ID   SDC4_HUMAN              Reviewed;         198 AA.
AC   P31431; O00773; Q16833; Q53FN9;
DT   01-JUL-1993, integrated into UniProtKB/Swiss-Prot.
DT   15-JUL-1998, sequence version 2.
DT   25-JAN-2012, entry version 122.
DE   RecName: Full=Syndecan-4;
DE            Short=SYND4;
DE   AltName: Full=Amphiglycan;
DE   AltName: Full=Ryudocan core protein;
DE   Flags: Precursor;
GN   Name=SDC4;
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], TISSUE SPECIFICITY, AND VARIANT LEU-12.
RC   TISSUE=Lung fibroblast;
RX   MEDLINE=92363936; PubMed=1500433; DOI=10.1083/jcb.118.4.961;
RA   David G., van der Schueren B., Marynen P., Cassiman J.-J.,
RA   van den Berghe H.;
RT   "Molecular cloning of amphiglycan, a novel integral membrane heparan
RT   sulfate proteoglycan expressed by epithelial and fibroblastic cells.";
RL   J. Cell Biol. 118:961-969(1992).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RX   MEDLINE=93176185; PubMed=7916598; DOI=10.1006/bbrc.1993.1122;
RA   Kojima T., Inazawa J., Takamatsu J., Rosenberg R.D., Saito H.;
RT   "Human ryudocan core protein: molecular cloning and characterization
RT   of the cDNA, and chromosomal localization of the gene.";
RL   Biochem. Biophys. Res. Commun. 190:814-822(1993).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC   TISSUE=Placenta;
RX   MEDLINE=96390006; PubMed=8797100;
RA   Takagi A., Kojima T., Tsuzuki S., Katsumi A., Yamazaki T., Sugiura I.,
RA   Hamaguchi M., Saito H.;
RT   "Structural organization and promoter activity of the human ryudocan
RT   gene.";
RL   J. Biochem. 119:979-984(1996).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT LEU-12.
RC   TISSUE=Stomach;
RA   Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y.,
RA   Tanaka A., Yokoyama S.;
RL   Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases.
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   MEDLINE=21638749; PubMed=11780052; DOI=10.1038/414865a;
RA   Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R.,
RA   Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L.,
RA   Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M.,
RA   Beasley O.P., Bird C.P., Blakey S.E., Bridgeman A.M., Brown A.J.,
RA   Buck D., Burrill W.D., Butler A.P., Carder C., Carter N.P.,
RA   Chapman J.C., Clamp M., Clark G., Clark L.N., Clark S.Y., Clee C.M.,
RA   Clegg S., Cobley V.E., Collier R.E., Connor R.E., Corby N.R.,
RA   Coulson A., Coville G.J., Deadman R., Dhami P.D., Dunn M.,
RA   Ellington A.G., Frankland J.A., Fraser A., French L., Garner P.,
RA   Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E.,
RA   Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J.,
RA   Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D.,
RA   Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S.,
RA   Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D.,
RA   Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A.,
RA   Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T.,
RA   Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I.,
RA   Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H.,
RA   Rice C.M., Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S.,
RA   Skuce C.D., Smith M.L., Soderlund C., Steward C.A., Sulston J.E.,
RA   Swann R.M., Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A.,
RA   Tracey A., Tromans A.C., Vaudin M., Wall M., Wallis J.M.,
RA   Whitehead S.L., Whittaker P., Willey D.L., Williams L., Williams S.A.,
RA   Wilming L., Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S.,
RA   Rogers J.;
RT   "The DNA sequence and comparative analysis of human chromosome 20.";
RL   Nature 414:865-871(2001).
RN   [6]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Lung;
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   [7]
RP   SHEDDING.
RX   PubMed=9169435; DOI=10.1074/jbc.272.23.14713;
RA   Subramanian S.V., Fitzgerald M.L., Bernfield M.;
RT   "Regulated shedding of syndecan-1 and -4 ectodomains by thrombin and
RT   growth factor receptor activation.";
RL   J. Biol. Chem. 272:14713-14720(1997).
RN   [8]
RP   INTERACTION WITH CDCP1.
RX   PubMed=16007225; DOI=10.1038/sj.onc.1208582;
RA   Bhatt A.S., Erdjument-Bromage H., Tempst P., Craik C.S., Moasser M.M.;
RT   "Adhesion signaling by a novel mitotic substrate of src kinases.";
RL   Oncogene 24:5333-5343(2005).
RN   [9]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-197, AND MASS
RP   SPECTROMETRY.
