BAG1_MOUSE
ID BAG1_MOUSE Reviewed; 355 AA.
AC Q60739; Q561N1; Q6IS45; Q9D7K6;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 15-JUL-1999, sequence version 3.
DT 03-AUG-2022, entry version 178.
DE RecName: Full=BAG family molecular chaperone regulator 1;
DE Short=BAG-1;
DE AltName: Full=Bcl-2-associated athanogene 1;
GN Name=Bag1;
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 TISSUE=Embryo;
RX PubMed=7834747; DOI=10.1016/0092-8674(95)90410-7;
RA Takayama S., Sato T., Krajewski S., Kochel K., Irie S., Millan J.A.,
RA Reed J.C.;
RT "Cloning and functional analysis of BAG-1: a novel Bcl-2-binding protein
RT with anti-cell death activity.";
RL Cell 80:279-284(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC STRAIN=C57BL/6J; TISSUE=Tongue;
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 GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=Czech II, and NMRI; TISSUE=Mammary tumor;
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 [6]
RP IDENTIFICATION OF ISOFORMS 1 AND 2, ALTERNATIVE INITIATION, SUBCELLULAR
RP LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=9396724; DOI=10.1042/bj3280807;
RA Packham G., Brimmell M., Cleveland J.L.;
RT "Mammalian cells express two differently localized Bag-1 isoforms generated
RT by alternative translation initiation.";
RL Biochem. J. 328:807-813(1997).
RN [7]
RP IDENTIFICATION OF ISOFORMS 1 AND 2, ALTERNATIVE INITIATION, SUBCELLULAR
RP LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=9679980;
RA Takayama S., Krajewski S., Krajewska M., Kitada S., Zapata J.M., Kochel K.,
RA Knee D., Scudiero D., Tudor G., Miller G.J., Miyashita T., Yamada M.,
RA Reed J.C.;
RT "Expression and location of Hsp70/Hsc-binding anti-apoptotic protein BAG-1
RT and its variants in normal tissues and tumor cell lines.";
RL Cancer Res. 58:3116-3131(1998).
RN [8]
RP FUNCTION.
RX PubMed=9873016; DOI=10.1074/jbc.274.2.781;
RA Takayama S., Xie Z., Reed J.C.;
RT "An evolutionarily conserved family of Hsp70/Hsc70 molecular chaperone
RT regulators.";
RL J. Biol. Chem. 274:781-786(1999).
RN [9]
RP INTERACTION WITH SIAH2, AND UBIQUITINATION.
RX PubMed=11257006; DOI=10.1242/jcs.114.7.1409;
RA Sourisseau T., Desbois C., Debure L., Bowtell D.D.L., Cato A.C.B.,
RA Schneikert J., Moyse E., Michel D.;
RT "Alteration of the stability of Bag-1 protein in the control of olfactory
RT neuronal apoptosis.";
RL J. Cell Sci. 114:1409-1416(2001).
RN [10]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Heart, Kidney, Lung, Spleen, and Testis;
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).
CC -!- FUNCTION: Co-chaperone for HSP70 and HSC70 chaperone proteins
CC (PubMed:9873016). Acts as a nucleotide-exchange factor (NEF) promoting
CC the release of ADP from the HSP70 and HSC70 proteins thereby triggering
CC client/substrate protein release. Nucleotide release is mediated via
CC its binding to the nucleotide-binding domain (NBD) of HSPA8/HSC70 where
CC as the substrate release is mediated via its binding to the substrate-
CC binding domain (SBD) of HSPA8/HSC70. Inhibits the pro-apoptotic
CC function of PPP1R15A, and has anti-apoptotic activity. Markedly
CC increases the anti-cell death function of BCL2 induced by various
CC stimuli (By similarity). {ECO:0000250|UniProtKB:Q99933,
CC ECO:0000269|PubMed:9873016}.
CC -!- SUBUNIT: Homodimer. Forms a heteromeric complex with HSP70/HSC70. Binds
CC to the ATPase domain of HSP/HSC70 chaperones. Interacts with NR3C1.
CC Interacts with the N-terminal region of STK19. Interacts with PPP1R15A.
CC Interacts with BCL2 in an ATP-dependent manner. Interacts with SIAH1,
CC HSPA8 (via NBD), HSPA1A (via NBD) and HSPA1B (via NBD) (By similarity).
CC Interacts with SIAH2 (PubMed:11257006). {ECO:0000250|UniProtKB:Q99933,
CC ECO:0000269|PubMed:11257006}.
CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Nucleus.
CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Cytoplasm.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative initiation; Named isoforms=2;
CC Name=1; Synonyms=BAG-1L, p50;
CC IsoId=Q60739-1; Sequence=Displayed;
CC Name=2; Synonyms=BAG-1S, p32;
CC IsoId=Q60739-2; Sequence=VSP_018667;
CC -!- TISSUE SPECIFICITY: Isoform 2 is expressed in the heart, lung, kidney
CC and spinal cord. Isoform 1 and isoform 2 are expressed in hematopoietic
CC cell lines. The levels of isoform 2 are relatively constant in all the
CC cell lines examined while the levels of isoform 1 are more variable (at
CC protein level). Isoform 1 is expressed in the lung and kidney. Isoform
CC 2 is expressed in various tissues, with highest levels in testis and
CC stomach. {ECO:0000269|PubMed:9396724, ECO:0000269|PubMed:9679980}.
CC -!- PTM: Ubiquitinated; mediated by SIAH1 or SIAH2 and leading to its
CC subsequent proteasomal degradation. {ECO:0000305|PubMed:11257006}.
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DR EMBL; AF022223; AAC34259.1; -; mRNA.
DR EMBL; AK009149; BAB26106.1; -; mRNA.
DR EMBL; AL837521; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH466538; EDL05422.1; -; Genomic_DNA.
DR EMBL; BC003722; AAH03722.2; -; mRNA.
DR EMBL; BC069918; AAH69918.2; -; mRNA.
DR EMBL; BC093509; AAH93509.2; -; mRNA.
DR CCDS; CCDS38713.1; -. [Q60739-1]
DR CCDS; CCDS51139.1; -. [Q60739-2]
DR RefSeq; NP_001165210.1; NM_001171739.1. [Q60739-2]
DR RefSeq; NP_033866.4; NM_009736.3.
DR PDB; 1I6Z; NMR; -; A=226-355.
DR PDB; 2LWP; NMR; -; A=137-233.
DR PDB; 2M8S; NMR; -; A=137-233.
DR PDBsum; 1I6Z; -.
DR PDBsum; 2LWP; -.
DR PDBsum; 2M8S; -.
DR AlphaFoldDB; Q60739; -.
DR BMRB; Q60739; -.
DR SMR; Q60739; -.
DR BioGRID; 198298; 29.
DR DIP; DIP-272N; -.
DR STRING; 10090.ENSMUSP00000030125; -.
DR iPTMnet; Q60739; -.
DR PhosphoSitePlus; Q60739; -.
DR EPD; Q60739; -.
DR MaxQB; Q60739; -.
DR PaxDb; Q60739; -.
DR PRIDE; Q60739; -.
DR ProteomicsDB; 277103; -. [Q60739-1]
DR ProteomicsDB; 277104; -. [Q60739-2]
DR Antibodypedia; 2968; 543 antibodies from 41 providers.
DR DNASU; 12017; -.
DR Ensembl; ENSMUST00000108089; ENSMUSP00000103724; ENSMUSG00000028416. [Q60739-2]
DR Ensembl; ENSMUST00000191273; ENSMUSP00000139864; ENSMUSG00000028416. [Q60739-2]
DR GeneID; 12017; -.
DR KEGG; mmu:12017; -.
DR CTD; 573; -.
DR MGI; MGI:108047; Bag1.
DR VEuPathDB; HostDB:ENSMUSG00000028416; -.
DR eggNOG; ENOG502RN5W; Eukaryota.
DR GeneTree; ENSGT00450000040296; -.
DR HOGENOM; CLU_055378_0_1_1; -.
DR InParanoid; Q60739; -.
DR OrthoDB; 1450573at2759; -.
DR PhylomeDB; Q60739; -.
DR Reactome; R-MMU-3371453; Regulation of HSF1-mediated heat shock response.
DR BioGRID-ORCS; 12017; 2 hits in 74 CRISPR screens.
DR ChiTaRS; Bag1; mouse.
DR EvolutionaryTrace; Q60739; -.
DR PRO; PR:Q60739; -.
DR Proteomes; UP000000589; Chromosome 4.
DR RNAct; Q60739; protein.
DR Bgee; ENSMUSG00000028416; Expressed in seminiferous tubule of testis and 268 other tissues.
DR ExpressionAtlas; Q60739; baseline and differential.
DR Genevisible; Q60739; MM.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0005829; C:cytosol; IDA:MGI.
DR GO; GO:0016020; C:membrane; IBA:GO_Central.
DR GO; GO:0005739; C:mitochondrion; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISO:MGI.
DR GO; GO:0000774; F:adenyl-nucleotide exchange factor activity; ISS:UniProtKB.
DR GO; GO:0051087; F:chaperone binding; IBA:GO_Central.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; ISO:MGI.
DR GO; GO:0006915; P:apoptotic process; IMP:MGI.
DR GO; GO:0051085; P:chaperone cofactor-dependent protein refolding; ISO:MGI.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IMP:MGI.
DR GO; GO:2000672; P:negative regulation of motor neuron apoptotic process; IMP:MGI.
DR GO; GO:0001933; P:negative regulation of protein phosphorylation; IMP:MGI.
DR GO; GO:0030182; P:neuron differentiation; IDA:MGI.
DR GO; GO:0014040; P:positive regulation of Schwann cell differentiation; ISO:MGI.
DR GO; GO:0070585; P:protein localization to mitochondrion; IMP:MGI.
