VASH1_HUMAN
ID VASH1_HUMAN Reviewed; 365 AA.
AC Q7L8A9; Q96H02; Q9UBF4; Q9Y629;
DT 12-APR-2005, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 03-AUG-2022, entry version 133.
DE RecName: Full=Tubulinyl-Tyr carboxypeptidase 1 {ECO:0000305};
DE EC=3.4.17.17 {ECO:0000269|PubMed:29146869, ECO:0000269|PubMed:31171830, ECO:0000269|PubMed:31235910};
DE AltName: Full=Tubulin carboxypeptidase 1 {ECO:0000303|PubMed:29146869};
DE AltName: Full=Tyrosine carboxypeptidase 1 {ECO:0000305};
DE Short=TTCP 1 {ECO:0000305};
DE AltName: Full=Vasohibin-1 {ECO:0000303|PubMed:15467828};
GN Name=VASH1 {ECO:0000312|HGNC:HGNC:19964};
GN Synonyms=KIAA1036 {ECO:0000303|PubMed:10470851}, VASH;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=10470851; DOI=10.1093/dnares/6.3.197;
RA Kikuno R., Nagase T., Ishikawa K., Hirosawa M., Miyajima N., Tanaka A.,
RA Kotani H., Nomura N., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XIV. The
RT complete sequences of 100 new cDNA clones from brain which code for large
RT proteins in vitro.";
RL DNA Res. 6:197-205(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Spinal cord;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12508121; DOI=10.1038/nature01348;
RA Heilig R., Eckenberg R., Petit J.-L., Fonknechten N., Da Silva C.,
RA Cattolico L., Levy M., Barbe V., De Berardinis V., Ureta-Vidal A.,
RA Pelletier E., Vico V., Anthouard V., Rowen L., Madan A., Qin S., Sun H.,
RA Du H., Pepin K., Artiguenave F., Robert C., Cruaud C., Bruels T.,
RA Jaillon O., Friedlander L., Samson G., Brottier P., Cure S., Segurens B.,
RA Aniere F., Samain S., Crespeau H., Abbasi N., Aiach N., Boscus D.,
RA Dickhoff R., Dors M., Dubois I., Friedman C., Gouyvenoux M., James R.,
RA Madan A., Mairey-Estrada B., Mangenot S., Martins N., Menard M., Oztas S.,
RA Ratcliffe A., Shaffer T., Trask B., Vacherie B., Bellemere C., Belser C.,
RA Besnard-Gonnet M., Bartol-Mavel D., Boutard M., Briez-Silla S.,
RA Combette S., Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C.,
RA Muselet D., Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P.,
RA Trybou A., Vega-Czarny N., Bataille E., Bluet E., Bordelais I., Dubois M.,
RA Dumont C., Guerin T., Haffray S., Hammadi R., Muanga J., Pellouin V.,
RA Robert D., Wunderle E., Gauguet G., Roy A., Sainte-Marthe L., Verdier J.,
RA Verdier-Discala C., Hillier L.W., Fulton L., McPherson J., Matsuda F.,
RA Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W., Quetier F.,
RA Waterston R., Hood L., Weissenbach J.;
RT "The DNA sequence and analysis of human chromosome 14.";
RL Nature 421:601-607(2003).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND INDUCTION.
RX PubMed=15467828; DOI=10.1172/jci200421152;
RA Watanabe K., Hasegawa Y., Yamashita H., Shimizu K., Ding Y., Abe M.,
RA Ohta H., Imagawa K., Hojo K., Maki H., Sonoda H., Sato Y.;
RT "Vasohibin as an endothelium-derived negative feedback regulator of
RT angiogenesis.";
RL J. Clin. Invest. 114:898-907(2004).
RN [6]
RP ALTERNATIVE SPLICING, AND INDUCTION.
RX PubMed=15649403; DOI=10.1016/j.bbrc.2004.12.073;
RA Shimizu K., Watanabe K., Yamashita H., Abe M., Yoshimatsu H., Ohta H.,
RA Sonoda H., Sato Y.;
RT "Gene regulation of a novel angiogenesis inhibitor, vasohibin, in
RT endothelial cells.";
RL Biochem. Biophys. Res. Commun. 327:700-706(2005).
RN [7]
RP FUNCTION, CLEAVAGE SITE, REGION, AND MUTAGENESIS OF ARG-29 AND ARG-76.
