TSP4_RAT
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 03-AUG-2022, entry version 150.
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.ENSRNOP00000062272; -.
DR GlyGen; P49744; 2 sites.
DR PhosphoSitePlus; P49744; -.
DR PaxDb; P49744; -.
DR PRIDE; P49744; -.
DR UCSC; RGD:62046; rat.
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:0031012; C:extracellular matrix; IDA:RGD.
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 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; PF00008; EGF; 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..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
