Q8TE56 (ATS17_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
A disintegrin and metalloproteinase with thrombospondin motifs 17
Short name=ADAM-TS 17
Short name=ADAM-TS17
Short name=ADAMTS-17
EC=3.4.24.-

Gene names

Name:

ADAMTS17

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	1095 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)

Subcellular location	Secreted › extracellular space › extracellular matrix By similarity.
Tissue specificity	Isoform 1 and isoform 2 are expressed at high levels in the lung, brain, whole eye and retina. Isoform 1 shows a weaker expression in the heart, kidney and skeletal muscle. Isoform 2 shows a weaker expression in the kidney, bone marrow and skeletal muscle. Isoform 1 and isoform 2 are expressed at high levels in the fetal heart, kidney, and whole eye, whereas a weak expression is seen in the fetal liver. Ref.5
Domain	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.
Involvement in disease	Weill-Marchesani-like syndrome (WMLS) [MIM:613195]: A disorder characterized by many of the key features of Weill-Marchesani syndrome, including lenticular myopia, ectopia lentis, glaucoma, spherophakia and short stature. However, the characteristic brachydactyly or decreased joint flexibility of Weill-Marchesani syndrome are absent. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.5
Sequence similarities	Contains 1 disintegrin domain. Contains 1 peptidase M12B domain. Contains 1 PLAC domain. Contains 5 TSP type-1 domains.

Ontologies

Keywords
Cellular component	Extracellular matrix Secreted
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Deafness Dwarfism
Domain	Repeat 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 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 zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Note: Additional isoforms may exist.

Isoform 1 (identifier: Q8TE56-1)

Also known as: a;

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: Q8TE56-2)

Also known as: b;