RX PubMed=16488400; DOI=10.1016/j.bbrc.2006.01.185;
RA Sonoda H., Ohta H., Watanabe K., Yamashita H., Kimura H., Sato Y.;
RT "Multiple processing forms and their biological activities of a novel
RT angiogenesis inhibitor vasohibin.";
RL Biochem. Biophys. Res. Commun. 342:640-646(2006).
RN [8]
RP FUNCTION, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=16707096; DOI=10.1016/j.bbrc.2006.04.176;
RA Yamashita H., Abe M., Watanabe K., Shimizu K., Moriya T., Sato A.,
RA Satomi S., Ohta H., Sonoda H., Sato Y.;
RT "Vasohibin prevents arterial neointimal formation through angiogenesis
RT inhibition.";
RL Biochem. Biophys. Res. Commun. 345:919-925(2006).
RN [9]
RP FUNCTION.
RX PubMed=19204325; DOI=10.1182/blood-2008-07-170316;
RA Kimura H., Miyashita H., Suzuki Y., Kobayashi M., Watanabe K., Sonoda H.,
RA Ohta H., Fujiwara T., Shimosegawa T., Sato Y.;
RT "Distinctive localization and opposed roles of vasohibin-1 and vasohibin-2
RT in the regulation of angiogenesis.";
RL Blood 113:4810-4818(2009).
RN [10]
RP INTERACTION WITH SVBP, SUBCELLULAR LOCATION, AND UBIQUITINATION.
RX PubMed=20736312; DOI=10.1242/jcs.067538;
RA Suzuki Y., Kobayashi M., Miyashita H., Ohta H., Sonoda H., Sato Y.;
RT "Isolation of a small vasohibin-binding protein (SVBP) and its role in
RT vasohibin secretion.";
RL J. Cell Sci. 123:3094-3101(2010).
RN [11]
RP IDENTIFICATION AS A PROTEASE, AND ACTIVE SITES.
RX PubMed=26794318; DOI=10.1093/bioinformatics/btv761;
RA Sanchez-Pulido L., Ponting C.P.;
RT "Vasohibins: new transglutaminase-like cysteine proteases possessing a non-
RT canonical Cys-His-Ser catalytic triad.";
RL Bioinformatics 32:1441-1445(2016).
RN [12]
RP SUBCELLULAR LOCATION, AND INTERACTION WITH SVBP.
RX PubMed=27879017; DOI=10.1002/pro.3089;
RA Kadonosono T., Yimchuen W., Tsubaki T., Shiozawa T., Suzuki Y.,
RA Kuchimaru T., Sato Y., Kizaka-Kondoh S.;
RT "Domain architecture of vasohibins required for their chaperone-dependent
RT unconventional extracellular release.";
RL Protein Sci. 26:452-463(2017).
RN [13]
RP FUNCTION, CATALYTIC ACTIVITY, INTERACTION WITH SVBP, ACTIVE SITE, AND
RP MUTAGENESIS OF CYS-169.
RX PubMed=29146869; DOI=10.1126/science.aao5676;
RA Nieuwenhuis J., Adamopoulos A., Bleijerveld O.B., Mazouzi A., Stickel E.,
RA Celie P., Altelaar M., Knipscheer P., Perrakis A., Blomen V.A.,
RA Brummelkamp T.R.;
RT "Vasohibins encode tubulin detyrosinating activity.";
RL Science 358:1453-1456(2017).
RN [14]
RP FUNCTION, AND MUTAGENESIS OF LYS-145 AND ARG-222.
RX PubMed=31235911; DOI=10.1038/s41594-019-0241-y;
RA Wang N., Bosc C., Ryul Choi S., Boulan B., Peris L., Olieric N., Bao H.,
RA Krichen F., Chen L., Andrieux A., Olieric V., Moutin M.J., Steinmetz M.O.,
RA Huang H.;
RT "Structural basis of tubulin detyrosination by the vasohibin-SVBP enzyme
RT complex.";
RL Nat. Struct. Mol. Biol. 26:571-582(2019).
RN [15] {ECO:0007744|PDB:6J7B, ECO:0007744|PDB:6J8F, ECO:0007744|PDB:6J8N, ECO:0007744|PDB:6J91, ECO:0007744|PDB:6J9H}
RP X-RAY CRYSTALLOGRAPHY (1.62 ANGSTROMS) OF 57-306 IN COMPLEX WITH SVBP,
RP CATALYTIC ACTIVITY, FUNCTION, MUTAGENESIS OF 74-TRP--TRP-78; TYR-134;
RP LYS-146; 165-LEU-PRO-166; CYS-169; HIS-204; SER-221 AND ARG-222, AND
RP INTERACTION WITH SVBP.
