Reviewed, UniProtKB/Swiss-Prot Q8TE60 (ATS18_HUMAN)

Names and origin

Protein names

Recommended name:
    A disintegrin and metalloproteinase with thrombospondin motifs 18
      Short name=ADAMTS-18
      Short name=ADAM-TS 18
      Short name=ADAM-TS18
    EC=3.4.24.-

Gene names

Name:	ADAMTS18
Synonyms:	ADAMTS21

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

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

Protein attributes

Sequence length	1221 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)

Cofactor	Binds 1 zinc ion per subunit By similarity.
Subcellular location	Secreted › extracellular space › extracellular matrix By similarity.
Tissue specificity	Expressed in fetal lung, liver, and kidney and in adult brain, prostate, submaxillary gland, and endothelium.
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.
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
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
Gene Ontology (GO)
Biological process	proteolysis Inferred from electronic annotation. Source: InterPro
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...

Alternative products

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

Isoform 1 (identifier: Q8TE60-1)

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: Q8TE60-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1064-1082: CSATCGLGVRKREMKCSEK → VWIRSHCWVRRLRPSWLTQ
     1083-1221: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 47	47	Potential
	Propeptide	48 – 284	237	By similarity		PRO_0000029200
	Chain	285 – 1221	937	A disintegrin and metalloproteinase with thrombospondin motifs 18		PRO_0000042163
Regions
	Domain	293 – 498	206	Peptidase M12B
	Domain	498 – 577	80	Disintegrin
	Domain	589 – 644	56	TSP type-1 1
	Domain	931 – 990	60	TSP type-1 2
	Domain	991 – 1049	59	TSP type-1 3
	Domain	1052 – 1116	65	TSP type-1 4
	Domain	1123 – 1178	56	TSP type-1 5
	Domain	1184 – 1221	38	PLAC
	Region	750 – 876	127	Spacer
	Motif	252 – 259	8	Cysteine switch By similarity
	Compositional bias	644 – 749	106	Cys-rich
Sites
	Active site	437	1	By similarity
	Metal binding	254	1	Zinc; in inhibited form By similarity
	Metal binding	436	1	Zinc; catalytic By similarity
	Metal binding	440	1	Zinc; catalytic By similarity
	Metal binding	446	1	Zinc; catalytic By similarity
Amino acid modifications
	Glycosylation	151	1	N-linked (GlcNAc...) Potential
	Glycosylation	190	1	N-linked (GlcNAc...) Potential
	Glycosylation	313	1	N-linked (GlcNAc...) Potential
	Glycosylation	745	1	N-linked (GlcNAc...) Potential
	Glycosylation	838	1	N-linked (GlcNAc...) Potential
	Glycosylation	909	1	N-linked (GlcNAc...) Potential
	Disulfide bond	414 ↔ 493		By similarity
	Disulfide bond	453 ↔ 477		By similarity
	Disulfide bond	601 ↔ 638		By similarity
	Disulfide bond	605 ↔ 643		By similarity
	Disulfide bond	616 ↔ 628		By similarity
Natural variations
	Alternative sequence	1064 – 1082	19	CSATC…KCSEK → VWIRSHCWVRRLRPSWLTQ in isoform 2.		VSP_015776
	Alternative sequence	1083 – 1221	139	Missing in isoform 2.		VSP_015777
	Natural variant	191	1	H → Y: dbSNP rs11643211. Ref.1		VAR_060231
	Natural variant	382	1	R → K in a colorectal cancer sample; somatic mutation. Ref.4		VAR_036152
	Natural variant	455	1	K → T in a colorectal cancer sample; somatic mutation. Ref.4		VAR_036153
	Natural variant	626	1	I → L: dbSNP rs11640912.		VAR_060232
	Natural variant	769	1	L → I: dbSNP rs9930984. Ref.2		VAR_057083
	Natural variant	946	1	A → S: dbSNP rs12935394. Ref.1		VAR_057084
	Natural variant	1080	1	S → R: dbSNP rs35478105. Ref.3		VAR_057085
	Natural variant	1159	1	S → T: dbSNP rs3743749.		VAR_057086
Experimental info
	Sequence conflict	323 – 324	2	NM → K in CAC83612. Ref.1
	Sequence conflict	410	1	I → T in CAC83612. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified September 27, 2005. Version 2. Checksum: 6259278C0492C27C	FASTA	1,221	135,141
	10 20 30 40 50 60 MECALLLACA FPAAGSGPPR GLAGLGRVAK ALQLCCLCCA SVAAALASDS SSGASGLNDD 70 80 90 100 110 120 YVFVTPVEVD SAGSYISHDI LHNGRKKRSA QNARSSLHYR FSAFGQELHL ELKPSAILSS 130 140 150 160 170 180 HFIVQVLGKD GASETQKPEV QQCFYQGFIR NDSSSSVAVS TCAGLSGLIR TRKNEFLISP 190 200 210 220 230 240 LPQLLAQEHN HSSPAGHHPH VLYKRTAEEK IQRYRGYPGS GRNYPGYSPS HIPHASQSRE 250 260 270 280 290 300 TEYHHRRLQK QHFCGRRKKY APKPPTEDTY LRFDEYGSSG RPRRSAGKSQ KGLNVETLVV 310 320 330 340 350 360 ADKKMVEKHG KGNVTTYILT VMNMVSGLFK DGTIGSDINV VVVSLILLEQ EPGGLLINHH 370 380 390 400 410 420 ADQSLNSFCQ WQSALIGKNG KRHDHAILLT GFDICSWKNE PCDTLGFAPI SGMCSKYRSC 430 440 450 460 470 480 TINEDTGLGL AFTIAHESGH NFGMIHDGEG NPCRKAEGNI MSPTLTGNNG VFSWSSCSRQ 490 500 510 520 530 540 YLKKFLSTPQ AGCLVDEPKQ AGQYKYPDKL PGQIYDADTQ CKWQFGAKAK LCSLGFVKDI 550 560 570 580 590 600 CKSLWCHRVG HRCETKFMPA AEGTVCGLSM WCRQGQCVKF GELGPRPIHG QWSAWSKWSE 610 620 630 640 650 660 CSRTCGGGVK FQERHCNNPK PQYGGIFCPG SSRIYQLCNI NPCNENSLDF RAQQCAEYNS 670 680 690 700 710 720 KPFRGWFYQW KPYTKVEEED RCKLYCKAEN FEFFFAMSGK VKDGTPCSPN KNDVCIDGVC 730 740 750 760 770 780 ELVGCDHELG SKAVSDACGV CKGDNSTCKF YKGLYLNQHK ANEYYPVVLI PAGARSIEIQ 790 800 810 820 830 840 ELQVSSSYLA VRSLSQKYYL TGGWSIDWPG EFPFAGTTFE YQRSFNRPER LYAPGPTNET 850 860 870 880 890 900 LVFEILMQGK NPGIAWKYAL PKVMNGTPPA TKRPAYTWSI VQSECSVSCG GGYINVKAIC 910 920 930 940 950 960 LRDQNTQVNS SFCSAKTKPV TEPKICNAFS CPAYWMPGEW STCSKACAGG QQSRKIQCVQ 970 980 990 1000 1010 1020 KKPFQKEEAV LHSLCPVSTP TQVQACNSHA CPPQWSLGPW SQCSKTCGRG VRKRELLCKG 1030 1040 1050 1060 1070 1080 SAAETLPESQ CTSLPRPELQ EGCVLGRCPK NSRLQWVASS WSECSATCGL GVRKREMKCS 1090 1100 1110 1120 1130 1140 EKGFQGKLIT FPERRCRNIK KPNLDLEETC NRRACPAHPV YNMVAGWYSL PWQQCTVTCG 1150 1160 1170 1180 1190 1200 GGVQTRSVHC VQQGRPSSSC LLHQKPPVLR ACNTNFCPAP EKREDPSCVD FFNWCHLVPQ 1210 1220 HGVCNHKFYG KQCCKSCTRK I
	Isoform 2. Checksum: D90D972FB37675A8	FASTA	1,082	119,742
	10 20 30 40 50 60 MECALLLACA FPAAGSGPPR GLAGLGRVAK ALQLCCLCCA SVAAALASDS SSGASGLNDD 70 80 90 100 110 120 YVFVTPVEVD SAGSYISHDI LHNGRKKRSA QNARSSLHYR FSAFGQELHL ELKPSAILSS 130 140 150 160 170 180 HFIVQVLGKD GASETQKPEV QQCFYQGFIR NDSSSSVAVS TCAGLSGLIR TRKNEFLISP 190 200 210 220 230 240 LPQLLAQEHN HSSPAGHHPH VLYKRTAEEK IQRYRGYPGS GRNYPGYSPS HIPHASQSRE 250 260 270 280 290 300 TEYHHRRLQK QHFCGRRKKY APKPPTEDTY LRFDEYGSSG RPRRSAGKSQ KGLNVETLVV 310 320 330 340 350 360 ADKKMVEKHG KGNVTTYILT VMNMVSGLFK DGTIGSDINV VVVSLILLEQ EPGGLLINHH 370 380 390 400 410 420 ADQSLNSFCQ WQSALIGKNG KRHDHAILLT GFDICSWKNE PCDTLGFAPI SGMCSKYRSC 430 440 450 460 470 480 TINEDTGLGL AFTIAHESGH NFGMIHDGEG NPCRKAEGNI MSPTLTGNNG VFSWSSCSRQ 490 500 510 520 530 540 YLKKFLSTPQ AGCLVDEPKQ AGQYKYPDKL PGQIYDADTQ CKWQFGAKAK LCSLGFVKDI 550 560 570 580 590 600 CKSLWCHRVG HRCETKFMPA AEGTVCGLSM WCRQGQCVKF GELGPRPIHG QWSAWSKWSE 610 620 630 640 650 660 CSRTCGGGVK FQERHCNNPK PQYGGIFCPG SSRIYQLCNI NPCNENSLDF RAQQCAEYNS 670 680 690 700 710 720 KPFRGWFYQW KPYTKVEEED RCKLYCKAEN FEFFFAMSGK VKDGTPCSPN KNDVCIDGVC 730 740 750 760 770 780 ELVGCDHELG SKAVSDACGV CKGDNSTCKF YKGLYLNQHK ANEYYPVVLI PAGARSIEIQ 790 800 810 820 830 840 ELQVSSSYLA VRSLSQKYYL TGGWSIDWPG EFPFAGTTFE YQRSFNRPER LYAPGPTNET 850 860 870 880 890 900 LVFEILMQGK NPGIAWKYAL PKVMNGTPPA TKRPAYTWSI VQSECSVSCG GGYINVKAIC 910 920 930 940 950 960 LRDQNTQVNS SFCSAKTKPV TEPKICNAFS CPAYWMPGEW STCSKACAGG QQSRKIQCVQ 970 980 990 1000 1010 1020 KKPFQKEEAV LHSLCPVSTP TQVQACNSHA CPPQWSLGPW SQCSKTCGRG VRKRELLCKG 1030 1040 1050 1060 1070 1080 SAAETLPESQ CTSLPRPELQ EGCVLGRCPK NSRLQWVASS WSEVWIRSHC WVRRLRPSWL TQ

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: 11867212] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), VARIANTS TYR-191 AND SER-946.
[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] (ISOFORM 1), VARIANT ILE-769. Tissue: Placenta.
[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: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 761-1221 (ISOFORM 1), VARIANT ARG-1080. Tissue: Cerebellum.
[4]	"The consensus coding sequences of human breast and colorectal cancers." Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E. Science 314:268-274(2006) [PubMed: 16959974] [Abstract] Cited for: VARIANTS [LARGE SCALE ANALYSIS] LYS-382 AND THR-455.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	AJ311903 mRNA. Translation: CAC83612.1. BC063283 mRNA. Translation: AAH63283.1. AK122677 mRNA. Translation: BAC85503.1. Different initiation.
IPI	IPI00291532. IPI00411930.
RefSeq	NP_955387.1.
UniGene	Hs.188746
3D structure databases
ModBase	Search...
Protein-protein interaction databases
STRING	Q8TE60.
Protein family/group databases
MEROPS	M12.028.
Proteomic databases
PRIDE	Q8TE60.
Genome annotation databases
Ensembl	ENST00000282849; ENSP00000282849; ENSG00000140873; Homo sapiens. [Genome view]
GeneID	170692.
KEGG	hsa:170692.
UCSC	uc002ffc.2. human. uc002ffe.1. human.
Organism-specific databases
CTD	170692.
GeneCards	GC16M075873.
HGNC	HGNC:17110. ADAMTS18.
MIM	607512. gene.
PharmGKB	PA24544.
GenAtlas	Search...
Phylogenomic databases
HOGENOM	HBG356151.
HOVERGEN	Q8TE60.
InParanoid	Q8TE60.
Gene expression databases
ArrayExpress	Q8TE60.
Bgee	Q8TE60.
CleanEx	HS_ADAMTS18.
Genevestigator	Q8TE60.
GermOnline	ENSG00000140873. Homo sapiens.
Family and domain databases
InterPro	IPR010294. ADAM_spacer1. IPR001590. Peptidase_M12B. IPR013273. Peptidase_M12B_ADAM-TS. IPR002870. Peptidase_M12B_N. IPR010909. PLAC. IPR000884. Thrombospondin_1_rpt. [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. 5 hits. [Graphical view]
PRINTS	PR01857. ADAMTSFAMILY.
SMART	SM00209. TSP1. 6 hits. [Graphical view]
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. False negative. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	89110.
SOURCE	Search...

Entry information

Entry name

ATS18_HUMAN

Accession

Primary (citable) accession number: Q8TE60
Secondary accession number(s): Q6P4R5, Q6ZWJ9

Entry history

Integrated into UniProtKB/Swiss-Prot:	March 25, 2003
Last sequence update:	September 27, 2005
Last modified:	December 15, 2009
This is version 75 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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.