THBS4

Protein identityUniProt · HPA

UniProt accession

P35443

Gene

THBS4

Ensembl

ENSG00000113296

Chromosome

5

Canonical length

961 aa

Protein class

Cancer-related genes, Plasma proteins, Predicted intracellular proteins, Predicted secreted proteins

Subcellular location

Vesicles

Secretome location

Secreted to extracellular matrix

Quaternary structure

Homopentamer

OverviewNCBI Gene

The protein encoded by this gene belongs to the thrombospondin protein family. Thrombospondin family members are adhesive glycoproteins that mediate cell-to-cell and cell-to-matrix interactions. This protein forms a pentamer and can bind to heparin and calcium. It is involved in local signaling in the developing and adult nervous system, and it contributes to spinal sensitization and neuropathic pain states. This gene is activated during the stromal response to invasive breast cancer. It may also play a role in inflammatory responses in Alzheimer's disease. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2015]

Canonical amino-acid sequenceUniProt

961 residues, UniProt reviewed canonical sequence.

>P35443|THBS4
     1  MLAPRGAAVL LLHLVLQRWL AAGAQATPQV FDLLPSSSQR LNPGALLPVL TDPALNDLYV
    61  ISTFKLQTKS SATIFGLYSS TDNSKYFEFT VMGRLNKAIL RYLKNDGKVH LVVFNNLQLA
   121  DGRRHRILLR LSNLQRGAGS LELYLDCIQV DSVHNLPRAF AGPSQKPETI ELRTFQRKPQ
   181  DFLEELKLVV RGSLFQVASL QDCFLQQSEP LAATGTGDFN RQFLGQMTQL NQLLGEVKDL
   241  LRQQVKETSF LRNTIAECQA CGPLKFQSPT PSTVVPPAPP APPTRPPRRC DSNPCFRGVQ
   301  CTDSRDGFQC GPCPEGYTGN GITCIDVDEC KYHPCYPGVH CINLSPGFRC DACPVGFTGP
   361  MVQGVGISFA KSNKQVCTDI DECRNGACVP NSICVNTLGS YRCGPCKPGY TGDQIRGCKA
   421  ERNCRNPELN PCSVNAQCIE ERQGDVTCVC GVGWAGDGYI CGKDVDIDSY PDEELPCSAR
   481  NCKKDNCKYV PNSGQEDADR DGIGDACDED ADGDGILNEQ DNCVLIHNVD QRNSDKDIFG
   541  DACDNCLSVL NNDQKDTDGD GRGDACDDDM DGDGIKNILD NCPKFPNRDQ RDKDGDGVGD
   601  ACDSCPDVSN PNQSDVDNDL VGDSCDTNQD SDGDGHQDST DNCPTVINSA QLDTDKDGIG
   661  DECDDDDDND GIPDLVPPGP DNCRLVPNPA QEDSNSDGVG DICESDFDQD QVIDRIDVCP
   721  ENAEVTLTDF RAYQTVVLDP EGDAQIDPNW VVLNQGMEIV QTMNSDPGLA VGYTAFNGVD
   781  FEGTFHVNTQ TDDDYAGFIF GYQDSSSFYV VMWKQTEQTY WQATPFRAVA EPGIQLKAVK
   841  SKTGPGEHLR NSLWHTGDTS DQVRLLWKDS RNVGWKDKVS YRWFLQHRPQ VGYIRVRFYE
   901  GSELVADSGV TIDTTMRGGR LGVFCFSQEN IIWSNLKYRC NDTIPEDFQE FQTQNFDRFD
   961  N

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against THBS4 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Secreted

Secreted

Yes

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.31

Highest tissue expression

235 nTPM

Expression across tissuesHPA

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.92

gnomAD pLI

0

gnomAD missense Z

1.21

DepMap mean gene effect

-0.09

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 3% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

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

Molecular functions

• calcium ion binding
• growth factor activity
• heparin binding
• integrin binding

Cellular components

• basement membrane
• endoplasmic reticulum
• extracellular exosome
• extracellular matrix
• extracellular region
• extracellular space
• sarcoplasmic reticulum

Protein domainsUniProt · Pfam · InterPro

• EGF-like domain
• EGF-like calcium-binding domain
• Thrombospondin, type 3-like repeat
• Thrombospondin, C-terminal
• Concanavalin A-like lectin/glucanase domain superfamily
• Thrombospondin, type 3 repeat
• EGF-like calcium-binding, conserved site
• Thrombospondin/cartilage oligomeric matrix protein, coiled-coil domain
• TSP type-3 repeat
• TSP/COMP, coiled-coil domain superfamily
• Thrombospondin-like, N-terminal domain
• EGF-like domain
• Thrombospondin type 3 repeat
• Thrombospondin C-terminal region
• Cartilage oligomeric matrix protein

KeywordsUniProt

• Calcium
• Cell adhesion
• Disulfide bond
• EGF-like domain
• Endoplasmic reticulum
• Extracellular matrix
• Glycoprotein
• Growth factor
• Mitogen
• Repeat
• Sarcoplasmic reticulum
• Secreted
• Signal
• Tissue remodeling
• Unfolded protein response

InteractionsUniProt · HPA

Protein binding partners of THBS4 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• NOTCH1
• PTBP3
• ATF6