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Q9Z1T2

- TSP4_MOUSE

UniProt

Q9Z1T2 - TSP4_MOUSE

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Protein
Thrombospondin-4
Gene
Thbs4, Tsp4
Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5 - Experimental evidence at protein leveli

Functioni

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.6 Publications

GO - Molecular functioni

  1. calcium ion binding Source: InterPro
  2. heparin binding Source: Ensembl
  3. protein binding Source: UniProtKB

GO - Biological processi

  1. behavioral response to pain Source: UniProtKB
  2. endothelial cell-cell adhesion Source: Ensembl
  3. myoblast migration Source: Ensembl
  4. negative regulation of angiogenesis Source: Ensembl
  5. positive regulation of cell division Source: UniProtKB-KW
  6. positive regulation of endothelial cell proliferation Source: Ensembl
  7. positive regulation of neutrophil chemotaxis Source: Ensembl
  8. positive regulation of peptidyl-tyrosine phosphorylation Source: Ensembl
  9. regulation of tissue remodeling Source: UniProtKB
  10. response to endoplasmic reticulum stress Source: UniProtKB
  11. response to unfolded protein Source: UniProtKB-KW
  12. tissue remodeling Source: UniProtKB-KW
Complete GO annotation...

Keywords - Molecular functioni

Growth factor, Mitogen

Keywords - Biological processi

Cell adhesion, Tissue remodeling, Unfolded protein response

Keywords - Ligandi

Calcium

Names & Taxonomyi

Protein namesi
Recommended name:
Thrombospondin-4
Gene namesi
Name:Thbs4
Synonyms:Tsp4
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589: Chromosome 13

Organism-specific databases

MGIiMGI:1101779. Thbs4.

Subcellular locationi

Endoplasmic reticulum. Sarcoplasmic reticulum. Secreted. Secretedextracellular space. Secretedextracellular spaceextracellular matrix 2 Publications

GO - Cellular componenti

  1. basement membrane Source: Ensembl
  2. endoplasmic reticulum Source: UniProtKB
  3. extracellular matrix Source: UniProtKB
  4. extracellular space Source: UniProtKB
  5. sarcoplasmic reticulum Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Endoplasmic reticulum, Extracellular matrix, Sarcoplasmic reticulum, Secreted

Pathology & Biotechi

Disruption phenotypei

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.4 Publications

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2626 Reviewed prediction
Add
BLAST
Chaini27 – 963937Thrombospondin-4
PRO_0000035853Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi260 – 260Interchain By similarity
Disulfide bondi263 – 263Interchain By similarity
Disulfide bondi292 ↔ 303 By similarity
Disulfide bondi297 ↔ 312 By similarity
Disulfide bondi315 ↔ 326 By similarity
Disulfide bondi332 ↔ 343 By similarity
Disulfide bondi337 ↔ 352 By similarity
Disulfide bondi355 ↔ 379 By similarity
Disulfide bondi385 ↔ 396 By similarity
Disulfide bondi390 ↔ 405 By similarity
Disulfide bondi408 ↔ 420 By similarity
Disulfide bondi426 ↔ 440 By similarity
Disulfide bondi434 ↔ 450 By similarity
Disulfide bondi452 ↔ 463 By similarity
Disulfide bondi479 ↔ 484 By similarity
Disulfide bondi489 ↔ 509 By similarity
Disulfide bondi525 ↔ 545 By similarity
Disulfide bondi548 ↔ 568 By similarity
Disulfide bondi584 ↔ 604 By similarity
Disulfide bondi607 ↔ 627 By similarity
Glycosylationi614 – 6141N-linked (GlcNAc...) Reviewed prediction
Disulfide bondi645 ↔ 665 By similarity
Glycosylationi650 – 6501N-linked (GlcNAc...) Reviewed prediction
Disulfide bondi685 ↔ 705 By similarity
Disulfide bondi721 ↔ 942 By similarity
Glycosylationi943 – 9431N-linked (GlcNAc...) Reviewed prediction

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiQ9Z1T2.
PRIDEiQ9Z1T2.

PTM databases

PhosphoSiteiQ9Z1T2.

Expressioni

Tissue specificityi

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).3 Publications

Gene expression databases

ArrayExpressiQ9Z1T2.
BgeeiQ9Z1T2.
CleanExiMM_THBS4.
GenevestigatoriQ9Z1T2.

