ID BAG5_MOUSE Reviewed; 447 AA. AC Q8CI32; Q3TVA8; Q8K175; Q9DAU0; DT 21-JUN-2005, integrated into UniProtKB/Swiss-Prot. DT 01-MAR-2003, sequence version 1. DT 27-MAR-2024, entry version 166. DE RecName: Full=BAG family molecular chaperone regulator 5; DE Short=BAG-5; DE AltName: Full=Bcl-2-associated athanogene 5; GN Name=Bag5; 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 [LARGE SCALE MRNA]. RC STRAIN=C57BL/6J; TISSUE=Placenta, 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 [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC STRAIN=Czech II, and FVB/N; 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 [3] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Brain, Lung, 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). RN [4] RP FUNCTION, INTERACTION WITH HSPA8, SUBCELLULAR LOCATION, AND MUTAGENESIS OF RP 197-ARG--TYR-447. RX PubMed=35044787; DOI=10.1126/scitranslmed.abf3274; RA Hakui H., Kioka H., Miyashita Y., Nishimura S., Matsuoka K., Kato H., RA Tsukamoto O., Kuramoto Y., Takuwa A., Takahashi Y., Saito S., Ohta K., RA Asanuma H., Fu H.Y., Shinomiya H., Yamada N., Ohtani T., Sawa Y., RA Kitakaze M., Takashima S., Sakata Y., Asano Y.; RT "Loss-of-function mutations in the co-chaperone protein BAG5 cause dilated RT cardiomyopathy requiring heart transplantation."; RL Sci. Transl. Med. 14:eabf3274-eabf3274(2022). RN [5] RP STRUCTURE BY NMR OF 1-86. RX PubMed=20223214; DOI=10.1016/j.str.2010.01.004; RA Arakawa A., Handa N., Ohsawa N., Shida M., Kigawa T., Hayashi F., RA Shirouzu M., Yokoyama S.; RT "The C-terminal BAG domain of BAG5 induces conformational changes of the RT Hsp70 nucleotide-binding domain for ADP-ATP exchange."; RL Structure 18:309-319(2010). CC -!- FUNCTION: Co-chaperone for HSP/HSP70 proteins. It functions as a CC nucleotide-exchange factor promoting the release of ADP from HSP70, CC thereby activating HSP70-mediated protein refolding (By similarity). CC Has an essential role in maintaining proteostasis at junctional CC membrane complexes (JMC), where it may function as a scaffold between CC the HSPA8 chaperone and JMC proteins enabling correct, HSPA8-dependent CC JMC protein folding (PubMed:35044787). Inhibits both auto- CC ubiquitination of PRKN and ubiquitination of target proteins by PRKN CC (By similarity). {ECO:0000250|UniProtKB:Q5QJC9, CC ECO:0000250|UniProtKB:Q9UL15, ECO:0000269|PubMed:35044787}. CC -!- SUBUNIT: Binds to the ATPase domain of HSP/HSP70 chaperones. Binds PRKN CC (By similarity). Interacts with HSPA8 (PubMed:35044787). Interacts with CC JPH2 (By similarity). {ECO:0000250, ECO:0000250|UniProtKB:Q9UL15, CC ECO:0000269|PubMed:35044787}. CC -!- SUBCELLULAR LOCATION: Note=In cardiomyocytes, localized at specialized CC membrane contact sites between T-tubules and the sarcoplasmic CC reticulum, known as junctional membrane complexes. CC {ECO:0000269|PubMed:35044787}. CC -!- DOMAIN: The fifth BAG domain is responsible for the interaction with CC HSP70 nucleotide-binding domain. {ECO:0000250}. CC -!