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Protein

BAG family molecular chaperone regulator 3

Gene

BAG3

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Co-chaperone for HSP70 and HSC70 chaperone proteins. Acts as a nucleotide-exchange factor (NEF) promoting the release of ADP from the HSP70 and HSC70 proteins thereby triggering client/substrate protein release. Nucleotide release is mediated via its binding to the nucleotide-binding domain (NBD) of HSPA8/HSC70 where as the substrate release is mediated via its binding to the substrate-binding domain (SBD) of HSPA8/HSC70 (PubMed:9873016, PubMed:27474739). Has anti-apoptotic activity (PubMed:10597216). Plays a role in the HSF1 nucleocytoplasmic transport (PubMed:26159920).5 Publications

GO - Molecular functioni

  • adenyl-nucleotide exchange factor activity Source: UniProtKB
  • cadherin binding Source: BHF-UCL
  • chaperone binding Source: InterPro
  • protein complex binding Source: Ensembl

GO - Biological processi

  • brain development Source: Ensembl
  • cellular response to heat Source: UniProtKB
  • cellular response to mechanical stimulus Source: Ensembl
  • extrinsic apoptotic signaling pathway in absence of ligand Source: Ensembl
  • extrinsic apoptotic signaling pathway via death domain receptors Source: MGI
  • negative regulation of apoptotic process Source: UniProtKB
  • negative regulation of striated muscle cell apoptotic process Source: Ensembl
  • negative regulation of transcription from RNA polymerase II promoter in response to stress Source: UniProtKB
  • positive regulation of protein export from nucleus Source: UniProtKB
  • positive regulation of transcription factor import into nucleus Source: UniProtKB
  • protein folding Source: UniProtKB
  • protein stabilization Source: Ensembl
  • regulation of cellular response to heat Source: Reactome
  • spinal cord development Source: Ensembl

Keywordsi

Molecular functionChaperone
Biological processApoptosis

Enzyme and pathway databases

ReactomeiR-HSA-3371453. Regulation of HSF1-mediated heat shock response.
SignaLinkiO95817.
SIGNORiO95817.

Names & Taxonomyi

Protein namesi
Recommended name:
BAG family molecular chaperone regulator 3
Short name:
BAG-3
Alternative name(s):
Bcl-2-associated athanogene 3
Bcl-2-binding protein Bis
Docking protein CAIR-1
Gene namesi
Name:BAG3
Synonyms:BIS
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 10

Organism-specific databases

HGNCiHGNC:939. BAG3.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
  • cytosol Source: HPA
  • neuron projection Source: Ensembl
  • nucleus Source: UniProtKB
  • plasma membrane Source: HPA
  • Z disc Source: Ensembl

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Involvement in diseasei

Myopathy, myofibrillar, 6 (MFM6)3 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA form of myofibrillar myopathy, a group of chronic neuromuscular disorders characterized at ultrastructural level by disintegration of the sarcomeric Z disc and myofibrils, and replacement of the normal myofibrillar markings by small dense granules, or larger hyaline masses, or amorphous material. MFM6 is characterized by early-onset of severe, progressive, diffuse muscle weakness associated with cardiomyopathy, severe respiratory insufficiency during adolescence, and a rigid spine in some patients.
See also OMIM:612954
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_063089209P → L in MFM6; interferes with the differentiation of skeletal muscle cells; does not cause functional alterations in cardiomyocyte cells. 3 PublicationsCorresponds to variant dbSNP:rs121918312Ensembl.1
Cardiomyopathy, dilated 1HH (CMD1HH)3 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA disorder characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia. Patients are at risk of premature death.
See also OMIM:613881
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_06547971R → W in CMD1HH. 1 PublicationCorresponds to variant dbSNP:rs387906874Ensembl.1
Natural variantiVAR_066781218R → W in CMD1HH; interferes with the assembly of Z-disks; increases stress-induced apoptosis. 1 PublicationCorresponds to variant dbSNP:rs397514506Ensembl.1
Natural variantiVAR_066785455E → K in CMD1HH. 1 PublicationCorresponds to variant dbSNP:rs397516881Ensembl.1
Natural variantiVAR_066786462L → P in CMD1HH; interferes with the assembly of Z-disks; increases stress-induced apoptosis. 1 PublicationCorresponds to variant dbSNP:rs397514507Ensembl.1
Natural variantiVAR_066787468V → M in CMD1HH. 1 Publication1
Natural variantiVAR_065480477R → H in CMD1HH. 1 PublicationCorresponds to variant dbSNP:rs387906876Ensembl.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi480 – 481RR → AA: Significant loss of interaction with HSPA8. 1 Publication2

