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Protein

A disintegrin and metalloproteinase with thrombospondin motifs 2

Gene

ADAMTS2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at transcript leveli

Functioni

Cleaves the propeptides of type I and II collagen prior to fibril assembly. Does not act on type III collagen. May also play a role in development that is independent of its role in collagen biosynthesis.

Catalytic activityi

Cleaves the N-propeptide of collagen chain alpha-1(I) at Pro-|-Gln and of alpha-1(II) and alpha-2(I) at Ala-|-Gln.

Cofactori

Zn2+By similarityNote: Binds 1 zinc ion per subunit.By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi408Zinc; catalyticPROSITE-ProRule annotation1
Active sitei409PROSITE-ProRule annotation1
Metal bindingi412Zinc; catalyticPROSITE-ProRule annotation1
Metal bindingi418Zinc; catalyticPROSITE-ProRule annotation1

GO - Molecular functioni

  • metalloendopeptidase activity Source: Reactome
  • metallopeptidase activity Source: ProtInc
  • zinc ion binding Source: InterPro

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Metalloprotease, Protease

Keywords - Biological processi

Collagen degradation

Keywords - Ligandi

Metal-binding, Zinc

Enzyme and pathway databases

BioCyciZFISH:HS01558-MONOMER.
ReactomeiR-HSA-1650814. Collagen biosynthesis and modifying enzymes.
R-HSA-5083635. Defective B3GALTL causes Peters-plus syndrome (PpS).
R-HSA-5173214. O-glycosylation of TSR domain-containing proteins.

Protein family/group databases

MEROPSiM12.301.

Names & Taxonomyi

Protein namesi
Recommended name:
A disintegrin and metalloproteinase with thrombospondin motifs 2 (EC:3.4.24.14)
Short name:
ADAM-TS 2
Short name:
ADAM-TS2
Short name:
ADAMTS-2
Alternative name(s):
Procollagen I N-proteinase
Short name:
PC I-NP
Procollagen I/II amino propeptide-processing enzyme
Procollagen N-endopeptidase
Short name:
pNPI
Gene namesi
Name:ADAMTS2
Synonyms:PCINP, PCPNI
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 5

Organism-specific databases

HGNCiHGNC:218. ADAMTS2.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Extracellular matrix, Secreted

Pathology & Biotechi

Involvement in diseasei

Ehlers-Danlos syndrome 7C (EDS7C)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA connective tissue disorder characterized by hyperextensible skin, atrophic cutaneous scars due to tissue fragility and joint hyperlaxity. Marked by extremely fragile tissues, hyperextensible skin and easy bruising. Facial skin contains numerous folds, as in the cutis laxa syndrome.
See also OMIM:225410

Keywords - Diseasei

Ehlers-Danlos syndrome

Organism-specific databases

DisGeNETi9509.
MalaCardsiADAMTS2.
MIMi225410. phenotype.
OpenTargetsiENSG00000087116.
Orphaneti1901. Ehlers-Danlos syndrome, dermatosparaxis type.
PharmGKBiPA24546.

Polymorphism and mutation databases

BioMutaiADAMTS2.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 29Sequence analysisAdd BLAST29
PropeptideiPRO_000002915830 – 253By similarityAdd BLAST224
ChainiPRO_0000029159254 – 1211A disintegrin and metalloproteinase with thrombospondin motifs 2Add BLAST958

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi112N-linked (GlcNAc...)Sequence analysis1
Glycosylationi251N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi343 ↔ 392By similarity
Disulfide bondi386 ↔ 465By similarity
Disulfide bondi425 ↔ 451By similarity
Disulfide bondi492 ↔ 517By similarity
Disulfide bondi503 ↔ 526By similarity
Disulfide bondi512 ↔ 545By similarity
Disulfide bondi539 ↔ 550By similarity
Disulfide bondi573 ↔ 610By similarity
Disulfide bondi577 ↔ 615By similarity
Disulfide bondi588 ↔ 600By similarity
Glycosylationi949N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi987 ↔ 1023By similarity
Disulfide bondi991 ↔ 1028By similarity
Glycosylationi993N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi1002 ↔ 1012By similarity
Glycosylationi1031N-linked (GlcNAc...)Sequence analysis1
Glycosylationi1098N-linked (GlcNAc...)Sequence analysis1
Glycosylationi1145N-linked (GlcNAc...)Sequence analysis1
Glycosylationi1150N-linked (GlcNAc...)Sequence analysis1

Post-translational modificationi

The precursor is cleaved by a furin endopeptidase.By similarity
Glycosylated. Can be O-fucosylated by POFUT2 on a serine or a threonine residue found within the consensus sequence C1-X(2)-(S/T)-C2-G of the TSP type-1 repeat domains where C1 and C2 are the first and second cysteine residue of the repeat, respectively. Fucosylated repeats can then be further glycosylated by the addition of a beta-1,3-glucose residue by the glucosyltransferase, B3GALTL. Fucosylation mediates the efficient secretion of ADAMTS family members. Also can be C-glycosylated with one or two mannose molecules on tryptophan residues within the consensus sequence W-X-X-W of the TPRs, and N-glycosylated. These other glycosylations can also facilitate secretion (By similarity).By similarity

Keywords - PTMi

Disulfide bond, Glycoprotein, Zymogen

Proteomic databases

EPDiO95450.
PaxDbiO95450.
PeptideAtlasiO95450.
PRIDEiO95450.

PTM databases

iPTMnetiO95450.
PhosphoSitePlusiO95450.

Expressioni

Tissue specificityi

Expressed at high level in skin, bone, tendon and aorta and at low levels in thymus and brain.

Gene expression databases

BgeeiENSG00000087116.
CleanExiHS_ADAMTS2.
GenevisibleiO95450. HS.

Organism-specific databases

HPAiHPA028444.

Interactioni

Subunit structurei

May belong to a multimeric complex. Binds specifically to collagen type XIV (By similarity).By similarity

Protein-protein interaction databases

BioGridi114887. 18 interactors.
IntActiO95450. 1 interactor.
STRINGi9606.ENSP00000251582.

Structurei

3D structure databases

ProteinModelPortaliO95450.
SMRiO95450.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini266 – 470Peptidase M12BPROSITE-ProRule annotationAdd BLAST205
Domaini480 – 560DisintegrinAdd BLAST81
Domaini561 – 616TSP type-1 1PROSITE-ProRule annotationAdd BLAST56
Domaini854 – 912TSP type-1 2PROSITE-ProRule annotationAdd BLAST59
Domaini914 – 971TSP type-1 3PROSITE-ProRule annotationAdd BLAST58
Domaini975 – 1029TSP type-1 4PROSITE-ProRule annotationAdd BLAST55
Domaini1059 – 1097PLACPROSITE-ProRule annotationAdd BLAST39

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni723 – 851SpacerAdd BLAST129

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi691 – 693Cell attachment siteSequence analysis3

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi40 – 43Poly-Ala4
Compositional biasi185 – 188Poly-Glu4
Compositional biasi618 – 722Cys-richAdd BLAST105

Domaini

The spacer domain and the TSP type-1 domains are important for a tight interaction with the extracellular matrix.

Sequence similaritiesi

Contains 1 disintegrin domain.Curated
Contains 1 peptidase M12B domain.PROSITE-ProRule annotation
Contains 1 PLAC domain.PROSITE-ProRule annotation
Contains 4 TSP type-1 domains.PROSITE-ProRule annotation

Keywords - Domaini

Repeat, Signal

Phylogenomic databases

eggNOGiENOG410INDA. Eukaryota.
ENOG410XSRH. LUCA.
GeneTreeiENSGT00760000118880.
HOGENOMiHOG000034222.
HOVERGENiHBG004314.
InParanoidiO95450.
KOiK08618.
OMAiIHEDSLN.
OrthoDBiEOG091G0790.
PhylomeDBiO95450.
TreeFamiTF313537.

Family and domain databases

Gene3Di3.40.390.10. 1 hit.
InterProiIPR010294. ADAM_spacer1.
IPR024079. MetalloPept_cat_dom.
IPR013275. Pept_M12B_ADAM-TS2.
IPR001590. Peptidase_M12B.
IPR013273. Peptidase_M12B_ADAM-TS.
IPR002870. Peptidase_M12B_N.
IPR010909. PLAC.
IPR000884. TSP1_rpt.
[Graphical view]
PfamiPF05986. ADAM_spacer1. 1 hit.
PF01562. Pep_M12B_propep. 1 hit.
PF01421. Reprolysin. 1 hit.
PF00090. TSP_1. 4 hits.
[Graphical view]
PRINTSiPR01859. ADAMTS2.
PR01857. ADAMTSFAMILY.
SMARTiSM00209. TSP1. 4 hits.
[Graphical view]
SUPFAMiSSF82895. SSF82895. 4 hits.
PROSITEiPS50215. ADAM_MEPRO. 1 hit.
PS50900. PLAC. 1 hit.
PS50092. TSP1. 4 hits.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform LpNPI (identifier: O95450-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MDPPAGAARR LLCPALLLLL LLLPPPLLPP PPPPANARLA AAADPPGGPL
60 70 80 90 100
GHGAERILAV PVRTDAQGRL VSHVVSAATS RAGVRARRAA PVRTPSFPGG
110 120 130 140 150
NEEEPGSHLF YNVTVFGRDL HLRLRPNARL VAPGATMEWQ GEKGTTRVEP
160 170 180 190 200
LLGSCLYVGD VAGLAEASSV ALSNCDGLAG LIRMEEEEFF IEPLEKGLAA
210 220 230 240 250
QEAEQGRVHV VYRRPPTSPP LGGPQALDTG ASLDSLDSLS RALGVLEEHA
260 270 280 290 300
NSSRRRARRH AADDDYNIEV LLGVDDSVVQ FHGKEHVQKY LLTLMNIVNE
310 320 330 340 350
IYHDESLGAH INVVLVRIIL LSYGKSMSLI EIGNPSQSLE NVCRWAYLQQ
360 370 380 390 400
KPDTGHDEYH DHAIFLTRQD FGPSGMQGYA PVTGMCHPVR SCTLNHEDGF
410 420 430 440 450
SSAFVVAHET GHVLGMEHDG QGNRCGDEVR LGSIMAPLVQ AAFHRFHWSR
460 470 480 490 500
CSQQELSRYL HSYDCLLDDP FAHDWPALPQ LPGLHYSMNE QCRFDFGLGY
510 520 530 540 550
MMCTAFRTFD PCKQLWCSHP DNPYFCKTKK GPPLDGTMCA PGKHCFKGHC
560 570 580 590 600
IWLTPDILKR DGSWGAWSPF GSCSRTCGTG VKFRTRQCDN PHPANGGRTC
610 620 630 640 650
SGLAYDFQLC SRQDCPDSLA DFREEQCRQW DLYFEHGDAQ HHWLPHEHRD
660 670 680 690 700
AKERCHLYCE SRETGEVVSM KRMVHDGTRC SYKDAFSLCV RGDCRKVGCD
710 720 730 740 750
GVIGSSKQED KCGVCGGDNS HCKVVKGTFT RSPKKHGYIK MFEIPAGARH
760 770 780 790 800
LLIQEVDATS HHLAVKNLET GKFILNEEND VDASSKTFIA MGVEWEYRDE
810 820 830 840 850
DGRETLQTMG PLHGTITVLV IPVGDTRVSL TYKYMIHEDS LNVDDNNVLE
860 870 880 890 900
EDSVVYEWAL KKWSPCSKPC GGGSQFTKYG CRRRLDHKMV HRGFCAALSK
910 920 930 940 950
PKAIRRACNP QECSQPVWVT GEWEPCSQTC GRTGMQVRSV RCIQPLHDNT
960 970 980 990 1000
TRSVHAKHCN DARPESRRAC SRELCPGRWR AGPWSQCSVT CGNGTQERPV
1010 1020 1030 1040 1050
LCRTADDSFG ICQEERPETA RTCRLGPCPR NISDPSKKSY VVQWLSRPDP
1060 1070 1080 1090 1100
DSPIRKISSK GHCQGDKSIF CRMEVLSRYC SIPGYNKLCC KSCNLYNNLT
1110 1120 1130 1140 1150
NVEGRIEPPP GKHNDIDVFM PTLPVPTVAM EVRPSPSTPL EVPLNASSTN
1160 1170 1180 1190 1200
ATEDHPETNA VDEPYKIHGL EDEVQPPNLI PRRPSPYEKT RNQRIQELID
1210
EMRKKEMLGK F
Length:1,211
Mass (Da):134,755
Last modified:December 16, 2008 - v2
Checksum:i6C4F2C2D46A1F925
GO
Isoform SpNPI (identifier: O95450-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     544-566: HCFKGHCIWLTPDILKRDGSWGA → FRPGAVAHACYPSTLGGQGRWIA
     567-1211: Missing.

Note: Has no significant N-procollagen peptidase activity.
Show »
Length:566
Mass (Da):61,756
Checksum:i4D0D641B94307BA2
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti1001L → P in CAA05880 (PubMed:10417273).Curated1
Sequence conflicti1089C → S in CAA05880 (PubMed:10417273).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_04792774V → M.Corresponds to variant rs2271211dbSNPEnsembl.1
Natural variantiVAR_047928241R → H.Corresponds to variant rs11750821dbSNPEnsembl.1
Natural variantiVAR_020058245V → I.Corresponds to variant rs398829dbSNPEnsembl.1
Natural variantiVAR_047929331E → K.Corresponds to variant rs17667857dbSNPEnsembl.1
Natural variantiVAR_047930665G → R.Corresponds to variant rs35372714dbSNPEnsembl.1
Natural variantiVAR_047931827R → Q.Corresponds to variant rs35445112dbSNPEnsembl.1
Natural variantiVAR_0200591177P → S.Corresponds to variant rs1054480dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_005497544 – 566HCFKG…GSWGA → FRPGAVAHACYPSTLGGQGR WIA in isoform SpNPI. 1 PublicationAdd BLAST23
Alternative sequenceiVSP_005498567 – 1211Missing in isoform SpNPI. 1 PublicationAdd BLAST645

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ003125 mRNA. Translation: CAA05880.1.
AC008544 Genomic DNA. No translation available.
AC010216 Genomic DNA. No translation available.
AC109479 Genomic DNA. No translation available.
CCDSiCCDS34311.1. [O95450-2]
CCDS4444.1. [O95450-1]
RefSeqiNP_055059.2. NM_014244.4. [O95450-1]
NP_067610.1. NM_021599.3. [O95450-2]
UniGeneiHs.23871.

Genome annotation databases

EnsembliENST00000251582; ENSP00000251582; ENSG00000087116. [O95450-1]
ENST00000274609; ENSP00000274609; ENSG00000087116. [O95450-2]
GeneIDi9509.
KEGGihsa:9509.
UCSCiuc003mjw.3. human. [O95450-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ003125 mRNA. Translation: CAA05880.1.
AC008544 Genomic DNA. No translation available.
AC010216 Genomic DNA. No translation available.
AC109479 Genomic DNA. No translation available.
CCDSiCCDS34311.1. [O95450-2]
CCDS4444.1. [O95450-1]
RefSeqiNP_055059.2. NM_014244.4. [O95450-1]
NP_067610.1. NM_021599.3. [O95450-2]
UniGeneiHs.23871.

