ID   TSP4_RAT                Reviewed;         980 AA.
AC   P49744;
DT   01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT   01-OCT-1996, sequence version 1.
DT   24-JAN-2024, entry version 156.
DE   RecName: Full=Thrombospondin-4;
DE   Flags: Precursor;
GN   Name=Thbs4; Synonyms=Tsp-4, Tsp4;
OS   Rattus norvegicus (Rat).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Rattus.
OX   NCBI_TaxID=10116;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   STRAIN=Lewis; TISSUE=Skeletal muscle;
RX   PubMed=7490284; DOI=10.1083/jcb.131.4.1083;
RA   Arber S., Caroni P.;
RT   "Thrombospondin-4, an extracellular matrix protein expressed in the
RT   developing and adult nervous system promotes neurite outgrowth.";
RL   J. Cell Biol. 131:1083-1094(1995).
RN   [2]
RP   FUNCTION, AND TISSUE SPECIFICITY.
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   [3]
RP   FUNCTION, AND TISSUE SPECIFICITY.
RX   PubMed=23649982; DOI=10.1002/j.1532-2149.2013.00326.x;
RA   Zeng J., Kim D., Li K.W., Sharp K., Steward O., Zaucke F., Luo Z.D.;
RT   "Thrombospondin-4 contributes to spinal cord injury-induced changes in
RT   nociception.";
RL   Eur. J. Pain 17:1458-1464(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:22745497, ECO:0000269|PubMed:23649982}.
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 (By similarity). {ECO:0000250}.
CC   -!- SUBCELLULAR LOCATION: Endoplasmic reticulum
CC       {ECO:0000250|UniProtKB:Q9Z1T2}. Sarcoplasmic reticulum
CC       {ECO:0000250|UniProtKB:Q9Z1T2}. Secreted
CC       {ECO:0000250|UniProtKB:Q9Z1T2}. Secreted, extracellular space
CC       {ECO:0000250|UniProtKB:Q9Z1T2}. Secreted, extracellular space,
CC       extracellular matrix {ECO:0000250|UniProtKB:Q9Z1T2}.
CC   -!- TISSUE SPECIFICITY: Mainly expressed in astrocytes, and in ressponse to
CC       peripheral nerve injury, significantly up-regulated in the dorsal
CC       spinal cord (at protein level). {ECO:0000269|PubMed:22745497,
CC       ECO:0000269|PubMed:23649982}.
CC   -!- SIMILARITY: Belongs to the thrombospondin family. {ECO:0000305}.
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DR   EMBL; X89963; CAA62002.1; -; mRNA.
DR   AlphaFoldDB; P49744; -.
DR   SMR; P49744; -.
DR   ComplexPortal; CPX-4106; Thrombospondin 4 complex.
DR   IntAct; P49744; 1.
DR   STRING; 10116.ENSRNOP00000074259; -.
DR   GlyCosmos; P49744; 2 sites, No reported glycans.
DR   GlyGen; P49744; 2 sites.
DR   PhosphoSitePlus; P49744; -.
DR   PaxDb; 10116-ENSRNOP00000062272; -.
DR   UCSC; RGD:62046; rat.
DR   AGR; RGD:62046; -.
DR   RGD; 62046; Thbs4.
DR   eggNOG; ENOG502QRK8; Eukaryota.
DR   InParanoid; P49744; -.
DR   PhylomeDB; P49744; -.
DR   Reactome; R-RNO-186797; Signaling by PDGF.
DR   PRO; PR:P49744; -.
DR   Proteomes; UP000002494; Unplaced.
DR   GO; GO:0005604; C:basement membrane; ISO:RGD.
DR   GO; GO:0062023; C:collagen-containing extracellular matrix; ISS:UniProtKB.
DR   GO; GO:0005783; C:endoplasmic reticulum; ISS:UniProtKB.
DR   GO; GO:0005615; C:extracellular space; ISS:UniProtKB.
DR   GO; GO:0031594; C:neuromuscular junction; IDA:RGD.
DR   GO; GO:0016529; C:sarcoplasmic reticulum; ISS:UniProtKB.
