VASH2_MOUSE
ID VASH2_MOUSE Reviewed; 355 AA.
AC Q8C5G2; Q3TR02; Q8BRA1; Q8R1R8;
DT 12-APR-2005, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 2.
DT 03-AUG-2022, entry version 111.
DE RecName: Full=Tubulinyl-Tyr carboxypeptidase 2 {ECO:0000305};
DE EC=3.4.17.17 {ECO:0000269|PubMed:29146868, ECO:0000269|PubMed:31324789};
DE AltName: Full=Vasohibin-2 {ECO:0000303|PubMed:19204325};
DE AltName: Full=Vasohibin-like protein;
GN Name=Vash2 {ECO:0000312|MGI:MGI:2444826}; Synonyms=Vashl;
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=Cerebellum, Gonad, and Head;
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].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Mammary tumor;
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 [4]
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 [5]
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 [6]
RP FUNCTION, CATALYTIC ACTIVITY, INTERACTION WITH SVBP, ACTIVE SITE, AND
RP MUTAGENESIS OF CYS-158.
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).
RN [7]
RP FUNCTION.
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 [8] {ECO:0007744|PDB:6JZC, ECO:0007744|PDB:6JZD, ECO:0007744|PDB:6JZE}
RP X-RAY CRYSTALLOGRAPHY (2.20 ANGSTROMS) OF 48-301 IN COMPLEX WITH SVBP,
RP INTERACTION WITH SVBP, FUNCTION, CATALYTIC ACTIVITY, AND MUTAGENESIS OF
RP LYS-119; ARG-134; LYS-135; LYS-157; CYS-158; LYS-183; HIS-193; SER-210;
RP ARG-211; ARG-212; LYS-218; LYS-238 AND LYS-247.
RX PubMed=31324789; DOI=10.1038/s41467-019-11277-8;
RA Zhou C., Yan L., Zhang W.H., Liu Z.;
RT "Structural basis of tubulin detyrosination by VASH2/SVBP heterodimer.";
RL Nat. Commun. 10:3212-3212(2019).
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 activator of
CC angiogenesis: expressed in infiltrating mononuclear cells in the
CC sprouting front to promote angiogenesis (PubMed:19204325). Plays a role
CC in axon formation (PubMed:31235911). {ECO:0000269|PubMed:19204325,
CC ECO:0000269|PubMed:29146868, ECO:0000269|PubMed:31235911}.
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, ECO:0000269|PubMed:31324789};
CC -!- SUBUNIT: Interacts with SVBP; interaction enhances VASH2 tyrosine
CC carboxypeptidase activity. {ECO:0000269|PubMed:29146868,
CC ECO:0000269|PubMed:31324789}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q86V25}.
CC Secreted {ECO:0000250|UniProtKB:Q86V25}. Cytoplasm, cytoskeleton
CC {ECO:0000250|UniProtKB:Q86V25}. Note=Mainly localizes in the cytoplasm.
CC Some fraction is secreted via a non-canonical secretion system;
CC interaction with SVBP promotes secretion. Associates with microtubules
CC (By similarity). {ECO:0000250|UniProtKB:Q86V25}.
CC -!- TISSUE SPECIFICITY: Preferentially expressed in bone marrow-derived
CC mononuclear cells at the sprouting front.
CC {ECO:0000269|PubMed:29146868}.
CC -!- SIMILARITY: Belongs to the transglutaminase-like superfamily. Vasohibin
CC family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH24141.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AK045261; BAC32286.1; -; mRNA.
DR EMBL; AK078596; BAC37339.1; -; mRNA.
DR EMBL; AK140989; BAE24539.1; -; mRNA.
DR EMBL; AK163193; BAE37229.1; -; mRNA.
DR EMBL; CH466555; EDL13013.1; -; Genomic_DNA.
DR EMBL; BC024141; AAH24141.1; ALT_INIT; mRNA.
DR CCDS; CCDS48482.1; -.
DR RefSeq; NP_659128.2; NM_144879.2.
DR PDB; 6JZC; X-ray; 2.20 A; A/B=1-355.
DR PDB; 6JZD; X-ray; 2.48 A; A=1-355.
DR PDB; 6JZE; X-ray; 2.51 A; A=47-355.
DR PDBsum; 6JZC; -.
DR PDBsum; 6JZD; -.
DR PDBsum; 6JZE; -.
DR AlphaFoldDB; Q8C5G2; -.
DR SMR; Q8C5G2; -.
