ID   ATS2_HUMAN              Reviewed;        1211 AA.
AC   O95450;
DT   01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT   16-DEC-2008, sequence version 2.
DT   09-DEC-2015, entry version 164.
DE   RecName: Full=A disintegrin and metalloproteinase with thrombospondin motifs 2;
DE            Short=ADAM-TS 2;
DE            Short=ADAM-TS2;
DE            Short=ADAMTS-2;
DE            EC=3.4.24.14;
DE   AltName: Full=Procollagen I N-proteinase;
DE            Short=PC I-NP;
DE   AltName: Full=Procollagen I/II amino propeptide-processing enzyme;
DE   AltName: Full=Procollagen N-endopeptidase;
DE            Short=pNPI;
DE   Flags: Precursor;
GN   Name=ADAMTS2; Synonyms=PCINP, PCPNI;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC   Catarrhini; Hominidae; Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS LPNPI AND SPNPI), AND INVOLVEMENT
RP   IN EDS7C.
RC   TISSUE=Skin;
RX   PubMed=10417273; DOI=10.1086/302504;
RA   Colige A., Sieron A.L., Li S.-W., Schwarze U., Petty E.,
RA   Wertelecki W., Wilcox W., Krakow D., Cohn D.H., Reardon W.,
RA   Byers P.H., Lapiere C.M., Prockop D.J., Nusgens B.V.;
RT   "Human Ehlers-Danlos syndrome type VII C and bovine dermatosparaxis
RT   are caused by mutations in the procollagen I N-proteinase gene.";
RL   Am. J. Hum. Genet. 65:308-317(1999).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=15372022; DOI=10.1038/nature02919;
RA   Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S.,
RA   Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M.,
RA   She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S.,
RA   Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M.,
RA   Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T.,
RA   Gomez M., Gonzales E., Goodstein D., Grigoriev I., Groza M.,
RA   Hammon N., Hawkins T., Haydu L., Israni S., Jett J., Kadner K.,
RA   Kimball H., Kobayashi A., Lopez F., Lou Y., Martinez D., Medina C.,
RA   Morgan J., Nandkeshwar R., Noonan J.P., Pitluck S., Pollard M.,
RA   Predki P., Priest J., Ramirez L., Retterer J., Rodriguez A.,
RA   Rogers S., Salamov A., Salazar A., Thayer N., Tice H., Tsai M.,
RA   Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J., Dickson M.,
RA   Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A., Rokhsar D.S.,
RA   Richardson P., Lucas S.M., Myers R.M., Rubin E.M.;
RT   "The DNA sequence and comparative analysis of human chromosome 5.";
RL   Nature 431:268-274(2004).
CC   -!- FUNCTION: Cleaves the propeptides of type I and II collagen prior
CC       to fibril assembly. Does not act on type III collagen. May also
CC       play a role in development that is independent of its role in
CC       collagen biosynthesis.
CC   -!- CATALYTIC ACTIVITY: Cleaves the N-propeptide of collagen chain
CC       alpha-1(I) at Pro-|-Gln and of alpha-1(II) and alpha-2(I) at
CC       Ala-|-Gln.
CC   -!- COFACTOR:
CC       Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000250};
CC       Note=Binds 1 zinc ion per subunit. {ECO:0000250};
CC   -!- SUBUNIT: May belong to a multimeric complex. Binds specifically to
CC       collagen type XIV (By similarity). {ECO:0000250}.
CC   -!- SUBCELLULAR LOCATION: Secreted, extracellular space, extracellular
CC       matrix {ECO:0000250}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=LpNPI;
CC         IsoId=O95450-1; Sequence=Displayed;
CC       Name=SpNPI;
CC         IsoId=O95450-2; Sequence=VSP_005497, VSP_005498;
CC         Note=Has no significant N-procollagen peptidase activity.;
CC   -!- TISSUE SPECIFICITY: Expressed at high level in skin, bone, tendon
CC       and aorta and at low levels in thymus and brain.
