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O15072

- ATS3_HUMAN

UniProt

O15072 - ATS3_HUMAN

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Protein
A disintegrin and metalloproteinase with thrombospondin motifs 3
Gene
ADAMTS3, KIAA0366
Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5 - Experimental evidence at transcript leveli

Functioni

Cleaves the propeptides of type II collagen prior to fibril assembly. Does not act on types I and III collagens.

Cofactori

Binds 1 zinc ion per subunit By similarity.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi398 – 3981Zinc; catalytic By similarity
Active sitei399 – 3991 By similarity
Metal bindingi402 – 4021Zinc; catalytic By similarity
Metal bindingi408 – 4081Zinc; catalytic By similarity

GO - Molecular functioni

  1. endopeptidase activity Source: BHF-UCL
  2. heparin binding Source: UniProtKB-KW
  3. metalloendopeptidase activity Source: UniProtKB
  4. protein binding Source: BHF-UCL
  5. zinc ion binding Source: UniProtKB

GO - Biological processi

  1. collagen biosynthetic process Source: BHF-UCL
  2. collagen catabolic process Source: UniProtKB
  3. collagen fibril organization Source: UniProtKB
  4. extracellular fibril organization Source: BHF-UCL
  5. extracellular matrix organization Source: Reactome
  6. positive regulation of vascular endothelial growth factor signaling pathway Source: BHF-UCL
  7. protein processing Source: BHF-UCL
  8. vascular endothelial growth factor production Source: BHF-UCL
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Metalloprotease, Protease

Keywords - Ligandi

Heparin-binding, 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

MEROPSiM12.220.

Names & Taxonomyi

Protein namesi
Recommended name:
A disintegrin and metalloproteinase with thrombospondin motifs 3 (EC:3.4.24.-)
Short name:
ADAM-TS 3
Short name:
ADAM-TS3
Short name:
ADAMTS-3
Alternative name(s):
Procollagen II N-proteinase
Short name:
PC II-NP
Procollagen II amino propeptide-processing enzyme
Gene namesi
Name:ADAMTS3
Synonyms:KIAA0366
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 4

Organism-specific databases

HGNCiHGNC:219. ADAMTS3.

Subcellular locationi

GO - Cellular componenti

  1. extracellular region Source: Reactome
  2. extracellular space Source: BHF-UCL
  3. extracellular vesicular exosome Source: UniProt
  4. proteinaceous extracellular matrix Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Extracellular matrix, Secreted

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA24547.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2020 Reviewed prediction
Add
BLAST
Propeptidei21 – 249229 By similarity
PRO_0000029162Add
BLAST
Chaini250 – 1205956A disintegrin and metalloproteinase with thrombospondin motifs 3
PRO_0000029163Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Glycosylationi83 – 831N-linked (GlcNAc...) Reviewed prediction
Glycosylationi119 – 1191N-linked (GlcNAc...) Reviewed prediction
Glycosylationi242 – 2421N-linked (GlcNAc...) Reviewed prediction
Disulfide bondi333 ↔ 382 By similarity
Glycosylationi345 – 3451N-linked (GlcNAc...) Reviewed prediction
Disulfide bondi376 ↔ 455 By similarity
Disulfide bondi415 ↔ 441 By similarity
Glycosylationi475 – 4751N-linked (GlcNAc...) Reviewed prediction
Disulfide bondi482 ↔ 507 By similarity
Disulfide bondi493 ↔ 516 By similarity
Disulfide bondi502 ↔ 535 By similarity
Disulfide bondi529 ↔ 540 By similarity
Disulfide bondi563 ↔ 600 By similarity
Disulfide bondi567 ↔ 605 By similarity
Disulfide bondi578 ↔ 590 By similarity
Glycosylationi814 – 8141N-linked (GlcNAc...) Reviewed prediction
Glycosylationi942 – 9421N-linked (GlcNAc...) Reviewed prediction
Disulfide bondi978 ↔ 1010 By similarity
Disulfide bondi982 ↔ 1015 By similarity
Disulfide bondi993 ↔ 999 By similarity

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

Cleavage on pair of basic residues, Disulfide bond, Glycoprotein, Zymogen

Proteomic databases

PaxDbiO15072.
PRIDEiO15072.

PTM databases

PhosphoSiteiO15072.

Expressioni

Tissue specificityi

Found in cartilage and skin.

Gene expression databases

ArrayExpressiO15072.
BgeeiO15072.
CleanExiHS_ADAMTS3.
GenevestigatoriO15072.

Organism-specific databases

HPAiHPA021368.
HPA021369.

