Full text data of SDCBP
SDCBP
(MDA9, SYCL)
[Confidence: medium (present in either hRBCD or BSc_CH or PM22954596)]
Syntenin-1 (Melanoma differentiation-associated protein 9; MDA-9; Pro-TGF-alpha cytoplasmic domain-interacting protein 18; TACIP18; Scaffold protein Pbp1; Syndecan-binding protein 1)
Syntenin-1 (Melanoma differentiation-associated protein 9; MDA-9; Pro-TGF-alpha cytoplasmic domain-interacting protein 18; TACIP18; Scaffold protein Pbp1; Syndecan-binding protein 1)
Comments
Isoform O00560-2 was detected.
Isoform O00560-2 was detected.
UniProt
O00560
ID SDCB1_HUMAN Reviewed; 298 AA.
AC O00560; B2R5Q7; B4DUH3; B7ZLN2; O00173; O43391; Q14CP2;
DT 02-MAY-2002, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-JUL-1997, sequence version 1.
DT 22-JAN-2014, entry version 143.
DE RecName: Full=Syntenin-1;
DE AltName: Full=Melanoma differentiation-associated protein 9;
DE Short=MDA-9;
DE AltName: Full=Pro-TGF-alpha cytoplasmic domain-interacting protein 18;
DE Short=TACIP18;
DE AltName: Full=Scaffold protein Pbp1;
DE AltName: Full=Syndecan-binding protein 1;
GN Name=SDCBP; Synonyms=MDA9, SYCL;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RA Lin J.J., Jiang H., Fisher P.B.;
RT "Characterization of a novel melanoma differentiation associated gene,
RT mda-9, that is down-regulated during terminal cell differentiation.";
RL Mol. Cell. Differ. 4:317-333(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), INTERACTION WITH SDC2, AND
RP VARIANT SER-69.
RX PubMed=9391086; DOI=10.1073/pnas.94.25.13683;
RA Grootjans J.J., Zimmermann P., Reekmans G., Smets A., Degeest G.,
RA Duerr J., David G.;
RT "Syntenin, a PDZ protein that binds syndecan cytoplasmic domains.";
RL Proc. Natl. Acad. Sci. U.S.A. 94:13683-13688(1997).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RA Burbelo P.D.;
RT "A new family of scaffold proteins.";
RL Submitted (JAN-1997) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=9511750; DOI=10.1016/S0378-1119(97)00562-3;
RA Lin J.J., Jiang H., Fisher P.B.;
RT "Melanoma differentiation associated gene-9, mda-9, is a human gamma
RT interferon responsive gene.";
RL Gene 207:105-110(1998).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3).
RC TISSUE=Rectum, and Urinary bladder;
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.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA 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.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., 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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16421571; DOI=10.1038/nature04406;
RA Nusbaum C., Mikkelsen T.S., Zody M.C., Asakawa S., Taudien S.,
RA Garber M., Kodira C.D., Schueler M.G., Shimizu A., Whittaker C.A.,
RA Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Yang X.,
RA Allen N.R., Anderson S., Asakawa T., Blechschmidt K., Bloom T.,
RA Borowsky M.L., Butler J., Cook A., Corum B., DeArellano K.,
RA DeCaprio D., Dooley K.T., Dorris L. III, Engels R., Gloeckner G.,
RA Hafez N., Hagopian D.S., Hall J.L., Ishikawa S.K., Jaffe D.B.,
RA Kamat A., Kudoh J., Lehmann R., Lokitsang T., Macdonald P.,
RA Major J.E., Matthews C.D., Mauceli E., Menzel U., Mihalev A.H.,
RA Minoshima S., Murayama Y., Naylor J.W., Nicol R., Nguyen C.,
RA O'Leary S.B., O'Neill K., Parker S.C.J., Polley A., Raymond C.K.,
RA Reichwald K., Rodriguez J., Sasaki T., Schilhabel M., Siddiqui R.,
RA Smith C.L., Sneddon T.P., Talamas J.A., Tenzin P., Topham K.,
RA Venkataraman V., Wen G., Yamazaki S., Young S.K., Zeng Q.,
RA Zimmer A.R., Rosenthal A., Birren B.W., Platzer M., Shimizu N.,
RA Lander E.S.;
RT "DNA sequence and analysis of human chromosome 8.";
RL Nature 439:331-335(2006).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [9]
RP PROTEIN SEQUENCE OF 2-14; 218-229 AND 289-298, CLEAVAGE OF INITIATOR
RP METHIONINE, ACETYLATION AT SER-2, AND MASS SPECTROMETRY.
RC TISSUE=Pre-B cell;
RA Bienvenut W.V., Sumpton D.P., Lilla S., Ozanne B.W.;
RL Submitted (FEB-2009) to UniProtKB.
RN [10]
RP INTERACTION WITH EPHB1 AND EPHA7.
RX PubMed=9883737; DOI=10.1016/S0896-6273(00)80663-7;
RA Torres R., Firestein B.L., Dong H., Staudinger J., Olson E.N.,
RA Huganir R.L., Bredt D.S., Gale N.W., Yancopoulos G.D.;
RT "PDZ proteins bind, cluster, and synaptically colocalize with Eph
RT receptors and their ephrin ligands.";
RL Neuron 21:1453-1463(1998).
RN [11]
RP FUNCTION, AND INTERACTION WITH TGFA.
RX PubMed=10230395; DOI=10.1016/S1097-2765(00)80470-0;
RA Fernandez-Larrea J., Merlos-Suarez A., Urena J.M., Baselga J.,
RA Arribas J.;
RT "A role for a PDZ protein in the early secretory pathway for the
RT targeting of proTGF-alpha to the cell surface.";
RL Mol. Cell 3:423-433(1999).
RN [12]
RP INTERACTION WITH SYNDECANS; NRXN2 AND EPHB1.
RX PubMed=10770943; DOI=10.1074/jbc.M002459200;
RA Grootjans J.J., Reekmans G., Ceulemans H., David G.;
RT "Syntenin-syndecan binding requires syndecan-synteny and the co-
RT operation of both PDZ domains of syntenin.";
RL J. Biol. Chem. 275:19933-19941(2000).
RN [13]
RP INTERACTION WITH NF2.
RX PubMed=11432873; DOI=10.1074/jbc.M105792200;
RA Jannatipour M., Dion P., Khan S., Jindal H., Fan X., Laganiere J.,
RA Chishti A.H., Rouleau G.A.;
RT "Schwannomin isoform-1 interacts with syntenin via PDZ domains.";
RL J. Biol. Chem. 276:33093-33100(2001).
RN [14]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=11179419; DOI=10.1091/mbc.12.2.339;
RA Zimmermann P., Tomatis D., Rosas M., Grootjans J.J., Leenaerts I.,
RA Degeest G., Reekmans G., Coomans C., David G.;
RT "Characterization of syntenin, a syndecan-binding PDZ protein, as a
RT component of cell adhesion sites and microfilaments.";
RL Mol. Biol. Cell 12:339-350(2001).
RN [15]
RP FUNCTION, AND INTERACTION WITH IL5RA.
RX PubMed=11498591; DOI=10.1126/science.1059157;
RA Geijsen N., Uings I.J., Pals C., Armstrong J., McKinnon M.,
RA Raaijmakers J.A.M., Lammers J.-W., Koenderman L., Coffer P.J.;
RT "Cytokine-specific transcriptional regulation through an IL-5Ralpha
RT interacting protein.";
RL Science 293:1136-1138(2001).
