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Protein

Thrombospondin-4

Gene

THBS4

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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 (By similarity).By similarity1 Publication

GO - Molecular functioni

  • calcium ion binding Source: UniProtKB
  • growth factor activity Source: UniProtKB-KW
  • heparin binding Source: UniProtKB
  • integrin binding Source: UniProtKB

GO - Biological processi

  • behavioral response to pain Source: UniProtKB
  • endothelial cell-cell adhesion Source: UniProtKB
  • myoblast migration Source: UniProtKB
  • negative regulation of angiogenesis Source: UniProtKB
  • positive regulation of cell division Source: UniProtKB-KW
  • positive regulation of endothelial cell proliferation Source: UniProtKB
  • positive regulation of neutrophil chemotaxis Source: UniProtKB
  • positive regulation of peptidyl-tyrosine phosphorylation Source: UniProtKB
  • regulation of tissue remodeling Source: UniProtKB
  • response to endoplasmic reticulum stress Source: UniProtKB
  • response to unfolded protein Source: UniProtKB-KW
  • tissue remodeling Source: UniProtKB-KW

Keywordsi

Molecular functionGrowth factor, Mitogen
Biological processCell adhesion, Tissue remodeling, Unfolded protein response
LigandCalcium

Enzyme and pathway databases

ReactomeiR-HSA-186797 Signaling by PDGF

Names & Taxonomyi

Protein namesi
Recommended name:
Thrombospondin-4
Gene namesi
Name:THBS4
Synonyms:TSP4
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 5

Organism-specific databases

EuPathDBiHostDB:ENSG00000113296.14
HGNCiHGNC:11788 THBS4
MIMi600715 gene
neXtProtiNX_P35443

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Endoplasmic reticulum, Extracellular matrix, Sarcoplasmic reticulum, Secreted

Pathology & Biotechi

Organism-specific databases

DisGeNETi7060
OpenTargetsiENSG00000113296
PharmGKBiPA36500

Polymorphism and mutation databases

BioMutaiTHBS4
DMDMi55977790

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 26Sequence analysisAdd BLAST26
ChainiPRO_000003585227 – 961Thrombospondin-4Add BLAST935

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi258InterchainCurated
Disulfide bondi261InterchainCurated
Disulfide bondi290 ↔ 301PROSITE-ProRule annotation
Disulfide bondi295 ↔ 310PROSITE-ProRule annotation
Disulfide bondi313 ↔ 324PROSITE-ProRule annotation
Disulfide bondi330 ↔ 341PROSITE-ProRule annotation
Disulfide bondi335 ↔ 350PROSITE-ProRule annotation
Disulfide bondi353 ↔ 377PROSITE-ProRule annotation
Disulfide bondi383 ↔ 394PROSITE-ProRule annotation
Disulfide bondi388 ↔ 403PROSITE-ProRule annotation
Disulfide bondi406 ↔ 418PROSITE-ProRule annotation
Disulfide bondi424 ↔ 438PROSITE-ProRule annotation
Disulfide bondi432 ↔ 448PROSITE-ProRule annotation
Disulfide bondi450 ↔ 461PROSITE-ProRule annotation
Disulfide bondi477 ↔ 482PROSITE-ProRule annotation
Disulfide bondi487 ↔ 507PROSITE-ProRule annotation
Disulfide bondi523 ↔ 543PROSITE-ProRule annotation
Disulfide bondi546 ↔ 566PROSITE-ProRule annotation
Disulfide bondi582 ↔ 602PROSITE-ProRule annotation
Disulfide bondi605 ↔ 625PROSITE-ProRule annotation
Glycosylationi612N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi643 ↔ 663PROSITE-ProRule annotation
Disulfide bondi683 ↔ 703PROSITE-ProRule annotation
Disulfide bondi719 ↔ 940PROSITE-ProRule annotation
Glycosylationi941N-linked (GlcNAc...) asparagineSequence analysis1

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

EPDiP35443
MaxQBiP35443
PaxDbiP35443
PeptideAtlasiP35443
PRIDEiP35443
ProteomicsDBi55063

PTM databases

iPTMnetiP35443
PhosphoSitePlusiP35443

Expressioni

Gene expression databases

BgeeiENSG00000113296
CleanExiHS_THBS4
ExpressionAtlasiP35443 baseline and differential
GenevisibleiP35443 HS

