BAG5_HUMAN
ID BAG5_HUMAN Reviewed; 447 AA.
AC Q9UL15; O94950; Q86W59;
DT 11-JAN-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 178.
DE RecName: Full=BAG family molecular chaperone regulator 5;
DE Short=BAG-5;
DE AltName: Full=Bcl-2-associated athanogene 5;
GN Name=BAG5; Synonyms=KIAA0873;
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] (ISOFORM 1).
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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=10048485; DOI=10.1093/dnares/5.6.355;
RA Nagase T., Ishikawa K., Suyama M., Kikuno R., Hirosawa M., Miyajima N.,
RA Tanaka A., Kotani H., Nomura N., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XII. The
RT complete sequences of 100 new cDNA clones from brain which code for large
RT proteins in vitro.";
RL DNA Res. 5:355-364(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12508121; DOI=10.1038/nature01348;
RA Heilig R., Eckenberg R., Petit J.-L., Fonknechten N., Da Silva C.,
RA Cattolico L., Levy M., Barbe V., De Berardinis V., Ureta-Vidal A.,
RA Pelletier E., Vico V., Anthouard V., Rowen L., Madan A., Qin S., Sun H.,
RA Du H., Pepin K., Artiguenave F., Robert C., Cruaud C., Bruels T.,
RA Jaillon O., Friedlander L., Samson G., Brottier P., Cure S., Segurens B.,
RA Aniere F., Samain S., Crespeau H., Abbasi N., Aiach N., Boscus D.,
RA Dickhoff R., Dors M., Dubois I., Friedman C., Gouyvenoux M., James R.,
RA Madan A., Mairey-Estrada B., Mangenot S., Martins N., Menard M., Oztas S.,
RA Ratcliffe A., Shaffer T., Trask B., Vacherie B., Bellemere C., Belser C.,
RA Besnard-Gonnet M., Bartol-Mavel D., Boutard M., Briez-Silla S.,
RA Combette S., Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C.,
RA Muselet D., Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P.,
RA Trybou A., Vega-Czarny N., Bataille E., Bluet E., Bordelais I., Dubois M.,
RA Dumont C., Guerin T., Haffray S., Hammadi R., Muanga J., Pellouin V.,
RA Robert D., Wunderle E., Gauguet G., Roy A., Sainte-Marthe L., Verdier J.,
RA Verdier-Discala C., Hillier L.W., Fulton L., McPherson J., Matsuda F.,
RA Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W., Quetier F.,
RA Waterston R., Hood L., Weissenbach J.;
RT "The DNA sequence and analysis of human chromosome 14.";
RL Nature 421:601-607(2003).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), AND VARIANT
RP TRP-157.
RC TISSUE=Brain;
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 IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [6]
RP INTERACTION WITH PRKN.
RX PubMed=24270810; DOI=10.1038/nature12748;
RA Hasson S.A., Kane L.A., Yamano K., Huang C.H., Sliter D.A., Buehler E.,
RA Wang C., Heman-Ackah S.M., Hessa T., Guha R., Martin S.E., Youle R.J.;
RT "High-content genome-wide RNAi screens identify regulators of parkin
RT upstream of mitophagy.";
RL Nature 504:291-295(2013).
RN [7]
RP STRUCTURE BY NMR OF 275-350, X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF
RP 341-447 IN COMPLEX WITH HSPA1, DOMAIN BAG, FUNCTION, AND SUBUNIT.
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: Inhibits both auto-ubiquitination of PRKN and ubiquitination
CC of target proteins by PRKN (By similarity). May function as a
CC nucleotide exchange factor for HSP/HSP70, promoting ADP release, and
CC activating Hsp70-mediated refolding. {ECO:0000250,
CC ECO:0000269|PubMed:20223214}.
CC -!- SUBUNIT: Binds to the ATPase domain of HSP/HSC70 chaperones. Binds
CC PRKN. {ECO:0000269|PubMed:20223214}.
CC -!- INTERACTION:
CC Q9UL15; Q8N9N5: BANP; NbExp=3; IntAct=EBI-356517, EBI-744695;
CC Q9UL15; Q96GN5: CDCA7L; NbExp=3; IntAct=EBI-356517, EBI-5278764;
CC Q9UL15; P17661: DES; NbExp=3; IntAct=EBI-356517, EBI-1055572;
CC Q9UL15; Q12805: EFEMP1; NbExp=3; IntAct=EBI-356517, EBI-536772;
CC Q9UL15; Q9BPY3: FAM118B; NbExp=3; IntAct=EBI-356517, EBI-726822;
CC Q9UL15; Q9NYA3: GOLGA6A; NbExp=3; IntAct=EBI-356517, EBI-11163335;
CC Q9UL15; P08107: HSPA1B; NbExp=6; IntAct=EBI-356517, EBI-629985;
CC Q9UL15; Q8N6L0: KASH5; NbExp=6; IntAct=EBI-356517, EBI-749265;
CC Q9UL15; Q6L8H1: KRTAP5-4; NbExp=3; IntAct=EBI-356517, EBI-11963072;
CC Q9UL15; Q5TA81: LCE2C; NbExp=3; IntAct=EBI-356517, EBI-11973993;
CC Q9UL15; Q38SD2: LRRK1; NbExp=3; IntAct=EBI-356517, EBI-1050422;
CC Q9UL15; Q5S007: LRRK2; NbExp=12; IntAct=EBI-356517, EBI-5323863;
CC Q9UL15; Q9Y6D9: MAD1L1; NbExp=7; IntAct=EBI-356517, EBI-742610;
CC Q9UL15; Q9NVV9: THAP1; NbExp=7; IntAct=EBI-356517, EBI-741515;
CC Q9UL15; O60784-2: TOM1; NbExp=3; IntAct=EBI-356517, EBI-12117154;
CC Q9UL15; P14373: TRIM27; NbExp=6; IntAct=EBI-356517, EBI-719493;
CC Q9UL15; Q53FC7; NbExp=2; IntAct=EBI-356517, EBI-9356749;
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9UL15-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9UL15-2; Sequence=VSP_037996;
CC -!- DOMAIN: The fifth BAG domain is responsible for the interaction with
CC HSP70 nucleotide-binding domain. {ECO:0000269|PubMed:20223214}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA74896.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AF095195; AAD16124.2; -; mRNA.
DR EMBL; AB020680; BAA74896.1; ALT_INIT; mRNA.
DR EMBL; AL139300; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC044216; AAH44216.2; -; mRNA.
DR EMBL; BC050551; AAH50551.1; -; mRNA.
DR CCDS; CCDS41995.1; -. [Q9UL15-1]
DR CCDS; CCDS9982.1; -. [Q9UL15-1]
DR RefSeq; NP_001015048.1; NM_001015048.2. [Q9UL15-1]
DR RefSeq; NP_001015049.1; NM_001015049.2. [Q9UL15-1]
DR RefSeq; NP_004864.1; NM_004873.3. [Q9UL15-1]
DR PDB; 2D9D; NMR; -; A=275-350.
DR PDB; 3A8Y; X-ray; 2.30 A; C/D=341-447.
DR PDBsum; 2D9D; -.
DR PDBsum; 3A8Y; -.
DR AlphaFoldDB; Q9UL15; -.
DR SMR; Q9UL15; -.
DR BioGRID; 114905; 347.
DR CORUM; Q9UL15; -.
DR DIP; DIP-53428N; -.
DR IntAct; Q9UL15; 95.
DR MINT; Q9UL15; -.
DR STRING; 9606.ENSP00000338814; -.
DR GlyGen; Q9UL15; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q9UL15; -.
DR MetOSite; Q9UL15; -.
DR PhosphoSitePlus; Q9UL15; -.
DR BioMuta; BAG5; -.
