LFG2_MOUSE
ID LFG2_MOUSE Reviewed; 317 AA.
AC Q8K097; Q3TY22; Q8K1F6; Q9D6K4;
DT 21-NOV-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2002, sequence version 1.
DT 03-AUG-2022, entry version 140.
DE RecName: Full=Protein lifeguard 2;
DE AltName: Full=Fas apoptotic inhibitory molecule 2;
DE AltName: Full=Neural membrane protein 35;
GN Name=Faim2; Synonyms=Kiaa0950, Lfg, Lfg2, Nmp35;
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] (ISOFORM 1).
RC STRAIN=C57BL/6J; TISSUE=Retina;
RA Sole C., Segura M.F., Bayascas J.R., Comella J.X.;
RT "Cloning and characterization of the long form of mouse lifeguard (LFG-L),
RT an anti Fas-apoptotic molecule.";
RL Submitted (JAN-2002) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=12693553; DOI=10.1093/dnares/10.1.35;
RA Okazaki N., Kikuno R., Ohara R., Inamoto S., Aizawa H., Yuasa S.,
RA Nakajima D., Nagase T., Ohara O., Koga H.;
RT "Prediction of the coding sequences of mouse homologues of KIAA gene: II.
RT The complete nucleotide sequences of 400 mouse KIAA-homologous cDNAs
RT identified by screening of terminal sequences of cDNA clones randomly
RT sampled from size-fractionated libraries.";
RL DNA Res. 10:35-48(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC STRAIN=C57BL/6J; TISSUE=Hippocampus, and Visual cortex;
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Retina;
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 [5]
RP FUNCTION, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=17635665; DOI=10.1111/j.1471-4159.2007.04767.x;
RA Fernandez M., Segura M.F., Sole C., Colino A., Comella J.X., Cena V.;
RT "Lifeguard/neuronal membrane protein 35 regulates Fas ligand-mediated
RT apoptosis in neurons via microdomain recruitment.";
RL J. Neurochem. 103:190-203(2007).
RN [6]
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 [7]
RP FUNCTION.
RX PubMed=21209208; DOI=10.1523/jneurosci.2188-10.2011;
RA Reich A., Spering C., Gertz K., Harms C., Gerhardt E., Kronenberg G.,
RA Nave K.A., Schwab M., Tauber S.C., Drinkut A., Harms K., Beier C.P.,
RA Voigt A., Goebbels S., Endres M., Schulz J.B.;
RT "Fas/CD95 regulatory protein Faim2 is neuroprotective after transient brain
RT ischemia.";
RL J. Neurosci. 31:225-233(2011).
RN [8]
RP FUNCTION, DISRUPTION PHENOTYPE, AND TISSUE SPECIFICITY.
RX PubMed=21957071; DOI=10.1073/pnas.1114226108;
RA Hurtado de Mendoza T., Perez-Garcia C.G., Kroll T.T., Hoong N.H.,
RA O'Leary D.D., Verma I.M.;
RT "Antiapoptotic protein Lifeguard is required for survival and maintenance
RT of Purkinje and granular cells.";
RL Proc. Natl. Acad. Sci. U.S.A. 108:17189-17194(2011).
CC -!- FUNCTION: Antiapoptotic protein which protects cells uniquely from Fas-
CC induced apoptosis. Regulates Fas-mediated apoptosis in neurons by
CC interfering with caspase-8 activation. Plays a role in cerebellar
CC development by affecting cerebellar size, internal granular layer (IGL)
CC thickness, and Purkinje cell (PC) development.
CC {ECO:0000269|PubMed:17635665, ECO:0000269|PubMed:21209208,
CC ECO:0000269|PubMed:21957071}.
CC -!- SUBUNIT: Interacts with FAS/TNFRSF6 and BAX. {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250}; Multi-pass membrane
CC protein {ECO:0000250}. Membrane raft {ECO:0000269|PubMed:17635665}.
CC Postsynaptic cell membrane {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=Long, LFG-L;
CC IsoId=Q8K097-1; Sequence=Displayed;
CC Name=2; Synonyms=Short, LFG-S;
CC IsoId=Q8K097-2; Sequence=VSP_008994;
CC -!- TISSUE SPECIFICITY: Brain. Highly expressed in cerebellum, also found
CC in cortex, olfactory bulb, and hippocampus.
CC {ECO:0000269|PubMed:17635665, ECO:0000269|PubMed:21957071}.
CC -!- DISRUPTION PHENOTYPE: Mice show reduced cerebellar size and internal
CC granular layer (IGL) thickness in early developmental stages, delayed
CC Purkinje Cell (PC) development, with an abnormal morphology and reduced
CC cellular density, increased caspase-8 and caspase-3 activity in PCs and
CC higher sensitivity to Fas-mediated apoptosis.
CC {ECO:0000269|PubMed:21957071}.
CC -!- SIMILARITY: Belongs to the BI1 family. LFG subfamily. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAC98056.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AF468028; AAM46781.1; -; mRNA.
DR EMBL; AK013476; BAB28874.1; -; mRNA.
DR EMBL; AK030513; BAC26999.1; -; mRNA.
DR EMBL; AK129246; BAC98056.1; ALT_INIT; mRNA.
DR EMBL; AK158960; BAE34742.1; -; mRNA.
DR EMBL; BC032278; AAH32278.1; -; mRNA.
DR CCDS; CCDS37203.1; -. [Q8K097-1]
DR CCDS; CCDS88840.1; -. [Q8K097-2]
DR RefSeq; NP_001033747.1; NM_001038658.2. [Q8K097-2]
DR RefSeq; NP_082500.2; NM_028224.4. [Q8K097-1]
DR RefSeq; XP_006521512.1; XM_006521449.3. [Q8K097-1]
DR AlphaFoldDB; Q8K097; -.
DR SMR; Q8K097; -.
DR BioGRID; 215353; 1.
DR STRING; 10090.ENSMUSP00000023750; -.
DR GlyGen; Q8K097; 1 site.
DR iPTMnet; Q8K097; -.
DR PhosphoSitePlus; Q8K097; -.
DR PaxDb; Q8K097; -.
DR PeptideAtlas; Q8K097; -.
DR PRIDE; Q8K097; -.
DR ProteomicsDB; 291940; -. [Q8K097-1]
DR ProteomicsDB; 291941; -. [Q8K097-2]
DR Antibodypedia; 14095; 270 antibodies from 32 providers.
DR DNASU; 72393; -.
DR Ensembl; ENSMUST00000023750; ENSMUSP00000023750; ENSMUSG00000023011. [Q8K097-1]
DR Ensembl; ENSMUST00000231171; ENSMUSP00000155195; ENSMUSG00000023011. [Q8K097-2]
DR GeneID; 72393; -.
DR KEGG; mmu:72393; -.
DR UCSC; uc007xpp.2; mouse. [Q8K097-2]
DR UCSC; uc007xpq.2; mouse. [Q8K097-1]
DR CTD; 23017; -.
DR MGI; MGI:1919643; Faim2.
DR VEuPathDB; HostDB:ENSMUSG00000023011; -.
DR eggNOG; KOG2322; Eukaryota.
DR GeneTree; ENSGT01050000244890; -.
DR HOGENOM; CLU_058671_3_2_1; -.
DR InParanoid; Q8K097; -.
DR OMA; YPGDTEM; -.
DR OrthoDB; 1290306at2759; -.
DR PhylomeDB; Q8K097; -.
DR TreeFam; TF319996; -.
DR BioGRID-ORCS; 72393; 0 hits in 71 CRISPR screens.
DR ChiTaRS; Faim2; mouse.
DR PRO; PR:Q8K097; -.
DR Proteomes; UP000000589; Chromosome 15.
DR RNAct; Q8K097; protein.
DR Bgee; ENSMUSG00000023011; Expressed in superior frontal gyrus and 94 other tissues.
DR Genevisible; Q8K097; MM.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:MGI.
DR GO; GO:0005794; C:Golgi apparatus; IDA:MGI.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0016020; C:membrane; IDA:MGI.
DR GO; GO:0045121; C:membrane raft; IDA:UniProtKB.
DR GO; GO:0045211; C:postsynaptic membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0097190; P:apoptotic signaling pathway; IMP:MGI.
DR GO; GO:0021681; P:cerebellar granular layer development; IMP:UniProtKB.
DR GO; GO:0021702; P:cerebellar Purkinje cell differentiation; IMP:UniProtKB.
DR GO; GO:0021680; P:cerebellar Purkinje cell layer development; IMP:UniProtKB.
DR GO; GO:0021549; P:cerebellum development; IMP:UniProtKB.
DR GO; GO:2001234; P:negative regulation of apoptotic signaling pathway; IMP:MGI.
DR GO; GO:1902042; P:negative regulation of extrinsic apoptotic signaling pathway via death domain receptors; ISO:MGI.
DR GO; GO:0043524; P:negative regulation of neuron apoptotic process; IMP:MGI.
DR GO; GO:0051402; P:neuron apoptotic process; IMP:MGI.
DR GO; GO:0043523; P:regulation of neuron apoptotic process; IMP:UniProtKB.
DR GO; GO:0002931; P:response to ischemia; IMP:MGI.
DR InterPro; IPR006214; Bax_inhibitor_1-related.
DR PANTHER; PTHR23291; PTHR23291; 1.
DR Pfam; PF01027; Bax1-I; 1.
PE 2: Evidence at transcript level;
KW Alternative splicing; Apoptosis; Cell membrane; Glycoprotein; Membrane;
KW Postsynaptic cell membrane; Reference proteome; Synapse; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..317
FT /note="Protein lifeguard 2"
FT /id="PRO_0000179088"
FT TRANSMEM 107..127
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 139..159
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 166..186
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 195..215
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 226..246
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 252..272
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 291..311
FT /note="Helical"
FT /evidence="ECO:0000255"
FT REGION 1..54
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1..20
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 192
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VAR_SEQ 72..84
FT /note="SGSSGYEGGFPAG -> R (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_008994"
FT CONFLICT 256
FT /note="A -> T (in Ref. 2; BAC98056)"
FT /evidence="ECO:0000305"
FT CONFLICT 312
FT /note="F -> Y (in Ref. 1; AAM46781)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 317 AA; 35258 MW; A62D51BA49BCDB15 CRC64;
MTQGKLSVAN KAPGTEGQQH QANGEKKDAP AVPSAPPSYE EATSGEGLKA GTFPQGPTAV
PLHPSWAYVD PSGSSGYEGG FPAGHHEHFT TFSWDDQKVR RLFIRKVYTI LLVQLLVTLA
VVALFTFCDV VKDYVQANPG WYWASYAVFF ATYLTLACCS GPRRHFPWNL ILLTIFTLSM
AYLTGMLSSY YNTTSVLLCL VITALVCLSV TIFSFQTKFD FTSCQGVLFV LLMTLFFSGL
LLAVLLPFQY VPWLHAVYAV LGAGVFTLFL AFDTQLLMGN RRHSLSPEEY IFGALNIYLD
IIYIFTFFLQ LFGTNRE
