GIMA5_MOUSE
ID GIMA5_MOUSE Reviewed; 308 AA.
AC Q8BWF2; Q501L7; Q549X3;
DT 14-NOV-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 03-AUG-2022, entry version 137.
DE RecName: Full=GTPase IMAP family member 5;
DE AltName: Full=GTPase of the immunity-associated protein 5 {ECO:0000303|PubMed:16509771};
DE AltName: Full=Immunity-associated nucleotide 4-like 1 protein;
DE AltName: Full=Immunity-associated protein 3;
GN Name=Gimap5; Synonyms=Ian4l1, Ian5 {ECO:0000303|PubMed:16509771}, Imap3;
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], FUNCTION, INTERACTION WITH BAD; BAK1; BAX;
RP BCL2; BCL2L1 AND BCL2L11, DEVELOPMENTAL STAGE, AND TISSUE SPECIFICITY.
RC TISSUE=Thymocyte;
RX PubMed=16509771; DOI=10.1371/journal.pbio.0040103;
RA Nitta T., Nasreen M., Seike T., Goji A., Ohigashi I., Miyazaki T., Ohta T.,
RA Kanno M., Takahama Y.;
RT "IAN family critically regulates survival and development of T
RT lymphocytes.";
RL PLoS Biol. 4:593-605(2006).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Kidney;
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 MRNA].
RC STRAIN=C57BL/6J; TISSUE=Kidney;
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 DISRUPTION PHENOTYPE.
RX PubMed=18796632; DOI=10.1182/blood-2008-03-146555;
RA Schulteis R.D., Chu H., Dai X., Chen Y., Edwards B., Haribhai D.,
RA Williams C.B., Malarkannan S., Hessner M.J., Glisic-Milosavljevic S.,
RA Jana S., Kerschen E.J., Ghosh S., Wang D., Kwitek A.E., Lernmark A.,
RA Gorski J., Weiler H.;
RT "Impaired survival of peripheral T cells, disrupted NK/NKT cell
RT development, and liver failure in mice lacking Gimap5.";
RL Blood 112:4905-4914(2008).
RN [5]
RP SUBCELLULAR LOCATION.
RX PubMed=21487483; DOI=10.4161/self.1.3.12819;
RA Wong V.W., Saunders A.E., Hutchings A., Pascall J.C., Carter C.,
RA Bright N.A., Walker S.A., Ktistakis N.T., Butcher G.W.;
RT "The autoimmunity-related GIMAP5 GTPase is a lysosome-associated protein.";
RL Self/Nonself 1:259-268(2010).
RN [6]
RP FUNCTION, INTERACTION WITH BCL2; BCL2L1; HSPA8 AND MCL1, TISSUE
RP SPECIFICITY, AND DISRUPTION PHENOTYPE.
RX PubMed=21502331; DOI=10.1084/jem.20101192;
RA Chen Y., Yu M., Dai X., Zogg M., Wen R., Weiler H., Wang D.;
RT "Critical role for Gimap5 in the survival of mouse hematopoietic stem and
RT progenitor cells.";
RL J. Exp. Med. 208:923-935(2011).
RN [7]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=25808953; DOI=10.1534/genetics.115.175596;
RA Jokinen R., Lahtinen T., Marttinen P., Myoehaenen M., Ruotsalainen P.,
RA Yeung N., Shvetsova A., Kastaniotis A.J., Hiltunen J.K., Oehman T.,
RA Nyman T.A., Weiler H., Battersby B.J.;
RT "Quantitative changes in Gimap3 and Gimap5 expression modify mitochondrial
RT DNA segregation in mice.";
RL Genetics 200:221-235(2015).
RN [8]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=29382851; DOI=10.1038/s41467-018-02897-7;
RA Patterson A.R., Endale M., Lampe K., Aksoylar H.I., Flagg A.,
RA Woodgett J.R., Hildeman D., Jordan M.B., Singh H., Kucuk Z., Bleesing J.,
RA Hoebe K.;
RT "Gimap5-dependent inactivation of GSK3beta is required for CD4+ T cell
RT homeostasis and prevention of immune pathology.";
RL Nat. Commun. 9:430-430(2018).
