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O95450

- ATS2_HUMAN

UniProt

O95450 - ATS2_HUMAN

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Protein
A disintegrin and metalloproteinase with thrombospondin motifs 2
Gene
ADAMTS2, PCINP, PCPNI
Organism
Homo sapiens (Human)
Status
Reviewed - 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

Binds 1 zinc ion per subunit By similarity.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi408 – 4081Zinc; catalytic By similarity
Active sitei409 – 4091 By similarity
Metal bindingi412 – 4121Zinc; catalytic By similarity
Metal bindingi418 – 4181Zinc; catalytic By similarity

GO - Molecular functioni

  1. metalloendopeptidase activity Source: ProtInc
  2. metallopeptidase activity Source: ProtInc
  3. zinc ion binding Source: InterPro

GO - Biological processi

  1. collagen catabolic process Source: UniProtKB-KW
  2. collagen fibril organization Source: Ensembl
  3. extracellular matrix organization Source: Reactome
  4. lung development Source: Ensembl
  5. protein processing Source: Ensembl
  6. skin development Source: Ensembl
  7. spermatogenesis Source: Ensembl
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Metalloprotease, Protease

Keywords - Biological processi

Collagen degradation

Keywords - Ligandi

Metal-binding, Zinc

Enzyme and pathway databases

ReactomeiREACT_121139. Collagen biosynthesis and modifying enzymes.
REACT_200626. 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
ProteomesiUP000005640: Chromosome 5

Organism-specific databases

HGNCiHGNC:218. ADAMTS2.

Subcellular locationi

GO - Cellular componenti

  1. extracellular region Source: Reactome
  2. proteinaceous extracellular matrix Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Extracellular matrix, Secreted

Pathology & Biotechi

Involvement in diseasei

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.1 Publication

Keywords - Diseasei

Ehlers-Danlos syndrome

Organism-specific databases

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

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2929 Reviewed prediction
Add
BLAST
Propeptidei30 – 253224 By similarity
PRO_0000029158Add
BLAST
Chaini254 – 1211958A disintegrin and metalloproteinase with thrombospondin motifs 2
PRO_0000029159Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi112 – 1121N-linked (GlcNAc...) Reviewed prediction
Glycosylationi251 – 2511N-linked (GlcNAc...) Reviewed prediction
Disulfide bondi343 ↔ 392 By similarity
Disulfide bondi386 ↔ 465 By similarity
Disulfide bondi425 ↔ 451 By similarity
Disulfide bondi492 ↔ 517 By similarity
Disulfide bondi503 ↔ 526 By similarity
Disulfide bondi512 ↔ 545 By similarity
Disulfide bondi539 ↔ 550 By similarity
Disulfide bondi573 ↔ 610 By similarity
Disulfide bondi577 ↔ 615 By similarity
Disulfide bondi588 ↔ 600 By similarity
Glycosylationi949 – 9491N-linked (GlcNAc...) Reviewed prediction
Disulfide bondi987 ↔ 1023 By similarity
Disulfide bondi991 ↔ 1028 By similarity
Glycosylationi993 – 9931N-linked (GlcNAc...) Reviewed prediction
Disulfide bondi1002 ↔ 1012 By similarity
Glycosylationi1031 – 10311N-linked (GlcNAc...) Reviewed prediction
Glycosylationi1098 – 10981N-linked (GlcNAc...) Reviewed prediction
Glycosylationi1145 – 11451N-linked (GlcNAc...) Reviewed prediction
Glycosylationi1150 – 11501N-linked (GlcNAc...) Reviewed prediction

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.

Keywords - PTMi

Disulfide bond, Glycoprotein, Zymogen

Proteomic databases

PaxDbiO95450.
PRIDEiO95450.

PTM databases

PhosphoSiteiO95450.

Expressioni

Tissue specificityi

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

Gene expression databases

BgeeiO95450.
CleanExiHS_ADAMTS2.
GenevestigatoriO95450.

Organism-specific databases

HPAiHPA028444.

Interactioni

Subunit structurei

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

Protein-protein interaction databases

BioGridi114887. 1 interaction.
IntActiO95450. 1 interaction.
STRINGi9606.ENSP00000251582.