Organism-specific databases

HPAiCAB004597
HPA042426

Interactioni

Subunit structurei

Homopentamer; disulfide-linked. Interacts with PTBP3. Interacts with NOTCH1 (By similarity). Interacts (via EGF-like 3; calcium-binding domain) with ATF6 and facilitates its processing, activation and nuclear translocation.By similarity3 Publications

GO - Molecular functioni

  • growth factor activity Source: UniProtKB-KW
  • integrin binding Source: UniProtKB

Protein-protein interaction databases

BioGridi112918, 3 interactors
ComplexPortaliCPX-1790 Thrombospondin 4 complex
IntActiP35443, 1 interactor
STRINGi9606.ENSP00000339730

Structurei

3D structure databases

ProteinModelPortaliP35443
SMRiP35443
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini27 – 192Laminin G-likeAdd BLAST166
Domaini286 – 325EGF-like 1PROSITE-ProRule annotationAdd BLAST40
Domaini326 – 363EGF-like 2; calcium-bindingPROSITE-ProRule annotationAdd BLAST38
Domaini379 – 419EGF-like 3; calcium-bindingPROSITE-ProRule annotationAdd BLAST41
Domaini420 – 462EGF-like 4PROSITE-ProRule annotationAdd BLAST43
Repeati463 – 495TSP type-3 1Add BLAST33
Repeati496 – 531TSP type-3 2Add BLAST36
Repeati532 – 554TSP type-3 3Add BLAST23
Repeati555 – 590TSP type-3 4Add BLAST36
Repeati591 – 613TSP type-3 5Add BLAST23
Repeati614 – 651TSP type-3 6Add BLAST38
Repeati652 – 691TSP type-3 7Add BLAST40
Repeati692 – 727TSP type-3 8Add BLAST36
Domaini731 – 945TSP C-terminalPROSITE-ProRule annotationAdd BLAST215

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi562 – 564Cell attachment siteSequence analysis3

Sequence similaritiesi

Belongs to the thrombospondin family.Curated

Keywords - Domaini

EGF-like domain, Repeat, Signal

Phylogenomic databases

eggNOGiENOG410IFQQ Eukaryota
ENOG410XQKE LUCA
GeneTreeiENSGT00850000132273
HOGENOMiHOG000007542
HOVERGENiHBG000636
InParanoidiP35443
KOiK04659
OMAiAECQACG
OrthoDBiEOG091G00TV
PhylomeDBiP35443
TreeFamiTF324917

Family and domain databases

Gene3Di4.10.1080.10, 3 hits
InterProiView protein in InterPro
IPR013320 ConA-like_dom_sf
IPR001881 EGF-like_Ca-bd_dom
IPR013032 EGF-like_CS
IPR000742 EGF-like_dom
IPR018097 EGF_Ca-bd_CS
IPR001791 Laminin_G
IPR024665 Thbs/COMP_coiled-coil
IPR037349 Thrombospondin
IPR003367 Thrombospondin_3-like_rpt
IPR017897 Thrombospondin_3_rpt
IPR008859 Thrombospondin_C
IPR028974 TSP_type-3_rpt
PANTHERiPTHR10199 PTHR10199, 1 hit
PfamiView protein in Pfam
PF11598 COMP, 1 hit
PF07645 EGF_CA, 2 hits
PF02412 TSP_3, 6 hits
PF05735 TSP_C, 1 hit
SMARTiView protein in SMART
SM00181 EGF, 4 hits
SM00179 EGF_CA, 3 hits
SM00210 TSPN, 1 hit
SUPFAMiSSF103647 SSF103647, 3 hits
SSF49899 SSF49899, 2 hits
PROSITEiView protein in PROSITE
PS01186 EGF_2, 1 hit
PS50026 EGF_3, 4 hits
PS01187 EGF_CA, 2 hits
PS51234 TSP3, 8 hits
PS51236 TSP_CTER, 1 hit

Sequencei

Sequence statusi: Complete.

