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Protein

A disintegrin and metalloproteinase with thrombospondin motifs 3

Gene

ADAMTS3

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: 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

Zn2+By similarityNote: Binds 1 zinc ion per subunit.By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi398Zinc; catalyticPROSITE-ProRule annotation1
Active sitei399PROSITE-ProRule annotation1
Metal bindingi402Zinc; catalyticPROSITE-ProRule annotation1
Metal bindingi408Zinc; catalyticPROSITE-ProRule annotation1

GO - Molecular functioni

  • endopeptidase activity Source: BHF-UCL
  • heparin binding Source: UniProtKB-KW
  • metalloendopeptidase activity Source: UniProtKB
  • zinc ion binding Source: UniProtKB

GO - Biological processi

  • collagen biosynthetic process Source: BHF-UCL
  • collagen catabolic process Source: UniProtKB
  • collagen fibril organization Source: UniProtKB
  • extracellular fibril organization Source: BHF-UCL
  • positive regulation of vascular endothelial growth factor signaling pathway Source: BHF-UCL
  • protein processing Source: BHF-UCL
  • 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

BioCyciZFISH:ENSG00000156140-MONOMER.
ReactomeiR-HSA-1650814. Collagen biosynthesis and modifying enzymes.
R-HSA-5083635. Defective B3GALTL causes Peters-plus syndrome (PpS).
R-HSA-5173214. 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
Proteomesi
  • UP000005640 Componenti: Chromosome 4

Organism-specific databases

HGNCiHGNC:219. ADAMTS3.

Subcellular locationi

GO - Cellular componenti

  • extracellular exosome Source: UniProtKB
  • extracellular region Source: Reactome
  • extracellular space Source: BHF-UCL
  • proteinaceous extracellular matrix Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Extracellular matrix, Secreted

Pathology & Biotechi

Organism-specific databases

DisGeNETi9508.
OpenTargetsiENSG00000156140.
PharmGKBiPA24547.

Polymorphism and mutation databases

BioMutaiADAMTS3.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 20Sequence analysisAdd BLAST20
PropeptideiPRO_000002916221 – 249By similarityAdd BLAST229
ChainiPRO_0000029163250 – 1205A disintegrin and metalloproteinase with thrombospondin motifs 3Add BLAST956

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi83N-linked (GlcNAc...)Sequence analysis1
Glycosylationi119N-linked (GlcNAc...)Sequence analysis1
Glycosylationi242N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi333 ↔ 382By similarity
Glycosylationi345N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi376 ↔ 455By similarity
Disulfide bondi415 ↔ 441By similarity
Glycosylationi475N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi482 ↔ 507By similarity
Disulfide bondi493 ↔ 516By similarity
Disulfide bondi502 ↔ 535By similarity
Disulfide bondi529 ↔ 540By similarity
Disulfide bondi563 ↔ 600By similarity
Disulfide bondi567 ↔ 605By similarity
Disulfide bondi578 ↔ 590By similarity
Glycosylationi814N-linked (GlcNAc...)Sequence analysis1
Glycosylationi942N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi978 ↔ 1010By similarity
Disulfide bondi982 ↔ 1015By similarity
Disulfide bondi993 ↔ 999By 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).By similarity

Keywords - PTMi

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

Proteomic databases

EPDiO15072.
PaxDbiO15072.
PeptideAtlasiO15072.
PRIDEiO15072.

PTM databases

iPTMnetiO15072.
PhosphoSitePlusiO15072.

Expressioni

Tissue specificityi

Found in cartilage and skin.

Gene expression databases

BgeeiENSG00000156140.
CleanExiHS_ADAMTS3.
GenevisibleiO15072. HS.

Organism-specific databases

HPAiHPA021368.
HPA021369.

Interactioni

Protein-protein interaction databases

IntActiO15072. 1 interactor.
STRINGi9606.ENSP00000286657.

