cleaved at the C-terminus to yield a SDF-
CC 1-alpha(1-67) intermediate before being processed at the N-terminus.
CC The C-terminal processing of isoform Alpha is reduced by binding to
CC heparin and, probably, cell surface proteoglycans.
CC {ECO:0000269|PubMed:14525775}.
CC -!- MASS SPECTROMETRY: [Isoform Alpha]: Mass=7959; Method=Electrospray;
CC Note=The measured range is 22-89.;
CC Evidence={ECO:0000269|PubMed:14525775};
CC -!- MASS SPECTROMETRY: [Isoform Alpha]: Mass=7606; Method=Electrospray;
CC Note=The measured range is 24-88.;
CC Evidence={ECO:0000269|PubMed:14525775};
CC -!- MASS SPECTROMETRY: [Isoform Beta]: Mass=8522; Method=Electrospray;
CC Note=The measured range is 22-93.;
CC Evidence={ECO:0000269|PubMed:14525775};
CC -!- MASS SPECTROMETRY: [Isoform Beta]: Mass=8297; Method=Electrospray;
CC Note=The measured range is 24-93.;
CC Evidence={ECO:0000269|PubMed:14525775};
CC -!- SIMILARITY: Belongs to the intercrine alpha (chemokine CxC) family.
CC {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Wikipedia; Note=SDF-1 entry;
CC URL="https://en.wikipedia.org/wiki/SDF-1_%28biology%29";
CC -!- WEB RESOURCE: Name=SeattleSNPs;
CC URL="http://pga.gs.washington.edu/data/cxcl12/";
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; L36033; AAB39332.1; -; mRNA.
DR EMBL; L36034; AAB39333.1; -; mRNA.
DR EMBL; DQ345517; ABC69270.1; -; mRNA.
DR EMBL; DQ345518; ABC69271.1; -; mRNA.
DR EMBL; DQ345519; ABC69272.1; -; mRNA.
DR EMBL; DQ345520; ABC69273.1; -; mRNA.
DR EMBL; U16752; AAA97434.1; -; mRNA.
DR EMBL; U19495; AAB40516.1; -; mRNA.
DR EMBL; AY644456; AAT76437.1; -; mRNA.
DR EMBL; AY874118; AAW82036.1; -; mRNA.
DR EMBL; CR450283; CAG29279.1; -; mRNA.
DR EMBL; AK292628; BAF85317.1; -; mRNA.
DR EMBL; AK311814; BAG34757.1; -; mRNA.
DR EMBL; AU120056; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; AY802782; AAV49999.1; -; Genomic_DNA.
DR EMBL; AL137026; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471160; EAW86619.1; -; Genomic_DNA.
DR EMBL; BC039893; AAH39893.1; -; mRNA.
DR CCDS; CCDS31186.1; -. [P48061-3]
DR CCDS; CCDS44373.1; -. [P48061-1]
DR CCDS; CCDS53527.1; -. [P48061-4]
DR CCDS; CCDS60518.1; -. [P48061-7]
DR CCDS; CCDS7207.1; -. [P48061-2]
DR PIR; G01540; G01540.
DR RefSeq; NP_000600.1; NM_000609.6. [P48061-1]
DR RefSeq; NP_001029058.1; NM_001033886.2. [P48061-3]
DR RefSeq; NP_001171605.1; NM_001178134.1. [P48061-4]
DR RefSeq; NP_001264919.1; NM_001277990.1. [P48061-7]
DR RefSeq; NP_954637.1; NM_199168.3. [P48061-2]
DR PDB; 1A15; X-ray; 2.20 A; A/B=22-88.
DR PDB; 1QG7; X-ray; 2.00 A; A/B=22-88.
DR PDB; 1SDF; NMR; -; A=22-88.
DR PDB; 1VMC; NMR; -; A=22-89.
DR PDB; 2J7Z; X-ray; 1.95 A; A/B=22-89.
DR PDB; 2K01; NMR; -; A/C=22-89.