RC   TISSUE=Lung carcinoma;
RX   PubMed=18083107; DOI=10.1016/j.cell.2007.11.025;
RA   Rikova K., Guo A., Zeng Q., Possemato A., Yu J., Haack H., Nardone J.,
RA   Lee K., Reeves C., Li Y., Hu Y., Tan Z., Stokes M., Sullivan L.,
RA   Mitchell J., Wetzel R., Macneill J., Ren J.M., Yuan J.,
RA   Bakalarski C.E., Villen J., Kornhauser J.M., Smith B., Li D., Zhou X.,
RA   Gygi S.P., Gu T.-L., Polakiewicz R.D., Rush J., Comb M.J.;
RT   "Global survey of phosphotyrosine signaling identifies oncogenic
RT   kinases in lung cancer.";
RL   Cell 131:1190-1203(2007).
RN   [10]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-197, AND MASS
RP   SPECTROMETRY.
RC   TISSUE=Mammary epithelium;
RX   PubMed=17389395; DOI=10.1073/pnas.0608638104;
RA   Wolf-Yadlin A., Hautaniemi S., Lauffenburger D.A., White F.M.;
RT   "Multiple reaction monitoring for robust quantitative proteomic
RT   analysis of cellular signaling networks.";
RL   Proc. Natl. Acad. Sci. U.S.A. 104:5860-5865(2007).
RN   [11]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-197, AND MASS
RP   SPECTROMETRY.
RC   TISSUE=Mammary epithelium;
RX   PubMed=19534553; DOI=10.1021/pr900044c;
RA   Heibeck T.H., Ding S.-J., Opresko L.K., Zhao R., Schepmoes A.A.,
RA   Yang F., Tolmachev A.V., Monroe M.E., Camp D.G. II, Smith R.D.,
RA   Wiley H.S., Qian W.-J.;
RT   "An extensive survey of tyrosine phosphorylation revealing new sites
RT   in human mammary epithelial cells.";
RL   J. Proteome Res. 8:3852-3861(2009).
RN   [12]
RP   STRUCTURE BY NMR OF 171-198.
RX   MEDLINE=21349687; PubMed=11456484; DOI=10.1021/bi002750r;
RA   Shin J., Lee W., Lee D., Koo B.-K., Han I., Lim Y., Woods A.,
RA   Couchman J.R., Oh E.-S.;
RT   "Solution structure of the dimeric cytoplasmic domain of syndecan-4.";
RL   Biochemistry 40:8471-8478(2001).
RN   [13]
RP   X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS) OF 193-198 IN COMPLEX WITH
RP   SDCBP.
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   [14]
RP   X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 182-198 IN COMPLEX WITH
RP   SDCBP.
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: Cell surface proteoglycan that bears heparan sulfate.
CC   -!- SUBUNIT: Homodimer. Interacts (via its cytoplasmic domain) with
CC       GIPC (via its PDZ domain). Interacts (via its cytoplasmic domain)
CC       with NUDT16L1 (By similarity). Interacts with CDCP1 and SDCBP.
CC   -!- SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane
CC       protein. Secreted. Note=Shedding of the ectodomain produces a
CC       soluble form (By similarity).
CC   -!- TISSUE SPECIFICITY: Expressed in epithelial and fibroblastic
CC       cells.
CC   -!- PTM: Shedding is enhanced by a number of factors such as
CC       heparanase, thrombin or EGF. Also by stress and wound healing.
CC       PMA-mediated shedding is inhibited by TIMP3.
CC   -!- SIMILARITY: Belongs to the syndecan proteoglycan family.
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DR   EMBL; X67016; CAA47406.1; -; mRNA.
DR   EMBL; D13292; BAA02550.1; -; mRNA.
DR   EMBL; D79206; BAA19613.1; -; Genomic_DNA.
DR   EMBL; AK222695; BAD96415.1; -; mRNA.
DR   EMBL; AK223243; BAD96963.1; -; mRNA.
DR   EMBL; AL021578; CAA16520.1; -; Genomic_DNA.
DR   EMBL; BC030805; AAH30805.1; -; mRNA.
DR   IPI; IPI00011564; -.
DR   PIR; JC1457; JC1457.
DR   RefSeq; NP_002990.2; NM_002999.3.
DR   UniGene; Hs.632267; -.
DR   PDB; 1EJP; NMR; -; A/B=171-198.
DR   PDB; 1EJQ; NMR; -; A/B=171-198.
DR   PDB; 1OBY; X-ray; 1.85 A; P/Q=193-198.
DR   PDB; 1YBO; X-ray; 2.30 A; C/D=182-198.
DR   PDBsum; 1EJP; -.