Keywords - Diseasei

Cardiomyopathy, Disease mutation, Myofibrillar myopathy

Organism-specific databases

DisGeNETi9531.
GeneReviewsiBAG3.
MalaCardsiBAG3.
MIMi612954. phenotype.
613881. phenotype.
OpenTargetsiENSG00000151929.
Orphaneti154. Familial isolated dilated cardiomyopathy.
199340. Muscular dystrophy, Selcen type.
PharmGKBiPA25239.

Polymorphism and mutation databases

BioMutaiBAG3.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedCombined sources
ChainiPRO_00000888682 – 575BAG family molecular chaperone regulator 3Add BLAST574

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylserineCombined sources1
Modified residuei136PhosphoserineBy similarity1
Modified residuei139Omega-N-methylarginineBy similarity1
Modified residuei173PhosphoserineCombined sources1
Modified residuei198PhosphoserineCombined sources1
Modified residuei261Omega-N-methylarginineBy similarity1
Modified residuei269PhosphoserineCombined sources1
Modified residuei274PhosphoserineCombined sources1
Modified residuei275PhosphoserineCombined sources1
Modified residuei279PhosphoserineCombined sources1
Modified residuei285PhosphothreonineCombined sources1
Modified residuei289PhosphoserineCombined sources1
Modified residuei291PhosphoserineCombined sources1
Modified residuei377PhosphoserineCombined sources1
Modified residuei385PhosphoserineCombined sources1
Modified residuei386PhosphoserineCombined sources1
Modified residuei406PhosphothreonineCombined sources1
Cross-linki445Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO1)Combined sources
Cross-linki445Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources

Keywords - PTMi

Acetylation, Isopeptide bond, Methylation, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiO95817.
MaxQBiO95817.
PaxDbiO95817.
PeptideAtlasiO95817.
PRIDEiO95817.

PTM databases

iPTMnetiO95817.
PhosphoSitePlusiO95817.

Miscellaneous databases

PMAP-CutDBiO95817.

Expressioni

Gene expression databases

BgeeiENSG00000151929.
CleanExiHS_BAG3.
ExpressionAtlasiO95817. baseline and differential.
GenevisibleiO95817. HS.

Organism-specific databases

HPAiHPA018493.
HPA020586.

Interactioni

Subunit structurei

Binds to the ATPase domain of HSP70/HSC70 chaperones (PubMed:9873016). Interacts with BCL2 (PubMed:10597216). Interacts with phospholipase C-gamma proteins (PubMed:10980614). Interacts with DNAJB6 (PubMed:22366786). Interacts (via BAG domain) with HSF1; this interaction occurs in normal and heat-shocked cells promoting HSF1 nucleocytoplasmic shuttling (PubMed:26159920). Interacts with HSPA8 (via NBD) (PubMed:27474739, PubMed:24318877). Interacts with HSPA1A (via NBD) and HSPA1B (via NBD) (PubMed:24318877). Interacts (via WW domain 1) with SYNPO2 (via PPPY motif) (PubMed:23434281). Interacts with HSPB8 (PubMed:28144995).9 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • cadherin binding Source: BHF-UCL
  • chaperone binding Source: InterPro
  • protein complex binding Source: Ensembl

Protein-protein interaction databases

BioGridi114907. 484 interactors.
DIPiDIP-41273N.
IntActiO95817. 129 interactors.
MINTiMINT-208995.
STRINGi9606.ENSP00000358081.