CC   -!- DOMAIN: The spacer domain and the TSP type-1 domains are important
CC       for a tight interaction with the extracellular matrix.
CC   -!- PTM: The precursor is cleaved by a furin endopeptidase.
CC       {ECO:0000250}.
CC   -!- PTM: Glycosylated. Can be O-fucosylated by POFUT2 on a serine or a
CC       threonine residue found within the consensus sequence C1-X(2)-
CC       (S/T)-C2-G of the TSP type-1 repeat domains where C1 and C2 are
CC       the first and second cysteine residue of the repeat, respectively.
CC       Fucosylated repeats can then be further glycosylated by the
CC       addition of a beta-1,3-glucose residue by the glucosyltransferase,
CC       B3GALTL. Fucosylation mediates the efficient secretion of ADAMTS
CC       family members. Also can be C-glycosylated with one or two mannose
CC       molecules on tryptophan residues within the consensus sequence W-
CC       X-X-W of the TPRs, and N-glycosylated. These other glycosylations
CC       can also facilitate secretion (By similarity). {ECO:0000250}.
CC   -!- DISEASE: Ehlers-Danlos syndrome 7C (EDS7C) [MIM:225410]: A
CC       connective tissue disorder characterized by hyperextensible skin,
CC       atrophic cutaneous scars due to tissue fragility and joint
CC       hyperlaxity. Marked by extremely fragile tissues, hyperextensible
CC       skin and easy bruising. Facial skin contains numerous folds, as in
CC       the cutis laxa syndrome. {ECO:0000269|PubMed:10417273}. Note=The
CC       disease is caused by mutations affecting the gene represented in
CC       this entry.
CC   -!- SIMILARITY: Contains 1 disintegrin domain. {ECO:0000305}.
CC   -!- SIMILARITY: Contains 1 peptidase M12B domain.
CC       {ECO:0000255|PROSITE-ProRule:PRU00276}.
CC   -!- SIMILARITY: Contains 1 PLAC domain. {ECO:0000255|PROSITE-
CC       ProRule:PRU00233}.
CC   -!- SIMILARITY: Contains 4 TSP type-1 domains. {ECO:0000255|PROSITE-
CC       ProRule:PRU00210}.
CC   -!- CAUTION: Has sometimes been referred to as ADAMTS3. {ECO:0000305}.
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DR   EMBL; AJ003125; CAA05880.1; -; mRNA.
DR   EMBL; AC008544; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AC010216; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AC109479; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   CCDS; CCDS34311.1; -. [O95450-2]
DR   CCDS; CCDS4444.1; -. [O95450-1]
DR   RefSeq; NP_055059.2; NM_014244.4. [O95450-1]
DR   RefSeq; NP_067610.1; NM_021599.2. [O95450-2]
DR   UniGene; Hs.23871; -.
DR   ProteinModelPortal; O95450; -.
DR   SMR; O95450; 268-766, 923-1010.
DR   BioGrid; 114887; 18.
DR   IntAct; O95450; 1.
DR   STRING; 9606.ENSP00000251582; -.
DR   MEROPS; M12.301; -.
DR   PhosphoSite; O95450; -.
DR   BioMuta; ADAMTS2; -.
DR   PaxDb; O95450; -.
DR   PRIDE; O95450; -.
DR   DNASU; 9509; -.
DR   Ensembl; ENST00000251582; ENSP00000251582; ENSG00000087116. [O95450-1]
DR   Ensembl; ENST00000274609; ENSP00000274609; ENSG00000087116. [O95450-2]
DR   GeneID; 9509; -.
DR   KEGG; hsa:9509; -.
DR   UCSC; uc003mjw.3; human. [O95450-1]
DR   UCSC; uc011dgm.2; human. [O95450-2]
DR   CTD; 9509; -.
DR   GeneCards; ADAMTS2; -.
DR   HGNC; HGNC:218; ADAMTS2.
DR   HPA; HPA028444; -.
DR   MalaCards; ADAMTS2; -.