DR STRING; 10090.ENSMUSP00000036768; -.
DR iPTMnet; Q8C5G2; -.
DR PhosphoSitePlus; Q8C5G2; -.
DR PaxDb; Q8C5G2; -.
DR PRIDE; Q8C5G2; -.
DR ProteomicsDB; 297910; -.
DR Antibodypedia; 47116; 152 antibodies from 22 providers.
DR DNASU; 226841; -.
DR Ensembl; ENSMUST00000047409; ENSMUSP00000036768; ENSMUSG00000037568.
DR Ensembl; ENSMUST00000166139; ENSMUSP00000127626; ENSMUSG00000037568.
DR GeneID; 226841; -.
DR KEGG; mmu:226841; -.
DR UCSC; uc007ebr.2; mouse.
DR CTD; 79805; -.
DR MGI; MGI:2444826; Vash2.
DR VEuPathDB; HostDB:ENSMUSG00000037568; -.
DR eggNOG; ENOG502QPPX; Eukaryota.
DR GeneTree; ENSGT00390000012703; -.
DR HOGENOM; CLU_061405_0_0_1; -.
DR InParanoid; Q8C5G2; -.
DR OMA; WGHVERV; -.
DR OrthoDB; 908291at2759; -.
DR PhylomeDB; Q8C5G2; -.
DR TreeFam; TF329370; -.
DR BioGRID-ORCS; 226841; 1 hit in 72 CRISPR screens.
DR PRO; PR:Q8C5G2; -.
DR Proteomes; UP000000589; Chromosome 1.
DR RNAct; Q8C5G2; protein.
DR Bgee; ENSMUSG00000037568; Expressed in humerus cartilage element and 155 other tissues.
DR Genevisible; Q8C5G2; MM.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0005856; C:cytoskeleton; IEA:UniProtKB-SubCell.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0003779; F:actin binding; IDA:UniProtKB.
DR GO; GO:0004181; F:metallocarboxypeptidase activity; IDA:UniProtKB.
DR GO; GO:0008017; F:microtubule binding; ISS:UniProtKB.
DR GO; GO:0061564; P:axon development; ISS:UniProtKB.
DR GO; GO:0140253; P:cell-cell fusion; ISO:MGI.
DR GO; GO:0060716; P:labyrinthine layer blood vessel development; IMP:MGI.
DR GO; GO:0060711; P:labyrinthine layer development; IMP:MGI.
DR GO; GO:0060674; P:placenta blood vessel development; IMP:MGI.
DR GO; GO:0045766; P:positive regulation of angiogenesis; IMP:MGI.
DR GO; GO:0001938; P:positive regulation of endothelial cell proliferation; ISO:MGI.
DR GO; GO:0006508; P:proteolysis; IDA:UniProtKB.
DR GO; GO:0045765; P:regulation of angiogenesis; IBA:GO_Central.
DR GO; GO:0000768; P:syncytium formation by plasma membrane fusion; IMP:MGI.
DR InterPro; IPR028131; VASH1.
DR PANTHER; PTHR15750; PTHR15750; 1.
DR Pfam; PF14822; Vasohibin; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Carboxypeptidase; Cytoplasm; Cytoskeleton; Hydrolase;
KW Phosphoprotein; Protease; Reference proteome; Secreted.
FT CHAIN 1..355
FT /note="Tubulinyl-Tyr carboxypeptidase 2"
FT /id="PRO_0000189983"
FT REGION 1..45
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 297..335
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 158
FT /evidence="ECO:0000269|PubMed:29146868,
FT ECO:0000305|PubMed:26794318"
FT ACT_SITE 193
FT /evidence="ECO:0000305|PubMed:26794318"
FT ACT_SITE 210
FT /evidence="ECO:0000305|PubMed:26794318"
FT MOD_RES 302
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q86V25"
FT MUTAGEN 119
FT /note="K->E: No effect on tyrosine carboxypeptidase
FT activity."
FT /evidence="ECO:0000269|PubMed:31324789"
FT MUTAGEN 134
FT /note="R->E: Slightly reduced tyrosine carboxypeptidase
FT activity."
FT /evidence="ECO:0000269|PubMed:31324789"
FT MUTAGEN 135
FT /note="K->E: Strongly reduced tyrosine carboxypeptidase
FT activity."
FT /evidence="ECO:0000269|PubMed:31324789"
FT MUTAGEN 157
FT /note="K->E: Strongly reduced tyrosine carboxypeptidase
FT activity."
