Reviewed, UniProtKB/Swiss-Prot Q9TT93 (ATS4_BOVIN)

Names and origin

Protein names

Recommended name:
    A disintegrin and metalloproteinase with thrombospondin motifs 4
      Short name=ADAMTS-4
      Short name=ADAM-TS 4
      Short name=ADAM-TS4
    EC=3.4.24.82
Alternative name(s):
    Aggrecanase-1
    ADMP-1

Gene names

Name:

ADAMTS4

Organism

Bos taurus (Bovine)

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.
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.
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	Direct protein sequencing
Gene Ontology (GO)
Biological process	glycoprotein catabolic process Inferred from sequence or structural similarity. Source: AgBase
Cellular component	proteinaceous extracellular matrix Inferred from sequence or structural similarity. Source: AgBase
Molecular function	metalloendopeptidase activity Inferred from electronic annotation. Source: InterPro zinc ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 51	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	83	Disintegrin
	Domain	520 – 575	56	TSP type-1
	Region	686 – 839	154	Spacer By similarity
	Motif	192 – 199	8	Cysteine switch By similarity
	Compositional bias	247 – 252	6	Poly-Ala
	Compositional bias	577 – 685	109	Cys-rich
Sites
	Active site	362	1	By similarity
	Metal binding	194	1	Zinc; in inhibited form By similarity
	Metal binding	361	1	Zinc; catalytic By similarity
	Metal binding	365	1	Zinc; catalytic By similarity
	Metal binding	371	1	Zinc; catalytic By similarity
Amino acid modifications
	Glycosylation	68	1	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)
	Q9TT93-1 [UniParc]. Last modified June 13, 2006. Version 3. Checksum: 1B488A27DF5B96B1	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

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: 10403768] [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: 10625599] [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. , Ellis D.M., Ross H., Wiswall B.H., Murphy K., Hillman M.C. Jr., Hollis G.F., Newton R.C., Magolda R.L., Trzaskos J.M., Arner E.C. Science 284:1664-1666(1999) [PubMed: 10356395] [Abstract] Cited for: PROTEIN SEQUENCE OF 213-239; 610-615 AND 626-637. Tissue: Cartilage.

Cross-references

Sequence databases
EMBLGenBankDDBJ	AF516915 mRNA. Translation: AAP47196.1. BC148059 mRNA. Translation: AAI48060.1. AF192770 mRNA. Translation: AAF07176.1.
IPI	IPI00694652.
RefSeq	NP_858053.1.
UniGene	Bt.15675
3D structure databases
HSSP	HSSP built from PDB template 4AIG based on UniProtKB P34179.
ModBase	Search...
Protein-protein interaction databases
STRING	Q9TT93.
Protein family/group databases
MEROPS	M12.221.
Genome annotation databases
Ensembl	ENSBTAT00000017583; ENSBTAP00000017583; ENSBTAG00000013210; Bos taurus. [Genome view] ENSBTAT00000052395; ENSBTAP00000049968; ENSBTAG00000013210; Bos taurus. [Genome view]
GeneID	286806.
KEGG	bta:286806.
Organism-specific databases
CTD	286806.
Phylogenomic databases
HOVERGEN	Q9TT93.
Enzyme and pathway databases
BRENDA	3.4.24.82. 251.
Family and domain databases
InterPro	IPR010294. ADAM_spacer1. IPR018358. Disintegrin_CS. IPR006025. Pept_M_Zn_BS. 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]
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...

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:	September 22, 2009
This is version 75 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)