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Protein

A disintegrin and metalloproteinase with thrombospondin motifs 1

Gene

ADAMTS1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Cleaves aggrecan, a cartilage proteoglycan, and may be involved in its turnover (By similarity). Has angiogenic inhibitor activity. Active metalloprotease, which may be associated with various inflammatory processes as well as development of cancer cachexia. May play a critical role in follicular rupture.By similarity1 Publication

Catalytic activityi

Cleaves aggrecan at the 1938-Glu-|-Leu-1939 site, within the chondroitin sulfate attachment domain.

Cofactori

Zn2+1 PublicationNote: Binds 1 zinc ion per subunit.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi198Zinc; in inhibited formBy similarity1
Metal bindingi261Calcium 11 Publication1
Metal bindingi261Calcium 21 Publication1
Metal bindingi344Calcium 11 Publication1
Metal bindingi344Calcium 2; via carbonyl oxygen1 Publication1
Metal bindingi351Calcium 11 Publication1
Metal bindingi401Zinc; catalytic1 Publication1
Active sitei402PROSITE-ProRule annotation1 Publication1
Metal bindingi405Zinc; catalytic1 Publication1
Metal bindingi411Zinc; catalytic1 Publication1
Metal bindingi462Calcium 1; via carbonyl oxygen1 Publication1
Metal bindingi465Calcium 11 Publication1
Metal bindingi465Calcium 21 Publication1

GO - Molecular functioni

  • heparin binding Source: UniProtKB-KW
  • metalloendopeptidase activity Source: Ensembl
  • metallopeptidase activity Source: ProtInc
  • zinc ion binding Source: InterPro

GO - Biological processi

  • heart trabecula formation Source: Ensembl
  • integrin-mediated signaling pathway Source: ProtInc
  • kidney development Source: Ensembl
  • negative regulation of cell proliferation Source: ProtInc
  • ovulation from ovarian follicle Source: Ensembl
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Metalloprotease, Protease

Keywords - Ligandi

Calcium, Heparin-binding, Metal-binding, Zinc

Enzyme and pathway databases

BioCyciZFISH:ENSG00000154734-MONOMER.
BRENDAi3.4.24.B11. 2681.
3.4.24.B12. 2681.
ReactomeiR-HSA-1474228. Degradation of the extracellular matrix.
R-HSA-5083635. Defective B3GALTL causes Peters-plus syndrome (PpS).
R-HSA-5173214. O-glycosylation of TSR domain-containing proteins.

Protein family/group databases

MEROPSiM12.222.

Names & Taxonomyi

Protein namesi
Recommended name:
A disintegrin and metalloproteinase with thrombospondin motifs 1 (EC:3.4.24.-)
Short name:
ADAM-TS 1
Short name:
ADAM-TS1
Short name:
ADAMTS-1
Alternative name(s):
METH-1
Gene namesi
Name:ADAMTS1
Synonyms:KIAA1346, METH1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 21

Organism-specific databases

HGNCiHGNC:217. ADAMTS1.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Extracellular matrix, Secreted

Pathology & Biotechi

Organism-specific databases

DisGeNETi9510.
OpenTargetsiENSG00000154734.
PharmGKBiPA24536.

Chemistry databases

ChEMBLiCHEMBL5133.
GuidetoPHARMACOLOGYi1674.

Polymorphism and mutation databases

BioMutaiADAMTS1.
DMDMi124053460.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 49Sequence analysisAdd BLAST49
PropeptideiPRO_000002915050 – 252By similarityAdd BLAST203
ChainiPRO_0000029151253 – 967A disintegrin and metalloproteinase with thrombospondin motifs 1Add BLAST715

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi333 ↔ 3851 Publication
Disulfide bondi362 ↔ 3671 Publication
Disulfide bondi379 ↔ 4621 Publication
Disulfide bondi417 ↔ 4461 Publication
Disulfide bondi488 ↔ 5111 Publication
Disulfide bondi499 ↔ 5211 Publication
Disulfide bondi506 ↔ 5401 Publication
Disulfide bondi534 ↔ 5451 Publication
Glycosylationi547N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi571 ↔ 608By similarity
Disulfide bondi575 ↔ 613By similarity
Disulfide bondi586 ↔ 598By similarity
Glycosylationi720N-linked (GlcNAc...)Sequence analysis1
Glycosylationi764N-linked (GlcNAc...)Sequence analysis1

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

EPDiQ9UHI8.
MaxQBiQ9UHI8.
PaxDbiQ9UHI8.
PeptideAtlasiQ9UHI8.
PRIDEiQ9UHI8.

PTM databases

iPTMnetiQ9UHI8.
PhosphoSitePlusiQ9UHI8.

Miscellaneous databases

PMAP-CutDBQ9UHI8.

