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Q9UHI8 (ATS1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 141. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
A disintegrin and metalloproteinase with thrombospondin motifs 1

Short name=ADAM-TS 1
Short name=ADAM-TS1
Short name=ADAMTS-1
EC=3.4.24.-
Alternative name(s):
METH-1
Gene names
Name:ADAMTS1
Synonyms:KIAA1346, METH1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length967 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.2

Catalytic activity

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

Cofactor

Binds 1 zinc ion per subunit. Ref.8

Subcellular location

Secretedextracellular spaceextracellular matrix By similarity.

Domain

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.

Post-translational modification

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.

Sequence similarities

Contains 1 disintegrin domain.

Contains 1 peptidase M12B domain.

Contains 3 TSP type-1 domains.

Sequence caution

The sequence AAD48080.1 differs from that shown. Reason: Erroneous initiation.

The sequence BAA92584.1 differs from that shown. Reason: Erroneous initiation.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 4949 Potential
Propeptide50 – 252203 By similarity
PRO_0000029150
Chain253 – 967715A disintegrin and metalloproteinase with thrombospondin motifs 1
PRO_0000029151

Regions

Domain258 – 467210Peptidase M12B
Domain476 – 55984Disintegrin
Domain559 – 61456TSP type-1 1
Domain854 – 90552TSP type-1 2
Domain908 – 96760TSP type-1 3
Region725 – 849125Spacer
Motif196 – 2038Cysteine switch By similarity
Compositional bias617 – 724108Cys-rich
Compositional bias843 – 8464Poly-Lys

Sites

Active site4021 Ref.8
Metal binding1981Zinc; in inhibited form By similarity
Metal binding2611Calcium 1
Metal binding2611Calcium 2
Metal binding3441Calcium 1
Metal binding3441Calcium 2; via carbonyl oxygen
Metal binding3511Calcium 1
Metal binding4011Zinc; catalytic
Metal binding4051Zinc; catalytic
Metal binding4111Zinc; catalytic
Metal binding4621Calcium 1; via carbonyl oxygen
Metal binding4651Calcium 1
Metal binding4651Calcium 2

Amino acid modifications

Glycosylation5471N-linked (GlcNAc...) Potential
Glycosylation7201N-linked (GlcNAc...) Potential
Glycosylation7641N-linked (GlcNAc...) Potential
Disulfide bond333 ↔ 385 Ref.8
Disulfide bond362 ↔ 367 Ref.8
Disulfide bond379 ↔ 462 Ref.8
Disulfide bond417 ↔ 446 Ref.8
Disulfide bond488 ↔ 511 Ref.8
Disulfide bond499 ↔ 521 Ref.8
Disulfide bond506 ↔ 540 Ref.8
Disulfide bond534 ↔ 545 Ref.8
Disulfide bond571 ↔ 608 By similarity
Disulfide bond575 ↔ 613 By similarity
Disulfide bond586 ↔ 598 By similarity

Natural variations

Natural variant2271A → P. Ref.1 Ref.2 Ref.3
Corresponds to variant rs428785 [ dbSNP | Ensembl ].
VAR_030001

Experimental info

Sequence conflict4681Q → H in AAF15317. Ref.1
Sequence conflict5611S → N in AAF15317. Ref.1

Secondary structure

............................................. 967
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q9UHI8 [UniParc].

Last modified January 23, 2007. Version 4.
Checksum: 334119D6310A05A7

FASTA967105,358
        10         20         30         40         50         60 
MQRAVPEGFG RRKLGSDMGN AERAPGSRSF GPVPTLLLLA AALLAVSDAL GRPSEEDEEL 

        70         80         90        100        110        120 
VVPELERAPG HGTTRLRLHA FDQQLDLELR PDSSFLAPGF TLQNVGRKSG SETPLPETDL 

       130        140        150        160        170        180 
AHCFYSGTVN GDPSSAAALS LCEGVRGAFY LLGEAYFIQP LPAASERLAT AAPGEKPPAP 

       190        200        210        220        230        240 
LQFHLLRRNR QGDVGGTCGV VDDEPRPTGK AETEDEDEGT EGEDEGAQWS PQDPALQGVG 

       250        260        270        280        290        300 
QPTGTGSIRK KRFVSSHRYV ETMLVADQSM AEFHGSGLKH YLLTLFSVAA RLYKHPSIRN 