DR PDB; 2K03; NMR; -; A/C=22-89.
DR PDB; 2K04; NMR; -; A/C=22-89.
DR PDB; 2K05; NMR; -; A/C=22-89.
DR PDB; 2KEC; NMR; -; A=22-89.
DR PDB; 2KED; NMR; -; A=22-89.
DR PDB; 2KEE; NMR; -; A=22-89.
DR PDB; 2KOL; NMR; -; A=22-89.
DR PDB; 2N55; NMR; -; A=22-89.
DR PDB; 2NWG; X-ray; 2.07 A; A/B=22-88.
DR PDB; 2SDF; NMR; -; A=22-88.
DR PDB; 3GV3; X-ray; 1.60 A; A=26-88.
DR PDB; 3HP3; X-ray; 2.20 A; A/B/C/D/E/F/G/H/I/J=22-88.
DR PDB; 4LMQ; X-ray; 2.77 A; D/F=29-89.
DR PDB; 4UAI; X-ray; 1.90 A; A/B=22-89.
DR PDB; 6SHR; X-ray; 1.75 A; A=26-89.
DR PDBsum; 1A15; -.
DR PDBsum; 1QG7; -.
DR PDBsum; 1SDF; -.
DR PDBsum; 1VMC; -.
DR PDBsum; 2J7Z; -.
DR PDBsum; 2K01; -.
DR PDBsum; 2K03; -.
DR PDBsum; 2K04; -.
DR PDBsum; 2K05; -.
DR PDBsum; 2KEC; -.
DR PDBsum; 2KED; -.
DR PDBsum; 2KEE; -.
DR PDBsum; 2KOL; -.
DR PDBsum; 2N55; -.
DR PDBsum; 2NWG; -.
DR PDBsum; 2SDF; -.
DR PDBsum; 3GV3; -.
DR PDBsum; 3HP3; -.
DR PDBsum; 4LMQ; -.
DR PDBsum; 4UAI; -.
DR PDBsum; 6SHR; -.
DR AlphaFoldDB; P48061; -.
DR BMRB; P48061; -.
DR SMR; P48061; -.
DR BioGRID; 112288; 31.
DR DIP; DIP-391N; -.
DR IntAct; P48061; 27.
DR MINT; P48061; -.
DR STRING; 9606.ENSP00000379140; -.
DR BindingDB; P48061; -.
DR ChEMBL; CHEMBL3286074; -.
DR DrugBank; DB05934; CTCE-0214.
DR DrugBank; DB06822; Tinzaparin.
DR DrugCentral; P48061; -.
DR iPTMnet; P48061; -.
DR PhosphoSitePlus; P48061; -.
DR BioMuta; CXCL12; -.
DR DMDM; 1352728; -.
DR EPD; P48061; -.
DR jPOST; P48061; -.
DR MassIVE; P48061; -.
DR PaxDb; P48061; -.
DR PeptideAtlas; P48061; -.
DR PRIDE; P48061; -.
DR ProteomicsDB; 55853; -. [P48061-1]
DR ProteomicsDB; 55854; -. [P48061-2]
DR ProteomicsDB; 55855; -. [P48061-3]
DR ProteomicsDB; 55856; -. [P48061-4]
DR ProteomicsDB; 55857; -. [P48061-5]
DR ProteomicsDB; 55858; -. [P48061-6]
DR ABCD; P48061; 3 sequenced antibodies.
DR Antibodypedia; 4314; 869 antibodies from 44 providers.
DR DNASU; 6387; -.
DR Ensembl; ENST00000343575.11; ENSP00000339913.6; ENSG00000107562.17. [P48061-2]
DR Ensembl; ENST00000374426.6; ENSP00000363548.2; ENSG00000107562.17. [P48061-3]
DR Ensembl; ENST00000374429.6; ENSP00000363551.2; ENSG00000107562.17. [P48061-1]
DR Ensembl; ENST00000395793.7; ENSP00000379139.3; ENSG00000107562.17. [P48061-7]
DR Ensembl; ENST00000395794.2; ENSP00000379140.2; ENSG00000107562.17. [P48061-4]
DR Ensembl; ENST00000395795.5; ENSP00000379141.5; ENSG00000107562.17. [P48061-7]
DR GeneID; 6387; -.