Expressioni

Gene expression databases

BgeeiENSG00000154734.
CleanExiHS_ADAMTS1.
ExpressionAtlasiQ9UHI8. baseline and differential.
GenevisibleiQ9UHI8. HS.

Organism-specific databases

HPAiCAB016394.
HPA031498.
HPA031499.

Interactioni

Protein-protein interaction databases

BioGridi114888. 18 interactors.
IntActiQ9UHI8. 2 interactors.
STRINGi9606.ENSP00000284984.

Chemistry databases

BindingDBiQ9UHI8.

Structurei

Secondary structure

1967
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi258 – 266Combined sources9
Helixi268 – 274Combined sources7
Helixi275 – 277Combined sources3
Helixi278 – 293Combined sources16
Helixi296 – 298Combined sources3
Beta strandi302 – 311Combined sources10
Helixi315 – 317Combined sources3
Helixi325 – 336Combined sources12
Helixi337 – 339Combined sources3
Beta strandi351 – 359Combined sources9
Beta strandi371 – 373Combined sources3
Turni381 – 383Combined sources3
Beta strandi385 – 389Combined sources5
Helixi395 – 406Combined sources12
Helixi415 – 417Combined sources3
Turni418 – 420Combined sources3
Helixi445 – 456Combined sources12
Turni457 – 460Combined sources4
Helixi461 – 464Combined sources4
Helixi478 – 481Combined sources4
Helixi484 – 492Combined sources9
Beta strandi510 – 513Combined sources4
Beta strandi520 – 523Combined sources4
Beta strandi538 – 541Combined sources4
Beta strandi544 – 548Combined sources5

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2JIHX-ray2.10A/B253-548[»]
2V4BX-ray2.00A/B253-548[»]
3Q2GX-ray2.30A/B256-548[»]
3Q2HX-ray2.33A/B256-548[»]
ProteinModelPortaliQ9UHI8.
SMRiQ9UHI8.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ9UHI8.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini258 – 467Peptidase M12BPROSITE-ProRule annotationAdd BLAST210
Domaini476 – 559DisintegrinAdd BLAST84
Domaini559 – 614TSP type-1 1PROSITE-ProRule annotationAdd BLAST56
Domaini854 – 905TSP type-1 2PROSITE-ProRule annotationAdd BLAST52
Domaini908 – 967TSP type-1 3PROSITE-ProRule annotationAdd BLAST60

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni725 – 849SpacerAdd BLAST125

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi196 – 203Cysteine switchBy similarity8

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi617 – 724Cys-richAdd BLAST108
Compositional biasi843 – 846Poly-Lys4

Domaini

The spacer domain and the TSP type-1 domains are important for a tight interaction with the extracellular matrix.
The conserved cysteine present in the cysteine-switch motif binds the catalytic zinc ion, thus inhibiting the enzyme. The dissociation of the cysteine from the zinc ion upon the activation-peptide release activates the enzyme.

Sequence similaritiesi

Contains 1 disintegrin domain.Curated
Contains 1 peptidase M12B domain.PROSITE-ProRule annotation
Contains 3 TSP type-1 domains.PROSITE-ProRule annotation

Keywords - Domaini

Repeat, Signal

Phylogenomic databases

eggNOGiKOG3538. Eukaryota.
ENOG410XPKZ. LUCA.
GeneTreeiENSGT00760000118880.
HOGENOMiHOG000004799.
HOVERGENiHBG004313.
InParanoidiQ9UHI8.
KOiK08617.
OMAiCPDNNGK.
OrthoDBiEOG091G00AX.
PhylomeDBiQ9UHI8.
TreeFamiTF331949.

Family and domain databases

Gene3Di3.40.390.10. 1 hit.
InterProiIPR006586. ADAM_Cys-rich.
IPR010294. ADAM_spacer1.
IPR024079. MetalloPept_cat_dom.
IPR013274. Pept_M12B_ADAM-TS1.
IPR001590. Peptidase_M12B.
IPR013273. Peptidase_M12B_ADAM-TS.
IPR002870. Peptidase_M12B_N.
IPR000884. TSP1_rpt.
[Graphical view]
PfamiPF05986. ADAM_spacer1. 1 hit.
PF01562. Pep_M12B_propep. 1 hit.
PF01421. Reprolysin. 1 hit.
PF00090. TSP_1. 3 hits.
[Graphical view]
PRINTSiPR01858. ADAMTS1.
PR01857. ADAMTSFAMILY.
SMARTiSM00608. ACR. 1 hit.
SM00209. TSP1. 3 hits.
[Graphical view]
SUPFAMiSSF82895. SSF82895. 3 hits.
PROSITEiPS50215. ADAM_MEPRO. 1 hit.
PS50092. TSP1. 3 hits.
PS00142. ZINC_PROTEASE. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