       310        320        330        340        350        360 
SVSLVVVKIL VIHDEQKGPE VTSNAALTLR NFCNWQKQHN PPSDRDAEHY DTAILFTRQD 

       370        380        390        400        410        420 
LCGSQTCDTL GMADVGTVCD PSRSCSVIED DGLQAAFTTA HELGHVFNMP HDDAKQCASL 

       430        440        450        460        470        480 
NGVNQDSHMM ASMLSNLDHS QPWSPCSAYM ITSFLDNGHG ECLMDKPQNP IQLPGDLPGT 

       490        500        510        520        530        540 
SYDANRQCQF TFGEDSKHCP DAASTCSTLW CTGTSGGVLV CQTKHFPWAD GTSCGEGKWC 

       550        560        570        580        590        600 
INGKCVNKTD RKHFDTPFHG SWGMWGPWGD CSRTCGGGVQ YTMRECDNPV PKNGGKYCEG 

       610        620        630        640        650        660 
KRVRYRSCNL EDCPDNNGKT FREEQCEAHN EFSKASFGSG PAVEWIPKYA GVSPKDRCKL 

       670        680        690        700        710        720 
ICQAKGIGYF FVLQPKVVDG TPCSPDSTSV CVQGQCVKAG CDRIIDSKKK FDKCGVCGGN 

       730        740        750        760        770        780 
GSTCKKISGS VTSAKPGYHD IITIPTGATN IEVKQRNQRG SRNNGSFLAI KAADGTYILN 

       790        800        810        820        830        840 
GDYTLSTLEQ DIMYKGVVLR YSGSSAALER IRSFSPLKEP LTIQVLTVGN ALRPKIKYTY 

       850        860        870        880        890        900 
FVKKKKESFN AIPTFSAWVI EEWGECSKSC ELGWQRRLVE CRDINGQPAS ECAKEVKPAS 

       910        920        930        940        950        960 
TRPCADHPCP QWQLGEWSSC SKTCGKGYKK RSLKCLSHDG GVLSHESCDP LKKPKHFIDF 


CTMAECS 

« Hide

References

« Hide 'large scale' references
[1]"Cloning, characterization and mapping on human chromosome 21 of the orthologue of murine Adamts-1."
Casas C., Pritchard M.A., Estivill X., Arbones M.L.
Submitted (JUL-1999) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT PRO-227.
[2]"METH-1, a human ortholog of ADAMTS-1, and METH-2 are members of a new family of proteins with angio-inhibitory activity."
Vazquez F., Hastings G., Ortega M.-A., Lane T.F., Oikemus S., Lombardo M., Iruela-Arispe M.L.
J. Biol. Chem. 274:23349-23357(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT PRO-227, FUNCTION.
Tissue: Heart.
[3]"Differential gene expression by endothelial cells in distinct angiogenic states."
Glienke J., Schmitt A.O., Pilarsky C., Hinzmann B., Weiss B., Rosenthal A., Thierauch K.H.
Eur. J. Biochem. 267:2820-2830(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT PRO-227.
Tissue: Endothelial cell.
[4]"Prediction of the coding sequences of unidentified human genes. XVI. The complete sequences of 150 new cDNA clones from brain which code for large proteins in vitro."
Nagase T., Kikuno R., Ishikawa K., Hirosawa M., Ohara O.
DNA Res. 7:65-73(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Brain.
[5]"The DNA sequence of human chromosome 21."
Hattori M., Fujiyama A., Taylor T.D., Watanabe H., Yada T., Park H.-S., Toyoda A., Ishii K., Totoki Y., Choi D.-K., Groner Y., Soeda E., Ohki M., Takagi T., Sakaki Y., Taudien S., Blechschmidt K., Polley A. expand/collapse author list , Menzel U., Delabar J., Kumpf K., Lehmann R., Patterson D., Reichwald K., Rump A., Schillhabel M., Schudy A., Zimmermann W., Rosenthal A., Kudoh J., Shibuya K., Kawasaki K., Asakawa S., Shintani A., Sasaki T., Nagamine K., Mitsuyama S., Antonarakis S.E., Minoshima S., Shimizu N., Nordsiek G., Hornischer K., Brandt P., Scharfe M., Schoen O., Desario A., Reichelt J., Kauer G., Bloecker H., Ramser J., Beck A., Klages S., Hennig S., Riesselmann L., Dagand E., Wehrmeyer S., Borzym K., Gardiner K., Nizetic D., Francis F., Lehrach H., Reinhardt R., Yaspo M.-L.
Nature 405:311-319(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]"The full-ORF clone resource of the German cDNA consortium."
Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I.
BMC Genomics 8:399-399(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 418-967.
Tissue: Melanoma.
[8]"Crystal structures of human ADAMTS-1 reveal a conserved catalytic domain and a disintegrin-like domain with a fold homologous to cysteine-rich domains."
Gerhardt S., Hassall G., Hawtin P., McCall E., Flavell L., Minshull C., Hargreaves D., Ting A., Pauptit R.A., Parker A.E., Abbott W.M.
J. Mol. Biol. 373:891-902(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 253-548 ALONE AND IN COMPLEX WITH INHIBITOR, ACTIVE SITE, COFACTOR, ZINC-BINDING SITES, CALCIUM-BINDING SITES, DISULFIDE BONDS.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
PIRT47158.
RefSeqNP_008919.3. NM_006988.3.
UniGeneHs.643357.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2JIHX-ray2.10A/B253-548[»]
2V4BX-ray2.00A/B253-548[»]
3Q2GX-ray2.30A/B256-548[»]
3Q2HX-ray2.33A/B256-548[»]
ProteinModelPortalQ9UHI8.
SMRQ9UHI8. Positions 256-844, 851-966.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid114888. 4 interactions.
IntActQ9UHI8. 2 interactions.
STRING9606.ENSP00000284984.