DR KEGG; hsa:6387; -.
DR MANE-Select; ENST00000343575.11; ENSP00000339913.6; NM_199168.4; NP_954637.1. [P48061-2]
DR UCSC; uc001jbf.5; human. [P48061-1]
DR CTD; 6387; -.
DR DisGeNET; 6387; -.
DR GeneCards; CXCL12; -.
DR HGNC; HGNC:10672; CXCL12.
DR HPA; ENSG00000107562; Low tissue specificity.
DR MalaCards; CXCL12; -.
DR MIM; 600835; gene.
DR neXtProt; NX_P48061; -.
DR OpenTargets; ENSG00000107562; -.
DR PharmGKB; PA35602; -.
DR VEuPathDB; HostDB:ENSG00000107562; -.
DR eggNOG; ENOG502S54U; Eukaryota.
DR GeneTree; ENSGT00390000014056; -.
DR HOGENOM; CLU_2262823_0_0_1; -.
DR InParanoid; P48061; -.
DR OMA; LMAIATH; -.
DR OrthoDB; 1462231at2759; -.
DR PhylomeDB; P48061; -.
DR TreeFam; TF353159; -.
DR PathwayCommons; P48061; -.
DR Reactome; R-HSA-1251985; Nuclear signaling by ERBB4.
DR Reactome; R-HSA-376176; Signaling by ROBO receptors.
DR Reactome; R-HSA-380108; Chemokine receptors bind chemokines.
DR Reactome; R-HSA-418594; G alpha (i) signalling events.
DR Reactome; R-HSA-9018519; Estrogen-dependent gene expression.
DR SignaLink; P48061; -.
DR SIGNOR; P48061; -.
DR BioGRID-ORCS; 6387; 11 hits in 1072 CRISPR screens.
DR ChiTaRS; CXCL12; human.
DR EvolutionaryTrace; P48061; -.
DR GeneWiki; Stromal_cell-derived_factor-1; -.
DR GenomeRNAi; 6387; -.
DR Pharos; P48061; Tchem.
DR PRO; PR:P48061; -.
DR Proteomes; UP000005640; Chromosome 10.
DR RNAct; P48061; protein.
DR Bgee; ENSG00000107562; Expressed in synovial joint and 196 other tissues.
DR Genevisible; P48061; HS.
DR GO; GO:0062023; C:collagen-containing extracellular matrix; HDA:BHF-UCL.
DR GO; GO:0005737; C:cytoplasm; IEA:Ensembl.
DR GO; GO:0009897; C:external side of plasma membrane; IBA:GO_Central.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IEA:Ensembl.
DR GO; GO:0008009; F:chemokine activity; IDA:UniProtKB.
DR GO; GO:0042379; F:chemokine receptor binding; IMP:UniProtKB.
DR GO; GO:0045236; F:CXCR chemokine receptor binding; IDA:BHF-UCL.
DR GO; GO:0008083; F:growth factor activity; IEA:UniProtKB-KW.
DR GO; GO:0005178; F:integrin binding; IDA:UniProtKB.
DR GO; GO:0005102; F:signaling receptor binding; TAS:ProtInc.
DR GO; GO:0008344; P:adult locomotory behavior; IEA:Ensembl.
DR GO; GO:0031100; P:animal organ regeneration; IEA:Ensembl.
DR GO; GO:0061844; P:antimicrobial humoral immune response mediated by antimicrobial peptide; IDA:UniProtKB.
DR GO; GO:0007411; P:axon guidance; IBA:GO_Central.
DR GO; GO:0008015; P:blood circulation; TAS:ProtInc.
DR GO; GO:0007155; P:cell adhesion; TAS:ProtInc.