3D structure databases

ProteinModelPortaliO95450.
SMRiO95450.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi114887. 18 interactors.
IntActiO95450. 1 interactor.
STRINGi9606.ENSP00000251582.

Protein family/group databases

MEROPSiM12.301.

PTM databases

iPTMnetiO95450.
PhosphoSitePlusiO95450.

Polymorphism and mutation databases

BioMutaiADAMTS2.

Proteomic databases

EPDiO95450.
PaxDbiO95450.
PeptideAtlasiO95450.
PRIDEiO95450.

Protocols and materials databases

DNASUi9509.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000251582; ENSP00000251582; ENSG00000087116. [O95450-1]
ENST00000274609; ENSP00000274609; ENSG00000087116. [O95450-2]
GeneIDi9509.
KEGGihsa:9509.
UCSCiuc003mjw.3. human. [O95450-1]

Organism-specific databases

CTDi9509.
DisGeNETi9509.
GeneCardsiADAMTS2.
HGNCiHGNC:218. ADAMTS2.
HPAiHPA028444.
MalaCardsiADAMTS2.
MIMi225410. phenotype.
604539. gene.
neXtProtiNX_O95450.
OpenTargetsiENSG00000087116.
Orphaneti1901. Ehlers-Danlos syndrome, dermatosparaxis type.
PharmGKBiPA24546.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410INDA. Eukaryota.
ENOG410XSRH. LUCA.
GeneTreeiENSGT00760000118880.
HOGENOMiHOG000034222.
HOVERGENiHBG004314.
InParanoidiO95450.
KOiK08618.
OMAiIHEDSLN.
OrthoDBiEOG091G0790.
PhylomeDBiO95450.
TreeFamiTF313537.

Enzyme and pathway databases

BioCyciZFISH:HS01558-MONOMER.
ReactomeiR-HSA-1650814. Collagen biosynthesis and modifying enzymes.
R-HSA-5083635. Defective B3GALTL causes Peters-plus syndrome (PpS).
R-HSA-5173214. O-glycosylation of TSR domain-containing proteins.

Miscellaneous databases

ChiTaRSiADAMTS2. human.
GeneWikiiADAMTS2.
GenomeRNAii9509.
PROiO95450.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000087116.
CleanExiHS_ADAMTS2.
GenevisibleiO95450. HS.

Family and domain databases

Gene3Di3.40.390.10. 1 hit.
InterProiIPR010294. ADAM_spacer1.
IPR024079. MetalloPept_cat_dom.
IPR013275. Pept_M12B_ADAM-TS2.
IPR001590. Peptidase_M12B.
IPR013273. Peptidase_M12B_ADAM-TS.
IPR002870. Peptidase_M12B_N.
IPR010909. PLAC.
IPR000884. TSP1_rpt.
[Graphical view]
PfamiPF05986. ADAM_spacer1. 1 hit.
PF01562. Pep_M12B_propep. 1 hit.
PF01421. Reprolysin. 1 hit.
PF00090. TSP_1. 4 hits.
[Graphical view]
PRINTSiPR01859. ADAMTS2.
PR01857. ADAMTSFAMILY.
SMARTiSM00209. TSP1. 4 hits.
[Graphical view]
SUPFAMiSSF82895. SSF82895. 4 hits.
PROSITEiPS50215. ADAM_MEPRO. 1 hit.
PS50900. PLAC. 1 hit.
PS50092. TSP1. 4 hits.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiATS2_HUMAN
AccessioniPrimary (citable) accession number: O95450
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 1, 2000
Last sequence update: December 16, 2008
Last modified: November 2, 2016
This is version 172 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Caution

Has sometimes been referred to as ADAMTS3.Curated

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 5
    Human chromosome 5: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. Peptidase families
    Classification of peptidase families and list of entries
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.