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Protein

Thrombospondin-4

Gene

THBS4

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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
  • 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
Complete GO annotation...

Keywords - Molecular functioni

Growth factor, Mitogen

Keywords - Biological processi

Cell adhesion, Tissue remodeling, Unfolded protein response

Keywords - Ligandi

Calcium

Enzyme and pathway databases

BioCyciZFISH:ENSG00000113296-MONOMER.
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

HGNCiHGNC:11788. THBS4.

Subcellular locationi

  • Endoplasmic reticulum By similarity
  • Sarcoplasmic reticulum By similarity
  • Secreted By similarity
  • Secretedextracellular space By similarity
  • Secretedextracellular spaceextracellular matrix By similarity

GO - Cellular componenti

  • basement membrane Source: UniProtKB
  • endoplasmic reticulum Source: UniProtKB
  • extracellular exosome Source: UniProtKB
  • extracellular matrix Source: UniProtKB
  • extracellular region Source: Reactome
  • extracellular space Source: UniProtKB
  • sarcoplasmic reticulum Source: UniProtKB
Complete GO annotation...

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...)Sequence analysis1
Disulfide bondi643 ↔ 663PROSITE-ProRule annotation
Disulfide bondi683 ↔ 703PROSITE-ProRule annotation
Disulfide bondi719 ↔ 940PROSITE-ProRule annotation
Glycosylationi941N-linked (GlcNAc...)Sequence analysis1

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

EPDiP35443.
MaxQBiP35443.
PaxDbiP35443.
PeptideAtlasiP35443.
PRIDEiP35443.

PTM databases

iPTMnetiP35443.
PhosphoSitePlusiP35443.

Expressioni

Gene expression databases

BgeeiENSG00000113296.
CleanExiHS_THBS4.
ExpressionAtlasiP35443. baseline and differential.
GenevisibleiP35443. HS.

Organism-specific databases

HPAiCAB004597.

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

  • integrin binding Source: UniProtKB

Protein-protein interaction databases

BioGridi112918. 2 interactors.
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
Contains 4 EGF-like domains.PROSITE-ProRule annotation
Contains 1 laminin G-like domain.Curated
Contains 1 TSP C-terminal (TSPC) domain.PROSITE-ProRule annotation
Contains 8 TSP type-3 repeats.PROSITE-ProRule annotation

Keywords - Domaini

EGF-like domain, Repeat, Signal

Phylogenomic databases

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

Family and domain databases

Gene3Di2.60.120.200. 1 hit.
4.10.1080.10. 2 hits.
InterProiIPR013320. ConA-like_dom.
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.
IPR003367. Thrombospondin_3-like_rpt.
IPR017897. Thrombospondin_3_rpt.
IPR008859. Thrombospondin_C.
IPR028974. TSP_type-3_rpt.
[Graphical view]
PfamiPF11598. COMP. 1 hit.
PF07645. EGF_CA. 2 hits.
PF02412. TSP_3. 6 hits.
PF05735. TSP_C. 1 hit.
[Graphical view]
SMARTiSM00181. EGF. 4 hits.
SM00179. EGF_CA. 3 hits.
SM00210. TSPN. 1 hit.
[Graphical view]
SUPFAMiSSF103647. SSF103647. 3 hits.
SSF49899. SSF49899. 2 hits.
PROSITEiPS01186. EGF_2. 1 hit.
PS50026. EGF_3. 4 hits.
PS01187. EGF_CA. 2 hits.
PS51234. TSP3. 8 hits.
PS51236. TSP_CTER. 1 hit.
[Graphical view]

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 → Q.1 PublicationCorresponds to variant rs17881847dbSNPEnsembl.1
Natural variantiVAR_019952387A → P Functional polymorphism; associated with a pro-atherogenic phenotype; results in gain of function. 3 PublicationsCorresponds to variant rs1866389dbSNPEnsembl.1
Natural variantiVAR_019953420A → V.3 PublicationsCorresponds to variant rs17882372dbSNPEnsembl.1
Natural variantiVAR_019954646V → I.1 PublicationCorresponds to variant rs2229396dbSNPEnsembl.1
Natural variantiVAR_052659737V → I.Corresponds to variant rs2229398dbSNPEnsembl.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

Cross-referencesi

Web resourcesi

SeattleSNPs

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.

3D structure databases

ProteinModelPortaliP35443.
SMRiP35443.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi112918. 2 interactors.
IntActiP35443. 1 interactor.
STRINGi9606.ENSP00000339730.

PTM databases

iPTMnetiP35443.
PhosphoSitePlusiP35443.

Polymorphism and mutation databases

BioMutaiTHBS4.
DMDMi55977790.

Proteomic databases

EPDiP35443.
MaxQBiP35443.
PaxDbiP35443.
PeptideAtlasiP35443.
PRIDEiP35443.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi7060.
DisGeNETi7060.
GeneCardsiTHBS4.
HGNCiHGNC:11788. THBS4.
HPAiCAB004597.
MIMi600715. gene.
neXtProtiNX_P35443.
OpenTargetsiENSG00000113296.
PharmGKBiPA36500.
GenAtlasiSearch...

Phylogenomic databases

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

Enzyme and pathway databases

BioCyciZFISH:ENSG00000113296-MONOMER.
ReactomeiR-HSA-186797. Signaling by PDGF.

Miscellaneous databases

GeneWikiiTHBS4.
GenomeRNAii7060.
PROiP35443.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000113296.
CleanExiHS_THBS4.
ExpressionAtlasiP35443. baseline and differential.
GenevisibleiP35443. HS.

Family and domain databases

Gene3Di2.60.120.200. 1 hit.
4.10.1080.10. 2 hits.
InterProiIPR013320. ConA-like_dom.
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.
IPR003367. Thrombospondin_3-like_rpt.
IPR017897. Thrombospondin_3_rpt.
IPR008859. Thrombospondin_C.
IPR028974. TSP_type-3_rpt.
[Graphical view]
PfamiPF11598. COMP. 1 hit.
PF07645. EGF_CA. 2 hits.
PF02412. TSP_3. 6 hits.
PF05735. TSP_C. 1 hit.
[Graphical view]
SMARTiSM00181. EGF. 4 hits.
SM00179. EGF_CA. 3 hits.
SM00210. TSPN. 1 hit.
[Graphical view]
SUPFAMiSSF103647. SSF103647. 3 hits.
SSF49899. SSF49899. 2 hits.
PROSITEiPS01186. EGF_2. 1 hit.
PS50026. EGF_3. 4 hits.
PS01187. EGF_CA. 2 hits.
PS51234. TSP3. 8 hits.
PS51236. TSP_CTER. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiTSP4_HUMAN
AccessioniPrimary (citable) accession number: P35443
Secondary accession number(s): B2R909, Q86TG2
Entry historyi
Integrated into UniProtKB/Swiss-Prot: June 1, 1994
Last sequence update: November 23, 2004
Last modified: November 2, 2016
This is version 168 of the entry and version 2 of the sequence. [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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.