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

Q9UHI8-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MQRAVPEGFG RRKLGSDMGN AERAPGSRSF GPVPTLLLLA AALLAVSDAL
60 70 80 90 100
GRPSEEDEEL VVPELERAPG HGTTRLRLHA FDQQLDLELR PDSSFLAPGF
110 120 130 140 150
TLQNVGRKSG SETPLPETDL AHCFYSGTVN GDPSSAAALS LCEGVRGAFY
160 170 180 190 200
LLGEAYFIQP LPAASERLAT AAPGEKPPAP LQFHLLRRNR QGDVGGTCGV
210 220 230 240 250
VDDEPRPTGK AETEDEDEGT EGEDEGAQWS PQDPALQGVG QPTGTGSIRK
260 270 280 290 300
KRFVSSHRYV ETMLVADQSM AEFHGSGLKH YLLTLFSVAA RLYKHPSIRN
310 320 330 340 350
SVSLVVVKIL VIHDEQKGPE VTSNAALTLR NFCNWQKQHN PPSDRDAEHY
360 370 380 390 400
DTAILFTRQD LCGSQTCDTL GMADVGTVCD PSRSCSVIED DGLQAAFTTA
410 420 430 440 450
HELGHVFNMP HDDAKQCASL NGVNQDSHMM ASMLSNLDHS QPWSPCSAYM
460 470 480 490 500
ITSFLDNGHG ECLMDKPQNP IQLPGDLPGT SYDANRQCQF TFGEDSKHCP
510 520 530 540 550
DAASTCSTLW CTGTSGGVLV CQTKHFPWAD GTSCGEGKWC INGKCVNKTD
560 570 580 590 600
RKHFDTPFHG SWGMWGPWGD CSRTCGGGVQ YTMRECDNPV PKNGGKYCEG
610 620 630 640 650
KRVRYRSCNL EDCPDNNGKT FREEQCEAHN EFSKASFGSG PAVEWIPKYA
660 670 680 690 700
GVSPKDRCKL ICQAKGIGYF FVLQPKVVDG TPCSPDSTSV CVQGQCVKAG
710 720 730 740 750
CDRIIDSKKK FDKCGVCGGN GSTCKKISGS VTSAKPGYHD IITIPTGATN
760 770 780 790 800
IEVKQRNQRG SRNNGSFLAI KAADGTYILN GDYTLSTLEQ DIMYKGVVLR
810 820 830 840 850
YSGSSAALER IRSFSPLKEP LTIQVLTVGN ALRPKIKYTY FVKKKKESFN
860 870 880 890 900
AIPTFSAWVI EEWGECSKSC ELGWQRRLVE CRDINGQPAS ECAKEVKPAS
910 920 930 940 950
TRPCADHPCP QWQLGEWSSC SKTCGKGYKK RSLKCLSHDG GVLSHESCDP
960
LKKPKHFIDF CTMAECS
Length:967
Mass (Da):105,358
Last modified:January 23, 2007 - v4
Checksum:i334119D6310A05A7
GO

Sequence cautioni

The sequence AAD48080 differs from that shown. Reason: Erroneous initiation.Curated
The sequence BAA92584 differs from that shown. Reason: Erroneous initiation.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti468Q → H in AAF15317 (Ref. 1) Curated1
Sequence conflicti561S → N in AAF15317 (Ref. 1) Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_030001227A → P.3 PublicationsCorresponds to variant rs428785dbSNPEnsembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF170084 mRNA. Translation: AAF15317.1.
AF060152 mRNA. Translation: AAD48080.1. Different initiation.
AF207664 mRNA. Translation: AAF23772.1.
AB037767 mRNA. Translation: BAA92584.1. Different initiation.
AP001697 Genomic DNA. Translation: BAA95502.1.
CH471079 Genomic DNA. Translation: EAX09951.1.
CH471079 Genomic DNA. Translation: EAX09952.1.
AL162080 mRNA. Translation: CAB82413.1.
CCDSiCCDS33524.1.
PIRiT47158.
RefSeqiNP_008919.3. NM_006988.4.
UniGeneiHs.643357.

