ID   ATS3_HUMAN              Reviewed;        1205 AA.
AC   O15072; A1L3U9; Q9BXZ8;
DT   01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT   11-JAN-2011, sequence version 4.
DT   13-FEB-2019, entry version 181.
DE   RecName: Full=A disintegrin and metalloproteinase with thrombospondin motifs 3;
DE            Short=ADAM-TS 3;
DE            Short=ADAM-TS3;
DE            Short=ADAMTS-3;
DE            EC=3.4.24.-;
DE   AltName: Full=Procollagen II N-proteinase;
DE            Short=PC II-NP;
DE   AltName: Full=Procollagen II amino propeptide-processing enzyme;
DE   Flags: Precursor;
GN   Name=ADAMTS3; Synonyms=KIAA0366;
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 [LARGE SCALE GENOMIC DNA].
RX   PubMed=15815621; DOI=10.1038/nature03466;
RA   Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H.,
RA   Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M.,
RA   Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E.,
RA   Kremitzki C., Oddy L., Du H., Sun H., Bradshaw-Cordum H., Ali J.,
RA   Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C.,
RA   Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J.,
RA   Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A.,
RA   Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K.,
RA   Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M.,
RA   Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA   McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA   Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N.,
RA   Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M.,
RA   Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E.,
RA   Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P.,
RA   Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A.,
RA   Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A.,
RA   Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T.,
RA   Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D.,
RA   Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X.,
RA   McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA   Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA   Miller W., Eichler E.E., Bork P., Suyama M., Torrents D.,
RA   Waterston R.H., Wilson R.K.;
RT   "Generation and annotation of the DNA sequences of human chromosomes 2
RT   and 4.";
RL   Nature 434:724-731(2005).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT LYS-138.
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA
RT   project: the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 1-227, AND VARIANT LYS-138.
RX   PubMed=11408482; DOI=10.1074/jbc.M103466200;
RA   Fernandes R.J., Hirohata S., Engle J.M., Colige A., Cohn D.H.,
RA   Eyre D.R., Apte S.S.;
RT   "Procollagen II amino propeptide processing by ADAMTS-3. Insights on
RT   dermatosparaxis.";
RL   J. Biol. Chem. 276:31502-31509(2001).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 5-1205, AND VARIANT LYS-138.
RC   TISSUE=Brain;
RX   PubMed=9205841; DOI=10.1093/dnares/4.2.141;
RA   Nagase T., Ishikawa K., Nakajima D., Ohira M., Seki N., Miyajima N.,
RA   Tanaka A., Kotani H., Nomura N., Ohara O.;
RT   "Prediction of the coding sequences of unidentified human genes. VII.
RT   The complete sequences of 100 new cDNA clones from brain which can
RT   code for large proteins in vitro.";
RL   DNA Res. 4:141-150(1997).
CC   -!- FUNCTION: Cleaves the propeptides of type II collagen prior to
CC       fibril assembly. Does not act on types I and III collagens.
CC   -!- COFACTOR:
CC       Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000250};
CC       Note=Binds 1 zinc ion per subunit. {ECO:0000250};
CC   -!- SUBCELLULAR LOCATION: Secreted, extracellular space, extracellular
CC       matrix {ECO:0000250}.
CC   -!- TISSUE SPECIFICITY: Found in cartilage and skin.
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   -!- CAUTION: Has sometimes been referred to as ADAMTS4. {ECO:0000305}.
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DR   EMBL; AC093790; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AC095056; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AC104814; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BC130287; AAI30288.1; -; mRNA.
DR   EMBL; BC132735; AAI32736.1; -; mRNA.
DR   EMBL; AF247668; AAK28400.1; -; mRNA.
DR   EMBL; AB002364; BAA20821.1; -; mRNA.
DR   CCDS; CCDS3553.1; -.
DR   RefSeq; NP_055058.2; NM_014243.2.
DR   UniGene; Hs.590919; -.
DR   ProteinModelPortal; O15072; -.
DR   SMR; O15072; -.
DR   IntAct; O15072; 2.
DR   STRING; 9606.ENSP00000286657; -.
DR   MEROPS; M12.220; -.
DR   iPTMnet; O15072; -.
DR   PhosphoSitePlus; O15072; -.
DR   BioMuta; ADAMTS3; -.
DR   EPD; O15072; -.
DR   jPOST; O15072; -.
DR   PaxDb; O15072; -.
DR   PeptideAtlas; O15072; -.
DR   PRIDE; O15072; -.
DR   ProteomicsDB; 48427; -.
DR   Ensembl; ENST00000286657; ENSP00000286657; ENSG00000156140.
DR   Ensembl; ENST00000622135; ENSP00000480055; ENSG00000156140.
DR   GeneID; 9508; -.
DR   KEGG; hsa:9508; -.
DR   UCSC; uc003hgk.2; human.
DR   CTD; 9508; -.
DR   DisGeNET; 9508; -.
DR   EuPathDB; HostDB:ENSG00000156140.8; -.
DR   GeneCards; ADAMTS3; -.
DR   H-InvDB; HIX0004274; -.
DR   HGNC; HGNC:219; ADAMTS3.
DR   HPA; HPA021368; -.
DR   HPA; HPA021369; -.
DR   MalaCards; ADAMTS3; -.
DR   MIM; 605011; gene.
DR   neXtProt; NX_O15072; -.
DR   OpenTargets; ENSG00000156140; -.
DR   Orphanet; 2136; Hennekam syndrome.
DR   PharmGKB; PA24547; -.
DR   eggNOG; ENOG410INDA; Eukaryota.
DR   eggNOG; ENOG410XSRH; LUCA.
DR   GeneTree; ENSGT00940000156085; -.
DR   HOGENOM; HOG000034222; -.
DR   HOVERGEN; HBG004314; -.
DR   InParanoid; O15072; -.
DR   KO; K08619; -.
DR   OMA; PYEHPDS; -.
DR   OrthoDB; 79609at2759; -.
DR   PhylomeDB; O15072; -.
DR   TreeFam; TF313537; -.
DR   Reactome; R-HSA-1650814; Collagen biosynthesis and modifying enzymes.
DR   Reactome; R-HSA-5083635; Defective B3GALTL causes Peters-plus syndrome (PpS).
DR   Reactome; R-HSA-5173214; O-glycosylation of TSR domain-containing proteins.
DR   ChiTaRS; ADAMTS3; human.
DR   GeneWiki; ADAMTS3; -.
DR   GenomeRNAi; 9508; -.
DR   PRO; PR:O15072; -.
DR   Proteomes; UP000005640; Chromosome 4.
DR   Bgee; ENSG00000156140; Expressed in 136 organ(s), highest expression level in caudate nucleus.
DR   Genevisible; O15072; HS.
DR   GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR   GO; GO:0031012; C:extracellular matrix; NAS:UniProtKB.
DR   GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR   GO; GO:0005615; C:extracellular space; IDA:BHF-UCL.
DR   GO; GO:0004175; F:endopeptidase activity; IDA:BHF-UCL.
DR   GO; GO:0008201; F:heparin binding; IEA:UniProtKB-KW.
DR   GO; GO:0004222; F:metalloendopeptidase activity; TAS:Reactome.
DR   GO; GO:0008270; F:zinc ion binding; NAS:UniProtKB.
DR   GO; GO:0032964; P:collagen biosynthetic process; IDA:BHF-UCL.
DR   GO; GO:0030574; P:collagen catabolic process; NAS:UniProtKB.
DR   GO; GO:0030199; P:collagen fibril organization; NAS:UniProtKB.
DR   GO; GO:1900748; P:positive regulation of vascular endothelial growth factor signaling pathway; IDA:BHF-UCL.
DR   GO; GO:0016485; P:protein processing; IDA:BHF-UCL.
DR   GO; GO:0097435; P:supramolecular fiber organization; IC:BHF-UCL.
DR   GO; GO:0010573; P:vascular endothelial growth factor production; IDA:BHF-UCL.
DR   Gene3D; 2.20.100.10; -; 4.
DR   Gene3D; 3.40.390.10; -; 1.
DR   InterPro; IPR010294; ADAM_spacer1.
DR   InterPro; IPR013273; ADAMTS/ADAMTS-like.
DR   InterPro; IPR024079; MetalloPept_cat_dom_sf.
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; PF05986; ADAM_spacer1; 1.
DR   Pfam; PF01562; Pep_M12B_propep; 1.
DR   Pfam; PF01421; Reprolysin; 1.
DR   Pfam; PF00090; TSP_1; 4.
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   Cleavage on pair of basic residues; Complete proteome; Disulfide bond;
KW   Extracellular matrix; Glycoprotein; Heparin-binding; Hydrolase;
KW   Metal-binding; Metalloprotease; Polymorphism; Protease;
KW   Reference proteome; Repeat; Secreted; Signal; Zinc; Zymogen.
FT   SIGNAL        1     20       {ECO:0000255}.
FT   PROPEP       21    249       {ECO:0000250}.
FT                                /FTId=PRO_0000029162.
FT   CHAIN       250   1205       A disintegrin and metalloproteinase with
FT                                thrombospondin motifs 3.
FT                                /FTId=PRO_0000029163.
FT   DOMAIN      256    460       Peptidase M12B. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00276}.
FT   DOMAIN      470    550       Disintegrin.
FT   DOMAIN      551    606       TSP type-1 1. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00210}.
FT   DOMAIN      845    905       TSP type-1 2. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00210}.
FT   DOMAIN      906    965       TSP type-1 3. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00210}.
FT   DOMAIN      966   1014       TSP type-1 4. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00210}.
FT   DOMAIN     1015   1054       PLAC. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00233}.
FT   REGION      713    844       Spacer.
FT   COMPBIAS    246    249       Poly-Arg.
FT   COMPBIAS    608    712       Cys-rich.
FT   ACT_SITE    399    399       {ECO:0000255|PROSITE-ProRule:PRU00276}.
FT   METAL       398    398       Zinc; catalytic. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00276}.
FT   METAL       402    402       Zinc; catalytic. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00276}.
FT   METAL       408    408       Zinc; catalytic. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00276}.
FT   CARBOHYD     83     83       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD    119    119       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD    242    242       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD    345    345       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD    475    475       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD    814    814       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   CARBOHYD    942    942       N-linked (GlcNAc...) asparagine.
FT                                {ECO:0000255}.
FT   DISULFID    333    382       {ECO:0000250}.
FT   DISULFID    376    455       {ECO:0000250}.
FT   DISULFID    415    441       {ECO:0000250}.
FT   DISULFID    482    507       {ECO:0000250}.
FT   DISULFID    493    516       {ECO:0000250}.
FT   DISULFID    502    535       {ECO:0000250}.
FT   DISULFID    529    540       {ECO:0000250}.
FT   DISULFID    563    600       {ECO:0000250}.
FT   DISULFID    567    605       {ECO:0000250}.
FT   DISULFID    578    590       {ECO:0000250}.
FT   DISULFID    978   1010       {ECO:0000250}.
FT   DISULFID    982   1015       {ECO:0000250}.
FT   DISULFID    993    999       {ECO:0000250}.
FT   VARIANT     138    138       R -> K (in dbSNP:rs788908).
FT                                {ECO:0000269|PubMed:11408482,
FT                                ECO:0000269|PubMed:15489334,
FT                                ECO:0000269|PubMed:9205841}.
FT                                /FTId=VAR_055012.
FT   VARIANT    1074   1074       S -> P (in dbSNP:rs35864003).
FT                                /FTId=VAR_055013.
FT   CONFLICT    857    857       C -> V (in Ref. 4; BAA20821).
FT                                {ECO:0000305}.
SQ   SEQUENCE   1205 AA;  135603 MW;  01FA661B1C6BFF1B CRC64;
     MVLLSLWLIA AALVEVRTSA DGQAGNEEMV QIDLPIKRYR EYELVTPVST NLEGRYLSHT
     LSASHKKRSA RDVSSNPEQL FFNITAFGKD FHLRLKPNTQ LVAPGAVVEW HETSLVPGNI
     TDPINNHQPG SATYRIRRTE PLQTNCAYVG DIVDIPGTSV AISNCDGLAG MIKSDNEEYF
     IEPLERGKQM EEEKGRIHVV YKRSAVEQAP IDMSKDFHYR ESDLEGLDDL GTVYGNIHQQ
     LNETMRRRRH AGENDYNIEV LLGVDDSVVR FHGKEHVQNY LLTLMNIVNE IYHDESLGVH
     INVVLVRMIM LGYAKSISLI ERGNPSRSLE NVCRWASQQQ RSDLNHSEHH DHAIFLTRQD
     FGPAGMQGYA PVTGMCHPVR SCTLNHEDGF SSAFVVAHET GHVLGMEHDG QGNRCGDETA
     MGSVMAPLVQ AAFHRYHWSR CSGQELKRYI HSYDCLLDDP FDHDWPKLPE LPGINYSMDE
     QCRFDFGVGY KMCTAFRTFD PCKQLWCSHP DNPYFCKTKK GPPLDGTECA AGKWCYKGHC
     MWKNANQQKQ DGNWGSWTKF GSCSRTCGTG VRFRTRQCNN PMPINGGQDC PGVNFEYQLC
     NTEECQKHFE DFRAQQCQQR NSHFEYQNTK HHWLPYEHPD PKKRCHLYCQ SKETGDVAYM
     KQLVHDGTHC SYKDPYSICV RGECVKVGCD KEIGSNKVED KCGVCGGDNS HCRTVKGTFT
     RTPRKLGYLK MFDIPPGARH VLIQEDEASP HILAIKNQAT GHYILNGKGE EAKSRTFIDL
     GVEWDYNIED DIESLHTDGP LHDPVIVLII PQENDTRSSL TYKYIIHEDS VPTINSNNVI
     QEELDTFEWA LKSWSQCSKP CGGGFQYTKY GCRRKSDNKM VHRSFCEANK KPKPIRRMCN
     IQECTHPLWV AEEWEHCTKT CGSSGYQLRT VRCLQPLLDG TNRSVHSKYC MGDRPESRRP
     CNRVPCPAQW KTGPWSECSV TCGEGTEVRQ VLCRAGDHCD GEKPESVRAC QLPPCNDEPC
     LGDKSIFCQM EVLARYCSIP GYNKLCCESC SKRSSTLPPP YLLEAAETHD DVISNPSDLP
     RSLVMPTSLV PYHSETPAKK MSLSSISSVG GPNAYAAFRP NSKPDGANLR QRSAQQAGSK
     TVRLVTVPSS PPTKRVHLSS ASQMAAASFF AASDSIGASS QARTSKKDGK IIDNRRPTRS
     STLER
//