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P35443 (TSP4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 142. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Thrombospondin-4
Gene names
Name:THBS4
Synonyms:TSP4
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length961 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Adhesive glycoprotein that mediates cell-to-cell and cell-to-matrix interactions and is involved in various processes including cellular proliferation, migration, adhesion and attachment, inflammatory response to CNS injury, regulation of vascular inflammation and adaptive responses of the heart to pressure overload and in myocardial function and remodeling. Binds to structural extracellular matrix (ECM) proteins and modulates the ECM in response to tissue damage, contributing to cardioprotective and adaptive ECM remodeling. Plays a role in ER stress response, via its interaction with the activating transcription factor 6 alpha (ATF6) which produces adaptive ER stress response factors and protects myocardium from pressure overload. May contribute to spinal presynaptic hypersensitivity and neuropathic pain states after peripheral nerve injury. May play a role in regulating protective astrogenesis from the subventricular zone (SVZ) niche after injury in a NOTCH1-dependent manner By similarity. Ref.6

Subunit structure

Homopentamer; disulfide-linked. Interacts with PTBP3. Interacts with NOTCH1 By similarity. Interacts (via EGF-like 3; calcium-binding domain) with ATF6 and facilitates its processing, activation and nuclear translocation. Ref.2 Ref.6 Ref.7

Subcellular location

Endoplasmic reticulum By similarity. Sarcoplasmic reticulum By similarity. Secreted. Secretedextracellular space By similarity. Secretedextracellular spaceextracellular matrix By similarity.

Sequence similarities

Belongs to the thrombospondin family.

Contains 4 EGF-like domains.

Contains 1 laminin G-like domain.

Contains 1 TSP C-terminal (TSPC) domain.

Contains 8 TSP type-3 repeats.

Ontologies

Keywords
   Biological processCell adhesion
Tissue remodeling
Unfolded protein response
   Cellular componentEndoplasmic reticulum
Extracellular matrix
Sarcoplasmic reticulum
Secreted
   Coding sequence diversityPolymorphism
   DomainEGF-like domain
Repeat
Signal
   LigandCalcium
   Molecular functionGrowth factor
Mitogen
   PTMDisulfide bond
Glycoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processbehavioral response to pain

Inferred from sequence or structural similarity. Source: UniProtKB

endothelial cell-cell adhesion

Inferred from direct assay PubMed 12952849. Source: UniProtKB

myoblast migration

Inferred from direct assay PubMed 7519904. Source: UniProtKB

negative regulation of angiogenesis

Inferred from expression pattern PubMed 18802666. Source: UniProtKB

positive regulation of cell division

Inferred from electronic annotation. Source: UniProtKB-KW

positive regulation of endothelial cell proliferation

Inferred from direct assay PubMed 12952849. Source: UniProtKB

positive regulation of neutrophil chemotaxis

Inferred from direct assay PubMed 16099885. Source: UniProtKB

positive regulation of peptidyl-tyrosine phosphorylation

Inferred from direct assay PubMed 16099885. Source: UniProtKB

regulation of tissue remodeling

Inferred from sequence or structural similarity. Source: UniProtKB

response to endoplasmic reticulum stress

Inferred from sequence or structural similarity. Source: UniProtKB

response to unfolded protein

Inferred from electronic annotation. Source: UniProtKB-KW

tissue remodeling

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componentbasement membrane

Inferred from direct assay PubMed 17927980. Source: UniProtKB

endoplasmic reticulum

Inferred from sequence or structural similarity. Source: UniProtKB

extracellular matrix

Inferred from sequence or structural similarity. Source: UniProtKB

extracellular region

Traceable author statement. Source: Reactome

extracellular space

Inferred from direct assay PubMed 12952849PubMed 18802666. Source: UniProtKB

sarcoplasmic reticulum

Inferred from sequence or structural similarity. Source: UniProtKB

   Molecular_functioncalcium ion binding

Inferred from direct assay PubMed 16246837Ref.2. Source: UniProtKB

heparin binding

Inferred from direct assay Ref.2. Source: UniProtKB

integrin binding

Inferred from direct assay PubMed 16099885. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2626 Potential
Chain27 – 961935Thrombospondin-4
PRO_0000035852