Interactioni

Subunit structurei

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 NOTCH1.2 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
Atf6F6VAN03EBI-6171531,EBI-6171558

Protein-protein interaction databases

IntActiQ9Z1T2. 1 interaction.

Structurei

3D structure databases

ProteinModelPortaliQ9Z1T2.
SMRiQ9Z1T2. Positions 220-264, 292-954.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini29 – 194166Laminin G-like
Add
BLAST
Domaini288 – 32740EGF-like 1
Add
BLAST
Domaini328 – 36538EGF-like 2; calcium-binding Reviewed prediction
Add
BLAST
Domaini381 – 41838EGF-like 3; calcium-binding Reviewed prediction
Add
BLAST
Domaini422 – 46443EGF-like 4
Add
BLAST
Repeati465 – 49733TSP type-3 1
Add
BLAST
Repeati498 – 53336TSP type-3 2
Add
BLAST
Repeati534 – 55623TSP type-3 3
Add
BLAST
Repeati557 – 59236TSP type-3 4
Add
BLAST
Repeati593 – 61523TSP type-3 5
Add
BLAST
Repeati616 – 65338TSP type-3 6
Add
BLAST
Repeati654 – 69340TSP type-3 7
Add
BLAST
Repeati694 – 72936TSP type-3 8
Add
BLAST
Domaini733 – 947215TSP C-terminal
Add
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi138 – 1403Cell attachment site Reviewed prediction
Motifi564 – 5663Cell attachment site Reviewed prediction

Sequence similaritiesi

Belongs to the thrombospondin family.
Contains 4 EGF-like domains.
Contains 8 TSP type-3 repeats.

Keywords - Domaini

EGF-like domain, Repeat, Signal

Phylogenomic databases

eggNOGiNOG12793.
GeneTreeiENSGT00550000074507.
HOGENOMiHOG000007542.
HOVERGENiHBG000636.
InParanoidiQ9Z1T2.
KOiK04659.
OMAiAECQACG.
OrthoDBiEOG76QFGD.
PhylomeDBiQ9Z1T2.
TreeFamiTF324917.

Family and domain databases

Gene3Di2.60.120.200. 1 hit.
4.10.1080.10. 2 hits.
InterProiIPR008985. 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]
PfamiPF11598. COMP. 1 hit.
PF00008. EGF. 1 hit.
PF07645. EGF_CA. 2 hits.
PF02412. TSP_3. 5 hits.
PF05735. TSP_C. 1 hit.
[Graphical view]
SMARTiSM00181. EGF. 2 hits.
SM00179. EGF_CA. 2 hits.
SM00210. TSPN. 1 hit.
[Graphical view]
SUPFAMiSSF103647. SSF103647. 3 hits.
SSF49899. SSF49899. 2 hits.
PROSITEiPS01186. 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]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q9Z1T2-1 [UniParc]FASTAAdd to Basket

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MPAPRAAAAA FLLLHLVLQP WQRTSAQATP QVFDLLPSSS QRLNPSALQP    50
VLTDPTLHEV YLISTFKLQS KSSATIFGLY SSSDNSKYFE FTVMGRLNKA 100
ILRYLKNDGK IHLVVFNNLQ LADGRRHRVL LRLSNLQRGD GSVELYLDCA 150
QADSVRNLPR AFSGLTQNPE SIELRTFQRK PQDFLEELKL VVRGSLFQVA 200
SLQDCFLQQS EPLAATSTGD FNRQFLGQMT QLNQLLGEVK DLLRQQVKET 250
SFLRNTIAEC QACGPLSFQS PTPNTLVPIA PPAPPTRPTR HCDSSPCFRG 300
VRCTDTRDGF QCGPCPDGYT GNGITCSDVD ECKYHPCYPG VRCVNLAPGF 350
RCDACPVGFT GPMVQGVGIN FAKTNKQVCT DVDECQNGAC VLNSICINTL 400
GSYRCGPCKP GYTGDQTRGC KTERSCRNPE QNPCSVHAQC IEERQGDVTC 450
VCGVGWAGDG YVCGKDVDID SYPDEELPCS ARNCKKDNCK YVPNSGQEDA 500
DRDGIGDACD EDADGDGILN EQDNCVLTHN IDQRNSDKDI FGDACDNCRM 550
VLNNDQKDTD GDGRGDACDD DMDGDGIKNI LDNCPRVPNR DQQDRDGDDV 600
GDACDSCPDV SNPNQSDVDN DLVGDSCDTN QDSDGDGHQD STDNCPTVIN 650
SSQLDTDKDG IGDECDDDDD NDGIPDLVPP GPDNCRLVPN PAQEDSNNDG 700
VGDICEADFD QDQVIDHIDV CPENAEITLT DFRAYQTVVL DPEGDAQIDP 750
NWVVLNQGME IVQTMNSDPG LAVGYTAFNG VDFEGTFHVN TQTDDDYAGF 800
IFGYQDSSSF YVVMWKQTEQ TYWQATPFRA VAEPGIQLKA VKSKTGPGEH 850
LRNSLWHTGD TSDQVRLLWK DSRNVGWKDK VSYRWFLQHR PQVGYIRVRF 900
YEGSELVADS GVTIDTTMRG GRLGVFCFSQ ENIIWSNLKY RCNDTIPEDF 950
QEFQTQSFDR LDN 963
Length:963
Mass (Da):106,366
Last modified:May 1, 1999 - v1
Checksum:iB8BA83B84F489FB1
GO

