Reviewed, UniProtKB/Swiss-Prot Q8BNJ2 (ATS4_MOUSE)

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

Mus musculus (Mouse)

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus

Protein attributes

Sequence length	833 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 By similarity.
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 By similarity. 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)
Biological process	proteolysis Inferred from direct assay. Source: MGI
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 – 49	49	Potential
	Propeptide	50 – 208	159	By similarity		PRO_0000029166
	Chain	209 – 833	625	A disintegrin and metalloproteinase with thrombospondin motifs 4		PRO_0000029167
Regions
	Domain	214 – 424	211	Peptidase M12B
	Domain	433 – 515	83	Disintegrin
	Domain	516 – 571	56	TSP type-1
	Region	682 – 833	152	Spacer
	Motif	188 – 195	8	Cysteine switch By similarity
Sites
	Active site	358	1	By similarity
	Metal binding	190	1	Zinc; in inhibited form By similarity
	Metal binding	357	1	Zinc; catalytic By similarity
	Metal binding	361	1	Zinc; catalytic By similarity
	Metal binding	367	1	Zinc; catalytic By similarity
Amino acid modifications
	Glycosylation	63	1	N-linked (GlcNAc...) Potential
	Glycosylation	299	1	N-linked (GlcNAc...) Potential
	Disulfide bond	335 ↔ 419		By similarity
	Disulfide bond	373 ↔ 403		By similarity
	Disulfide bond	528 ↔ 565		By similarity
	Disulfide bond	532 ↔ 570		By similarity
	Disulfide bond	543 ↔ 555		By similarity
Experimental info
	Sequence conflict	18	1	Q → R in AAH27773. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Q8BNJ2-1 [UniParc]. Last modified May 10, 2005. Version 2. Checksum: 6512B9ED2617F3A4	FASTA	833	90,070
	10 20 30 40 50 60 MSQMGLHPRR GLTGHWLQRF QPCLPLHTVQ WRRLLLLAFL LSLAWPASPL PREEEIVFPE 70 80 90 100 110 120 KLNGSSILPG SGVPARLLYR LPAFGEMLLL ELEQDPGVQV EGLTVQYLGQ APEMLGGAEP 130 140 150 160 170 180 GTYLTGTING DPESVASLHW DGGALLGVLQ YRGAELHLQP LEGGALNSAG GPGAHILRRK 190 200 210 220 230 240 SPASSQGPMC TVKAPSGSPS PISRRTKRFA SLSRFVETLV VADDKMAAFH GTGLKRYLLT 250 260 270 280 290 300 VMAAAAKAFK HPSIRNPVNL VVTRLVILGS GQEGPQVGPS AAQTLRSFCT WQRGLNTPND 310 320 330 340 350 360 SDPDHFDTAI LFTRQDLCGV STCDTLGMAD VGTVCDPARS CAIVEDDGLQ SAFTAAHELG 370 380 390 400 410 420 HVFNMLHDNS KPCTNLNGQG GSSRHVMAPV MAHVDPEEPW SPCSARFITD FLDNGYGHCL 430 440 450 460 470 480 LDKPEAPLHL PATFPGKDYD ADRQCQLTFG PDSSHCPQLP PPCAALWCSG HLNGHAMCQT 490 500 510 520 530 540 KHSPWADGTP CGSSQACMGG RCLHVDQLKD FNVPQAGGWG PWGPWGDCSR TCGGGVQFSS 550 560 570 580 590 600 RDCTRPVPRN GGKYCEGRRT RFRSCNTENC PHGSALTFRE EQCAAYNHRT DLFKSFPGPM 610 620 630 640 650 660 DWVPRYTGVA PRDQCKLTCQ ARALGYYYVL EPRVADGTPC SPDTSSVCVQ GRCIHAGCDR 670 680 690 700 710 720 IIGSKKKFDK CMVCGGDGSR CSKQSGSFKK FRYGYSDVVT IPAGATHILV RQQGGSGLKS 730 740 750 760 770 780 IYLALKLSDG SYALNGEYTL MPSPTDVVLP GAVSLRYSGA TAASETLSGH GPLAQPLTLQ 790 800 810 820 830 VLVAGNPQNA RLRYSFFVPR PVPSTPRPPP QDWLQRRAEI LKILRKRPWA GRK

References

[1]	"The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y. Science 309:1559-1563(2005) [PubMed: 16141072] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: C57BL/6J.
[2]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: FVB/N. Tissue: Mammary tumor.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AK083534 mRNA. Translation: BAC38944.1. Different initiation. BC027773 mRNA. Translation: AAH27773.1.
IPI	IPI00469188.
RefSeq	NP_766433.1.
UniGene	Mm.475917
3D structure databases
SMR	Q8BNJ2. Positions 211-503, 213-656.
ModBase	Search...
Protein-protein interaction databases
STRING	Q8BNJ2.
Protein family/group databases
MEROPS	M12.221.
Proteomic databases
PRIDE	Q8BNJ2.
Genome annotation databases
Ensembl	ENSMUST00000006570; ENSMUSP00000006570; ENSMUSG00000006403; Mus musculus. [Genome view] ENSMUST00000111315; ENSMUSP00000106947; ENSMUSG00000006403; Mus musculus. [Genome view]
GeneID	240913.
KEGG	mmu:240913.
UCSC	uc007dnn.1. mouse.
Organism-specific databases
CTD	240913.
MGI	MGI:1339949. Adamts4.
Phylogenomic databases
HOVERGEN	Q8BNJ2.
InParanoid	Q8BNJ2.
OrthoDB	EOG91RSDV.
Enzyme and pathway databases
BRENDA	3.4.24.82. 244.
Gene expression databases
ArrayExpress	Q8BNJ2.
Bgee	Q8BNJ2.
Genevestigator	Q8BNJ2.
GermOnline	ENSMUSG00000006403. Mus musculus.
Family and domain databases
InterPro	IPR010294. ADAM_spacer1. 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...
Other Resources
SOURCE	Search...

Entry information

Entry name

ATS4_MOUSE

Accession

Primary (citable) accession number: Q8BNJ2
Secondary accession number(s): Q8K384

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 10, 2005
Last sequence update:	May 10, 2005
Last modified:	January 19, 2010
This is version 64 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)