- SEQUENCE CAUTION: CC Sequence=AAH27827.1; Type=Erroneous initiation; Evidence={ECO:0000305}; CC Sequence=BAB24105.1; Type=Frameshift; 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; AK005534; BAB24105.1; ALT_FRAME; mRNA. DR EMBL; AK160246; BAE35711.1; -; mRNA. DR EMBL; BC027827; AAH27827.1; ALT_INIT; mRNA. DR EMBL; BC037642; AAH37642.1; -; mRNA. DR CCDS; CCDS26185.1; -. DR RefSeq; NP_001311409.1; NM_001324480.1. DR RefSeq; NP_001311410.1; NM_001324481.1. DR RefSeq; NP_001311411.1; NM_001324482.1. DR RefSeq; NP_081680.1; NM_027404.2. DR RefSeq; XP_006516280.1; XM_006516217.3. DR PDB; 1UGO; NMR; -; A=1-86. DR PDBsum; 1UGO; -. DR AlphaFoldDB; Q8CI32; -. DR SMR; Q8CI32; -. DR BioGRID; 214005; 10. DR IntAct; Q8CI32; 5. DR MINT; Q8CI32; -. DR STRING; 10090.ENSMUSP00000051049; -. DR iPTMnet; Q8CI32; -. DR PhosphoSitePlus; Q8CI32; -. DR SwissPalm; Q8CI32; -. DR EPD; Q8CI32; -. DR MaxQB; Q8CI32; -. DR PaxDb; 10090-ENSMUSP00000051049; -. DR PeptideAtlas; Q8CI32; -. DR ProteomicsDB; 277105; -. DR Pumba; Q8CI32; -. DR Antibodypedia; 36; 624 antibodies from 36 providers. DR DNASU; 70369; -. DR Ensembl; ENSMUST00000054636.7; ENSMUSP00000051049.7; ENSMUSG00000049792.7. DR Ensembl; ENSMUST00000160576.2; ENSMUSP00000125183.2; ENSMUSG00000049792.7. DR GeneID; 70369; -. DR KEGG; mmu:70369; -. DR UCSC; uc007pdr.3; mouse. DR AGR; MGI:1917619; -. DR CTD; 9529; -. DR MGI; MGI:1917619; Bag5. DR VEuPathDB; HostDB:ENSMUSG00000049792; -. DR eggNOG; KOG4361; Eukaryota. DR GeneTree; ENSGT00940000158888; -. DR HOGENOM; CLU_579940_0_0_1; -. DR InParanoid; Q8CI32; -. DR OMA; MGNQHPA; -. DR OrthoDB; 4022185at2759; -. DR PhylomeDB; Q8CI32; -. DR TreeFam; TF102014; -. DR Reactome; R-MMU-3371453; Regulation of HSF1-mediated heat shock response. DR BioGRID-ORCS; 70369; 2 hits in 78 CRISPR screens. DR ChiTaRS; Bag5; mouse. DR EvolutionaryTrace; Q8CI32; -. DR PRO; PR:Q8CI32; -. DR Proteomes; UP000000589; Chromosome 12. DR RNAct; Q8CI32; Protein. DR Bgee; ENSMUSG00000049792; Expressed in seminiferous tubule of testis and 244 other cell types or tissues. DR ExpressionAtlas; Q8CI32; baseline and differential. DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central. DR GO; GO:0005829; C:cytosol; ISS:ParkinsonsUK-UCL. DR GO; GO:0016234; C:inclusion body; ISS:BHF-UCL. DR GO; GO:0030314; C:junctional membrane complex; IDA:UniProtKB. DR GO; GO:0016020; C:membrane; IBA:GO_Central. DR GO; GO:0005739; C:mitochondrion; ISS:ParkinsonsUK-UCL. DR GO; GO:0005634; C:nucleus; ISS:ParkinsonsUK-UCL. DR GO; GO:0048471; C:perinuclear region of cytoplasm; ISS:BHF-UCL. DR GO; GO:0000774; F:adenyl-nucleotide exchange factor activity; IBA:GO_Central. DR GO; GO:0019901; F:protein kinase binding; ISO:MGI. DR GO; GO:0051087; F:protein-folding chaperone binding; ISS:BHF-UCL. DR GO; GO:0031625; F:ubiquitin protein ligase binding; ISO:MGI. DR GO; GO:0007030; P:Golgi organization; ISS:ParkinsonsUK-UCL. DR GO; GO:0010977; P:negative regulation of neuron projection development; ISS:ParkinsonsUK-UCL. DR GO; GO:1902176; P:negative regulation of oxidative stress-induced intrinsic apoptotic signaling pathway; ISS:ParkinsonsUK-UCL. DR GO; GO:0032435; P:negative regulation of proteasomal ubiquitin-dependent protein catabolic process; ISS:ParkinsonsUK-UCL. DR GO; GO:0061084; P:negative