Interactioni

Protein-protein interaction databases

STRINGi9606.ENSP00000286657.

Structurei

3D structure databases

ProteinModelPortaliO15072.
SMRiO15072. Positions 258-824.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini256 – 460205Peptidase M12B
Add
BLAST
Domaini470 – 55081Disintegrin
Add
BLAST
Domaini551 – 60656TSP type-1 1
Add
BLAST
Domaini845 – 90561TSP type-1 2
Add
BLAST
Domaini906 – 96560TSP type-1 3
Add
BLAST
Domaini966 – 101449TSP type-1 4
Add
BLAST
Domaini1015 – 105440PLAC
Add
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni713 – 844132Spacer
Add
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi246 – 2494Poly-Arg
Compositional biasi608 – 712105Cys-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.
InParanoidiO15072.
KOiK08619.
OMAiAEEWEHC.
OrthoDBiEOG76HQ0N.
PhylomeDBiO15072.
TreeFamiTF313537.

Family and domain databases

Gene3Di3.40.390.10. 1 hit.
InterProiIPR010294. ADAM_spacer1.
IPR024079. MetalloPept_cat_dom.
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]
PRINTSiPR01857. 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]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

O15072-1 [UniParc]FASTAAdd to Basket

« Hide

MVLLSLWLIA AALVEVRTSA DGQAGNEEMV QIDLPIKRYR EYELVTPVST     50
NLEGRYLSHT LSASHKKRSA RDVSSNPEQL FFNITAFGKD FHLRLKPNTQ 100
LVAPGAVVEW HETSLVPGNI TDPINNHQPG SATYRIRRTE PLQTNCAYVG 150
DIVDIPGTSV AISNCDGLAG MIKSDNEEYF IEPLERGKQM EEEKGRIHVV 200
YKRSAVEQAP IDMSKDFHYR ESDLEGLDDL GTVYGNIHQQ LNETMRRRRH 250
AGENDYNIEV LLGVDDSVVR FHGKEHVQNY LLTLMNIVNE IYHDESLGVH 300
INVVLVRMIM LGYAKSISLI ERGNPSRSLE NVCRWASQQQ RSDLNHSEHH 350
DHAIFLTRQD FGPAGMQGYA PVTGMCHPVR SCTLNHEDGF SSAFVVAHET 400
GHVLGMEHDG QGNRCGDETA MGSVMAPLVQ AAFHRYHWSR CSGQELKRYI 450
HSYDCLLDDP FDHDWPKLPE LPGINYSMDE QCRFDFGVGY KMCTAFRTFD 500
PCKQLWCSHP DNPYFCKTKK GPPLDGTECA AGKWCYKGHC MWKNANQQKQ 550
DGNWGSWTKF GSCSRTCGTG VRFRTRQCNN PMPINGGQDC PGVNFEYQLC 600
NTEECQKHFE DFRAQQCQQR NSHFEYQNTK HHWLPYEHPD PKKRCHLYCQ 650
SKETGDVAYM KQLVHDGTHC SYKDPYSICV RGECVKVGCD KEIGSNKVED 700
KCGVCGGDNS HCRTVKGTFT RTPRKLGYLK MFDIPPGARH VLIQEDEASP 750
HILAIKNQAT GHYILNGKGE EAKSRTFIDL GVEWDYNIED DIESLHTDGP 800
LHDPVIVLII PQENDTRSSL TYKYIIHEDS VPTINSNNVI QEELDTFEWA 850
LKSWSQCSKP CGGGFQYTKY GCRRKSDNKM VHRSFCEANK KPKPIRRMCN 900
IQECTHPLWV AEEWEHCTKT CGSSGYQLRT VRCLQPLLDG TNRSVHSKYC 950
MGDRPESRRP CNRVPCPAQW KTGPWSECSV TCGEGTEVRQ VLCRAGDHCD 1000
GEKPESVRAC QLPPCNDEPC LGDKSIFCQM EVLARYCSIP GYNKLCCESC 1050
SKRSSTLPPP YLLEAAETHD DVISNPSDLP RSLVMPTSLV PYHSETPAKK 1100
MSLSSISSVG GPNAYAAFRP NSKPDGANLR QRSAQQAGSK TVRLVTVPSS 1150
PPTKRVHLSS ASQMAAASFF AASDSIGASS QARTSKKDGK IIDNRRPTRS 1200
STLER 1205
Length:1,205
Mass (Da):135,603
Last modified:January 11, 2011 - v4
Checksum:i01FA661B1C6BFF1B
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti138 – 1381R → K.3 Publications
Corresponds to variant rs788908 [ dbSNP | Ensembl ].
VAR_055012
Natural varianti1074 – 10741S → P.
Corresponds to variant rs35864003 [ dbSNP | Ensembl ].
VAR_055013

