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Protein

BAG family molecular chaperone regulator 1

Gene

BAG1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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:27474739, PubMed:9873016, PubMed:24318877). Inhibits the pro-apoptotic function of PPP1R15A, and has anti-apoptotic activity (PubMed:12724406). Markedly increases the anti-cell death function of BCL2 induced by various stimuli (PubMed:9305631).5 Publications

GO - Molecular functioni

  • adenyl-nucleotide exchange factor activity Source: UniProtKB
  • chaperone binding Source: InterPro
  • signal transducer activity, downstream of receptor Source: ProtInc
  • ubiquitin protein ligase binding Source: ARUK-UCL

GO - Biological processi

  • apoptotic process Source: UniProtKB-KW
  • cell surface receptor signaling pathway Source: ProtInc
  • chaperone cofactor-dependent protein refolding Source: UniProtKB
  • negative regulation of apoptotic process Source: ProtInc
  • regulation of cellular response to heat Source: Reactome

Keywordsi

Molecular functionChaperone
Biological processApoptosis

Enzyme and pathway databases

ReactomeiR-HSA-3371453 Regulation of HSF1-mediated heat shock response
SIGNORiQ99933

Names & Taxonomyi

Protein namesi
Recommended name:
BAG family molecular chaperone regulator 1
Short name:
BAG-1
Alternative name(s):
Bcl-2-associated athanogene 1
Gene namesi
Name:BAG1
Synonyms:HAP
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi

Organism-specific databases

EuPathDBiHostDB:ENSG00000107262.17
HGNCiHGNC:937 BAG1
MIMi601497 gene
neXtProtiNX_Q99933

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi308 – 309RK → AA: Significant loss of interaction with HSPA8. 1 Publication2

Organism-specific databases

DisGeNETi573
OpenTargetsiENSG00000107262
PharmGKBiPA25237

Polymorphism and mutation databases

BioMutaiBAG1
DMDMi296439462

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000888651 – 345BAG family molecular chaperone regulator 1Add BLAST345

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei223PhosphoserineCombined sources1

Post-translational modificationi

Ubiquitinated; mediated by SIAH1 or SIAH2 and leading to its subsequent proteasomal degradation.Curated

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ99933
MaxQBiQ99933
PaxDbiQ99933
PeptideAtlasiQ99933
PRIDEiQ99933

PTM databases

iPTMnetiQ99933
PhosphoSitePlusiQ99933

Expressioni

Tissue specificityi

Isoform 4 is the most abundantly expressed isoform. It is ubiquitously expressed throughout most tissues, except the liver, colon, breast and uterine myometrium. Isoform 1 is expressed in the ovary and testis. Isoform 4 is expressed in several types of tumor cell lines, and at consistently high levels in leukemia and lymphoma cell lines. Isoform 1 is expressed in the prostate, breast and leukemia cell lines. Isoform 3 is the least abundant isoform in tumor cell lines (at protein level).1 Publication

Inductioni

Up-regulated during differentiation of bladder epithelial cells and down-regulated during differentiation of prostate epithelium.1 Publication

Gene expression databases

BgeeiENSG00000107262
CleanExiHS_BAG1
ExpressionAtlasiQ99933 baseline and differential
GenevisibleiQ99933 HS

Organism-specific databases

HPAiCAB002486
HPA018121

Interactioni

Subunit structurei

Homodimer. Forms a heteromeric complex with HSP70/HSC70 (PubMed:9305631). Binds to the ATPase domain of HSP/HSC70 chaperones. Isoform 1, isoform 3 and isoform 4 but not isoform 2 interact with HSPA8/HSC70 (PubMed:27474739, PubMed:24318877, PubMed:9305631, PubMed:9679980). Interacts with NR3C1 (PubMed:10477749). Interacts with the N-terminal region of STK19 (PubMed:15986447). Interacts with PPP1R15A (PubMed:12724406). Interacts with BCL2 in an ATP-dependent manner. Isoform 2 does not interact with BCL2 (PubMed:9305631). Interacts with SIAH1 (PubMed:9582267). Interacts with HSPA8 (via NBD) (PubMed:27474739, PubMed:24318877). Interacts with HSPA1A (via NBD) and HSPA1B (via NBD) (PubMed:24318877). Interacts with SIAH2 (By similarity).By similarity9 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • chaperone binding Source: InterPro
  • ubiquitin protein ligase binding Source: ARUK-UCL

Protein-protein interaction databases

BioGridi107049, 143 interactors
CORUMiQ99933
DIPiDIP-3341N
IntActiQ99933, 40 interactors
MINTiQ99933
STRINGi9606.ENSP00000420514

Structurei

Secondary structure

1345
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi144 – 149Combined sources6
Beta strandi151 – 159Combined sources9
Beta strandi163 – 167Combined sources5
Helixi170 – 180Combined sources11
Turni185 – 187Combined sources3
Beta strandi189 – 192Combined sources4
Beta strandi195 – 197Combined sources3
Beta strandi200 – 203Combined sources4
Helixi204 – 207Combined sources4
Beta strandi211 – 219Combined sources9
Helixi224 – 259Combined sources36
Beta strandi260 – 262Combined sources3
Helixi264 – 272Combined sources9
Helixi275 – 292Combined sources18
Helixi302 – 327Combined sources26

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1HX1X-ray1.90B222-334[»]
1WXVNMR-A144-222[»]
3FZFX-ray2.20B222-334[»]
3FZHX-ray2.00B222-334[»]
3FZKX-ray2.10B222-334[»]
3FZLX-ray2.20B222-334[»]
3FZMX-ray2.30B222-334[»]
3LDQX-ray1.90B222-334[»]
3M3ZX-ray2.10B222-334[»]
5AQFX-ray1.88B/D222-334[»]
5AQGX-ray2.24B/D/F222-334[»]
5AQHX-ray2.00B222-334[»]
5AQIX-ray1.98B/D222-334[»]
5AQJX-ray1.96B/D/F222-334[»]
5AQKX-ray2.09B222-334[»]
5AQLX-ray1.69B/D222-334[»]
5AQMX-ray1.63B/D222-334[»]
5AQNX-ray2.45B/D/F222-334[»]
5AQOX-ray2.12B/D/F222-334[»]
5AQPX-ray2.08B/D/F222-334[»]
5AQQX-ray2.72B/D/F222-334[»]
5AQRX-ray1.91B/D/F222-334[»]
5AQSX-ray2.00B/D222-334[»]
5AQTX-ray1.90B222-334[»]
5AQUX-ray1.92B222-334[»]
5AQVX-ray1.75B222-334[»]
ProteinModelPortaliQ99933
SMRiQ99933
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ99933

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati96 – 10116
Repeati102 – 10726
Repeati108 – 11336
Repeati114 – 11946
Repeati120 – 12556
Repeati126 – 13166
Repeati132 – 13776
Domaini144 – 224Ubiquitin-likePROSITE-ProRule annotationAdd BLAST81
Domaini246 – 326BAGPROSITE-ProRule annotationAdd BLAST81

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni96 – 1377 X 6 AA tandem repeat of E-E-X(4)Add BLAST42
Regioni172 – 219Interaction with HSPA8Add BLAST48
Regioni216 – 345Interaction with PPP1R15A1 PublicationAdd BLAST130

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi4 – 82Arg-richAdd BLAST79

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiENOG410IHYI Eukaryota
ENOG4111SUG LUCA
GeneTreeiENSGT00450000040296
HOVERGENiHBG000236
InParanoidiQ99933
KOiK09555
PhylomeDBiQ99933

Family and domain databases

Gene3Di1.20.58.120, 1 hit
InterProiView protein in InterPro
IPR017093 BAG-1
IPR036533 BAG_dom_sf
IPR003103 BAG_domain
IPR029071 Ubiquitin-like_domsf
IPR000626 Ubiquitin_dom
PANTHERiPTHR12329:SF16 PTHR12329:SF16, 1 hit
PfamiView protein in Pfam
PF02179 BAG, 1 hit
PF00240 ubiquitin, 1 hit
SMARTiView protein in SMART
SM00264 BAG, 1 hit
SM00213 UBQ, 1 hit
SUPFAMiSSF54236 SSF54236, 1 hit
SSF63491 SSF63491, 1 hit
PROSITEiView protein in PROSITE
PS51035 BAG, 1 hit
PS50053 UBIQUITIN_2, 1 hit

Sequences (4)i

Sequence statusi: Complete.

This entry describes 4 isoformsi produced by alternative splicing and alternative initiation. AlignAdd to basket

Isoform 1 (identifier: Q99933-1) [UniParc]FASTAAdd to basket
Also known as: BAG-1L, p50

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MAQRGGARRP RGDRERLGSR LRALRPGREP RQSEPPAQRG PPPSGRPPAR
60 70 80 90 100
STASGHDRPT RGAAAGARRP RMKKKTRRRS TRSEELTRSE ELTLSEEATW
110 120 130 140 150
SEEATQSEEA TQGEEMNRSQ EVTRDEESTR SEEVTREEMA AAGLTVTVTH
160 170 180 190 200
SNEKHDLHVT SQQGSSEPVV QDLAQVVEEV IGVPQSFQKL IFKGKSLKEM
210 220 230 240 250
ETPLSALGIQ DGCRVMLIGK KNSPQEEVEL KKLKHLEKSV EKIADQLEEL
260 270 280 290 300
NKELTGIQQG FLPKDLQAEA LCKLDRRVKA TIEQFMKILE EIDTLILPEN
310 320 330 340
FKDSRLKRKG LVKKVQAFLA ECDTVEQNIC QETERLQSTN FALAE
Length:345
Mass (Da):38,779
Last modified:May 18, 2010 - v4
Checksum:i8B40EF078C66335F
GO
Isoform 2 (identifier: Q99933-2) [UniParc]FASTAAdd to basket
Also known as: BAG1V, HAPV

The sequence of this isoform differs from the canonical sequence as follows:
     302-345: KDSRLKRKGLVKKVQAFLAECDTVEQNICQETERLQSTNFALAE → PTLTLVLNEK

Note: Produced by alternative splicing.
Show »
Length:311
Mass (Da):34,866
Checksum:i1F94BA55E21694D3
GO
Isoform 3 (identifier: Q99933-3) [UniParc]FASTAAdd to basket
Also known as: BAG-1M, RAP46

The sequence of this isoform differs from the canonical sequence as follows:
     1-71: Missing.