DR GO; GO:0060326; P:cell chemotaxis; IDA:UniProtKB.
DR GO; GO:0006874; P:cellular calcium ion homeostasis; TAS:ProtInc.
DR GO; GO:1990869; P:cellular response to chemokine; IMP:BHF-UCL.
DR GO; GO:0038146; P:chemokine (C-X-C motif) ligand 12 signaling pathway; IMP:BHF-UCL.
DR GO; GO:0070098; P:chemokine-mediated signaling pathway; IDA:BHF-UCL.
DR GO; GO:0006935; P:chemotaxis; TAS:UniProtKB.
DR GO; GO:0006952; P:defense response; IEA:InterPro.
DR GO; GO:0050966; P:detection of mechanical stimulus involved in sensory perception of pain; IEA:Ensembl.
DR GO; GO:0050965; P:detection of temperature stimulus involved in sensory perception of pain; IEA:Ensembl.
DR GO; GO:0007186; P:G protein-coupled receptor signaling pathway; TAS:ProtInc.
DR GO; GO:0006955; P:immune response; TAS:ProtInc.
DR GO; GO:0050930; P:induction of positive chemotaxis; IBA:GO_Central.
DR GO; GO:0033622; P:integrin activation; IDA:UniProtKB.
DR GO; GO:0031640; P:killing of cells of another organism; IDA:UniProtKB.
DR GO; GO:2000669; P:negative regulation of dendritic cell apoptotic process; IDA:BHF-UCL.
DR GO; GO:1902230; P:negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage; IDA:BHF-UCL.
DR GO; GO:1903237; P:negative regulation of leukocyte tethering or rolling; IDA:UniProtKB.
DR GO; GO:0001764; P:neuron migration; IEA:Ensembl.
DR GO; GO:0048842; P:positive regulation of axon extension involved in axon guidance; IEA:Ensembl.
DR GO; GO:0090280; P:positive regulation of calcium ion import; TAS:BHF-UCL.
DR GO; GO:0045785; P:positive regulation of cell adhesion; IDA:MGI.
DR GO; GO:0030335; P:positive regulation of cell migration; IBA:GO_Central.
DR GO; GO:0033603; P:positive regulation of dopamine secretion; IEA:Ensembl.
DR GO; GO:0001938; P:positive regulation of endothelial cell proliferation; IEA:Ensembl.
DR GO; GO:0090026; P:positive regulation of monocyte chemotaxis; IDA:UniProtKB.
DR GO; GO:0045666; P:positive regulation of neuron differentiation; IEA:Ensembl.
DR GO; GO:2000406; P:positive regulation of T cell migration; IDA:MGI.
DR GO; GO:0008064; P:regulation of actin polymerization or depolymerization; TAS:ProtInc.
DR GO; GO:0009408; P:response to heat; IEA:Ensembl.
DR GO; GO:0001666; P:response to hypoxia; IEA:Ensembl.
DR GO; GO:0043434; P:response to peptide hormone; IEA:Ensembl.
DR GO; GO:0009314; P:response to radiation; IEA:Ensembl.
DR GO; GO:1990478; P:response to ultrasound; IEA:Ensembl.
DR GO; GO:0009615; P:response to virus; TAS:ProtInc.
DR GO; GO:0007165; P:signal transduction; TAS:ProtInc.
DR GO; GO:0010818; P:T cell chemotaxis; IDA:UniProtKB.
DR GO; GO:0022029; P:telencephalon cell migration; IEA:Ensembl.
DR CDD; cd00273; Chemokine_CXC; 1.
DR InterPro; IPR001811; Chemokine_IL8-like_dom.
DR InterPro; IPR033899; CXC_Chemokine_domain.
DR InterPro; IPR039813; CXCL12.
DR InterPro; IPR036048; Interleukin_8-like_sf.
DR PANTHER; PTHR18837; PTHR18837; 1.
DR Pfam; PF00048; IL8; 1.
DR SMART; SM00199; SCY; 1.