The sequence of this isoform differs from the canonical sequence as follows:
     1-243: Missing.
     713-745: ALKDSGKGSINSDWKIELPGEFQIAGTTVRYVR → GYIEAAVIPAGARRIRVVEDKPAHSFLGKTQMT
     746-1095: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 27	27	Potential
	Propeptide	28 – 223	196	By similarity		PRO_0000029198
	Chain	224 – 1095	872	A disintegrin and metalloproteinase with thrombospondin motifs 17		PRO_0000029199
Regions
	Domain	232 – 452	221	Peptidase M12B
	Domain	453 – 542	90	Disintegrin
	Domain	543 – 598	56	TSP type-1 1
	Domain	800 – 860	61	TSP type-1 2
	Domain	861 – 922	62	TSP type-1 3
	Domain	925 – 968	44	TSP type-1 4
	Domain	972 – 1029	58	TSP type-1 5
	Domain	1045 – 1084	40	PLAC
	Region	702 – 779	78	Spacer
	Motif	199 – 206	8	Cysteine switch By similarity
	Compositional bias	60 – 120	61	Arg-rich
	Compositional bias	599 – 701	103	Cys-rich
Sites
	Active site	390	1	By similarity
	Metal binding	201	1	Zinc; in inhibited form By similarity
	Metal binding	389	1	Zinc; catalytic By similarity
	Metal binding	393	1	Zinc; catalytic By similarity
	Metal binding	399	1	Zinc; catalytic By similarity
Amino acid modifications
	Glycosylation	167	1	N-linked (GlcNAc...) Potential
	Glycosylation	483	1	N-linked (GlcNAc...) Potential
	Glycosylation	785	1	N-linked (GlcNAc...) Potential
	Glycosylation	790	1	N-linked (GlcNAc...) Potential
	Glycosylation	832	1	N-linked (GlcNAc...) Potential
	Glycosylation	839	1	N-linked (GlcNAc...) Potential
	Glycosylation	894	1	N-linked (GlcNAc...) Potential
	Disulfide bond	367 ↔ 447		By similarity
	Disulfide bond	406 ↔ 431		By similarity
	Disulfide bond	555 ↔ 592		By similarity
	Disulfide bond	559 ↔ 597		By similarity
	Disulfide bond	570 ↔ 582		By similarity
	Disulfide bond	873 ↔ 916		By similarity
	Disulfide bond	877 ↔ 921		By similarity
	Disulfide bond	888 ↔ 905		By similarity
Natural variations
	Alternative sequence	1 – 243	243	Missing in isoform 2.		VSP_040331
	Alternative sequence	713 – 745	33	ALKDS…VRYVR → GYIEAAVIPAGARRIRVVED KPAHSFLGKTQMT in isoform 2.		VSP_040332
	Alternative sequence	746 – 1095	350	Missing in isoform 2.		VSP_040333
	Natural variant	216	1	S → L. Ref.5 Corresponds to variant rs7496668 [ dbSNP | Ensembl ].		VAR_057081
	Natural variant	482	1	M → T. Ref.5 Corresponds to variant rs28567966 [ dbSNP | Ensembl ].		VAR_057082
	Natural variant	566	1	R → T. Ref.2		VAR_064041
	Natural variant	1094	1	N → S. Ref.1 Ref.5 Corresponds to variant rs2573652 [ dbSNP | Ensembl ].		VAR_060317
Experimental info
	Sequence conflict	702	1	V → A in BAD18500. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (a) [UniParc]. Last modified May 18, 2010. Version 2. Checksum: A5D7A40484754D5D	FASTA	1,095	121,127
	10 20 30 40 50 60 MCDGALLPPL VLPVLLLLVW GLDPGTAVGD AAADVEVVLP WRVRPDDVHL PPLPAAPGPR 70 80 90 100 110 120 RRRRPRTPPA APRARPGERA LLLHLPAFGR DLYLQLRRDL RFLSRGFEVE EAGAARRRGR 130 140 150 160 170 180 PAELCFYSGR VLGHPGSLVS LSACGAAGGL VGLIQLGQEQ VLIQPLNNSQ GPFSGREHLI 190 200 210 220 230 240 RRKWSLTPSP SAEAQRPEQL CKVLTEKKKP TWGRPSRDWR ERRNAIRLTS EHTVETLVVA 250 260 270 280 290 300 DADMVQYHGA EAAQRFILTV MNMVYNMFQH QSLGIKINIQ VTKLVLLRQR PAKLSIGHHG 310 320 330 340 350 360 ERSLESFCHW QNEEYGGARY LGNNQVPGGK DDPPLVDAAV FVTRTDFCVH KDEPCDTVGI 370 380 390 400 410 420 AYLGGVCSAK RKCVLAEDNG LNLAFTIAHE LGHNLGMNHD DDHSSCAGRS HIMSGEWVKG 430 440 450 460 470 480 RNPSDLSWSS CSRDDLENFL KSKVSTCLLV TDPRSQHTVR LPHKLPGMHY SANEQCQILF 490 500 510 520 530 540 GMNATFCRNM EHLMCAGLWC LVEGDTSCKT KLDPPLDGTE CGADKWCRAG ECVSKTPIPE 550 560 570 580 590 600 HVDGDWSPWG AWSMCSRTCG TGARFRQRKC DNPPPGPGGT HCPGASVEHA VCENLPCPKG 610 620 630 640 650 660 LPSFRDQQCQ AHDRLSPKKK GLLTAVVVDD KPCELYCSPL GKESPLLVAD RVLDGTPCGP 670 680 690 700 710 720 YETDLCVHGK CQKIGCDGII GSAAKEDRCG VCSGDGKTCH LVKGDFSHAR GTALKDSGKG 730 740 750 760 770 780 SINSDWKIEL PGEFQIAGTT VRYVRRGLWE KISAKGPTKL PLHLMVLLFH DQDYGIHYEY 790 800 810 820 830 840 TVPVNRTAEN QSEPEKPQDS LFIWTHSGWE GCSVQCGGGE RRTIVSCTRI VNKTTTLVND 850 860 870 880 890 900 SDCPQASRPE PQVRRCNLHP CQSRWVAGPW SPCSATCEKG FQHREVTCVY QLQNGTHVAT 910 920 930 940 950 960 RPLYCPGPRP AAVQSCEGQD CLSIWEASEW SQCSASCGKG VWKRTVACTN SQGKCDASTR 970 980 990 1000 1010 1020 PRAEEACEDY SGCYEWKTGD WSTCSSTCGK GLQSRVVQCM HKVTGRHGSE CPALSKPAPY 1030 1040 1050 1060 1070 1080 RQCYQEVCND RINANTITSP RLAALTYKCT RDQWTVYCRV IREKNLCQDM RWYQRCCQTC 1090 RDFYANKMRQ PPPNS
	Isoform 2 (b) [UniParc]. Checksum: 6CABF495FDC4AE21	FASTA	502	54,757
	10 20 30 40 50 60 MVQYHGAEAA QRFILTVMNM VYNMFQHQSL GIKINIQVTK LVLLRQRPAK LSIGHHGERS 70 80 90 100 110 120 LESFCHWQNE EYGGARYLGN NQVPGGKDDP PLVDAAVFVT RTDFCVHKDE PCDTVGIAYL 130 140 150 160 170 180 GGVCSAKRKC VLAEDNGLNL AFTIAHELGH NLGMNHDDDH SSCAGRSHIM SGEWVKGRNP 190 200 210 220 230 240 SDLSWSSCSR DDLENFLKSK VSTCLLVTDP RSQHTVRLPH KLPGMHYSAN EQCQILFGMN 250 260 270 280 290 300 ATFCRNMEHL MCAGLWCLVE GDTSCKTKLD PPLDGTECGA DKWCRAGECV SKTPIPEHVD 310 320 330 340 350 360 GDWSPWGAWS MCSRTCGTGA RFRQRKCDNP PPGPGGTHCP GASVEHAVCE NLPCPKGLPS 370 380 390 400 410 420 FRDQQCQAHD RLSPKKKGLL TAVVVDDKPC ELYCSPLGKE SPLLVADRVL DGTPCGPYET 430 440 450 460 470 480 DLCVHGKCQK IGCDGIIGSA AKEDRCGVCS GDGKTCHLVK GDFSHARGTG YIEAAVIPAG 490 500 ARRIRVVEDK PAHSFLGKTQ MT

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning, expression analysis, and structural characterization of seven novel human ADAMTSs, a family of metalloproteinases with disintegrin and thrombospondin-1 domains." Cal S., Obaya A.J., Llamazares M., Garabaya C., Quesada V., Lopez-Otin C. Gene 283:49-62(2002) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT SER-1094.
[2]	"Genetic variation in ADAMTS17 gene." Tan J., Davila S., Hibberd M.L., Seielstad M. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT THR-566.
[3]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Tissue: Thymus.
[4]	"Analysis of the DNA sequence and duplication history of human chromosome 15." Zody M.C., Garber M., Sharpe T., Young S.K., Rowen L., O'Neill K., Whittaker C.A., Kamal M., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Kodira C.D., Madan A., Qin S., Yang X., Abbasi N., Abouelleil A. , Arachchi H.M., Baradarani L., Birditt B., Bloom S., Bloom T., Borowsky M.L., Burke J., Butler J., Cook A., DeArellano K., DeCaprio D., Dorris L. III, Dors M., Eichler E.E., Engels R., Fahey J., Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G., Johnson E., Jones C., Kamat A., Kaur A., Locke D.P., Madan A., Munson G., Jaffe D.B., Lui A., Macdonald P., Mauceli E., Naylor J.W., Nesbitt R., Nicol R., O'Leary S.B., Ratcliffe A., Rounsley S., She X., Sneddon K.M.B., Stewart S., Sougnez C., Stone S.M., Topham K., Vincent D., Wang S., Zimmer A.R., Birren B.W., Hood L., Lander E.S., Nusbaum C. Nature 440:671-675(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"Homozygous mutations in ADAMTS10 and ADAMTS17 cause lenticular myopia, ectopia lentis, glaucoma, spherophakia, and short stature." Morales J., Al-Sharif L., Khalil D.S., Shinwari J.M., Bavi P., Al-Mahrouqi R.A., Al-Rajhi A., Alkuraya F.S., Meyer B.F., Al Tassan N. Am. J. Hum. Genet. 85:558-568(2009) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS LEU-216; THR-482 AND SER-1094, INVOLVEMENT IN WMLS, ALTERNATIVE SPLICING, TISSUE SPECIFICITY.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AJ315735 mRNA. Translation: CAC86016.1. DQ217943 Genomic DNA. Translation: ABB70740.1. AK131344 mRNA. Translation: BAD18500.1. AC015723 Genomic DNA. No translation available. AC022710 Genomic DNA. No translation available. AC084855 Genomic DNA. No translation available. AC113187 Genomic DNA. No translation available.
IPI	IPI00152635. IPI00442191.
RefSeq	NP_620688.2. NM_139057.2.
UniGene	Hs.513200.
3D structure databases
ProteinModelPortal	Q8TE56.
SMR	Q8TE56. Positions 234-785, 798-972, 975-1031.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000268070.
Protein family/group databases
MEROPS	M12.027.
PTM databases
PhosphoSite	Q8TE56.
Polymorphism databases
DMDM	296434401.
Proteomic databases
PaxDb	Q8TE56.
PRIDE	Q8TE56.
Protocols and materials databases
DNASU	170691.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000268070; ENSP00000268070; ENSG00000140470.
GeneID	170691.
KEGG	hsa:170691.
UCSC	uc002bvv.1. human. uc002bvx.1. human.
Organism-specific databases
CTD	170691.
GeneCards	GC15M100511.
H-InvDB	HIX0012615.
HGNC	HGNC:17109. ADAMTS17.
MIM	607511. gene. 613195. phenotype.
neXtProt	NX_Q8TE56.
Orphanet	3449. Weill-Marchesani syndrome.
PharmGKB	PA24543.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG259740.
HOGENOM	HOG000004800.
HOVERGEN	HBG050621.
InParanoid	Q8TE56.
KO	K08631.
OMA	QSCEGQD.
OrthoDB	EOG480HVW.
PhylomeDB	Q8TE56.
Gene expression databases
ArrayExpress	Q8TE56.
Bgee	Q8TE56.
CleanEx	HS_ADAMTS17.
Genevestigator	Q8TE56.
GermOnline	ENSG00000140470. Homo sapiens.
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. IPR010909. PLAC. IPR000884. Thrombospondin_1_rpt. IPR007087. Znf_C2H2. [Graphical view]
Pfam	PF05986. ADAM_spacer1. 1 hit. PF01562. Pep_M12B_propep. 1 hit. PF08686. PLAC. 1 hit. PF01421. Reprolysin. 1 hit. PF00090. TSP_1. 4 hits. [Graphical view]
PRINTS	PR01857. ADAMTSFAMILY.
SMART	SM00209. TSP1. 5 hits. [Graphical view]
SUPFAM	SSF82895. TSP1. 5 hits.
PROSITE	PS50215. ADAM_MEPRO. 1 hit. PS00546. CYSTEINE_SWITCH. False negative. PS00427. DISINTEGRIN_1. False negative. PS50214. DISINTEGRIN_2. False negative. PS50900. PLAC. 1 hit. PS50092. TSP1. 5 hits. PS00142. ZINC_PROTEASE. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	ADAMTS17. human.
GenomeRNAi	170691.
NextBio	89106.
SOURCE	Search...

Entry information

Entry name

ATS17_HUMAN

Accession

Primary (citable) accession number: Q8TE56
Secondary accession number(s): Q2I7G4, Q6ZN75

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 28, 2003
Last sequence update:	May 18, 2010
Last modified:	May 1, 2013
This is version 105 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.