DR   MIM; 225410; phenotype.
DR   MIM; 604539; gene.
DR   neXtProt; NX_O95450; -.
DR   Orphanet; 1901; Ehlers-Danlos syndrome, dermatosparaxis type.
DR   PharmGKB; PA24546; -.
DR   eggNOG; ENOG410INDA; Eukaryota.
DR   eggNOG; ENOG410XSRH; LUCA.
DR   GeneTree; ENSGT00760000118880; -.
DR   HOGENOM; HOG000034222; -.
DR   HOVERGEN; HBG004314; -.
DR   InParanoid; O95450; -.
DR   KO; K08618; -.
DR   OMA; IHEDSLN; -.
DR   OrthoDB; EOG76HQ0N; -.
DR   PhylomeDB; O95450; -.
DR   TreeFam; TF313537; -.
DR   Reactome; R-HSA-1650814; Collagen biosynthesis and modifying enzymes.
DR   Reactome; R-HSA-5173214; O-glycosylation of TSR domain-containing proteins.
DR   ChiTaRS; ADAMTS2; human.
DR   GeneWiki; ADAMTS2; -.
DR   GenomeRNAi; 9509; -.
DR   NextBio; 35632; -.
DR   PRO; PR:O95450; -.
DR   Proteomes; UP000005640; Chromosome 5.
DR   Bgee; O95450; -.
DR   CleanEx; HS_ADAMTS2; -.
DR   Genevisible; O95450; HS.
DR   GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR   GO; GO:0005578; C:proteinaceous extracellular matrix; IEA:UniProtKB-SubCell.
DR   GO; GO:0004222; F:metalloendopeptidase activity; TAS:ProtInc.
DR   GO; GO:0008237; F:metallopeptidase activity; TAS:ProtInc.
DR   GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR   GO; GO:0030574; P:collagen catabolic process; IEA:UniProtKB-KW.
DR   GO; GO:0030199; P:collagen fibril organization; IEA:Ensembl.
DR   GO; GO:0030198; P:extracellular matrix organization; TAS:Reactome.
DR   GO; GO:0030324; P:lung development; IEA:Ensembl.
DR   GO; GO:0016485; P:protein processing; IEA:Ensembl.
DR   GO; GO:0043588; P:skin development; IEA:Ensembl.
DR   GO; GO:0007283; P:spermatogenesis; IEA:Ensembl.
DR   Gene3D; 3.40.390.10; -; 1.
DR   InterPro; IPR010294; ADAM_spacer1.
DR   InterPro; IPR024079; MetalloPept_cat_dom.
DR   InterPro; IPR013275; Pept_M12B_ADAM-TS2.
DR   InterPro; IPR001590; Peptidase_M12B.
DR   InterPro; IPR013273; Peptidase_M12B_ADAM-TS.
DR   InterPro; IPR002870; Peptidase_M12B_N.
DR   InterPro; IPR010909; PLAC.
DR   InterPro; IPR000884; TSP1_rpt.
DR   Pfam; PF05986; ADAM_spacer1; 1.
DR   Pfam; PF01562; Pep_M12B_propep; 1.
DR   Pfam; PF01421; Reprolysin; 1.
DR   Pfam; PF00090; TSP_1; 4.
DR   PRINTS; PR01859; ADAMTS2.
DR   PRINTS; PR01857; ADAMTSFAMILY.
DR   SMART; SM00209; TSP1; 4.
DR   SUPFAM; SSF82895; SSF82895; 4.
DR   PROSITE; PS50215; ADAM_MEPRO; 1.
DR   PROSITE; PS50900; PLAC; 1.
DR   PROSITE; PS50092; TSP1; 4.
PE   2: Evidence at transcript level;
KW   Alternative splicing; Collagen degradation; Complete proteome;
KW   Disulfide bond; Ehlers-Danlos syndrome; Extracellular matrix;
KW   Glycoprotein; Hydrolase; Metal-binding; Metalloprotease; Polymorphism;
KW   Protease; Reference proteome; Repeat; Secreted; Signal; Zinc; Zymogen.