DR SUPFAM; SSF54117; SSF54117; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Chemotaxis; Cytokine; Disulfide bond;
KW Growth factor; Host-virus interaction; Reference proteome; Secreted;
KW Signal.
FT SIGNAL 1..21
FT /evidence="ECO:0000255"
FT CHAIN 22..93
FT /note="Stromal cell-derived factor 1"
FT /id="PRO_0000005109"
FT CHAIN 24..93
FT /note="SDF-1-beta(3-72)"
FT /id="PRO_0000005110"
FT CHAIN 24..88
FT /note="SDF-1-alpha(3-67)"
FT /id="PRO_0000005111"
FT REGION 29..33
FT /note="Receptor and heparin binding"
FT /evidence="ECO:0000305"
FT REGION 39..41
FT /note="Receptor binding"
FT REGION 48..50
FT /note="Receptor binding"
FT REGION 60..70
FT /note="Receptor binding"
FT MOTIF 22..23
FT /note="Receptor activation motif"
FT BINDING 41..51
FT /ligand="heparin"
FT /ligand_id="ChEBI:CHEBI:28304"
FT BINDING 62
FT /ligand="heparin"
FT /ligand_id="ChEBI:CHEBI:28304"
FT BINDING 69
FT /ligand="heparin"
FT /ligand_id="ChEBI:CHEBI:28304"
FT BINDING 85
FT /ligand="heparin"
FT /ligand_id="ChEBI:CHEBI:28304"
FT SITE 45
FT /note="Important for integrin interaction and activation"
FT /evidence="ECO:0000269|PubMed:29301984"
FT SITE 46
FT /note="Important for dimer formation"
FT SITE 48
FT /note="Important for integrin interaction and activation"
FT /evidence="ECO:0000269|PubMed:29301984"
FT SITE 64
FT /note="Important for integrin interaction and activation"
FT /evidence="ECO:0000269|PubMed:29301984"
FT DISULFID 30..55
FT DISULFID 32..71
FT VAR_SEQ 39..93
FT /note="VARANVKHLKILNTPNCALQIVARLKNNNRQVCIDPKLKWIQEYLEKALNKR
FT FKM -> YCTCLIRVSFHGATPLTQGSWVLYSLSCAGGETGLREPGPMVSPRVESHQEG
FT RLGVPGPVNLGKA (in isoform 7)"
FT /evidence="ECO:0000303|PubMed:16344560"
FT /id="VSP_054781"
FT VAR_SEQ 89..93
FT /note="KRFKM -> NLISAAPAGKRVIAGARALHPSPPRACPTARALCEIRLWPPPE
FT WSWPSPGDV (in isoform Delta)"
FT /evidence="ECO:0000303|PubMed:16626895"
FT /id="VSP_042118"
FT VAR_SEQ 89..93
FT /note="KRFKM -> NC (in isoform Epsilon)"
FT /evidence="ECO:0000303|PubMed:16626895"
FT /id="VSP_042119"
FT VAR_SEQ 90..93
FT /note="Missing (in isoform Alpha)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:15489334, ECO:0000303|PubMed:7490086,
FT ECO:0000303|Ref.4, ECO:0000303|Ref.6, ECO:0000303|Ref.7"
FT /id="VSP_001056"
FT VAR_SEQ 90..93
FT /note="RFKM -> GRREEKVGKKEKIGKKKRQKKRKAAQKRKN (in isoform
FT Gamma)"
FT /evidence="ECO:0000303|PubMed:16626895, ECO:0000303|Ref.5"
FT /id="VSP_041209"
FT VAR_SEQ 90..93
FT /note="RFKM -> IWLYGNAETSR (in isoform Theta)"
FT /evidence="ECO:0000303|PubMed:16626895"
FT /id="VSP_042120"
FT MUTAGEN 22..23
FT /note="Missing: Abolished CXCR4 activation ability, but
FT only slightly impaired binding to the receptor."
FT /evidence="ECO:0000269|PubMed:9384579"
FT MUTAGEN 22
FT /note="K->A: Loss of chemotactic activity."
