UniProtKB - O15072 (ATS3_HUMAN)
Protein
A disintegrin and metalloproteinase with thrombospondin motifs 3
Gene
ADAMTS3
Organism
Homo sapiens (Human)
Status
Functioni
Cleaves the propeptides of type II collagen prior to fibril assembly. Does not act on types I and III collagens.
Caution
Has sometimes been referred to as ADAMTS4.Curated
Cofactori
Zn2+By similarityNote: Binds 1 zinc ion per subunit.By similarity
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Metal bindingi | 398 | Zinc; catalyticPROSITE-ProRule annotation | 1 | |
Active sitei | 399 | PROSITE-ProRule annotation | 1 | |
Metal bindingi | 402 | Zinc; catalyticPROSITE-ProRule annotation | 1 | |
Metal bindingi | 408 | Zinc; catalyticPROSITE-ProRule annotation | 1 |
GO - Molecular functioni
- endopeptidase activity Source: BHF-UCL
- heparin binding Source: UniProtKB-KW
- metalloendopeptidase activity Source: GO_Central
- 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 matrix organization Source: GO_Central
- positive regulation of vascular endothelial growth factor signaling pathway Source: BHF-UCL
- protein processing Source: BHF-UCL
- supramolecular fiber organization Source: BHF-UCL
- vascular endothelial growth factor production Source: BHF-UCL
Keywordsi
Molecular function | Heparin-binding, Hydrolase, Metalloprotease, Protease |
Ligand | Metal-binding, Zinc |
Enzyme and pathway databases
PathwayCommonsi | O15072 |
Reactomei | R-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
MEROPSi | M12.220 |
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 |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
EuPathDBi | HostDB:ENSG00000156140.8 |
HGNCi | HGNC:219, ADAMTS3 |
MIMi | 605011, gene |
neXtProti | NX_O15072 |
Subcellular locationi
Extracellular region or secreted
- Secreted 1 Publication
- extracellular matrix By similarity
Extracellular region or secreted
- extracellular exosome Source: UniProtKB
- extracellular matrix Source: GO_Central
- extracellular region Source: Reactome
- extracellular space Source: BHF-UCL
Keywords - Cellular componenti
Extracellular matrix, SecretedPathology & Biotechi
Involvement in diseasei
Hennekam lymphangiectasia-lymphedema syndrome 3 (HKLLS3)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA form of Hennekam lymphangiectasia-lymphedema syndrome, a generalized lymph-vessels dysplasia characterized by intestinal lymphangiectasia with severe lymphedema of the limbs, genitalia and face. In addition, affected individuals have unusual facies and some manifest mental retardation. HKLLS3 is characterized by widespread congenital edema, facial dysmorphism and protein-losing enteropathy of variable severity. HKLLS3 transmission pattern is consistent with autosomal recessive inheritance.
Related information in OMIMFeature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_081558 | 168 | L → P in HKLLS3; affects proteolytic maturation and impairs secretion. 1 PublicationCorresponds to variant dbSNP:rs1177851177EnsemblClinVar. | 1 | |
Natural variantiVAR_081559 | 291 | I → T in HKLLS3; affects proteolytic maturation and impairs secretion. 1 PublicationCorresponds to variant dbSNP:rs61757480EnsemblClinVar. | 1 |
Keywords - Diseasei
Disease mutationOrganism-specific databases
DisGeNETi | 9508 |
MalaCardsi | ADAMTS3 |
MIMi | 618154, phenotype |
OpenTargetsi | ENSG00000156140 |
Orphaneti | 2136, Hennekam syndrome |
PharmGKBi | PA24547 |
Miscellaneous databases
Pharosi | O15072, Tbio |
Polymorphism and mutation databases
BioMutai | ADAMTS3 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Signal peptidei | 1 – 20 | Sequence analysisAdd BLAST | 20 | |
PropeptideiPRO_0000029162 | 21 – 249 | By similarityAdd BLAST | 229 | |
ChainiPRO_0000029163 | 250 – 1205 | A disintegrin and metalloproteinase with thrombospondin motifs 3Add BLAST | 956 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Glycosylationi | 83 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 119 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 242 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Disulfide bondi | 333 ↔ 382 | By similarity | ||
Glycosylationi | 345 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Disulfide bondi | 376 ↔ 455 | By similarity | ||
Disulfide bondi | 415 ↔ 441 | By similarity | ||
Glycosylationi | 475 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Disulfide bondi | 482 ↔ 507 | By similarity | ||
Disulfide bondi | 493 ↔ 516 | By similarity | ||
Disulfide bondi | 502 ↔ 535 | By similarity | ||
Disulfide bondi | 529 ↔ 540 | By similarity | ||
Disulfide bondi | 563 ↔ 600 | By similarity | ||
Disulfide bondi | 567 ↔ 605 | By similarity | ||
Disulfide bondi | 578 ↔ 590 | By similarity | ||
Glycosylationi | 814 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 942 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Disulfide bondi | 978 ↔ 1010 | By similarity | ||
Disulfide bondi | 982 ↔ 1015 | By similarity | ||
Disulfide bondi | 993 ↔ 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-X2-(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, ZymogenProteomic databases
EPDi | O15072 |
MassIVEi | O15072 |
PaxDbi | O15072 |
PeptideAtlasi | O15072 |
PRIDEi | O15072 |
ProteomicsDBi | 48427 |
PTM databases
GlyGeni | O15072, 7 sites |
iPTMneti | O15072 |
PhosphoSitePlusi | O15072 |
Expressioni
Tissue specificityi
Found in cartilage and skin.
