LFG4_HUMAN
ID LFG4_HUMAN Reviewed; 238 AA.
AC Q9HC24; Q542Z6; Q9UHY5; Q9Y3C2;
DT 14-AUG-2001, integrated into UniProtKB/Swiss-Prot.
DT 08-FEB-2011, sequence version 3.
DT 03-AUG-2022, entry version 149.
DE RecName: Full=Protein lifeguard 4;
DE AltName: Full=Golgi anti-apoptotic protein;
DE AltName: Full=Protein S1R;
DE AltName: Full=Transmembrane BAX inhibitor motif-containing protein 4;
DE AltName: Full=Z-protein;
GN Name=TMBIM4; Synonyms=GAAP, LFG4; ORFNames=CGI-119;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Goldberger O., Smith T., Minta J., Goldberger G.;
RT "Identification and phylogeny of a novel family of eukaryotic membrane
RT proteins related to a glutamate binding protein (GBP).";
RL Submitted (SEP-1999) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT THR-88.
RX PubMed=10810093; DOI=10.1101/gr.10.5.703;
RA Lai C.-H., Chou C.-Y., Ch'ang L.-Y., Liu C.-S., Lin W.-C.;
RT "Identification of novel human genes evolutionarily conserved in
RT Caenorhabditis elegans by comparative proteomics.";
RL Genome Res. 10:703-713(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT THR-88.
RC TISSUE=Adrenal gland;
RX PubMed=10931946; DOI=10.1073/pnas.160270997;
RA Hu R.-M., Han Z.-G., Song H.-D., Peng Y.-D., Huang Q.-H., Ren S.-X.,
RA Gu Y.-J., Huang C.-H., Li Y.-B., Jiang C.-L., Fu G., Zhang Q.-H., Gu B.-W.,
RA Dai M., Mao Y.-F., Gao G.-F., Rong R., Ye M., Zhou J., Xu S.-H., Gu J.,
RA Shi J.-X., Jin W.-R., Zhang C.-K., Wu T.-M., Huang G.-Y., Chen Z.,
RA Chen M.-D., Chen J.-L.;
RT "Gene expression profiling in the human hypothalamus-pituitary-adrenal axis
RT and full-length cDNA cloning.";
RL Proc. Natl. Acad. Sci. U.S.A. 97:9543-9548(2000).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT THR-88.
RC TISSUE=Placenta;
RX PubMed=16303743; DOI=10.1093/dnares/12.2.117;
RA Otsuki T., Ota T., Nishikawa T., Hayashi K., Suzuki Y., Yamamoto J.,
RA Wakamatsu A., Kimura K., Sakamoto K., Hatano N., Kawai Y., Ishii S.,
RA Saito K., Kojima S., Sugiyama T., Ono T., Okano K., Yoshikawa Y.,
RA Aotsuka S., Sasaki N., Hattori A., Okumura K., Nagai K., Sugano S.,
RA Isogai T.;
RT "Signal sequence and keyword trap in silico for selection of full-length
RT human cDNAs encoding secretion or membrane proteins from oligo-capped cDNA
RT libraries.";
RL DNA Res. 12:117-126(2005).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16541075; DOI=10.1038/nature04569;
RA Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y.,
RA Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C.,
RA Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C.,
RA Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R.,
RA Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E.,
RA Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y.,
RA Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G.,
RA Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H.,
RA Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S.,
RA Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M.,
RA Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H.,
RA Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q.,
RA Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V.,
RA Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E.,
RA Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K.,
RA Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D.,
RA Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R.,
RA David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E.,
RA D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N.,
RA Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N.,
RA Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R.,
RA Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S.,
RA LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H.,
RA Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P.,
RA Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G.,
RA Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E.,
RA Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S.,
RA Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O.,
RA Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J.,
RA Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A.,
RA Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M.,
RA Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I.,
RA Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A.,
RA Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y.,
RA Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A.,
RA Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F.,
RA Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L.,
RA Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G.,
RA Gibbs R.A.;
RT "The finished DNA sequence of human chromosome 12.";
RL Nature 440:346-351(2006).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 [7]
RP FUNCTION, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=17319741; DOI=10.1371/journal.ppat.0030017;
RA Gubser C., Bergamaschi D., Hollinshead M., Lu X., van Kuppeveld F.J.,
RA Smith G.L.;
RT "A new inhibitor of apoptosis from vaccinia virus and eukaryotes.";
RL PLoS Pathog. 3:E17-E17(2007).
RN [8]
RP GENE FAMILY, AND NOMENCLATURE.
RX PubMed=19784873; DOI=10.1007/s10495-009-0402-2;
RA Hu L., Smith T.F., Goldberger G.;
RT "LFG: a candidate apoptosis regulatory gene family.";
RL Apoptosis 14:1255-1265(2009).
RN [9]
RP FUNCTION, AND INTERACTION WITH ITPR3.
RX PubMed=19553469; DOI=10.1091/mbc.e09-05-0385;
RA de Mattia F., Gubser C., van Dommelen M.M., Visch H.J., Distelmaier F.,
RA Postigo A., Luyten T., Parys J.B., de Smedt H., Smith G.L., Willems P.H.,
RA van Kuppeveld F.J.;
RT "Human Golgi antiapoptotic protein modulates intracellular calcium
RT fluxes.";
RL Mol. Biol. Cell 20:3638-3645(2009).
RN [10]
RP SUBCELLULAR LOCATION, AND TOPOLOGY.
RX PubMed=22418439; DOI=10.1074/jbc.m111.336149;
RA Carrara G., Saraiva N., Gubser C., Johnson B.F., Smith G.L.;
RT "Six-transmembrane topology for Golgi anti-apoptotic protein (GAAP) and Bax
RT inhibitor 1 (BI-1) provides model for the transmembrane Bax inhibitor-
RT containing motif (TMBIM) family.";
RL J. Biol. Chem. 287:15896-15905(2012).
CC -!- FUNCTION: Anti-apoptotic protein which can inhibit apoptosis induced by
CC intrinsic and extrinsic apoptotic stimuli. Can modulate both
CC capacitative Ca2+ entry and inositol 1,4,5-trisphosphate (IP3)-mediated
CC Ca2+ release. {ECO:0000269|PubMed:17319741,
CC ECO:0000269|PubMed:19553469}.
CC -!- SUBUNIT: Interacts with ITPR3. {ECO:0000269|PubMed:19553469}.
CC -!- SUBCELLULAR LOCATION: Golgi apparatus membrane
CC {ECO:0000269|PubMed:17319741, ECO:0000269|PubMed:22418439}; Multi-pass
CC membrane protein {ECO:0000269|PubMed:17319741,
CC ECO:0000269|PubMed:22418439}.
CC -!- SIMILARITY: Belongs to the BI1 family. LFG subfamily. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAD34114.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AF182041; AAG16898.1; -; mRNA.
DR EMBL; AF151877; AAD34114.1; ALT_INIT; mRNA.
DR EMBL; AF113127; AAF14868.1; -; mRNA.
DR EMBL; AK075069; BAC11384.1; -; mRNA.
DR EMBL; AC078927; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC020613; -; NOT_ANNOTATED_CDS; mRNA.
DR CCDS; CCDS41805.1; -.
DR RefSeq; NP_001269535.1; NM_001282606.1.
DR RefSeq; NP_001269538.1; NM_001282609.1.
DR RefSeq; NP_001269539.1; NM_001282610.1.
DR RefSeq; NP_057140.2; NM_016056.3.
DR AlphaFoldDB; Q9HC24; -.
DR SMR; Q9HC24; -.
DR BioGRID; 119653; 13.
DR IntAct; Q9HC24; 4.
DR TCDB; 1.A.14.3.6; the calcium transporter a (cata) (formerly the testis-enhanced gene transfer (tegt) family.
DR iPTMnet; Q9HC24; -.
DR PhosphoSitePlus; Q9HC24; -.
DR BioMuta; TMBIM4; -.
DR DMDM; 322510100; -.
DR EPD; Q9HC24; -.
DR MassIVE; Q9HC24; -.
DR PaxDb; Q9HC24; -.
DR PeptideAtlas; Q9HC24; -.
DR PRIDE; Q9HC24; -.
DR ProteomicsDB; 81628; -.
DR Antibodypedia; 53205; 110 antibodies from 20 providers.
DR DNASU; 51643; -.
DR Ensembl; ENST00000358230.8; ENSP00000350965.3; ENSG00000155957.19.
DR GeneID; 51643; -.
DR KEGG; hsa:51643; -.
DR MANE-Select; ENST00000358230.8; ENSP00000350965.3; NM_016056.4; NP_057140.2.
DR UCSC; uc001stc.5; human.
DR CTD; 51643; -.
DR DisGeNET; 51643; -.
DR GeneCards; TMBIM4; -.
DR HGNC; HGNC:24257; TMBIM4.
DR HPA; ENSG00000155957; Low tissue specificity.
DR neXtProt; NX_Q9HC24; -.
DR OpenTargets; ENSG00000155957; -.
DR PharmGKB; PA142670805; -.
DR VEuPathDB; HostDB:ENSG00000155957; -.
DR GeneTree; ENSGT01050000244940; -.
DR HOGENOM; CLU_058671_0_2_1; -.
DR InParanoid; Q9HC24; -.
DR OMA; SHNAYAE; -.
DR OrthoDB; 1290306at2759; -.
DR PhylomeDB; Q9HC24; -.
DR TreeFam; TF321860; -.
DR PathwayCommons; Q9HC24; -.
DR SignaLink; Q9HC24; -.
DR BioGRID-ORCS; 51643; 12 hits in 1083 CRISPR screens.
DR ChiTaRS; TMBIM4; human.
DR GeneWiki; TMBIM4; -.
DR GenomeRNAi; 51643; -.
DR Pharos; Q9HC24; Tbio.
DR PRO; PR:Q9HC24; -.
DR Proteomes; UP000005640; Chromosome 12.
DR RNAct; Q9HC24; protein.
DR Bgee; ENSG00000155957; Expressed in buccal mucosa cell and 198 other tissues.
DR ExpressionAtlas; Q9HC24; baseline and differential.
DR Genevisible; Q9HC24; HS.
DR GO; GO:0000139; C:Golgi membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005795; C:Golgi stack; IDA:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0016020; C:membrane; IBA:GO_Central.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IMP:UniProtKB.
DR GO; GO:0050848; P:regulation of calcium-mediated signaling; IDA:UniProtKB.
DR InterPro; IPR006214; Bax_inhibitor_1-related.
DR PANTHER; PTHR23291; PTHR23291; 1.
DR Pfam; PF01027; Bax1-I; 1.
PE 1: Evidence at protein level;
KW Apoptosis; Golgi apparatus; Membrane; Reference proteome; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..238
FT /note="Protein lifeguard 4"
FT /id="PRO_0000179092"
FT TOPO_DOM 1..38
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 39..59
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 60..68
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 69..89
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 90..97
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 98..118
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 119..120
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 121..141
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 142..151
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 152..172
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 173..175
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 176..196
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 197..208
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT INTRAMEM 209..229
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 230..238
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT VARIANT 2
FT /note="A -> V (in dbSNP:rs11176070)"
FT /id="VAR_055547"
FT VARIANT 88
FT /note="I -> T (in dbSNP:rs8793)"
FT /evidence="ECO:0000269|PubMed:10810093,
FT ECO:0000269|PubMed:10931946, ECO:0000269|PubMed:16303743"
FT /id="VAR_014946"
SQ SEQUENCE 238 AA; 26971 MW; 30CD39CF7F38564E CRC64;
MADPDPRYPR SSIEDDFNYG SSVASATVHI RMAFLRKVYS ILSLQVLLTT VTSTVFLYFE
SVRTFVHESP ALILLFALGS LGLIFALILN RHKYPLNLYL LFGFTLLEAL TVAVVVTFYD
VYIILQAFIL TTTVFFGLTV YTLQSKKDFS KFGAGLFALL WILCLSGFLK FFFYSEIMEL
VLAAAGALLF CGFIIYDTHS LMHKLSPEEY VLAAISLYLD IINLFLHLLR FLEAVNKK