Chemistry

BindingDBQ9UHI8.
ChEMBLCHEMBL5133.

Protein family/group databases

MEROPSM12.222.

PTM databases

PhosphoSiteQ9UHI8.

Polymorphism databases

DMDM124053460.

Proteomic databases

PaxDbQ9UHI8.
PeptideAtlasQ9UHI8.
PRIDEQ9UHI8.

Protocols and materials databases

DNASU9510.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000284984; ENSP00000284984; ENSG00000154734.
GeneID9510.
KEGGhsa:9510.
UCSCuc002ymf.3. human.

Organism-specific databases

CTD9510.
GeneCardsGC21M028208.
HGNCHGNC:217. ADAMTS1.
HPACAB016394.
HPA031498.
HPA031499.
MIM605174. gene.
neXtProtNX_Q9UHI8.
PharmGKBPA24536.
HUGESearch...
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG291688.
HOGENOMHOG000004799.
HOVERGENHBG004313.
InParanoidQ9UHI8.
KOK08617.
OMACPDNNGK.
OrthoDBEOG7WDN1M.
PhylomeDBQ9UHI8.
TreeFamTF331949.

Enzyme and pathway databases

ReactomeREACT_118779. Extracellular matrix organization.

Gene expression databases

ArrayExpressQ9UHI8.
BgeeQ9UHI8.
CleanExHS_ADAMTS1.
GenevestigatorQ9UHI8.

Family and domain databases

Gene3D3.40.390.10. 1 hit.
InterProIPR006586. 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. Thrombospondin_1_rpt.
[Graphical view]
PfamPF05986. ADAM_spacer1. 1 hit.
PF01562. Pep_M12B_propep. 1 hit.
PF01421. Reprolysin. 1 hit.
PF00090. TSP_1. 3 hits.
[Graphical view]
PRINTSPR01858. ADAMTS1.
PR01857. ADAMTSFAMILY.
SMARTSM00608. ACR. 1 hit.
SM00209. TSP1. 3 hits.
[Graphical view]
SUPFAMSSF82895. SSF82895. 3 hits.
PROSITEPS50215. ADAM_MEPRO. 1 hit.
PS50092. TSP1. 3 hits.
PS00142. ZINC_PROTEASE. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSADAMTS1. human.
EvolutionaryTraceQ9UHI8.
GeneWikiADAMTS1.
GenomeRNAi9510.
NextBio35638.
PMAP-CutDBQ9UHI8.
PROQ9UHI8.
SOURCESearch...

Entry information

Entry nameATS1_HUMAN
AccessionPrimary (citable) accession number: Q9UHI8
Secondary accession number(s): D3DSD5 expand/collapse secondary AC list , Q9NSJ8, Q9P2K0, Q9UH83, Q9UP80
Entry history
Integrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: January 23, 2007
Last modified: April 16, 2014
This is version 141 of the entry and version 4 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Peptidase families

Classification of peptidase families and list of entries

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 21

Human chromosome 21: entries, gene names and cross-references to MIM