RN [16]
RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS], AND MASS SPECTROMETRY.
RC TISSUE=Melanoma;
RX PubMed=12643545; DOI=10.1021/pr025562r;
RA Basrur V., Yang F., Kushimoto T., Higashimoto Y., Yasumoto K.,
RA Valencia J., Muller J., Vieira W.D., Watabe H., Shabanowitz J.,
RA Hearing V.J., Hunt D.F., Appella E.;
RT "Proteomic analysis of early melanosomes: identification of novel
RT melanosomal proteins.";
RL J. Proteome Res. 2:69-79(2003).
RN [17]
RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS], AND MASS SPECTROMETRY.
RC TISSUE=Melanoma;
RX PubMed=17081065; DOI=10.1021/pr060363j;
RA Chi A., Valencia J.C., Hu Z.-Z., Watabe H., Yamaguchi H.,
RA Mangini N.J., Huang H., Canfield V.A., Cheng K.C., Yang F., Abe R.,
RA Yamagishi S., Shabanowitz J., Hearing V.J., Wu C., Appella E.,
RA Hunt D.F.;
RT "Proteomic and bioinformatic characterization of the biogenesis and
RT function of melanosomes.";
RL J. Proteome Res. 5:3135-3144(2006).
RN [18]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, AND MASS SPECTROMETRY.
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [19]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [20]
RP X-RAY CRYSTALLOGRAPHY (1.94 ANGSTROMS) OF 113-273.
RX PubMed=12679023; DOI=10.1016/S0969-2126(03)00052-2;
RA Kang B.S., Cooper D.R., Jelen F., Devedjiev Y., Derewenda U.,
RA Dauter Z., Otlewski J., Derewenda Z.S.;
RT "PDZ tandem of human syntenin: crystal structure and functional
RT properties.";
RL Structure 11:459-468(2003).
RN [21]
RP X-RAY CRYSTALLOGRAPHY (1.35 ANGSTROMS) OF 197-270 IN COMPLEXES WITH
RP IL5RA AND SDC4.
RX PubMed=12842047; DOI=10.1016/S0969-2126(03)00125-4;
RA Kang B.S., Cooper D.R., Devedjiev Y., Derewenda U., Derewenda Z.S.;
RT "Molecular roots of degenerate specificity in syntenin's PDZ2 domain:
RT reassessment of the PDZ recognition paradigm.";
RL Structure 11:845-853(2003).
RN [22]
RP X-RAY CRYSTALLOGRAPHY (0.73 ANGSTROMS) OF 197-273.
RX PubMed=15081807; DOI=10.1016/j.jmb.2004.02.057;
RA Kang B.S., Devedjiev Y., Derewenda U., Derewenda Z.S.;
RT "The PDZ2 domain of syntenin at ultra-high resolution: bridging the
RT gap between macromolecular and small molecule crystallography.";
RL J. Mol. Biol. 338:483-493(2004).
RN [23]
RP X-RAY CRYSTALLOGRAPHY (1.56 ANGSTROMS) OF 113-273 IN COMPLEXES WITH
RP C-TERMINAL PEPTIDES FROM NEUREXIN; EPHB1 AND SDC4.
RX PubMed=16533050; DOI=10.1021/bi052225y;
RA Grembecka J., Cierpicki T., Devedjiev Y., Derewenda U., Kang B.S.,
RA Bushweller J.H., Derewenda Z.S.;
RT "The binding of the PDZ tandem of syntenin to target proteins.";
RL Biochemistry 45:3674-3683(2006).
CC -!- FUNCTION: Seems to function as an adapter protein. In adherens
CC junctions may function to couple syndecans to cytoskeletal
CC proteins or signaling components. Seems to couple transcription
CC factor SOX4 to the IL-5 receptor (IL5RA). May also play a role in
CC vesicular trafficking. Seems to be required for the targeting of
CC TGFA to the cell surface in the early secretory pathway.
CC -!- SUBUNIT: Monomer and homodimer (By similarity). Interacts with
CC SDC1, SDC2, SDC3, SDC4, NRXN2, EPHA7, EPHB1, NF2 isoform 1, TGFA
CC and IL5RA. Interacts with neurofascin, SDCBP2 and PTPRJ (By
CC similarity).
CC -!- INTERACTION:
CC Self; NbExp=4; IntAct=EBI-727004, EBI-727004;
CC O75084:FZD7; NbExp=4; IntAct=EBI-727004, EBI-746917;
CC -!- SUBCELLULAR LOCATION: Cell junction, focal adhesion. Cell
CC junction, adherens junction. Cell membrane; Peripheral membrane
CC protein. Endoplasmic reticulum membrane; Peripheral membrane
CC protein. Nucleus. Melanosome. Cytoplasm, cytosol. Cytoplasm,
CC cytoskeleton. Note=Mainly membrane-associated. Localized to
CC adherens junctions, focal adhesions and endoplasmic reticulum.
CC Colocalized with actin stress fibers. Also found in the nucleus.
CC Identified by mass spectrometry in melanosome fractions from stage
CC I to stage IV.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=O00560-1; Sequence=Displayed;
CC Name=2;
CC IsoId=O00560-2; Sequence=VSP_038375;
CC Name=3;
CC IsoId=O00560-3; Sequence=VSP_038374;
CC -!- TISSUE SPECIFICITY: Widely expressed. Expressed in fetal kidney,
CC liver, lung and brain. In adult highest expression in heart and
CC placenta.
CC -!- INDUCTION: By IFNG/IFN-gamma in melanoma cells.
CC -!- PTM: Phosphorylated on tyrosine residues.
CC -!- SIMILARITY: Contains 2 PDZ (DHR) domains.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology
CC and Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/SDCBPID44377ch8q12.html";
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DR EMBL; AF006636; AAC52050.1; -; mRNA.
DR EMBL; AF000652; AAB97144.1; -; mRNA.
DR EMBL; U83463; AAB51246.1; -; mRNA.
DR EMBL; AK300647; BAG62335.1; -; mRNA.
DR EMBL; AK312274; BAG35204.1; -; mRNA.
DR EMBL; AC068522; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471068; EAW86814.1; -; Genomic_DNA.
DR EMBL; BC113674; AAI13675.1; -; mRNA.
DR EMBL; BC113676; AAI13677.1; -; mRNA.
DR EMBL; BC143915; AAI43916.1; -; mRNA.
DR EMBL; BC143916; AAI43917.1; -; mRNA.
DR PIR; JC6537; JC6537.
DR RefSeq; NP_001007068.1; NM_001007067.1.
DR RefSeq; NP_001007069.1; NM_001007068.1.
DR RefSeq; NP_001007070.1; NM_001007069.1.
DR RefSeq; NP_001007071.1; NM_001007070.1.
DR RefSeq; NP_005616.2; NM_005625.3.
DR UniGene; Hs.200804; -.
DR PDB; 1N99; X-ray; 1.94 A; A/B=113-273.
DR PDB; 1NTE; X-ray; 1.24 A; A=197-273.
DR PDB; 1OBX; X-ray; 1.35 A; A=197-270.
DR PDB; 1OBY; X-ray; 1.85 A; A/B=197-270.
DR PDB; 1OBZ; X-ray; 1.69 A; A/B=113-273.
DR PDB; 1R6J; X-ray; 0.73 A; A=197-273.