Structurei

3D structure databases

ProteinModelPortaliO15072.
SMRiO15072.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini256 – 460Peptidase M12BPROSITE-ProRule annotationAdd BLAST205
Domaini470 – 550DisintegrinAdd BLAST81
Domaini551 – 606TSP type-1 1PROSITE-ProRule annotationAdd BLAST56
Domaini845 – 905TSP type-1 2PROSITE-ProRule annotationAdd BLAST61
Domaini906 – 965TSP type-1 3PROSITE-ProRule annotationAdd BLAST60
Domaini966 – 1014TSP type-1 4PROSITE-ProRule annotationAdd BLAST49
Domaini1015 – 1054PLACPROSITE-ProRule annotationAdd BLAST40

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni713 – 844SpacerAdd BLAST132

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi246 – 249Poly-Arg4
Compositional biasi608 – 712Cys-richAdd BLAST105

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.Curated
Contains 1 peptidase M12B domain.PROSITE-ProRule annotation
Contains 1 PLAC domain.PROSITE-ProRule annotation
Contains 4 TSP type-1 domains.PROSITE-ProRule annotation

Keywords - Domaini

Repeat, Signal

Phylogenomic databases

eggNOGiENOG410INDA. Eukaryota.
ENOG410XSRH. LUCA.
GeneTreeiENSGT00760000118880.
HOGENOMiHOG000034222.
HOVERGENiHBG004314.
InParanoidiO15072.
KOiK08619.
OMAiAEEWEHC.
OrthoDBiEOG091G0790.
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. TSP1_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

        10         20         30         40         50
MVLLSLWLIA AALVEVRTSA DGQAGNEEMV QIDLPIKRYR EYELVTPVST
60 70 80 90 100
NLEGRYLSHT LSASHKKRSA RDVSSNPEQL FFNITAFGKD FHLRLKPNTQ
110 120 130 140 150
LVAPGAVVEW HETSLVPGNI TDPINNHQPG SATYRIRRTE PLQTNCAYVG
160 170 180 190 200
DIVDIPGTSV AISNCDGLAG MIKSDNEEYF IEPLERGKQM EEEKGRIHVV
210 220 230 240 250
YKRSAVEQAP IDMSKDFHYR ESDLEGLDDL GTVYGNIHQQ LNETMRRRRH
260 270 280 290 300
AGENDYNIEV LLGVDDSVVR FHGKEHVQNY LLTLMNIVNE IYHDESLGVH
310 320 330 340 350
INVVLVRMIM LGYAKSISLI ERGNPSRSLE NVCRWASQQQ RSDLNHSEHH
360 370 380 390 400
DHAIFLTRQD FGPAGMQGYA PVTGMCHPVR SCTLNHEDGF SSAFVVAHET
410 420 430 440 450
GHVLGMEHDG QGNRCGDETA MGSVMAPLVQ AAFHRYHWSR CSGQELKRYI
460 470 480 490 500
HSYDCLLDDP FDHDWPKLPE LPGINYSMDE QCRFDFGVGY KMCTAFRTFD
510 520 530 540 550
PCKQLWCSHP DNPYFCKTKK GPPLDGTECA AGKWCYKGHC MWKNANQQKQ
560 570 580 590 600
DGNWGSWTKF GSCSRTCGTG VRFRTRQCNN PMPINGGQDC PGVNFEYQLC
610 620 630 640 650
NTEECQKHFE DFRAQQCQQR NSHFEYQNTK HHWLPYEHPD PKKRCHLYCQ
660 670 680 690 700
SKETGDVAYM KQLVHDGTHC SYKDPYSICV RGECVKVGCD KEIGSNKVED
710 720 730 740 750
KCGVCGGDNS HCRTVKGTFT RTPRKLGYLK MFDIPPGARH VLIQEDEASP
760 770 780 790 800
HILAIKNQAT GHYILNGKGE EAKSRTFIDL GVEWDYNIED DIESLHTDGP
810 820 830 840 850
LHDPVIVLII PQENDTRSSL TYKYIIHEDS VPTINSNNVI QEELDTFEWA
860 870 880 890 900
LKSWSQCSKP CGGGFQYTKY GCRRKSDNKM VHRSFCEANK KPKPIRRMCN
910 920 930 940 950
IQECTHPLWV AEEWEHCTKT CGSSGYQLRT VRCLQPLLDG TNRSVHSKYC
960 970 980 990 1000
MGDRPESRRP CNRVPCPAQW KTGPWSECSV TCGEGTEVRQ VLCRAGDHCD
1010 1020 1030 1040 1050
GEKPESVRAC QLPPCNDEPC LGDKSIFCQM EVLARYCSIP GYNKLCCESC
1060 1070 1080 1090 1100
SKRSSTLPPP YLLEAAETHD DVISNPSDLP RSLVMPTSLV PYHSETPAKK
1110 1120 1130 1140 1150
MSLSSISSVG GPNAYAAFRP NSKPDGANLR QRSAQQAGSK TVRLVTVPSS
1160 1170 1180 1190 1200
PPTKRVHLSS ASQMAAASFF AASDSIGASS QARTSKKDGK IIDNRRPTRS