DR   PDBsum; 1EJQ; -.
DR   PDBsum; 1OBY; -.
DR   PDBsum; 1YBO; -.
DR   ProteinModelPortal; P31431; -.
DR   SMR; P31431; 171-198.
DR   DIP; DIP-29945N; -.
DR   IntAct; P31431; 2.
DR   MINT; MINT-140673; -.
DR   STRING; P31431; -.
DR   TCDB; 9.A.35.1.1; peptide translocating syndecan family.
DR   PhosphoSite; P31431; -.
DR   DMDM; 2851418; -.
DR   PRIDE; P31431; -.
DR   Ensembl; ENST00000372733; ENSP00000361818; ENSG00000124145.
DR   GeneID; 6385; -.
DR   KEGG; hsa:6385; -.
DR   UCSC; uc002xnu.1; human.
DR   CTD; 6385; -.
DR   GeneCards; GC20M043953; -.
DR   H-InvDB; HIX0015856; -.
DR   HGNC; HGNC:10661; SDC4.
DR   HPA; CAB013240; -.
DR   HPA; HPA005716; -.
DR   MIM; 600017; gene.
DR   neXtProt; NX_P31431; -.
DR   PharmGKB; PA35591; -.
DR   eggNOG; prNOG05282; -.
DR   HOGENOM; HBG278903; -.
DR   HOVERGEN; HBG004501; -.
DR   InParanoid; P31431; -.
DR   OMA; NHIPERA; -.
DR   OrthoDB; EOG4MSD0Z; -.
DR   PhylomeDB; P31431; -.
DR   Pathway_Interaction_DB; syndecan_pathway; Proteogylcan syndecan-mediated signaling events.
DR   Pathway_Interaction_DB; syndecan_4_pathway; Syndecan-4-mediated signaling events.
DR   NextBio; 24792; -.
DR   PMAP-CutDB; P31431; -.
DR   ArrayExpress; P31431; -.
DR   Bgee; P31431; -.
DR   CleanEx; HS_SDC4; -.
DR   Genevestigator; P31431; -.
DR   GermOnline; ENSG00000124145; Homo sapiens.
DR   GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR   GO; GO:0005887; C:integral to plasma membrane; NAS:UniProtKB.
DR   GO; GO:0008092; F:cytoskeletal protein binding; IEA:InterPro.
DR   GO; GO:0070053; F:thrombospondin receptor activity; IMP:BHF-UCL.
DR   InterPro; IPR003585; Neurexin-like.
DR   InterPro; IPR001050; Syndecan.
DR   KO; K06257; -.
DR   PANTHER; PTHR10915; Syndecan; 1.
DR   Pfam; PF01034; Syndecan; 1.
DR   SMART; SM00294; 4.1m; 1.
DR   PROSITE; PS00964; SYNDECAN; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Complete proteome; Glycoprotein; Heparan sulfate;
KW   Membrane; Phosphoprotein; Polymorphism; Proteoglycan;
KW   Reference proteome; Secreted; Signal; Transmembrane;
KW   Transmembrane helix.
FT   SIGNAL        1     18       Potential.
FT   CHAIN        19    198       Syndecan-4.
FT                                /FTId=PRO_0000033511.
FT   TOPO_DOM     19    145       Extracellular (Potential).
FT   TRANSMEM    146    170       Helical; (Potential).
FT   TOPO_DOM    171    198       Cytoplasmic (Potential).
FT   MOD_RES     197    197       Phosphotyrosine.
FT   CARBOHYD     39     39       O-linked (Xyl...) (heparan sulfate) (By
FT                                similarity).
FT   CARBOHYD     61     61       O-linked (Xyl...) (heparan sulfate)
FT                                (Potential).
FT   CARBOHYD     63     63       O-linked (Xyl...) (heparan sulfate)
FT                                (Potential).
FT   VARIANT      12     12       F -> L (in dbSNP:rs4458268).
FT                                /FTId=VAR_021851.
FT   STRAND      196    198
SQ   SEQUENCE   198 AA;  21642 MW;  8229AA2733F77A10 CRC64;
     MAPARLFALL LFFVGGVAES IRETEVIDPQ DLLEGRYFSG ALPDDEDVVG PGQESDDFEL
     SGSGDLDDLE DSMIGPEVVH PLVPLDNHIP ERAGSGSQVP TEPKKLEENE VIPKRISPVE
     ESEDVSNKVS MSSTVQGSNI FERTEVLAAL IVGGIVGILF AVFLILLLMY RMKKKDEGSY
     DLGKKPIYKK APTNEFYA
//