RN [9]
RP FUNCTION, TISSUE SPECIFICITY, AND SUBCELLULAR LOCATION.
RX PubMed=33956074; DOI=10.1084/jem.20201745;
RA Drzewiecki K., Choi J., Brancale J., Leney-Greene M.A., Sari S., Dalgic B.,
RA Uenluesoy Aksu A., Evirgen Sahin G., Ozen A., Baris S., Karakoc-Aydiner E.,
RA Jain D., Kleiner D., Schmalz M., Radhakrishnan K., Zhang J., Hoebe K.,
RA Su H.C., Pereira J.P., Lenardo M.J., Lifton R.P., Vilarinho S.;
RT "GIMAP5 maintains liver endothelial cell homeostasis and prevents portal
RT hypertension.";
RL J. Exp. Med. 218:0-0(2021).
CC -!- FUNCTION: Plays a role in T lymphocyte development and the optimal
CC generation of CD4/CD8 double-positive thymocytes (PubMed:16509771).
CC Inhibitor of GSK3A. May act by sequestering GSK3A in cytoplasmic
CC vesicles and impairing its translocation to the nucleus. Consequently,
CC impairs GSK3A-dependent transcriptional program and regulation of the
CC DNA damage response occurring during T cells proliferation
CC (PubMed:29382851). Required for the survival of bone marrow
CC hematopoietic stem cells, as well as of peripheral T cells, natural
CC killer (NK) and NK T-cell development and the maintenance of normal
CC liver function (PubMed:18796632, PubMed:21502331). May promote the
CC survival of mature T lymphocytes upon cytokine withdrawal
CC (PubMed:16509771). May regulate Ca(2+) homeostasis by modulating
CC lysosomal Ca(2+) stores, preventing its accumulation in the absence of
CC T cell activation (By similarity). May play a role in mitochondrial DNA
CC segregation in hematopoietic tissues (PubMed:25808953). Is a regulator
CC of liver endothelial cell homeostasis (PubMed:33956074).
CC {ECO:0000250|UniProtKB:Q8K3L6, ECO:0000269|PubMed:16509771,
CC ECO:0000269|PubMed:18796632, ECO:0000269|PubMed:21502331,
CC ECO:0000269|PubMed:25808953, ECO:0000269|PubMed:29382851,
CC ECO:0000269|PubMed:33956074}.
CC -!- SUBUNIT: Interacts with BAD, BAK1, BAX, BCL2, BCL2L1/Bcl-xL and
CC BCL2L11/BimEL (PubMed:16509771, PubMed:21502331). The interaction with
CC BAX is increased, when cells initiate apoptosis upon IL2 withdrawal
CC (PubMed:16509771). Forms a complex with BCL2L1 or MCL1 and HSPA8/HSC70;
CC the interaction between HSPA8 and BCL2L1 or MCL1 is impaired in the
CC absence of GIMAP5 (PubMed:21502331). May interact (via N-terminus) with
CC microtubules (By similarity). {ECO:0000250|UniProtKB:Q8K3L6,
CC ECO:0000269|PubMed:16509771, ECO:0000269|PubMed:21502331}.
CC -!- INTERACTION:
CC Q8BWF2; P10417: Bcl2; NbExp=3; IntAct=EBI-15572348, EBI-526314;
CC Q8BWF2; Q07812: BAX; Xeno; NbExp=2; IntAct=EBI-15572348, EBI-516580;
CC Q8BWF2; Q07817-1: BCL2L1; Xeno; NbExp=3; IntAct=EBI-15572348, EBI-287195;
CC -!- SUBCELLULAR LOCATION: Lysosome {ECO:0000269|PubMed:33956074}. Lysosome
CC membrane {ECO:0000269|PubMed:21487483, ECO:0000269|PubMed:29382851};
CC Single-pass type IV membrane protein {ECO:0000305}. Endosome,
CC multivesicular body membrane {ECO:0000269|PubMed:21487483}; Single-pass
CC type IV membrane protein {ECO:0000305}. Endosome membrane
CC {ECO:0000250|UniProtKB:Q8K3L6}; Single-pass type IV membrane protein
CC {ECO:0000250|UniProtKB:Q8K3L6}.
