VASH1_MOUSE
ID VASH1_MOUSE Reviewed; 375 AA.
AC Q8C1W1; E9QKT9; Q8C394;
DT 12-APR-2005, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 4.
DT 03-AUG-2022, entry version 117.
DE RecName: Full=Tubulinyl-Tyr carboxypeptidase 1 {ECO:0000305};
DE EC=3.4.17.17 {ECO:0000269|PubMed:29146868};
DE AltName: Full=Tyrosine carboxypeptidase 1 {ECO:0000305};
DE Short=TTCP 1 {ECO:0000305};
DE AltName: Full=Vasohibin-1 {ECO:0000303|PubMed:19204325};
GN Name=Vash1 {ECO:0000312|MGI:MGI:2442543}; Synonyms=Vash;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Embryonic brain;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [3]
RP FUNCTION, AND TISSUE SPECIFICITY.
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 [4]
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 [5]
RP FUNCTION, CATALYTIC ACTIVITY, INTERACTION WITH SVBP, ACTIVE SITE,
RP IDENTIFICATION BY MASS SPECTROMETRY, AND MUTAGENESIS OF CYS-179.
RX PubMed=29146868; DOI=10.1126/science.aao4165;
RA Aillaud C., Bosc C., Peris L., Bosson A., Heemeryck P., Van Dijk J.,
RA Le Friec J., Boulan B., Vossier F., Sanman L.E., Syed S., Amara N.,
RA Coute Y., Lafanechere L., Denarier E., Delphin C., Pelletier L.,
RA Humbert S., Bogyo M., Andrieux A., Rogowski K., Moutin M.J.;
RT "Vasohibins/SVBP are tubulin carboxypeptidases (TCPs) that regulate neuron
RT differentiation.";
RL Science 358:1448-1453(2017).
CC -!- FUNCTION: Tyrosine carboxypeptidase that removes the C-terminal
CC tyrosine residue of alpha-tubulin, thereby regulating microtubule
CC dynamics and function (PubMed:29146868). Acts as an angiogenesis
CC inhibitor: inhibits migration, proliferation and network formation by
CC endothelial cells as well as angiogenesis (PubMed:19204325). This
CC inhibitory effect is selective to endothelial cells as it does not
CC affect the migration of smooth muscle cells or fibroblasts (By
CC similarity). {ECO:0000250|UniProtKB:Q7L8A9,
CC ECO:0000269|PubMed:19204325, ECO:0000269|PubMed:29146868}.
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:29146868};
CC -!- SUBUNIT: Interacts with SVBP; interaction enhances VASH1 tyrosine
CC carboxypeptidase activity. {ECO:0000269|PubMed:29146868}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q7L8A9}.
CC Secreted {ECO:0000250|UniProtKB:Q7L8A9}. Note=Mainly localizes in the
CC cytoplasm. Some fraction is secreted via a non-canonical secretion
CC system; interaction with SVBP promotes secretion.
CC {ECO:0000250|UniProtKB:Q7L8A9}.
CC -!- TISSUE SPECIFICITY: Expressed at low level in proliferating endothelial
CC cells at the sprouting front but highly expressed in nonproliferating
CC endothelial cells in the termination zone.
CC {ECO:0000269|PubMed:19204325}.
CC -!- PTM: Ubiquitinated in vitro. {ECO:0000250|UniProtKB:Q7L8A9}.
CC -!- SIMILARITY: Belongs to the transglutaminase-like superfamily. Vasohibin
CC family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAC41121.1; Type=Frameshift; 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; AK090166; BAC41121.1; ALT_FRAME; mRNA.
DR EMBL; AC102689; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS49118.1; -.
DR RefSeq; NP_796328.2; NM_177354.4.
DR AlphaFoldDB; Q8C1W1; -.
DR SMR; Q8C1W1; -.
DR BioGRID; 231969; 1.
DR STRING; 10090.ENSMUSP00000021681; -.
DR iPTMnet; Q8C1W1; -.
DR PhosphoSitePlus; Q8C1W1; -.
DR MaxQB; Q8C1W1; -.
DR PaxDb; Q8C1W1; -.
DR PRIDE; Q8C1W1; -.
DR ProteomicsDB; 297974; -.
DR Antibodypedia; 10; 298 antibodies from 34 providers.
DR DNASU; 238328; -.
DR Ensembl; ENSMUST00000021681; ENSMUSP00000021681; ENSMUSG00000021256.
DR GeneID; 238328; -.
DR KEGG; mmu:238328; -.
DR UCSC; uc007ohx.2; mouse.
DR CTD; 22846; -.
DR MGI; MGI:2442543; Vash1.
DR VEuPathDB; HostDB:ENSMUSG00000021256; -.