DR PDB; 1V1T; X-ray; 1.80 A; A/B=113-273.
DR PDB; 1W9E; X-ray; 1.56 A; A/B=113-273.
DR PDB; 1W9O; X-ray; 2.25 A; A/B=113-273.
DR PDB; 1W9Q; X-ray; 1.70 A; A/B=113-273.
DR PDB; 1YBO; X-ray; 2.30 A; A/B=113-273.
DR PDBsum; 1N99; -.
DR PDBsum; 1NTE; -.
DR PDBsum; 1OBX; -.
DR PDBsum; 1OBY; -.
DR PDBsum; 1OBZ; -.
DR PDBsum; 1R6J; -.
DR PDBsum; 1V1T; -.
DR PDBsum; 1W9E; -.
DR PDBsum; 1W9O; -.
DR PDBsum; 1W9Q; -.
DR PDBsum; 1YBO; -.
DR ProteinModelPortal; O00560; -.
DR SMR; O00560; 113-273.
DR DIP; DIP-42705N; -.
DR IntAct; O00560; 50.
DR MINT; MINT-5002159; -.
DR STRING; 9606.ENSP00000260130; -.
DR PhosphoSite; O00560; -.
DR PaxDb; O00560; -.
DR PRIDE; O00560; -.
DR DNASU; 6386; -.
DR Ensembl; ENST00000260130; ENSP00000260130; ENSG00000137575.
DR Ensembl; ENST00000413219; ENSP00000411771; ENSG00000137575.
DR Ensembl; ENST00000422546; ENSP00000391687; ENSG00000137575.
DR Ensembl; ENST00000424270; ENSP00000395351; ENSG00000137575.
DR Ensembl; ENST00000447182; ENSP00000409288; ENSG00000137575.
DR GeneID; 6386; -.
DR KEGG; hsa:6386; -.
DR UCSC; uc003xtn.3; human.
DR CTD; 6386; -.
DR GeneCards; GC08P059515; -.
DR HGNC; HGNC:10662; SDCBP.
DR HPA; CAB012245; -.
DR HPA; HPA023840; -.
DR MIM; 602217; gene.
DR neXtProt; NX_O00560; -.
DR PharmGKB; PA35592; -.
DR eggNOG; NOG140434; -.
DR HOGENOM; HOG000231604; -.
DR HOVERGEN; HBG053211; -.
DR InParanoid; O00560; -.
DR KO; K17254; -.
DR OrthoDB; EOG75MVWZ; -.
DR PhylomeDB; O00560; -.
DR Reactome; REACT_111045; Developmental Biology.
DR SignaLink; O00560; -.
DR ChiTaRS; SDCBP; human.
DR EvolutionaryTrace; O00560; -.
DR GeneWiki; SDCBP; -.
DR GenomeRNAi; 6386; -.
DR NextBio; 24796; -.
DR PRO; PR:O00560; -.
DR ArrayExpress; O00560; -.
DR Bgee; O00560; -.
DR CleanEx; HS_SDCBP; -.
DR Genevestigator; O00560; -.
DR GO; GO:0005912; C:adherens junction; NAS:UniProtKB.
DR GO; GO:0005856; C:cytoskeleton; NAS:UniProtKB.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0070062; C:extracellular vesicular exosome; IDA:UniProtKB.
DR GO; GO:0005925; C:focal adhesion; IEA:UniProtKB-SubCell.
DR GO; GO:0005895; C:interleukin-5 receptor complex; ISS:UniProtKB.
DR GO; GO:0042470; C:melanosome; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; NAS:UniProtKB.
DR GO; GO:0008093; F:cytoskeletal adaptor activity; NAS:UniProtKB.
DR GO; GO:0005137; F:interleukin-5 receptor binding; ISS:UniProtKB.
DR GO; GO:0045545; F:syndecan binding; NAS:UniProtKB.
DR GO; GO:0030036; P:actin cytoskeleton organization; NAS:UniProtKB.
DR GO; GO:0007411; P:axon guidance; TAS:Reactome.
DR GO; GO:0035556; P:intracellular signal transduction; NAS:UniProtKB.
DR GO; GO:0046330; P:positive regulation of JNK cascade; IC:BHF-UCL.
DR GO; GO:0042327; P:positive regulation of phosphorylation; IDA:BHF-UCL.
DR GO; GO:0006612; P:protein targeting to membrane; NAS:UniProtKB.
DR GO; GO:0007265; P:Ras protein signal transduction; IEA:Ensembl.
DR GO; GO:0006930; P:substrate-dependent cell migration, cell extension; NAS:UniProtKB.
DR GO; GO:0007268; P:synaptic transmission; NAS:UniProtKB.
DR InterPro; IPR001478; PDZ.
DR Pfam; PF00595; PDZ; 2.
DR SMART; SM00228; PDZ; 2.
DR SUPFAM; SSF50156; SSF50156; 2.
DR PROSITE; PS50106; PDZ; 2.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Cell junction;
KW Cell membrane; Complete proteome; Cytoplasm; Cytoskeleton;
KW Direct protein sequencing; Endoplasmic reticulum; Membrane; Nucleus;
KW Phosphoprotein; Polymorphism; Reference proteome; Repeat.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 298 Syntenin-1.
FT /FTId=PRO_0000184001.
FT DOMAIN 114 193 PDZ 1.
FT DOMAIN 198 273 PDZ 2.
FT MOD_RES 2 2 N-acetylserine.
FT VAR_SEQ 12 17 Missing (in isoform 3).
FT /FTId=VSP_038374.
FT VAR_SEQ 81 81 Missing (in isoform 2).
FT /FTId=VSP_038375.
FT VARIANT 26 26 P -> T (in dbSNP:rs11550282).
FT /FTId=VAR_053699.
FT VARIANT 69 69 N -> S (in dbSNP:rs1127509).
FT /FTId=VAR_013160.
FT CONFLICT 62 62 N -> S (in Ref. 2; AAB51246).
FT STRAND 113 118
FT STRAND 121 123
FT STRAND 126 132
FT STRAND 135 141
FT HELIX 146 149
FT STRAND 157 161
FT HELIX 171 180
FT STRAND 183 191
FT STRAND 197 202
FT STRAND 205 208
FT STRAND 211 214
FT STRAND 217 221
FT HELIX 226 230
FT STRAND 234 241
FT HELIX 251 260
FT STRAND 263 271
SQ SEQUENCE 298 AA; 32444 MW; 574E1349F86F949F CRC64;
MSLYPSLEDL KVDKVIQAQT AFSANPANPA ILSEASAPIP HDGNLYPRLY PELSQYMGLS
LNEEEIRANV AVVSGAPLQG QLVARPSSIN YMVAPVTGND VGIRRAEIKQ GIREVILCKD
QDGKIGLRLK SIDNGIFVQL VQANSPASLV GLRFGDQVLQ INGENCAGWS SDKAHKVLKQ
AFGEKITMTI RDRPFERTIT MHKDSTGHVG FIFKNGKITS IVKDSSAARN GLLTEHNICE
INGQNVIGLK DSQIADILST SGTVVTITIM PAFIFEHIIK RMAPSIMKSL MDHTIPEV
//
ID SDCB1_HUMAN Reviewed; 298 AA.
AC O00560; B2R5Q7; B4DUH3; B7ZLN2; O00173; O43391; Q14CP2;
DT 02-MAY-2002, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-JUL-1997, sequence version 1.