RX PubMed=31171830; DOI=10.1038/s41422-019-0187-y;
RA Liao S., Rajendraprasad G., Wang N., Eibes S., Gao J., Yu H., Wu G., Tu X.,
RA Huang H., Barisic M., Xu C.;
RT "Molecular basis of vasohibins-mediated detyrosination and its impact on
RT spindle function and mitosis.";
RL Cell Res. 29:533-547(2019).
RN [16] {ECO:0007744|PDB:6NVQ}
RP X-RAY CRYSTALLOGRAPHY (2.10 ANGSTROMS) OF 61-301 IN COMPLEX WITH SVBP,
RP INTERACTION WITH SVBP, FUNCTION, AND MUTAGENESIS OF TYR-134; LYS-146;
RP LYS-168; CYS-169; LYS-194; ARG-203; HIS-204; SER-221; ARG-222; ARG-223;
RP LEU-226; TYR-247; LYS-258 AND LYS-276.
RX PubMed=31270470; DOI=10.1038/s41594-019-0254-6;
RA Adamopoulos A., Landskron L., Heidebrecht T., Tsakou F., Bleijerveld O.B.,
RA Altelaar M., Nieuwenhuis J., Celie P.H.N., Brummelkamp T.R., Perrakis A.;
RT "Crystal structure of the tubulin tyrosine carboxypeptidase complex VASH1-
RT SVBP.";
RL Nat. Struct. Mol. Biol. 26:567-570(2019).
RN [17] {ECO:0007744|PDB:6OCF, ECO:0007744|PDB:6OCG, ECO:0007744|PDB:6OCH}
RP X-RAY CRYSTALLOGRAPHY (1.83 ANGSTROMS) OF 58-305 IN COMPLEX WITH SVBP,
RP INTERACTION WITH SVBP, FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL
RP PROPERTIES, AND MUTAGENESIS OF 77-MET--VAL-81; MET-77; VAL-81; TYR-134;
RP PHE-141; LYS-146; LYS-168; CYS-169; LYS-194; ARG-203; HIS-204; SER-221;
RP ARG-222; LYS-256; LYS-258 AND LYS-276.
RX PubMed=31235910; DOI=10.1038/s41594-019-0242-x;
RA Li F., Hu Y., Qi S., Luo X., Yu H.;
RT "Structural basis of tubulin detyrosination by vasohibins.";
RL Nat. Struct. Mol. Biol. 26:583-591(2019).
CC -!- FUNCTION: Tyrosine carboxypeptidase that removes the C-terminal
CC tyrosine residue of alpha-tubulin, thereby regulating microtubule
CC dynamics and function (PubMed:29146869, PubMed:31270470,
CC PubMed:31235910, PubMed:31171830, PubMed:31235911). Critical for
CC spindle function and accurate chromosome segregation during mitosis
CC since microtuble detyronisation regulates mitotic spindle length and
CC postioning (PubMed:31171830). Acts as an angiogenesis inhibitor:
CC inhibits migration, proliferation and network formation by endothelial
CC cells as well as angiogenesis (PubMed:15467828, PubMed:16488400,
CC PubMed:16707096, PubMed:19204325). This inhibitory effect is selective
CC to endothelial cells as it does not affect the migration of smooth
CC muscle cells or fibroblasts (PubMed:15467828, PubMed:16488400,
CC PubMed:16707096). {ECO:0000269|PubMed:15467828,
CC ECO:0000269|PubMed:16488400, ECO:0000269|PubMed:16707096,
CC ECO:0000269|PubMed:19204325, ECO:0000269|PubMed:29146869,
CC ECO:0000269|PubMed:31171830, ECO:0000269|PubMed:31235910,
CC ECO:0000269|PubMed:31235911, ECO:0000269|PubMed:31270470}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=C-terminal L-alpha-aminoacyl-L-glutamyl-L-glutamyl-L-tyrosyl-
CC [tubulin] + H2O = C-terminal L-alpha-aminoacyl-L-glutamyl-L-glutamyl-
CC [tubulin] + L-tyrosine; Xref=Rhea:RHEA:57444, Rhea:RHEA-COMP:16434,
CC Rhea:RHEA-COMP:16435, ChEBI:CHEBI:15377, ChEBI:CHEBI:58315,
CC ChEBI:CHEBI:149554, ChEBI:CHEBI:149555; EC=3.4.17.17;
CC Evidence={ECO:0000269|PubMed:29146869, ECO:0000269|PubMed:31171830,
CC ECO:0000269|PubMed:31235910};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=7.9 uM for alpha-tubulin C-terminal tail
CC {ECO:0000269|PubMed:31235910};
CC Note=kcat is 44.5 min(-1) for alpha-tubulin C-terminal tail.
