GIMA5_RAT
ID GIMA5_RAT Reviewed; 326 AA.
AC Q8K3L6; Q5YEJ2; Q5YEJ3; Q8K3L7;
DT 14-NOV-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2002, sequence version 1.
DT 03-AUG-2022, entry version 122.
DE RecName: Full=GTPase IMAP family member 5;
DE AltName: Full=Immunity-associated nucleotide 4 protein;
DE Short=IAN-4;
DE AltName: Full=Immunity-associated nucleotide 4-like 1 protein;
GN Name=Gimap5;
GN Synonyms=Ian4 {ECO:0000303|PubMed:12031988, ECO:0000303|PubMed:12930893,
GN ECO:0000303|PubMed:15307172}, Ian4l1 {ECO:0000303|PubMed:15474297}, Iddm1,
GN Lyp;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), VARIANTS VAL-174 AND
RP ILE-221, TISSUE SPECIFICITY, AND INVOLVEMENT IN INSULIN-DEPENDENT DIABETES
RP AND T-CELL LYMPHOPENIA.
RC STRAIN=BB; TISSUE=Thymus;
RX PubMed=12031988; DOI=10.2337/diabetes.51.6.1972;
RA Hornum L., Romer J., Markholst H.;
RT "The diabetes-prone BB rat carries a frameshift mutation in Ian4, a
RT positional candidate of Iddm1.";
RL Diabetes 51:1972-1979(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2).
RC STRAIN=BB; TISSUE=Thymus;
RX PubMed=15474297; DOI=10.1016/j.gene.2004.06.034;
RA Andersen U.N., Markholst H., Hornum L.;
RT "The antiapoptotic gene Ian4l1 in the rat: genomic organization and
RT promoter characterization.";
RL Gene 341:141-148(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC 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 TISSUE SPECIFICITY.
RX PubMed=12930893; DOI=10.1073/pnas.1832170100;
RA Pandarpurkar M., Wilson-Fritch L., Corvera S., Markholst H., Hornum L.,
RA Greiner D.L., Mordes J.P., Rossini A.A., Bortell R.;
RT "Ian4 is required for mitochondrial integrity and T cell survival.";
RL Proc. Natl. Acad. Sci. U.S.A. 100:10382-10387(2003).
RN [5]
RP FUNCTION.
RX PubMed=15307172; DOI=10.1002/eji.200324751;
RA Lang J.A., Kominski D., Bellgrau D., Scheinman R.I.;
RT "Partial activation precedes apoptotic death in T cells harboring an IAN
RT gene mutation.";
RL Eur. J. Immunol. 34:2396-2406(2004).
RN [6]
RP TISSUE SPECIFICITY.
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 [7]
RP FUNCTION, INTERACTION WITH MICROTUBULES, SUBCELLULAR LOCATION, TOPOLOGY,
RP TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RX PubMed=28223986; DOI=10.3389/fimmu.2017.00094;
RA Serrano D., Ghobadi F., Boulay G., Ilangumaran S., Lavoie C.,
RA Ramanathan S.;
RT "GTPase of the immune-associated nucleotide protein 5 regulates the
RT lysosomal calcium compartment in T lymphocytes.";
RL Front. Immunol. 8:94-94(2017).
CC -!- FUNCTION: Required for mitochondrial integrity and T-cell survival. May
CC contribute to T-cell quiescence. {ECO:0000269|PubMed:12930893,
CC ECO:0000269|PubMed:15307172}.
CC -!- FUNCTION: Plays a role in T lymphocyte development and the optimal
CC generation of CD4/CD8 double-positive thymocytes (By similarity).
CC Inhibitor of GSK3A, possibly 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 (By
CC similarity). Required for the survival of peripheral T cells, natural
CC killer (NK) and NK T-cell development and the maintenance of normal
CC liver function (By similarity). Promotes the survival of quiescent T-
CC cells (PubMed:15307172). May regulate Ca(2+) homeostasis by modulating
CC lysosomal Ca(2+) stores, preventing its accumulation in the absence of
CC T cell activation (PubMed:28223986). May play a role in mitochondrial
CC DNA segregation in hematopoietic tissues (By similarity). Is a
CC regulator of liver endothelial cell homeostasis (By similarity).
CC {ECO:0000250|UniProtKB:Q8BWF2, ECO:0000250|UniProtKB:Q96F15,
CC ECO:0000269|PubMed:15307172, ECO:0000269|PubMed:28223986}.
CC -!- SUBUNIT: Interacts with BAD, BAK1, BAX, BCL2, BCL2L1/Bcl-xL and
CC BCL2L11/BimEL (By similarity). The interaction with BAX is increased,
CC when cells initiate apoptosis upon IL2 withdrawal (By similarity).