DR eggNOG; ENOG502QPPX; Eukaryota.
DR GeneTree; ENSGT00390000012703; -.
DR HOGENOM; CLU_061405_0_1_1; -.
DR InParanoid; Q8C1W1; -.
DR OMA; MDEETWE; -.
DR OrthoDB; 908291at2759; -.
DR PhylomeDB; Q8C1W1; -.
DR TreeFam; TF329370; -.
DR BioGRID-ORCS; 238328; 3 hits in 72 CRISPR screens.
DR ChiTaRS; Vash1; mouse.
DR PRO; PR:Q8C1W1; -.
DR Proteomes; UP000000589; Chromosome 12.
DR RNAct; Q8C1W1; protein.
DR Bgee; ENSMUSG00000021256; Expressed in embryonic brain and 65 other tissues.
DR GO; GO:0045177; C:apical part of cell; ISO:MGI.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0005783; C:endoplasmic reticulum; ISO:MGI.
DR GO; GO:0005615; C:extracellular space; ISO:MGI.
DR GO; GO:0003779; F:actin binding; IDA:UniProtKB.
DR GO; GO:0004181; F:metallocarboxypeptidase activity; IDA:UniProtKB.
DR GO; GO:0001525; P:angiogenesis; ISO:MGI.
DR GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0060716; P:labyrinthine layer blood vessel development; IMP:MGI.
DR GO; GO:0016525; P:negative regulation of angiogenesis; IDA:MGI.
DR GO; GO:0043537; P:negative regulation of blood vessel endothelial cell migration; ISO:MGI.
DR GO; GO:0010596; P:negative regulation of endothelial cell migration; ISO:MGI.
DR GO; GO:0001937; P:negative regulation of endothelial cell proliferation; ISO:MGI.
DR GO; GO:1901491; P:negative regulation of lymphangiogenesis; ISO:MGI.
DR GO; GO:0060674; P:placenta blood vessel development; IMP:MGI.
DR GO; GO:0010628; P:positive regulation of gene expression; ISO: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; ISO:MGI.
DR GO; GO:0009611; P:response to wounding; ISO: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 Carboxypeptidase; Cell cycle; Cytoplasm; Growth arrest; Hydrolase;
KW Protease; Reference proteome; Secreted; Ubl conjugation.
FT CHAIN 1..375
FT /note="Tubulinyl-Tyr carboxypeptidase 1"
FT /id="PRO_0000189981"
FT REGION 1..69
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 309..375
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 329..375
FT /note="Involved in heparin-binding and antiangiogenic
FT activity"
FT /evidence="ECO:0000250|UniProtKB:Q7L8A9"
FT COMPBIAS 9..23
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 343..363
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 179
FT /evidence="ECO:0000269|PubMed:29146868,
FT ECO:0000305|PubMed:26794318"
FT ACT_SITE 214
FT /evidence="ECO:0000305|PubMed:26794318"
FT ACT_SITE 231
FT /evidence="ECO:0000305|PubMed:26794318"
FT SITE 39..40
FT /note="Cleavage"
FT /evidence="ECO:0000250|UniProtKB:Q7L8A9"
FT SITE 86..87
FT /note="Cleavage"
FT /evidence="ECO:0000250|UniProtKB:Q7L8A9"
FT MUTAGEN 179
FT /note="C->A: Abolished tyrosine carboxypeptidase activity."
FT /evidence="ECO:0000269|PubMed:29146868"
FT CONFLICT 2
FT /note="P -> A (in Ref. 1; BAC41121)"
FT /evidence="ECO:0000305"
FT CONFLICT 157
FT /note="S -> G (in Ref. 1; BAC41121)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 375 AA; 41875 MW; 82F7348A17B32B6D CRC64;
MPGGKKVVPS GSSSASPNAA ATTTAAAAAA AAAPHSGTKR LETTEGASAQ RDEEPEEEGE
EDLRDGGVPF FINRGGLPVD EATWERMWKH VAKIHPDGEK VALRIRGATD LPKIPIPSVP
TFQPTTPVPE RLEAVQRYIR ELQYNHTGTQ FFEIKKSRPL TGLMDLAKEM TKEALPIKCL
EAVILGIYLT NSMPTLERFP ISFKTYFSGN YFRHIVLGVN FGGRYGALGM SRREDLMYKP
PAFRTLSELV LDYEAAYGRC WHVLKKVKLG QCVSHDPHSV EQIEWKHSVL DVERLGREDF
RKELERHARD MRLKIGKGTG PPSPTKDRKK DVSSPQRAQS SPHRRNSRSE RRPSGEKKPA
EPKAMPDLSG YQIRV