CC {ECO:0000269|PubMed:31235910};
CC -!- SUBUNIT: Interacts with SVBP; interaction enhances VASH1 tyrosine
CC carboxypeptidase activity. {ECO:0000269|PubMed:20736312,
CC ECO:0000269|PubMed:27879017, ECO:0000269|PubMed:29146869,
CC ECO:0000269|PubMed:31171830, ECO:0000269|PubMed:31235910,
CC ECO:0000269|PubMed:31270470}.
CC -!- INTERACTION:
CC Q7L8A9; P49366: DHPS; NbExp=3; IntAct=EBI-10256546, EBI-741925;
CC Q7L8A9-1; Q8N300: SVBP; NbExp=2; IntAct=EBI-21497569, EBI-21497577;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:15467828,
CC ECO:0000269|PubMed:27879017}. Secreted {ECO:0000269|PubMed:15467828,
CC ECO:0000269|PubMed:16707096, ECO:0000269|PubMed:20736312,
CC ECO:0000269|PubMed:27879017}. Note=Mainly localizes in the cytoplasm
CC (PubMed:27879017). Some fraction is secreted via a non-canonical
CC secretion system; interaction with SVBP promotes secretion
CC (PubMed:27879017). {ECO:0000269|PubMed:27879017}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q7L8A9-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q7L8A9-2; Sequence=VSP_013324, VSP_013325;
CC -!- TISSUE SPECIFICITY: Preferentially expressed in endothelial cells
CC (PubMed:15467828, PubMed:16707096). Highly expressed in fetal organs
CC (PubMed:15467828). Expressed in brain and placenta, and at lower level
CC in heart and kidney (PubMed:15467828). Highly detected in microvessels
CC endothelial cells of atherosclerotic lesions (PubMed:16707096).
CC {ECO:0000269|PubMed:15467828, ECO:0000269|PubMed:16707096}.
CC -!- INDUCTION: By VEGF. {ECO:0000269|PubMed:15467828,
CC ECO:0000269|PubMed:15649403}.
CC -!- PTM: 2 major forms (42 and 36 kDa) and 2 minors (32 and 27 kDa) may be
CC processed by proteolytic cleavage (PubMed:16488400). The largest form
CC (42 kDa) seems to be secreted and the other major form (63 kDa) seems
CC to accumulate within the cells or pericellular milieu
CC (PubMed:16488400). Polypeptide consisting of Met-77 to Arg-318 may
CC correspond to the 27 kDa form and that consisting of Met-77 to Val-365
CC may correspond to the 36 kDa form (PubMed:16488400).
CC {ECO:0000269|PubMed:16488400}.
CC -!- PTM: Ubiquitinated in vitro. {ECO:0000269|PubMed:20736312}.
CC -!- SIMILARITY: Belongs to the transglutaminase-like superfamily. Vasohibin
CC family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAD44361.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
CC Sequence=BAA82988.2; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AB028959; BAA82988.2; ALT_INIT; mRNA.
DR EMBL; AL832588; CAD89941.1; -; mRNA.
DR EMBL; AC007376; AAF02829.1; -; Genomic_DNA.
DR EMBL; AF111169; AAD44361.1; ALT_SEQ; Genomic_DNA.
DR EMBL; BC009031; AAH09031.1; -; mRNA.
DR EMBL; BC051896; AAH51896.1; -; mRNA.
DR CCDS; CCDS9851.1; -. [Q7L8A9-1]
DR RefSeq; NP_055724.1; NM_014909.4. [Q7L8A9-1]
DR PDB; 6J4U; X-ray; 2.00 A; A=57-307.
DR PDB; 6J7B; X-ray; 1.62 A; A=57-306.
DR PDB; 6J8F; X-ray; 2.28 A; B=69-306.
DR PDB; 6J8N; X-ray; 1.95 A; B/D=69-306.
DR PDB; 6J8O; X-ray; 1.85 A; B=69-306.
DR PDB; 6J91; X-ray; 3.50 A; B=69-306.
DR PDB; 6J9H; X-ray; 2.31 A; B/D=69-306.
DR PDB; 6K81; X-ray; 2.28 A; A=1-365.
DR PDB; 6LPG; X-ray; 2.30 A; A=56-310.