CC Forms a complex with BCL2L1 or MCL1 and HSPA8/HSC70; the interaction
CC between HSPA8 and BCL2L1 or MCL1 is impaired in the absence of GIMAP5
CC (By similarity). May interact (via N-terminus) with microtubules
CC (Probable). {ECO:0000250|UniProtKB:Q8BWF2,
CC ECO:0000305|PubMed:28223986}.
CC -!- SUBCELLULAR LOCATION: Lysosome membrane {ECO:0000269|PubMed:28223986};
CC Single-pass type IV membrane protein {ECO:0000269|PubMed:28223986}.
CC Endosome, multivesicular body membrane {ECO:0000269|PubMed:21487483};
CC Single-pass type IV membrane protein {ECO:0000305}. Endosome membrane
CC {ECO:0000269|PubMed:28223986}; Single-pass type IV membrane protein
CC {ECO:0000269|PubMed:28223986}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=Long, IAN4L1L, Gimap5v1 {ECO:0000303|PubMed:28223986};
CC IsoId=Q8K3L6-1; Sequence=Displayed;
CC Name=2; Synonyms=Short, IAN4L1S, Gimap5v2
CC {ECO:0000303|PubMed:28223986};
CC IsoId=Q8K3L6-2; Sequence=VSP_008962;
CC -!- TISSUE SPECIFICITY: Primarily expressed in spleen, heart, lung and
CC intestine and, at lower levels, in kidney, stomach and muscle
CC (PubMed:12031988). Expressed in thymus and lymph nodes (at protein
CC level) (PubMed:12031988, PubMed:12930893, PubMed:21487483). In the
CC spleen, expressed in periarteriolar lymphatic sheets (PubMed:12031988).
CC Isoform 2: Expressed at higher levels in T lymphocytes compared to
CC isoform 1 (PubMed:28223986). {ECO:0000269|PubMed:12031988,
CC ECO:0000269|PubMed:12930893, ECO:0000269|PubMed:21487483,
CC ECO:0000269|PubMed:28223986}.
CC -!- DEVELOPMENTAL STAGE: Down-regulated during T lymphocyte activation.
CC {ECO:0000269|PubMed:28223986}.
CC -!- DISEASE: Note=Diabetes-prone biobreeding (DP-BB) rats have a frameshift
CC mutation in Gimap5, which results in a truncated protein in which the
CC C-terminal 215 amino acids, including the membrane anchor, are replaced
CC by 19 other amino acids. These animals exhibit life-long T-cell
CC lymphopenia, including lack of regulatory T cells, and spontaneously
CC develop insulin-dependent diabetes resembling human type 1 diabetes.
CC {ECO:0000269|PubMed:12031988}.
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; AY055776; AAL17698.1; -; mRNA.
DR EMBL; AY055777; AAL17699.2; -; mRNA.
DR EMBL; AY550018; AAS56933.1; -; mRNA.
DR EMBL; AY550019; AAS56934.1; -; mRNA.
DR EMBL; AY550020; AAS56935.1; -; mRNA.
DR EMBL; AY550021; AAS56936.1; -; mRNA.
DR EMBL; AY550022; AAS56937.1; -; mRNA.
DR EMBL; AY550023; AAS56938.1; -; mRNA.
DR EMBL; BC092561; AAH92561.1; -; mRNA.
DR RefSeq; NP_001029085.1; NM_001033913.1. [Q8K3L6-1]
DR RefSeq; NP_663713.1; NM_145680.3. [Q8K3L6-2]
DR RefSeq; XP_006236519.1; XM_006236457.3. [Q8K3L6-1]
DR RefSeq; XP_006236520.1; XM_006236458.3. [Q8K3L6-2]
DR RefSeq; XP_008761093.1; XM_008762871.2. [Q8K3L6-2]
DR AlphaFoldDB; Q8K3L6; -.
DR SMR; Q8K3L6; -.
DR STRING; 10116.ENSRNOP00000055929; -.
DR PaxDb; Q8K3L6; -.
DR PRIDE; Q8K3L6; -.
DR Ensembl; ENSRNOT00000059156; ENSRNOP00000055929; ENSRNOG00000008416. [Q8K3L6-2]
DR Ensembl; ENSRNOT00000084927; ENSRNOP00000072663; ENSRNOG00000008416. [Q8K3L6-1]
DR Ensembl; ENSRNOT00000115571; ENSRNOP00000078457; ENSRNOG00000008416. [Q8K3L6-1]
DR GeneID; 246774; -.
DR KEGG; rno:246774; -.
DR UCSC; RGD:628871; rat. [Q8K3L6-1]
DR CTD; 55340; -.