DR DMDM; 12643895; -.
DR EPD; Q9UL15; -.
DR jPOST; Q9UL15; -.
DR MassIVE; Q9UL15; -.
DR MaxQB; Q9UL15; -.
DR PaxDb; Q9UL15; -.
DR PeptideAtlas; Q9UL15; -.
DR PRIDE; Q9UL15; -.
DR ProteomicsDB; 84927; -. [Q9UL15-1]
DR ProteomicsDB; 84928; -. [Q9UL15-2]
DR Antibodypedia; 36; 561 antibodies from 36 providers.
DR DNASU; 9529; -.
DR Ensembl; ENST00000299204.6; ENSP00000299204.4; ENSG00000166170.12. [Q9UL15-1]
DR Ensembl; ENST00000337322.5; ENSP00000338814.5; ENSG00000166170.12. [Q9UL15-1]
DR Ensembl; ENST00000445922.2; ENSP00000391713.2; ENSG00000166170.12. [Q9UL15-1]
DR GeneID; 9529; -.
DR KEGG; hsa:9529; -.
DR MANE-Select; ENST00000299204.6; ENSP00000299204.4; NM_001015048.3; NP_001015048.1.
DR UCSC; uc001ynh.3; human. [Q9UL15-1]
DR CTD; 9529; -.
DR DisGeNET; 9529; -.
DR GeneCards; BAG5; -.
DR HGNC; HGNC:941; BAG5.
DR HPA; ENSG00000166170; Tissue enriched (testis).
DR MIM; 603885; gene.
DR neXtProt; NX_Q9UL15; -.
DR OpenTargets; ENSG00000166170; -.
DR PharmGKB; PA25241; -.
DR VEuPathDB; HostDB:ENSG00000166170; -.
DR eggNOG; KOG4361; Eukaryota.
DR GeneTree; ENSGT00940000158888; -.
DR HOGENOM; CLU_579940_0_0_1; -.
DR InParanoid; Q9UL15; -.
DR OMA; VWDVLGN; -.
DR OrthoDB; 902874at2759; -.
DR PhylomeDB; Q9UL15; -.
DR TreeFam; TF102014; -.
DR PathwayCommons; Q9UL15; -.
DR Reactome; R-HSA-3371453; Regulation of HSF1-mediated heat shock response.
DR SignaLink; Q9UL15; -.
DR SIGNOR; Q9UL15; -.
DR BioGRID-ORCS; 9529; 4 hits in 1076 CRISPR screens.
DR EvolutionaryTrace; Q9UL15; -.
DR GeneWiki; BAG5; -.
DR GenomeRNAi; 9529; -.
DR Pharos; Q9UL15; Tbio.
DR PRO; PR:Q9UL15; -.
DR Proteomes; UP000005640; Chromosome 14.
DR RNAct; Q9UL15; protein.
DR Bgee; ENSG00000166170; Expressed in sperm and 205 other tissues.
DR ExpressionAtlas; Q9UL15; baseline and differential.
DR Genevisible; Q9UL15; HS.
DR GO; GO:0005829; C:cytosol; IDA:ParkinsonsUK-UCL.
DR GO; GO:0016234; C:inclusion body; IDA:BHF-UCL.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; IDA:ParkinsonsUK-UCL.
DR GO; GO:0005634; C:nucleus; IDA:ParkinsonsUK-UCL.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:BHF-UCL.
DR GO; GO:0000774; F:adenyl-nucleotide exchange factor activity; IBA:GO_Central.
DR GO; GO:0051087; F:chaperone binding; IPI:BHF-UCL.
DR GO; GO:0019901; F:protein kinase binding; IPI:ParkinsonsUK-UCL.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; IPI:ParkinsonsUK-UCL.
DR GO; GO:0007030; P:Golgi organization; IMP:ParkinsonsUK-UCL.
DR GO; GO:0010977; P:negative regulation of neuron projection development; IDA:ParkinsonsUK-UCL.