Gene expression databases
Bgeei | ENSG00000156140, Expressed in caudate nucleus and 154 other tissues |
Genevisiblei | O15072, HS |
Organism-specific databases
HPAi | ENSG00000156140, Low tissue specificity |
Interactioni
Binary interactionsi
O15072
With | #Exp. | IntAct |
---|---|---|
UBQLN2 [Q9UHD9] | 3 | EBI-12200127,EBI-947187 |
Protein-protein interaction databases
BioGRIDi | 114886, 2 interactors |
IntActi | O15072, 2 interactors |
STRINGi | 9606.ENSP00000286657 |
Miscellaneous databases
RNActi | O15072, protein |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 256 – 460 | Peptidase M12BPROSITE-ProRule annotationAdd BLAST | 205 | |
Domaini | 470 – 550 | DisintegrinAdd BLAST | 81 | |
Domaini | 551 – 606 | TSP type-1 1PROSITE-ProRule annotationAdd BLAST | 56 | |
Domaini | 845 – 905 | TSP type-1 2PROSITE-ProRule annotationAdd BLAST | 61 | |
Domaini | 906 – 965 | TSP type-1 3PROSITE-ProRule annotationAdd BLAST | 60 | |
Domaini | 966 – 1014 | TSP type-1 4PROSITE-ProRule annotationAdd BLAST | 49 | |
Domaini | 1015 – 1054 | PLACPROSITE-ProRule annotationAdd BLAST | 40 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 713 – 844 | SpacerAdd BLAST | 132 |
Compositional bias
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Compositional biasi | 246 – 249 | Poly-Arg | 4 | |
Compositional biasi | 608 – 712 | Cys-richAdd BLAST | 105 |
Domaini
The spacer domain and the TSP type-1 domains are important for a tight interaction with the extracellular matrix.
Keywords - Domaini
Repeat, SignalPhylogenomic databases
eggNOGi | KOG3538, Eukaryota |
GeneTreei | ENSGT00940000156085 |
HOGENOMi | CLU_000660_4_1_1 |
InParanoidi | O15072 |
OMAi | KYCVGDR |
OrthoDBi | 79609at2759 |
PhylomeDBi | O15072 |
TreeFami | TF313537 |
Family and domain databases
Gene3Di | 2.20.100.10, 4 hits 3.40.390.10, 1 hit |
InterProi | View protein in InterPro IPR041645, ADAM_CR_2 IPR010294, ADAM_spacer1 IPR013273, ADAMTS/ADAMTS-like IPR024079, MetalloPept_cat_dom_sf IPR001590, Peptidase_M12B IPR002870, Peptidase_M12B_N IPR010909, PLAC IPR000884, TSP1_rpt IPR036383, TSP1_rpt_sf |
Pfami | View protein in Pfam PF17771, ADAM_CR_2, 1 hit PF05986, ADAM_spacer1, 1 hit PF01562, Pep_M12B_propep, 1 hit PF01421, Reprolysin, 1 hit PF00090, TSP_1, 1 hit |
PRINTSi | PR01857, ADAMTSFAMILY |
SMARTi | View protein in SMART SM00209, TSP1, 4 hits |
SUPFAMi | SSF82895, SSF82895, 4 hits |
PROSITEi | View protein in PROSITE PS50215, ADAM_MEPRO, 1 hit PS50900, PLAC, 1 hit PS50092, TSP1, 4 hits |
i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
O15072-1 [UniParc]FASTAAdd to basket
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
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 857 | C → V in BAA20821 (PubMed:9205841).Curated | 1 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_055012 | 138 | R → K3 PublicationsCorresponds to variant dbSNP:rs788908Ensembl. | 1 | |
Natural variantiVAR_081558 | 168 | L → P in HKLLS3; affects proteolytic maturation and impairs secretion. 1 PublicationCorresponds to variant dbSNP:rs1177851177EnsemblClinVar. | 1 | |
Natural variantiVAR_081559 | 291 | I → T in HKLLS3; affects proteolytic maturation and impairs secretion. 1 PublicationCorresponds to variant dbSNP:rs61757480EnsemblClinVar. | 1 | |
Natural variantiVAR_055013 | 1074 | S → P. Corresponds to variant dbSNP:rs35864003EnsemblClinVar. | 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 |
CCDSi | CCDS3553.1 |
RefSeqi | NP_055058.2, NM_014243.2 |
Genome annotation databases
Ensembli | ENST00000286657; ENSP00000286657; ENSG00000156140 ENST00000622135; ENSP00000480055; ENSG00000156140 |
GeneIDi | 9508 |
KEGGi | hsa:9508 |