DR PDB; 6NVQ; X-ray; 2.10 A; C=1-315.
DR PDB; 6OCF; X-ray; 2.10 A; A=58-305.
DR PDB; 6OCG; X-ray; 1.83 A; A=59-305.
DR PDB; 6OCH; X-ray; 2.00 A; A/C=61-302.
DR PDB; 6WSL; EM; 3.10 A; C/G=52-310.
DR PDBsum; 6J4U; -.
DR PDBsum; 6J7B; -.
DR PDBsum; 6J8F; -.
DR PDBsum; 6J8N; -.
DR PDBsum; 6J8O; -.
DR PDBsum; 6J91; -.
DR PDBsum; 6J9H; -.
DR PDBsum; 6K81; -.
DR PDBsum; 6LPG; -.
DR PDBsum; 6NVQ; -.
DR PDBsum; 6OCF; -.
DR PDBsum; 6OCG; -.
DR PDBsum; 6OCH; -.
DR PDBsum; 6WSL; -.
DR AlphaFoldDB; Q7L8A9; -.
DR SMR; Q7L8A9; -.
DR BioGRID; 116518; 24.
DR IntAct; Q7L8A9; 8.
DR STRING; 9606.ENSP00000167106; -.
DR iPTMnet; Q7L8A9; -.
DR PhosphoSitePlus; Q7L8A9; -.
DR BioMuta; VASH1; -.
DR DMDM; 62511163; -.
DR MassIVE; Q7L8A9; -.
DR PaxDb; Q7L8A9; -.
DR PeptideAtlas; Q7L8A9; -.
DR PRIDE; Q7L8A9; -.
DR ProteomicsDB; 68834; -. [Q7L8A9-1]
DR ProteomicsDB; 68835; -. [Q7L8A9-2]
DR Antibodypedia; 10; 298 antibodies from 34 providers.
DR DNASU; 22846; -.
DR Ensembl; ENST00000167106.9; ENSP00000167106.4; ENSG00000071246.11. [Q7L8A9-1]
DR Ensembl; ENST00000554237.1; ENSP00000451613.1; ENSG00000071246.11. [Q7L8A9-2]
DR GeneID; 22846; -.
DR KEGG; hsa:22846; -.
DR MANE-Select; ENST00000167106.9; ENSP00000167106.4; NM_014909.5; NP_055724.1.
DR UCSC; uc001xss.4; human. [Q7L8A9-1]
DR CTD; 22846; -.
DR DisGeNET; 22846; -.
DR GeneCards; VASH1; -.
DR HGNC; HGNC:19964; VASH1.
DR HPA; ENSG00000071246; Tissue enhanced (retina).
DR MIM; 609011; gene.
DR neXtProt; NX_Q7L8A9; -.
DR OpenTargets; ENSG00000071246; -.
DR PharmGKB; PA134941450; -.
DR VEuPathDB; HostDB:ENSG00000071246; -.
DR eggNOG; ENOG502QPPX; Eukaryota.
DR GeneTree; ENSGT00390000012703; -.
DR HOGENOM; CLU_061405_0_1_1; -.
DR InParanoid; Q7L8A9; -.
DR OMA; MDEETWE; -.
DR OrthoDB; 908291at2759; -.
DR PhylomeDB; Q7L8A9; -.
DR TreeFam; TF329370; -.
DR PathwayCommons; Q7L8A9; -.
DR Reactome; R-HSA-8955332; Carboxyterminal post-translational modifications of tubulin.
DR SignaLink; Q7L8A9; -.
DR BioGRID-ORCS; 22846; 7 hits in 1077 CRISPR screens.
DR ChiTaRS; VASH1; human.
DR GeneWiki; VASH1; -.
DR GenomeRNAi; 22846; -.
DR Pharos; Q7L8A9; Tbio.
DR PRO; PR:Q7L8A9; -.
DR Proteomes; UP000005640; Chromosome 14.
DR RNAct; Q7L8A9; protein.
DR Bgee; ENSG00000071246; Expressed in ganglionic eminence and 113 other tissues.
DR ExpressionAtlas; Q7L8A9; baseline and differential.
DR Genevisible; Q7L8A9; HS.
DR GO; GO:0045177; C:apical part of cell; IDA:MGI.
DR GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:UniProtKB.
DR GO; GO:0005615; C:extracellular space; IDA:UniProtKB.
DR GO; GO:0003779; F:actin binding; IDA:UniProtKB.
DR GO; GO:0004181; F:metallocarboxypeptidase activity; IDA:UniProtKB.
DR GO; GO:0001525; P:angiogenesis; IDA:MGI.
DR GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0060716; P:labyrinthine layer blood vessel development; IEA:Ensembl.
DR GO; GO:0016525; P:negative regulation of angiogenesis; IDA:UniProtKB.
DR GO; GO:0043537; P:negative regulation of blood vessel endothelial cell migration; IDA:UniProtKB.
DR GO; GO:0010596; P:negative regulation of endothelial cell migration; IGI:MGI.
DR GO; GO:0001937; P:negative regulation of endothelial cell proliferation; IDA:UniProtKB.
DR GO; GO:1901491; P:negative regulation of lymphangiogenesis; IGI:MGI.
DR GO; GO:0006508; P:proteolysis; IDA:UniProtKB.
DR GO; GO:0045765; P:regulation of angiogenesis; IBA:GO_Central.
DR GO; GO:2000772; P:regulation of cellular senescence; IMP:MGI.
DR GO; GO:0009611; P:response to wounding; IDA:MGI.
DR InterPro; IPR028131; VASH1.
DR InterPro; IPR028132; Vasohibin-1.
DR PANTHER; PTHR15750; PTHR15750; 1.
DR PANTHER; PTHR15750:SF5; PTHR15750:SF5; 1.
DR Pfam; PF14822; Vasohibin; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Carboxypeptidase; Cell cycle;
KW Cytoplasm; Growth arrest; Hydrolase; Protease; Reference proteome;
KW Secreted; Ubl conjugation.
FT CHAIN 1..365
FT /note="Tubulinyl-Tyr carboxypeptidase 1"
FT /id="PRO_0000189980"
FT REGION 1..59
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 299..365
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 319..365
FT /note="Involved in heparin-binding and antiangiogenic
FT activity"
FT /evidence="ECO:0000269|PubMed:16488400"
FT COMPBIAS 333..353
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 169
FT /evidence="ECO:0000269|PubMed:29146869,
FT ECO:0000305|PubMed:26794318"
FT ACT_SITE 204
FT /evidence="ECO:0000305|PubMed:26794318"
FT ACT_SITE 221
FT /evidence="ECO:0000305|PubMed:26794318"
FT SITE 29..30
FT /note="Cleavage"
FT /evidence="ECO:0000305|PubMed:16488400"
FT SITE 76..77
FT /note="Cleavage"
FT /evidence="ECO:0000305|PubMed:16488400"
FT VAR_SEQ 177..204
FT /note="IYLTNSMPTLERFPISFKTYFSGNYFRH -> MYPSSPEGEGSGLLWASASC
FT SESEGGVG (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_013324"
FT VAR_SEQ 205..365
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_013325"
FT MUTAGEN 29
FT /note="R->A: Disappearance of 42 kDa processed form."
FT /evidence="ECO:0000269|PubMed:16488400"
FT MUTAGEN 74..78
FT /note="WERMW->AERMA: Strongly reduced interaction with
FT SVBP."
FT /evidence="ECO:0000269|PubMed:31171830"
FT MUTAGEN 76
FT /note="R->A: Disappearance of 36, 32 and 27 kDa processed
FT forms."
FT /evidence="ECO:0000269|PubMed:16488400"
FT MUTAGEN 77..81
FT /note="MWKHV->RWKHR: No effect on tyrosine carboxypeptidase
FT activity on alpha-tubulin."
FT /evidence="ECO:0000269|PubMed:31235910"
FT MUTAGEN 77
FT /note="M->R: No effect on tyrosine carboxypeptidase
FT activity on alpha-tubulin. Reduced tyrosine
FT carboxypeptidase activity on alpha-tubulin; when associated
FT with R-141. Abolished tyrosine carboxypeptidase activity on
FT alpha-tubulin; when associated with R-81 and R-141."
FT /evidence="ECO:0000269|PubMed:31235910"
FT MUTAGEN 81
FT /note="V->R: No effect on tyrosine carboxypeptidase
FT activity on alpha-tubulin. Reduced tyrosine
FT carboxypeptidase activity on alpha-tubulin; when associated
FT with R-141. Abolished tyrosine carboxypeptidase activity on
FT alpha-tubulin; when associated with R-77 and R-141."
FT /evidence="ECO:0000269|PubMed:31235910"
FT MUTAGEN 134
FT /note="Y->A,F: Abolished tyrosine carboxypeptidase activity
FT on alpha-tubulin."
