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) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › 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.14
Subcellular location	Isoform 1: Membrane; Single-pass type I membrane protein. Secreted Ref.13. Note: Shedding of the ectodomain produces a soluble form By similarity. Ref.13 Isoform 2: Secreted Ref.13.
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	Alternative splicing Polymorphism
Domain	Signal Transmembrane Transmembrane helix
PTM	Glycoprotein Heparan sulfate Proteoglycan
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	carbohydrate metabolic process Traceable author statement. Source: Reactome chondroitin sulfate metabolic process Traceable author statement. Source: Reactome glycosaminoglycan biosynthetic process Traceable author statement. Source: Reactome glycosaminoglycan catabolic process Traceable author statement. Source: Reactome positive regulation of focal adhesion assembly Inferred from electronic annotation. Source: Compara positive regulation of protein kinase activity Inferred from electronic annotation. Source: Compara positive regulation of stress fiber assembly Inferred from electronic annotation. Source: Compara ureteric bud development Inferred from electronic annotation. Source: Compara
Cellular_component	Golgi lumen Traceable author statement. Source: Reactome cell surface Inferred from electronic annotation. Source: Compara costamere Inferred from electronic annotation. Source: Compara extracellular region Inferred from electronic annotation. Source: UniProtKB-SubCell focal adhesion Inferred from electronic annotation. Source: Compara integral to plasma membrane Non-traceable author statement Ref.1. Source: UniProtKB lysosomal lumen Traceable author statement. Source: Reactome membrane raft Inferred from electronic annotation. Source: Compara
Molecular_function	thrombospondin receptor activity Inferred from mutant phenotype PubMed 17879962. Source: BHF-UCL
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
PRKCA	P17252	2	EBI-3913237,EBI-1383528

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P31431-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: P31431-2)

The sequence of this isoform differs from the canonical sequence as follows:
     149-198: ALIVGGIVGILFAVFLILLLMYRMKKKDEGSYDLGKKPIYKKAPTNEFYA → GCPEH

Note: Soluble form, lacks the transmembrane domain.

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

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

Alternative sequence

149 – 198

50

ALIVG…NEFYA → GCPEH in isoform 2.

VSP_044449

Natural variant

12

1

F → L. Ref.1 Ref.6
Corresponds to variant rs4458268 [ dbSNP | Ensembl ].

VAR_021851

Secondary structure

1

.

.

.

.

198

Helix Strand Turn

Details...

Beta strand

192 – 194

3

Beta strand

196 – 198

3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [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
	Isoform 2 [UniParc]. Checksum: 25AD50751A7D2642	FASTA	153	16,545
	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 ESEDVSNKVS MSSTVQGSNI FERTEVLAGC PEH

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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), 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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Tissue: Placenta.
[4]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Thalamus.
[5]	"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)." Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B. Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[6]	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] (ISOFORM 1), VARIANT LEU-12. Tissue: Stomach.
[7]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]	Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[9]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Lung.
[10]	"The WashU-Merck EST project." Hillier L., Clark N., Dubuque T., Elliston K., Hawkins M., Holman M., Hultman M., Kucaba T., Le M., Lennon G., Marra M., Parsons J., Rifkin L., Rohlfing T., Soares M., Tan F., Trevaskis E., Waterston R. , Williamson A., Wohldmann P., Wilson R. Submitted (MAR-2000) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 75-153 (ISOFORM 2).
[11]	"Generation and analysis of 280,000 human expressed sequence tags." Hillier L.D., Lennon G., Becker M., Bonaldo M.F., Chiapelli B., Chissoe S., Dietrich N., DuBuque T., Favello A., Gish W., Hawkins M., Hultman M., Kucaba T., Lacy M., Le M., Le N., Mardis E., Moore B. , Morris M., Parsons J., Prange C., Rifkin L., Rohlfing T., Schellenberg K., Bento Soares M., Tan F., Thierry-Meg J., Trevaskis E., Underwood K., Wohldman P., Waterston R., Wilson R., Marra M. Genome Res. 6:807-828(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 125-153 (ISOFORM 2). Tissue: Uterus.
[12]	"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] [Europe PMC] [Abstract] Cited for: SHEDDING.
[13]	"Widespread production of novel soluble protein isoforms by alternative splicing removal of transmembrane anchoring domains." Xing Y., Xu Q., Lee C. FEBS Lett. 555:572-578(2003) [PubMed] [Europe PMC] [Abstract] Cited for: ALTERNATIVE SPLICING (ISOFORM 2), SUBCELLULAR LOCATION.
[14]	"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] [Europe PMC] [Abstract] Cited for: INTERACTION WITH CDCP1.
[15]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[16]	"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] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR OF 171-198.
[17]	"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] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS) OF 193-198 IN COMPLEX WITH SDCBP.
[18]	"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] [Europe PMC] [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.
AK312507 mRNA. Translation: BAG35408.1.
CR542045 mRNA. Translation: CAG46842.1.
CR542074 mRNA. Translation: CAG46871.1.
AK222695 mRNA. Translation: BAD96415.1.
AK223243 mRNA. Translation: BAD96963.1.
AL021578 Genomic DNA. Translation: CAA16520.1.
CH471077 Genomic DNA. Translation: EAW75861.1.
CH471077 Genomic DNA. Translation: EAW75862.1.
BC030805 mRNA. Translation: AAH30805.1.
AA151028 mRNA. No translation available.
AA258502 mRNA. No translation available.

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.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-29945N.

IntAct

P31431. 3 interactions.

MINT

MINT-140673.

STRING

9606.ENSP00000361818.

Protein family/group databases

TCDB

9.A.35.1.1. peptide translocating syndecan family.

PTM databases

PhosphoSite

P31431.

Polymorphism databases

DMDM

2851418.

Proteomic databases

PaxDb

P31431.

PRIDE

P31431.

Protocols and materials databases

DNASU

6385.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000372733; ENSP00000361818; ENSG00000124145.

GeneID

6385.

KEGG

hsa:6385.

UCSC

uc002xnu.3. human.

Organism-specific databases

CTD

6385.

GeneCards

GC20M043953.

HGNC

HGNC:10661. SDC4.

HPA

CAB013240.
HPA005716.

MIM

600017. gene.

neXtProt

NX_P31431.

PharmGKB

PA35591.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG83582.

HOGENOM

HOG000263414.

HOVERGEN

HBG004501.

InParanoid

P31431.

KO

K16338.

OMA

EGRYFSG.

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.

Reactome

REACT_111217. Metabolism.
REACT_116125. Disease.

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]

PANTHER

PTHR10915. PTHR10915. 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

ChiTaRS

SDC4. human.

EvolutionaryTrace

P31431.

GenomeRNAi

6385.

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, Q6FGN3

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 1, 1993
Last sequence update:	July 15, 1998
Last modified:	May 1, 2013
This is version 136 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.