ADAMTS3 ADAM metallopeptidase with thrombospondin type 1 motif 3 [Homo sapiens (human)] - Gene

Summary

Official Symbol: ADAMTS3provided by HGNC
Official Full Name: ADAM metallopeptidase with thrombospondin type 1 motif 3provided by HGNC
Primary source: HGNC:HGNC:219
See related: Ensembl:ENSG00000156140 MIM:605011; AllianceGenome:HGNC:219
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: HKLLS3; ADAMTS-4
Summary: This gene encodes a member of the ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) protein family. Members of the 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 encoded preproprotein is proteolytically processed to generate the mature protease. This protease, a member of the procollagen aminopropeptidase subfamily of proteins, may play a role in the processing of type II fibrillar collagen in articular cartilage. [provided by RefSeq, Feb 2016]
Expression: Broad expression in testis (RPKM 1.4), ovary (RPKM 1.0) and 22 other tissues See more
Orthologs: mouse all
NEW: Try the new Gene table
Try the new Transcript table

Genomic context

Location:: 4q13.3

Exon count:: 24

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	4	NC_000004.12 (72280969..72569221, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	4	NC_060928.1 (75623227..75912559, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	4	NC_000004.11 (73146686..73434938, complement)

Chromosome 4 - NC_000004.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

Go to the top of the page Help

Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

Go to the top of the page Help

See details

Project title: HPA RNA-seq normal tissues 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

Go to the top of the page Help

GeneRIFs: Gene References Into Functions

What's a GeneRIF?

ADAMTS3 restricts cancer invasion in models of early breast cancer progression through enhanced fibronectin degradation.
Title: ADAMTS3 restricts cancer invasion in models of early breast cancer progression through enhanced fibronectin degradation.
There is report of one family supporting mutations in ADAMTS3 as causative for the phenotype labeled as HKLLS3. Here, we report an additional case of HKLLS that appears to be associated with homozygous nonsense mutation of ADAMTS3.
Title: An additional case of Hennekam lymphangiectasia-lymphedema syndrome caused by loss-of-function mutation in ADAMTS3.
Molecular cloning and in silico analysis identify potential transcription factor binding sites in the ADAMTS3 promoter region and show that SP1 downregulated ADAMTS3 transcriptional activity in osteosarcoma cell lines. As consistent with the transcriptional activity, mRNA, and protein expression levels were also decreased by SP1.
Title: SP1-mediated downregulation of ADAMTS3 gene expression in osteosarcoma models.
Results corroborate the recent in vitro and murine data that suggest a close functional interaction between ADAMTS3 and CCBE1 in triggering VEGFR3 signaling, a cornerstone for the differentiation and function of lymphatic endothelial cells.
Title: Loss of ADAMTS3 activity causes Hennekam lymphangiectasia-lymphedema syndrome 3.
Findings suggest that these MMP16 rs10090371, ADAMTS3 rs788935, TLL2 rs10882807 and MMP9 rs3918251 may be promising prognostic biomarkers for cutaneous melanoma specific survival (CMSS).
Title: Genetic variants in the metzincin metallopeptidase family genes predict melanoma survival.
The pregnancy loss rate seems to be affected by both ADAMTS-3 and ADAMTS-16.
Title: ADAMTS-3, -13, -16, and -19 levels in patients with habitual abortion.
Data indicate that ADAMTS2 and 3 cleave the amino-propeptide of fibrillar collagens and regulate blood vessels homeostasis and lymphangiogenesis. [review]
Title: The procollagen N-proteinases ADAMTS2, 3 and 14 in pathophysiology.
ADAMTS-2, -3, and -13 expression, but not that of ADAMTS-14, are increased in plaques causing AMI compared those associated with stable angina.
Title: Expression of ADAMTS-2, -3, -13, and -14 in culprit coronary lesions in patients with acute myocardial infarction or stable angina.
Observational study of gene-disease association. (HuGE Navigator)
Title: Genetic association analysis of the IGFBP7, ADAMTS3, and IL8 genes as the potential osteoarthritis susceptibility that maps to chromosome 4q.
extracellular matrix degrading enzyme
Title: [ADAMTS family--new extracellular matrix degrading enzyme].

Submit: New GeneRIF Correction

Phenotypes

Go to the top of the page Help

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

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Hennekam lymphangiectasia-lymphedema syndrome 3 MedGen: C4748408 OMIM: 618154 GeneReviews: Not available	not available

EBI GWAS Catalog

Description
Genome-wide association scan for survival on dialysis in African-Americans with type 2 diabetes. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association scan of dental caries in the permanent dentition. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association study identifies multiple loci influencing human serum metabolite levels. EBI GWAS Catalog EBI GWAS CatalogPubMed
Hundreds of variants clustered in genomic loci and biological pathways affect human height. EBI GWAS Catalog EBI GWAS CatalogPubMed
Meta-analysis of genome-wide association studies of adult height in East Asians identifies 17 novel loci. EBI GWAS Catalog EBI GWAS CatalogPubMed
Novel Loci for metabolic networks and multi-tissue expression studies reveal genes for atherosclerosis. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

Go to the top of the page Help

See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

Go to the top of the page Help

Protein interactions

Protein	Gene	Interaction	Pubs
Vif	vif	HIV-1 Vif upregulates the expression of ADAM metallopeptidase with thrombospondin type 1 motif 3 protein (ADAMTS3) in Vif-expression T cells	PubMed

Go to the HIV-1, Human Interaction Database

Interactions

Go to the top of the page Help

Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

Go to the top of the page Help

Markers

RH120789 (e-PCR)
- UniSTS:132869

G33602 (e-PCR)
- UniSTS:72731

SHGC-67364 (e-PCR)
- UniSTS:38700

D4S1389 (e-PCR)
- UniSTS:14140

RH120844 (e-PCR)
- UniSTS:133499

SHGC-59735 (e-PCR)
- UniSTS:3967

HSC2JD032 (e-PCR)
- UniSTS:75668

ADAMTS3_678 (e-PCR)
- UniSTS:276970

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables endopeptidase activity	IDA Inferred from Direct Assay more info	PubMed
enables heparin binding	IEA Inferred from Electronic Annotation more info
enables metalloendopeptidase activity	IBA Inferred from Biological aspect of Ancestor more info
enables metalloendopeptidase activity	NAS Non-traceable Author Statement more info	PubMed
enables metalloendopeptidase activity	TAS Traceable Author Statement more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables zinc ion binding	NAS Non-traceable Author Statement more info	PubMed

Process	Evidence Code	Pubs
involved_in collagen biosynthetic process	IDA Inferred from Direct Assay more info	PubMed
involved_in collagen catabolic process	NAS Non-traceable Author Statement more info	PubMed
involved_in collagen fibril organization	IC Inferred by Curator more info	PubMed
involved_in collagen fibril organization	NAS Non-traceable Author Statement more info	PubMed
involved_in collagen fibril organization	TAS Traceable Author Statement more info
involved_in extracellular matrix organization	IBA Inferred from Biological aspect of Ancestor more info
involved_in in utero embryonic development	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of vascular endothelial growth factor signaling pathway	IDA Inferred from Direct Assay more info	PubMed
involved_in protein processing	IDA Inferred from Direct Assay more info	PubMed
involved_in proteolysis	IBA Inferred from Biological aspect of Ancestor more info
involved_in supramolecular fiber organization	IC Inferred by Curator more info	PubMed
involved_in vascular endothelial growth factor production	IDA Inferred from Direct Assay more info	PubMed

Component	Evidence Code	Pubs
colocalizes_with collagen-containing extracellular matrix	TAS Traceable Author Statement more info	PubMed
located_in extracellular exosome	HDA more info	PubMed
is_active_in extracellular matrix	IBA Inferred from Biological aspect of Ancestor more info
located_in extracellular matrix	NAS Non-traceable Author Statement 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