Genome annotation databases

EnsembliENST00000284984; ENSP00000284984; ENSG00000154734.
GeneIDi9510.
KEGGihsa:9510.
UCSCiuc002ymf.4. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF170084 mRNA. Translation: AAF15317.1.
AF060152 mRNA. Translation: AAD48080.1. Different initiation.
AF207664 mRNA. Translation: AAF23772.1.
AB037767 mRNA. Translation: BAA92584.1. Different initiation.
AP001697 Genomic DNA. Translation: BAA95502.1.
CH471079 Genomic DNA. Translation: EAX09951.1.
CH471079 Genomic DNA. Translation: EAX09952.1.
AL162080 mRNA. Translation: CAB82413.1.
CCDSiCCDS33524.1.
PIRiT47158.
RefSeqiNP_008919.3. NM_006988.4.
UniGeneiHs.643357.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2JIHX-ray2.10A/B253-548[»]
2V4BX-ray2.00A/B253-548[»]
3Q2GX-ray2.30A/B256-548[»]
3Q2HX-ray2.33A/B256-548[»]
ProteinModelPortaliQ9UHI8.
SMRiQ9UHI8.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi114888. 18 interactors.
IntActiQ9UHI8. 2 interactors.
STRINGi9606.ENSP00000284984.

Chemistry databases

BindingDBiQ9UHI8.
ChEMBLiCHEMBL5133.
GuidetoPHARMACOLOGYi1674.

Protein family/group databases

MEROPSiM12.222.

PTM databases

iPTMnetiQ9UHI8.
PhosphoSitePlusiQ9UHI8.

Polymorphism and mutation databases

BioMutaiADAMTS1.
DMDMi124053460.

Proteomic databases

EPDiQ9UHI8.
MaxQBiQ9UHI8.
PaxDbiQ9UHI8.
PeptideAtlasiQ9UHI8.
PRIDEiQ9UHI8.

Protocols and materials databases

DNASUi9510.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000284984; ENSP00000284984; ENSG00000154734.
GeneIDi9510.
KEGGihsa:9510.
UCSCiuc002ymf.4. human.

Organism-specific databases

CTDi9510.
DisGeNETi9510.
GeneCardsiADAMTS1.
HGNCiHGNC:217. ADAMTS1.
HPAiCAB016394.
HPA031498.
HPA031499.
MIMi605174. gene.
neXtProtiNX_Q9UHI8.
OpenTargetsiENSG00000154734.
PharmGKBiPA24536.
HUGEiSearch...
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3538. Eukaryota.
ENOG410XPKZ. LUCA.
GeneTreeiENSGT00760000118880.
HOGENOMiHOG000004799.
HOVERGENiHBG004313.
InParanoidiQ9UHI8.
KOiK08617.
OMAiCPDNNGK.
OrthoDBiEOG091G00AX.
PhylomeDBiQ9UHI8.
TreeFamiTF331949.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000154734-MONOMER.
BRENDAi3.4.24.B11. 2681.
3.4.24.B12. 2681.
ReactomeiR-HSA-1474228. Degradation of the extracellular matrix.
R-HSA-5083635. Defective B3GALTL causes Peters-plus syndrome (PpS).
R-HSA-5173214. O-glycosylation of TSR domain-containing proteins.

Miscellaneous databases

ChiTaRSiADAMTS1. human.
EvolutionaryTraceiQ9UHI8.
GeneWikiiADAMTS1.
GenomeRNAii9510.
PMAP-CutDBQ9UHI8.
PROiQ9UHI8.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000154734.
CleanExiHS_ADAMTS1.
ExpressionAtlasiQ9UHI8. baseline and differential.
GenevisibleiQ9UHI8. HS.

Family and domain databases

Gene3Di3.40.390.10. 1 hit.
InterProiIPR006586. ADAM_Cys-rich.
IPR010294. ADAM_spacer1.
IPR024079. MetalloPept_cat_dom.
IPR013274. Pept_M12B_ADAM-TS1.
IPR001590. Peptidase_M12B.
IPR013273. Peptidase_M12B_ADAM-TS.
IPR002870. Peptidase_M12B_N.
IPR000884. TSP1_rpt.
[Graphical view]
PfamiPF05986. ADAM_spacer1. 1 hit.
PF01562. Pep_M12B_propep. 1 hit.
PF01421. Reprolysin. 1 hit.
PF00090. TSP_1. 3 hits.
[Graphical view]
PRINTSiPR01858. ADAMTS1.
PR01857. ADAMTSFAMILY.
SMARTiSM00608. ACR. 1 hit.
SM00209. TSP1. 3 hits.
[Graphical view]
SUPFAMiSSF82895. SSF82895. 3 hits.
PROSITEiPS50215. ADAM_MEPRO. 1 hit.
PS50092. TSP1. 3 hits.
PS00142. ZINC_PROTEASE. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiATS1_HUMAN
AccessioniPrimary (citable) accession number: Q9UHI8
Secondary accession number(s): D3DSD5
, Q9NSJ8, Q9P2K0, Q9UH83, Q9UP80
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: January 23, 2007
Last modified: November 2, 2016
This is version 166 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

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 21
    Human chromosome 21: 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. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Peptidase families
    Classification of peptidase families and list of entries
  7. 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.