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Database: UniProt
Entry: Q9Z1T2
LinkDB: Q9Z1T2
Original site: Q9Z1T2 
ID   TSP4_MOUSE              Reviewed;         963 AA.
AC   Q9Z1T2; Q9QYS3; Q9WUE0;
DT   24-MAY-2004, integrated into UniProtKB/Swiss-Prot.
DT   01-MAY-1999, sequence version 1.
DT   13-FEB-2019, entry version 141.
DE   RecName: Full=Thrombospondin-4;
DE   Flags: Precursor;
GN   Name=Thbs4; Synonyms=Tsp4;
OS   Mus musculus (Mouse).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha;
OC   Muroidea; Muridae; Murinae; Mus; Mus.
OX   NCBI_TaxID=10090;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
RX   PubMed=10501972; DOI=10.1007/s003359901149;
RA   Newton G., Weremowicz S., Morton C.C., Jenkins N.A., Gilbert D.J.,
RA   Copeland N.G., Lawler J.;
RT   "The thrombospondin-4 gene.";
RL   Mamm. Genome 10:1010-1016(1999).
RN   [2]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Brain, and Kidney;
RX   PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA   Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA   Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT   "A tissue-specific atlas of mouse protein phosphorylation and
RT   expression.";
RL   Cell 143:1174-1189(2010).
RN   [3]
RP   FUNCTION.
RX   PubMed=20884877; DOI=10.1161/CIRCRESAHA.110.232371;
RA   Frolova E.G., Pluskota E., Krukovets I., Burke T., Drumm C.,
RA   Smith J.D., Blech L., Febbraio M., Bornstein P., Plow E.F.,
RA   Stenina O.I.;
RT   "Thrombospondin-4 regulates vascular inflammation and atherogenesis.";
RL   Circ. Res. 107:1313-1325(2010).
RN   [4]
RP   FUNCTION, AND DISRUPTION PHENOTYPE.
RX   PubMed=22034490; DOI=10.1161/CIRCRESAHA.111.256743;
RA   Cingolani O.H., Kirk J.A., Seo K., Koitabashi N., Lee D.I.,
RA   Ramirez-Correa G., Bedja D., Barth A.S., Moens A.L., Kass D.A.;
RT   "Thrombospondin-4 is required for stretch-mediated contractility
RT   augmentation in cardiac muscle.";
RL   Circ. Res. 109:1410-1414(2011).
RN   [5]
RP   FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH ATF6, AND TISSUE
RP   SPECIFICITY.
RX   PubMed=22682248; DOI=10.1016/j.cell.2012.03.050;
RA   Lynch J.M., Maillet M., Vanhoutte D., Schloemer A., Sargent M.A.,
RA   Blair N.S., Lynch K.A., Okada T., Aronow B.J., Osinska H., Prywes R.,
RA   Lorenz J.N., Mori K., Lawler J., Robbins J., Molkentin J.D.;
RT   "A thrombospondin-dependent pathway for a protective ER stress
RT   response.";
RL   Cell 149:1257-1268(2012).
RN   [6]
RP   FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND DISRUPTION
RP   PHENOTYPE.
RX   PubMed=22362893; DOI=10.1096/fj.11-190728;
RA   Frolova E.G., Sopko N., Blech L., Popovic Z.B., Li J., Vasanji A.,
RA   Drumm C., Krukovets I., Jain M.K., Penn M.S., Plow E.F., Stenina O.I.;
RT   "Thrombospondin-4 regulates fibrosis and remodeling of the myocardium
RT   in response to pressure overload.";
RL   FASEB J. 26:2363-2373(2012).
RN   [7]
RP   FUNCTION, TISSUE SPECIFICITY, AND DISRUPTION PHENOTYPE.
RX   PubMed=22745497; DOI=10.1523/JNEUROSCI.6494-11.2012;
RA   Kim D.S., Li K.W., Boroujerdi A., Peter Yu Y., Zhou C.Y., Deng P.,
RA   Park J., Zhang X., Lee J., Corpe M., Sharp K., Steward O., Eroglu C.,
RA   Barres B., Zaucke F., Xu Z.C., Luo Z.D.;
RT   "Thrombospondin-4 contributes to spinal sensitization and neuropathic
RT   pain states.";
RL   J. Neurosci. 32:8977-8987(2012).
RN   [8]
RP   FUNCTION, TISSUE SPECIFICITY, DISRUPTION PHENOTYPE, AND INTERACTION
RP   WITH NOTCH1.
RX   PubMed=23615612; DOI=10.1038/nature12069;
RA   Benner E.J., Luciano D., Jo R., Abdi K., Paez-Gonzalez P., Sheng H.,
RA   Warner D.S., Liu C., Eroglu C., Kuo C.T.;
RT   "Protective astrogenesis from the SVZ niche after injury is controlled
RT   by Notch modulator Thbs4.";
RL   Nature 497:369-373(2013).
CC   -!- FUNCTION: Adhesive glycoprotein that mediates cell-to-cell and
CC       cell-to-matrix interactions and is involved in various processes
CC       including cellular proliferation, migration, adhesion and
CC       attachment, inflammatory response to CNS injury, regulation of
CC       vascular inflammation and adaptive responses of the heart to
CC       pressure overload and in myocardial function and remodeling. Binds
CC       to structural extracellular matrix (ECM) proteins and modulates
CC       the ECM in response to tissue damage, contributing to
CC       cardioprotective and adaptive ECM remodeling. Plays a role in ER
CC       stress response, via its interaction with the activating
CC       transcription factor 6 alpha (ATF6) which produces adaptive ER
CC       stress response factors and protects myocardium from pressure
CC       overload. May contribute to spinal presynaptic hypersensitivity
CC       and neuropathic pain states after peripheral nerve injury. May
CC       play a role in regulating protective astrogenesis from the
CC       subventricular zone (SVZ) niche after injury in a NOTCH1-dependent
CC       manner. {ECO:0000269|PubMed:20884877, ECO:0000269|PubMed:22034490,
CC       ECO:0000269|PubMed:22362893, ECO:0000269|PubMed:22682248,
CC       ECO:0000269|PubMed:22745497, ECO:0000269|PubMed:23615612}.
CC   -!- SUBUNIT: Homopentamer; disulfide-linked. Interacts with PTBP3 (By
CC       similarity). Interacts (via EGF-like 3; calcium-binding domain)
CC       with ATF6 and facilitates its processing, activation and nuclear
CC       translocation. Interacts with NOTCH1. {ECO:0000250,
CC       ECO:0000269|PubMed:22682248, ECO:0000269|PubMed:23615612}.
CC   -!- INTERACTION:
CC       F6VAN0:Atf6; NbExp=3; IntAct=EBI-6171531, EBI-6171558;
CC   -!- SUBCELLULAR LOCATION: Endoplasmic reticulum
CC       {ECO:0000269|PubMed:22682248}. Sarcoplasmic reticulum
CC       {ECO:0000269|PubMed:22682248}. Secreted
CC       {ECO:0000269|PubMed:22682248}. Secreted, extracellular space
CC       {ECO:0000269|PubMed:22682248}. Secreted, extracellular space,
CC       extracellular matrix {ECO:0000269|PubMed:22362893,
CC       ECO:0000269|PubMed:22682248}.
CC   -!- TISSUE SPECIFICITY: Heart. Up-regulated in the heart in response
CC       to ischemic injury and pathology (at protein level). Astrocytes;
CC       expressed at high levels in subventricular zone (SVZ)-derived
CC       astrocytes and at low levels in cortical astrocytes. In response
CC       to peripheral nerve injury, significantly up-regulated in the
CC       dorsal spinal cord (at protein level).
CC       {ECO:0000269|PubMed:22362893, ECO:0000269|PubMed:22745497,
CC       ECO:0000269|PubMed:23615612}.
CC   -!- DISRUPTION PHENOTYPE: On exposure to acute pressure overload, mice
CC       exhibit a marked increase in: heart weight and fibrosis,
CC       cardiomyocyte size and number of apoptotic cells in the
CC       myocardium, deposition of extracellular matrix (ECM) and levels of
CC       interstitial collagens. The increased ECM deposition is
CC       accompanied by changes in functional parameters of the heart and
CC       decreased vessel density. Mice also show defective induction of
CC       the ER stress response in the heart. Do not exhibit peripheral
CC       nerve injury-induced behavioral hypersensitivities such as
CC       thermal/mechanical hyperalgesia and tactile allodynia but show
CC       severe defects in cortical-injury-induced subventricular zone
CC       astrogenesis. {ECO:0000269|PubMed:22034490,
CC       ECO:0000269|PubMed:22362893, ECO:0000269|PubMed:22745497,
CC       ECO:0000269|PubMed:23615612}.
CC   -!- SIMILARITY: Belongs to the thrombospondin family. {ECO:0000305}.
DR   EMBL; AF102887; AAC73003.1; -; mRNA.
