P31431 (SDC4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Syndecan-4
Short name=SYND4

Alternative name(s):
Amphiglycan
Ryudocan core protein

Gene names

Name:

SDC4

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	198 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Cell surface proteoglycan that bears heparan sulfate.
Subunit structure	Homodimer. Interacts (via its cytoplasmic domain) with GIPC (via its PDZ domain). Interacts (via its cytoplasmic domain) with NUDT16L1 By similarity. Interacts with CDCP1 and SDCBP. Ref.8
Subcellular location	Membrane; Single-pass type I membrane protein. Secreted. Note: Shedding of the ectodomain produces a soluble form By similarity.
Tissue specificity	Expressed in epithelial and fibroblastic cells. Ref.1
Post-translational modification	Shedding is enhanced by a number of factors such as heparanase, thrombin or EGF. Also by stress and wound healing. PMA-mediated shedding is inhibited by TIMP3.
Sequence similarities	Belongs to the syndecan proteoglycan family.

Ontologies

Keywords
Cellular component	Membrane Secreted
Coding sequence diversity	Polymorphism
Domain	Signal Transmembrane Transmembrane helix
PTM	Glycoprotein Heparan sulfate Phosphoprotein Proteoglycan
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Cellular component	extracellular region Inferred from electronic annotation. Source: UniProtKB-SubCell integral to plasma membrane Non-traceable author statement Ref.1. Source: UniProtKB
Molecular function	cytoskeletal protein binding Inferred from electronic annotation. Source: InterPro thrombospondin receptor activity Inferred from mutant phenotype. Source: BHF-UCL
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 18

18

Potential

Chain

19 – 198

180

Syndecan-4

PRO_0000033511

Regions

Topological domain

19 – 145

127

Extracellular Potential

Transmembrane

146 – 170

25

Helical; Potential

Topological domain

171 – 198

28

Cytoplasmic Potential

Amino acid modifications

Modified residue

197

1

Phosphotyrosine Ref.9 Ref.10 Ref.11

Glycosylation

39

1

O-linked (Xyl...) (heparan sulfate) By similarity

Glycosylation

61

1

O-linked (Xyl...) (heparan sulfate) Potential

Glycosylation

63

1

O-linked (Xyl...) (heparan sulfate) Potential

Natural variations

Natural variant

12

1

F → L. Ref.1 Ref.4
Corresponds to variant rs4458268 [ dbSNP | Ensembl ].

VAR_021851

Secondary structure

1

.

.

198

Helix Strand Turn

Details...

Beta strand

196 – 198

3

Sequences

	Sequence		Length	Mass (Da)
	P31431 [UniParc]. Last modified July 15, 1998. Version 2. Checksum: 8229AA2733F77A10	FASTA	198	21,642
	10 20 30 40 50 60 MAPARLFALL LFFVGGVAES IRETEVIDPQ DLLEGRYFSG ALPDDEDVVG PGQESDDFEL 70 80 90 100 110 120 SGSGDLDDLE DSMIGPEVVH PLVPLDNHIP ERAGSGSQVP TEPKKLEENE VIPKRISPVE 130 140 150 160 170 180 ESEDVSNKVS MSSTVQGSNI FERTEVLAAL IVGGIVGILF AVFLILLLMY RMKKKDEGSY 190 DLGKKPIYKK APTNEFYA

