Q8TE60 (ATS18_HUMAN) Reviewed, UniProtKB/Swiss-Prot
Last modified
January 25, 2012.
Version 91.
History...
Names·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order
Names·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize orderNames and origin
| Protein names | Recommended name: A disintegrin and metalloproteinase with thrombospondin motifs 18 Short name=ADAM-TS 18 Short name=ADAM-TS18 Short name=ADAMTS-18 EC=3.4.24.- | ||||
| Gene names |
| ||||
| Organism | Homo sapiens (Human) | ||||
| 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 protein 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. |
| Involvement in disease | Defects in ADAMTS18 are the cause of Knobloch syndrome type 2 (KNO2) [MIM:608454]. A developmental disorder primarily characterized by typical eye abnormalities, including high myopia, cataracts, dislocated lens, vitreoretinal degeneration, and retinal detachment, with occipital skull defects, which can range from occipital encephalocele to occult cutis aplasia. Ref.6 |
| Sequence similarities | Contains 1 disintegrin domain. Contains 1 peptidase M12B domain. Contains 1 PLAC domain. Contains 5 TSP type-1 domains. |
| Sequence caution | The sequence BAC85503.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended. The sequence CAC83612.1 differs from that shown. Reason: Probable intron retention. The sequence CAC83612.1 differs from that shown. Reason: Aberrant splicing. |
Ontologies
| Keywords | |
|---|---|
| Cellular component | Extracellular matrix Secreted |
| Coding sequence diversity | Alternative splicing Polymorphism |
| Disease | Disease mutation |
| 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 bindingInferred from electronic annotation. Source: InterPro |
| 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. | ||||||
| Note: No experimental confirmation available. |
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 | 179 | 1 | S → L in KNO2. Ref.6 | VAR_066554 | |||||||
| Natural variant | 191 | 1 | Y → H. Ref.3 Corresponds to variant rs11643211 [ dbSNP | Ensembl ]. | VAR_060231 | |||||||
| Natural variant | 382 | 1 | R → K in a colorectal cancer sample; somatic mutation. Ref.5 | VAR_036152 | |||||||
| Natural variant | 455 | 1 | K → T in a colorectal cancer sample; somatic mutation. Ref.5 | VAR_036153 | |||||||
| Natural variant | 626 | 1 | L → I. Ref.1 Ref.3 Corresponds to variant rs11640912 [ dbSNP | Ensembl ]. | VAR_060232 | |||||||
| Natural variant | 769 | 1 | L → I. Ref.3 Corresponds to variant rs9930984 [ dbSNP | Ensembl ]. | VAR_057083 | |||||||
| Natural variant | 946 | 1 | A → S. Ref.1 Corresponds to variant rs12935394 [ dbSNP | Ensembl ]. | VAR_057084 | |||||||
| Natural variant | 1080 | 1 | S → R. Ref.4 Corresponds to variant rs35478105 [ dbSNP | Ensembl ]. | VAR_057085 | |||||||
| Natural variant | 1159 | 1 | S → T. Corresponds to variant rs3743749 [ dbSNP | Ensembl ]. | VAR_057086 | |||||||
Experimental info | |||||||||||
| Sequence conflict | 410 | 1 | I → T in CAC83612. Ref.1 | ||||||||
Sequences
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References
| « Hide '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 ILE-626 AND SER-946. |
| [2] | "The sequence and analysis of duplication-rich human chromosome 16." Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., Xie G., Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E., Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J. Pennacchio L.A.Nature 432:988-994(2004) [PubMed: 15616553] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. |
| [3] | "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), VARIANTS HIS-191; ILE-626 AND ILE-769. Tissue: Placenta. |
| [4] | "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. 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. |
| [5] | "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. Velculescu V.E.Science 314:268-274(2006) [PubMed: 16959974] [Abstract] Cited for: VARIANTS [LARGE SCALE ANALYSIS] LYS-382 AND THR-455. |
| [6] | "Identification of ADAMTS18 as a gene mutated in Knobloch syndrome." Aldahmesh M.A., Khan A.O., Mohamed J.Y., Alkuraya H., Ahmed H., Bobis S., Al-Mesfer S., Alkuraya F.S. J. Med. Genet. 48:597-601(2011) [PubMed: 21862674] [Abstract] Cited for: VARIANT KNO2 LEU-179. |
| + | Additional computationally mapped references. |
Cross-references
Sequence databases | |
|---|---|
| EMBL GenBank DDBJ | AJ311903 mRNA. Translation: CAC83612.1. Sequence problems. AC009139 Genomic DNA. No translation available. AC010548 Genomic DNA. No translation available. AC025284 Genomic DNA. No translation available. BC063283 mRNA. Translation: AAH63283.1. AK122677 mRNA. Translation: BAC85503.1. Different initiation. |
| IPI | IPI00291532. IPI00411930. |
| RefSeq | NP_955387.1. NM_199355.2. |
| UniGene | Hs.188746. |
3D structure databases | |
| ProteinModelPortal | Q8TE60. |
| SMR | Q8TE60. Positions 290-863, 869-1179. |
| ModBase | Search... |
Protein-protein interaction databases | |
| STRING | Q8TE60. |
Protein family/group databases | |
| MEROPS | M12.028. |
PTM databases | |
| PhosphoSite | Q8TE60. |
Polymorphism databases | |
| DMDM | 296439427. |
Proteomic databases | |
| PRIDE | Q8TE60. |
Protocols and materials databases | |
| StructuralBiologyKnowledgebase | Search... |
Genome annotation databases | |
| Ensembl | ENST00000282849; ENSP00000282849; ENSG00000140873. |
| GeneID | 170692. |
| KEGG | hsa:170692. |
| UCSC | uc002ffc.2. human. uc002ffe.1. human. |
Organism-specific databases | |
| CTD | 170692. |
| GeneCards | GC16M077316. |
| H-InvDB | HIX0026938. |
| HGNC | HGNC:17110. ADAMTS18. |
| HPA | HPA044326. |
| MIM | 607512. gene. 608454. phenotype. |
| neXtProt | NX_Q8TE60. |
| GenAtlas | Search... |
Phylogenomic databases | |
| GeneTree | ENSGT00550000074469. |
| HOGENOM | HBG356151. |
| HOVERGEN | HBG004315. |
| InParanoid | Q8TE60. |
| OMA | SHIPHAS. |
| OrthoDB | EOG4DNF3K. |
| PhylomeDB | 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. IPR024079. MetalloPept_cat_dom. IPR001590. Peptidase_M12B. IPR013273. Peptidase_M12B_ADAM-TS. IPR002870. Peptidase_M12B_N. IPR010909. PLAC. IPR000884. Thrombospondin_1_rpt. [Graphical view] |
| Gene3D | G3DSA:3.40.390.10. G3DSA:3.40.390.10. 1 hit. |
| KO | K08632. |
| 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] |
| SUPFAM | SSF82895. TSP1. 6 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. False negative. [Graphical view] |
| ProtoNet | Search... |
Other | |
| NextBio | 89110. |
| SOURCE | Search... |
Entry information
| Entry name | ATS18_HUMAN | ||||||||
| Accession | Primary (citable) accession number: Q8TE60 Secondary accession number(s): Q6P4R5, Q6ZWJ9 | ||||||||
| Entry 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. | ||||||||
Relevant documents
| Peptidase families Classification of peptidase families and list of entries |
| Human chromosome 16 Human chromosome 16: entries, gene names and cross-references to MIM |
| Human entries with polymorphisms or disease mutations List of human entries with polymorphisms or disease mutations |
| Human polymorphisms and disease mutations Index of human polymorphisms and disease mutations |
| MIM cross-references Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot |
| SIMILARITY comments Index of protein domains and families |

Clusters with