DR GO; GO:1902176; P:negative regulation of oxidative stress-induced intrinsic apoptotic signaling pathway; IDA:ParkinsonsUK-UCL.
DR GO; GO:0032435; P:negative regulation of proteasomal ubiquitin-dependent protein catabolic process; IDA: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; IDA:ARUK-UCL.
DR GO; GO:0051444; P:negative regulation of ubiquitin-protein transferase activity; ISS:BHF-UCL.
DR GO; GO:0070997; P:neuron death; ISS:BHF-UCL.
DR GO; GO:0006457; P:protein folding; TAS:ProtInc.
DR GO; GO:0050821; P:protein stabilization; IDA:ARUK-UCL.
DR GO; GO:0090083; P:regulation of inclusion body assembly; IMP:BHF-UCL.
DR GO; GO:0051438; P:regulation of ubiquitin-protein transferase activity; TAS:ParkinsonsUK-UCL.
DR Gene3D; 1.20.58.120; -; 5.
DR InterPro; IPR039773; BAG_chaperone_regulator.
DR InterPro; IPR036533; BAG_dom_sf.
DR InterPro; IPR003103; BAG_domain.
DR PANTHER; PTHR12329; PTHR12329; 1.
DR Pfam; PF02179; BAG; 4.
DR SMART; SM00264; BAG; 4.
DR SUPFAM; SSF63491; SSF63491; 4.
DR PROSITE; PS51035; BAG; 4.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Chaperone; Reference proteome; Repeat.
FT CHAIN 1..447
FT /note="BAG family molecular chaperone regulator 5"
FT /id="PRO_0000088872"
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 VAR_SEQ 1
FT /note="M -> MRFHWLPTLSEPFDRNQELETCIRPLWTPSGSACETEHNKSM (in
FT isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_037996"
FT VARIANT 157
FT /note="C -> W (in dbSNP:rs17854644)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_058712"
FT HELIX 277..295
FT /evidence="ECO:0007829|PDB:2D9D"
FT TURN 299..301
FT /evidence="ECO:0007829|PDB:2D9D"
FT HELIX 302..317
FT /evidence="ECO:0007829|PDB:2D9D"
FT HELIX 318..320
FT /evidence="ECO:0007829|PDB:2D9D"
FT HELIX 326..350
FT /evidence="ECO:0007829|PDB:2D9D"
FT TURN 356..358
FT /evidence="ECO:0007829|PDB:3A8Y"
FT HELIX 364..384
FT /evidence="ECO:0007829|PDB:3A8Y"
FT HELIX 393..410
FT /evidence="ECO:0007829|PDB:3A8Y"
FT HELIX 418..442
FT /evidence="ECO:0007829|PDB:3A8Y"
SQ SEQUENCE 447 AA; 51200 MW; 0D3F7EA6B612C1F5 CRC64;
MDMGNQHPSI SRLQEIQKEV KSVEQQVIGF SGLSDDKNYK KLERILTKQL FEIDSVDTEG
KGDIQQARKR AAQETERLLK ELEQNANHPH RIEIQNIFEE AQSLVREKIV PFYNGGNCVT
DEFEEGIQDI ILRLTHVKTG GKISLRKARY HTLTKICAVQ EIIEDCMKKQ PSLPLSEDAH
PSVAKINFVM CEVNKARGVL IALLMGVNNN ETCRHLSCVL SGLIADLDAL DVCGRTEIRN
YRREVVEDIN KLLKYLDLEE EADTTKAFDL RQNHSILKIE KVLKRMREIK NELLQAQNPS
ELYLSSKTEL QGLIGQLDEV SLEKNPCIRE ARRRAVIEVQ TLITYIDLKE ALEKRKLFAC
EEHPSHKAVW NVLGNLSEIQ GEVLSFDGNR TDKNYIRLEE LLTKQLLALD AVDPQGEEKC
KAARKQAVRL AQNILSYLDL KSDEWEY
