B2CL2_MOUSE
ID B2CL2_MOUSE Reviewed; 193 AA.
AC P70345; Q545Q4; Q6A093; Q8CFR2; Q8CGL4; Q9CYW5;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1997, sequence version 1.
DT 03-AUG-2022, entry version 175.
DE RecName: Full=Bcl-2-like protein 2;
DE Short=Bcl2-L-2;
DE AltName: Full=Apoptosis regulator Bcl-W;
DE AltName: Full=c98;
GN Name=Bcl2l2; Synonyms=Bclw, Kiaa0271;
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), AND FUNCTION.
RX PubMed=8761287;
RA Gibson L., Holmgreen S.P., Huang D.C., Bernard O., Copeland N.G.,
RA Jenkins N.A., Sutherland G.R., Baker E., Adams J.M., Cory S.;
RT "Bcl-w, a novel member of the Bcl-2 family, promotes cell survival.";
RL Oncogene 13:665-675(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND DISRUPTION PHENOTYPE.
RC STRAIN=C57BL/10J;
RX PubMed=9500547; DOI=10.1038/ng0398-251;
RA Ross A.J., Waymire K.G., Moss J.E., Parlow A.F., Skinner M.K.,
RA Russell L.D., Macgregor G.R.;
RT "Testicular degeneration in Bclw-deficient mice.";
RL Nat. Genet. 18:251-256(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, AND INDUCTION.
RC STRAIN=C57BL/6J; TISSUE=Skin;
RX PubMed=14746907; DOI=10.1016/j.bbaexp.2003.11.006;
RA Su H.-Y., Cheng W.T.K., Chen S.-C., Lin C.-T., Lien Y.-Y., Liu H.-J.,
RA Gilmour R.S.;
RT "Mouse keratinocytes express c98, a novel gene homologous to bcl-2, that is
RT stimulated by insulin-like growth factor 1 and prevents dexamethasone-
RT induced apoptosis.";
RL Biochim. Biophys. Acta 1676:127-137(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC STRAIN=C57BL/6J; TISSUE=Lung, and Testis;
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Pancreatic islet;
RX PubMed=15368895; DOI=10.1093/dnares/11.3.205;
RA Okazaki N., Kikuno R., Ohara R., Inamoto S., Koseki H., Hiraoka S.,
RA Saga Y., Seino S., Nishimura M., Kaisho T., Hoshino K., Kitamura H.,
RA Nagase T., Ohara O., Koga H.;
RT "Prediction of the coding sequences of mouse homologues of KIAA gene: IV.
RT The complete nucleotide sequences of 500 mouse KIAA-homologous cDNAs
RT identified by screening of terminal sequences of cDNA clones randomly
RT sampled from size-fractionated libraries.";
RL DNA Res. 11:205-218(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC STRAIN=C57BL/6J; 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 [7]
RP FUNCTION, AND DEVELOPMENTAL STAGE.
RX PubMed=11784036; DOI=10.1006/dbio.2001.0445;
RA Ross A.J., Amy S.P., Mahar P.L., Lindsten T., Knudson C.M., Thompson C.B.,
RA Korsmeyer S.J., MacGregor G.R.;
RT "BCLW mediates survival of postmitotic Sertoli cells by regulating BAX
RT activity.";
RL Dev. Biol. 239:295-308(2001).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, and Lung;
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 [9]
RP INTERACTION WITH HIF3A.
RX PubMed=21546903; DOI=10.1038/cdd.2011.47;
RA Torii S., Goto Y., Ishizawa T., Hoshi H., Goryo K., Yasumoto K.,
RA Fukumura H., Sogawa K.;
RT "Pro-apoptotic activity of inhibitory PAS domain protein (IPAS), a negative
RT regulator of HIF-1, through binding to pro-survival Bcl-2 family
RT proteins.";
RL Cell Death Differ. 18:1711-1725(2011).
CC -!- FUNCTION: Promotes cell survival. Blocks dexamethasone-induced
CC apoptosis. Mediates survival of postmitotic Sertoli cells by
CC suppressing death-promoting activity of BAX.
CC {ECO:0000269|PubMed:11784036, ECO:0000269|PubMed:14746907,
CC ECO:0000269|PubMed:8761287}.
CC -!- SUBUNIT: Interacts with HIF3A isoform 2 (via C-terminus domain)
CC (PubMed:21546903). Interacts with BOP (By similarity). {ECO:0000250,
CC ECO:0000269|PubMed:21546903}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion membrane {ECO:0000250}; Peripheral
CC membrane protein {ECO:0000250}. Note=Loosely associated with the
CC mitochondrial membrane in healthy cells. During apoptosis, tightly
CC bound to the membrane (By similarity). {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P70345-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P70345-2; Sequence=VSP_014780;
CC -!- TISSUE SPECIFICITY: Expressed in almost all myeloid cell lines and in a
CC wide range of tissues, with highest levels in brain, colon, and
CC salivary gland.
CC -!- DEVELOPMENTAL STAGE: Expressed in both mitotic and postmitotic Sertoli
CC cells. {ECO:0000269|PubMed:11784036}.
CC -!- INDUCTION: By Igf1. {ECO:0000269|PubMed:14746907}.
CC -!- DOMAIN: The BH4 motif seems to be involved in the anti-apoptotic
CC function.
CC -!- DOMAIN: The BH1 and BH2 motifs form a hydrophobic groove which acts as
CC a docking site for the BH3 domain of some pro-apoptotic proteins. The
CC C-terminal residues of BCL2L2 fold into the BH3-binding cleft and
CC modulate pro-survival activity by regulating ligand access. When BH3
CC domain-containing proteins bind, they displace the C-terminus, allowing
CC its insertion into the membrane and neutralizing the pro-survival
CC activity of BCL2L2 (By similarity). {ECO:0000250}.
CC -!- DISRUPTION PHENOTYPE: Mice are sterile due to arrest in spermatogenesis
CC associated with a gradual loss of germ and Sertoli cells from the
CC testis. {ECO:0000269|PubMed:9500547}.
CC -!- SIMILARITY: Belongs to the Bcl-2 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAD32203.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; U59746; AAB09056.1; -; mRNA.
DR EMBL; AF030769; AAB86430.1; -; mRNA.
DR EMBL; AY170344; AAO13177.2; -; mRNA.
DR EMBL; AK004680; BAB23468.1; -; mRNA.
DR EMBL; AK013244; BAB28740.1; -; mRNA.
DR EMBL; AK015644; BAB29912.1; -; mRNA.
DR EMBL; AK172925; BAD32203.1; ALT_FRAME; mRNA.
DR EMBL; BC040369; AAH40369.1; -; mRNA.
DR CCDS; CCDS27103.1; -. [P70345-1]
DR RefSeq; NP_031563.1; NM_007537.1. [P70345-1]
DR RefSeq; XP_006518520.1; XM_006518457.3. [P70345-1]
DR RefSeq; XP_006518521.1; XM_006518458.2. [P70345-1]
DR AlphaFoldDB; P70345; -.
DR SMR; P70345; -.
DR BioGRID; 198325; 3.
DR ComplexPortal; CPX-310; BIK:BCL-w complex.
DR STRING; 10090.ENSMUSP00000022806; -.
DR PhosphoSitePlus; P70345; -.
DR MaxQB; P70345; -.
DR PaxDb; P70345; -.
DR PeptideAtlas; P70345; -.
DR PRIDE; P70345; -.
DR ProteomicsDB; 277140; -. [P70345-1]
DR ProteomicsDB; 277141; -. [P70345-2]
DR Antibodypedia; 3670; 436 antibodies from 38 providers.
DR DNASU; 12050; -.
DR Ensembl; ENSMUST00000022806; ENSMUSP00000022806; ENSMUSG00000089682. [P70345-1]
DR Ensembl; ENSMUST00000133397; ENSMUSP00000116385; ENSMUSG00000089682. [P70345-2]
DR GeneID; 12050; -.
DR KEGG; mmu:12050; -.
DR UCSC; uc007txe.1; mouse. [P70345-1]
DR UCSC; uc007txf.1; mouse. [P70345-2]
DR CTD; 599; -.
DR MGI; MGI:108052; Bcl2l2.
DR VEuPathDB; HostDB:ENSMUSG00000089682; -.
DR eggNOG; KOG4728; Eukaryota.
DR GeneTree; ENSGT01050000244953; -.
DR HOGENOM; CLU_085401_0_2_1; -.
DR InParanoid; P70345; -.
DR OMA; DVARWMT; -.
DR OrthoDB; 1218929at2759; -.
DR PhylomeDB; P70345; -.
DR TreeFam; TF315834; -.
DR BioGRID-ORCS; 12050; 0 hits in 72 CRISPR screens.
DR ChiTaRS; Bcl2l2; mouse.
DR PRO; PR:P70345; -.
DR Proteomes; UP000000589; Chromosome 14.
DR RNAct; P70345; protein.
DR Bgee; ENSMUSG00000089682; Expressed in medial dorsal nucleus of thalamus and 251 other tissues.
DR ExpressionAtlas; P70345; baseline and differential.
DR Genevisible; P70345; MM.
DR GO; GO:0097136; C:Bcl-2 family protein complex; ISO:MGI.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0005829; C:cytosol; IDA:MGI.
DR GO; GO:0031966; C:mitochondrial membrane; IDA:MGI.
DR GO; GO:0005741; C:mitochondrial outer membrane; IBA:GO_Central.
DR GO; GO:0005739; C:mitochondrion; ISO:MGI.
DR GO; GO:0051400; F:BH domain binding; ISO:MGI.
DR GO; GO:0097718; F:disordered domain specific binding; ISO:MGI.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0046982; F:protein heterodimerization activity; IBA:GO_Central.
DR GO; GO:0042803; F:protein homodimerization activity; IBA:GO_Central.
DR GO; GO:0044877; F:protein-containing complex binding; ISO:MGI.
DR GO; GO:0006915; P:apoptotic process; ISO:MGI.
DR GO; GO:0007420; P:brain development; IEA:Ensembl.
DR GO; GO:1904646; P:cellular response to amyloid-beta; IEA:Ensembl.
DR GO; GO:0071392; P:cellular response to estradiol stimulus; IEA:Ensembl.
DR GO; GO:1905430; P:cellular response to glycine; IEA:Ensembl.
DR GO; GO:0097192; P:extrinsic apoptotic signaling pathway in absence of ligand; IDA:MGI.
DR GO; GO:0008630; P:intrinsic apoptotic signaling pathway in response to DNA damage; IBA:GO_Central.
DR GO; GO:0043066; P:negative regulation of apoptotic process; ISO:MGI.
DR GO; GO:2001243; P:negative regulation of intrinsic apoptotic signaling pathway; IBA:GO_Central.
DR GO; GO:0035795; P:negative regulation of mitochondrial membrane permeability; ISO:MGI.
DR GO; GO:0090201; P:negative regulation of release of cytochrome c from mitochondria; ISO:MGI.
DR GO; GO:0042981; P:regulation of apoptotic process; ISO:MGI.
DR GO; GO:0002931; P:response to ischemia; IEA:Ensembl.
DR GO; GO:0060011; P:Sertoli cell proliferation; IGI:MGI.
DR CDD; cd06845; Bcl-2_like; 1.
DR Gene3D; 1.10.437.10; -; 1.
DR InterPro; IPR013280; Apop_reg_BclW.
DR InterPro; IPR036834; Bcl-2-like_sf.
DR InterPro; IPR046371; Bcl-2_BH1-3.
DR InterPro; IPR026298; Bcl-2_fam.
DR InterPro; IPR002475; Bcl2-like.
DR InterPro; IPR020717; Bcl2_BH1_motif_CS.
DR InterPro; IPR020726; Bcl2_BH2_motif_CS.
DR InterPro; IPR003093; Bcl2_BH4.
DR InterPro; IPR020731; Bcl2_BH4_motif_CS.
DR PANTHER; PTHR11256; PTHR11256; 1.
DR PANTHER; PTHR11256:SF51; PTHR11256:SF51; 1.
DR Pfam; PF00452; Bcl-2; 1.
DR Pfam; PF02180; BH4; 1.
DR PRINTS; PR01865; APOPREGBCLW.
DR PRINTS; PR01862; BCL2FAMILY.
DR SMART; SM00337; BCL; 1.
DR SMART; SM00265; BH4; 1.
DR SUPFAM; SSF56854; SSF56854; 1.
DR PROSITE; PS50062; BCL2_FAMILY; 1.
DR PROSITE; PS01080; BH1; 1.
DR PROSITE; PS01258; BH2; 1.
DR PROSITE; PS01260; BH4_1; 1.
DR PROSITE; PS50063; BH4_2; 1.
PE 1: Evidence at protein level;
KW Acetylation; Alternative splicing; Apoptosis; Membrane; Mitochondrion;
KW Reference proteome.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:Q92843"
FT CHAIN 2..193
FT /note="Bcl-2-like protein 2"
FT /id="PRO_0000143067"
FT MOTIF 9..29
FT /note="BH4"
FT MOTIF 85..104
FT /note="BH1"
FT MOTIF 136..151
FT /note="BH2"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0000250|UniProtKB:Q92843"
FT VAR_SEQ 145..193
FT /note="AEFTALYGDGALEEARRLREGNWASVRTVLTGAVALGALVTVGAFFASK ->
FT VRSSQLLLSASLYKVGLHGKIGPLMGGWGCAGKG (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:16141072"
FT /id="VSP_014780"
FT CONFLICT 16
FT /note="D -> Y (in Ref. 3; AAO13177)"
FT /evidence="ECO:0000305"
FT CONFLICT 21
FT /note="K -> Q (in Ref. 3; AAO13177)"
FT /evidence="ECO:0000305"
FT CONFLICT 53..54
FT /note="FE -> LQ (in Ref. 3; AAO13177)"
FT /evidence="ECO:0000305"
FT CONFLICT 63
FT /note="D -> H (in Ref. 3; AAO13177)"
FT /evidence="ECO:0000305"
FT CONFLICT 114
FT /note="E -> H (in Ref. 3; AAO13177)"
FT /evidence="ECO:0000305"
FT CONFLICT 136
FT /note="D -> Y (in Ref. 3; AAO13177)"
FT /evidence="ECO:0000305"
FT CONFLICT 192
FT /note="S -> Y (in Ref. 3; AAO13177)"
FT /evidence="ECO:0000305"
FT CONFLICT P70345-2:177
FT /note="K -> R (in Ref. 4; BAB28740)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 193 AA; 20790 MW; 36CA185F5945DFB4 CRC64;
MATPASTPDT RALVADFVGY KLRQKGYVCG AGPGEGPAAD PLHQAMRAAG DEFETRFRRT
FSDLAAQLHV TPGSAQQRFT QVSDELFQGG PNWGRLVAFF VFGAALCAES VNKEMEPLVG
QVQDWMVAYL ETRLADWIHS SGGWAEFTAL YGDGALEEAR RLREGNWASV RTVLTGAVAL
GALVTVGAFF ASK
