THBS4 thrombospondin 4 [Homo sapiens (human)] - Gene

Summary

Official Symbol: THBS4provided by HGNC
Official Full Name: thrombospondin 4provided by HGNC
Primary source: HGNC:HGNC:11788
See related: Ensembl:ENSG00000113296 MIM:600715; AllianceGenome:HGNC:11788
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: TSP4; TSP-4
Summary: 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]
Expression: Biased expression in fat (RPKM 161.8), heart (RPKM 56.3) and 1 other tissue See more
Orthologs: mouse all
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Genomic context

Location:: 5q14.1

Exon count:: 29

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	5	NC_000005.10 (79991332..80083287)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	5	NC_060929.1 (80475183..80567137)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	5	NC_000005.9 (79287155..79379110)

Chromosome 5 - NC_000005.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Stimulation with THBS4 activates pathways that regulate proliferation, migration and inflammation in primary human keratinocytes.
Title: Stimulation with THBS4 activates pathways that regulate proliferation, migration and inflammation in primary human keratinocytes.
THBS4/integrin alpha2 axis mediates BM-MSCs to promote angiogenesis in gastric cancer associated with chronic Helicobacter pylori infection.
Title: THBS4/integrin α2 axis mediates BM-MSCs to promote angiogenesis in gastric cancer associated with chronic Helicobacter pylori infection.
Pathological Significance and Prognostic Roles of Thrombospondin-3, 4 and 5 in Bladder Cancer.
Title: Pathological Significance and Prognostic Roles of Thrombospondin-3, 4 and 5 in Bladder Cancer.
Spatiotemporal distribution of thrombospondin-4 and -5 in cartilage during endochondral bone formation and repair.
Title: Spatiotemporal distribution of thrombospondin-4 and -5 in cartilage during endochondral bone formation and repair.
THBS4 promotes HCC progression by regulating ITGB1 via FAK/PI3K/AKT pathway.
Title: THBS4 promotes HCC progression by regulating ITGB1 via FAK/PI3K/AKT pathway.
Thrombospondin-4 increases with the severity of peripheral arterial disease and is associated with diabetes.
Title: Thrombospondin-4 increases with the severity of peripheral arterial disease and is associated with diabetes.
THBS4 silencing regulates the cancer stem cell-like properties in prostate cancer via blocking the PI3K/Akt pathway.
Title: THBS4 silencing regulates the cancer stem cell-like properties in prostate cancer via blocking the PI3K/Akt pathway.
THBS4 is expressed on cancer-associated fibroblasts in the gastric cancer microenvironment.
Title: The clinicopathological significance of Thrombospondin-4 expression in the tumor microenvironment of gastric cancer.
In this study the authors have identified a GXKGHR motif on the collagen II helix to bind to COMP, using a recombinantly expressed collagen II peptide library. This binding sequence is conserved throughout evolution and they demonstrate that TSP-4 binds to the same sequence.
Title: COMP and TSP-4 interact specifically with the novel GXKGHR motif only found in fibrillar collagens.
TGF-b1, by activating both Smad3 and p38, induces TSP-4, which in turn not only presents a positive feedback regulation on the activation of Smad3 and p38, but also essentially mediates TGF-b1-induced hypertrophic scar (HS) formation formation
Title: Thrombospondin-4 critically controls transforming growth factor β1 induced hypertrophic scar formation.

Submit: New GeneRIF Correction See all GeneRIFs (40)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

EBI GWAS Catalog

Description
Genetic Variants Associated with Serum Thyroid Stimulating Hormone (TSH) Levels in European Americans and African Americans from the eMERGE Network. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