FT /evidence="ECO:0000269|PubMed:17357154,
FT ECO:0000269|PubMed:9384579"
FT MUTAGEN 22
FT /note="K->R: Abolished CXCR4 activation ability, but only
FT slightly impaired binding to the receptor."
FT /evidence="ECO:0000269|PubMed:17357154,
FT ECO:0000269|PubMed:9384579"
FT MUTAGEN 22
FT /note="Missing: Abolished CXCR4 activation ability, but
FT only slightly impaired binding to the receptor."
FT /evidence="ECO:0000269|PubMed:17357154,
FT ECO:0000269|PubMed:9384579"
FT MUTAGEN 23
FT /note="P->G: Abolished CXCR4 activation ability, but only
FT slightly impaired binding to the receptor."
FT /evidence="ECO:0000269|PubMed:9384579"
FT MUTAGEN 25..27
FT /note="SLS->AQA: Significantly impaired CXCR4 activation
FT ability, but only slightly impaired binding to the
FT receptor."
FT /evidence="ECO:0000269|PubMed:9384579"
FT MUTAGEN 28
FT /note="Y->A: Impaired CXCR4 activation ability, but only
FT slightly impaired binding to the receptor."
FT /evidence="ECO:0000269|PubMed:9384579"
FT MUTAGEN 28
FT /note="Y->H: No significant effect on CXCR4 binding or
FT activation."
FT /evidence="ECO:0000269|PubMed:9384579"
FT MUTAGEN 29
FT /note="R->K: Slightly impaired binding and activation of
FT CXCR4."
FT /evidence="ECO:0000269|PubMed:17264079,
FT ECO:0000269|PubMed:9384579"
FT MUTAGEN 29
FT /note="R->Q: Greatly impaired chemotactic activity and
FT enhanced inhibition by heparin."
FT /evidence="ECO:0000269|PubMed:17264079,
FT ECO:0000269|PubMed:9384579"
FT MUTAGEN 33..38
FT /note="RFFESH->AAAAAA: Significantly decreased chemotactic
FT activity."
FT /evidence="ECO:0000269|PubMed:10954912"
FT MUTAGEN 33
FT /note="R->A: Significantly decreased anti-HIV-1 and
FT chemotactic activities."
FT /evidence="ECO:0000269|PubMed:10954912,
FT ECO:0000269|PubMed:17264079"
FT MUTAGEN 33
FT /note="R->Q: Slightly impaired chemotactic activity and
FT enhanced inhibition by heparin. Greatly impaired
FT chemotactic activity; when associated with Q-29."
FT /evidence="ECO:0000269|PubMed:10954912,
FT ECO:0000269|PubMed:17264079"
FT MUTAGEN 34
FT /note="F->A: No effect on anti-HIV-1 and chemotactic
FT activities. Slightly impaired chemotactic activity and no
FT effect on inhibition by heparin; when associated with A-
FT 35."
FT /evidence="ECO:0000269|PubMed:10954912"
FT MUTAGEN 35
FT /note="F->A: No effect on anti-HIV-1 and chemotactic
FT activities. Slightly impaired chemotactic activity and no
FT effect on inhibition by heparin; when associated with A-
FT 34."
FT /evidence="ECO:0000269|PubMed:10954912"
FT MUTAGEN 36..38
FT /note="ESH->QSN: Slightly impaired chemotactic activity, no
FT effect on inhibition by heparin."
FT /evidence="ECO:0000269|PubMed:17264079"
FT MUTAGEN 36
FT /note="E->A: No effect on anti-HIV-1 and chemotactic
FT activities."
FT /evidence="ECO:0000269|PubMed:10954912"
FT MUTAGEN 37
FT /note="S->A: No effect on anti-HIV-1 and chemotactic
FT activities."
FT /evidence="ECO:0000269|PubMed:10954912"
FT MUTAGEN 38
FT /note="H->A: No effect on anti-HIV-1 and chemotactic
FT activities."