DR   EMBL; AF130461; AAD27642.1; -; Genomic_DNA.
DR   EMBL; AH007739; AAD32714.1; -; Genomic_DNA.
DR   CCDS; CCDS26684.1; -.
DR   RefSeq; NP_035712.1; NM_011582.3.
DR   UniGene; Mm.20865; -.
DR   ProteinModelPortal; Q9Z1T2; -.
DR   SMR; Q9Z1T2; -.
DR   ComplexPortal; CPX-3025; Thrombospondin 4 complex.
DR   IntAct; Q9Z1T2; 1.
DR   STRING; 10090.ENSMUSP00000022213; -.
DR   PhosphoSitePlus; Q9Z1T2; -.
DR   MaxQB; Q9Z1T2; -.
DR   PaxDb; Q9Z1T2; -.
DR   PRIDE; Q9Z1T2; -.
DR   Ensembl; ENSMUST00000022213; ENSMUSP00000022213; ENSMUSG00000021702.
DR   GeneID; 21828; -.
DR   KEGG; mmu:21828; -.
DR   UCSC; uc007rku.2; mouse.
DR   CTD; 7060; -.
DR   MGI; MGI:1101779; Thbs4.
DR   eggNOG; ENOG410IFQQ; Eukaryota.
DR   eggNOG; ENOG410XQKE; LUCA.
DR   GeneTree; ENSGT00940000155227; -.
DR   HOGENOM; HOG000007542; -.
DR   HOVERGEN; HBG000636; -.
DR   InParanoid; Q9Z1T2; -.
DR   KO; K04659; -.
DR   OMA; CFRGVRC; -.
DR   OrthoDB; 120983at2759; -.
DR   PhylomeDB; Q9Z1T2; -.
DR   TreeFam; TF324917; -.
DR   Reactome; R-MMU-186797; Signaling by PDGF.
DR   PRO; PR:Q9Z1T2; -.
DR   Proteomes; UP000000589; Chromosome 13.
DR   Bgee; ENSMUSG00000021702; Expressed in 159 organ(s), highest expression level in tarsal region.
DR   ExpressionAtlas; Q9Z1T2; baseline and differential.
DR   Genevisible; Q9Z1T2; MM.
DR   GO; GO:0005604; C:basement membrane; ISO:MGI.
DR   GO; GO:0062023; C:collagen-containing extracellular matrix; IDA:UniProtKB.
DR   GO; GO:0005783; C:endoplasmic reticulum; IDA:UniProtKB.
DR   GO; GO:0031012; C:extracellular matrix; ISO:MGI.
DR   GO; GO:0005615; C:extracellular space; IDA:UniProtKB.
DR   GO; GO:0031594; C:neuromuscular junction; ISO:MGI.
DR   GO; GO:0016529; C:sarcoplasmic reticulum; IDA:UniProtKB.
DR   GO; GO:0005509; F:calcium ion binding; ISO:MGI.
DR   GO; GO:0005518; F:collagen binding; ISO:MGI.
DR   GO; GO:0005201; F:extracellular matrix structural constituent; HDA:BHF-UCL.
DR   GO; GO:0001968; F:fibronectin binding; ISO:MGI.
DR   GO; GO:0008083; F:growth factor activity; IEA:UniProtKB-KW.
DR   GO; GO:0008201; F:heparin binding; ISO:MGI.
DR   GO; GO:0005178; F:integrin binding; ISO:MGI.
DR   GO; GO:0043237; F:laminin-1 binding; ISO:MGI.
DR   GO; GO:0048266; P:behavioral response to pain; IMP:UniProtKB.
DR   GO; GO:0071603; P:endothelial cell-cell adhesion; ISO:MGI.
DR   GO; GO:0051451; P:myoblast migration; ISO:MGI.
DR   GO; GO:0016525; P:negative regulation of angiogenesis; IEA:Ensembl.
DR   GO; GO:0007399; P:nervous system development; ISO:MGI.
DR   GO; GO:0048812; P:neuron projection morphogenesis; ISO:MGI.
DR   GO; GO:0051781; P:positive regulation of cell division; IEA:UniProtKB-KW.
DR   GO; GO:0001938; P:positive regulation of endothelial cell proliferation; ISO:MGI.
DR   GO; GO:0090023; P:positive regulation of neutrophil chemotaxis; ISO:MGI.
DR   GO; GO:0050731; P:positive regulation of peptidyl-tyrosine phosphorylation; ISO:MGI.
DR   GO; GO:0051260; P:protein homooligomerization; ISO:MGI.