DT 22-JAN-2014, entry version 143.
DE RecName: Full=Syntenin-1;
DE AltName: Full=Melanoma differentiation-associated protein 9;
DE Short=MDA-9;
DE AltName: Full=Pro-TGF-alpha cytoplasmic domain-interacting protein 18;
DE Short=TACIP18;
DE AltName: Full=Scaffold protein Pbp1;
DE AltName: Full=Syndecan-binding protein 1;
GN Name=SDCBP; Synonyms=MDA9, SYCL;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RA Lin J.J., Jiang H., Fisher P.B.;
RT "Characterization of a novel melanoma differentiation associated gene,
RT mda-9, that is down-regulated during terminal cell differentiation.";
RL Mol. Cell. Differ. 4:317-333(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), INTERACTION WITH SDC2, AND
RP VARIANT SER-69.
RX PubMed=9391086; DOI=10.1073/pnas.94.25.13683;
RA Grootjans J.J., Zimmermann P., Reekmans G., Smets A., Degeest G.,
RA Duerr J., David G.;
RT "Syntenin, a PDZ protein that binds syndecan cytoplasmic domains.";
RL Proc. Natl. Acad. Sci. U.S.A. 94:13683-13688(1997).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RA Burbelo P.D.;
RT "A new family of scaffold proteins.";
RL Submitted (JAN-1997) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=9511750; DOI=10.1016/S0378-1119(97)00562-3;
RA Lin J.J., Jiang H., Fisher P.B.;
RT "Melanoma differentiation associated gene-9, mda-9, is a human gamma
RT interferon responsive gene.";
RL Gene 207:105-110(1998).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3).
RC TISSUE=Rectum, and Urinary bladder;
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.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA 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.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., 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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16421571; DOI=10.1038/nature04406;
RA Nusbaum C., Mikkelsen T.S., Zody M.C., Asakawa S., Taudien S.,
RA Garber M., Kodira C.D., Schueler M.G., Shimizu A., Whittaker C.A.,
RA Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Yang X.,
RA Allen N.R., Anderson S., Asakawa T., Blechschmidt K., Bloom T.,
RA Borowsky M.L., Butler J., Cook A., Corum B., DeArellano K.,
RA DeCaprio D., Dooley K.T., Dorris L. III, Engels R., Gloeckner G.,
RA Hafez N., Hagopian D.S., Hall J.L., Ishikawa S.K., Jaffe D.B.,
RA Kamat A., Kudoh J., Lehmann R., Lokitsang T., Macdonald P.,
RA Major J.E., Matthews C.D., Mauceli E., Menzel U., Mihalev A.H.,
RA Minoshima S., Murayama Y., Naylor J.W., Nicol R., Nguyen C.,
RA O'Leary S.B., O'Neill K., Parker S.C.J., Polley A., Raymond C.K.,
RA Reichwald K., Rodriguez J., Sasaki T., Schilhabel M., Siddiqui R.,
RA Smith C.L., Sneddon T.P., Talamas J.A., Tenzin P., Topham K.,
RA Venkataraman V., Wen G., Yamazaki S., Young S.K., Zeng Q.,
RA Zimmer A.R., Rosenthal A., Birren B.W., Platzer M., Shimizu N.,
RA Lander E.S.;
RT "DNA sequence and analysis of human chromosome 8.";
RL Nature 439:331-335(2006).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [9]
RP PROTEIN SEQUENCE OF 2-14; 218-229 AND 289-298, CLEAVAGE OF INITIATOR
RP METHIONINE, ACETYLATION AT SER-2, AND MASS SPECTROMETRY.
RC TISSUE=Pre-B cell;
RA Bienvenut W.V., Sumpton D.P., Lilla S., Ozanne B.W.;
RL Submitted (FEB-2009) to UniProtKB.
RN [10]
RP INTERACTION WITH EPHB1 AND EPHA7.
RX PubMed=9883737; DOI=10.1016/S0896-6273(00)80663-7;
RA Torres R., Firestein B.L., Dong H., Staudinger J., Olson E.N.,
RA Huganir R.L., Bredt D.S., Gale N.W., Yancopoulos G.D.;
RT "PDZ proteins bind, cluster, and synaptically colocalize with Eph
RT receptors and their ephrin ligands.";
RL Neuron 21:1453-1463(1998).
RN [11]
RP FUNCTION, AND INTERACTION WITH TGFA.
RX PubMed=10230395; DOI=10.1016/S1097-2765(00)80470-0;
RA Fernandez-Larrea J., Merlos-Suarez A., Urena J.M., Baselga J.,
RA Arribas J.;
RT "A role for a PDZ protein in the early secretory pathway for the
RT targeting of proTGF-alpha to the cell surface.";
RL Mol. Cell 3:423-433(1999).
RN [12]
RP INTERACTION WITH SYNDECANS; NRXN2 AND EPHB1.
RX PubMed=10770943; DOI=10.1074/jbc.M002459200;
RA Grootjans J.J., Reekmans G., Ceulemans H., David G.;
RT "Syntenin-syndecan binding requires syndecan-synteny and the co-
RT operation of both PDZ domains of syntenin.";
RL J. Biol. Chem. 275:19933-19941(2000).
RN [13]
RP INTERACTION WITH NF2.
RX PubMed=11432873; DOI=10.1074/jbc.M105792200;
RA Jannatipour M., Dion P., Khan S., Jindal H., Fan X., Laganiere J.,
RA Chishti A.H., Rouleau G.A.;
RT "Schwannomin isoform-1 interacts with syntenin via PDZ domains.";
RL J. Biol. Chem. 276:33093-33100(2001).
RN [14]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=11179419; DOI=10.1091/mbc.12.2.339;
RA Zimmermann P., Tomatis D., Rosas M., Grootjans J.J., Leenaerts I.,
RA Degeest G., Reekmans G., Coomans C., David G.;
RT "Characterization of syntenin, a syndecan-binding PDZ protein, as a
RT component of cell adhesion sites and microfilaments.";
RL Mol. Biol. Cell 12:339-350(2001).
RN [15]
RP FUNCTION, AND INTERACTION WITH IL5RA.
RX PubMed=11498591; DOI=10.1126/science.1059157;
RA Geijsen N., Uings I.J., Pals C., Armstrong J., McKinnon M.,
RA Raaijmakers J.A.M., Lammers J.-W., Koenderman L., Coffer P.J.;
RT "Cytokine-specific transcriptional regulation through an IL-5Ralpha
RT interacting protein.";
RL Science 293:1136-1138(2001).
RN [16]
RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS], AND MASS SPECTROMETRY.
RC TISSUE=Melanoma;
RX PubMed=12643545; DOI=10.1021/pr025562r;
RA Basrur V., Yang F., Kushimoto T., Higashimoto Y., Yasumoto K.,
RA Valencia J., Muller J., Vieira W.D., Watabe H., Shabanowitz J.,
RA Hearing V.J., Hunt D.F., Appella E.;
RT "Proteomic analysis of early melanosomes: identification of novel
RT melanosomal proteins.";
RL J. Proteome Res. 2:69-79(2003).
RN [17]
RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS], AND MASS SPECTROMETRY.