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

P35443-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MLAPRGAAVL LLHLVLQRWL AAGAQATPQV FDLLPSSSQR LNPGALLPVL
60 70 80 90 100
TDPALNDLYV ISTFKLQTKS SATIFGLYSS TDNSKYFEFT VMGRLNKAIL
110 120 130 140 150
RYLKNDGKVH LVVFNNLQLA DGRRHRILLR LSNLQRGAGS LELYLDCIQV
160 170 180 190 200
DSVHNLPRAF AGPSQKPETI ELRTFQRKPQ DFLEELKLVV RGSLFQVASL
210 220 230 240 250
QDCFLQQSEP LAATGTGDFN RQFLGQMTQL NQLLGEVKDL LRQQVKETSF
260 270 280 290 300
LRNTIAECQA CGPLKFQSPT PSTVVPPAPP APPTRPPRRC DSNPCFRGVQ
310 320 330 340 350
CTDSRDGFQC GPCPEGYTGN GITCIDVDEC KYHPCYPGVH CINLSPGFRC
360 370 380 390 400
DACPVGFTGP MVQGVGISFA KSNKQVCTDI DECRNGACVP NSICVNTLGS
410 420 430 440 450
YRCGPCKPGY TGDQIRGCKA ERNCRNPELN PCSVNAQCIE ERQGDVTCVC
460 470 480 490 500
GVGWAGDGYI CGKDVDIDSY PDEELPCSAR NCKKDNCKYV PNSGQEDADR
510 520 530 540 550
DGIGDACDED ADGDGILNEQ DNCVLIHNVD QRNSDKDIFG DACDNCLSVL
560 570 580 590 600
NNDQKDTDGD GRGDACDDDM DGDGIKNILD NCPKFPNRDQ RDKDGDGVGD
610 620 630 640 650
ACDSCPDVSN PNQSDVDNDL VGDSCDTNQD SDGDGHQDST DNCPTVINSA
660 670 680 690 700
QLDTDKDGIG DECDDDDDND GIPDLVPPGP DNCRLVPNPA QEDSNSDGVG
710 720 730 740 750
DICESDFDQD QVIDRIDVCP ENAEVTLTDF RAYQTVVLDP EGDAQIDPNW
760 770 780 790 800
VVLNQGMEIV QTMNSDPGLA VGYTAFNGVD FEGTFHVNTQ TDDDYAGFIF
810 820 830 840 850
GYQDSSSFYV VMWKQTEQTY WQATPFRAVA EPGIQLKAVK SKTGPGEHLR
860 870 880 890 900
NSLWHTGDTS DQVRLLWKDS RNVGWKDKVS YRWFLQHRPQ VGYIRVRFYE
910 920 930 940 950
GSELVADSGV TIDTTMRGGR LGVFCFSQEN IIWSNLKYRC NDTIPEDFQE
960
FQTQNFDRFD N
Length:961
Mass (Da):105,869
Last modified:November 23, 2004 - v2
Checksum:i18F867AA5FFDA54B
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti96N → S no nucleotide entry (PubMed:8350346).Curated1
Sequence conflicti96N → S in CAA79635 (PubMed:7852353).Curated1
Sequence conflicti276P → A no nucleotide entry (PubMed:8350346).Curated1
Sequence conflicti276P → A in CAA79635 (PubMed:7852353).Curated1
Sequence conflicti737V → G no nucleotide entry (PubMed:8350346).Curated1
Sequence conflicti737V → G in CAA79635 (PubMed:7852353).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_01995155L → Q1 PublicationCorresponds to variant dbSNP:rs17881847Ensembl.1
Natural variantiVAR_019952387A → P Functional polymorphism; associated with a pro-atherogenic phenotype. 3 PublicationsCorresponds to variant dbSNP:rs1866389Ensembl.1
Natural variantiVAR_019953420A → V3 PublicationsCorresponds to variant dbSNP:rs17882372Ensembl.1
Natural variantiVAR_019954646V → I1 PublicationCorresponds to variant dbSNP:rs2229396Ensembl.1
Natural variantiVAR_052659737V → I. Corresponds to variant dbSNP:rs2229398Ensembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Z19585 mRNA Translation: CAA79635.1
AK313587 mRNA Translation: BAG36356.1
AY566253 Genomic DNA Translation: AAS66982.1
BC050456 mRNA Translation: AAH50456.1
CCDSiCCDS4049.1
PIRiA55710 TSHUP4
RefSeqiNP_001293141.1, NM_001306212.1
NP_001293142.1, NM_001306213.1
NP_001293143.1, NM_001306214.1
NP_003239.2, NM_003248.5
UniGeneiHs.211426

Genome annotation databases

EnsembliENST00000350881; ENSP00000339730; ENSG00000113296
GeneIDi7060
KEGGihsa:7060
UCSCiuc021yaw.2 human

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Entry informationi

Entry nameiTSP4_HUMAN
AccessioniPrimary (citable) accession number: P35443
Secondary accession number(s): B2R909, Q86TG2
Entry historyiIntegrated into UniProtKB/Swiss-Prot: June 1, 1994
Last sequence update: November 23, 2004
Last modified: July 18, 2018
This is version 180 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 5
    Human chromosome 5: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

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