MARC_15765-15766:1041972257:1 (e-PCR)
- UniSTS:267896

THBS4 (e-PCR)
- UniSTS:504996

SHGC-12514 (e-PCR)
- UniSTS:4078

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables calcium ion binding	IDA Inferred from Direct Assay more info	PubMed
enables growth factor activity	IEA Inferred from Electronic Annotation more info
enables heparin binding	IDA Inferred from Direct Assay more info	PubMed
enables integrin binding	IDA Inferred from Direct Assay more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in behavioral response to pain	ISS Inferred from Sequence or Structural Similarity more info
involved_in endothelial cell-cell adhesion	IDA Inferred from Direct Assay more info	PubMed
involved_in myoblast migration	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of angiogenesis	IEP Inferred from Expression Pattern more info	PubMed
involved_in positive regulation of cell division	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of endothelial cell proliferation	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of neutrophil chemotaxis	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of peptidyl-tyrosine phosphorylation	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of tissue remodeling	ISS Inferred from Sequence or Structural Similarity more info
involved_in response to endoplasmic reticulum stress	IBA Inferred from Biological aspect of Ancestor more info
involved_in response to endoplasmic reticulum stress	ISS Inferred from Sequence or Structural Similarity more info
involved_in response to unfolded protein	IEA Inferred from Electronic Annotation more info
involved_in signal transduction	IEA Inferred from Electronic Annotation more info
involved_in tissue remodeling	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
located_in basement membrane	IDA Inferred from Direct Assay more info	PubMed
is_active_in collagen-containing extracellular matrix	IBA Inferred from Biological aspect of Ancestor more info
located_in collagen-containing extracellular matrix	ISS Inferred from Sequence or Structural Similarity more info
located_in endoplasmic reticulum	ISS Inferred from Sequence or Structural Similarity more info
located_in extracellular exosome	HDA more info	PubMed
located_in extracellular region	TAS Traceable Author Statement more info
located_in extracellular space	IDA Inferred from Direct Assay more info	PubMed
located_in sarcoplasmic reticulum	ISS Inferred from Sequence or Structural Similarity more info

General protein information

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Preferred Names: thrombospondin-4

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_047084.1 RefSeqGene

Range

49038..96977

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001306212.2 → NP_001293141.1 thrombospondin-4 isoform b

See identical proteins and their annotated locations for NP_001293141.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) contains alternate 5' exon structure, and it thus differs in the 5' UTR and initiates translation at a downstream in-frame start codon, compared to variant 1. The encoded isoform (b) is shorter at the N-terminus, compared to isoform a. Variants 2, 3 and 4 all encode isoform b.

Source sequence(s)

BC050456, DC310687, DC342285

Consensus CDS

CCDS78027.1

UniProtKB/TrEMBL

B7Z832, E7ES19

Conserved Domains (8) summary

cd00054
Location:288 → 322

EGF_CA; Calcium-binding EGF-like domain, present in a large number of membrane-bound and extracellular (mostly animal) proteins. Many of these proteins require calcium for their biological function and calcium-binding sites have been found to be located at the ...

sd00001
Location:500 → 522

TSP3; TSP3 repeat_short [structural motif]

sd00002
Location:405 → 440

TSP3; TSP3 repeat_long [structural motif]

pfam00008
Location:199 → 229

EGF; EGF-like domain

pfam02412
Location:406 → 440

TSP_3; Thrombospondin type 3 repeat

pfam05735
Location:654 → 851

TSP_C; Thrombospondin C-terminal region

cd16080
Location:128 → 171

TSP-4cc; Coiled coil region of thrombospondin-4 (TSP-4)

cl22861
Location:1 → 101

LamG; Laminin G domain; Laminin G-like domains are usually Ca++ mediated receptors that can have binding sites for steroids, beta1 integrins, heparin, sulfatides, fibulin-1, and alpha-dystroglycans. Proteins that contain LamG domains serve a variety of ...
NM_001306213.2 → NP_001293142.1 thrombospondin-4 isoform b

See identical proteins and their annotated locations for NP_001293142.1

Status: REVIEWED

Description

Transcript Variant: This variant (3) contains alternate 5' exon structure, and it thus differs in the 5' UTR and initiates translation at a downstream in-frame start codon, compared to variant 1. The encoded isoform (b) is shorter at the N-terminus, compared to isoform a. Variants 2, 3 and 4 all encode isoform b.