RC TISSUE=Melanoma;
RX PubMed=17081065; DOI=10.1021/pr060363j;
RA Chi A., Valencia J.C., Hu Z.-Z., Watabe H., Yamaguchi H.,
RA Mangini N.J., Huang H., Canfield V.A., Cheng K.C., Yang F., Abe R.,
RA Yamagishi S., Shabanowitz J., Hearing V.J., Wu C., Appella E.,
RA Hunt D.F.;
RT "Proteomic and bioinformatic characterization of the biogenesis and
RT function of melanosomes.";
RL J. Proteome Res. 5:3135-3144(2006).
RN [18]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, AND MASS SPECTROMETRY.
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [19]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [20]
RP X-RAY CRYSTALLOGRAPHY (1.94 ANGSTROMS) OF 113-273.
RX PubMed=12679023; DOI=10.1016/S0969-2126(03)00052-2;
RA Kang B.S., Cooper D.R., Jelen F., Devedjiev Y., Derewenda U.,
RA Dauter Z., Otlewski J., Derewenda Z.S.;
RT "PDZ tandem of human syntenin: crystal structure and functional
RT properties.";
RL Structure 11:459-468(2003).
RN [21]
RP X-RAY CRYSTALLOGRAPHY (1.35 ANGSTROMS) OF 197-270 IN COMPLEXES WITH
RP IL5RA AND SDC4.
RX PubMed=12842047; DOI=10.1016/S0969-2126(03)00125-4;
RA Kang B.S., Cooper D.R., Devedjiev Y., Derewenda U., Derewenda Z.S.;
RT "Molecular roots of degenerate specificity in syntenin's PDZ2 domain:
RT reassessment of the PDZ recognition paradigm.";
RL Structure 11:845-853(2003).
RN [22]
RP X-RAY CRYSTALLOGRAPHY (0.73 ANGSTROMS) OF 197-273.
RX PubMed=15081807; DOI=10.1016/j.jmb.2004.02.057;
RA Kang B.S., Devedjiev Y., Derewenda U., Derewenda Z.S.;
RT "The PDZ2 domain of syntenin at ultra-high resolution: bridging the
RT gap between macromolecular and small molecule crystallography.";
RL J. Mol. Biol. 338:483-493(2004).
RN [23]
RP X-RAY CRYSTALLOGRAPHY (1.56 ANGSTROMS) OF 113-273 IN COMPLEXES WITH
RP C-TERMINAL PEPTIDES FROM NEUREXIN; EPHB1 AND SDC4.
RX PubMed=16533050; DOI=10.1021/bi052225y;
RA Grembecka J., Cierpicki T., Devedjiev Y., Derewenda U., Kang B.S.,
RA Bushweller J.H., Derewenda Z.S.;
RT "The binding of the PDZ tandem of syntenin to target proteins.";
RL Biochemistry 45:3674-3683(2006).
CC -!- FUNCTION: Seems to function as an adapter protein. In adherens
CC junctions may function to couple syndecans to cytoskeletal
CC proteins or signaling components. Seems to couple transcription
CC factor SOX4 to the IL-5 receptor (IL5RA). May also play a role in
CC vesicular trafficking. Seems to be required for the targeting of
CC TGFA to the cell surface in the early secretory pathway.
CC -!- SUBUNIT: Monomer and homodimer (By similarity). Interacts with
CC SDC1, SDC2, SDC3, SDC4, NRXN2, EPHA7, EPHB1, NF2 isoform 1, TGFA
CC and IL5RA. Interacts with neurofascin, SDCBP2 and PTPRJ (By
CC similarity).
CC -!- INTERACTION:
CC Self; NbExp=4; IntAct=EBI-727004, EBI-727004;
CC O75084:FZD7; NbExp=4; IntAct=EBI-727004, EBI-746917;
CC -!- SUBCELLULAR LOCATION: Cell junction, focal adhesion. Cell
CC junction, adherens junction. Cell membrane; Peripheral membrane
CC protein. Endoplasmic reticulum membrane; Peripheral membrane
CC protein. Nucleus. Melanosome. Cytoplasm, cytosol. Cytoplasm,
CC cytoskeleton. Note=Mainly membrane-associated. Localized to
CC adherens junctions, focal adhesions and endoplasmic reticulum.
CC Colocalized with actin stress fibers. Also found in the nucleus.
CC Identified by mass spectrometry in melanosome fractions from stage
CC I to stage IV.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=O00560-1; Sequence=Displayed;
CC Name=2;
CC IsoId=O00560-2; Sequence=VSP_038375;
CC Name=3;
CC IsoId=O00560-3; Sequence=VSP_038374;
CC -!- TISSUE SPECIFICITY: Widely expressed. Expressed in fetal kidney,
CC liver, lung and brain. In adult highest expression in heart and
CC placenta.
CC -!- INDUCTION: By IFNG/IFN-gamma in melanoma cells.
CC -!- PTM: Phosphorylated on tyrosine residues.
CC -!- SIMILARITY: Contains 2 PDZ (DHR) domains.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology
CC and Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/SDCBPID44377ch8q12.html";
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DR EMBL; AF006636; AAC52050.1; -; mRNA.
DR EMBL; AF000652; AAB97144.1; -; mRNA.
DR EMBL; U83463; AAB51246.1; -; mRNA.
DR EMBL; AK300647; BAG62335.1; -; mRNA.
DR EMBL; AK312274; BAG35204.1; -; mRNA.
DR EMBL; AC068522; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471068; EAW86814.1; -; Genomic_DNA.
DR EMBL; BC113674; AAI13675.1; -; mRNA.
DR EMBL; BC113676; AAI13677.1; -; mRNA.
DR EMBL; BC143915; AAI43916.1; -; mRNA.
DR EMBL; BC143916; AAI43917.1; -; mRNA.
DR PIR; JC6537; JC6537.
DR RefSeq; NP_001007068.1; NM_001007067.1.
DR RefSeq; NP_001007069.1; NM_001007068.1.
DR RefSeq; NP_001007070.1; NM_001007069.1.
DR RefSeq; NP_001007071.1; NM_001007070.1.
DR RefSeq; NP_005616.2; NM_005625.3.
DR UniGene; Hs.200804; -.
DR PDB; 1N99; X-ray; 1.94 A; A/B=113-273.
DR PDB; 1NTE; X-ray; 1.24 A; A=197-273.
DR PDB; 1OBX; X-ray; 1.35 A; A=197-270.
DR PDB; 1OBY; X-ray; 1.85 A; A/B=197-270.
DR PDB; 1OBZ; X-ray; 1.69 A; A/B=113-273.
DR PDB; 1R6J; X-ray; 0.73 A; A=197-273.
DR PDB; 1V1T; X-ray; 1.80 A; A/B=113-273.
DR PDB; 1W9E; X-ray; 1.56 A; A/B=113-273.
DR PDB; 1W9O; X-ray; 2.25 A; A/B=113-273.
DR PDB; 1W9Q; X-ray; 1.70 A; A/B=113-273.
DR PDB; 1YBO; X-ray; 2.30 A; A/B=113-273.
DR PDBsum; 1N99; -.
DR PDBsum; 1NTE; -.
DR PDBsum; 1OBX; -.
DR PDBsum; 1OBY; -.
DR PDBsum; 1OBZ; -.
DR PDBsum; 1R6J; -.
DR PDBsum; 1V1T; -.
DR PDBsum; 1W9E; -.
DR PDBsum; 1W9O; -.
DR PDBsum; 1W9Q; -.
DR PDBsum; 1YBO; -.
DR ProteinModelPortal; O00560; -.
DR SMR; O00560; 113-273.
DR DIP; DIP-42705N; -.
DR IntAct; O00560; 50.
DR MINT; MINT-5002159; -.
DR STRING; 9606.ENSP00000260130; -.
DR PhosphoSite; O00560; -.
DR PaxDb; O00560; -.
DR PRIDE; O00560; -.
DR DNASU; 6386; -.
DR Ensembl; ENST00000260130; ENSP00000260130; ENSG00000137575.
DR Ensembl; ENST00000413219; ENSP00000411771; ENSG00000137575.
DR Ensembl; ENST00000422546; ENSP00000391687; ENSG00000137575.
DR Ensembl; ENST00000424270; ENSP00000395351; ENSG00000137575.
DR Ensembl; ENST00000447182; ENSP00000409288; ENSG00000137575.
DR GeneID; 6386; -.
DR KEGG; hsa:6386; -.
DR UCSC; uc003xtn.3; human.
DR CTD; 6386; -.
DR GeneCards; GC08P059515; -.
DR HGNC; HGNC:10662; SDCBP.
DR HPA; CAB012245; -.
DR HPA; HPA023840; -.
DR MIM; 602217; gene.
DR neXtProt; NX_O00560; -.
DR PharmGKB; PA35592; -.
DR eggNOG; NOG140434; -.
DR HOGENOM; HOG000231604; -.
DR HOVERGEN; HBG053211; -.
DR InParanoid; O00560; -.
DR KO; K17254; -.
DR OrthoDB; EOG75MVWZ; -.
DR PhylomeDB; O00560; -.
DR Reactome; REACT_111045; Developmental Biology.
DR SignaLink; O00560; -.
DR ChiTaRS; SDCBP; human.
DR EvolutionaryTrace; O00560; -.
DR GeneWiki; SDCBP; -.
DR GenomeRNAi; 6386; -.
DR NextBio; 24796; -.
DR PRO; PR:O00560; -.
DR ArrayExpress; O00560; -.
DR Bgee; O00560; -.
DR CleanEx; HS_SDCBP; -.
DR Genevestigator; O00560; -.
DR GO; GO:0005912; C:adherens junction; NAS:UniProtKB.
DR GO; GO:0005856; C:cytoskeleton; NAS:UniProtKB.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0070062; C:extracellular vesicular exosome; IDA:UniProtKB.
DR GO; GO:0005925; C:focal adhesion; IEA:UniProtKB-SubCell.
DR GO; GO:0005895; C:interleukin-5 receptor complex; ISS:UniProtKB.
DR GO; GO:0042470; C:melanosome; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; NAS:UniProtKB.
DR GO; GO:0008093; F:cytoskeletal adaptor activity; NAS:UniProtKB.
DR GO; GO:0005137; F:interleukin-5 receptor binding; ISS:UniProtKB.
DR GO; GO:0045545; F:syndecan binding; NAS:UniProtKB.
DR GO; GO:0030036; P:actin cytoskeleton organization; NAS:UniProtKB.
DR GO; GO:0007411; P:axon guidance; TAS:Reactome.
DR GO; GO:0035556; P:intracellular signal transduction; NAS:UniProtKB.
DR GO; GO:0046330; P:positive regulation of JNK cascade; IC:BHF-UCL.
DR GO; GO:0042327; P:positive regulation of phosphorylation; IDA:BHF-UCL.
DR GO; GO:0006612; P:protein targeting to membrane; NAS:UniProtKB.
DR GO; GO:0007265; P:Ras protein signal transduction; IEA:Ensembl.
DR GO; GO:0006930; P:substrate-dependent cell migration, cell extension; NAS:UniProtKB.
DR GO; GO:0007268; P:synaptic transmission; NAS:UniProtKB.
DR InterPro; IPR001478; PDZ.
DR Pfam; PF00595; PDZ; 2.
DR SMART; SM00228; PDZ; 2.
DR SUPFAM; SSF50156; SSF50156; 2.
DR PROSITE; PS50106; PDZ; 2.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Cell junction;
KW Cell membrane; Complete proteome; Cytoplasm; Cytoskeleton;
KW Direct protein sequencing; Endoplasmic reticulum; Membrane; Nucleus;
KW Phosphoprotein; Polymorphism; Reference proteome; Repeat.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 298 Syntenin-1.
FT /FTId=PRO_0000184001.
FT DOMAIN 114 193 PDZ 1.
FT DOMAIN 198 273 PDZ 2.
FT MOD_RES 2 2 N-acetylserine.
FT VAR_SEQ 12 17 Missing (in isoform 3).
FT /FTId=VSP_038374.
FT VAR_SEQ 81 81 Missing (in isoform 2).
FT /FTId=VSP_038375.
FT VARIANT 26 26 P -> T (in dbSNP:rs11550282).
FT /FTId=VAR_053699.
FT VARIANT 69 69 N -> S (in dbSNP:rs1127509).
FT /FTId=VAR_013160.
FT CONFLICT 62 62 N -> S (in Ref. 2; AAB51246).
FT STRAND 113 118
FT STRAND 121 123
FT STRAND 126 132
FT STRAND 135 141
FT HELIX 146 149
FT STRAND 157 161
FT HELIX 171 180
FT STRAND 183 191
FT STRAND 197 202
FT STRAND 205 208
FT STRAND 211 214
FT STRAND 217 221
FT HELIX 226 230
FT STRAND 234 241
FT HELIX 251 260
FT STRAND 263 271
SQ SEQUENCE 298 AA; 32444 MW; 574E1349F86F949F CRC64;
MSLYPSLEDL KVDKVIQAQT AFSANPANPA ILSEASAPIP HDGNLYPRLY PELSQYMGLS
LNEEEIRANV AVVSGAPLQG QLVARPSSIN YMVAPVTGND VGIRRAEIKQ GIREVILCKD
QDGKIGLRLK SIDNGIFVQL VQANSPASLV GLRFGDQVLQ INGENCAGWS SDKAHKVLKQ
AFGEKITMTI RDRPFERTIT MHKDSTGHVG FIFKNGKITS IVKDSSAARN GLLTEHNICE
INGQNVIGLK DSQIADILST SGTVVTITIM PAFIFEHIIK RMAPSIMKSL MDHTIPEV
//
MIM
602217
*RECORD*
*FIELD* NO
602217
*FIELD* TI
*602217 SYNDECAN-BINDING PROTEIN; SDCBP
;;SYNTENIN;;
PRO-TGF-ALPHA CYTOPLASMIC DOMAIN-INTERACTING PROTEIN 18; TACIP18;;
read moreMELANOMA DIFFERENTIATION-ASSOCIATED GENE 9; MDA9
*FIELD* TX
CLONING
The syndecans (e.g., SDC1; 186355) are transmembrane proteoglycans that
place structurally heterogeneous heparan sulfate chains at the cell
surface and a highly conserved polypeptide in the cytoplasm. Versatile
heparan sulfate moieties support various processes of molecular
recognition, signaling, and trafficking. Grootjans et al. (1997)
reported the identification of a protein that binds to the cytoplasmic
domains of the syndecans in yeast 2-hybrid screens and other assays.
This protein, designated syntenin, contains a tandem repeat of PDZ
domains that reacts with the FYA (phe-tyr-ala) C-terminal amino acid
sequence of the syndecans. Proteins produced by fusion of green
fluorescent protein and syntenin colocalized to plasma membranes and
intracellular vesicles with syndecans. Cells that overexpress the fusion
protein showed numerous cell surface extensions, suggesting effects of
syntenin on cytoskeleton-membrane organization. Grootjans et al. (1997)
proposed that syntenin may function as an adaptor that couples syndecans
to cytoskeletal proteins or cytosolic downstream signal-effectors.
Fernandez-Larrea et al. (1999) used the 2-hybrid screen to identify
pro-TGF-alpha (190170) cytoplasmic domain-binding proteins, which they
referred to as TACIPs (pro-TGF-alpha cytoplasmic domain-interacting
proteins), involved in the trafficking of pro-TGF-alpha. They cloned 2
such proteins, TACIP1 and TACIP18, both of which showed a lack of
interaction with a pro-TGF-alpha C-terminal mutant that does not reach
the cell surface. TACIP1 and TACP18 are identical to the PDZ proteins
alpha-1-syntrophin (601017) and syntenin, respectively. Fernandez-Larrea
et al. (1999) noted that TACIP18/syntenin had also been identified as
melanoma differentiation-associated gene-9, or MDA9, by Lin et al.
(1998).
GENE FUNCTION
PDZ domains are known to bind to the C terminus of a variety of
transmembrane proteins. Accordingly, Fernandez-Larrea et al. (1999)
demonstrated that the PDZ domains of TACIP1 and TACIP18 are responsible
for the interaction with the cytoplasmic domain of pro-TGF-alpha.
Analysis of a panel of pro-TGF-alpha C-terminal mutants showed that
mutations that prevented the binding to TACIP1, but not to TACIP18, did
not disrupt the transport of pro-TGF-alpha to the cell surface in vivo.
Furthermore, the cytoplasmic domain of syndecan-2 (142460), which is
also known to bind TACIP18, efficiently replaces that of pro-TGF-alpha,
since pro-TGF-alpha/syndecan chimeric molecules were transported to the
cell surface with normal kinetics. Mutations that prevented the binding
of TACIP18 to the cytoplasmic domain of syndecans also interfered with
the normal trafficking of pro-TGF-alpha/syndecan chimeras, further
supporting a role for TACIP18 in the trafficking of pro-TGF-alpha.
Unlike the majority of PDZ proteins, which localize near the plasma
membrane, TACIP18 localizes early in the secretory pathway. In vivo,
TACIP18 specifically interacted with immature pro-TGF-alpha in a
perinuclear area that colocalizes with endoplasmic reticulum markers.
The interleukin-5 (IL5; 147850) receptor consists of the IL5-specific
alpha subunit (IL5RA; 147851) and the signal-transducing beta-subunit,
CFS2RB (138981), which is shared with IL3 (147740) and GMCSF (138960).
Using a yeast 2-hybrid screen of a granulocyte cDNA library with the
cytoplasmic domain of IL5RA as bait, Geijsen et al. (2001) identified an
interaction of IL5RA with syntenin. GST pull-down, BIAcore,
coimmunoprecipitation, and deletion mutant analyses confirmed an
association of syntenin with the last 15 C-terminal residues of IL5RA;
syntenin did not interact with CFS2RB. Within this 15-residue stretch of
IL5RA, the C-terminal phenylalanine is critical. Deletion of either of
the 2 tandem PDZ domains of syntenin, which are known to interact with
C-terminal peptide sequences, abrogated the IL5RA-syntenin interaction.
A second 2-hybrid screen identified the mouse transcriptional factor
Sox4 (184430) as a binding partner for syntenin but not for IL5RA. The
syntenin-Sox4 interaction occurs outside of the PDZ domains of syntenin.
Luciferase reporter analysis and fluorescence microscopy showed that
IL5, but not IL3, induces cytoplasmic and nuclear expression of syntenin
and, in a syntenin- and cytoplasmic IL5RA-dependent manner, of Sox4.
Geijsen et al. (2001) concluded that syntenin acts as an adaptor
molecule in the IL5RA-mediated activation of SOX4. They also noted that
mice lacking either Il5ra or Sox4 have defects in B-cell development.
Zimmermann et al. (2002) showed that the PDZ domains of several proteins
bind phosphatidylinositol 4,5-bisphosphate (PIP2). High-affinity binding
of syntenin to PIP2-containing lipid layers required both of its PDZ
domains. Competition and mutagenesis experiments revealed that the
protein- and the PIP2-binding sites in the PDZ domains overlap. Overlay
assays indicated that the 2 PDZ domains of syntenin cooperate in binding
to cognate peptides and PIP2. Experiments on living cells demonstrated
PIP2-dependent and peptide-dependent modes of plasma membrane
association of the PDZ domains of syntenin. These observations suggested
that local changes in phosphoinositide concentration control the
association of PDZ proteins with their target receptors at the plasma
membrane.
*FIELD* RF
1. Fernandez-Larrea, J.; Merlos-Suarez, A.; Urena, J. M.; Baselga,
J.; Arribas, J.: A role for a PDZ protein in the early secretory
pathway for the targeting of proTGF-alpha to the cell surface. Molec.
Cell 3: 423-433, 1999.
2. Geijsen, N.; Uings, I. J.; Pals, C.; Armstrong, J.; McKinnon, M.;
Raaijmakers, J. A. M.; Lammers, J.-W. J.; Koenderman, L.; Coffer,
P. J.: Cytokine-specific transcriptional regulation through an IL-5R-alpha
interacting protein. Science 293: 1136-1138, 2001.
3. Grootjans, J. J.; Zimmermann, P.; Reekmans, G.; Smets, A.; Degeest,
G.; Durr, J.; David, G.: Syntenin, a PDZ protein that binds syndecan
cytoplasmic domains. Proc. Nat. Acad. Sci. 94: 13683-13688, 1997.
4. Lin, J. J.; Jiang, H.; Fisher, P. B.: Melanoma differentiation
associated gene-9, mda-9, is a human gamma interferon responsive gene. Gene 207:
105-110, 1998.
5. Zimmermann, P.; Meerschaert, K.; Reekmans, G.; Leenaerts, I.; Small,
J. V.; Vandekerckhove, J.; David, G.; Gettermans, J.: PIP2-PDZ domain
binding controls the association of syntenin with the plasma membrane. Molec.
Cell 9: 1215-1225, 2002.
*FIELD* CN
Stylianos E. Antonarakis - updated: 9/18/2002
Paul J. Converse - updated: 8/16/2001
Stylianos E. Antonarakis - updated: 7/2/1999
*FIELD* CD
Victor A. McKusick: 12/23/1997
*FIELD* ED
mgross: 09/18/2002
mgross: 9/18/2002
mgross: 8/16/2001
psherman: 7/19/1999
mgross: 7/9/1999
kayiaros: 7/2/1999
alopez: 7/7/1998
alopez: 2/13/1998
alopez: 1/13/1998
dholmes: 12/24/1997
*RECORD*
*FIELD* NO
602217
*FIELD* TI
*602217 SYNDECAN-BINDING PROTEIN; SDCBP
;;SYNTENIN;;
PRO-TGF-ALPHA CYTOPLASMIC DOMAIN-INTERACTING PROTEIN 18; TACIP18;;
read moreMELANOMA DIFFERENTIATION-ASSOCIATED GENE 9; MDA9
*FIELD* TX
CLONING
The syndecans (e.g., SDC1; 186355) are transmembrane proteoglycans that
place structurally heterogeneous heparan sulfate chains at the cell
surface and a highly conserved polypeptide in the cytoplasm. Versatile
heparan sulfate moieties support various processes of molecular
recognition, signaling, and trafficking. Grootjans et al. (1997)
reported the identification of a protein that binds to the cytoplasmic
domains of the syndecans in yeast 2-hybrid screens and other assays.
