ADAMTS2 ADAM metallopeptidase with thrombospondin type 1 motif 2 [Homo sapiens (human)] - Gene

Summary

Official Symbol: ADAMTS2provided by HGNC
Official Full Name: ADAM metallopeptidase with thrombospondin type 1 motif 2provided by HGNC
Primary source: HGNC:HGNC:218
See related: Ensembl:ENSG00000087116 MIM:604539; AllianceGenome:HGNC:218
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: NPI; PNPI; PCINP; PCPNI; PCI-NP; PC I-NP; ADAM-TS2; ADAMTS-2; ADAMTS-3; EDSDERMS
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 procollagen N-proteinase. This proteinase excises the N-propeptide of the fibrillar procollagens types I-III and type V. Mutations in this gene cause Ehlers-Danlos syndrome type VIIC, a recessively inherited connective-tissue disorder. 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 endometrium (RPKM 11.5), placenta (RPKM 8.1) and 21 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 5q35.3

Exon count:: 25

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	5	NC_000005.10 (179110853..179345461, complement)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	5	NC_060929.1 (179664045..179898855, complement)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	5	NC_000005.9 (178537854..178772462, complement)

Chromosome 5 - NC_000005.10 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?

Opposing roles for ADAMTS2 and ADAMTS14 in myofibroblast differentiation and function.
Title: Opposing roles for ADAMTS2 and ADAMTS14 in myofibroblast differentiation and function.
Genome-wide association study of early ischaemic stroke risk in Brazilian individuals with sickle cell disease implicates ADAMTS2 and CDK18 and uncovers novel loci.
Title: Genome-wide association study of early ischaemic stroke risk in Brazilian individuals with sickle cell disease implicates ADAMTS2 and CDK18 and uncovers novel loci.
Mutations in the TBX15-ADAMTS2 pathway associate with a novel soft palate dysplasia.
Title: Mutations in the TBX15-ADAMTS2 pathway associate with a novel soft palate dysplasia.
ADAMTS12, a new candidate gene for pediatric stroke.
Title: ADAMTS12, a new candidate gene for pediatric stroke.
Dopaminergic control of ADAMTS2 expression through cAMP/CREB and ERK: molecular effects of antipsychotics.
Title: Dopaminergic control of ADAMTS2 expression through cAMP/CREB and ERK: molecular effects of antipsychotics.
Our research revealed that partial microduplication of ADAMTS2 (chr5:178728830-178997692) might be benign and not correlate with disorders. And there might exist phenotypic diversities of 5q35.3 duplications.
Title: Prenatal diagnosis of a 5q35.3 microduplication involving part of the ADAMTS2 locus: a likely benign variant without apparent phenotypic abnormality: Case series.
ADAMTS-2, collagen type-1, TIMP-3 and papilin levels of the uterosacral ligament play essential roles in the etiopathogenesis of pelvic organ prolapse among postmenopausal women without stress urinary incontinence.
Title: The role of ADAMTS-2, collagen type-1, TIMP-3 and papilin levels of uterosacral and cardinal ligaments in the etiopathogenesis of pelvic organ prolapse among women without stress urinary incontinence.
We identified three novel homozygous loss-of-function mutations (c.2927_2928delCT, p.(Pro976Argfs*42); c.669_670dupG, p.(Pro224Argfs*24); and c.2751-2A>T) and one compound heterozygous mutation (c.2T>C, p.? and c.884_887delTGAA, p.(Met295Thrfs26*)) in ADAMTS2 in five patients from four unrelated families
Title: Expanding the clinical and mutational spectrum of the Ehlers-Danlos syndrome, dermatosparaxis type.
Data indicate that ADAMTS2 and 3 cleave the amino-propeptide of fibrillar collagens and regulate blood vessels homeostasis and lymphangiogenesis. Also, ADAMTS2 deficiency leads to the dermatosparactic type of Ehlers-Danlos syndrome. [review]
Title: The procollagen N-proteinases ADAMTS2, 3 and 14 in pathophysiology.
IL-1a is a strong positive regulator of ADAMTS-2 and ADAMTS-3 expression.
Title: Induction of human ADAMTS-2 gene expression by IL-1α is mediated by a multiple crosstalk of MEK/JNK and PI3K pathways in osteoblast like cells.

Submit: New GeneRIF Correction See all GeneRIFs (17)

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

Associated conditions

Description	Tests
Ehlers-Danlos syndrome, dermatosparaxis type MedGen: C2700425 OMIM: 225410 GeneReviews: Not available	Compare labs

EBI GWAS Catalog

Description
A genome-wide association study identifies a gene network of ADAMTS genes in the predisposition to pediatric stroke. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association for abdominal subcutaneous and visceral adipose reveals a novel locus for visceral fat in women. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association scan of the time to onset of attention deficit hyperactivity disorder. 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)

HIV-1 interactions

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Protein interactions

Protein	Gene	Interaction	Pubs
Envelope surface glycoprotein gp120	env	HIV-1 gp120-treated vaginal epithelial cells show upregulation of ADAM metallopeptidase with thrombospondin type 1 motif-2 (ADAMTS2) expression as compared to untreated control	PubMed