FT /evidence="ECO:0000269|PubMed:10954912"
FT MUTAGEN 41
FT /note="R->A: No effect on CXCR4 activation."
FT /evidence="ECO:0000269|PubMed:18799424"
FT MUTAGEN 45..48
FT /note="KHLK->SSLS: Loss of heparin-binding capacity."
FT /evidence="ECO:0000269|PubMed:10446158"
FT MUTAGEN 45
FT /note="K->E: Loss of integrin activation; when associated
FT with E-48 or E-64."
FT /evidence="ECO:0000269|PubMed:29301984"
FT MUTAGEN 45
FT /note="K->S: 55-fold reduction in binding affinity for Link
FT domain of TNFAIP6; when associated with S-46 and S-48."
FT /evidence="ECO:0000269|PubMed:27044744"
FT MUTAGEN 46
FT /note="H->A: Reduced dimerization in neutral pH. Eliminates
FT the pH dependence of dimerization."
FT /evidence="ECO:0000269|PubMed:15741341,
FT ECO:0000269|PubMed:17264079, ECO:0000269|PubMed:18799424"
FT MUTAGEN 46
FT /note="H->L: No significant effect on dimerization in
FT neutral pH. Eliminates the pH dependence of dimerization."
FT /evidence="ECO:0000269|PubMed:15741341,
FT ECO:0000269|PubMed:17264079, ECO:0000269|PubMed:18799424"
FT MUTAGEN 46
FT /note="H->N: Slightly impaired CXCR4 activation and clear
FT resistance to inhibition by heparin; when associated with
FT Q-48; Q-62; Q-68 and N-69."
FT /evidence="ECO:0000269|PubMed:15741341,
FT ECO:0000269|PubMed:17264079, ECO:0000269|PubMed:18799424"
FT MUTAGEN 46
FT /note="H->R: No effect on CXCR4 activation. Impaired dimer
FT formation, leading to increased chemotactic activity.
FT Eliminates the pH dependence of dimerization."
FT /evidence="ECO:0000269|PubMed:15741341,
FT ECO:0000269|PubMed:17264079, ECO:0000269|PubMed:18799424"
FT MUTAGEN 46
FT /note="H->S: 55-fold reduction in binding affinity for Link
FT domain of TNFAIP6; when associated with S-45 and S-48."
FT /evidence="ECO:0000269|PubMed:27044744"
FT MUTAGEN 48
FT /note="K->A: Impaired CXCR4 activation."
FT /evidence="ECO:0000269|PubMed:17264079,
FT ECO:0000269|PubMed:18799424"
FT MUTAGEN 48
FT /note="K->E: Impaired CXCR4 activation. Loss of integrin
FT activation; when associated with E-45 or E-64."
FT /evidence="ECO:0000269|PubMed:17264079,
FT ECO:0000269|PubMed:18799424, ECO:0000269|PubMed:29301984"
FT MUTAGEN 48
FT /note="K->Q: Slightly impaired CXCR4 activation and clear
FT resistance to inhibition by heparin; when associated with
FT N-46; Q-62; Q-68 and N-69."
FT /evidence="ECO:0000269|PubMed:17264079,
FT ECO:0000269|PubMed:18799424"
FT MUTAGEN 48
FT /note="K->S: 55-fold reduction in binding affinity for Link
FT domain of TNFAIP6; when associated with S-45 and S-46."
FT /evidence="ECO:0000269|PubMed:27044744"
FT MUTAGEN 52..56
FT /note="TPNCA->GPGCG: Slightly impaired chemotactic
FT activity, no effect on inhibition by heparin."
FT /evidence="ECO:0000269|PubMed:17264079"
FT MUTAGEN 57
FT /note="L->C: Formation of an intermolecular disulfide bond,
FT leading to a locked dimer; when associated with C-86. No
FT effect on CXCR4 activation, but loss of chemotactic
FT activity; when associated with C-86."
FT MUTAGEN 60
FT /note="V->A: Impaired CXCR4 activation."
