Q9UP79 (ATS8_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
A disintegrin and metalloproteinase with thrombospondin motifs 8
Short name=ADAM-TS 8
Short name=ADAM-TS8
Short name=ADAMTS-8
EC=3.4.24.-

Alternative name(s):
METH-2
METH-8

Gene names

Name:	ADAMTS8
Synonyms:	METH2

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	889 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	Has anti-angiogenic properties.
Cofactor	Binds 1 zinc ion per subunit By similarity.
Subcellular location	Secreted › extracellular space › extracellular matrix By similarity.
Tissue specificity	Highly expressed in adult and fetal lung, lower expression in brain, placenta, heart, stomach and fetal brain and kidney.
Domain	The spacer domain and the TSP type-1 domains are important for a tight interaction with the extracellular matrix.
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 2 TSP type-1 domains.

Ontologies

Keywords
Cellular component	Extracellular matrix Secreted
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	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	negative regulation of cell proliferation Traceable author statement Ref.1. Source: ProtInc proteolysis Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	proteinaceous extracellular matrix Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	heparin binding Inferred from electronic annotation. Source: UniProtKB-KW integrin binding Traceable author statement Ref.1. Source: ProtInc low affinity phosphate transmembrane transporter activity Traceable author statement Ref.3. Source: ProtInc metalloendopeptidase activity Inferred from electronic annotation. Source: InterPro metallopeptidase activity Traceable author statement Ref.1. 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 – 26	26	Potential
	Propeptide	27 – 213	187	By similarity		PRO_0000029178
	Chain	214 – 889	676	A disintegrin and metalloproteinase with thrombospondin motifs 8		PRO_0000029179
Regions
	Domain	219 – 429	211	Peptidase M12B
	Domain	438 – 525	88	Disintegrin
	Domain	526 – 581	56	TSP type-1 1
	Domain	833 – 888	56	TSP type-1 2
	Region	690 – 831	142	Spacer
	Compositional bias	201 – 204	4	Poly-Pro
	Compositional bias	583 – 689	107	Cys-rich
Sites
	Active site	364	1	By similarity
	Metal binding	363	1	Zinc; catalytic By similarity
	Metal binding	367	1	Zinc; catalytic By similarity
	Metal binding	373	1	Zinc; catalytic By similarity
Amino acid modifications
	Glycosylation	344	1	N-linked (GlcNAc...) Potential
	Glycosylation	400	1	N-linked (GlcNAc...) Potential
	Glycosylation	465	1	N-linked (GlcNAc...) Potential
	Glycosylation	490	1	N-linked (GlcNAc...) Potential
	Glycosylation	599	1	N-linked (GlcNAc...) Potential
	Disulfide bond	341 ↔ 424		By similarity
	Disulfide bond	379 ↔ 408		By similarity
	Disulfide bond	538 ↔ 575		By similarity
	Disulfide bond	542 ↔ 580		By similarity
	Disulfide bond	553 ↔ 565		By similarity
Experimental info
	Sequence conflict	2	1	L → F in AAD48081. Ref.1
	Sequence conflict	11 – 12	2	PP → LPF in AAD48081. Ref.1
	Sequence conflict	194	1	E → R in AAF25806. Ref.3
	Sequence conflict	412 – 439	28	YLTEL…LPTGL → FSGCHLQGWIHFKYLCKCVS ELKCDLMP in AAF25806. Ref.3
	Sequence conflict	430	1	A → G in AAD48081. Ref.1
	Sequence conflict	525	1	A → V in AAD48081. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Q9UP79 [UniParc]. Last modified November 30, 2010. Version 2. Checksum: E1767A6524BCEBAB	FASTA	889	96,460
	10 20 30 40 50 60 MLPAPAAPRW PPLLLLLLLL LPLARGAPAR PAAGGQASEL VVPTRLPGSA GELALHLSAF 70 80 90 100 110 120 GKGFVLRLAP DDSFLAPEFK IERLGGSGRA TGGERGLRGC FFSGTVNGEP ESLAAVSLCR 130 140 150 160 170 180 GLSGSFLLDG EEFTIQPQGA GGSLAQPHRL QRWGPAGARP LPRGPEWEVE TGEGQRQERG 190 200 210 220 230 240 DHQEDSEEES QEEEAEGASE PPPPLGATSR TKRFVSEARF VETLLVADAS MAAFYGADLQ 250 260 270 280 290 300 NHILTLMSVA ARIYKHPSIK NSINLMVVKV LIVEDEKWGP EVSDNGGLTL RNFCNWQRRF 310 320 330 340 350 360 NQPSDRHPEH YDTAILLTRQ NFCGQEGLCD TLGVADIGTI CDPNKSCSVI EDEGLQAAHT 370 380 390 400 410 420 LAHELGHVLS MPHDDSKPCT RLFGPMGKHH VMAPLFVHLN QTLPWSPCSA MYLTELLDGG 430 440 450 460 470 480 HGDCLLDAPA AALPLPTGLP GRMALYQLDQ QCRQIFGPDF RHCPNTSAQD VCAQLWCHTD 490 500 510 520 530 540 GAEPLCHTKN GSLPWADGTP CGPGHLCSEG SCLPEEEVER PKPVADGGWA PWGPWGECSR 550 560 570 580 590 600 TCGGGVQFSH RECKDPEPQN GGRYCLGRRA KYQSCHTEEC PPDGKSFREQ QCEKYNAYNY 610 620 630 640 650 660 TDMDGNLLQW VPKYAGVSPR DRCKLFCRAR GRSEFKVFEA KVIDGTLCGP ETLAICVRGQ 670 680 690 700 710 720 CVKAGCDHVV DSPRKLDKCG VCGGKGNSCR KVSGSLTPTN YGYNDIVTIP AGATNIDVKQ 730 740 750 760 770 780 RSHPGVQNDG NYLALKTADG QYLLNGNLAI SAIEQDILVK GTILKYSGSI ATLERLQSFR 790 800 810 820 830 840 PLPEPLTVQL LTVPGEVFPP KVKYTFFVPN DVDFSMQSSK ERATTNIIQP LLHAQWVLGD 850 860 870 880 WSECSSTCGA GWQRRTVECR DPSGQASATC NKALKPEDAK PCESQLCPL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"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]. Tissue: Lung.
[2]	"Human chromosome 11 DNA sequence and analysis including novel gene identification." Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K., Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T., Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G. , Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C., Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A., Hattori M., Rogers J., Lander E.S., Sakaki Y. Nature 440:497-500(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]	"ADAM-TS8, a novel metalloprotease of the ADAM-TS family located on mouse chromosome 9 and human chromosome 11." Georgiadis K.E., Hirohata S., Seldin M.F., Apte S.S. Genomics 62:312-315(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 194-439.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF060153 mRNA. Translation: AAD48081.1. AP002986 Genomic DNA. No translation available. AF175283 mRNA. Translation: AAF25806.1.
IPI	IPI00298650.
RefSeq	NP_008968.4. NM_007037.4.
UniGene	Hs.271605.
3D structure databases
ProteinModelPortal	Q9UP79.
SMR	Q9UP79. Positions 219-809, 837-888.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000257359.
Protein family/group databases
MEROPS	M12.226.
PTM databases
PhosphoSite	Q9UP79.
Polymorphism databases
DMDM	12643905.
Proteomic databases
PaxDb	Q9UP79.
PRIDE	Q9UP79.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000257359; ENSP00000257359; ENSG00000134917.
GeneID	11095.
KEGG	hsa:11095.
UCSC	uc001qgg.4. human.
Organism-specific databases
CTD	11095.
GeneCards	GC11M130308.
H-InvDB	HIX0026131.
HGNC	HGNC:224. ADAMTS8.
MIM	605175. gene.
neXtProt	NX_Q9UP79.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG285519.
HOGENOM	HOG000004799.
HOVERGEN	HBG004313.
InParanoid	Q9UP79.
KO	K08623.
PhylomeDB	Q9UP79.
Gene expression databases
Bgee	Q9UP79.
CleanEx	HS_ADAMTS8.
Genevestigator	Q9UP79.
Family and domain databases
Gene3D	3.40.390.10. 1 hit.
InterPro	IPR010294. ADAM_spacer1. IPR024079. MetalloPept_cat_dom. IPR013277. Pept_M12B_ADAM-TS8. 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. 2 hits. [Graphical view]
PRINTS	PR01861. ADAMTS8. PR01857. ADAMTSFAMILY.
SMART	SM00209. TSP1. 2 hits. [Graphical view]
SUPFAM	SSF82895. TSP1. 2 hits.
PROSITE	PS50215. ADAM_MEPRO. 1 hit. PS00427. DISINTEGRIN_1. False negative. PS50214. DISINTEGRIN_2. False negative. PS50092. TSP1. 2 hits. PS00142. ZINC_PROTEASE. 1 hit. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	11095.
NextBio	42178.
SOURCE	Search...

Entry information

Entry name

ATS8_HUMAN

Accession

Primary (citable) accession number: Q9UP79
Secondary accession number(s): Q9NZS0

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 1, 2000
Last sequence update:	November 30, 2010
Last modified:	May 1, 2013
This is version 122 of the entry and version 2 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.