TGTP2_MOUSE
ID TGTP2_MOUSE Reviewed; 415 AA.
AC Q3T9E4;
DT 02-NOV-2016, integrated into UniProtKB/Swiss-Prot.
DT 02-NOV-2016, sequence version 2.
DT 03-AUG-2022, entry version 100.
DE RecName: Full=T-cell-specific guanine nucleotide triphosphate-binding protein 2;
DE EC=3.6.5.- {ECO:0000269|PubMed:9725230};
DE AltName: Full=Interferon-gamma-inducible GTPase Ifggb6 protein {ECO:0000303|PubMed:22892676};
DE AltName: Full=T-cell-specific guanine nucleotide triphosphate-binding protein {ECO:0000303|PubMed:7836757};
GN Name=Tgtp2;
GN Synonyms=Ifggb6 {ECO:0000303|PubMed:22892676},
GN Irgb6 {ECO:0000303|PubMed:22892676}, Mg21 {ECO:0000303|PubMed:9725230},
GN Tgtp {ECO:0000303|PubMed:7836757};
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 [MRNA], INDUCTION BY TCR STIMULATION, AND TISSUE
RP SPECIFICITY.
RC TISSUE=Thymocyte;
RX PubMed=7836757;
RA Carlow D.A., Marth J., Clark-Lewis I., Teh H.S.;
RT "Isolation of a gene encoding a developmentally regulated T cell-specific
RT protein with a guanine nucleotide triphosphate-binding motif.";
RL J. Immunol. 154:1724-1734(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=NOD; TISSUE=Spleen, and Thymus;
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 [3]
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 [4]
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 [5]
RP INDUCTION BY IFNG, AND TISSUE SPECIFICITY.
RX PubMed=7884320; DOI=10.1002/jlb.57.3.477;
RA Lafuse W.P., Brown D., Castle L., Zwilling B.S.;
RT "Cloning and characterization of a novel cDNA that is IFN-gamma-induced in
RT mouse peritoneal macrophages and encodes a putative GTP-binding protein.";
RL J. Leukoc. Biol. 57:477-483(1995).
RN [6]
RP FUNCTION, INDUCTION BY IFNG, AND CATALYTIC ACTIVITY.
RX PubMed=9725230;
RA Carlow D.A., Teh S.J., Teh H.S.;
RT "Specific antiviral activity demonstrated by TGTP, a member of a new family
RT of interferon-induced GTPases.";
RL J. Immunol. 161:2348-2355(1998).
RN [7]
RP GENOMIC ORGANIZATION OF P47 GTPASE CLUSTER.
RX PubMed=16277747; DOI=10.1186/gb-2005-6-11-r92;
RA Bekpen C., Hunn J.P., Rohde C., Parvanova I., Guethlein L., Dunn D.M.,
RA Glowalla E., Leptin M., Howard J.C.;
RT "The interferon-inducible p47 (IRG) GTPases in vertebrates: loss of the
RT cell autonomous resistance mechanism in the human lineage.";
RL Genome Biol. 6:R92.1-R92.18(2005).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY, SUBCELLULAR LOCATION, INDUCTION BY
RP TNF, AND TISSUE SPECIFICITY.
RX PubMed=19285957; DOI=10.1016/j.bbrc.2009.03.043;
RA Yamada K., Akimoto H., Ogawa Y., Kinumi T., Kamagata Y., Ohmiya Y.;
RT "Upregulation of immunity-related GTPase (IRG) proteins by TNF-alpha in
RT murine astrocytes.";
RL Biochem. Biophys. Res. Commun. 382:434-439(2009).
RN [9]
RP FUNCTION.
RX PubMed=19265156; DOI=10.4049/jimmunol.0804190;
RA Zhao Y., Ferguson D.J., Wilson D.C., Howard J.C., Sibley L.D., Yap G.S.;
RT "Virulent Toxoplasma gondii evade immunity-related GTPase-mediated parasite
RT vacuole disruption within primed macrophages.";
RL J. Immunol. 182:3775-3781(2009).
RN [10]
RP IDENTIFICATION.
RX PubMed=22892676; DOI=10.1007/s10142-012-0291-2;
RA Premzl M.;
RT "Comparative genomic analysis of eutherian interferon-gamma-inducible
RT GTPases.";
RL Funct. Integr. Genomics 12:599-607(2012).