regulation of protein refolding; ISS:BHF-UCL. DR GO; GO:0031397; P:negative regulation of protein ubiquitination; ISS:ParkinsonsUK-UCL. DR GO; GO:0051444; P:negative regulation of ubiquitin-protein transferase activity; ISS:BHF-UCL. DR GO; GO:0050821; P:protein stabilization; ISO:MGI. DR GO; GO:0090083; P:regulation of inclusion body assembly; ISS:BHF-UCL. DR Gene3D; 1.20.58.120; BAG domain; 5. DR InterPro; IPR039773; BAG_chaperone_regulator. DR InterPro; IPR036533; BAG_dom_sf. DR InterPro; IPR003103; BAG_domain. DR PANTHER; PTHR12329:SF2; BAG FAMILY MOLECULAR CHAPERONE REGULATOR 5; 1. DR PANTHER; PTHR12329; BCL2-ASSOCIATED ATHANOGENE; 1. DR Pfam; PF02179; BAG; 4. DR SMART; SM00264; BAG; 4. DR SUPFAM; SSF63491; BAG domain; 4. DR PROSITE; PS51035; BAG; 4. DR Genevisible; Q8CI32; MM. PE 1: Evidence at protein level; KW 3D-structure; Chaperone; Reference proteome; Repeat. FT CHAIN 1..447 FT /note="BAG family molecular chaperone regulator 5" FT /id="PRO_0000088873" FT DOMAIN 9..86 FT /note="BAG 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00369" FT DOMAIN 95..167 FT /note="BAG 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00369" FT DOMAIN 182..260 FT /note="BAG 3" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00369" FT DOMAIN 275..350 FT /note="BAG 4" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00369" FT DOMAIN 365..442 FT /note="BAG 5" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00369" FT MUTAGEN 197..447 FT /note="Missing: Results in lack of BAG5 at junctional FT membrane complexes in cardiomyocytes from homozygous mutant FT mice, disruption of junctional membrane complex structure, FT and calcium handling abnormalities. Homozygous mutant mice FT exhibit ventricular dilatation and arrhythmogenicity." FT /evidence="ECO:0000269|PubMed:35044787" FT CONFLICT 6 FT /note="Q -> H (in Ref. 1; BAB24105)" FT /evidence="ECO:0000305" FT CONFLICT 23 FT /note="I -> K (in Ref. 1; BAB24105)" FT /evidence="ECO:0000305" FT CONFLICT 36 FT /note="D -> E (in Ref. 1; BAB24105)" FT /evidence="ECO:0000305" FT CONFLICT 52 FT /note="E -> G (in Ref. 1; BAB24105)" FT /evidence="ECO:0000305" FT CONFLICT 142 FT /note="K -> E (in Ref. 1; BAB24105)" FT /evidence="ECO:0000305" FT CONFLICT 148 FT /note="A -> S (in Ref. 1; BAB24105)" FT /evidence="ECO:0000305" FT CONFLICT 341 FT /note="I -> T (in Ref. 2; AAH27827)" FT /evidence="ECO:0000305" FT HELIX 10..22 FT /evidence="ECO:0007829|PDB:1UGO" FT HELIX 24..28 FT /evidence="ECO:0007829|PDB:1UGO" FT HELIX 38..55 FT /evidence="ECO:0007829|PDB:1UGO" FT HELIX 62..86 FT /evidence="ECO:0007829|PDB:1UGO" SQ SEQUENCE 447 AA; 50943 MW; 72E2C5472DA95416 CRC64; MDMGNQHPSI SRLQEIQREV KAIEPQVVGF SGLSDDKNYK RLERILTKQL FEIDSVDTEG KGDIQQARKR AAQETERLLK ELEQNANHPH RIEIQNIFKE AQALVKDKIV PFYSGGNCVT DEFEEGIQDI ILRLTHVKTG GKVSLRKARY RTLTKICAVQ EVIEDCMKKQ PSLPLSEDVH PSVAKINSVM CEVNKARGTL IALLMGVDSS ETCRHLSCVL SGLIADLDAL DVCGRTEIRN YRREVVEDIN KLLKYLDLEE EADSTHAFDL GQNHSIIKIE NVLKRMREIK NELLQAQSPP ELYLRAKTEL QGLIGQLDEV SLEKNPCIRE ARRRAVIEVQ ILITYLDLKE ALEKRKLFPC EEHPPHKAVW EILGNLSEIL GEVLSFGGNR TDKNYIRLEE LLTKQLLALD AVDPQGEEKC KAARKQAVKL AQNILSYLDM KSDEWEY //