FT /evidence="ECO:0000269|PubMed:31171830,
FT ECO:0000269|PubMed:31235910, ECO:0000269|PubMed:31270470"
FT MUTAGEN 141
FT /note="F->R: No effect on tyrosine carboxypeptidase
FT activity on alpha-tubulin. Reduced tyrosine
FT carboxypeptidase activity on alpha-tubulin; when associated
FT with R-77. Reduced tyrosine carboxypeptidase activity on
FT alpha-tubulin; when associated with R-81. Abolished
FT tyrosine carboxypeptidase activity on alpha-tubulin; when
FT associated with R-77 and R-81."
FT /evidence="ECO:0000269|PubMed:31235910"
FT MUTAGEN 145
FT /note="K->A,E: Reduced tyrosine carboxypeptidase activity
FT on alpha-tubulin."
FT /evidence="ECO:0000269|PubMed:31235911"
FT MUTAGEN 146
FT /note="K->A,E: Abolished tyrosine carboxypeptidase activity
FT on alpha-tubulin. Abolished tyrosine carboxypeptidase
FT activity on alpha-tubulin; when associated with A-222."
FT /evidence="ECO:0000269|PubMed:31171830,
FT ECO:0000269|PubMed:31235910, ECO:0000269|PubMed:31270470"
FT MUTAGEN 165..166
FT /note="LP->EE: Almost abolished interaction with VASH1."
FT /evidence="ECO:0000269|PubMed:31171830"
FT MUTAGEN 168
FT /note="K->E: Abolished tyrosine carboxypeptidase activity
FT on alpha-tubulin."
FT /evidence="ECO:0000269|PubMed:31235910,
FT ECO:0000269|PubMed:31270470"
FT MUTAGEN 169
FT /note="C->A,S: Abolished tyrosine carboxypeptidase activity
FT on alpha-tubulin."
FT /evidence="ECO:0000269|PubMed:29146869,
FT ECO:0000269|PubMed:31171830, ECO:0000269|PubMed:31235910,
FT ECO:0000269|PubMed:31270470"
FT MUTAGEN 194
FT /note="K->E: No effect on tyrosine carboxypeptidase
FT activity on alpha-tubulin. No effect on tyrosine
FT carboxypeptidase activity on alpha-tubulin; when associated
FT with E-256. No effect on tyrosine carboxypeptidase activity
FT on alpha-tubulin; when associated with E-258. No effect on
FT tyrosine carboxypeptidase activity on alpha-tubulin; when
FT associated with E-276."
FT /evidence="ECO:0000269|PubMed:31235910,
FT ECO:0000269|PubMed:31270470"
FT MUTAGEN 203
FT /note="R->E: No effect on tyrosine carboxypeptidase
FT activity on alpha-tubulin. Strongly reduced tyrosine
FT carboxypeptidase activity on alpha-tubulin; when associated
FT with E-258. Reduced tyrosine carboxypeptidase activity on
FT alpha-tubulin; when associated with E-258. Reduced tyrosine
FT carboxypeptidase activity on alpha-tubulin; when associated
FT with E-256. Reduced tyrosine carboxypeptidase activity on
FT alpha-tubulin; when associated with E-276."
FT /evidence="ECO:0000269|PubMed:31235910,
FT ECO:0000269|PubMed:31270470"
FT MUTAGEN 204
FT /note="H->A: Abolished tyrosine carboxypeptidase activity
FT on alpha-tubulin."
FT /evidence="ECO:0000269|PubMed:31171830,
FT ECO:0000269|PubMed:31235910, ECO:0000269|PubMed:31270470"
FT MUTAGEN 221
FT /note="S->A: Abolished tyrosine carboxypeptidase activity
FT on alpha-tubulin."
FT /evidence="ECO:0000269|PubMed:31171830,
FT ECO:0000269|PubMed:31235910, ECO:0000269|PubMed:31270470"
FT MUTAGEN 222
FT /note="R->A,E: Abolished tyrosine carboxypeptidase activity
FT on alpha-tubulin. Abolished tyrosine carboxypeptidase
FT activity on alpha-tubulin; when associated with A-146."
FT /evidence="ECO:0000269|PubMed:31171830,
FT ECO:0000269|PubMed:31235910, ECO:0000269|PubMed:31235911,
FT ECO:0000269|PubMed:31270470"
FT MUTAGEN 222
FT /note="R->Q: Reduced tyrosine carboxypeptidase activity on
FT alpha-tubulin."
FT /evidence="ECO:0000269|PubMed:31235911"
FT MUTAGEN 223
FT /note="R->E: Slightly reduced tyrosine carboxypeptidase
FT activity on alpha-tubulin."