RN [11]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver, Lung, and Spleen;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [12]
RP FUNCTION, AND INDUCTION BY IFNG.
RX PubMed=24563254; DOI=10.4049/jimmunol.1302822;
RA Ohshima J., Lee Y., Sasai M., Saitoh T., Su Ma J., Kamiyama N.,
RA Matsuura Y., Pann-Ghill S., Hayashi M., Ebisu S., Takeda K., Akira S.,
RA Yamamoto M.;
RT "Role of mouse and human autophagy proteins in IFN-gamma-induced cell-
RT autonomous responses against Toxoplasma gondii.";
RL J. Immunol. 192:3328-3335(2014).
CC -!- FUNCTION: Involved in innate cell-autonomous resistance to
CC intracellular pathogens, such as Toxoplasma gondii. During avirulent
CC type II T. gondii infection, recruited to the parasitophorous vacuole
CC (PV) membrane, leading to PV vesiculation and rupture, and subsequent
CC digestion of the parasite within the cytosol (PubMed:19265156,
CC PubMed:24563254). Not recruited to virulent type I T. gondii PV
CC membrane (PubMed:19265156). May confer an antiviral state for vesicular
CC stomatitis virus (PubMed:9725230). {ECO:0000269|PubMed:19265156,
CC ECO:0000269|PubMed:24563254, ECO:0000269|PubMed:9725230}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=GTP + H2O = GDP + H(+) + phosphate; Xref=Rhea:RHEA:19669,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:37565,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:58189;
CC Evidence={ECO:0000269|PubMed:9725230};
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:19285957}.
CC Endoplasmic reticulum {ECO:0000269|PubMed:19285957}. Golgi apparatus
CC {ECO:0000269|PubMed:19285957}. Note=In astrocytes stimulated with IFNG
CC or TNF, diffuse cytoplasmic localization decreases and the protein
CC partially relocalizes to the endoplasmic reticulum and Golgi apparatus
CC (PubMed:19285957). Due to sequence similarity with Tgtp1, it is
CC impossible to assign unambiguously experimental data published in the
CC literature to Tgtp1 or Tgtp2 gene (Probable).
CC {ECO:0000269|PubMed:19285957, ECO:0000305|PubMed:22892676}.
CC -!- TISSUE SPECIFICITY: Expressed in thymus and lymph nodes, predominantly
CC T-cells. Not expressed by immature CD4(+) CD8(+) thymocytes (at protein
CC level) (PubMed:7836757). Expressed in IFNG-stimulated macrophages
CC (PubMed:7884320). Expressed at low levels in unstimulated astrocytes
CC (PubMed:19285957). Due to sequence similarity with Tgtp1, it is
CC impossible to assign unambiguously experimental data published in the
CC literature to Tgtp1 or Tgtp2 gene. {ECO:0000269|PubMed:19285957,
CC ECO:0000269|PubMed:7836757, ECO:0000269|PubMed:7884320}.
CC -!- INDUCTION: In macrophages, up-regulated by IFNG, but not by IL2, IL4,
CC IL10, nor TNF (PubMed:7884320). Up-regulated by IFNG in lymph node
CC cells and thymocytes and other cell types (PubMed:7836757,
CC PubMed:9725230, PubMed:24563254). In astrocytes, up-regulated by TNF
CC and IFNG; when both cytokines are combined, the effect is synergistic
CC (PubMed:19285957). Due to sequence similarity with Tgtp1, it is
CC impossible to assign unambiguously experimental data published in the
CC literature to Tgtp1 or Tgtp2 gene (Probable).
CC {ECO:0000269|PubMed:19285957, ECO:0000269|PubMed:24563254,
CC ECO:0000269|PubMed:7836757, ECO:0000269|PubMed:7884320,
CC ECO:0000269|PubMed:9725230, ECO:0000305|PubMed:22892676}.
CC -!- SIMILARITY: Belongs to the TRAFAC class dynamin-like GTPase
CC superfamily. IRG family. {ECO:0000255|PROSITE-ProRule:PRU01053,
CC ECO:0000305}.
CC -!- CAUTION: The gene Tgtp1 belongs to a large family of eutherian IFNG-
CC inducible GTPases, called immunity-related p47 GTPases, which comprises
CC a variable amount of paralogs depending upon the species studied. In
CC C57BL/6J mice, there is over 20 genes, whereas humans have only one
CC ortholog. Tgtp2 closest paralog is Tgtp1. Both genes encode identical
CC proteins. At the nucleotide sequence level, their CDSs differ at only 4
CC positions. Consequently it is almost impossible to assign unambiguously
CC to one gene or the other experimental data published in the literature.
CC {ECO:0000305|PubMed:16277747, ECO:0000305|PubMed:22892676}.
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DR EMBL; L38444; AAA64914.1; -; mRNA.
DR EMBL; AK088858; BAC40617.1; -; mRNA.
DR EMBL; AK172580; BAE43078.1; -; mRNA.
DR EMBL; FR734026; CBY65989.1; -; Genomic_DNA.
DR EMBL; AL645688; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS48781.1; -.
DR PIR; I56251; I56251.
DR RefSeq; NP_001138636.1; NM_001145164.1.
DR RefSeq; NP_035709.3; NM_011579.3.
DR PDB; 7VES; X-ray; 2.00 A; A=1-415.
DR PDB; 7VEX; X-ray; 1.51 A; A=1-415.
DR PDBsum; 7VES; -.
DR PDBsum; 7VEX; -.
DR AlphaFoldDB; Q3T9E4; -.
DR SMR; Q3T9E4; -.
DR PeptideAtlas; Q3T9E4; -.
DR PRIDE; Q3T9E4; -.
DR DNASU; 21822; -.
DR Ensembl; ENSMUST00000046745; ENSMUSP00000045025; ENSMUSG00000078921.
DR Ensembl; ENSMUST00000068063; ENSMUSP00000069914; ENSMUSG00000078922.
DR GeneID; 100039796; -.
DR GeneID; 21822; -.
DR KEGG; mmu:100039796; -.
DR KEGG; mmu:21822; -.
DR CTD; 100039796; -.
DR CTD; 21822; -.
DR MGI; MGI:3710083; Tgtp2.
DR VEuPathDB; HostDB:ENSMUSG00000078921; -.
DR VEuPathDB; HostDB:ENSMUSG00000078922; -.
DR OMA; LMANLKC; -.
DR OrthoDB; 688334at2759; -.
DR PhylomeDB; Q3T9E4; -.
DR BioGRID-ORCS; 100039796; 1 hit in 37 CRISPR screens.
DR BioGRID-ORCS; 21822; 4 hits in 39 CRISPR screens.
DR ChiTaRS; Tgtp1; mouse.
DR PRO; PR:Q3T9E4; -.
DR Proteomes; UP000000589; Chromosome 11.
DR RNAct; Q3T9E4; protein.
DR Bgee; ENSMUSG00000078921; Expressed in thymus and 70 other tissues.
DR ExpressionAtlas; Q3T9E4; baseline and differential.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IBA:GO_Central.
DR GO; GO:0005794; C:Golgi apparatus; IEA:UniProtKB-SubCell.
DR GO; GO:0005525; F:GTP binding; IEA:UniProtKB-KW.
DR GO; GO:0003924; F:GTPase activity; IBA:GO_Central.
DR GO; GO:0035458; P:cellular response to interferon-beta; IBA:GO_Central.
DR GO; GO:0006952; P:defense response; IBA:GO_Central.
DR GO; GO:0045087; P:innate immune response; IEA:UniProtKB-KW.
DR Gene3D; 3.40.50.300; -; 1.
DR InterPro; IPR030385; G_IRG_dom.
DR InterPro; IPR007743; Immunity-related_GTPase-like.
DR InterPro; IPR027417; P-loop_NTPase.
DR Pfam; PF05049; IIGP; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
DR PROSITE; PS51716; G_IRG; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cytoplasm; Endoplasmic reticulum; Golgi apparatus;
KW GTP-binding; Hydrolase; Immunity; Innate immunity; Nucleotide-binding;
KW Reference proteome.
