ATS2_HUMAN
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 03-AUG-2022, entry version 212.
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; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS LPNPI AND SPNPI), AND INVOLVEMENT IN
RP EDSDERMS.
RC TISSUE=Skin;
RX PubMed=10417273; DOI=10.1086/302504;
RA Colige A., Sieron A.L., Li S.-W., Schwarze U., Petty E., Wertelecki W.,
RA Wilcox W., Krakow D., Cohn D.H., Reardon W., Byers P.H., Lapiere C.M.,
RA Prockop D.J., Nusgens B.V.;
RT "Human Ehlers-Danlos syndrome type VII C and bovine dermatosparaxis are
RT 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., Gomez M.,
RA Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T.,
RA Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A.,
RA Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R.,
RA Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L.,
RA Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N.,
RA Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J.,
RA Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A.,
RA Rokhsar D.S., 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).
RN [3]
RP FUNCTION.
RX PubMed=31152061; DOI=10.1074/jbc.ra119.007806;
RA Rosell-Garcia T., Paradela A., Bravo G., Dupont L., Bekhouche M.,
RA Colige A., Rodriguez-Pascual F.;
RT "Differential cleavage of lysyl oxidase by the metalloproteinases BMP1 and
RT ADAMTS2/14 regulates collagen binding through a tyrosine sulfate domain.";
RL J. Biol. Chem. 294:11087-11100(2019).
CC -!- FUNCTION: Cleaves the propeptides of type I and II collagen prior to
CC fibril assembly (By similarity). Does not act on type III collagen (By
CC similarity). Cleaves lysyl oxidase LOX at a site downstream of its
CC propeptide cleavage site to produce a short LOX form with reduced
CC collagen-binding activity (PubMed:31152061).
CC {ECO:0000250|UniProtKB:P79331, ECO:0000269|PubMed:31152061}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Cleaves the N-propeptide of collagen chain alpha1(I) at Pro-|-
CC Gln and of alpha1(II) and alpha2(I) at Ala-|-Gln.; EC=3.4.24.14;
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 -!- TISSUE SPECIFICITY: Expressed at high level in skin, bone, tendon and
CC aorta and at low levels in thymus and brain.
CC -!- DOMAIN: The spacer domain and the TSP type-1 domains are important for
CC a tight interaction with the extracellular matrix.
CC -!- PTM: The precursor is cleaved by a furin endopeptidase. {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)-(S/T)-C2-
CC G of the TSP type-1 repeat domains where C1 and C2 are the first and
CC second cysteine residue of the repeat, respectively. Fucosylated
CC repeats can then be further glycosylated by the addition of a beta-1,3-
CC glucose residue by the glucosyltransferase, B3GALTL. Fucosylation
CC mediates the efficient secretion of ADAMTS family members. Can also be
CC C-glycosylated with one or two mannose molecules on tryptophan residues
CC within the consensus sequence W-X-X-W of the TPRs, and N-glycosylated.
CC These other glycosylations can also facilitate secretion (By
CC similarity). {ECO:0000250}.
CC -!- DISEASE: Ehlers-Danlos syndrome, dermatosparaxis type (EDSDERMS)
CC [MIM:225410]: A form of Ehlers-Danlos syndrome, a group of connective
CC tissue disorders characterized by skin hyperextensibility, articular
CC hypermobility, and tissue fragility. EDSDERMS is an autosomal recessive
CC form characterized by extreme skin fragility and easy bruising, large
CC fontanels, blue sclerae, puffy eyelids, micrognathia, umbilical hernia,
CC and short fingers. Joint hypermobility becomes more important with age.
CC {ECO:0000269|PubMed:10417273}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- MISCELLANEOUS: [Isoform SpNPI]: Has no significant N-procollagen
CC peptidase activity. {ECO:0000305}.
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_021599.3. [O95450-2]
DR AlphaFoldDB; O95450; -.
DR SMR; O95450; -.
DR BioGRID; 114887; 53.
DR IntAct; O95450; 16.
DR STRING; 9606.ENSP00000251582; -.
DR MEROPS; M12.301; -.
DR GlyGen; O95450; 9 sites, 1 O-linked glycan (1 site).
DR iPTMnet; O95450; -.
DR PhosphoSitePlus; O95450; -.
DR BioMuta; ADAMTS2; -.
DR jPOST; O95450; -.
DR MassIVE; O95450; -.
DR PaxDb; O95450; -.