CC -!- TISSUE SPECIFICITY: Expressed in thymus (in thymocytes), spleen (in
CC splenocytes), lymph node and lung (PubMed:16509771). Highly expressed
CC in T lymphocytes (PubMed:16509771, PubMed:21502331). Expressed in B
CC cells and in distinct lineages of hematopoietic bone marrow cells,
CC including natural killer, B, T, myeloid and erythroid lineages
CC (PubMed:21502331). Expressed in liver endothelial cells
CC (PubMed:33956074). {ECO:0000269|PubMed:16509771,
CC ECO:0000269|PubMed:21502331, ECO:0000269|PubMed:33956074}.
CC -!- DEVELOPMENTAL STAGE: Up-regulated upon the maturation of CD4/CD8
CC double-positive to CD4 single-positive thymocytes.
CC {ECO:0000269|PubMed:16509771}.
CC -!- DISRUPTION PHENOTYPE: Knockout mice are born at the expected Mendelian
CC rate, with a normal sex ratio, but have a median survival of only 15
CC weeks. They exhibit chronic hepatic hematopoiesis and, in later stages,
CC show pronounced hepatocyte apoptosis, leading to lethal liver failure.
CC Loss of GIMAP5 function impairs peripheral T-cell survival, imposes a
CC complete block of natural killer (NK) and NK T-cell development
CC (PubMed:18796632). Mutant mice show progressive multilineage failure of
CC bone marrow and hematopoiesis. Compared with that of wild-type
CC counterparts, the bone marrow contains more hematopoietic stem cells,
CC but fewer lineage-committed hematopoietic progenitors
CC (PubMed:21502331). {ECO:0000269|PubMed:18796632,
CC ECO:0000269|PubMed:21502331}.
CC -!- SIMILARITY: Belongs to the TRAFAC class TrmE-Era-EngA-EngB-Septin-like
CC GTPase superfamily. AIG1/Toc34/Toc159-like paraseptin GTPase family.
CC IAN subfamily. {ECO:0000305}.
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DR EMBL; AB126961; BAD06929.1; -; mRNA.
DR EMBL; AK052694; BAC35100.1; -; mRNA.
DR EMBL; BC095995; AAH95995.1; -; mRNA.
DR CCDS; CCDS20114.1; -.
DR RefSeq; NP_778200.1; NM_175035.5.
DR RefSeq; XP_006506293.1; XM_006506230.3.
DR RefSeq; XP_006506294.1; XM_006506231.3.
DR RefSeq; XP_006506295.1; XM_006506232.3.
DR AlphaFoldDB; Q8BWF2; -.
DR SMR; Q8BWF2; -.
DR DIP; DIP-29183N; -.
DR IntAct; Q8BWF2; 6.
DR STRING; 10090.ENSMUSP00000056820; -.
DR iPTMnet; Q8BWF2; -.
DR PhosphoSitePlus; Q8BWF2; -.
DR EPD; Q8BWF2; -.
DR MaxQB; Q8BWF2; -.
DR PaxDb; Q8BWF2; -.
DR PRIDE; Q8BWF2; -.
DR ProteomicsDB; 265746; -.
DR DNASU; 317757; -.
DR Ensembl; ENSMUST00000055558; ENSMUSP00000056820; ENSMUSG00000043505.
DR GeneID; 317757; -.
DR KEGG; mmu:317757; -.
DR UCSC; uc009bvs.1; mouse.
DR CTD; 55340; -.
DR MGI; MGI:2442232; Gimap5.
DR VEuPathDB; HostDB:ENSMUSG00000043505; -.
DR eggNOG; ENOG502RB0C; Eukaryota.
DR GeneTree; ENSGT00940000154844; -.
DR HOGENOM; CLU_010468_1_1_1; -.
DR InParanoid; Q8BWF2; -.
DR OMA; KGKYGAM; -.
DR OrthoDB; 1092873at2759; -.
DR PhylomeDB; Q8BWF2; -.
DR TreeFam; TF330845; -.
DR BioGRID-ORCS; 317757; 3 hits in 73 CRISPR screens.
DR ChiTaRS; Gimap3; mouse.
DR PRO; PR:Q8BWF2; -.
DR Proteomes; UP000000589; Chromosome 6.
DR RNAct; Q8BWF2; protein.
