| IED ID | IndEnz0002001100 |
| Enzyme Type ID | protease001100 |
| Protein Name |
Tubulinyl-Tyr carboxypeptidase 1 EC 3.4.17.17 Tubulin carboxypeptidase 1 Tyrosine carboxypeptidase 1 TTCP 1 Vasohibin-1 |
| Gene Name | VASH1 KIAA1036 VASH |
| Organism | Homo sapiens (Human) |
| Taxonomic Lineage | cellular organisms Eukaryota Opisthokonta Metazoa Eumetazoa Bilateria Deuterostomia Chordata Craniata Vertebrata Gnathostomata (jawed vertebrates) Teleostomi Euteleostomi Sarcopterygii Dipnotetrapodomorpha Tetrapoda Amniota Mammalia Theria Eutheria Boreoeutheria Euarchontoglires Primates Haplorrhini Simiiformes Catarrhini Hominoidea (apes) Hominidae (great apes) Homininae Homo Homo sapiens (Human) |
| Enzyme Sequence | MPGGKKVAGGGSSGATPTSAAATAPSGVRRLETSEGTSAQRDEEPEEEGEEDLRDGGVPFFVNRGGLPVDEATWERMWKHVAKIHPDGEKVAQRIRGATDLPKIPIPSVPTFQPSTPVPERLEAVQRYIRELQYNHTGTQFFEIKKSRPLTGLMDLAKEMTKEALPIKCLEAVILGIYLTNSMPTLERFPISFKTYFSGNYFRHIVLGVNFAGRYGALGMSRREDLMYKPPAFRTLSELVLDFEAAYGRCWHVLKKVKLGQSVSHDPHSVEQIEWKHSVLDVERLGRDDFRKELERHARDMRLKIGKGTGPPSPTKDRKKDVSSPQRAQSSPHRRNSRSERRPSGDKKTSEPKAMPDLNGYQIRV |
| Enzyme Length | 365 |
| Uniprot Accession Number | Q7L8A9 |
| Absorption | |
| Active Site | ACT_SITE 169; /evidence="ECO:0000269|PubMed:29146869, ECO:0000305|PubMed:26794318"; ACT_SITE 204; /evidence="ECO:0000305|PubMed:26794318"; ACT_SITE 221; /evidence="ECO:0000305|PubMed:26794318" |
| Activity Regulation | |
| Binding Site | |
| Calcium Binding | |
| catalytic Activity | CATALYTIC ACTIVITY: Reaction=C-terminal L-alpha-aminoacyl-L-glutamyl-L-glutamyl-L-tyrosyl-[tubulin] + H2O = C-terminal L-alpha-aminoacyl-L-glutamyl-L-glutamyl-[tubulin] + L-tyrosine; Xref=Rhea:RHEA:57444, Rhea:RHEA-COMP:16434, Rhea:RHEA-COMP:16435, ChEBI:CHEBI:15377, ChEBI:CHEBI:58315, ChEBI:CHEBI:149554, ChEBI:CHEBI:149555; EC=3.4.17.17; Evidence={ECO:0000269|PubMed:29146869, ECO:0000269|PubMed:31171830, ECO:0000269|PubMed:31235910}; |
| DNA Binding | |
| EC Number | 3.4.17.17 |
| Enzyme Function | FUNCTION: Tyrosine carboxypeptidase that removes the C-terminal tyrosine residue of alpha-tubulin, thereby regulating microtubule dynamics and function (PubMed:29146869, PubMed:31270470, PubMed:31235910, PubMed:31171830, PubMed:31235911). Critical for spindle function and accurate chromosome segregation during mitosis since microtuble detyronisation regulates mitotic spindle length and postioning (PubMed:31171830). Acts as an angiogenesis inhibitor: inhibits migration, proliferation and network formation by endothelial cells as well as angiogenesis (PubMed:15467828, PubMed:16488400, PubMed:16707096, PubMed:19204325). This inhibitory effect is selective to endothelial cells as it does not affect the migration of smooth muscle cells or fibroblasts (PubMed:15467828, PubMed:16488400, PubMed:16707096). {ECO:0000269|PubMed:15467828, ECO:0000269|PubMed:16488400, ECO:0000269|PubMed:16707096, ECO:0000269|PubMed:19204325, ECO:0000269|PubMed:29146869, ECO:0000269|PubMed:31171830, ECO:0000269|PubMed:31235910, ECO:0000269|PubMed:31235911, ECO:0000269|PubMed:31270470}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | |
| Features | Active site (3); Alternative sequence (2); Beta strand (10); Chain (1); Compositional bias (1); Erroneous gene model prediction (1); Erroneous initiation (1); Helix (8); Mutagenesis (25); Region (3); Site (2); Turn (1) |
| Keywords | 3D-structure;Alternative splicing;Carboxypeptidase;Cell cycle;Cytoplasm;Growth arrest;Hydrolase;Protease;Reference proteome;Secreted;Ubl conjugation |
| Interact With | P49366; Q8N300 |
| Induction | INDUCTION: By VEGF. {ECO:0000269|PubMed:15467828, ECO:0000269|PubMed:15649403}. |
| Subcellular Location | SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:15467828, ECO:0000269|PubMed:27879017}. Secreted {ECO:0000269|PubMed:15467828, ECO:0000269|PubMed:16707096, ECO:0000269|PubMed:20736312, ECO:0000269|PubMed:27879017}. Note=Mainly localizes in the cytoplasm (PubMed:27879017). Some fraction is secreted via a non-canonical secretion system; interaction with SVBP promotes secretion (PubMed:27879017). {ECO:0000269|PubMed:27879017}. |
| Modified Residue | |
| Post Translational Modification | PTM: 2 major forms (42 and 36 kDa) and 2 minors (32 and 27 kDa) may be processed by proteolytic cleavage (PubMed:16488400). The largest form (42 kDa) seems to be secreted and the other major form (63 kDa) seems to accumulate within the cells or pericellular milieu (PubMed:16488400). Polypeptide consisting of Met-77 to Arg-318 may correspond to the 27 kDa form and that consisting of Met-77 to Val-365 may correspond to the 36 kDa form (PubMed:16488400). {ECO:0000269|PubMed:16488400}.; PTM: Ubiquitinated in vitro. {ECO:0000269|PubMed:20736312}. |
| Signal Peptide | |
| Structure 3D | Electron microscopy (1); X-ray crystallography (13) |
| Cross Reference PDB | 6J4U; 6J7B; 6J8F; 6J8N; 6J8O; 6J91; 6J9H; 6K81; 6LPG; 6NVQ; 6OCF; 6OCG; 6OCH; 6WSL; |
| Mapped Pubmed ID | 18325046; 19037993; 19057892; 19179360; 19498005; 19587360; 19682397; 20035291; 20133819; 20167561; 21302448; 22101788; 22438034; 22564651; 22569265; 22675166; 22865127; 23056314; 23100270; 23324451; 23591203; 23651239; 24366689; 24390792; 24444468; 24748406; 25145408; 25184477; 25275025; 25416956; 25468068; 25797264; 25843115; 25957412; 26460696; 26666821; 26893100; 27080222; 27169581; 27325558; 27842054; 28287633; 28314285; 28656230; 29057763; 29146868; 30213517; 30254211; 31091528; 31823788; 31908845; 32272864; 32341517; 32494966; 32773040; 33021501; 33052495; 33231681; 33491841; 34819292; 7452228; |
| Motif | |
| Gene Encoded By | |
| Mass | 40,957 |
| Kinetics | BIOPHYSICOCHEMICAL PROPERTIES: Kinetic parameters: KM=7.9 uM for alpha-tubulin C-terminal tail {ECO:0000269|PubMed:31235910}; Note=kcat is 44.5 min(-1) for alpha-tubulin C-terminal tail. {ECO:0000269|PubMed:31235910}; |
| Metal Binding | |
| Rhea ID | RHEA:57444 |
| Cross Reference Brenda |