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti40 – 401S → P in AAD27642. 1 Publication
Sequence conflicti290 – 2901R → H in AAD32714. 1 Publication

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
AF102887 mRNA. Translation: AAC73003.1.
AF130461 Genomic DNA. Translation: AAD27642.1.
AH007739 Genomic DNA. Translation: AAD32714.1.
CCDSiCCDS26684.1.
RefSeqiNP_035712.1. NM_011582.3.
UniGeneiMm.20865.

Genome annotation databases

EnsembliENSMUST00000022213; ENSMUSP00000022213; ENSMUSG00000021702.
GeneIDi21828.
KEGGimmu:21828.
UCSCiuc007rku.2. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
AF102887 mRNA. Translation: AAC73003.1 .
AF130461 Genomic DNA. Translation: AAD27642.1 .
AH007739 Genomic DNA. Translation: AAD32714.1 .
CCDSi CCDS26684.1.
RefSeqi NP_035712.1. NM_011582.3.
UniGenei Mm.20865.

3D structure databases

ProteinModelPortali Q9Z1T2.
SMRi Q9Z1T2. Positions 220-264, 292-954.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

IntActi Q9Z1T2. 1 interaction.

PTM databases

PhosphoSitei Q9Z1T2.

Proteomic databases

PaxDbi Q9Z1T2.
PRIDEi Q9Z1T2.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSMUST00000022213 ; ENSMUSP00000022213 ; ENSMUSG00000021702 .
GeneIDi 21828.
KEGGi mmu:21828.
UCSCi uc007rku.2. mouse.

Organism-specific databases

CTDi 7060.
MGIi MGI:1101779. Thbs4.

Phylogenomic databases

eggNOGi NOG12793.
GeneTreei ENSGT00550000074507.
HOGENOMi HOG000007542.
HOVERGENi HBG000636.
InParanoidi Q9Z1T2.
KOi K04659.
OMAi AECQACG.
OrthoDBi EOG76QFGD.
PhylomeDBi Q9Z1T2.
TreeFami TF324917.

Miscellaneous databases

NextBioi 301264.
PROi Q9Z1T2.
SOURCEi Search...

Gene expression databases

ArrayExpressi Q9Z1T2.
Bgeei Q9Z1T2.
CleanExi MM_THBS4.
Genevestigatori Q9Z1T2.

Family and domain databases

Gene3Di 2.60.120.200. 1 hit.
4.10.1080.10. 2 hits.
InterProi IPR008985. 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 ]
Pfami PF11598. COMP. 1 hit.
PF00008. EGF. 1 hit.
PF07645. EGF_CA. 2 hits.
PF02412. TSP_3. 5 hits.
PF05735. TSP_C. 1 hit.
[Graphical view ]
SMARTi SM00181. EGF. 2 hits.
SM00179. EGF_CA. 2 hits.
SM00210. TSPN. 1 hit.
[Graphical view ]
SUPFAMi SSF103647. SSF103647. 3 hits.
SSF49899. SSF49899. 2 hits.
PROSITEi PS01186. 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 ]
ProtoNeti Search...

Publicationsi

  1. Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
  2. 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. 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. 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.

Entry informationi

Entry nameiTSP4_MOUSE
AccessioniPrimary (citable) accession number: Q9Z1T2
Secondary accession number(s): Q9QYS3, Q9WUE0
Entry historyi
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 statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi