ATS3_HUMAN
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 03-AUG-2022, entry version 199.
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; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC 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., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., 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., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., 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., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 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 project:
RT 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., Eyre D.R.,
RA 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. The
RT complete sequences of 100 new cDNA clones from brain which can code for
RT large proteins in vitro.";
RL DNA Res. 4:141-150(1997).
RN [5]
RP INVOLVEMENT IN HKLLS3, VARIANTS HKLLS3 PRO-168 AND THR-291,
RP CHARACTERIZATION OF VARIANTS HKLLS3 PRO-168 AND THR-291, AND SUBCELLULAR
RP LOCATION.
RX PubMed=28985353; DOI=10.1093/hmg/ddx297;
RA Brouillard P., Dupont L., Helaers R., Coulie R., Tiller G.E., Peeden J.,
RA Colige A., Vikkula M.;
RT "Loss of ADAMTS3 activity causes Hennekam lymphangiectasia-lymphedema
RT syndrome 3.";
RL Hum. Mol. Genet. 26:4095-4104(2017).
CC -!- FUNCTION: Cleaves the propeptides of type II collagen prior to fibril
CC 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 -!- INTERACTION:
CC O15072; Q9UHD9: UBQLN2; NbExp=3; IntAct=EBI-12200127, EBI-947187;
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:28985353}. Secreted,
CC extracellular space, extracellular matrix {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Found in cartilage and skin.
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: Hennekam lymphangiectasia-lymphedema syndrome 3 (HKLLS3)
CC [MIM:618154]: A form of Hennekam lymphangiectasia-lymphedema syndrome,
CC a generalized lymph-vessels dysplasia characterized by intestinal
CC lymphangiectasia with severe lymphedema of the limbs, genitalia and
CC face. In addition, affected individuals have unusual facies and some
CC manifest intellectual disability. HKLLS3 is characterized by widespread
CC congenital edema, facial dysmorphism and protein-losing enteropathy of
CC variable severity. HKLLS3 transmission pattern is consistent with
CC autosomal recessive inheritance. {ECO:0000269|PubMed:28985353}.
CC Note=The disease is caused by variants affecting the gene represented
CC in this entry.
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 AlphaFoldDB; O15072; -.
DR SMR; O15072; -.
DR BioGRID; 114886; 4.
DR IntAct; O15072; 2.
DR STRING; 9606.ENSP00000286657; -.
DR MEROPS; M12.220; -.
DR GlyGen; O15072; 7 sites.
DR iPTMnet; O15072; -.
DR PhosphoSitePlus; O15072; -.
DR BioMuta; ADAMTS3; -.
DR EPD; O15072; -.
DR MassIVE; O15072; -.
DR PaxDb; O15072; -.
DR PeptideAtlas; O15072; -.
DR PRIDE; O15072; -.
DR ProteomicsDB; 48427; -.
DR Antibodypedia; 12997; 53 antibodies from 17 providers.
DR DNASU; 9508; -.
DR Ensembl; ENST00000286657.10; ENSP00000286657.4; ENSG00000156140.10.
DR Ensembl; ENST00000622135.1; ENSP00000480055.1; ENSG00000156140.10.
DR GeneID; 9508; -.
DR KEGG; hsa:9508; -.
DR MANE-Select; ENST00000286657.10; ENSP00000286657.4; NM_014243.3; NP_055058.2.
DR UCSC; uc003hgk.2; human.
DR CTD; 9508; -.
DR DisGeNET; 9508; -.
DR GeneCards; ADAMTS3; -.
DR HGNC; HGNC:219; ADAMTS3.
DR HPA; ENSG00000156140; Tissue enhanced (retina).
DR MalaCards; ADAMTS3; -.
DR MIM; 605011; gene.
DR MIM; 618154; phenotype.
DR neXtProt; NX_O15072; -.
DR OpenTargets; ENSG00000156140; -.
DR Orphanet; 2136; Hennekam syndrome.
DR PharmGKB; PA24547; -.
DR VEuPathDB; HostDB:ENSG00000156140; -.
DR eggNOG; KOG3538; Eukaryota.
DR GeneTree; ENSGT00940000156085; -.
DR HOGENOM; CLU_000660_4_1_1; -.
DR InParanoid; O15072; -.
DR OMA; KYCVGDR; -.
DR OrthoDB; 79609at2759; -.
DR PhylomeDB; O15072; -.
DR TreeFam; TF313537; -.
DR BRENDA; 3.4.24.14; 2681.
DR PathwayCommons; O15072; -.
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; O15072; -.
DR BioGRID-ORCS; 9508; 17 hits in 1080 CRISPR screens.
DR ChiTaRS; ADAMTS3; human.
DR GeneWiki; ADAMTS3; -.
DR GenomeRNAi; 9508; -.
DR Pharos; O15072; Tbio.
DR PRO; PR:O15072; -.
DR Proteomes; UP000005640; Chromosome 4.
DR RNAct; O15072; protein.
DR Bgee; ENSG00000156140; Expressed in endothelial cell and 126 other tissues.
DR Genevisible; O15072; HS.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0031012; C:extracellular matrix; IBA:GO_Central.
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; IBA:GO_Central.
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; TAS:Reactome.
DR GO; GO:0030198; P:extracellular matrix organization; IBA:GO_Central.
DR GO; GO:0001701; P:in utero embryonic development; IEA:Ensembl.
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; 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; 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; 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 1: Evidence at protein level;
KW Cleavage on pair of basic residues; Disease variant; Disulfide bond;
KW Extracellular matrix; Glycoprotein; Heparin-binding; Hydrolase;
KW Metal-binding; Metalloprotease; Protease; Reference proteome; Repeat;
KW Secreted; Signal; Zinc; Zymogen.
FT SIGNAL 1..20
FT /evidence="ECO:0000255"
FT PROPEP 21..249
FT /evidence="ECO:0000250"
FT /id="PRO_0000029162"
FT CHAIN 250..1205
FT /note="A disintegrin and metalloproteinase with
FT thrombospondin motifs 3"
FT /id="PRO_0000029163"
FT DOMAIN 256..460
FT /note="Peptidase M12B"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00276"
FT DOMAIN 470..550
FT /note="Disintegrin"
FT DOMAIN 551..606
FT /note="TSP type-1 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00210"
FT DOMAIN 845..905
FT /note="TSP type-1 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00210"
FT DOMAIN 906..965
FT /note="TSP type-1 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00210"
FT DOMAIN 966..1014
FT /note="TSP type-1 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00210"
FT DOMAIN 1015..1054
FT /note="PLAC"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00233"
FT REGION 713..844
FT /note="Spacer"
FT REGION 1174..1205
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1186..1205
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 399
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00276"
FT BINDING 398
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00276"
FT BINDING 402
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
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 CARBOHYD 83
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 119
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 242
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 345
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 475
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 814
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 942
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 333..382
FT /evidence="ECO:0000250"
FT DISULFID 376..455
FT /evidence="ECO:0000250"
FT DISULFID 415..441
FT /evidence="ECO:0000250"
FT DISULFID 482..507
FT /evidence="ECO:0000250"
FT DISULFID 493..516
FT /evidence="ECO:0000250"
FT DISULFID 502..535
FT /evidence="ECO:0000250"
FT DISULFID 529..540
FT /evidence="ECO:0000250"
FT DISULFID 563..600
FT /evidence="ECO:0000250"
FT DISULFID 567..605
FT /evidence="ECO:0000250"
FT DISULFID 578..590
FT /evidence="ECO:0000250"
FT DISULFID 978..1010
FT /evidence="ECO:0000250"
FT DISULFID 982..1015
FT /evidence="ECO:0000250"
FT DISULFID 993..999
FT /evidence="ECO:0000250"
FT VARIANT 138
FT /note="R -> K (in dbSNP:rs788908)"
FT /evidence="ECO:0000269|PubMed:11408482,
FT ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:9205841"
FT /id="VAR_055012"
FT VARIANT 168
FT /note="L -> P (in HKLLS3; affects proteolytic maturation
FT and impairs secretion; dbSNP:rs1177851177)"
FT /evidence="ECO:0000269|PubMed:28985353"
FT /id="VAR_081558"
FT VARIANT 291
FT /note="I -> T (in HKLLS3; affects proteolytic maturation
FT and impairs secretion; dbSNP:rs61757480)"
FT /evidence="ECO:0000269|PubMed:28985353"
FT /id="VAR_081559"
FT VARIANT 1074
FT /note="S -> P (in dbSNP:rs35864003)"
FT /id="VAR_055013"
FT CONFLICT 857
FT /note="C -> V (in Ref. 4; BAA20821)"
FT /evidence="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