General protein information

Go to the top of the page Help

Preferred Names: A disintegrin and metalloproteinase with thrombospondin motifs 3

Names: ADAM-TS 3; ADAM-TS3; ADAMTS-3; PC II-NP; a disintegrin-like and metalloprotease (reprolysin type) with thrombospondin type 1 motif, 3; procollagen II N-proteinase; procollagen II amino propeptide-processing enzyme; zinc metalloendopeptidase

NP_055058.2

EC 3.4.24.-

XP_011530723.1

EC 3.4.24.-

XP_011530724.1

EC 3.4.24.-

XP_054207261.1

EC 3.4.24.-

XP_054207262.1

EC 3.4.24.-

NCBI Reference Sequences (RefSeq)

Go to the top of the page Help

NEW Try the new Transcript table

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_046955.1 RefSeqGene

Range

4579..292831

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_014243.3 → NP_055058.2 A disintegrin and metalloproteinase with thrombospondin motifs 3 preproprotein

See identical proteins and their annotated locations for NP_055058.2

Status: REVIEWED

Source sequence(s)

AB002364, AC104814, AF247668, AK295131, BC016451, BC130287

Consensus CDS

CCDS3553.1

UniProtKB/Swiss-Prot

A1L3U9, O15072, Q9BXZ8

Related

ENSP00000286657.4, ENST00000286657.10

Conserved Domains (6) summary

smart00209
Location:554 → 605

TSP1; Thrombospondin type 1 repeats

cd04273
Location:256 → 457

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:258 → 460

Reprolysin; Reprolysin (M12B) family zinc metalloprotease

pfam01562
Location:66 → 200

Pep_M12B_propep; Reprolysin family propeptide

pfam05986
Location:713 → 827

ADAM_spacer1; ADAM-TS Spacer 1

pfam08686
Location:1023 → 1051

PLAC; PLAC (protease and lacunin) domain

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000004.12 Reference GRCh38.p14 Primary Assembly

Range

72280969..72569221 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_011532422.4 → XP_011530724.1 A disintegrin and metalloproteinase with thrombospondin motifs 3 isoform X2

Conserved Domains (6) summary

smart00209
Location:526 → 577

TSP1; Thrombospondin type 1 repeats

cd04273
Location:228 → 429

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:230 → 432

Reprolysin; Reprolysin (M12B) family zinc metalloprotease

pfam01562
Location:38 → 172

Pep_M12B_propep; Reprolysin family propeptide

pfam05986
Location:685 → 799

ADAM_spacer1; ADAM-TS Spacer 1

pfam08686
Location:995 → 1023

PLAC; PLAC (protease and lacunin) domain
XM_011532421.2 → XP_011530723.1 A disintegrin and metalloproteinase with thrombospondin motifs 3 isoform X1

Conserved Domains (6) summary

smart00209
Location:535 → 586

TSP1; Thrombospondin type 1 repeats

cd04273
Location:237 → 438

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:239 → 441

Reprolysin; Reprolysin (M12B) family zinc metalloprotease

pfam01562
Location:47 → 181

Pep_M12B_propep; Reprolysin family propeptide

pfam05986
Location:694 → 808

ADAM_spacer1; ADAM-TS Spacer 1

pfam08686
Location:1004 → 1032

PLAC; PLAC (protease and lacunin) domain

Alternate T2T-CHM13v2.0

Genomic

NC_060928.1 Alternate T2T-CHM13v2.0

Range

75623227..75912559 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_054351287.1 → XP_054207262.1 A disintegrin and metalloproteinase with thrombospondin motifs 3 isoform X2
XM_054351286.1 → XP_054207261.1 A disintegrin and metalloproteinase with thrombospondin motifs 3 isoform X1