FT /evidence="ECO:0000269|PubMed:18799424"
FT MUTAGEN 62
FT /note="R->A: No effect on CXCR4 activation."
FT /evidence="ECO:0000269|PubMed:17264079,
FT ECO:0000269|PubMed:18799424"
FT MUTAGEN 62
FT /note="R->Q: Slightly impaired CXCR4 activation and clear
FT resistance to inhibition by heparin; when associated with
FT N-46; Q-48; Q-68 and N-69."
FT /evidence="ECO:0000269|PubMed:17264079,
FT ECO:0000269|PubMed:18799424"
FT MUTAGEN 64
FT /note="K->E: Loss of integrin activation; when associated
FT with E-45 or E-48."
FT /evidence="ECO:0000269|PubMed:29301984"
FT MUTAGEN 68
FT /note="R->A: Impaired CXCR4 activation."
FT /evidence="ECO:0000269|PubMed:17264079,
FT ECO:0000269|PubMed:18799424"
FT MUTAGEN 68
FT /note="R->E: Greatly impaired CXCR4 activation."
FT /evidence="ECO:0000269|PubMed:17264079,
FT ECO:0000269|PubMed:18799424"
FT MUTAGEN 68
FT /note="R->Q: Slightly impaired CXCR4 activation and clear
FT resistance to inhibition by heparin; when associated with
FT N-46; Q-48; Q-62 and N-69."
FT /evidence="ECO:0000269|PubMed:17264079,
FT ECO:0000269|PubMed:18799424"
FT MUTAGEN 69
FT /note="Q->N: Slightly impaired CXCR4 activation and clear
FT resistance to inhibition by heparin; when associated with
FT N-46; Q-48; Q-62 and Q-68."
FT /evidence="ECO:0000269|PubMed:17264079"
FT MUTAGEN 70
FT /note="V->A: Impaired CXCR4 activation."
FT /evidence="ECO:0000269|PubMed:18799424"
FT MUTAGEN 81
FT /note="E->A: No effect on CXCR4 activation."
FT /evidence="ECO:0000269|PubMed:18799424"
FT MUTAGEN 84
FT /note="E->A: No effect on CXCR4 activation."
FT /evidence="ECO:0000269|PubMed:18799424"
FT MUTAGEN 85
FT /note="K->A: No effect on CXCR4 activation."
FT /evidence="ECO:0000269|PubMed:18799424"
FT MUTAGEN 86
FT /note="A->C: Formation of an intermolecular disulfide bond,
FT leading to a locked dimer; when associated with C-57. No
FT effect on CXCR4 activation, but loss of chemotactic
FT activity; when associated with C-57."
FT HELIX 24..26
FT /evidence="ECO:0007829|PDB:4UAI"
FT STRAND 27..29
FT /evidence="ECO:0007829|PDB:2K01"
FT STRAND 31..34
FT /evidence="ECO:0007829|PDB:3HP3"
FT STRAND 36..38
FT /evidence="ECO:0007829|PDB:1VMC"
FT HELIX 41..43
FT /evidence="ECO:0007829|PDB:3GV3"
FT STRAND 44..49
FT /evidence="ECO:0007829|PDB:3GV3"
FT TURN 53..55
FT /evidence="ECO:0007829|PDB:1QG7"
FT STRAND 59..63
FT /evidence="ECO:0007829|PDB:3GV3"
FT TURN 64..66
FT /evidence="ECO:0007829|PDB:3GV3"
FT STRAND 69..72
FT /evidence="ECO:0007829|PDB:3GV3"
FT HELIX 79..86
FT /evidence="ECO:0007829|PDB:3GV3"
SQ SEQUENCE 93 AA; 10666 MW; 505B5A29C2B44E8D CRC64;
MNAKVVVVLV LVLTALCLSD GKPVSLSYRC PCRFFESHVA RANVKHLKIL NTPNCALQIV
ARLKNNNRQV CIDPKLKWIQ EYLEKALNKR FKM