FT   SIGNAL        1     29       {ECO:0000255}.
FT   PROPEP       30    253       {ECO:0000250}.
FT                                /FTId=PRO_0000029158.
FT   CHAIN       254   1211       A disintegrin and metalloproteinase with
FT                                thrombospondin motifs 2.
FT                                /FTId=PRO_0000029159.
FT   DOMAIN      266    470       Peptidase M12B. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00276}.
FT   DOMAIN      480    560       Disintegrin.
FT   DOMAIN      561    616       TSP type-1 1. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00210}.
FT   DOMAIN      854    912       TSP type-1 2. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00210}.
FT   DOMAIN      914    971       TSP type-1 3. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00210}.
FT   DOMAIN      975   1029       TSP type-1 4. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00210}.
FT   DOMAIN     1059   1097       PLAC. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00233}.
FT   REGION      723    851       Spacer.
FT   MOTIF       691    693       Cell attachment site. {ECO:0000255}.
FT   COMPBIAS     40     43       Poly-Ala.
FT   COMPBIAS    185    188       Poly-Glu.
FT   COMPBIAS    618    722       Cys-rich.
FT   ACT_SITE    409    409       {ECO:0000255|PROSITE-ProRule:PRU00276}.
FT   METAL       408    408       Zinc; catalytic. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00276}.
FT   METAL       412    412       Zinc; catalytic. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00276}.
FT   METAL       418    418       Zinc; catalytic. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00276}.
FT   CARBOHYD    112    112       N-linked (GlcNAc...). {ECO:0000255}.
FT   CARBOHYD    251    251       N-linked (GlcNAc...). {ECO:0000255}.
FT   CARBOHYD    949    949       N-linked (GlcNAc...). {ECO:0000255}.
FT   CARBOHYD    993    993       N-linked (GlcNAc...). {ECO:0000255}.
FT   CARBOHYD   1031   1031       N-linked (GlcNAc...). {ECO:0000255}.
FT   CARBOHYD   1098   1098       N-linked (GlcNAc...). {ECO:0000255}.
FT   CARBOHYD   1145   1145       N-linked (GlcNAc...). {ECO:0000255}.
FT   CARBOHYD   1150   1150       N-linked (GlcNAc...). {ECO:0000255}.
FT   DISULFID    343    392       {ECO:0000250}.
FT   DISULFID    386    465       {ECO:0000250}.
FT   DISULFID    425    451       {ECO:0000250}.
FT   DISULFID    492    517       {ECO:0000250}.
FT   DISULFID    503    526       {ECO:0000250}.
FT   DISULFID    512    545       {ECO:0000250}.
FT   DISULFID    539    550       {ECO:0000250}.
FT   DISULFID    573    610       {ECO:0000250}.
FT   DISULFID    577    615       {ECO:0000250}.
FT   DISULFID    588    600       {ECO:0000250}.
FT   DISULFID    987   1023       {ECO:0000250}.
FT   DISULFID    991   1028       {ECO:0000250}.
FT   DISULFID   1002   1012       {ECO:0000250}.
FT   VAR_SEQ     544    566       HCFKGHCIWLTPDILKRDGSWGA -> FRPGAVAHACYPST
FT                                LGGQGRWIA (in isoform SpNPI).
FT                                {ECO:0000303|PubMed:10417273}.
FT                                /FTId=VSP_005497.
FT   VAR_SEQ     567   1211       Missing (in isoform SpNPI).
FT                                {ECO:0000303|PubMed:10417273}.
FT                                /FTId=VSP_005498.
FT   VARIANT      74     74       V -> M (in dbSNP:rs2271211).
FT                                /FTId=VAR_047927.
FT   VARIANT     241    241       R -> H (in dbSNP:rs11750821).
FT                                /FTId=VAR_047928.
FT   VARIANT     245    245       V -> I (in dbSNP:rs398829).