DR   GO; GO:0034103; P:regulation of tissue remodeling; IMP:UniProtKB.
DR   GO; GO:0034976; P:response to endoplasmic reticulum stress; IMP:UniProtKB.
DR   GO; GO:0006986; P:response to unfolded protein; IEA:UniProtKB-KW.
DR   GO; GO:0048771; P:tissue remodeling; IEA:UniProtKB-KW.
DR   Gene3D; 4.10.1080.10; -; 3.
DR   InterPro; IPR013320; ConA-like_dom_sf.
DR   InterPro; IPR001881; EGF-like_Ca-bd_dom.
DR   InterPro; IPR013032; EGF-like_CS.
DR   InterPro; IPR000742; EGF-like_dom.
DR   InterPro; IPR018097; EGF_Ca-bd_CS.
DR   InterPro; IPR001791; Laminin_G.
DR   InterPro; IPR024665; Thbs/COMP_coiled-coil.
DR   InterPro; IPR037349; Thrombospondin.
DR   InterPro; IPR003367; Thrombospondin_3-like_rpt.
DR   InterPro; IPR017897; Thrombospondin_3_rpt.
DR   InterPro; IPR008859; Thrombospondin_C.
DR   InterPro; IPR028974; TSP_type-3_rpt.
DR   PANTHER; PTHR10199; PTHR10199; 1.
DR   Pfam; PF11598; COMP; 1.
DR   Pfam; PF07645; EGF_CA; 2.
DR   Pfam; PF02412; TSP_3; 5.
DR   Pfam; PF05735; TSP_C; 1.
DR   SMART; SM00181; EGF; 4.
DR   SMART; SM00179; EGF_CA; 3.
DR   SMART; SM00210; TSPN; 1.
DR   SUPFAM; SSF103647; SSF103647; 3.
DR   SUPFAM; SSF49899; SSF49899; 2.
DR   PROSITE; PS01186; EGF_2; 1.
DR   PROSITE; PS50026; EGF_3; 4.
DR   PROSITE; PS01187; EGF_CA; 2.
DR   PROSITE; PS51234; TSP3; 8.
DR   PROSITE; PS51236; TSP_CTER; 1.
PE   1: Evidence at protein level;
KW   Calcium; Cell adhesion; Complete proteome; Disulfide bond;
KW   EGF-like domain; Endoplasmic reticulum; Extracellular matrix;
KW   Glycoprotein; Growth factor; Mitogen; Reference proteome; Repeat;
KW   Sarcoplasmic reticulum; Secreted; Signal; Tissue remodeling;
KW   Unfolded protein response.
FT   SIGNAL        1     26       {ECO:0000255}.
FT   CHAIN        27    963       Thrombospondin-4.
FT                                /FTId=PRO_0000035853.
FT   DOMAIN       29    194       Laminin G-like.
FT   DOMAIN      288    327       EGF-like 1. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00076}.
FT   DOMAIN      328    365       EGF-like 2; calcium-binding.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00076}.
FT   DOMAIN      381    418       EGF-like 3; calcium-binding.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00076}.
FT   DOMAIN      422    464       EGF-like 4. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00076}.
FT   REPEAT      465    497       TSP type-3 1.
FT   REPEAT      498    533       TSP type-3 2.
FT   REPEAT      534    556       TSP type-3 3.
FT   REPEAT      557    592       TSP type-3 4.
FT   REPEAT      593    615       TSP type-3 5.
FT   REPEAT      616    653       TSP type-3 6.
FT   REPEAT      654    693       TSP type-3 7.
FT   REPEAT      694    729       TSP type-3 8.
FT   DOMAIN      733    947       TSP C-terminal. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00635}.
FT   MOTIF       138    140       Cell attachment site. {ECO:0000255}.
FT   MOTIF       564    566       Cell attachment site. {ECO:0000255}.
FT   CARBOHYD    614    614       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD    650    650       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD    943    943       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   DISULFID    260    260       Interchain. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00076}.
FT   DISULFID    263    263       Interchain. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00076}.
FT   DISULFID    292    303       {ECO:0000255|PROSITE-ProRule:PRU00076}.
FT   DISULFID    297    312       {ECO:0000255|PROSITE-ProRule:PRU00076}.
FT   DISULFID    315    326       {ECO:0000255|PROSITE-ProRule:PRU00076}.
FT   DISULFID    332    343       {ECO:0000255|PROSITE-ProRule:PRU00076}.