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Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

bac51964S (e-PCR)
- UniSTS:181530

bac52194T (e-PCR)
- UniSTS:181559

SHGC-143243 (e-PCR)
- UniSTS:171835

RH44727 (e-PCR)
- UniSTS:41276

SHGC-155422 (e-PCR)
- UniSTS:185419

SGC33801 (e-PCR)
- UniSTS:45172

RH44368 (e-PCR)
- UniSTS:90015

WI-10789 (e-PCR)
- UniSTS:73636

D5S1382 (e-PCR)
- UniSTS:149191

G09291 (e-PCR)
- UniSTS:70652

RH12250 (e-PCR)
- UniSTS:56572

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	TAS Traceable Author Statement more info	PubMed
enables zinc ion binding	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
involved_in collagen catabolic process	IEA Inferred from Electronic Annotation more info
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 lung development	IEA Inferred from Electronic Annotation more info
involved_in protein processing	IEA Inferred from Electronic Annotation more info
involved_in proteolysis	IBA Inferred from Biological aspect of Ancestor more info
involved_in skin development	IEA Inferred from Electronic Annotation more info
involved_in spermatogenesis	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
located_in collagen-containing extracellular matrix	IEA Inferred from Electronic Annotation more info
is_active_in extracellular matrix	IBA Inferred from Biological aspect of Ancestor more info
located_in extracellular region	TAS Traceable Author Statement more info

General protein information

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Preferred Names: A disintegrin and metalloproteinase with thrombospondin motifs 2

Names: a disintegrin-like and metalloprotease (reprolysin type) with thrombospondin type 1 motif, 2; procollagen I N-proteinase; procollagen I/II amino propeptide-processing enzyme; procollagen N-endopeptidase

NP_055059.2

EC 3.4.24.14

NP_067610.1

EC 3.4.24.14

XP_047273851.1

EC 3.4.24.14

XP_047273852.1

EC 3.4.24.14

XP_054209801.1

EC 3.4.24.14

XP_054209802.1

EC 3.4.24.14

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_023212.3 RefSeqGene

Range

4868..239476

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_014244.5 → NP_055059.2 A disintegrin and metalloproteinase with thrombospondin motifs 2 isoform 1 preproprotein

See identical proteins and their annotated locations for NP_055059.2

Status: REVIEWED

Description

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

Source sequence(s)

AC008544, AC010216, AC109479, AJ003125, CA445758, DA928965

Consensus CDS

CCDS4444.1

UniProtKB/Swiss-Prot

O95450

UniProtKB/TrEMBL

A0A1B0GTY3

Related

ENSP00000251582.7, ENST00000251582.12

Conserved Domains (6) summary

smart00209
Location:564 → 616

TSP1; Thrombospondin type 1 repeats

cd04273
Location:266 → 467

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 ...

pfam05986
Location:723 → 837

ADAM_spacer1; ADAM-TS Spacer 1

pfam01562
Location:91 → 212

Pep_M12B_propep; Reprolysin family propeptide

pfam17771
Location:482 → 551

ADAM_CR_2; ADAM cysteine-rich domain

pfam19030
Location:979 → 1028

TSP1_ADAMTS; Thrombospondin type 1 domain
NM_021599.4 → NP_067610.1 A disintegrin and metalloproteinase with thrombospondin motifs 2 isoform 2 precursor

See identical proteins and their annotated locations for NP_067610.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) lacks several exons and includes an alternate exon in the 3' coding region and 3' UTR, compared to variant 1. It encodes isoform 2, which is shorter and has a distinct C-terminus, compared to isoform 1. Isoform 2 lacks the TSP type-1 domains compared to isoform 1 but may undergo proteolytic processing similar to isoform 1.

Source sequence(s)

AC010216, AC109479, AK308213, BM512469

Consensus CDS

CCDS34311.1

UniProtKB/Swiss-Prot

O95450

Related

ENSP00000274609.5, ENST00000274609.5

Conserved Domains (3) summary

cd04273
Location:266 → 467

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:268 → 470

Reprolysin; Reprolysin (M12B) family zinc metalloprotease

pfam01562
Location:100 → 211

Pep_M12B_propep; Reprolysin family propeptide

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

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

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000005.10 Reference GRCh38.p14 Primary Assembly

Range

179110853..179345461 complement

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_047417895.1 → XP_047273851.1 A disintegrin and metalloproteinase with thrombospondin motifs 2 isoform X1
XM_047417896.1 → XP_047273852.1 A disintegrin and metalloproteinase with thrombospondin motifs 2 isoform X2

Reference GRCh38.p14 PATCHES

Genomic

NW_016107298.1 Reference GRCh38.p14 PATCHES

Range

20229..110168 complement

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GenBank, FASTA, Sequence Viewer (Graphics)

Alternate T2T-CHM13v2.0

Genomic

NC_060929.1 Alternate T2T-CHM13v2.0

Range

179664045..179898855 complement

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_054353826.1 → XP_054209801.1 A disintegrin and metalloproteinase with thrombospondin motifs 2 isoform X1
XM_054353827.1 → XP_054209802.1 A disintegrin and metalloproteinase with thrombospondin motifs 2 isoform X2