A disintegrin and metalloproteinase with thrombospondin motifs 4 precursor

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Q9TT93 (ATS4_BOVIN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 3, 2013. Version 98. History...

Clusters with 100%, 90%, 50% identity |

Documents (2) |

Third-party data

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Names·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents Customize order

Names and origin

Protein names

Recommended name:
A disintegrin and metalloproteinase with thrombospondin motifs 4
Short name=ADAM-TS 4
Short name=ADAM-TS4
Short name=ADAMTS-4
EC=3.4.24.82

Alternative name(s):
ADMP-1
Aggrecanase-1

Gene names

Name:

ADAMTS4

Organism

Bos taurus (Bovine) [Reference proteome]

Taxonomic identifier

9913 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Laurasiatheria › Cetartiodactyla › Ruminantia › Pecora › Bovidae › Bovinae › Bos

Protein attributes

Sequence length	839 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. May play an important role in the destruction of aggrecan in arthritic diseases. Cleaves aggrecan at the '392-Glu-\|-Ala-393' site.
Catalytic activity	Glutamyl endopeptidase; bonds cleaved include 370-Thr-Glu-Gly-Glu-\|-Ala-Arg-Gly-Ser-377 in the interglobular domain of mammalian aggrecan.
Cofactor	Binds 1 zinc ion per subunit By similarity.
Subunit structure	Interacts with SRPX2 By similarity.
Subcellular location	Secreted › extracellular space › extracellular matrix By similarity.
Induction	By interleukin-1.
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 1 TSP type-1 domain.
Caution	Has sometimes been referred to as ADAMTS2.

Ontologies

Keywords
Cellular component	Extracellular matrix Secreted
Domain	Signal
Ligand	Metal-binding Zinc
Molecular function	Hydrolase Metalloprotease Protease
PTM	Cleavage on pair of basic residues Disulfide bond Glycoprotein Zymogen
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	proteolysis Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	proteinaceous extracellular matrix Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	metalloendopeptidase activity Inferred from electronic annotation. Source: InterPro metallopeptidase activity Inferred from sequence or structural similarity. Source: AgBase 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 – 51

Potential

Propeptide

52 – 212

161

PRO_0000239802

Chain

213 – 839

627

A disintegrin and metalloproteinase with thrombospondin motifs 4

PRO_0000078209

Regions

Domain

218 – 428

211

Peptidase M12B

Domain

437 – 519

Disintegrin

Domain

520 – 575

TSP type-1

Region

686 – 839

154

Spacer By similarity

Motif

192 – 199

Cysteine switch By similarity

Compositional bias

247 – 252

Poly-Ala

Compositional bias

577 – 685

109

Cys-rich

Sites

Active site

362

By similarity

Metal binding

194

Zinc; in inhibited form By similarity

Metal binding

361

Zinc; catalytic By similarity

Metal binding

365

Zinc; catalytic By similarity

Metal binding

371

Zinc; catalytic By similarity

Amino acid modifications

Glycosylation

N-linked (GlcNAc...) Potential

Disulfide bond

339 ↔ 423

By similarity

Disulfide bond

377 ↔ 407

By similarity

Disulfide bond

532 ↔ 569

By similarity

Disulfide bond

536 ↔ 574

By similarity

Disulfide bond

547 ↔ 559

By similarity

Sequences

Sequence

Length

Mass (Da)

Tools

Q9TT93 [UniParc].

Last modified June 13, 2006. Version 3.
Checksum: 1B488A27DF5B96B1
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FASTA

839

90,280

        10         20         30         40         50         60 
MSHMDSHPGR GLADGWLWGI QPRLLLPTVP VSGSRLVWLL LLASLLPSAW PASPLPREEE 

        70         80         90        100        110        120 
IVFPEKLNGS VLPGLGAPAR LLYRLPAFGE TLLLELEKDP GVQVEGLTVQ YLGRAPELLG 

       130        140        150        160        170        180 
GAEPGTYLTG TINGDPESVA SLHWDGGALL GVLQYRGTEL HIQPLEGGAP NSAGGPGAHI 

       190        200        210        220        230        240 
LRRKSPVSGQ GPMCNVKAPP GKPSPSPRRA KRFASLSRFV ETLVVADDKM AAFHGAGLKR 

       250        260        270        280        290        300 
YLLTVMAAAA KAFKHPSIRN PVSLVVTRLV VLGPGEEGPQ VGPSAAQTLR SFCAWQRGLN 

       310        320        330        340        350        360 
TPDDADPGHF DTAILFTRQD LCGVSTCDTL GMADVGTVCD PARSCAIVED DGLQSAFTAA 

       370        380        390        400        410        420 
HELGHVFSML HDNSKQCTGL NGPESTSRHV MAPVMAHVDP EEPWSPCSAR FITDFLDNGF 

       430        440        450        460        470        480 
GHCLLDKPEA PLHLPVTFPG KDYDADRQCQ LTFGPDSRHC PQLPPPCAAL WCSGHLNGHA 

       490        500        510        520        530        540 
MCQTKHSPWA DGTPCGPAQA CMGGRCLHVD QLQAFNVPQA GGWGPWGSWG DCSRSCGGGV 

       550        560        570        580        590        600 
QFSSRDCTRP VPRNGGKYCE GRRTRFRSCN TQDCPTGSAL TFREEQCAAY NHRTDLFKNF 

       610        620        630        640        650        660 
PGPMDWVPRY TGVAPRDQCK LTCQTRALGY YYVLDPRVAD GTPCSPDSSS VCVQGRCIHA 

       670        680        690        700        710        720 
GCDRVIGSKK KFDKCMVCGG DGSSCSKQSG SFKKFRYGYN NVVTIPAGAT HILVRQQGSP 

       730        740        750        760        770        780 
SVRSLYLALK LPDGSYALNG EYTLIPSPTD VVLPGAVSLR YSGATAASET LSGHGPLAEP 

       790        800        810        820        830 
LTLQVLVAGN PQNARLRYSF FVPRPRPVPS TPRPTPQDWL RRKSQILEIL RRRSWAGRK

« Hide

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning and characterization of bovine aggrecanase-1." Arai M., Anderson D., Annis B., Collins-Racie L., Corcoran C., DiBlasio-Smith E., Morris E., Dorner A., LaVallie E. Submitted (MAY-2002) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	NIH - Mammalian Gene Collection (MGC) project Submitted (JUN-2007) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: Hereford. Tissue: Thalamus.
[3]	"Expression of ADAMTS homologues in articular cartilage." Flannery C.R., Little C.B., Hughes C.E., Caterson B. Biochem. Biophys. Res. Commun. 260:318-322(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 332-531. Tissue: Cartilage.
[4]	"n-3 fatty acids specifically modulate catabolic factors involved in articular cartilage degradation." Curtis C.L., Hughes C.E., Flannery C.R., Little C.B., Harwood J.L., Caterson B. J. Biol. Chem. 275:721-724(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 332-531. Tissue: Cartilage chondrocyte.
[5]	"Purification and cloning of aggrecanase-1: a member of the ADAMTS family of proteins." Tortorella M.D., Burn T.C., Pratta M.A., Abbaszade I., Hollis J.M., Liu R.-Q., Rosenfeld S.A., Copeland R.A., Decicco C.P., Wynn R., Rockwell A., Yang F., Duke J.L., Solomon K., George H., Bruckner R., Nagase H., Itoh Y. Arner E.C. Science 284:1664-1666(1999) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 213-239; 610-615 AND 626-637. Tissue: Cartilage.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF516915 mRNA. Translation: AAP47196.1. BC148059 mRNA. Translation: AAI48060.1. AF192770 mRNA. Translation: AAF07176.1.
IPI	IPI00905470.
RefSeq	NP_858053.1. NM_181667.1.
UniGene	Bt.15675.
3D structure databases
ProteinModelPortal	Q9TT93.
SMR	Q9TT93. Positions 215-507.
ModBase	Search...
Protein family/group databases
MEROPS	M12.221.
Proteomic databases
PRIDE	Q9TT93.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
GeneID	286806.
KEGG	bta:286806.
Organism-specific databases
CTD	9507.
Phylogenomic databases
eggNOG	NOG271890.
HOGENOM	HOG000004799.
HOVERGEN	HBG004313.
KO	K07764.
Family and domain databases
Gene3D	3.40.390.10. 1 hit.
InterPro	IPR010294. ADAM_spacer1. IPR024079. MetalloPept_cat_dom. 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. 1 hit. [Graphical view]
PRINTS	PR01857. ADAMTSFAMILY.
SMART	SM00209. TSP1. 1 hit. [Graphical view]
SUPFAM	SSF82895. TSP1. 1 hit.
PROSITE	PS50215. ADAM_MEPRO. 1 hit. PS00427. DISINTEGRIN_1. False negative. PS50214. DISINTEGRIN_2. False negative. PS50092. TSP1. 1 hit. PS00142. ZINC_PROTEASE. 1 hit. [Graphical view]
ProtoNet	Search...
Other
BindingDB	Q9TT93.
ChEMBL	CHEMBL3874.
NextBio	20806460.

Entry information

Entry name

ATS4_BOVIN

Accession

Primary (citable) accession number: Q9TT93
Secondary accession number(s): A6QLR5, Q7YS95

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 1, 2000
Last sequence update:	June 13, 2006
Last modified:	April 3, 2013
This is version 98 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Relevant documents

Peptidase families

Classification of peptidase families and list of entries

SIMILARITY comments

Index of protein domains and families

Names·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents

Preferred order of sections

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Sequence annotation (Features)

Molecule processing

Regions

Sites

Amino acid modifications

Sequences

References

Cross-references

Sequence databases

3D structure databases

Protein family/group databases

Proteomic databases

Protocols and materials databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Family and domain databases

Other

Entry information

Relevant documents