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular cloning of amphiglycan, a novel integral membrane heparan sulfate proteoglycan expressed by epithelial and fibroblastic cells." David G., van der Schueren B., Marynen P., Cassiman J.-J., van den Berghe H. J. Cell Biol. 118:961-969(1992) [PubMed: 1500433] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, VARIANT LEU-12. Tissue: Lung fibroblast.
[2]	"Human ryudocan core protein: molecular cloning and characterization of the cDNA, and chromosomal localization of the gene." Kojima T., Inazawa J., Takamatsu J., Rosenberg R.D., Saito H. Biochem. Biophys. Res. Commun. 190:814-822(1993) [PubMed: 7916598] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	"Structural organization and promoter activity of the human ryudocan gene." Takagi A., Kojima T., Tsuzuki S., Katsumi A., Yamazaki T., Sugiura I., Hamaguchi M., Saito H. J. Biochem. 119:979-984(1996) [PubMed: 8797100] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Tissue: Placenta.
[4]	Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S. Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT LEU-12. Tissue: Stomach.
[5]	"The DNA sequence and comparative analysis of human chromosome 20." Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R., Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L., Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P., Bird C.P., Blakey S.E. , Bridgeman A.M., Brown A.J., Buck D., Burrill W.D., Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G., Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E., Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D., Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P., Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E., Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J., Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D., Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S., Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D., Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A., Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T., Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I., Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M., Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D., Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M., Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A., Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L., Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L., Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J. Nature 414:865-871(2001) [PubMed: 11780052] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Lung.
[7]	"Regulated shedding of syndecan-1 and -4 ectodomains by thrombin and growth factor receptor activation." Subramanian S.V., Fitzgerald M.L., Bernfield M. J. Biol. Chem. 272:14713-14720(1997) [PubMed: 9169435] [Abstract] Cited for: SHEDDING.
[8]	"Adhesion signaling by a novel mitotic substrate of src kinases." Bhatt A.S., Erdjument-Bromage H., Tempst P., Craik C.S., Moasser M.M. Oncogene 24:5333-5343(2005) [PubMed: 16007225] [Abstract] Cited for: INTERACTION WITH CDCP1.
[9]	"Global survey of phosphotyrosine signaling identifies oncogenic kinases in lung cancer." Rikova K., Guo A., Zeng Q., Possemato A., Yu J., Haack H., Nardone J., Lee K., Reeves C., Li Y., Hu Y., Tan Z., Stokes M., Sullivan L., Mitchell J., Wetzel R., Macneill J., Ren J.M. , Yuan J., Bakalarski C.E., Villen J., Kornhauser J.M., Smith B., Li D., Zhou X., Gygi S.P., Gu T.-L., Polakiewicz R.D., Rush J., Comb M.J. Cell 131:1190-1203(2007) [PubMed: 18083107] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-197, MASS SPECTROMETRY. Tissue: Lung carcinoma.
[10]	"Multiple reaction monitoring for robust quantitative proteomic analysis of cellular signaling networks." Wolf-Yadlin A., Hautaniemi S., Lauffenburger D.A., White F.M. Proc. Natl. Acad. Sci. U.S.A. 104:5860-5865(2007) [PubMed: 17389395] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-197, MASS SPECTROMETRY. Tissue: Mammary epithelium.
[11]	"An extensive survey of tyrosine phosphorylation revealing new sites in human mammary epithelial cells." Heibeck T.H., Ding S.-J., Opresko L.K., Zhao R., Schepmoes A.A., Yang F., Tolmachev A.V., Monroe M.E., Camp D.G. II, Smith R.D., Wiley H.S., Qian W.-J. J. Proteome Res. 8:3852-3861(2009) [PubMed: 19534553] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-197, MASS SPECTROMETRY. Tissue: Mammary epithelium.
[12]	"Solution structure of the dimeric cytoplasmic domain of syndecan-4." Shin J., Lee W., Lee D., Koo B.-K., Han I., Lim Y., Woods A., Couchman J.R., Oh E.-S. Biochemistry 40:8471-8478(2001) [PubMed: 11456484] [Abstract] Cited for: STRUCTURE BY NMR OF 171-198.
[13]	"Molecular roots of degenerate specificity in syntenin's PDZ2 domain: reassessment of the PDZ recognition paradigm." Kang B.S., Cooper D.R., Devedjiev Y., Derewenda U., Derewenda Z.S. Structure 11:845-853(2003) [PubMed: 12842047] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS) OF 193-198 IN COMPLEX WITH SDCBP.
[14]	"The binding of the PDZ tandem of syntenin to target proteins." Grembecka J., Cierpicki T., Devedjiev Y., Derewenda U., Kang B.S., Bushweller J.H., Derewenda Z.S. Biochemistry 45:3674-3683(2006) [PubMed: 16533050] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 182-198 IN COMPLEX WITH SDCBP.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

X67016 mRNA. Translation: CAA47406.1.
D13292 mRNA. Translation: BAA02550.1.
D79206 Genomic DNA. Translation: BAA19613.1.
AK222695 mRNA. Translation: BAD96415.1.
AK223243 mRNA. Translation: BAD96963.1.
AL021578 Genomic DNA. Translation: CAA16520.1.
BC030805 mRNA. Translation: AAH30805.1.

IPI

IPI00011564.

PIR

JC1457.

RefSeq

NP_002990.2. NM_002999.3.

UniGene

Hs.632267.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1EJP	NMR	-	A/B	171-198	[»]
1EJQ	NMR	-	A/B	171-198	[»]
1OBY	X-ray	1.85	P/Q	193-198	[»]
1YBO	X-ray	2.30	C/D	182-198	[»]

ProteinModelPortal

P31431.

SMR

P31431. Positions 171-198.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-29945N.

IntAct

P31431. 2 interactions.

MINT

MINT-140673.

STRING

P31431.

Protein family/group databases

TCDB

9.A.35.1.1. peptide translocating syndecan family.

PTM databases

PhosphoSite

P31431.

Polymorphism databases

DMDM

2851418.

Proteomic databases

PRIDE

P31431.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000372733; ENSP00000361818; ENSG00000124145.

GeneID

6385.

KEGG

hsa:6385.

UCSC

uc002xnu.1. human.

Organism-specific databases

CTD

6385.

GeneCards

GC20M043953.

H-InvDB

HIX0015856.

HGNC

HGNC:10661. SDC4.

HPA

CAB013240.
HPA005716.

MIM

600017. gene.

neXtProt

NX_P31431.

PharmGKB

PA35591.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG05282.

HOGENOM

HBG278903.

HOVERGEN

HBG004501.

InParanoid

P31431.

OMA

NHIPERA.

OrthoDB

EOG4MSD0Z.

PhylomeDB

P31431.

Enzyme and pathway databases

Pathway_Interaction_DB

syndecan_pathway. Proteogylcan syndecan-mediated signaling events.
syndecan_4_pathway. Syndecan-4-mediated signaling events.

Gene expression databases

ArrayExpress

P31431.

Bgee

P31431.

CleanEx

HS_SDC4.

Genevestigator

P31431.

GermOnline

ENSG00000124145. Homo sapiens.

Family and domain databases

InterPro

IPR003585. Neurexin-like.
IPR001050. Syndecan.
[Graphical view]

KO

K06257.

PANTHER

PTHR10915. Syndecan. 1 hit.

Pfam

PF01034. Syndecan. 1 hit.
[Graphical view]

SMART

SM00294. 4.1m. 1 hit.
[Graphical view]

PROSITE

PS00964. SYNDECAN. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

NextBio

24792.

PMAP-CutDB

P31431.

SOURCE

Search...

Entry information

Entry name

SDC4_HUMAN

Accession

Primary (citable) accession number: P31431
Secondary accession number(s): O00773, Q16833, Q53FN9

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 1, 1993
Last sequence update:	July 15, 1998
Last modified:	January 25, 2012
This is version 122 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.