FT   DISULFID    337    352       {ECO:0000255|PROSITE-ProRule:PRU00076}.
FT   DISULFID    355    379       {ECO:0000255|PROSITE-ProRule:PRU00076}.
FT   DISULFID    385    396       {ECO:0000255|PROSITE-ProRule:PRU00076}.
FT   DISULFID    390    405       {ECO:0000255|PROSITE-ProRule:PRU00076}.
FT   DISULFID    408    420       {ECO:0000255|PROSITE-ProRule:PRU00076}.
FT   DISULFID    426    440       {ECO:0000255|PROSITE-ProRule:PRU00076}.
FT   DISULFID    434    450       {ECO:0000255|PROSITE-ProRule:PRU00076}.
FT   DISULFID    452    463       {ECO:0000255|PROSITE-ProRule:PRU00076}.
FT   DISULFID    479    484       {ECO:0000255|PROSITE-ProRule:PRU00076}.
FT   DISULFID    489    509       {ECO:0000255|PROSITE-ProRule:PRU00076}.
FT   DISULFID    525    545       {ECO:0000255|PROSITE-ProRule:PRU00076}.
FT   DISULFID    548    568       {ECO:0000255|PROSITE-ProRule:PRU00076}.
FT   DISULFID    584    604       {ECO:0000255|PROSITE-ProRule:PRU00076}.
FT   DISULFID    607    627       {ECO:0000255|PROSITE-ProRule:PRU00076}.
FT   DISULFID    645    665       {ECO:0000255|PROSITE-ProRule:PRU00076}.
FT   DISULFID    685    705       {ECO:0000255|PROSITE-ProRule:PRU00076}.
FT   DISULFID    721    942       {ECO:0000255|PROSITE-ProRule:PRU00076}.
FT   CONFLICT     40     40       S -> P (in Ref. 1; AAD27642).
FT                                {ECO:0000305}.
FT   CONFLICT    290    290       R -> H (in Ref. 1; AAD32714).
FT                                {ECO:0000305}.
SQ   SEQUENCE   963 AA;  106366 MW;  B8BA83B84F489FB1 CRC64;
     MPAPRAAAAA FLLLHLVLQP WQRTSAQATP QVFDLLPSSS QRLNPSALQP VLTDPTLHEV
     YLISTFKLQS KSSATIFGLY SSSDNSKYFE FTVMGRLNKA ILRYLKNDGK IHLVVFNNLQ
     LADGRRHRVL LRLSNLQRGD GSVELYLDCA QADSVRNLPR AFSGLTQNPE SIELRTFQRK
     PQDFLEELKL VVRGSLFQVA SLQDCFLQQS EPLAATSTGD FNRQFLGQMT QLNQLLGEVK
     DLLRQQVKET SFLRNTIAEC QACGPLSFQS PTPNTLVPIA PPAPPTRPTR HCDSSPCFRG
     VRCTDTRDGF QCGPCPDGYT GNGITCSDVD ECKYHPCYPG VRCVNLAPGF RCDACPVGFT
     GPMVQGVGIN FAKTNKQVCT DVDECQNGAC VLNSICINTL GSYRCGPCKP GYTGDQTRGC
     KTERSCRNPE QNPCSVHAQC IEERQGDVTC VCGVGWAGDG YVCGKDVDID SYPDEELPCS
     ARNCKKDNCK YVPNSGQEDA DRDGIGDACD EDADGDGILN EQDNCVLTHN IDQRNSDKDI
     FGDACDNCRM VLNNDQKDTD GDGRGDACDD DMDGDGIKNI LDNCPRVPNR DQQDRDGDDV
     GDACDSCPDV SNPNQSDVDN DLVGDSCDTN QDSDGDGHQD STDNCPTVIN SSQLDTDKDG
     IGDECDDDDD NDGIPDLVPP GPDNCRLVPN PAQEDSNNDG VGDICEADFD QDQVIDHIDV
     CPENAEITLT DFRAYQTVVL DPEGDAQIDP NWVVLNQGME IVQTMNSDPG LAVGYTAFNG
     VDFEGTFHVN TQTDDDYAGF IFGYQDSSSF YVVMWKQTEQ TYWQATPFRA VAEPGIQLKA
     VKSKTGPGEH LRNSLWHTGD TSDQVRLLWK DSRNVGWKDK VSYRWFLQHR PQVGYIRVRF
     YEGSELVADS GVTIDTTMRG GRLGVFCFSQ ENIIWSNLKY RCNDTIPEDF QEFQTQSFDR
     LDN
//
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