Source sequence(s)

BC050456, DC310687, DC342285, DC376500

Consensus CDS

CCDS78027.1

UniProtKB/TrEMBL

B7Z832, E7ES19

Conserved Domains (8) summary

cd00054
Location:288 → 322

EGF_CA; Calcium-binding EGF-like domain, present in a large number of membrane-bound and extracellular (mostly animal) proteins. Many of these proteins require calcium for their biological function and calcium-binding sites have been found to be located at the ...

sd00001
Location:500 → 522

TSP3; TSP3 repeat_short [structural motif]

sd00002
Location:405 → 440

TSP3; TSP3 repeat_long [structural motif]

pfam00008
Location:199 → 229

EGF; EGF-like domain

pfam02412
Location:406 → 440

TSP_3; Thrombospondin type 3 repeat

pfam05735
Location:654 → 851

TSP_C; Thrombospondin C-terminal region

cd16080
Location:128 → 171

TSP-4cc; Coiled coil region of thrombospondin-4 (TSP-4)

cl22861
Location:1 → 101

LamG; Laminin G domain; Laminin G-like domains are usually Ca++ mediated receptors that can have binding sites for steroids, beta1 integrins, heparin, sulfatides, fibulin-1, and alpha-dystroglycans. Proteins that contain LamG domains serve a variety of ...
NM_001306214.2 → NP_001293143.1 thrombospondin-4 isoform b

See identical proteins and their annotated locations for NP_001293143.1

Status: REVIEWED

Description

Transcript Variant: This variant (4) contains an alternate 5' terminal exon, and it thus differs in the 5' UTR and initiates translation at a downstream in-frame start codon, compared to variant 1. The encoded isoform (b) is shorter at the N-terminus, compared to isoform a. Variants 2, 3 and 4 all encode isoform b.

Source sequence(s)

AK302842, BC050456

Consensus CDS

CCDS78027.1

UniProtKB/TrEMBL

B7Z832, E7ES19

Related

ENSP00000422298.1, ENST00000511733.1

Conserved Domains (8) summary

cd00054
Location:288 → 322

EGF_CA; Calcium-binding EGF-like domain, present in a large number of membrane-bound and extracellular (mostly animal) proteins. Many of these proteins require calcium for their biological function and calcium-binding sites have been found to be located at the ...

sd00001
Location:500 → 522

TSP3; TSP3 repeat_short [structural motif]

sd00002
Location:405 → 440

TSP3; TSP3 repeat_long [structural motif]

pfam00008
Location:199 → 229

EGF; EGF-like domain

pfam02412
Location:406 → 440

TSP_3; Thrombospondin type 3 repeat

pfam05735
Location:654 → 851

TSP_C; Thrombospondin C-terminal region

cd16080
Location:128 → 171

TSP-4cc; Coiled coil region of thrombospondin-4 (TSP-4)

cl22861
Location:1 → 101

LamG; Laminin G domain; Laminin G-like domains are usually Ca++ mediated receptors that can have binding sites for steroids, beta1 integrins, heparin, sulfatides, fibulin-1, and alpha-dystroglycans. Proteins that contain LamG domains serve a variety of ...
NM_003248.6 → NP_003239.2 thrombospondin-4 isoform a precursor

See identical proteins and their annotated locations for NP_003239.2

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longest transcript and encodes the longer isoform (a).

Source sequence(s)

AC112184, BC050456

Consensus CDS

CCDS4049.1

UniProtKB/Swiss-Prot

B2R909, P35443, Q86TG2

UniProtKB/TrEMBL

B7Z832

Related

ENSP00000339730.2, ENST00000350881.6

Conserved Domains (8) summary

smart00210
Location:24 → 192

TSPN; Thrombospondin N-terminal -like domains

cd00054
Location:379 → 413

EGF_CA; Calcium-binding EGF-like domain, present in a large number of membrane-bound and extracellular (mostly animal) proteins. Many of these proteins require calcium for their biological function and calcium-binding sites have been found to be located at the ...

sd00001
Location:591 → 613

TSP3; TSP3 repeat_short [structural motif]

sd00002
Location:496 → 531

TSP3; TSP3 repeat_long [structural motif]

pfam00008
Location:290 → 320

EGF; EGF-like domain

pfam02412
Location:497 → 531

TSP_3; Thrombospondin type 3 repeat

pfam05735
Location:745 → 942

TSP_C; Thrombospondin C-terminal region

cd16080
Location:219 → 262

TSP-4cc; Coiled coil region of thrombospondin-4 (TSP-4)