Structurei

3D structure databases

ProteinModelPortaliO95817.
SMRiO95817.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini20 – 54WW 1PROSITE-ProRule annotationAdd BLAST35
Domaini124 – 154WW 2PROSITE-ProRule annotationAdd BLAST31
Domaini421 – 498BAGPROSITE-ProRule annotationAdd BLAST78

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi180 – 187Poly-Ser8

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiKOG0940. Eukaryota.
KOG4361. Eukaryota.
COG5021. LUCA.
GeneTreeiENSGT00530000063256.
HOGENOMiHOG000050234.
HOVERGENiHBG003419.
InParanoidiO95817.
KOiK09557.
OMAiQTGWPFF.
OrthoDBiEOG091G08LY.
PhylomeDBiO95817.
TreeFamiTF102013.

Family and domain databases

CDDicd00201. WW. 1 hit.
Gene3Di1.20.58.120. 1 hit.
InterProiView protein in InterPro
IPR003103. BAG_domain.
IPR001202. WW_dom.
PfamiView protein in Pfam
PF02179. BAG. 1 hit.
PF00397. WW. 1 hit.
SMARTiView protein in SMART
SM00264. BAG. 1 hit.
SM00456. WW. 1 hit.
SUPFAMiSSF51045. SSF51045. 1 hit.
SSF63491. SSF63491. 1 hit.
PROSITEiView protein in PROSITE
PS51035. BAG. 1 hit.
PS01159. WW_DOMAIN_1. 1 hit.
PS50020. WW_DOMAIN_2. 1 hit.

