ADAMTS4 ADAM metallopeptidase with thrombospondin type 1 motif 4 [Homo sapiens (human)] - Gene

Summary

Official Symbol: ADAMTS4provided by HGNC
Official Full Name: ADAM metallopeptidase with thrombospondin type 1 motif 4provided by HGNC
Primary source: HGNC:HGNC:220
See related: Ensembl:ENSG00000158859 MIM:603876; AllianceGenome:HGNC:220
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: ADMP-1; ADAMTS-2; ADAMTS-4
Summary: This gene encodes a member of the ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) protein family. Members of this family share several distinct protein modules, including a propeptide region, a metalloproteinase domain, a disintegrin-like domain, and a thrombospondin type 1 (TS) motif. Individual members of this family differ in the number of C-terminal TS motifs, and some have unique C-terminal domains. The enzyme encoded by this gene lacks a C-terminal TS motif. The encoded preproprotein is proteolytically processed to generate the mature protease. This protease is responsible for the degradation of aggrecan, a major proteoglycan of cartilage, and brevican, a brain-specific extracellular matrix protein. The expression of this gene is upregulated in arthritic disease and this may contribute to disease progression through the degradation of aggrecan. Alternative splicing results in multiple transcript variants, at least one of which encodes an isoform that is proteolytically processed. [provided by RefSeq, Feb 2016]
Expression: Broad expression in gall bladder (RPKM 12.3), appendix (RPKM 11.7) and 19 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 1q23.3

Exon count:: 9

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	1	NC_000001.11 (161184302..161199054, complement)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	1	NC_060925.1 (160321737..160336495, complement)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	1	NC_000001.10 (161154092..161168844, complement)

Chromosome 1 - NC_000001.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

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?

ADAMTS4 is a crucial proteolytic enzyme for versican cleavage in the amnion at parturition.
Title: ADAMTS4 is a crucial proteolytic enzyme for versican cleavage in the amnion at parturition.
Oxidized LDL-mediated upregulation of ADAMTS-4 in monocytes/macrophages involves ROS-NF-kappaB-SIRT-1 pathway.
Title: Oxidized LDL-mediated upregulation of ADAMTS-4 in monocytes/macrophages involves ROS-NF-κB-SIRT-1 pathway.
ADAMTS4 is involved in the production of the Alzheimer disease amyloid biomarker APP669-711.
Title: ADAMTS4 is involved in the production of the Alzheimer disease amyloid biomarker APP669-711.
Identification of Adamts4 as a novel adult cardiac injury biomarker with therapeutic implications in patients with cardiac injuries.
Title: Identification of Adamts4 as a novel adult cardiac injury biomarker with therapeutic implications in patients with cardiac injuries.
The Role of ADAMTS-4 in Atherosclerosis and Vessel Wall Abnormalities.
Title: The Role of ADAMTS-4 in Atherosclerosis and Vessel Wall Abnormalities.
Synergistic upregulation of ADAMTS4 (aggrecanase-1) by cytokines and its suppression in knee osteoarthritic synovial fibroblasts.
Title: Synergistic upregulation of ADAMTS4 (aggrecanase-1) by cytokines and its suppression in knee osteoarthritic synovial fibroblasts.
ADAMTS proteoglycanases downregulation with impaired oocyte quality in PCOS.
Title: ADAMTS proteoglycanases downregulation with impaired oocyte quality in PCOS.
Interrelationship of Osteopontin, MMP-9 and ADAMTS4 in Patients With Osteoarthritis Undergoing Total Joint Arthroplasty.
Title: Interrelationship of Osteopontin, MMP-9 and ADAMTS4 in Patients With Osteoarthritis Undergoing Total Joint Arthroplasty.
The utility of synovial fluid levels of ADAMTS9 and ADAMTS4 in predicting treatment responses to intraarticular steroid injections in patients with knee osteoarthritis
Title: The utility of synovial fluid levels of ADAMTS9 and ADAMTS4 in predicting treatment responses to intraarticular steroid injections in patients with knee osteoarthritis.
Requirement for C-mannosylation to be secreted and activated a disintegrin and metalloproteinase with thrombospondin motifs 4 (ADAMTS4).
Title: Requirement for C-mannosylation to be secreted and activated a disintegrin and metalloproteinase with thrombospondin motifs 4 (ADAMTS4).

Submit: New GeneRIF Correction See all GeneRIFs (109)

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

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

96 (e-PCR), detects polymorphism
- UniSTS:16942

PMC156606P3 (e-PCR)
- UniSTS:271410

D8S2279 (e-PCR)
- UniSTS:473907

D10S16 (e-PCR)
- UniSTS:155756

D11S3114 (e-PCR)
- UniSTS:152207

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables metalloendopeptidase activity	IBA Inferred from Biological aspect of Ancestor more info
enables metalloendopeptidase activity	TAS Traceable Author Statement more info
enables metallopeptidase activity	IDA Inferred from Direct Assay more info	PubMed
enables peptidase activity	IDA Inferred from Direct Assay more info	PubMed
enables protease binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables zinc ion binding	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
involved_in extracellular matrix disassembly	TAS Traceable Author Statement more info
involved_in extracellular matrix organization	IBA Inferred from Biological aspect of Ancestor more info
involved_in proteolysis	IBA Inferred from Biological aspect of Ancestor more info
involved_in proteolysis	IEA Inferred from Electronic Annotation more info
involved_in skeletal system development	TAS Traceable Author Statement more info	PubMed

Component	Evidence Code	Pubs
located_in collagen-containing extracellular matrix	HDA more info	PubMed
is_active_in extracellular matrix	IBA Inferred from Biological aspect of Ancestor more info
located_in extracellular region	TAS Traceable Author Statement more info
located_in extracellular space	IDA Inferred from Direct Assay more info	PubMed
located_in nuclear speck	IDA Inferred from Direct Assay more info

General protein information

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Preferred Names: A disintegrin and metalloproteinase with thrombospondin motifs 4

Names: ADAM-TS 4; ADAM-TS4; a disintegrin-like and metalloprotease (reprolysin type) with thrombospondin type 1 motif, 4; aggrecanase-1; epididymis secretory sperm binding protein

NP_001307265.1

EC 3.4.24.82

NP_005090.3

EC 3.4.24.82

XP_047290860.1

EC 3.4.24.82

XP_054195683.1

EC 3.4.24.82

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.

mRNA and Protein(s)

NM_001320336.3 → NP_001307265.1 A disintegrin and metalloproteinase with thrombospondin motifs 4 isoform 2 precursor

Status: REVIEWED

Description

Transcript Variant: This variant (2, also known as ADAMTS4_v1) uses an alternate splice site in the 3' coding region resulting in a frameshift compared to variant 1. The encoded isoform (2) has a longer and distinct C-terminus compared to isoform 1, but may undergo proteolytic processing similar to isoform 1.

Source sequence(s)

AA603151, AB014588, AF148213, AL590714, AY358886, BC063293, DA098917, DQ364570

UniProtKB/TrEMBL

A8K6A8

Conserved Domains (5) summary

smart00209
Location:531 → 575

TSP1; Thrombospondin type 1 repeats

cd04273
Location:218 → 425

ZnMc_ADAMTS_like; Zinc-dependent metalloprotease, ADAMTS_like subgroup. ADAMs (A Disintegrin And Metalloprotease) are glycoproteins, which play roles in cell signaling, cell fusion, and cell-cell interactions. This particular subfamily represents domain architectures that ...

pfam01421
Location:218 → 428

Reprolysin; Reprolysin (M12B) family zinc metalloprotease

pfam01562
Location:70 → 181

Pep_M12B_propep; Reprolysin family propeptide

cl15456
Location:438 → 509

ADAM_CR; ADAM cysteine-rich
NM_005099.6 → NP_005090.3 A disintegrin and metalloproteinase with thrombospondin motifs 4 isoform 1 preproprotein

See identical proteins and their annotated locations for NP_005090.3

Status: REVIEWED

Description

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

Source sequence(s)

AA603151, AB014588, AF148213, AL590714, AY358886, BC063293, DA098917

Consensus CDS

CCDS1223.1

UniProtKB/Swiss-Prot

O75173, Q2HYD0, Q5VTW2, Q6P4Q8, Q6UWA8, Q9UN83

UniProtKB/TrEMBL

A8K6A8

Related

ENSP00000356975.4, ENST00000367996.6

Conserved Domains (6) summary

smart00209
Location:531 → 575

TSP1; Thrombospondin type 1 repeats

cd04273
Location:218 → 425

ZnMc_ADAMTS_like; Zinc-dependent metalloprotease, ADAMTS_like subgroup. ADAMs (A Disintegrin And Metalloprotease) are glycoproteins, which play roles in cell signaling, cell fusion, and cell-cell interactions. This particular subfamily represents domain architectures that ...

pfam01421
Location:218 → 428

Reprolysin; Reprolysin (M12B) family zinc metalloprotease

pfam01562
Location:70 → 181

Pep_M12B_propep; Reprolysin family propeptide

pfam05986
Location:687 → 802

ADAM_spacer1; ADAM-TS Spacer 1

cl15456
Location:438 → 509

ADAM_CR; ADAM cysteine-rich