TSP4_MOUSE
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 03-AUG-2022, entry version 159.
DE RecName: Full=Thrombospondin-4;
DE Flags: Precursor;
GN Name=Thbs4; Synonyms=Tsp4;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC 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 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., Smith J.D.,
RA Blech L., Febbraio M., Bornstein P., Plow E.F., 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 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 in
RT 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., Park J.,
RA Zhang X., Lee J., Corpe M., Sharp K., Steward O., Eroglu C., Barres B.,
RA Zaucke F., Xu Z.C., Luo Z.D.;
RT "Thrombospondin-4 contributes to spinal sensitization and neuropathic pain
RT states.";
RL J. Neurosci. 32:8977-8987(2012).
RN [8]
RP FUNCTION, TISSUE SPECIFICITY, DISRUPTION PHENOTYPE, AND INTERACTION WITH
RP 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 by
RT Notch modulator Thbs4.";
RL Nature 497:369-373(2013).
CC -!- FUNCTION: Adhesive glycoprotein that mediates cell-to-cell and cell-to-
CC matrix interactions and is involved in various processes including
CC cellular proliferation, migration, adhesion and attachment,
CC inflammatory response to CNS injury, regulation of vascular
CC inflammation and adaptive responses of the heart to pressure overload
CC and in myocardial function and remodeling. Binds to structural
CC extracellular matrix (ECM) proteins and modulates the ECM in response
CC to tissue damage, contributing to cardioprotective and adaptive ECM
CC remodeling. Plays a role in ER stress response, via its interaction
CC with the activating transcription factor 6 alpha (ATF6) which produces
CC adaptive ER stress response factors and protects myocardium from
CC pressure overload. May contribute to spinal presynaptic
CC hypersensitivity and neuropathic pain states after peripheral nerve
CC injury. May 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) with
CC 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 Q9Z1T2; 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 {ECO:0000269|PubMed:22682248}.
CC Secreted, extracellular space {ECO:0000269|PubMed:22682248}. Secreted,
CC extracellular space, extracellular matrix {ECO:0000269|PubMed:22362893,
CC ECO:0000269|PubMed:22682248}.
CC -!- TISSUE SPECIFICITY: Heart. Up-regulated in the heart in response to
CC ischemic injury and pathology (at protein level). Astrocytes; expressed
CC at high levels in subventricular zone (SVZ)-derived astrocytes and at
CC low levels in cortical astrocytes. In response to peripheral nerve
CC injury, significantly up-regulated in the dorsal spinal cord (at
CC protein level). {ECO:0000269|PubMed:22362893,
CC ECO:0000269|PubMed:22745497, ECO:0000269|PubMed:23615612}.
CC -!- DISRUPTION PHENOTYPE: On exposure to acute pressure overload, mice
CC exhibit a marked increase in: heart weight and fibrosis, cardiomyocyte
CC size and number of apoptotic cells in the myocardium, deposition of
CC extracellular matrix (ECM) and levels of interstitial collagens. The
CC increased ECM deposition is accompanied by changes in functional
CC parameters of the heart and decreased vessel density. Mice also show
CC defective induction of the ER stress response in the heart. Do not
CC exhibit peripheral nerve injury-induced behavioral hypersensitivities
CC such as 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}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
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 AlphaFoldDB; Q9Z1T2; -.
DR SMR; Q9Z1T2; -.
DR ComplexPortal; CPX-3025; Thrombospondin 4 complex.
DR IntAct; Q9Z1T2; 1.
DR STRING; 10090.ENSMUSP00000022213; -.
DR GlyGen; Q9Z1T2; 3 sites.
DR PhosphoSitePlus; Q9Z1T2; -.
DR CPTAC; non-CPTAC-3954; -.
DR MaxQB; Q9Z1T2; -.
DR PaxDb; Q9Z1T2; -.
DR PRIDE; Q9Z1T2; -.
DR ProteomicsDB; 297998; -.