FT CHAIN 1..415
FT /note="T-cell-specific guanine nucleotide triphosphate-
FT binding protein 2"
FT /id="PRO_0000437943"
FT DOMAIN 55..237
FT /note="IRG-type G"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01053"
FT BINDING 64..71
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250"
FT BINDING 89..93
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250"
FT BINDING 218..220
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250"
FT CONFLICT 399
FT /note="E -> G (in Ref. 2; BAE43078)"
FT /evidence="ECO:0000305"
FT HELIX 1..12
FT /evidence="ECO:0007829|PDB:7VEX"
FT HELIX 16..18
FT /evidence="ECO:0007829|PDB:7VEX"
FT HELIX 23..34
FT /evidence="ECO:0007829|PDB:7VEX"
FT HELIX 38..54
FT /evidence="ECO:0007829|PDB:7VEX"
FT STRAND 57..63
FT /evidence="ECO:0007829|PDB:7VEX"
FT HELIX 69..77
FT /evidence="ECO:0007829|PDB:7VEX"
FT STRAND 99..102
FT /evidence="ECO:0007829|PDB:7VEX"
FT STRAND 109..115
FT /evidence="ECO:0007829|PDB:7VEX"
FT HELIX 117..119
FT /evidence="ECO:0007829|PDB:7VEX"
FT HELIX 124..130
FT /evidence="ECO:0007829|PDB:7VEX"
FT HELIX 133..135
FT /evidence="ECO:0007829|PDB:7VEX"
FT STRAND 137..145
FT /evidence="ECO:0007829|PDB:7VEX"
FT HELIX 149..160
FT /evidence="ECO:0007829|PDB:7VEX"
FT STRAND 165..169
FT /evidence="ECO:0007829|PDB:7VEX"
FT HELIX 172..182
FT /evidence="ECO:0007829|PDB:7VEX"
FT TURN 184..186
FT /evidence="ECO:0007829|PDB:7VEX"
FT HELIX 189..205
FT /evidence="ECO:0007829|PDB:7VEX"
FT STRAND 208..210
FT /evidence="ECO:0007829|PDB:7VEX"
FT STRAND 214..216
FT /evidence="ECO:0007829|PDB:7VEX"
FT HELIX 227..237
FT /evidence="ECO:0007829|PDB:7VEX"
FT HELIX 240..242
FT /evidence="ECO:0007829|PDB:7VEX"
FT HELIX 243..249
FT /evidence="ECO:0007829|PDB:7VEX"
FT STRAND 252..254
FT /evidence="ECO:0007829|PDB:7VEX"
FT HELIX 255..276
FT /evidence="ECO:0007829|PDB:7VEX"
FT STRAND 279..281
FT /evidence="ECO:0007829|PDB:7VEX"
FT HELIX 288..294
FT /evidence="ECO:0007829|PDB:7VEX"
FT HELIX 296..305
FT /evidence="ECO:0007829|PDB:7VEX"
FT HELIX 310..319
FT /evidence="ECO:0007829|PDB:7VEX"
FT HELIX 324..328
FT /evidence="ECO:0007829|PDB:7VEX"
FT HELIX 333..335
FT /evidence="ECO:0007829|PDB:7VEX"
FT HELIX 345..359
FT /evidence="ECO:0007829|PDB:7VEX"
FT TURN 360..364
FT /evidence="ECO:0007829|PDB:7VEX"
FT HELIX 372..391
FT /evidence="ECO:0007829|PDB:7VEX"
FT HELIX 394..399
FT /evidence="ECO:0007829|PDB:7VEX"
FT TURN 411..413
FT /evidence="ECO:0007829|PDB:7VEX"
SQ SEQUENCE 415 AA; 47121 MW; 3AFB5F940242952A CRC64;
MAWASSFDAF FKNFKRESKI ISEYDITLIM TYIEENKLQK AVSVIEKVLR DIESAPLHIA
VTGETGAGKS TFINTLRGVG HEEKGAAPTG AIETTMKRTP YPHPKLPNVT IWDLPGIGTT
NFTPQNYLTE MKFGEYDFFI IISATRFKEN DAQLAKAIAQ MGMNFYFVRT KIDSDLDNEQ
KFKPKSFNKE EVLKNIKDYC SNHLQESLDS EPPVFLVSNV DISKYDFPKL ETKLLQDLPA
HKRHVFSLSL QSLTEATINY KRDSLKQKVF LEAMKAGALA TIPLGGMISD ILENLDETFN
LYRSYFGLDD ASLENIAQDL NMSVDDFKVH LRFPHLFAEH NDESLEDKLF KYIKHISSVT
GGPVAAVTYY RMAYYLQNLF LDTAANDAIA LLNSKALFEK KVGPYISEPP EYWEA
