Q9UHI8 (ATS1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	967 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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 By similarity.
Subcellular location	Secreted › extracellular space › extracellular 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.

Ontologies

Keywords
Cellular component	Extracellular matrix Secreted
Coding sequence diversity	Polymorphism
Domain	Repeat Signal
Ligand	Heparin-binding Metal-binding Zinc
Molecular function	Hydrolase Metalloprotease Protease
PTM	Cleavage on pair of basic residues Disulfide bond Glycoprotein Zymogen
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	heart trabecula formation Inferred from electronic annotation. Source: Compara integrin-mediated signaling pathway Traceable author statement PubMed 8995297. Source: ProtInc kidney development Inferred from electronic annotation. Source: Compara negative regulation of cell proliferation Traceable author statement Ref.2. Source: ProtInc ovulation from ovarian follicle Inferred from electronic annotation. Source: Compara proteolysis Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	basement membrane Inferred from electronic annotation. Source: Compara cytoplasmic vesicle Inferred from electronic annotation. Source: Compara
Molecular_function	heparin binding Inferred from electronic annotation. Source: UniProtKB-KW metalloendopeptidase activity Inferred from electronic annotation. Source: Compara metallopeptidase activity Traceable author statement Ref.2. Source: ProtInc zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 49

49

Potential

Propeptide

50 – 252

203

By similarity

PRO_0000029150

Chain

253 – 967

715

A disintegrin and metalloproteinase with thrombospondin motifs 1

PRO_0000029151

Regions

Domain

258 – 467

210

Peptidase M12B

Domain

476 – 559

84

Disintegrin

Domain

559 – 614

56

TSP type-1 1

Domain

854 – 905

52

TSP type-1 2

Domain

908 – 967

60

TSP type-1 3

Region

725 – 849

125

Spacer

Motif

196 – 203

8

Cysteine switch By similarity

Compositional bias

617 – 724

108

Cys-rich

Compositional bias

843 – 846

4

Poly-Lys

Sites

Active site

402

1

By similarity

Metal binding

198

1

Zinc; in inhibited form By similarity

Metal binding

401

1

Zinc; catalytic By similarity

Metal binding

405

1

Zinc; catalytic By similarity

Metal binding

411

1

Zinc; catalytic By similarity

Amino acid modifications

Glycosylation

547

1

N-linked (GlcNAc...) Potential

Glycosylation

720

1

N-linked (GlcNAc...) Potential

Glycosylation

764

1

N-linked (GlcNAc...) Potential

Disulfide bond

379 ↔ 462

By similarity

Disulfide bond

417 ↔ 446

By similarity

Disulfide bond

571 ↔ 608

By similarity

Disulfide bond

575 ↔ 613

By similarity

Disulfide bond

586 ↔ 598

By similarity

Natural variations

Natural variant

227

1

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

VAR_030001

Experimental info

Sequence conflict

468

1

Q → H in AAF15317. Ref.1

Sequence conflict

561

1

S → N in AAF15317. Ref.1

Secondary structure

1

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967

Helix Strand Turn

Details...

Beta strand

258 – 266

9

Helix

268 – 274

7

Helix

275 – 277

3

Helix

278 – 293

16

Helix

296 – 298

3

Beta strand

302 – 311

10

Helix

315 – 317

3

Helix

325 – 336

12

Helix

337 – 339

3

Beta strand

351 – 359

9

Beta strand

371 – 373

3

Turn

381 – 383

3

Beta strand

385 – 389

5

Helix

395 – 406

12

Helix

415 – 417

3

Turn

418 – 420

3

Helix

445 – 456

12

Turn

457 – 460

4

Helix

461 – 464

4

Helix

478 – 481

4

Helix

484 – 492

9

Beta strand

510 – 513

4

Beta strand

520 – 523

4

Beta strand

538 – 541

4

Beta strand

544 – 548

5

Sequences

	Sequence		Length	Mass (Da)
	Q9UHI8 [UniParc]. Last modified January 23, 2007. Version 4. Checksum: 334119D6310A05A7	FASTA	967	105,358
	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

References

	« Hide 'large scale' referencesShow '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. , 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. , 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.
+	Additional computationally mapped references.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

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.

IPI

IPI00005908.

PIR

T47158.

RefSeq

NP_008919.3. NM_006988.3.

UniGene

Hs.643357.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2JIH	X-ray	2.10	A/B	253-548	[»]
2V4B	X-ray	2.00	A/B	253-548	[»]
3Q2G	X-ray	2.30	A/B	256-548	[»]
3Q2H	X-ray	2.33	A/B	256-548	[»]

ProteinModelPortal

Q9UHI8.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q9UHI8. 2 interactions.

STRING

9606.ENSP00000284984.

Protein family/group databases

MEROPS

M12.222.

PTM databases

PhosphoSite

Q9UHI8.

Polymorphism databases

DMDM

124053460.

Proteomic databases

PaxDb

Q9UHI8.

PeptideAtlas

Q9UHI8.

PRIDE

Q9UHI8.

Protocols and materials databases

DNASU

9510.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000284984; ENSP00000284984; ENSG00000154734.

GeneID

9510.

KEGG

hsa:9510.

UCSC

uc002ymf.3. human.

Organism-specific databases

CTD

9510.

GeneCards

GC21M028208.

HGNC

HGNC:217. ADAMTS1.

HPA

CAB016394.

MIM

605174. gene.

neXtProt

NX_Q9UHI8.

PharmGKB

PA24536.

HUGE

Search...

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG291688.

HOGENOM

HOG000004799.

HOVERGEN

HBG004313.

InParanoid

Q9UHI8.

KO

K08617.

OMA

CSWQKQH.

OrthoDB

EOG4933H3.

PhylomeDB

Q9UHI8.

Gene expression databases

ArrayExpress

Q9UHI8.

Bgee

Q9UHI8.

CleanEx

HS_ADAMTS1.

Genevestigator

Q9UHI8.

GermOnline

ENSG00000154734. Homo sapiens.

Family and domain databases

Gene3D

3.40.390.10. 1 hit.

InterPro

IPR006586. 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]

Pfam

PF05986. ADAM_spacer1. 1 hit.
PF01562. Pep_M12B_propep. 1 hit.
PF01421. Reprolysin. 1 hit.
PF00090. TSP_1. 3 hits.
[Graphical view]

PRINTS

PR01858. ADAMTS1.
PR01857. ADAMTSFAMILY.

SMART

SM00608. ACR. 1 hit.
SM00209. TSP1. 3 hits.
[Graphical view]

SUPFAM

SSF82895. TSP1. 3 hits.

PROSITE

PS50215. ADAM_MEPRO. 1 hit.
PS00427. DISINTEGRIN_1. False negative.
PS50214. DISINTEGRIN_2. False negative.
PS50092. TSP1. 3 hits.
PS00142. ZINC_PROTEASE. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

Q9UHI8.

ChEMBL

CHEMBL5133.

ChiTaRS

ADAMTS1. human.

EvolutionaryTrace

Q9UHI8.

GenomeRNAi

9510.

NextBio

35638.

PMAP-CutDB

Q9UHI8.

SOURCE

Search...

Entry information

Entry name

ATS1_HUMAN

Accession

Primary (citable) accession number: Q9UHI8
Secondary accession number(s): D3DSD5 , Q9NSJ8, Q9P2K0, Q9UH83, Q9UP80

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 30, 2000
Last sequence update:	January 23, 2007
Last modified:	May 1, 2013
This is version 133 of the entry and version 4 of the sequence. [Complete history]

Entry status

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.