STLER
Length:1,205
Mass (Da):135,603
Last modified:January 11, 2011 - v4
Checksum:i01FA661B1C6BFF1B
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti857C → V in BAA20821 (PubMed:9205841).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_055012138R → K.3 PublicationsCorresponds to variant rs788908dbSNPEnsembl.1
Natural variantiVAR_0550131074S → P.Corresponds to variant rs35864003dbSNPEnsembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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.
ENST00000622135; ENSP00000480055; ENSG00000156140.
GeneIDi9508.
KEGGihsa:9508.
UCSCiuc003hgk.2. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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.

3D structure databases

ProteinModelPortaliO15072.
SMRiO15072.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiO15072. 1 interactor.
STRINGi9606.ENSP00000286657.

Protein family/group databases

MEROPSiM12.220.

PTM databases

iPTMnetiO15072.
PhosphoSitePlusiO15072.

Polymorphism and mutation databases

BioMutaiADAMTS3.

Proteomic databases

EPDiO15072.
PaxDbiO15072.
PeptideAtlasiO15072.
PRIDEiO15072.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000286657; ENSP00000286657; ENSG00000156140.
ENST00000622135; ENSP00000480055; ENSG00000156140.
GeneIDi9508.
KEGGihsa:9508.
UCSCiuc003hgk.2. human.

Organism-specific databases

CTDi9508.
DisGeNETi9508.
GeneCardsiADAMTS3.
H-InvDBHIX0004274.
HGNCiHGNC:219. ADAMTS3.
HPAiHPA021368.
HPA021369.
MIMi605011. gene.
neXtProtiNX_O15072.
OpenTargetsiENSG00000156140.
PharmGKBiPA24547.
HUGEiSearch...
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410INDA. Eukaryota.
ENOG410XSRH. LUCA.
GeneTreeiENSGT00760000118880.
HOGENOMiHOG000034222.
HOVERGENiHBG004314.
InParanoidiO15072.
KOiK08619.
OMAiAEEWEHC.
OrthoDBiEOG091G0790.
PhylomeDBiO15072.
TreeFamiTF313537.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000156140-MONOMER.
ReactomeiR-HSA-1650814. Collagen biosynthesis and modifying enzymes.
R-HSA-5083635. Defective B3GALTL causes Peters-plus syndrome (PpS).
R-HSA-5173214. O-glycosylation of TSR domain-containing proteins.

Miscellaneous databases

ChiTaRSiADAMTS3. human.
GeneWikiiADAMTS3.
GenomeRNAii9508.
PROiO15072.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000156140.
CleanExiHS_ADAMTS3.
GenevisibleiO15072. HS.

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. TSP1_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]
ProtoNetiSearch...

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: November 30, 2016
This is version 164 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.Curated

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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.