UCSCi | uc003hgk.2, human |
Keywords - Coding sequence diversityi
PolymorphismSimilar proteinsi
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 |
CCDSi | CCDS3553.1 |
RefSeqi | NP_055058.2, NM_014243.2 |
3D structure databases
ModBasei | Search... |
SWISS-MODEL-Workspacei | Submit a new modelling project... |
Protein-protein interaction databases
BioGRIDi | 114886, 2 interactors |
IntActi | O15072, 2 interactors |
STRINGi | 9606.ENSP00000286657 |
Protein family/group databases
MEROPSi | M12.220 |
PTM databases
GlyGeni | O15072, 7 sites |
iPTMneti | O15072 |
PhosphoSitePlusi | O15072 |
Polymorphism and mutation databases
BioMutai | ADAMTS3 |
Proteomic databases
EPDi | O15072 |
MassIVEi | O15072 |
PaxDbi | O15072 |
PeptideAtlasi | O15072 |
PRIDEi | O15072 |
ProteomicsDBi | 48427 |
Protocols and materials databases
Antibodypediai | 12997, 51 antibodies |
Genome annotation databases
Ensembli | ENST00000286657; ENSP00000286657; ENSG00000156140 ENST00000622135; ENSP00000480055; ENSG00000156140 |
GeneIDi | 9508 |
KEGGi | hsa:9508 |
UCSCi | uc003hgk.2, human |
Organism-specific databases
CTDi | 9508 |
DisGeNETi | 9508 |
EuPathDBi | HostDB:ENSG00000156140.8 |
GeneCardsi | ADAMTS3 |
HGNCi | HGNC:219, ADAMTS3 |
HPAi | ENSG00000156140, Low tissue specificity |
MalaCardsi | ADAMTS3 |
MIMi | 605011, gene 618154, phenotype |
neXtProti | NX_O15072 |
OpenTargetsi | ENSG00000156140 |
Orphaneti | 2136, Hennekam syndrome |
PharmGKBi | PA24547 |
HUGEi | Search... |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG3538, Eukaryota |
GeneTreei | ENSGT00940000156085 |
HOGENOMi | CLU_000660_4_1_1 |
InParanoidi | O15072 |
OMAi | KYCVGDR |
OrthoDBi | 79609at2759 |
PhylomeDBi | O15072 |
TreeFami | TF313537 |
Enzyme and pathway databases
PathwayCommonsi | O15072 |
Reactomei | R-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
BioGRID-ORCSi | 9508, 11 hits in 844 CRISPR screens |
ChiTaRSi | ADAMTS3, human |
GeneWikii | ADAMTS3 |
GenomeRNAii | 9508 |
Pharosi | O15072, Tbio |
PROi | PR:O15072 |
RNActi | O15072, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000156140, Expressed in caudate nucleus and 154 other tissues |
Genevisiblei | O15072, HS |
Family and domain databases
Gene3Di | 2.20.100.10, 4 hits 3.40.390.10, 1 hit |
InterProi | View protein in InterPro IPR041645, ADAM_CR_2 IPR010294, ADAM_spacer1 IPR013273, ADAMTS/ADAMTS-like IPR024079, MetalloPept_cat_dom_sf IPR001590, Peptidase_M12B IPR002870, Peptidase_M12B_N IPR010909, PLAC IPR000884, TSP1_rpt IPR036383, TSP1_rpt_sf |
Pfami | View protein in Pfam PF17771, ADAM_CR_2, 1 hit PF05986, ADAM_spacer1, 1 hit PF01562, Pep_M12B_propep, 1 hit PF01421, Reprolysin, 1 hit PF00090, TSP_1, 1 hit |
PRINTSi | PR01857, ADAMTSFAMILY |
SMARTi | View protein in SMART SM00209, TSP1, 4 hits |
SUPFAMi | SSF82895, SSF82895, 4 hits |
PROSITEi | View protein in PROSITE PS50215, ADAM_MEPRO, 1 hit PS50900, PLAC, 1 hit PS50092, TSP1, 4 hits |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | ATS3_HUMAN | |
Accessioni | O15072Primary (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: | December 2, 2020 | |
This is version 192 of the entry and version 4 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any 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
Keywords - Technical termi
Reference proteomeDocuments
- Human chromosome 4
Human chromosome 4: entries, gene names and cross-references to MIM - Human polymorphisms and disease mutations
Index of human polymorphisms and disease mutations - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - Human entries with polymorphisms or disease mutations
List of human entries with polymorphisms or disease mutations