Reviewed, UniProtKB/Swiss-Prot Q5RFQ8 (ATS4_PONAB)

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

Gene names

Name:

ADAMTS4

Organism

Pongo abelii (Sumatran orangutan)

Taxonomic identifier

9601 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Pongo

Protein attributes

Sequence length	837 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at transcript 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.
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.

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
Gene Ontology (GO)
Cellular component	proteinaceous extracellular matrix Inferred from electronic annotation. Source: UniProtKB-SubCell
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	By similarity		PRO_0000239803
	Chain	213 – 837	625	A disintegrin and metalloproteinase with thrombospondin motifs 4		PRO_0000239804
Regions
	Domain	218 – 428	211	Peptidase M12B
	Domain	437 – 519	83	Disintegrin
	Domain	520 – 575	56	TSP type-1
	Region	686 – 837	152	Spacer By similarity
	Motif	192 – 199	8	Cysteine switch By similarity
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)
	Q5RFQ8-1 [UniParc]. Last modified December 21, 2004. Version 1. Checksum: 08F5E69F65CF6B4C	FASTA	837	90,262
	10 20 30 40 50 60 MSQTGSHPGR GLAGRWLWGA QPCLLLPIVP LSWLVWLLLL LLASLLPSAR LASPLPREEE 70 80 90 100 110 120 IVFPEKLNGS VLPGSGAPAR LLCRLQAFGE TLLLELEHDS GVQVEGLTVQ YLGQAPELLG 130 140 150 160 170 180 GAEPGTYLTG TINGEPESVA SLHWDGGALL GVLQYRGAEL HLQPLEGGTP NSAGGPGAHI 190 200 210 220 230 240 LRRKSPASGQ GPMCNVKAPL GSPSPRPRRA KRFASLSRFV ETLVVADDKM AAFHGAGLKR 250 260 270 280 290 300 YLLTVMAAAA KAFKHPSIRN PVSLVVTRLV ILGSGEEGPQ VGPSAAQTLR SFCAWQRGLN 310 320 330 340 350 360 TPEDSDPDHF DTAILFTRQD LCGVSTCDTL GMADVGTVCD PARSCAIVED DGLQSAYTAA 370 380 390 400 410 420 HELGHVFNML HDNSKPCISL NGPLSTSRHV MAPVMAHVDP EEPWSPCSAR FITDFLDNGY 430 440 450 460 470 480 GHCLLDKPEA PLHLPVTFPG KDYDADRQCQ LTFGPDSRHC PQLPPPCAAL WCSGHLNGHA 490 500 510 520 530 540 MCQTKHSPWA DGTPCGPAQA CMGGRCLHMD QLQDFNIPQA GGWGPWGPWG DCSRTCGGGV 550 560 570 580 590 600 QFSSRDCTRP VPRNGGKYCE GRRTRFRSCN TEDCPTGSVL TFREEQCAAY NHCTDLFKSF 610 620 630 640 650 660 PGPMDWVPRY TGVAPQDQCK LTCQARALGY YYVLEPRVVD GTPCSPDSSS VCVQGRCIHA 670 680 690 700 710 720 GCDRIIGSKK KFDKCMVCGG DGSGCSKQSG SFRKFRYGYN NVVTIPTGAT HILVRQQGNP 730 740 750 760 770 780 GHRSIYLALK LPDGSYALNG EYTLMPSPTD VVLPGAISLR YSGATAASET LSGHGPLAQP 790 800 810 820 830 LTLQVLVAGN PQDARLRYSF FVPRPTPSTP HPTPQDWLHR RAQILEILRR RPWVGRK

References

[1]	The German cDNA consortium Submitted (NOV-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Kidney.

Cross-references

Sequence databases
EMBLGenBankDDBJ	CR857094 mRNA. Translation: CAH89399.1.
UniGene	Pab.12192
3D structure databases
ModBase	Search...
Protein family/group databases
MEROPS	M12.221.
Phylogenomic databases
HOVERGEN	Q5RFQ8.
Enzyme and pathway databases
BRENDA	3.4.24.82. 269192.
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_PONAB

Accession

Primary (citable) accession number: Q5RFQ8

Entry history

Integrated into UniProtKB/Swiss-Prot:	June 13, 2006
Last sequence update:	December 21, 2004
Last modified:	September 22, 2009
This is version 29 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)