DR Antibodypedia; 3891; 175 antibodies from 26 providers.
DR DNASU; 21828; -.
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 VEuPathDB; HostDB:ENSMUSG00000021702; -.
DR eggNOG; ENOG502QRK8; Eukaryota.
DR GeneTree; ENSGT00940000155227; -.
DR HOGENOM; CLU_009257_1_1_1; -.
DR InParanoid; Q9Z1T2; -.
DR OMA; PRVPNRD; -.
DR OrthoDB; 120983at2759; -.
DR PhylomeDB; Q9Z1T2; -.
DR TreeFam; TF324917; -.
DR Reactome; R-MMU-186797; Signaling by PDGF.
DR BioGRID-ORCS; 21828; 8 hits in 74 CRISPR screens.
DR ChiTaRS; Thbs4; mouse.
DR PRO; PR:Q9Z1T2; -.
DR Proteomes; UP000000589; Chromosome 13.
DR RNAct; Q9Z1T2; protein.
DR Bgee; ENSMUSG00000021702; Expressed in tarsal region and 147 other tissues.
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: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:0042802; F:identical protein 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: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; -; 2.
DR InterPro; IPR013320; ConA-like_dom_sf.
DR InterPro; IPR001881; EGF-like_Ca-bd_dom.
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; IPR003367; Thrombospondin_3-like_rpt.
DR InterPro; IPR017897; Thrombospondin_3_rpt.
DR InterPro; IPR008859; Thrombospondin_C.
DR InterPro; IPR028974; TSP_type-3_rpt.
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; Disulfide bond; EGF-like domain;
KW Endoplasmic reticulum; Extracellular matrix; Glycoprotein; Growth factor;
KW Mitogen; Reference proteome; Repeat; Sarcoplasmic reticulum; Secreted;
KW Signal; Tissue remodeling; Unfolded protein response.
FT SIGNAL 1..26
FT /evidence="ECO:0000255"
FT CHAIN 27..963
FT /note="Thrombospondin-4"
FT /id="PRO_0000035853"
FT DOMAIN 29..194
FT /note="Laminin G-like"
FT DOMAIN 288..327
FT /note="EGF-like 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 328..365
FT /note="EGF-like 2; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 381..418
FT /note="EGF-like 3; calcium-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 422..464
FT /note="EGF-like 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT REPEAT 465..497
FT /note="TSP type-3 1"
FT REPEAT 498..533
FT /note="TSP type-3 2"
FT REPEAT 534..556
FT /note="TSP type-3 3"
FT REPEAT 557..592
FT /note="TSP type-3 4"
FT REPEAT 593..615
FT /note="TSP type-3 5"
FT REPEAT 616..653
FT /note="TSP type-3 6"
FT REPEAT 654..693
FT /note="TSP type-3 7"
FT REPEAT 694..729
FT /note="TSP type-3 8"
FT DOMAIN 733..947
FT /note="TSP C-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00635"
FT REGION 579..676
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 138..140
FT /note="Cell attachment site"
FT /evidence="ECO:0000255"
FT MOTIF 564..566
FT /note="Cell attachment site"
FT /evidence="ECO:0000255"
FT COMPBIAS 588..602
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 608..630
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 640..656
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 660..674
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 614
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 650
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 943
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 260
FT /note="Interchain"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 263
FT /note="Interchain"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 292..303
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 297..312
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 315..326
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 332..343
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 337..352
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 355..379
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 385..396
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 390..405
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 408..420
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 426..440
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 434..450
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 452..463
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 479..484
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 489..509
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 525..545
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 548..568
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 584..604
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 607..627
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 645..665
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 685..705
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DISULFID 721..942
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT CONFLICT 40
FT /note="S -> P (in Ref. 1; AAD27642)"
FT /evidence="ECO:0000305"
FT CONFLICT 290
FT /note="R -> H (in Ref. 1; AAD32714)"
FT /evidence="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