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

O95817-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MSAATHSPMM QVASGNGDRD PLPPGWEIKI DPQTGWPFFV DHNSRTTTWN
60 70 80 90 100
DPRVPSEGPK ETPSSANGPS REGSRLPPAR EGHPVYPQLR PGYIPIPVLH
110 120 130 140 150
EGAENRQVHP FHVYPQPGMQ RFRTEAAAAA PQRSQSPLRG MPETTQPDKQ
160 170 180 190 200
CGQVAAAAAA QPPASHGPER SQSPAASDCS SSSSSASLPS SGRSSLGSHQ
210 220 230 240 250
LPRGYISIPV IHEQNVTRPA AQPSFHQAQK THYPAQQGEY QTHQPVYHKI
260 270 280 290 300
QGDDWEPRPL RAASPFRSSV QGASSREGSP ARSSTPLHSP SPIRVHTVVD
310 320 330 340 350
RPQQPMTHRE TAPVSQPENK PESKPGPVGP ELPPGHIPIQ VIRKEVDSKP
360 370 380 390 400
VSQKPPPPSE KVEVKVPPAP VPCPPPSPGP SAVPSSPKSV ATEERAAPST
410 420 430 440 450
APAEATPPKP GEAEAPPKHP GVLKVEAILE KVQGLEQAVD NFEGKKTDKK
460 470 480 490 500
YLMIEEYLTK ELLALDSVDP EGRADVRQAR RDGVRKVQTI LEKLEQKAID
510 520 530 540 550
VPGQVQVYEL QPSNLEADQP LQAIMEMGAV AADKGKKNAG NAEDPHTETQ
560 570
QPEATAAATS NPSSMTDTPG NPAAP
Length:575
Mass (Da):61,595
Last modified:January 11, 2001 - v3
Checksum:iA6328A44F37A406A
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti227Q → K in AAD16122 (PubMed:9873016).Curated1
Sequence conflicti237Q → R in AAD16122 (PubMed:9873016).Curated1
Sequence conflicti304Missing in CAB70824 (PubMed:17974005).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_04834471R → Q1 PublicationCorresponds to variant dbSNP:rs35434411Ensembl.1
Natural variantiVAR_06547971R → W in CMD1HH. 1 PublicationCorresponds to variant dbSNP:rs387906874Ensembl.1
Natural variantiVAR_06677777P → L1 PublicationCorresponds to variant dbSNP:rs141355480Ensembl.1
Natural variantiVAR_06677894I → F1 PublicationCorresponds to variant dbSNP:rs145393807Ensembl.1
Natural variantiVAR_066779115P → S1 PublicationCorresponds to variant dbSNP:rs774241343Ensembl.1
Natural variantiVAR_048345151C → R2 PublicationsCorresponds to variant dbSNP:rs2234962Ensembl.1
Natural variantiVAR_066780155A → T1 PublicationCorresponds to variant dbSNP:rs61756328Ensembl.1
Natural variantiVAR_063089209P → L in MFM6; interferes with the differentiation of skeletal muscle cells; does not cause functional alterations in cardiomyocyte cells. 3 PublicationsCorresponds to variant dbSNP:rs121918312Ensembl.1
Natural variantiVAR_066781218R → W in CMD1HH; interferes with the assembly of Z-disks; increases stress-induced apoptosis. 1 PublicationCorresponds to variant dbSNP:rs397514506Ensembl.1
Natural variantiVAR_066782258R → W Polymorphism; no functional consequences. 2 PublicationsCorresponds to variant dbSNP:rs117671123Ensembl.1
Natural variantiVAR_066783300D → N1 PublicationCorresponds to variant dbSNP:rs78439745Ensembl.1
Natural variantiVAR_066784380P → S1 PublicationCorresponds to variant dbSNP:rs144692954Ensembl.1
Natural variantiVAR_048346405A → V. Corresponds to variant dbSNP:rs11199064Ensembl.1
Natural variantiVAR_048347407P → L2 PublicationsCorresponds to variant dbSNP:rs3858340Ensembl.1
Natural variantiVAR_066785455E → K in CMD1HH. 1 PublicationCorresponds to variant dbSNP:rs397516881Ensembl.1
Natural variantiVAR_066786462L → P in CMD1HH; interferes with the assembly of Z-disks; increases stress-induced apoptosis. 1 PublicationCorresponds to variant dbSNP:rs397514507Ensembl.1
Natural variantiVAR_066787468V → M in CMD1HH. 1 Publication1
Natural variantiVAR_065480477R → H in CMD1HH. 1 PublicationCorresponds to variant dbSNP:rs387906876Ensembl.1
Natural variantiVAR_066788553E → D1 PublicationCorresponds to variant dbSNP:rs763530097Ensembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF095193 mRNA. Translation: AAD16122.2.
AF127139 mRNA. Translation: AAF26839.1.
AF071218 mRNA. Translation: AAF69592.2.
AK291333 mRNA. Translation: BAF84022.1.
AL137582 mRNA. Translation: CAB70824.1.
BC006418 mRNA. Translation: AAH06418.1.
BC014656 mRNA. Translation: AAH14656.1.
BC107786 mRNA. Translation: AAI07787.1.
CCDSiCCDS7615.1.
RefSeqiNP_004272.2. NM_004281.3.
UniGeneiHs.523309.

Genome annotation databases

EnsembliENST00000369085; ENSP00000358081; ENSG00000151929.
GeneIDi9531.
KEGGihsa:9531.
UCSCiuc001lem.4. human.

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Entry informationi

Entry nameiBAG3_HUMAN
AccessioniPrimary (citable) accession number: O95817
Secondary accession number(s): A8K5L8
, Q3B763, Q9NT20, Q9P120
Entry historyiIntegrated into UniProtKB/Swiss-Prot: January 11, 2001
Last sequence update: January 11, 2001
Last modified: August 30, 2017
This is version 177 of the entry and version 3 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 10
    Human chromosome 10: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot