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O95450 (ATS2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 148. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
A disintegrin and metalloproteinase with thrombospondin motifs 2

Short name=ADAM-TS 2
Short name=ADAM-TS2
Short name=ADAMTS-2
EC=3.4.24.14
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 names
Name:ADAMTS2
Synonyms:PCINP, PCPNI
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length1211 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at transcript level

General annotation (Comments)

Function

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 activity

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.

Cofactor

Binds 1 zinc ion per subunit By similarity.

Subunit structure

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

Subcellular location

Secretedextracellular spaceextracellular matrix By similarity.

Tissue specificity

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

Domain

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

Post-translational modification

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.

Involvement in disease

Ehlers-Danlos syndrome 7C (EDS7C) [MIM:225410]: A 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.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.1

Sequence similarities

Contains 1 disintegrin domain.

Contains 1 peptidase M12B domain.

Contains 1 PLAC domain.

Contains 4 TSP type-1 domains.

Caution

Has sometimes been referred to as ADAMTS3.

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform LpNPI (identifier: O95450-1)

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.
Isoform SpNPI (identifier: O95450-2)

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.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2929 Potential
Propeptide30 – 253224 By similarity
PRO_0000029158
Chain254 – 1211958A disintegrin and metalloproteinase with thrombospondin motifs 2
PRO_0000029159

Regions

Domain266 – 470205Peptidase M12B
Domain480 – 56081Disintegrin
Domain561 – 61656TSP type-1 1
Domain854 – 91259TSP type-1 2
Domain914 – 97158TSP type-1 3
Domain975 – 102955TSP type-1 4
Domain1059 – 109739PLAC
Region723 – 851129Spacer
Motif691 – 6933Cell attachment site Potential
Compositional bias40 – 434Poly-Ala
Compositional bias185 – 1884Poly-Glu
Compositional bias618 – 722105Cys-rich

Sites

Active site4091 By similarity
Metal binding4081Zinc; catalytic By similarity
Metal binding4121Zinc; catalytic By similarity
Metal binding4181Zinc; catalytic By similarity

Amino acid modifications

Glycosylation1121N-linked (GlcNAc...) Potential
Glycosylation2511N-linked (GlcNAc...) Potential
Glycosylation9491N-linked (GlcNAc...) Potential
Glycosylation9931N-linked (GlcNAc...) Potential
Glycosylation10311N-linked (GlcNAc...) Potential
Glycosylation10981N-linked (GlcNAc...) Potential
Glycosylation11451N-linked (GlcNAc...) Potential
Glycosylation11501N-linked (GlcNAc...) Potential
Disulfide bond343 ↔ 392 By similarity
Disulfide bond386 ↔ 465 By similarity
Disulfide bond425 ↔ 451 By similarity
Disulfide bond492 ↔ 517 By similarity
Disulfide bond503 ↔ 526 By similarity
Disulfide bond512 ↔ 545 By similarity
Disulfide bond539 ↔ 550 By similarity
Disulfide bond573 ↔ 610 By similarity
Disulfide bond577 ↔ 615 By similarity
Disulfide bond588 ↔ 600 By similarity
Disulfide bond987 ↔ 1023 By similarity
Disulfide bond991 ↔ 1028 By similarity
Disulfide bond1002 ↔ 1012 By similarity

Natural variations

Alternative sequence544 – 56623HCFKG…GSWGA → FRPGAVAHACYPSTLGGQGR WIA in isoform SpNPI.
VSP_005497
Alternative sequence567 – 1211645Missing in isoform SpNPI.
VSP_005498
Natural variant741V → M.
Corresponds to variant rs2271211 [ dbSNP | Ensembl ].
VAR_047927
Natural variant2411R → H.
Corresponds to variant rs11750821 [ dbSNP | Ensembl ].
VAR_047928
Natural variant2451V → I.
Corresponds to variant rs398829 [ dbSNP | Ensembl ].
VAR_020058
Natural variant3311E → K.
Corresponds to variant rs17667857 [ dbSNP | Ensembl ].
VAR_047929
Natural variant6651G → R.
Corresponds to variant rs35372714 [ dbSNP | Ensembl ].
VAR_047930
Natural variant8271R → Q.
Corresponds to variant rs35445112 [ dbSNP | Ensembl ].
VAR_047931
Natural variant11771P → S.
Corresponds to variant rs1054480 [ dbSNP | Ensembl ].
VAR_020059

Experimental info

Sequence conflict10011L → P in CAA05880. Ref.1
Sequence conflict10891C → S in CAA05880. Ref.1

Sequences

Sequence LengthMass (Da)Tools
Isoform LpNPI [UniParc].

Last modified December 16, 2008. Version 2.
Checksum: 6C4F2C2D46A1F925

FASTA1,211134,755
        10         20         30         40         50         60 
MDPPAGAARR LLCPALLLLL LLLPPPLLPP PPPPANARLA AAADPPGGPL GHGAERILAV 

        70         80         90        100        110        120 
PVRTDAQGRL VSHVVSAATS RAGVRARRAA PVRTPSFPGG NEEEPGSHLF YNVTVFGRDL 

       130        140        150        160        170        180 
HLRLRPNARL VAPGATMEWQ GEKGTTRVEP LLGSCLYVGD VAGLAEASSV ALSNCDGLAG 

       190        200        210        220        230        240 
LIRMEEEEFF IEPLEKGLAA QEAEQGRVHV VYRRPPTSPP LGGPQALDTG ASLDSLDSLS 

       250        260        270        280        290        300 
RALGVLEEHA NSSRRRARRH AADDDYNIEV LLGVDDSVVQ FHGKEHVQKY LLTLMNIVNE 

       310        320        330        340        350        360 
IYHDESLGAH INVVLVRIIL LSYGKSMSLI EIGNPSQSLE NVCRWAYLQQ KPDTGHDEYH 

       370        380        390        400        410        420 
DHAIFLTRQD FGPSGMQGYA PVTGMCHPVR SCTLNHEDGF SSAFVVAHET GHVLGMEHDG 

       430        440        450        460        470        480 
QGNRCGDEVR LGSIMAPLVQ AAFHRFHWSR CSQQELSRYL HSYDCLLDDP FAHDWPALPQ 

       490        500        510        520        530        540 
LPGLHYSMNE QCRFDFGLGY MMCTAFRTFD PCKQLWCSHP DNPYFCKTKK GPPLDGTMCA 

       550        560        570        580        590        600 
PGKHCFKGHC IWLTPDILKR DGSWGAWSPF GSCSRTCGTG VKFRTRQCDN PHPANGGRTC 

       610        620        630        640        650        660 
SGLAYDFQLC SRQDCPDSLA DFREEQCRQW DLYFEHGDAQ HHWLPHEHRD AKERCHLYCE 

       670        680        690        700        710        720 
SRETGEVVSM KRMVHDGTRC SYKDAFSLCV RGDCRKVGCD GVIGSSKQED KCGVCGGDNS 

       730        740        750        760        770        780 
HCKVVKGTFT RSPKKHGYIK MFEIPAGARH LLIQEVDATS HHLAVKNLET GKFILNEEND 

       790        800        810        820        830        840 
VDASSKTFIA MGVEWEYRDE DGRETLQTMG PLHGTITVLV IPVGDTRVSL TYKYMIHEDS 

       850        860        870        880        890        900 
LNVDDNNVLE EDSVVYEWAL KKWSPCSKPC GGGSQFTKYG CRRRLDHKMV HRGFCAALSK 

       910        920        930        940        950        960 
PKAIRRACNP QECSQPVWVT GEWEPCSQTC GRTGMQVRSV RCIQPLHDNT TRSVHAKHCN 

       970        980        990       1000       1010       1020 
DARPESRRAC SRELCPGRWR AGPWSQCSVT CGNGTQERPV LCRTADDSFG ICQEERPETA 

      1030       1040       1050       1060       1070       1080 
RTCRLGPCPR NISDPSKKSY VVQWLSRPDP DSPIRKISSK GHCQGDKSIF CRMEVLSRYC 

      1090       1100       1110       1120       1130       1140 
SIPGYNKLCC KSCNLYNNLT NVEGRIEPPP GKHNDIDVFM PTLPVPTVAM EVRPSPSTPL 

      1150       1160       1170       1180       1190       1200 
EVPLNASSTN ATEDHPETNA VDEPYKIHGL EDEVQPPNLI PRRPSPYEKT RNQRIQELID 

      1210 
EMRKKEMLGK F 

« Hide

Isoform SpNPI [UniParc].

Checksum: 4D0D641B94307BA2
Show »

FASTA56661,756

References

« Hide 'large scale' references
[1]"Human Ehlers-Danlos syndrome type VII C and bovine dermatosparaxis are caused by mutations in the procollagen I N-proteinase gene."
Colige A., Sieron A.L., Li S.-W., Schwarze U., Petty E., Wertelecki W., Wilcox W., Krakow D., Cohn D.H., Reardon W., Byers P.H., Lapiere C.M., Prockop D.J., Nusgens B.V.
Am. J. Hum. Genet. 65:308-317(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS LPNPI AND SPNPI), INVOLVEMENT IN EDS7C.
Tissue: Skin.
[2]"The DNA sequence and comparative analysis of human chromosome 5."
Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S., Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M., She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S. expand/collapse author list , Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M., Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R., Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J., Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A., Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M.
Nature 431:268-274(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AJ003125 mRNA. Translation: CAA05880.1.
AC008544 Genomic DNA. No translation available.
AC010216 Genomic DNA. No translation available.
AC109479 Genomic DNA. No translation available.
RefSeqNP_055059.2. NM_014244.4.
NP_067610.1. NM_021599.2.
UniGeneHs.23871.

3D structure databases

ProteinModelPortalO95450.
SMRO95450. Positions 268-839, 859-1010.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid114887. 1 interaction.
IntActO95450. 1 interaction.
STRING9606.ENSP00000251582.

Protein family/group databases

MEROPSM12.301.

PTM databases

PhosphoSiteO95450.

Proteomic databases

PaxDbO95450.
PRIDEO95450.

Protocols and materials databases

DNASU9509.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000251582; ENSP00000251582; ENSG00000087116. [O95450-1]
ENST00000274609; ENSP00000274609; ENSG00000087116. [O95450-2]
GeneID9509.
KEGGhsa:9509.
UCSCuc003mjw.3. human. [O95450-1]
uc011dgm.2. human. [O95450-2]

Organism-specific databases

CTD9509.
GeneCardsGC05M178537.
HGNCHGNC:218. ADAMTS2.
HPAHPA028444.
MIM225410. phenotype.
604539. gene.
neXtProtNX_O95450.
Orphanet1901. Ehlers-Danlos syndrome, dermatosparaxis type.
PharmGKBPA24546.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG307411.
HOGENOMHOG000034222.
HOVERGENHBG004314.
InParanoidO95450.
KOK08618.
OMAIHEDSLN.
OrthoDBEOG76HQ0N.
PhylomeDBO95450.
TreeFamTF313537.

Enzyme and pathway databases

ReactomeREACT_118779. Extracellular matrix organization.

Gene expression databases

BgeeO95450.
CleanExHS_ADAMTS2.
GenevestigatorO95450.

Family and domain databases

Gene3D3.40.390.10. 1 hit.
InterProIPR010294. 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. Thrombospondin_1_rpt.
[Graphical view]
PfamPF05986. ADAM_spacer1. 1 hit.
PF01562. Pep_M12B_propep. 1 hit.
PF01421. Reprolysin. 1 hit.
PF00090. TSP_1. 4 hits.
[Graphical view]
PRINTSPR01859. ADAMTS2.
PR01857. ADAMTSFAMILY.
SMARTSM00209. TSP1. 4 hits.
[Graphical view]
SUPFAMSSF82895. SSF82895. 4 hits.
PROSITEPS50215. ADAM_MEPRO. 1 hit.
PS50900. PLAC. 1 hit.
PS50092. TSP1. 4 hits.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSADAMTS2. human.
GeneWikiADAMTS2.
GenomeRNAi9509.
NextBio35632.
PROO95450.
SOURCESearch...

Entry information

Entry nameATS2_HUMAN
AccessionPrimary (citable) accession number: O95450
Entry history
Integrated into UniProtKB/Swiss-Prot: December 1, 2000
Last sequence update: December 16, 2008
Last modified: April 16, 2014
This is version 148 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Peptidase families

Classification of peptidase families and list of entries

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 5

Human chromosome 5: entries, gene names and cross-references to MIM