This protein, designated syntenin, contains a tandem repeat of PDZ
domains that reacts with the FYA (phe-tyr-ala) C-terminal amino acid
sequence of the syndecans. Proteins produced by fusion of green
fluorescent protein and syntenin colocalized to plasma membranes and
intracellular vesicles with syndecans. Cells that overexpress the fusion
protein showed numerous cell surface extensions, suggesting effects of
syntenin on cytoskeleton-membrane organization. Grootjans et al. (1997)
proposed that syntenin may function as an adaptor that couples syndecans
to cytoskeletal proteins or cytosolic downstream signal-effectors.
Fernandez-Larrea et al. (1999) used the 2-hybrid screen to identify
pro-TGF-alpha (190170) cytoplasmic domain-binding proteins, which they
referred to as TACIPs (pro-TGF-alpha cytoplasmic domain-interacting
proteins), involved in the trafficking of pro-TGF-alpha. They cloned 2
such proteins, TACIP1 and TACIP18, both of which showed a lack of
interaction with a pro-TGF-alpha C-terminal mutant that does not reach
the cell surface. TACIP1 and TACP18 are identical to the PDZ proteins
alpha-1-syntrophin (601017) and syntenin, respectively. Fernandez-Larrea
et al. (1999) noted that TACIP18/syntenin had also been identified as
melanoma differentiation-associated gene-9, or MDA9, by Lin et al.
(1998).
GENE FUNCTION
PDZ domains are known to bind to the C terminus of a variety of
transmembrane proteins. Accordingly, Fernandez-Larrea et al. (1999)
demonstrated that the PDZ domains of TACIP1 and TACIP18 are responsible
for the interaction with the cytoplasmic domain of pro-TGF-alpha.
Analysis of a panel of pro-TGF-alpha C-terminal mutants showed that
mutations that prevented the binding to TACIP1, but not to TACIP18, did
not disrupt the transport of pro-TGF-alpha to the cell surface in vivo.
Furthermore, the cytoplasmic domain of syndecan-2 (142460), which is
also known to bind TACIP18, efficiently replaces that of pro-TGF-alpha,
since pro-TGF-alpha/syndecan chimeric molecules were transported to the
cell surface with normal kinetics. Mutations that prevented the binding
of TACIP18 to the cytoplasmic domain of syndecans also interfered with
the normal trafficking of pro-TGF-alpha/syndecan chimeras, further
supporting a role for TACIP18 in the trafficking of pro-TGF-alpha.
Unlike the majority of PDZ proteins, which localize near the plasma
membrane, TACIP18 localizes early in the secretory pathway. In vivo,
TACIP18 specifically interacted with immature pro-TGF-alpha in a
perinuclear area that colocalizes with endoplasmic reticulum markers.
The interleukin-5 (IL5; 147850) receptor consists of the IL5-specific
alpha subunit (IL5RA; 147851) and the signal-transducing beta-subunit,
CFS2RB (138981), which is shared with IL3 (147740) and GMCSF (138960).
Using a yeast 2-hybrid screen of a granulocyte cDNA library with the
cytoplasmic domain of IL5RA as bait, Geijsen et al. (2001) identified an
interaction of IL5RA with syntenin. GST pull-down, BIAcore,
coimmunoprecipitation, and deletion mutant analyses confirmed an
association of syntenin with the last 15 C-terminal residues of IL5RA;
syntenin did not interact with CFS2RB. Within this 15-residue stretch of
IL5RA, the C-terminal phenylalanine is critical. Deletion of either of
the 2 tandem PDZ domains of syntenin, which are known to interact with
C-terminal peptide sequences, abrogated the IL5RA-syntenin interaction.
A second 2-hybrid screen identified the mouse transcriptional factor
Sox4 (184430) as a binding partner for syntenin but not for IL5RA. The
syntenin-Sox4 interaction occurs outside of the PDZ domains of syntenin.
Luciferase reporter analysis and fluorescence microscopy showed that
IL5, but not IL3, induces cytoplasmic and nuclear expression of syntenin
and, in a syntenin- and cytoplasmic IL5RA-dependent manner, of Sox4.
Geijsen et al. (2001) concluded that syntenin acts as an adaptor
molecule in the IL5RA-mediated activation of SOX4. They also noted that
mice lacking either Il5ra or Sox4 have defects in B-cell development.
Zimmermann et al. (2002) showed that the PDZ domains of several proteins
bind phosphatidylinositol 4,5-bisphosphate (PIP2). High-affinity binding
of syntenin to PIP2-containing lipid layers required both of its PDZ
domains. Competition and mutagenesis experiments revealed that the
protein- and the PIP2-binding sites in the PDZ domains overlap. Overlay
assays indicated that the 2 PDZ domains of syntenin cooperate in binding
to cognate peptides and PIP2. Experiments on living cells demonstrated
PIP2-dependent and peptide-dependent modes of plasma membrane
association of the PDZ domains of syntenin. These observations suggested
that local changes in phosphoinositide concentration control the
association of PDZ proteins with their target receptors at the plasma
membrane.
*FIELD* RF
1. Fernandez-Larrea, J.; Merlos-Suarez, A.; Urena, J. M.; Baselga,
J.; Arribas, J.: A role for a PDZ protein in the early secretory
pathway for the targeting of proTGF-alpha to the cell surface. Molec.
Cell 3: 423-433, 1999.
2. Geijsen, N.; Uings, I. J.; Pals, C.; Armstrong, J.; McKinnon, M.;
Raaijmakers, J. A. M.; Lammers, J.-W. J.; Koenderman, L.; Coffer,
P. J.: Cytokine-specific transcriptional regulation through an IL-5R-alpha
interacting protein. Science 293: 1136-1138, 2001.
3. Grootjans, J. J.; Zimmermann, P.; Reekmans, G.; Smets, A.; Degeest,
G.; Durr, J.; David, G.: Syntenin, a PDZ protein that binds syndecan
cytoplasmic domains. Proc. Nat. Acad. Sci. 94: 13683-13688, 1997.
4. Lin, J. J.; Jiang, H.; Fisher, P. B.: Melanoma differentiation
associated gene-9, mda-9, is a human gamma interferon responsive gene. Gene 207:
105-110, 1998.
5. Zimmermann, P.; Meerschaert, K.; Reekmans, G.; Leenaerts, I.; Small,
J. V.; Vandekerckhove, J.; David, G.; Gettermans, J.: PIP2-PDZ domain
binding controls the association of syntenin with the plasma membrane. Molec.
Cell 9: 1215-1225, 2002.
*FIELD* CN
Stylianos E. Antonarakis - updated: 9/18/2002
Paul J. Converse - updated: 8/16/2001
Stylianos E. Antonarakis - updated: 7/2/1999
*FIELD* CD
Victor A. McKusick: 12/23/1997
*FIELD* ED
mgross: 09/18/2002
mgross: 9/18/2002
mgross: 8/16/2001
psherman: 7/19/1999
mgross: 7/9/1999
kayiaros: 7/2/1999
alopez: 7/7/1998
alopez: 2/13/1998
alopez: 1/13/1998
dholmes: 12/24/1997