DR Bgee; ENSMUSG00000043505; Expressed in mesenteric lymph node and 73 other tissues.
DR Genevisible; Q8BWF2; MM.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005765; C:lysosomal membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005739; C:mitochondrion; ISO:MGI.
DR GO; GO:0032585; C:multivesicular body membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005525; F:GTP binding; IEA:UniProtKB-KW.
DR GO; GO:0043011; P:myeloid dendritic cell differentiation; ISO:MGI.
DR GO; GO:0043066; P:negative regulation of apoptotic process; ISO:MGI.
DR GO; GO:0032689; P:negative regulation of interferon-gamma production; ISO:MGI.
DR GO; GO:0050995; P:negative regulation of lipid catabolic process; ISO:MGI.
DR GO; GO:0045019; P:negative regulation of nitric oxide biosynthetic process; ISO:MGI.
DR GO; GO:0050868; P:negative regulation of T cell activation; ISO:MGI.
DR GO; GO:0010524; P:positive regulation of calcium ion transport into cytosol; ISO:MGI.
DR GO; GO:0032831; P:positive regulation of CD4-positive, CD25-positive, alpha-beta regulatory T cell differentiation; ISO:MGI.
DR GO; GO:0045588; P:positive regulation of gamma-delta T cell differentiation; ISO:MGI.
DR GO; GO:0002925; P:positive regulation of humoral immune response mediated by circulating immunoglobulin; ISO:MGI.
DR GO; GO:0045838; P:positive regulation of membrane potential; ISO:MGI.
DR GO; GO:0002729; P:positive regulation of natural killer cell cytokine production; ISO:MGI.
DR GO; GO:0045954; P:positive regulation of natural killer cell mediated cytotoxicity; ISO:MGI.
DR GO; GO:0046902; P:regulation of mitochondrial membrane permeability; ISO:MGI.
DR GO; GO:0043029; P:T cell homeostasis; ISO:MGI.
DR GO; GO:0001659; P:temperature homeostasis; ISO:MGI.
DR Gene3D; 3.40.50.300; -; 1.
DR InterPro; IPR006703; G_AIG1.
DR InterPro; IPR045058; GIMA/IAN/Toc.
DR InterPro; IPR027417; P-loop_NTPase.
DR PANTHER; PTHR10903; PTHR10903; 1.
DR Pfam; PF04548; AIG1; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
DR PROSITE; PS51720; G_AIG1; 1.
PE 1: Evidence at protein level;
KW Endosome; GTP-binding; Lysosome; Membrane; Nucleotide-binding;
KW Reference proteome; Transmembrane; Transmembrane helix.
FT CHAIN 1..308
FT /note="GTPase IMAP family member 5"
FT /id="PRO_0000190991"
FT TOPO_DOM 1..283
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 284..304
FT /note="Helical; Anchor for type IV membrane protein"
FT /evidence="ECO:0000255"
FT TOPO_DOM 305..308
FT /note="Mitochondrial intermembrane"
FT /evidence="ECO:0000255"
FT DOMAIN 24..227
FT /note="AIG1-type G"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01057"
FT BINDING 33..41
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:Q8WWP7"
FT BINDING 54
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:Q9UG22"
FT BINDING 151..153
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:Q8WWP7"
FT BINDING 188
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:Q8WWP7"
FT CONFLICT 94
FT /note="D -> V (in Ref. 3; AAH95995)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 308 AA; 34653 MW; DCF85C07B989A3BC CRC64;
MEHLQKSTYG TIVQGPEAHC VQESSCLRIL LVGKSGCGKS ATGNSILRRP AFQSRLRGQS
VTRTSQAETG TWEGRSILVV DTPPIFESKA QNQDMDKDIG DCYLLCAPGP HVLLLVTQLG
RFTAEDAMAV RMVKEVFGVG VMRHMIVLFT RKEDLEEKSL EEFVTHTDNR SLRSLTQECG
RRYCAFNNRA SGEEQQGQLA ELMALVRRLE QECEGSFHSN DLFLHAEALL REGYSVHQEA
YRCYLAKVRQ EVEKQRRELE EQEGSWIAKM ICTVKSCWSS HTAACALLIV LGLTLLTTFI
NLCISRCK