Regions

Domain27 – 192166Laminin G-like
Domain286 – 32540EGF-like 1
Domain326 – 36338EGF-like 2; calcium-binding Potential
Domain379 – 41941EGF-like 3; calcium-binding Potential
Domain420 – 46243EGF-like 4
Repeat463 – 49533TSP type-3 1
Repeat496 – 53136TSP type-3 2
Repeat532 – 55423TSP type-3 3
Repeat555 – 59036TSP type-3 4
Repeat591 – 61323TSP type-3 5
Repeat614 – 65138TSP type-3 6
Repeat652 – 69140TSP type-3 7
Repeat692 – 72736TSP type-3 8
Domain731 – 945215TSP C-terminal
Motif562 – 5643Cell attachment site Potential

Amino acid modifications

Glycosylation6121N-linked (GlcNAc...) Potential
Glycosylation9411N-linked (GlcNAc...) Potential
Disulfide bond258Interchain Probable
Disulfide bond261Interchain Probable
Disulfide bond290 ↔ 301 By similarity
Disulfide bond295 ↔ 310 By similarity
Disulfide bond313 ↔ 324 By similarity
Disulfide bond330 ↔ 341 By similarity
Disulfide bond335 ↔ 350 By similarity
Disulfide bond353 ↔ 377 By similarity
Disulfide bond383 ↔ 394 By similarity
Disulfide bond388 ↔ 403 By similarity
Disulfide bond406 ↔ 418 By similarity
Disulfide bond424 ↔ 438 By similarity
Disulfide bond432 ↔ 448 By similarity
Disulfide bond450 ↔ 461 By similarity
Disulfide bond477 ↔ 482 By similarity
Disulfide bond487 ↔ 507 By similarity
Disulfide bond523 ↔ 543 By similarity
Disulfide bond546 ↔ 566 By similarity
Disulfide bond582 ↔ 602 By similarity
Disulfide bond605 ↔ 625 By similarity
Disulfide bond643 ↔ 663 By similarity
Disulfide bond683 ↔ 703 By similarity
Disulfide bond719 ↔ 940 By similarity

Natural variations

Natural variant551L → Q. Ref.4
Corresponds to variant rs17881847 [ dbSNP | Ensembl ].
VAR_019951
Natural variant3871A → P Gain of function mutation; resulting in a pro-atherogenic phenotype. Ref.3 Ref.4 Ref.11
Corresponds to variant rs1866389 [ dbSNP | Ensembl ].
VAR_019952
Natural variant4201A → V. Ref.1 Ref.2 Ref.4
Corresponds to variant rs17882372 [ dbSNP | Ensembl ].
VAR_019953
Natural variant6461V → I. Ref.4
Corresponds to variant rs2229396 [ dbSNP | Ensembl ].
VAR_019954
Natural variant7371V → I.
Corresponds to variant rs2229398 [ dbSNP | Ensembl ].
VAR_052659

Experimental info

Sequence conflict961N → S no nucleotide entry Ref.1
Sequence conflict961N → S in CAA79635. Ref.2
Sequence conflict2761P → A no nucleotide entry Ref.1
Sequence conflict2761P → A in CAA79635. Ref.2
Sequence conflict7371V → G no nucleotide entry Ref.1
Sequence conflict7371V → G in CAA79635. Ref.2

Sequences

Sequence LengthMass (Da)Tools
P35443 [UniParc].

Last modified November 23, 2004. Version 2.
Checksum: 18F867AA5FFDA54B

FASTA961105,869
        10         20         30         40         50         60 
MLAPRGAAVL LLHLVLQRWL AAGAQATPQV FDLLPSSSQR LNPGALLPVL TDPALNDLYV 

        70         80         90        100        110        120 
ISTFKLQTKS SATIFGLYSS TDNSKYFEFT VMGRLNKAIL RYLKNDGKVH LVVFNNLQLA 

       130        140        150        160        170        180 
DGRRHRILLR LSNLQRGAGS LELYLDCIQV DSVHNLPRAF AGPSQKPETI ELRTFQRKPQ 