Structurei

3D structure databases

ProteinModelPortaliO95450.
SMRiO95450. Positions 268-766, 923-1010.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini266 – 470205Peptidase M12B
Add
BLAST
Domaini480 – 56081Disintegrin
Add
BLAST
Domaini561 – 61656TSP type-1 1
Add
BLAST
Domaini854 – 91259TSP type-1 2
Add
BLAST
Domaini914 – 97158TSP type-1 3
Add
BLAST
Domaini975 – 102955TSP type-1 4
Add
BLAST
Domaini1059 – 109739PLAC
Add
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni723 – 851129Spacer
Add
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi691 – 6933Cell attachment site Reviewed prediction

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi40 – 434Poly-Ala
Compositional biasi185 – 1884Poly-Glu
Compositional biasi618 – 722105Cys-rich
Add
BLAST

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.
Contains 1 PLAC domain.
Contains 4 TSP type-1 domains.

Keywords - Domaini

Repeat, Signal

Phylogenomic databases

eggNOGiNOG307411.
HOGENOMiHOG000034222.
HOVERGENiHBG004314.
InParanoidiO95450.
KOiK08618.
OMAiIHEDSLN.
OrthoDBiEOG76HQ0N.
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. Thrombospondin_1_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. Align

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

MDPPAGAARR LLCPALLLLL LLLPPPLLPP PPPPANARLA AAADPPGGPL     50
GHGAERILAV PVRTDAQGRL VSHVVSAATS RAGVRARRAA PVRTPSFPGG 100
NEEEPGSHLF YNVTVFGRDL HLRLRPNARL VAPGATMEWQ GEKGTTRVEP 150
LLGSCLYVGD VAGLAEASSV ALSNCDGLAG LIRMEEEEFF IEPLEKGLAA 200
QEAEQGRVHV VYRRPPTSPP LGGPQALDTG ASLDSLDSLS RALGVLEEHA 250
NSSRRRARRH AADDDYNIEV LLGVDDSVVQ FHGKEHVQKY LLTLMNIVNE 300
IYHDESLGAH INVVLVRIIL LSYGKSMSLI EIGNPSQSLE NVCRWAYLQQ 350
KPDTGHDEYH DHAIFLTRQD FGPSGMQGYA PVTGMCHPVR SCTLNHEDGF 400
SSAFVVAHET GHVLGMEHDG QGNRCGDEVR LGSIMAPLVQ AAFHRFHWSR 450
CSQQELSRYL HSYDCLLDDP FAHDWPALPQ LPGLHYSMNE QCRFDFGLGY 500
MMCTAFRTFD PCKQLWCSHP DNPYFCKTKK GPPLDGTMCA PGKHCFKGHC 550
IWLTPDILKR DGSWGAWSPF GSCSRTCGTG VKFRTRQCDN PHPANGGRTC 600
SGLAYDFQLC SRQDCPDSLA DFREEQCRQW DLYFEHGDAQ HHWLPHEHRD 650
AKERCHLYCE SRETGEVVSM KRMVHDGTRC SYKDAFSLCV RGDCRKVGCD 700
GVIGSSKQED KCGVCGGDNS HCKVVKGTFT RSPKKHGYIK MFEIPAGARH 750
LLIQEVDATS HHLAVKNLET GKFILNEEND VDASSKTFIA MGVEWEYRDE 800
DGRETLQTMG PLHGTITVLV IPVGDTRVSL TYKYMIHEDS LNVDDNNVLE 850
EDSVVYEWAL KKWSPCSKPC GGGSQFTKYG CRRRLDHKMV HRGFCAALSK 900
PKAIRRACNP QECSQPVWVT GEWEPCSQTC GRTGMQVRSV RCIQPLHDNT 950
TRSVHAKHCN DARPESRRAC SRELCPGRWR AGPWSQCSVT CGNGTQERPV 1000
LCRTADDSFG ICQEERPETA RTCRLGPCPR NISDPSKKSY VVQWLSRPDP 1050
DSPIRKISSK GHCQGDKSIF CRMEVLSRYC SIPGYNKLCC KSCNLYNNLT 1100
NVEGRIEPPP GKHNDIDVFM PTLPVPTVAM EVRPSPSTPL EVPLNASSTN 1150
ATEDHPETNA VDEPYKIHGL EDEVQPPNLI PRRPSPYEKT RNQRIQELID 1200
EMRKKEMLGK F 1211
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