DR   GO; GO:0005509; F:calcium ion binding; ISO:RGD.
DR   GO; GO:0005518; F:collagen binding; IDA:RGD.
DR   GO; GO:0001968; F:fibronectin binding; IDA:RGD.
DR   GO; GO:0008083; F:growth factor activity; IEA:UniProtKB-KW.
DR   GO; GO:0008201; F:heparin binding; ISO:RGD.
DR   GO; GO:0042802; F:identical protein binding; IPI:RGD.
DR   GO; GO:0005178; F:integrin binding; ISO:RGD.
DR   GO; GO:0043237; F:laminin-1 binding; IDA:RGD.
DR   GO; GO:0048266; P:behavioral response to pain; IMP:UniProtKB.
DR   GO; GO:0071603; P:endothelial cell-cell adhesion; ISO:RGD.
DR   GO; GO:0051451; P:myoblast migration; ISO:RGD.
DR   GO; GO:0016525; P:negative regulation of angiogenesis; ISO:RGD.
DR   GO; GO:0007399; P:nervous system development; IDA:RGD.
DR   GO; GO:0048812; P:neuron projection morphogenesis; IDA:RGD.
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:RGD.
DR   GO; GO:0090023; P:positive regulation of neutrophil chemotaxis; ISO:RGD.
DR   GO; GO:0050731; P:positive regulation of peptidyl-tyrosine phosphorylation; ISO:RGD.
DR   GO; GO:0034103; P:regulation of tissue remodeling; ISS:UniProtKB.
DR   GO; GO:0034976; P:response to endoplasmic reticulum stress; ISS:UniProtKB.
DR   GO; GO:0006986; P:response to unfolded protein; IEA:UniProtKB-KW.
DR   GO; GO:0048771; P:tissue remodeling; IEA:UniProtKB-KW.
DR   CDD; cd00054; EGF_CA; 3.
DR   CDD; cd16080; TSP-4cc; 1.
DR   Gene3D; 1.20.5.10; -; 1.
DR   Gene3D; 2.60.120.200; -; 2.
DR   Gene3D; 2.10.25.10; Laminin; 4.
DR   Gene3D; 4.10.1080.10; TSP type-3 repeat; 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; IPR003367; Thrombospondin_3-like_rpt.
DR   InterPro; IPR017897; Thrombospondin_3_rpt.
DR   InterPro; IPR008859; Thrombospondin_C.
DR   InterPro; IPR024665; TSP/COMP_coiled-coil.
DR   InterPro; IPR046970; TSP/COMP_coiled-coil_sf.
DR   InterPro; IPR028974; TSP_type-3_rpt.
DR   InterPro; IPR048287; TSPN-like_N.
DR   PANTHER; PTHR10199; THROMBOSPONDIN; 1.
DR   PANTHER; PTHR10199:SF92; THROMBOSPONDIN-4; 1.
DR   Pfam; PF11598; COMP; 1.
DR   Pfam; PF00008; EGF; 1.
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; SSF58006; Assembly domain of cartilage oligomeric matrix protein; 1.
DR   SUPFAM; SSF49899; Concanavalin A-like lectins/glucanases; 2.
DR   SUPFAM; SSF57196; EGF/Laminin; 1.
DR   SUPFAM; SSF103647; TSP type-3 repeat; 3.