FT                                /FTId=VAR_020058.
FT   VARIANT     331    331       E -> K (in dbSNP:rs17667857).
FT                                /FTId=VAR_047929.
FT   VARIANT     665    665       G -> R (in dbSNP:rs35372714).
FT                                /FTId=VAR_047930.
FT   VARIANT     827    827       R -> Q (in dbSNP:rs35445112).
FT                                /FTId=VAR_047931.
FT   VARIANT    1177   1177       P -> S (in dbSNP:rs1054480).
FT                                /FTId=VAR_020059.
FT   CONFLICT   1001   1001       L -> P (in Ref. 1; CAA05880).
FT                                {ECO:0000305}.
FT   CONFLICT   1089   1089       C -> S (in Ref. 1; CAA05880).
FT                                {ECO:0000305}.
SQ   SEQUENCE   1211 AA;  134755 MW;  6C4F2C2D46A1F925 CRC64;
     MDPPAGAARR LLCPALLLLL LLLPPPLLPP PPPPANARLA AAADPPGGPL GHGAERILAV
     PVRTDAQGRL VSHVVSAATS RAGVRARRAA PVRTPSFPGG NEEEPGSHLF YNVTVFGRDL
     HLRLRPNARL VAPGATMEWQ GEKGTTRVEP LLGSCLYVGD VAGLAEASSV ALSNCDGLAG
     LIRMEEEEFF IEPLEKGLAA QEAEQGRVHV VYRRPPTSPP LGGPQALDTG ASLDSLDSLS
     RALGVLEEHA NSSRRRARRH AADDDYNIEV LLGVDDSVVQ FHGKEHVQKY LLTLMNIVNE
     IYHDESLGAH INVVLVRIIL LSYGKSMSLI EIGNPSQSLE NVCRWAYLQQ KPDTGHDEYH
     DHAIFLTRQD FGPSGMQGYA PVTGMCHPVR SCTLNHEDGF SSAFVVAHET GHVLGMEHDG
     QGNRCGDEVR LGSIMAPLVQ AAFHRFHWSR CSQQELSRYL HSYDCLLDDP FAHDWPALPQ
     LPGLHYSMNE QCRFDFGLGY MMCTAFRTFD PCKQLWCSHP DNPYFCKTKK GPPLDGTMCA
     PGKHCFKGHC IWLTPDILKR DGSWGAWSPF GSCSRTCGTG VKFRTRQCDN PHPANGGRTC
     SGLAYDFQLC SRQDCPDSLA DFREEQCRQW DLYFEHGDAQ HHWLPHEHRD AKERCHLYCE
     SRETGEVVSM KRMVHDGTRC SYKDAFSLCV RGDCRKVGCD GVIGSSKQED KCGVCGGDNS
     HCKVVKGTFT RSPKKHGYIK MFEIPAGARH LLIQEVDATS HHLAVKNLET GKFILNEEND
     VDASSKTFIA MGVEWEYRDE DGRETLQTMG PLHGTITVLV IPVGDTRVSL TYKYMIHEDS
     LNVDDNNVLE EDSVVYEWAL KKWSPCSKPC GGGSQFTKYG CRRRLDHKMV HRGFCAALSK
     PKAIRRACNP QECSQPVWVT GEWEPCSQTC GRTGMQVRSV RCIQPLHDNT TRSVHAKHCN
     DARPESRRAC SRELCPGRWR AGPWSQCSVT CGNGTQERPV LCRTADDSFG ICQEERPETA
     RTCRLGPCPR NISDPSKKSY VVQWLSRPDP DSPIRKISSK GHCQGDKSIF CRMEVLSRYC
     SIPGYNKLCC KSCNLYNNLT NVEGRIEPPP GKHNDIDVFM PTLPVPTVAM EVRPSPSTPL
     EVPLNASSTN ATEDHPETNA VDEPYKIHGL EDEVQPPNLI PRRPSPYEKT RNQRIQELID
     EMRKKEMLGK F
//