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti857 – 8571C → V in BAA20821. 1 Publication

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
AC093790 Genomic DNA. No translation available.
AC095056 Genomic DNA. No translation available.
AC104814 Genomic DNA. No translation available.
BC130287 mRNA. Translation: AAI30288.1.
BC132735 mRNA. Translation: AAI32736.1.
AF247668 mRNA. Translation: AAK28400.1.
AB002364 mRNA. Translation: BAA20821.1.
CCDSiCCDS3553.1.
RefSeqiNP_055058.2. NM_014243.2.
UniGeneiHs.590919.

Genome annotation databases

EnsembliENST00000286657; ENSP00000286657; ENSG00000156140.
GeneIDi9508.
KEGGihsa:9508.
UCSCiuc003hgk.2. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
AC093790 Genomic DNA. No translation available.
AC095056 Genomic DNA. No translation available.
AC104814 Genomic DNA. No translation available.
BC130287 mRNA. Translation: AAI30288.1 .
BC132735 mRNA. Translation: AAI32736.1 .
AF247668 mRNA. Translation: AAK28400.1 .
AB002364 mRNA. Translation: BAA20821.1 .
CCDSi CCDS3553.1.
RefSeqi NP_055058.2. NM_014243.2.
UniGenei Hs.590919.

3D structure databases

ProteinModelPortali O15072.
SMRi O15072. Positions 258-824.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

STRINGi 9606.ENSP00000286657.

Protein family/group databases

MEROPSi M12.220.

PTM databases

PhosphoSitei O15072.

Proteomic databases

PaxDbi O15072.
PRIDEi O15072.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000286657 ; ENSP00000286657 ; ENSG00000156140 .
GeneIDi 9508.
KEGGi hsa:9508.
UCSCi uc003hgk.2. human.

Organism-specific databases

CTDi 9508.
GeneCardsi GC04M073136.
H-InvDB HIX0004274.
HGNCi HGNC:219. ADAMTS3.
HPAi HPA021368.
HPA021369.
MIMi 605011. gene.
neXtProti NX_O15072.
PharmGKBi PA24547.
HUGEi Search...
GenAtlasi Search...

Phylogenomic databases

eggNOGi NOG307411.
HOGENOMi HOG000034222.
HOVERGENi HBG004314.
InParanoidi O15072.
KOi K08619.
OMAi AEEWEHC.
OrthoDBi EOG76HQ0N.
PhylomeDBi O15072.
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

GeneWikii ADAMTS3.
GenomeRNAii 9508.
NextBioi 35628.
PROi O15072.
SOURCEi Search...

Gene expression databases

ArrayExpressi O15072.
Bgeei O15072.
CleanExi HS_ADAMTS3.
Genevestigatori O15072.

Family and domain databases

Gene3Di 3.40.390.10. 1 hit.
InterProi IPR010294. ADAM_spacer1.
IPR024079. MetalloPept_cat_dom.
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 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. "Generation and annotation of the DNA sequences of human chromosomes 2 and 4."
    Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H.
    , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K.
    Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  2. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT LYS-138.
  3. "Procollagen II amino propeptide processing by ADAMTS-3. Insights on dermatosparaxis."
    Fernandes R.J., Hirohata S., Engle J.M., Colige A., Cohn D.H., Eyre D.R., Apte S.S.
    J. Biol. Chem. 276:31502-31509(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-227, VARIANT LYS-138.
  4. "Prediction of the coding sequences of unidentified human genes. VII. The complete sequences of 100 new cDNA clones from brain which can code for large proteins in vitro."
    Nagase T., Ishikawa K., Nakajima D., Ohira M., Seki N., Miyajima N., Tanaka A., Kotani H., Nomura N., Ohara O.
    DNA Res. 4:141-150(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 5-1205, VARIANT LYS-138.
    Tissue: Brain.

Entry informationi

Entry nameiATS3_HUMAN
AccessioniPrimary (citable) accession number: O15072
Secondary accession number(s): A1L3U9, Q9BXZ8
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 1, 2000
Last sequence update: January 11, 2011
Last modified: September 3, 2014
This is version 145 of the entry and version 4 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

Caution

Has sometimes been referred to as ADAMTS4.

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 4
    Human chromosome 4: 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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