Note: Produced by alternative initiation at Met-72 of isoform 1.
Show »
Length:274
Mass (Da):31,117
Checksum:iC13E200ED63A2CF0
GO
Isoform 4 (identifier: Q99933-4) [UniParc]FASTAAdd to basket
Also known as: BAG-1, p32

The sequence of this isoform differs from the canonical sequence as follows:
     1-115: Missing.

Note: Produced by alternative initiation at Met-116 of isoform 1.
Show »
Length:230
Mass (Da):25,989
Checksum:iD4B34A8F54DE684D
GO

Sequence cautioni

The sequence AAD11467 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence AAD25045 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence BAD96469 differs from that shown. Unusual initiator. The initiator methionine is coded by a non-canonical CTG leucine codon.Curated
The sequence CAA84624 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence CAH72516 differs from that shown. Reason: Erroneous gene model prediction.Curated
The sequence CAH72518 differs from that shown. Reason: Erroneous gene model prediction.Curated
The sequence CAH72741 differs from that shown. Reason: Erroneous gene model prediction.Curated
The sequence CAH72742 differs from that shown. Reason: Erroneous gene model prediction.Curated
The sequence EAW58515 differs from that shown. Reason: Erroneous gene model prediction.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti45G → R in AAC34258 (PubMed:8812483).Curated1
Sequence conflicti45G → R in BAD96469 (Ref. 5) Curated1
Sequence conflicti45G → R in AAH01936 (PubMed:15489334).Curated1
Sequence conflicti45G → R in AAH14774 (PubMed:15489334).Curated1
Sequence conflicti79R → F in AAD11467 (PubMed:8812483).Curated1
Sequence conflicti84E → K in AAD11467 (PubMed:8812483).Curated1
Sequence conflicti90E → K in AAD11467 (PubMed:8812483).Curated1
Sequence conflicti245D → N in AAD11467 (PubMed:8812483).Curated1
Sequence conflicti293D → H in AAD11467 (PubMed:8812483).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0383941 – 115Missing in isoform 4. CuratedAdd BLAST115
Alternative sequenceiVSP_0383951 – 71Missing in isoform 3. CuratedAdd BLAST71
Alternative sequenceiVSP_000453302 – 345KDSRL…FALAE → PTLTLVLNEK in isoform 2. 1 PublicationAdd BLAST44

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Z35491 mRNA Translation: CAA84624.1 Different initiation.
U46917 mRNA Translation: AAD11467.1 Different initiation.
AF022224 mRNA Translation: AAC34258.1
AF116273 mRNA Translation: AAD25045.1 Different initiation.
AK222749 mRNA Translation: BAD96469.1 Different initiation.
AL161445, AL356472 Genomic DNA Translation: CAH72516.1 Sequence problems.
AL161445, AL356472 Genomic DNA Translation: CAH72517.1
AL161445, AL356472 Genomic DNA Translation: CAH72518.1 Sequence problems.
AL356472, AL161445 Genomic DNA Translation: CAH72741.1 Sequence problems.
AL356472, AL161445 Genomic DNA Translation: CAH72742.1 Sequence problems.
AL356472, AL161445 Genomic DNA Translation: CAH72743.1
CH471071 Genomic DNA Translation: EAW58514.1
CH471071 Genomic DNA Translation: EAW58515.1 Sequence problems.
BC001936 mRNA Translation: AAH01936.2
BC014774 mRNA Translation: AAH14774.2
CCDSiCCDS35004.1 [Q99933-1]
CCDS55301.1 [Q99933-4]
RefSeqiNP_001165886.1, NM_001172415.1 [Q99933-4]
NP_004314.5, NM_004323.5
UniGeneiHs.377484

Genome annotation databases

EnsembliENST00000379704; ENSP00000369026; ENSG00000107262 [Q99933-4]
ENST00000641048; ENSP00000493185; ENSG00000107262 [Q99933-1]
GeneIDi573
KEGGihsa:573
UCSCiuc064sos.1 human [Q99933-1]

Keywords - Coding sequence diversityi

Alternative initiation, Alternative splicing

Entry informationi

Entry nameiBAG1_HUMAN
AccessioniPrimary (citable) accession number: Q99933
Secondary accession number(s): O75315
, Q14414, Q53H32, Q5VZE8, Q5VZE9, Q5VZF0, Q96TG2, Q9Y2V4
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: May 18, 2010
Last modified: May 23, 2018
This is version 187 of the entry and version 4 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

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 9
    Human chromosome 9: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references

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