DR PeptideAtlas; O95450; -.
DR PRIDE; O95450; -.
DR ProteomicsDB; 50883; -. [O95450-1]
DR ProteomicsDB; 50884; -. [O95450-2]
DR Antibodypedia; 17642; 181 antibodies from 29 providers.
DR DNASU; 9509; -.
DR Ensembl; ENST00000251582.12; ENSP00000251582.7; ENSG00000087116.16. [O95450-1]
DR Ensembl; ENST00000274609.5; ENSP00000274609.5; ENSG00000087116.16. [O95450-2]
DR Ensembl; ENST00000639107.1; ENSP00000492365.1; ENSG00000283802.3. [O95450-2]
DR Ensembl; ENST00000639986.2; ENSP00000492346.1; ENSG00000283802.3. [O95450-1]
DR GeneID; 9509; -.
DR KEGG; hsa:9509; -.
DR MANE-Select; ENST00000251582.12; ENSP00000251582.7; NM_014244.5; NP_055059.2.
DR UCSC; uc003mjw.3; human. [O95450-1]
DR CTD; 9509; -.
DR DisGeNET; 9509; -.
DR GeneCards; ADAMTS2; -.
DR HGNC; HGNC:218; ADAMTS2.
DR HPA; ENSG00000087116; Low tissue specificity.
DR MalaCards; ADAMTS2; -.
DR MIM; 225410; phenotype.
DR MIM; 604539; gene.
DR neXtProt; NX_O95450; -.
DR OpenTargets; ENSG00000087116; -.
DR Orphanet; 1901; Dermatosparaxis Ehlers-Danlos syndrome.
DR PharmGKB; PA24546; -.
DR VEuPathDB; HostDB:ENSG00000087116; -.
DR eggNOG; KOG3538; Eukaryota.
DR GeneTree; ENSGT00940000156647; -.
DR HOGENOM; CLU_000660_4_1_1; -.
DR InParanoid; O95450; -.
DR OMA; VPYKIHG; -.
DR OrthoDB; 79609at2759; -.
DR PhylomeDB; O95450; -.
DR TreeFam; TF313537; -.
DR BRENDA; 3.4.24.14; 2681.
DR PathwayCommons; O95450; -.
DR Reactome; R-HSA-1650814; Collagen biosynthesis and modifying enzymes.
DR Reactome; R-HSA-5083635; Defective B3GALTL causes PpS.
DR Reactome; R-HSA-5173214; O-glycosylation of TSR domain-containing proteins.
DR SignaLink; O95450; -.
DR BioGRID-ORCS; 9509; 15 hits in 1069 CRISPR screens.
DR ChiTaRS; ADAMTS2; human.
DR GeneWiki; ADAMTS2; -.
DR GenomeRNAi; 9509; -.
DR Pharos; O95450; Tbio.
DR PRO; PR:O95450; -.
DR Proteomes; UP000005640; Chromosome 5.
DR RNAct; O95450; protein.
DR Bgee; ENSG00000087116; Expressed in stromal cell of endometrium and 93 other tissues.
DR ExpressionAtlas; O95450; baseline and differential.
DR Genevisible; O95450; HS.
DR GO; GO:0062023; C:collagen-containing extracellular matrix; IEA:InterPro.
DR GO; GO:0031012; C:extracellular matrix; IBA:GO_Central.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0004222; F:metalloendopeptidase activity; IBA:GO_Central.
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; TAS:Reactome.
DR GO; GO:0030198; P:extracellular matrix organization; IBA:GO_Central.
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; 2.20.100.10; -; 4.
DR Gene3D; 3.40.390.10; -; 1.
DR InterPro; IPR013273; ADAMTS/ADAMTS-like.
DR InterPro; IPR041645; ADAMTS_CR_2.
DR InterPro; IPR045371; ADAMTS_CR_3.
DR InterPro; IPR010294; ADAMTS_spacer1.
DR InterPro; IPR024079; MetalloPept_cat_dom_sf.
DR InterPro; IPR013275; Pept_M12B_ADAM-TS2.
DR InterPro; IPR001590; Peptidase_M12B.
DR InterPro; IPR002870; Peptidase_M12B_N.
DR InterPro; IPR010909; PLAC.
DR InterPro; IPR000884; TSP1_rpt.
DR InterPro; IPR036383; TSP1_rpt_sf.
DR Pfam; PF17771; ADAM_CR_2; 1.
DR Pfam; PF19236; ADAM_CR_3; 1.
DR Pfam; PF05986; ADAM_spacer1; 1.
DR Pfam; PF01562; Pep_M12B_propep; 1.
DR Pfam; PF01421; Reprolysin; 1.
DR Pfam; PF00090; TSP_1; 1.
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; Disulfide bond;
KW Ehlers-Danlos syndrome; Extracellular matrix; Glycoprotein; Hydrolase;
KW Metal-binding; Metalloprotease; Protease; Reference proteome; Repeat;
KW Secreted; Signal; Zinc; Zymogen.
FT SIGNAL 1..29
FT /evidence="ECO:0000255"
FT PROPEP 30..253
FT /evidence="ECO:0000250"
FT /id="PRO_0000029158"
FT CHAIN 254..1211
FT /note="A disintegrin and metalloproteinase with
FT thrombospondin motifs 2"
FT /id="PRO_0000029159"
FT DOMAIN 266..470
FT /note="Peptidase M12B"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00276"
FT DOMAIN 480..560
FT /note="Disintegrin"
FT DOMAIN 561..616
FT /note="TSP type-1 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00210"
FT DOMAIN 854..912
FT /note="TSP type-1 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00210"
FT DOMAIN 914..971
FT /note="TSP type-1 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00210"
FT DOMAIN 975..1029
FT /note="TSP type-1 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00210"
FT DOMAIN 1059..1097
FT /note="PLAC"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00233"
FT REGION 723..851
FT /note="Spacer"
FT REGION 1170..1191
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 691..693
FT /note="Cell attachment site"
FT /evidence="ECO:0000255"
FT ACT_SITE 409
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00276"
FT BINDING 408
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00276"
FT BINDING 412
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00276"
FT BINDING 418
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00276"
FT CARBOHYD 112
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 251
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 949
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 993
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1031
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1098
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1145
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 1150
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 343..392
FT /evidence="ECO:0000250"
FT DISULFID 386..465
FT /evidence="ECO:0000250"
FT DISULFID 425..451
FT /evidence="ECO:0000250"
FT DISULFID 492..517
FT /evidence="ECO:0000250"
FT DISULFID 503..526
FT /evidence="ECO:0000250"
FT DISULFID 512..545
FT /evidence="ECO:0000250"
FT DISULFID 539..550
FT /evidence="ECO:0000250"
FT DISULFID 573..610
FT /evidence="ECO:0000250"
FT DISULFID 577..615
FT /evidence="ECO:0000250"
FT DISULFID 588..600
FT /evidence="ECO:0000250"
FT DISULFID 987..1023
FT /evidence="ECO:0000250"
FT DISULFID 991..1028
FT /evidence="ECO:0000250"
FT DISULFID 1002..1012
FT /evidence="ECO:0000250"
FT VAR_SEQ 544..566
FT /note="HCFKGHCIWLTPDILKRDGSWGA -> FRPGAVAHACYPSTLGGQGRWIA
FT (in isoform SpNPI)"
FT /evidence="ECO:0000303|PubMed:10417273"
FT /id="VSP_005497"
FT VAR_SEQ 567..1211
FT /note="Missing (in isoform SpNPI)"
FT /evidence="ECO:0000303|PubMed:10417273"
FT /id="VSP_005498"
FT VARIANT 74
FT /note="V -> M (in dbSNP:rs2271211)"
FT /id="VAR_047927"
FT VARIANT 241
FT /note="R -> H (in dbSNP:rs11750821)"
FT /id="VAR_047928"
FT VARIANT 245
FT /note="V -> I (in dbSNP:rs398829)"
FT /id="VAR_020058"
FT VARIANT 331
FT /note="E -> K (in dbSNP:rs17667857)"
FT /id="VAR_047929"
FT VARIANT 665
FT /note="G -> R (in dbSNP:rs35372714)"
FT /id="VAR_047930"
FT VARIANT 827
FT /note="R -> Q (in dbSNP:rs35445112)"
FT /id="VAR_047931"
FT VARIANT 1177
FT /note="P -> S (in dbSNP:rs1054480)"
FT /id="VAR_020059"
FT CONFLICT 1001
FT /note="L -> P (in Ref. 1; CAA05880)"
FT /evidence="ECO:0000305"
FT CONFLICT 1089
FT /note="C -> S (in Ref. 1; CAA05880)"
FT /evidence="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