DR GO; GO:0006468; P:protein phosphorylation; IMP:MGI.
DR GO; GO:0050821; P:protein stabilization; IBA:GO_Central.
DR Gene3D; 1.20.58.120; -; 1.
DR IDEAL; IID50180; -.
DR InterPro; IPR017093; BAG-1.
DR InterPro; IPR039773; BAG_chaperone_regulator.
DR InterPro; IPR036533; BAG_dom_sf.
DR InterPro; IPR003103; BAG_domain.
DR InterPro; IPR000626; Ubiquitin-like_dom.
DR InterPro; IPR029071; Ubiquitin-like_domsf.
DR PANTHER; PTHR12329; PTHR12329; 1.
DR PANTHER; PTHR12329:SF16; PTHR12329:SF16; 1.
DR Pfam; PF02179; BAG; 1.
DR Pfam; PF00240; ubiquitin; 1.
DR SMART; SM00264; BAG; 1.
DR SMART; SM00213; UBQ; 1.
DR SUPFAM; SSF54236; SSF54236; 1.
DR SUPFAM; SSF63491; SSF63491; 1.
DR PROSITE; PS51035; BAG; 1.
DR PROSITE; PS50053; UBIQUITIN_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative initiation; Apoptosis; Chaperone; Cytoplasm;
KW Nucleus; Reference proteome; Repeat; Ubl conjugation.
FT CHAIN 1..355
FT /note="BAG family molecular chaperone regulator 1"
FT /id="PRO_0000002782"
FT REPEAT 103..108
FT /note="1"
FT REPEAT 111..116
FT /note="2"
FT REPEAT 117..122
FT /note="3"
FT REPEAT 123..128
FT /note="4"
FT REPEAT 129..134
FT /note="5"
FT REPEAT 141..146
FT /note="6"
FT REPEAT 147..152
FT /note="7"
FT DOMAIN 154..234
FT /note="Ubiquitin-like"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00214"
FT DOMAIN 256..336
FT /note="BAG"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00369"
FT REGION 1..112
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 111..209
FT /note="7 X 6 AA tandem repeat of E-E-X(4)"
FT REGION 132..151
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 182..229
FT /note="Interaction with HSPA8"
FT /evidence="ECO:0000250"
FT REGION 226..355
FT /note="Interaction with PPP1R15A"
FT /evidence="ECO:0000250"
FT COMPBIAS 7..36
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 38..55
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 1..136
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_018667"
FT CONFLICT 64
FT /note="P -> A (in Ref. 5; AAH93509/AAH69918/AAH03722)"
FT /evidence="ECO:0000305"
FT STRAND 149..153
FT /evidence="ECO:0007829|PDB:2LWP"
FT STRAND 155..160
FT /evidence="ECO:0007829|PDB:2LWP"
FT STRAND 163..168
FT /evidence="ECO:0007829|PDB:2LWP"
FT STRAND 171..173
FT /evidence="ECO:0007829|PDB:2LWP"
FT STRAND 175..177
FT /evidence="ECO:0007829|PDB:2LWP"
FT HELIX 180..191
FT /evidence="ECO:0007829|PDB:2LWP"
FT HELIX 195..197
FT /evidence="ECO:0007829|PDB:2LWP"
FT STRAND 200..202
FT /evidence="ECO:0007829|PDB:2LWP"
FT STRAND 205..210
FT /evidence="ECO:0007829|PDB:2M8S"
FT TURN 215..218
FT /evidence="ECO:0007829|PDB:2LWP"
FT STRAND 220..222
FT /evidence="ECO:0007829|PDB:2LWP"
FT STRAND 226..228
FT /evidence="ECO:0007829|PDB:1I6Z"
FT HELIX 234..268
FT /evidence="ECO:0007829|PDB:1I6Z"
FT STRAND 270..272
FT /evidence="ECO:0007829|PDB:1I6Z"
FT HELIX 274..303
FT /evidence="ECO:0007829|PDB:1I6Z"
FT HELIX 312..346
FT /evidence="ECO:0007829|PDB:1I6Z"
SQ SEQUENCE 355 AA; 39740 MW; 077A765CA869D3A7 CRC64;
MAGRSAARRP RGDREPLGPR LRAPRPAREP RQSESRAERG LPPSQRSSVR SAASGHDRST
RGAPAGACKP RVKKKVRPRS SQSEKVGSSS RELTRSKKVT RSKNVTGTQV EEVTKIEEAT
QTEEVTVAEE VTQTDNMAKT EEMVQTEEME TPRLSVIVTH SNERYDLLVT PQQGNSEPVV
QDLAQLVEEA TGVPLPFQKL IFKGKSLKEM ETPLSALGMQ NGCRVMLIGE KSNPEEEVEL
KKLKDLEVSA EKIANHLQEL NKELSGIQQG FLAKELQAEA LCKLDRKVKA TIEQFMKILE
EIDTMVLPEQ FKDSRLKRKN LVKKVQVFLA ECDTVEQYIC QETERLQSTN LALAE