       190        200        210        220        230        240 
DFLEELKLVV RGSLFQVASL QDCFLQQSEP LAATGTGDFN RQFLGQMTQL NQLLGEVKDL 

       250        260        270        280        290        300 
LRQQVKETSF LRNTIAECQA CGPLKFQSPT PSTVVPPAPP APPTRPPRRC DSNPCFRGVQ 

       310        320        330        340        350        360 
CTDSRDGFQC GPCPEGYTGN GITCIDVDEC KYHPCYPGVH CINLSPGFRC DACPVGFTGP 

       370        380        390        400        410        420 
MVQGVGISFA KSNKQVCTDI DECRNGACVP NSICVNTLGS YRCGPCKPGY TGDQIRGCKA 

       430        440        450        460        470        480 
ERNCRNPELN PCSVNAQCIE ERQGDVTCVC GVGWAGDGYI CGKDVDIDSY PDEELPCSAR 

       490        500        510        520        530        540 
NCKKDNCKYV PNSGQEDADR DGIGDACDED ADGDGILNEQ DNCVLIHNVD QRNSDKDIFG 

       550        560        570        580        590        600 
DACDNCLSVL NNDQKDTDGD GRGDACDDDM DGDGIKNILD NCPKFPNRDQ RDKDGDGVGD 

       610        620        630        640        650        660 
ACDSCPDVSN PNQSDVDNDL VGDSCDTNQD SDGDGHQDST DNCPTVINSA QLDTDKDGIG 

       670        680        690        700        710        720 
DECDDDDDND GIPDLVPPGP DNCRLVPNPA QEDSNSDGVG DICESDFDQD QVIDRIDVCP 

       730        740        750        760        770        780 
ENAEVTLTDF RAYQTVVLDP EGDAQIDPNW VVLNQGMEIV QTMNSDPGLA VGYTAFNGVD 

       790        800        810        820        830        840 
FEGTFHVNTQ TDDDYAGFIF GYQDSSSFYV VMWKQTEQTY WQATPFRAVA EPGIQLKAVK 

       850        860        870        880        890        900 
SKTGPGEHLR NSLWHTGDTS DQVRLLWKDS RNVGWKDKVS YRWFLQHRPQ VGYIRVRFYE 

       910        920        930        940        950        960 
GSELVADSGV TIDTTMRGGR LGVFCFSQEN IIWSNLKYRC NDTIPEDFQE FQTQNFDRFD 


N 

« Hide

References

« Hide 'large scale' references
[1]"The evolution of the thrombospondin gene family."
Lawler J., Duquette M., Urry L., McHenry K., Smith T.F.
J. Mol. Evol. 36:509-516(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT VAL-420.
Tissue: Heart.
[2]"Characterization of human thrombospondin-4."
Lawler J., McHenry K., Duquette M., Derick L.
J. Biol. Chem. 270:2809-2814(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT VAL-420, SUBUNIT.
[3]"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. expand/collapse author list , 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], VARIANT PRO-387.
Tissue: Synovium.
[4]SeattleSNPs variation discovery resource
Submitted (MAR-2004) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS GLN-55; PRO-387; VAL-420 AND ILE-646.
[5]"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].
Tissue: PNS.
[6]"Regulator of differentiation 1 (ROD1) binds to the amphipathic C-terminal peptide of thrombospondin-4 and is involved in its mitogenic activity."
Sadvakassova G., Dobocan M.C., Difalco M.R., Congote L.F.
J. Cell. Physiol. 220:672-679(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN CELL PROLIFERATION, INTERACTION WITH PTBP3.
[7]"A thrombospondin-dependent pathway for a protective ER stress response."
Lynch J.M., Maillet M., Vanhoutte D., Schloemer A., Sargent M.A., Blair N.S., Lynch K.A., Okada T., Aronow B.J., Osinska H., Prywes R., Lorenz J.N., Mori K., Lawler J., Robbins J., Molkentin J.D.
Cell 149:1257-1268(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH ATF6.
[8]"ATF6 [corrected] and thrombospondin 4: the dynamic duo of the adaptive endoplasmic reticulum stress response."
Doroudgar S., Glembotski C.C.
Circ. Res. 112:9-12(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW.
[9]Erratum
Doroudgar S., Glembotski C.C.
Circ. Res. 112:E31-E31(2013)
[10]"Thrombospondins: old players, new games."
Stenina-Adognravi O.
Curr. Opin. Lipidol. 24:401-409(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW.
[11]"Thrombospondin-4 polymorphism (A387P) predicts cardiovascular risk in postinfarction patients with high HDL cholesterol and C-reactive protein levels."
Corsetti J.P., Ryan D., Moss A.J., McCarthy J., Goldenberg I., Zareba W., Sparks C.E.
Thromb. Haemost. 106:1170-1178(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: CHARACTERIZATION OF VARIANT PRO-387.
+Additional computationally mapped references.

Web resources

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
Z19585 mRNA. Translation: CAA79635.1.
AK313587 mRNA. Translation: BAG36356.1.
AY566253 Genomic DNA. Translation: AAS66982.1.
BC050456 mRNA. Translation: AAH50456.1.
PIRTSHUP4. A55710.
RefSeqNP_003239.2. NM_003248.4.
UniGeneHs.211426.

3D structure databases

ProteinModelPortalP35443.
SMRP35443. Positions 218-262, 290-952.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

IntActP35443. 1 interaction.
STRING9606.ENSP00000339730.

PTM databases

PhosphoSiteP35443.

Polymorphism databases

DMDM55977790.

Proteomic databases

PaxDbP35443.
PeptideAtlasP35443.
PRIDEP35443.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000350881; ENSP00000339730; ENSG00000113296.
GeneID7060.
KEGGhsa:7060.
UCSCuc021yaw.1. human.

Organism-specific databases

CTD7060.
GeneCardsGC05P079287.
HGNCHGNC:11788. THBS4.
HPACAB004597.
MIM600715. gene.
neXtProtNX_P35443.
PharmGKBPA36500.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG12793.
HOGENOMHOG000007542.
HOVERGENHBG000636.
InParanoidP35443.
KOK04659.
OMAAECQACG.
OrthoDBEOG76QFGD.
PhylomeDBP35443.
TreeFamTF324917.

Enzyme and pathway databases

ReactomeREACT_111102. Signal Transduction.

Gene expression databases

ArrayExpressP35443.
BgeeP35443.
CleanExHS_THBS4.
GenevestigatorP35443.

Family and domain databases

Gene3D2.60.120.200. 1 hit.
InterProIPR008985. ConA-like_lec_gl_sf.
IPR013320. ConA-like_subgrp.
IPR000742. EG-like_dom.
IPR001881. EGF-like_Ca-bd_dom.
IPR013032. EGF-like_CS.
IPR018097. EGF_Ca-bd_CS.
IPR001791. Laminin_G.
IPR024665. Thbs/COMP_coiled-coil.
IPR003367. Thrombospondin_3-like_rpt.
IPR017897. Thrombospondin_3_rpt.
IPR008859. Thrombospondin_C.
[Graphical view]
PfamPF11598. COMP. 1 hit.
PF07645. EGF_CA. 2 hits.
PF02412. TSP_3. 6 hits.
PF05735. TSP_C. 1 hit.
[Graphical view]
SMARTSM00181. EGF. 2 hits.
SM00179. EGF_CA. 2 hits.
SM00210. TSPN. 1 hit.
[Graphical view]
SUPFAMSSF49899. SSF49899. 2 hits.
PROSITEPS01186. EGF_2. 1 hit.
PS50026. EGF_3. 4 hits.
PS01187. EGF_CA. 2 hits.
PS51234. TSP3. 8 hits.
PS51236. TSP_CTER. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiTHBS4.
GenomeRNAi7060.
NextBio27609.
PROP35443.
SOURCESearch...

Entry information

Entry nameTSP4_HUMAN
AccessionPrimary (citable) accession number: P35443
Secondary accession number(s): B2R909, Q86TG2
Entry history
Integrated into UniProtKB/Swiss-Prot: June 1, 1994
Last sequence update: November 23, 2004
Last modified: April 16, 2014
This is version 142 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 5

Human chromosome 5: entries, gene names and cross-references to MIM