DR RGD; 628871; Gimap5.
DR eggNOG; ENOG502RB0C; Eukaryota.
DR GeneTree; ENSGT00940000154844; -.
DR InParanoid; Q8K3L6; -.
DR OMA; KGKYGAM; -.
DR OrthoDB; 1092873at2759; -.
DR PhylomeDB; Q8K3L6; -.
DR TreeFam; TF330845; -.
DR PRO; PR:Q8K3L6; -.
DR Proteomes; UP000002494; Chromosome 4.
DR Bgee; ENSRNOG00000008416; Expressed in thymus and 17 other tissues.
DR ExpressionAtlas; Q8K3L6; baseline and differential.
DR Genevisible; Q8K3L6; RN.
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; IDA:RGD.
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; IMP:RGD.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IMP:RGD.
DR GO; GO:0032689; P:negative regulation of interferon-gamma production; IMP:RGD.
DR GO; GO:0050995; P:negative regulation of lipid catabolic process; IMP:RGD.
DR GO; GO:0045019; P:negative regulation of nitric oxide biosynthetic process; IMP:RGD.
DR GO; GO:0050868; P:negative regulation of T cell activation; IMP:RGD.
DR GO; GO:0010524; P:positive regulation of calcium ion transport into cytosol; IMP:RGD.
DR GO; GO:0032831; P:positive regulation of CD4-positive, CD25-positive, alpha-beta regulatory T cell differentiation; IMP:RGD.
DR GO; GO:0045588; P:positive regulation of gamma-delta T cell differentiation; IMP:RGD.
DR GO; GO:0002925; P:positive regulation of humoral immune response mediated by circulating immunoglobulin; IMP:RGD.
DR GO; GO:0045838; P:positive regulation of membrane potential; IMP:RGD.
DR GO; GO:0002729; P:positive regulation of natural killer cell cytokine production; IMP:RGD.
DR GO; GO:0045954; P:positive regulation of natural killer cell mediated cytotoxicity; IMP:RGD.
DR GO; GO:0046902; P:regulation of mitochondrial membrane permeability; IMP:RGD.
DR GO; GO:0030217; P:T cell differentiation; IEP:RGD.
DR GO; GO:0043029; P:T cell homeostasis; IMP:RGD.
DR GO; GO:0001659; P:temperature homeostasis; IMP:RGD.
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 Alternative splicing; Endosome; GTP-binding; Lysosome; Membrane;
KW Nucleotide-binding; Reference proteome; Transmembrane; Transmembrane helix.
FT CHAIN 1..326
FT /note="GTPase IMAP family member 5"
FT /id="PRO_0000190992"
FT TOPO_DOM 1..297
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305|PubMed:28223986"
FT TRANSMEM 298..318
FT /note="Helical; Anchor for type IV membrane protein"
FT /evidence="ECO:0000305|PubMed:28223986"
FT TOPO_DOM 319..326
FT /note="Lumenal"
FT /evidence="ECO:0000305|PubMed:28223986"
FT DOMAIN 42..245
FT /note="AIG1-type G"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01057"
FT BINDING 51..59
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:Q8WWP7"
FT BINDING 72
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:Q9UG22"
FT BINDING 169..171
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:Q8WWP7"
FT BINDING 206
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:Q8WWP7"
FT VAR_SEQ 1..32
FT /note="MEDHGFEELSTRTHDLNVRRLTKGNINFLLST -> MEGLQKSTYGTIVE
FT (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:12031988,
FT ECO:0000303|PubMed:15474297"
FT /id="VSP_008962"
FT VARIANT 174
FT /note="A -> V"
FT /evidence="ECO:0000269|PubMed:12031988"
FT VARIANT 221
FT /note="M -> I"
FT /evidence="ECO:0000269|PubMed:12031988"
SQ SEQUENCE 326 AA; 37266 MW; 1452F22932FB5F51 CRC64;
MEDHGFEELS TRTHDLNVRR LTKGNINFLL STGQETYSVE DSGLLRILLV GKSGCGKSAT
GNSILRRPAF ESRLRGQSVT RTSQAEMGTW EGRSFLVVDT PPIFESKIQN QDMDKDIGNC
YLMCAPGPHV LLLVTQLGRY TVEDAMAVRM VKQIFGVGVM RYMIVLFTHK EDLADESLEE
FVTHTGNLDL HRLVQECGRR YCAFNNKASG EEQQGQLAEL MALVRRLEQE HEGSFHSNDL
FVYTQVFLRG GYSEHQEPYK FYLTKVRQEV EKQKRELEEQ EGSWMAKMLC RVTSCLDWHI
AVSVLLIVLG LTLLITLINM YIGRWK