FT /evidence="ECO:0000269|PubMed:31324789"
FT MUTAGEN 158
FT /note="C->A: Abolished tyrosine carboxypeptidase activity."
FT /evidence="ECO:0000269|PubMed:29146868,
FT ECO:0000269|PubMed:31324789"
FT MUTAGEN 183
FT /note="K->E: No effect on tyrosine carboxypeptidase
FT activity."
FT /evidence="ECO:0000269|PubMed:31324789"
FT MUTAGEN 193
FT /note="H->A: Strongly reduced tyrosine carboxypeptidase
FT activity."
FT /evidence="ECO:0000269|PubMed:31324789"
FT MUTAGEN 210
FT /note="S->A: Strongly reduced tyrosine carboxypeptidase
FT activity."
FT /evidence="ECO:0000269|PubMed:31324789"
FT MUTAGEN 211
FT /note="R->E: Strongly reduced tyrosine carboxypeptidase
FT activity."
FT /evidence="ECO:0000269|PubMed:31324789"
FT MUTAGEN 212
FT /note="R->E: Strongly reduced tyrosine carboxypeptidase
FT activity."
FT /evidence="ECO:0000269|PubMed:31324789"
FT MUTAGEN 218
FT /note="K->E: Strongly reduced tyrosine carboxypeptidase
FT activity."
FT /evidence="ECO:0000269|PubMed:31324789"
FT MUTAGEN 238
FT /note="K->E: Reduced tyrosine carboxypeptidase activity."
FT /evidence="ECO:0000269|PubMed:31324789"
FT MUTAGEN 247
FT /note="K->E: Reduced tyrosine carboxypeptidase activity."
FT /evidence="ECO:0000269|PubMed:31324789"
FT CONFLICT 341
FT /note="A -> D (in Ref. 1; BAC37339)"
FT /evidence="ECO:0000305"
FT HELIX 60..73
FT /evidence="ECO:0007829|PDB:6JZC"
FT HELIX 77..84
FT /evidence="ECO:0007829|PDB:6JZC"
FT HELIX 107..121
FT /evidence="ECO:0007829|PDB:6JZC"
FT STRAND 126..131
FT /evidence="ECO:0007829|PDB:6JZC"
FT HELIX 139..152
FT /evidence="ECO:0007829|PDB:6JZC"
FT HELIX 158..169
FT /evidence="ECO:0007829|PDB:6JZC"
FT STRAND 176..186
FT /evidence="ECO:0007829|PDB:6JZC"
FT STRAND 189..200
FT /evidence="ECO:0007829|PDB:6JZC"
FT STRAND 203..207
FT /evidence="ECO:0007829|PDB:6JZC"
FT HELIX 213..215
FT /evidence="ECO:0007829|PDB:6JZC"
FT STRAND 218..224
FT /evidence="ECO:0007829|PDB:6JZC"
FT HELIX 225..237
FT /evidence="ECO:0007829|PDB:6JZC"
FT TURN 238..240
FT /evidence="ECO:0007829|PDB:6JZC"
FT STRAND 242..248
FT /evidence="ECO:0007829|PDB:6JZC"
FT STRAND 266..269
FT /evidence="ECO:0007829|PDB:6JZC"
FT HELIX 271..273
FT /evidence="ECO:0007829|PDB:6JZC"
FT HELIX 276..291
FT /evidence="ECO:0007829|PDB:6JZC"
FT TURN 298..300
FT /evidence="ECO:0007829|PDB:6JZE"
SQ SEQUENCE 355 AA; 40499 MW; 74B25608F2297D14 CRC64;
MTGSAADTHR CPHPKITKGT RSRSSHARPV SLATSGGSEE EDKDGGVLFH VNKSGFPIDS
HTWERMWLHV AKVHPRGGEM VGAIRNAAFL AKPSIPQVPN YRLSMTIPDW LQAIQNYMKT
LQYNHTGTQF FEIRKMRPLS GLMETAKEMT RESLPIKCLE AVILGIYLTN GQPSIERFPI
SFKTYFSGNY FHHVVLGIYC NGYYGSLGMS RRAELMDKPL TFRTLSDLVF DFEDSYKKYL
HTVKKVKIGL YVPHEPHSFQ PIEWKQLVLN VSKMLRADIR KELEKYARDM RMKILKPASA
HSPTQVRSRG KSLSPRRRQA SPPRRLGRRD KSPALTEKKV ADLGTLNEVG YQIRI