FT /evidence="ECO:0000269|PubMed:31270470"
FT MUTAGEN 226
FT /note="L->A: Slightly reduced tyrosine carboxypeptidase
FT activity on alpha-tubulin."
FT /evidence="ECO:0000269|PubMed:31270470"
FT MUTAGEN 247
FT /note="Y->F: Slightly reduced tyrosine carboxypeptidase
FT activity on alpha-tubulin."
FT /evidence="ECO:0000269|PubMed:31270470"
FT MUTAGEN 256
FT /note="K->E: No effect on tyrosine carboxypeptidase
FT activity on alpha-tubulin; when associated with E-194.
FT Reduced tyrosine carboxypeptidase activity on alpha-
FT tubulin; when associated with E-203."
FT /evidence="ECO:0000269|PubMed:31235910"
FT MUTAGEN 258
FT /note="K->E: No effect on tyrosine carboxypeptidase
FT activity on alpha-tubulin. No effect on tyrosine
FT carboxypeptidase activity on alpha-tubulin; when associated
FT with E-194. Strognly reduced tyrosine carboxypeptidase
FT activity on alpha-tubulin; when associated with E-203."
FT /evidence="ECO:0000269|PubMed:31235910,
FT ECO:0000269|PubMed:31270470"
FT MUTAGEN 276
FT /note="K->E: No effect on tyrosine carboxypeptidase
FT activity on alpha-tubulin. No effect on tyrosine
FT carboxypeptidase activity on alpha-tubulin; when associated
FT with E-194. Reduced tyrosine carboxypeptidase activity on
FT alpha-tubulin; when associated with E-203."
FT /evidence="ECO:0000269|PubMed:31235910,
FT ECO:0000269|PubMed:31270470"
FT STRAND 63..68
FT /evidence="ECO:0007829|PDB:6OCF"
FT HELIX 71..84
FT /evidence="ECO:0007829|PDB:6J7B"
FT STRAND 85..87
FT /evidence="ECO:0007829|PDB:6OCG"
FT HELIX 88..95
FT /evidence="ECO:0007829|PDB:6J7B"
FT HELIX 118..132
FT /evidence="ECO:0007829|PDB:6J7B"
FT STRAND 137..142
FT /evidence="ECO:0007829|PDB:6J7B"
FT STRAND 146..149
FT /evidence="ECO:0007829|PDB:6OCF"
FT HELIX 150..163
FT /evidence="ECO:0007829|PDB:6J7B"
FT HELIX 169..178
FT /evidence="ECO:0007829|PDB:6J7B"
FT TURN 179..182
FT /evidence="ECO:0007829|PDB:6J7B"
FT STRAND 186..197
FT /evidence="ECO:0007829|PDB:6J7B"
FT STRAND 200..211
FT /evidence="ECO:0007829|PDB:6J7B"
FT STRAND 214..218
FT /evidence="ECO:0007829|PDB:6J7B"
FT HELIX 224..226
FT /evidence="ECO:0007829|PDB:6J7B"
FT STRAND 229..235
FT /evidence="ECO:0007829|PDB:6J7B"
FT HELIX 236..249
FT /evidence="ECO:0007829|PDB:6J7B"
FT STRAND 253..259
FT /evidence="ECO:0007829|PDB:6J7B"
FT STRAND 277..281
FT /evidence="ECO:0007829|PDB:6J7B"
FT HELIX 282..303
FT /evidence="ECO:0007829|PDB:6J7B"
SQ SEQUENCE 365 AA; 40957 MW; CEE39875FA9DA70B CRC64;
MPGGKKVAGG GSSGATPTSA AATAPSGVRR LETSEGTSAQ RDEEPEEEGE EDLRDGGVPF
FVNRGGLPVD EATWERMWKH VAKIHPDGEK VAQRIRGATD LPKIPIPSVP TFQPSTPVPE
RLEAVQRYIR ELQYNHTGTQ FFEIKKSRPL TGLMDLAKEM TKEALPIKCL EAVILGIYLT
NSMPTLERFP ISFKTYFSGN YFRHIVLGVN FAGRYGALGM SRREDLMYKP PAFRTLSELV
LDFEAAYGRC WHVLKKVKLG QSVSHDPHSV EQIEWKHSVL DVERLGRDDF RKELERHARD
MRLKIGKGTG PPSPTKDRKK DVSSPQRAQS SPHRRNSRSE RRPSGDKKTS EPKAMPDLNG
YQIRV
