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Q9Z1T2 (TSP4_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 106. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Thrombospondin-4
Gene names
Name:Thbs4
Synonyms:Tsp4
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length963 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. Ref.2 Ref.3 Ref.4 Ref.5 Ref.6 Ref.7

Subunit structure

Homopentamer; disulfide-linked. Interacts with PTBP3 By similarity. Interacts (via EGF-like 3; calcium-binding domain) with ATF6 and facilitates its processing, activation and nuclear translocation. Interacts with NOTCH1. Ref.4 Ref.7

Subcellular location

Endoplasmic reticulum. Sarcoplasmic reticulum. Secreted. Secretedextracellular space. Secretedextracellular spaceextracellular matrix Ref.4 Ref.5.

Tissue specificity

Heart. Up-regulated in the heart in response to ischemic injury and pathology (at protein level). Astrocytes; expressed at high levels in subventricular zone (SVZ)-derived astrocytes and at low levels in cortical astrocytes. In response to peripheral nerve injury, significantly up-regulated in the dorsal spinal cord (at protein level). Ref.5 Ref.6 Ref.7

Disruption phenotype

On exposure to acute pressure overload, mice exhibit a marked increase in: heart weight and fibrosis, cardiomyocyte size and number of apoptotic cells in the myocardium, deposition of extracellular matrix (ECM) and levels of interstitial collagens. The increased ECM deposition is accompanied by changes in functional parameters of the heart and decreased vessel density. Mice also show defective induction of the ER stress response in the heart. Do not exhibit peripheral nerve injury-induced behavioral hypersensitivities such as thermal/mechanical hyperalgesia and tactile allodynia but show severe defects in cortical-injury-induced subventricular zone astrogenesis. Ref.3 Ref.5 Ref.6 Ref.7

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
   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 mutant phenotype Ref.6. Source: UniProtKB

endothelial cell-cell adhesion

Inferred from electronic annotation. Source: Ensembl

myoblast migration

Inferred from electronic annotation. Source: Ensembl

negative regulation of angiogenesis

Inferred from electronic annotation. Source: Ensembl

positive regulation of cell division

Inferred from electronic annotation. Source: UniProtKB-KW

positive regulation of endothelial cell proliferation

Inferred from electronic annotation. Source: Ensembl

positive regulation of neutrophil chemotaxis

Inferred from electronic annotation. Source: Ensembl

positive regulation of peptidyl-tyrosine phosphorylation

Inferred from electronic annotation. Source: Ensembl

regulation of tissue remodeling

Inferred from mutant phenotype Ref.5. Source: UniProtKB

response to endoplasmic reticulum stress

Inferred from mutant phenotype Ref.4. 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 electronic annotation. Source: Ensembl

endoplasmic reticulum

Inferred from direct assay Ref.4. Source: UniProtKB

extracellular matrix

Inferred from direct assay Ref.5. Source: UniProtKB

extracellular space

Inferred from direct assay Ref.4. Source: UniProtKB

sarcoplasmic reticulum

Inferred from direct assay Ref.4. Source: UniProtKB

   Molecular_functioncalcium ion binding

Inferred from electronic annotation. Source: InterPro

heparin binding

Inferred from electronic annotation. Source: Ensembl

protein binding

Inferred from physical interaction Ref.4. Source: UniProtKB

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

Atf6F6VAN03EBI-6171531,EBI-6171558

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2626 Potential
Chain27 – 963937Thrombospondin-4
PRO_0000035853

Regions

Domain29 – 194166Laminin G-like
Domain288 – 32740EGF-like 1
Domain328 – 36538EGF-like 2; calcium-binding Potential
Domain381 – 41838EGF-like 3; calcium-binding Potential
Domain422 – 46443EGF-like 4
Repeat465 – 49733TSP type-3 1
Repeat498 – 53336TSP type-3 2
Repeat534 – 55623TSP type-3 3
Repeat557 – 59236TSP type-3 4
Repeat593 – 61523TSP type-3 5
Repeat616 – 65338TSP type-3 6
Repeat654 – 69340TSP type-3 7
Repeat694 – 72936TSP type-3 8
Domain733 – 947215TSP C-terminal
Motif138 – 1403Cell attachment site Potential
Motif564 – 5663Cell attachment site Potential

Amino acid modifications

Glycosylation6141N-linked (GlcNAc...) Potential
Glycosylation6501N-linked (GlcNAc...) Potential
Glycosylation9431N-linked (GlcNAc...) Potential
Disulfide bond260Interchain By similarity
Disulfide bond263Interchain By similarity
Disulfide bond292 ↔ 303 By similarity
Disulfide bond297 ↔ 312 By similarity
Disulfide bond315 ↔ 326 By similarity
Disulfide bond332 ↔ 343 By similarity
Disulfide bond337 ↔ 352 By similarity
Disulfide bond355 ↔ 379 By similarity
Disulfide bond385 ↔ 396 By similarity
Disulfide bond390 ↔ 405 By similarity
Disulfide bond408 ↔ 420 By similarity
Disulfide bond426 ↔ 440 By similarity
Disulfide bond434 ↔ 450 By similarity
Disulfide bond452 ↔ 463 By similarity
Disulfide bond479 ↔ 484 By similarity
Disulfide bond489 ↔ 509 By similarity
Disulfide bond525 ↔ 545 By similarity
Disulfide bond548 ↔ 568 By similarity
Disulfide bond584 ↔ 604 By similarity
Disulfide bond607 ↔ 627 By similarity
Disulfide bond645 ↔ 665 By similarity
Disulfide bond685 ↔ 705 By similarity
Disulfide bond721 ↔ 942 By similarity

Experimental info

Sequence conflict401S → P in AAD27642. Ref.1
Sequence conflict2901R → H in AAD32714. Ref.1

Sequences

Sequence LengthMass (Da)Tools
Q9Z1T2 [UniParc].

Last modified May 1, 1999. Version 1.
Checksum: B8BA83B84F489FB1

FASTA963106,366
        10         20         30         40         50         60 
MPAPRAAAAA FLLLHLVLQP WQRTSAQATP QVFDLLPSSS QRLNPSALQP VLTDPTLHEV 

        70         80         90        100        110        120 
YLISTFKLQS KSSATIFGLY SSSDNSKYFE FTVMGRLNKA ILRYLKNDGK IHLVVFNNLQ 

       130        140        150        160        170        180 
LADGRRHRVL LRLSNLQRGD GSVELYLDCA QADSVRNLPR AFSGLTQNPE SIELRTFQRK 

       190        200        210        220        230        240 
PQDFLEELKL VVRGSLFQVA SLQDCFLQQS EPLAATSTGD FNRQFLGQMT QLNQLLGEVK 

       250        260        270        280        290        300 
DLLRQQVKET SFLRNTIAEC QACGPLSFQS PTPNTLVPIA PPAPPTRPTR HCDSSPCFRG 

       310        320        330        340        350        360 
VRCTDTRDGF QCGPCPDGYT GNGITCSDVD ECKYHPCYPG VRCVNLAPGF RCDACPVGFT 

       370        380        390        400        410        420 
GPMVQGVGIN FAKTNKQVCT DVDECQNGAC VLNSICINTL GSYRCGPCKP GYTGDQTRGC 

       430        440        450        460        470        480 
KTERSCRNPE QNPCSVHAQC IEERQGDVTC VCGVGWAGDG YVCGKDVDID SYPDEELPCS 

       490        500        510        520        530        540 
ARNCKKDNCK YVPNSGQEDA DRDGIGDACD EDADGDGILN EQDNCVLTHN IDQRNSDKDI 

       550        560        570        580        590        600 
FGDACDNCRM VLNNDQKDTD GDGRGDACDD DMDGDGIKNI LDNCPRVPNR DQQDRDGDDV 

       610        620        630        640        650        660 
GDACDSCPDV SNPNQSDVDN DLVGDSCDTN QDSDGDGHQD STDNCPTVIN SSQLDTDKDG 

       670        680        690        700        710        720 
IGDECDDDDD NDGIPDLVPP GPDNCRLVPN PAQEDSNNDG VGDICEADFD QDQVIDHIDV 

       730        740        750        760        770        780 
CPENAEITLT DFRAYQTVVL DPEGDAQIDP NWVVLNQGME IVQTMNSDPG LAVGYTAFNG 

       790        800        810        820        830        840 
VDFEGTFHVN TQTDDDYAGF IFGYQDSSSF YVVMWKQTEQ TYWQATPFRA VAEPGIQLKA 

       850        860        870        880        890        900 
VKSKTGPGEH LRNSLWHTGD TSDQVRLLWK DSRNVGWKDK VSYRWFLQHR PQVGYIRVRF 

       910        920        930        940        950        960 
YEGSELVADS GVTIDTTMRG GRLGVFCFSQ ENIIWSNLKY RCNDTIPEDF QEFQTQSFDR 


LDN 

« Hide

References

[1]"The thrombospondin-4 gene."
Newton G., Weremowicz S., Morton C.C., Jenkins N.A., Gilbert D.J., Copeland N.G., Lawler J.
Mamm. Genome 10:1010-1016(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
[2]"Thrombospondin-4 regulates vascular inflammation and atherogenesis."
Frolova E.G., Pluskota E., Krukovets I., Burke T., Drumm C., Smith J.D., Blech L., Febbraio M., Bornstein P., Plow E.F., Stenina O.I.
Circ. Res. 107:1313-1325(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[3]"Thrombospondin-4 is required for stretch-mediated contractility augmentation in cardiac muscle."
Cingolani O.H., Kirk J.A., Seo K., Koitabashi N., Lee D.I., Ramirez-Correa G., Bedja D., Barth A.S., Moens A.L., Kass D.A.
Circ. Res. 109:1410-1414(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, DISRUPTION PHENOTYPE.
[4]"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: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH ATF6.
[5]"Thrombospondin-4 regulates fibrosis and remodeling of the myocardium in response to pressure overload."
Frolova E.G., Sopko N., Blech L., Popovic Z.B., Li J., Vasanji A., Drumm C., Krukovets I., Jain M.K., Penn M.S., Plow E.F., Stenina O.I.
FASEB J. 26:2363-2373(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, DISRUPTION PHENOTYPE.
[6]"Thrombospondin-4 contributes to spinal sensitization and neuropathic pain states."
Kim D.S., Li K.W., Boroujerdi A., Peter Yu Y., Zhou C.Y., Deng P., Park J., Zhang X., Lee J., Corpe M., Sharp K., Steward O., Eroglu C., Barres B., Zaucke F., Xu Z.C., Luo Z.D.
J. Neurosci. 32:8977-8987(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, TISSUE SPECIFICITY, DISRUPTION PHENOTYPE.
[7]"Protective astrogenesis from the SVZ niche after injury is controlled by Notch modulator Thbs4."
Benner E.J., Luciano D., Jo R., Abdi K., Paez-Gonzalez P., Sheng H., Warner D.S., Liu C., Eroglu C., Kuo C.T.
Nature 497:369-373(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, TISSUE SPECIFICITY, DISRUPTION PHENOTYPE, INTERACTION WITH NOTCH1.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF102887 mRNA. Translation: AAC73003.1.
AF130461 Genomic DNA. Translation: AAD27642.1.
AH007739 Genomic DNA. Translation: AAD32714.1.
CCDSCCDS26684.1.
RefSeqNP_035712.1. NM_011582.3.
UniGeneMm.20865.

3D structure databases

ProteinModelPortalQ9Z1T2.
SMRQ9Z1T2. Positions 220-264, 292-954.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

IntActQ9Z1T2. 1 interaction.

PTM databases

PhosphoSiteQ9Z1T2.

Proteomic databases

PaxDbQ9Z1T2.
PRIDEQ9Z1T2.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000022213; ENSMUSP00000022213; ENSMUSG00000021702.
GeneID21828.
KEGGmmu:21828.
UCSCuc007rku.2. mouse.

Organism-specific databases

CTD7060.
MGIMGI:1101779. Thbs4.

Phylogenomic databases

eggNOGNOG12793.
GeneTreeENSGT00550000074507.
HOGENOMHOG000007542.
HOVERGENHBG000636.
InParanoidQ9Z1T2.
KOK04659.
OMAAECQACG.
OrthoDBEOG76QFGD.
PhylomeDBQ9Z1T2.
TreeFamTF324917.

Gene expression databases

ArrayExpressQ9Z1T2.
BgeeQ9Z1T2.
CleanExMM_THBS4.
GenevestigatorQ9Z1T2.

Family and domain databases

Gene3D2.60.120.200. 1 hit.
4.10.1080.10. 2 hits.
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.
IPR028974. TSP_type-3_rpt.
[Graphical view]
PfamPF11598. COMP. 1 hit.
PF00008. EGF. 1 hit.
PF07645. EGF_CA. 2 hits.
PF02412. TSP_3. 5 hits.
PF05735. TSP_C. 1 hit.
[Graphical view]
SMARTSM00181. EGF. 2 hits.
SM00179. EGF_CA. 2 hits.
SM00210. TSPN. 1 hit.
[Graphical view]
SUPFAMSSF103647. SSF103647. 3 hits.
SSF49899. 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

NextBio301264.
PROQ9Z1T2.
SOURCESearch...

Entry information

Entry nameTSP4_MOUSE
AccessionPrimary (citable) accession number: Q9Z1T2
Secondary accession number(s): Q9QYS3, Q9WUE0
Entry history
Integrated into UniProtKB/Swiss-Prot: May 24, 2004
Last sequence update: May 1, 1999
Last modified: July 9, 2014
This is version 106 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot