Q9UKP5 (ATS6_HUMAN) Reviewed, UniProtKB/Swiss-Prot
Last modified
May 1, 2013.
Version 120.
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 6 Short name=ADAM-TS 6 Short name=ADAM-TS6 Short name=ADAMTS-6 EC=3.4.24.- | ||
| Gene names |
| ||
| Organism | Homo sapiens (Human) [Reference 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 | 1117 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 at low levels in placenta and barely detectable in a number of other tissues. |
| Induction | Isoform 1 and isoform 2 expressions are up-regulated by TNF in retinal pigment epithelial cells. Ref.2 Ref.6 |
| 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 1 PLAC domain. Contains 5 TSP type-1 domains. |
Ontologies
| Keywords | |
|---|---|
| Cellular component | Extracellular matrix Secreted |
| Coding sequence diversity | Alternative splicing |
| 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 metallopeptidase activityTraceable author statement Ref.1. Source: ProtInc zinc ion bindingInferred from electronic annotation. Source: InterPro |
| Complete GO annotation... | |
Alternative products
| This entry describes 4 isoforms produced by alternative splicing. [Align] [Select] | ||||||
| Isoform 1 (identifier: Q9UKP5-1) Also known as: Variant 2; 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: Q9UKP5-2) Also known as: Variant 1; The sequence of this isoform differs from the canonical sequence as follows: 422-504: TKGHEAAKLM...GATSRQCKYG → RKVMKQQNYGSSHYCEYQSFFLVCLQSRFHHQLFR 860-908: VQRQEVVCKR...CPPEWFIGDW → KMPTRQPTQR...SCNLAKETLL 909-1117: Missing. | ||||||
| Note: Contains critical point mutations in the region encoding the catalytic domain as well as 2 point mutations compared with genomic sequence. May either be a rare polymorphism or may have arisen through a combination of aberrant RNA editing and point mutation/sequencing error. | ||||||
| Isoform 3 (identifier: Q9UKP5-3) Also known as: Variant 3; The sequence of this isoform differs from the canonical sequence as follows: 457-468: DSGRGTCLDNEP → EFLKLGDSISGS 469-1117: Missing. | ||||||
| Isoform 4 (identifier: Q9UKP5-4) Also known as: Variant 4; The sequence of this isoform differs from the canonical sequence as follows: 283-292: AKLYRDSSLG → RLPNFTVIPA 293-1117: Missing. |
Sequence annotation (Features)
| Feature key | Position(s) | Length | Description | Graphical view | Feature identifier | ||||||
Molecule processing | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Signal peptide | 1 – 21 | 21 | Potential | ||||||||
| Propeptide | 22 – 244 | 223 | By similarity | PRO_0000029174 | |||||||
| Chain | 245 – 1117 | 873 | A disintegrin and metalloproteinase with thrombospondin motifs 6 | PRO_0000029175 | |||||||
Regions | |||||||||||
| Domain | 250 – 468 | 219 | Peptidase M12B | ||||||||
| Domain | 495 – 557 | 63 | Disintegrin | ||||||||
| Domain | 558 – 613 | 56 | TSP type-1 1 | ||||||||
| Domain | 840 – 900 | 61 | TSP type-1 2 | ||||||||
| Domain | 902 – 960 | 59 | TSP type-1 3 | ||||||||
| Domain | 962 – 1007 | 46 | TSP type-1 4 | ||||||||
| Domain | 1018 – 1073 | 56 | TSP type-1 5 | ||||||||
| Domain | 1079 – 1117 | 39 | PLAC | ||||||||
| Region | 717 – 843 | 127 | Spacer | ||||||||
Sites | |||||||||||
| Active site | 404 | 1 | By similarity | ||||||||
| Metal binding | 403 | 1 | Zinc; catalytic By similarity | ||||||||
| Metal binding | 407 | 1 | Zinc; catalytic By similarity | ||||||||
| Metal binding | 413 | 1 | Zinc; catalytic By similarity | ||||||||
Amino acid modifications | |||||||||||
| Glycosylation | 99 | 1 | N-linked (GlcNAc...) Potential | ||||||||
| Glycosylation | 172 | 1 | N-linked (GlcNAc...) Potential | ||||||||
| Glycosylation | 222 | 1 | N-linked (GlcNAc...) Potential | ||||||||
| Glycosylation | 234 | 1 | N-linked (GlcNAc...) Potential | ||||||||
| Glycosylation | 724 | 1 | N-linked (GlcNAc...) Potential | ||||||||
| Glycosylation | 956 | 1 | N-linked (GlcNAc...) Potential | ||||||||
| Disulfide bond | 381 ↔ 463 | By similarity | |||||||||
| Disulfide bond | 420 ↔ 447 | By similarity | |||||||||
| Disulfide bond | 570 ↔ 607 | By similarity | |||||||||
| Disulfide bond | 574 ↔ 612 | By similarity | |||||||||
| Disulfide bond | 585 ↔ 597 | By similarity | |||||||||
| Disulfide bond | 911 ↔ 954 | By similarity | |||||||||
| Disulfide bond | 915 ↔ 959 | By similarity | |||||||||
| Disulfide bond | 926 ↔ 943 | By similarity | |||||||||
Natural variations | |||||||||||
| Alternative sequence | 283 – 292 | 10 | AKLYRDSSLG → RLPNFTVIPA in isoform 4. | VSP_037093 | |||||||
| Alternative sequence | 293 – 1117 | 825 | Missing in isoform 4. | VSP_037094 | |||||||
| Alternative sequence | 422 – 504 | 83 | TKGHE…QCKYG → RKVMKQQNYGSSHYCEYQSF FLVCLQSRFHHQLFR in isoform 2. | VSP_037095 | |||||||
| Alternative sequence | 457 – 468 | 12 | DSGRG…LDNEP → EFLKLGDSISGS in isoform 3. | VSP_037096 | |||||||
| Alternative sequence | 469 – 1117 | 649 | Missing in isoform 3. | VSP_037097 | |||||||
| Alternative sequence | 860 – 908 | 49 | VQRQE…FIGDW → KMPTRQPTQRARWRTKHILS YALCLLKKLIGNISCRFASS CNLAKETLL in isoform 2. | VSP_037098 | |||||||
| Alternative sequence | 909 – 1117 | 209 | Missing in isoform 2. | VSP_037099 | |||||||
Experimental info | |||||||||||
| Sequence conflict | 4 | 1 | L → S in AAW47399. Ref.2 | ||||||||
| Sequence conflict | 24 | 1 | D → G in AAW47398. Ref.2 | ||||||||
| Sequence conflict | 83 | 1 | S → P in AAW47398. Ref.2 | ||||||||
| Sequence conflict | 229 | 1 | Y → H in AAW47397. Ref.2 | ||||||||
| Sequence conflict | 406 | 1 | G → V in AAD56357. Ref.1 | ||||||||
| Sequence conflict | 426 | 1 | E → G in AAD56357. Ref.1 | ||||||||
| Sequence conflict | 426 | 1 | E → G in AAW47397. Ref.2 | ||||||||
| Sequence conflict | 588 – 589 | 2 | PA → LK in BAD92922. Ref.4 | ||||||||
| Sequence conflict | 712 | 1 | D → G in AAD56357. Ref.1 | ||||||||
Sequences
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References
| « Hide 'large scale' references | |
| [1] | "ADAM-TS5, ADAM-TS6, and ADAM-TS7, novel members of a new family of zinc metalloproteases." Hurskainen T.L., Hirohata S., Seldin M.F., Apte S.S. J. Biol. Chem. 274:25555-25563(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). |
| [2] | "Analysis of full length ADAMTS6 transcript reveals alternative splicing and a role for the 5' untranslated region in translational control." Bevitt D.J., Li Z., Lindrop J.L., Barker M.D., Clarke M.P., McKie N. Gene 359:99-110(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 3 AND 4), INDUCTION. |
| [3] | "The DNA sequence and comparative analysis of human chromosome 5." Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S., Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M., She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S. Rubin E.M.Nature 431:268-274(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. |
| [4] | Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S., Ohara O., Nagase T., Kikuno R.F. Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 588-1117 (ISOFORM 1). Tissue: Brain. |
| [5] | "The full-ORF clone resource of the German cDNA consortium." Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I. BMC Genomics 8:399-399(2007) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 804-1117 (ISOFORM 1). Tissue: Uterus. |
| [6] | "Expression of ADAMTS metalloproteinases in the retinal pigment epithelium derived cell line ARPE-19: transcriptional regulation by TNFalpha." Bevitt D.J., Mohamed J., Catterall J.B., Li Z., Arris C.E., Hiscott P., Sheridan C., Langton K.P., Barker M.D., Clarke M.P., McKie N. Biochim. Biophys. Acta 1626:83-91(2003) [PubMed] [Europe PMC] [Abstract] Cited for: INDUCTION. |
| + | Additional computationally mapped references. |
Cross-references
Sequence databases | |
|---|---|
| EMBL GenBank DDBJ | AF140674 mRNA. Translation: AAD56357.1. AY692424 mRNA. Translation: AAW47397.1. AY692425 mRNA. Translation: AAW47398.1. AY692426 mRNA. Translation: AAW47399.1. AC008847 Genomic DNA. No translation available. AC008868 Genomic DNA. No translation available. AC025176 Genomic DNA. No translation available. AC025186 Genomic DNA. No translation available. AC099505 Genomic DNA. No translation available. AB209685 mRNA. Translation: BAD92922.1. CR749356 mRNA. Translation: CAH18209.1. |
| IPI | IPI00296965. IPI00658047. IPI00929566. IPI00967682. |
| RefSeq | NP_922932.2. NM_197941.2. |
| UniGene | Hs.482291. |
3D structure databases | |
| ProteinModelPortal | Q9UKP5. |
| ModBase | Search... |
Protein family/group databases | |
| MEROPS | M12.230. |
PTM databases | |
| PhosphoSite | Q9UKP5. |
Polymorphism databases | |
| DMDM | 229462816. |
Proteomic databases | |
| PaxDb | Q9UKP5. |
| PRIDE | Q9UKP5. |
Protocols and materials databases | |
| StructuralBiologyKnowledgebase | Search... |
Genome annotation databases | |
| Ensembl | ENST00000381052; ENSP00000424377; ENSG00000049192. ENST00000381055; ENSP00000370443; ENSG00000049192. ENST00000536360; ENSP00000440995; ENSG00000049192. |
| GeneID | 11174. |
| KEGG | hsa:11174. |
| UCSC | uc003jtp.3. human. |
Organism-specific databases | |
| CTD | 11174. |
| GeneCards | GC05M064526. |
| HGNC | HGNC:222. ADAMTS6. |
| HPA | HPA027216. |
| MIM | 605008. gene. |
| neXtProt | NX_Q9UKP5. |
| PharmGKB | PA24550. |
| GenAtlas | Search... |
Phylogenomic databases | |
| eggNOG | NOG237764. |
| HOGENOM | HOG000004800. |
| HOVERGEN | HBG004315. |
| KO | K08621. |
| OMA | EKGWCYQ. |
| OrthoDB | EOG4N30N3. |
Gene expression databases | |
| ArrayExpress | Q9UKP5. |
| Bgee | Q9UKP5. |
| CleanEx | HS_ADAMTS6. |
| Genevestigator | Q9UKP5. |
| GermOnline | ENSG00000049192. 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. [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. 5 hits. [Graphical view] |
| SUPFAM | SSF82895. TSP1. 5 hits. |
| PROSITE | PS50215. ADAM_MEPRO. 1 hit. PS00427. DISINTEGRIN_1. False negative. PS50214. DISINTEGRIN_2. False negative. PS50900. PLAC. 1 hit. PS50092. TSP1. 4 hits. PS00142. ZINC_PROTEASE. 1 hit. [Graphical view] |
| ProtoNet | Search... |
Other | |
| GenomeRNAi | 11174. |
| NextBio | 42521. |
| SOURCE | Search... |
Entry information
| Entry name | ATS6_HUMAN | ||||||||
| Accession | Primary (citable) accession number: Q9UKP5 Secondary accession number(s): Q59EX6 Q68DL1 | ||||||||
| 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 5 Human chromosome 5: entries, gene names and cross-references to MIM |
| 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