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti74 – 741V → M.
Corresponds to variant rs2271211 [ dbSNP | Ensembl ].
VAR_047927
Natural varianti241 – 2411R → H.
Corresponds to variant rs11750821 [ dbSNP | Ensembl ].
VAR_047928
Natural varianti245 – 2451V → I.
Corresponds to variant rs398829 [ dbSNP | Ensembl ].
VAR_020058
Natural varianti331 – 3311E → K.
Corresponds to variant rs17667857 [ dbSNP | Ensembl ].
VAR_047929
Natural varianti665 – 6651G → R.
Corresponds to variant rs35372714 [ dbSNP | Ensembl ].
VAR_047930
Natural varianti827 – 8271R → Q.
Corresponds to variant rs35445112 [ dbSNP | Ensembl ].
VAR_047931
Natural varianti1177 – 11771P → S.
Corresponds to variant rs1054480 [ dbSNP | Ensembl ].
VAR_020059

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei544 – 56623HCFKG…GSWGA → FRPGAVAHACYPSTLGGQGR WIA in isoform SpNPI.
VSP_005497Add
BLAST
Alternative sequencei567 – 1211645Missing in isoform SpNPI.
VSP_005498Add
BLAST

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti1001 – 10011L → P in CAA05880. 1 Publication
Sequence conflicti1089 – 10891C → S in CAA05880. 1 Publication

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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_021599.2. [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]
uc011dgm.2. human. [O95450-2]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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.
CCDSi CCDS34311.1. [O95450-2 ]
CCDS4444.1. [O95450-1 ]
RefSeqi NP_055059.2. NM_014244.4. [O95450-1 ]
NP_067610.1. NM_021599.2. [O95450-2 ]
UniGenei Hs.23871.

3D structure databases

ProteinModelPortali O95450.
SMRi O95450. Positions 268-766, 923-1010.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 114887. 1 interaction.
IntActi O95450. 1 interaction.
STRINGi 9606.ENSP00000251582.

Protein family/group databases

MEROPSi M12.301.

PTM databases

PhosphoSitei O95450.

Proteomic databases

PaxDbi O95450.
PRIDEi O95450.

Protocols and materials databases

DNASUi 9509.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000251582 ; ENSP00000251582 ; ENSG00000087116 . [O95450-1 ]
ENST00000274609 ; ENSP00000274609 ; ENSG00000087116 . [O95450-2 ]
GeneIDi 9509.
KEGGi hsa:9509.
UCSCi uc003mjw.3. human. [O95450-1 ]
uc011dgm.2. human. [O95450-2 ]

Organism-specific databases

CTDi 9509.
GeneCardsi GC05M178537.
HGNCi HGNC:218. ADAMTS2.
HPAi HPA028444.
MIMi 225410. phenotype.
604539. gene.
neXtProti NX_O95450.
Orphaneti 1901. Ehlers-Danlos syndrome, dermatosparaxis type.
PharmGKBi PA24546.
GenAtlasi Search...

Phylogenomic databases

eggNOGi NOG307411.
HOGENOMi HOG000034222.
HOVERGENi HBG004314.
InParanoidi O95450.
KOi K08618.
OMAi IHEDSLN.
OrthoDBi EOG76HQ0N.
PhylomeDBi O95450.
TreeFami TF313537.

Enzyme and pathway databases

Reactomei REACT_121139. Collagen biosynthesis and modifying enzymes.
REACT_200626. O-glycosylation of TSR domain-containing proteins.

Miscellaneous databases

ChiTaRSi ADAMTS2. human.
GeneWikii ADAMTS2.
GenomeRNAii 9509.
NextBioi 35632.
PROi O95450.
SOURCEi Search...

Gene expression databases

Bgeei O95450.
CleanExi HS_ADAMTS2.
Genevestigatori O95450.

Family and domain databases

Gene3Di 3.40.390.10. 1 hit.
InterProi IPR010294. 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 ]
Pfami PF05986. ADAM_spacer1. 1 hit.
PF01562. Pep_M12B_propep. 1 hit.
PF01421. Reprolysin. 1 hit.
PF00090. TSP_1. 4 hits.
[Graphical view ]
PRINTSi PR01859. ADAMTS2.
PR01857. ADAMTSFAMILY.
SMARTi SM00209. TSP1. 4 hits.
[Graphical view ]
SUPFAMi SSF82895. SSF82895. 4 hits.
PROSITEi PS50215. ADAM_MEPRO. 1 hit.
PS50900. PLAC. 1 hit.
PS50092. TSP1. 4 hits.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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.
    , 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].

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: September 3, 2014
This is version 152 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

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

External Data

Dasty 3

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