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..42
FT                   /evidence="ECO:0000255"
FT   CHAIN           43..980
FT                   /note="Thrombospondin-4"
FT                   /id="PRO_0000035854"
FT   DOMAIN          43..210
FT                   /note="Laminin G-like"
FT   DOMAIN          304..343
FT                   /note="EGF-like 1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DOMAIN          344..381
FT                   /note="EGF-like 2; calcium-binding"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DOMAIN          397..434
FT                   /note="EGF-like 3; calcium-binding"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DOMAIN          438..481
FT                   /note="EGF-like 4"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   REPEAT          482..514
FT                   /note="TSP type-3 1"
FT   REPEAT          515..550
FT                   /note="TSP type-3 2"
FT   REPEAT          551..573
FT                   /note="TSP type-3 3"
FT   REPEAT          574..609
FT                   /note="TSP type-3 4"
FT   REPEAT          610..632
FT                   /note="TSP type-3 5"
FT   REPEAT          633..670
FT                   /note="TSP type-3 6"
FT   REPEAT          671..710
FT                   /note="TSP type-3 7"
FT   REPEAT          711..746
FT                   /note="TSP type-3 8"
FT   DOMAIN          750..964
FT                   /note="TSP C-terminal"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00635"
FT   REGION          596..691
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        605..619
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        625..647
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        657..671
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        677..691
FT                   /note="Acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   CARBOHYD        631
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        960
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   DISULFID        276
FT                   /note="Interchain"
FT                   /evidence="ECO:0000305"
FT   DISULFID        279
FT                   /note="Interchain"
FT                   /evidence="ECO:0000305"
FT   DISULFID        308..319
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DISULFID        313..328
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DISULFID        331..342
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DISULFID        348..359
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DISULFID        353..368
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DISULFID        371..395
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DISULFID        401..412
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DISULFID        406..421
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DISULFID        424..436
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DISULFID        442..456
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DISULFID        450..466
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DISULFID        468..480
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DISULFID        496..501
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DISULFID        506..526
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DISULFID        542..562
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DISULFID        565..585
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DISULFID        601..621
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DISULFID        624..644
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DISULFID        662..682
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DISULFID        702..722
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT   DISULFID        738..959
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
SQ   SEQUENCE   980 AA;  108214 MW;  056D41EB6E206FCF CRC64;
     MTMITPSSKL TLTKGNKSWS STRCGAFLLL HLVLQPWQRA GAQATPQVFD LLPSSSQRLN
     PAALQPVLTD PTLHELYVIS TFKLQSKSSA TIFGLYSSSD NSKYFEFTVM GRLNKAILRY
     LKDDGKIHLV VFNNLQLADG RRHRILLRLS NLQRGAGSVE LYLDCVQVDS VNNLPRAFSG
     LTQNPQAIEL RTFQRKPQDF LEELKLVVRG SLFQVASLQD CFLQQSEPLA ATGTGDFNRQ
     FLGQMTQLNQ LLGEVKDLLR QQVKETSFLR NTIAECQACG PLSFQSPTPN TLVPIAPPAP
     PTRPTRRCDS SPCFRGVRCT DTRDGFQCGP CPDGYTGNGI TCSDVDECKY HPCYPGVRCT
     NLAPGFRCDA CPVGFTGPMV QGVGINFAKT NKQVCTDVDE CRNGACVLNS ICINTLGSYR
     CGPCKPGYTG DQTRGCRTER SCRNPEQNPC SVHAQCIEER QGDVTCVCGV GWAGRAGYVC
     GKDVDIDSYP DEELPCSARN CKKDNCKYVP NSGQEDADRD GIGDACDEDA DGDGILNEQD
     NCVLTHNVDQ RNTDKDIFGD ACDNCRGVLN NDQKDTDGDG KGDACDDDMD GDGIKNILDN
     CPRVPNRDQQ DRDGDGVGDA CDSCPDVSNP NQSDVDNDLV GDSCDTNQDS DGDGHQDSTD
     NCPTVINSAQ LDTDKDGIGD ECDDDDDNDG MPDLFPPGPD NCRLVPNPAQ EDSNNDGVGD
     ICEADFDQDK VIDRIDVCPE NAEITLTDFR AYQTVVLDPE GDAQIDPNWV VLNQGMEIVQ
     TMNSDPGLAV GYTAFNGVDF EGTFHVNTQT DDDYAGFIFG YQDSSSFYVV MWKQTEQTYW
     QATPFRAVAE PGIQLKAVKS KTGPGEHLRN SLWHTGDTSD QVRLLWKDSR NVGWKDKVSY
     RWFLQHRPQV GYIRVRFYEG SELVADSGVT IDTTMRGGRL GVFCFSQENI IWSNLKYRCN
     DTIPEDFQEF QIQTFDRLDN
//