Reviewed,
UniProtKB/Swiss-Prot Q99933 (BAG1_HUMAN)
Last modified
July 22, 2008.
Version 88.
History...
Clusters with 100%,
90%,
50% identity |
Documents (5) |
Third-party data |
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Names and origin
| Protein names | Recommended name: BAG family molecular chaperone regulator 1 Short name=BAG-1 Alternative name(s): Bcl-2-associated athanogene 1 Glucocorticoid receptor-associated protein RAP46 | ||||
| Gene names |
| ||||
| Organism | Homo sapiens (Human) | ||||
| Taxonomic identifier | 9606 [NCBI] | ||||
| Taxonomic lineage | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Protein attributes
| Sequence length | 345 AA. |
| Sequence status | Complete. |
| Sequence processing | The displayed sequence is not processed. |
| Protein existence | Evidence at protein level. |
General annotation (Comments)
| Function | Inhibits the chaperone activity of HSP70/HSC70 by promoting substrate release. Inhibits the pro-apoptotic function of PPP1R15A, and has anti-apoptotic activity. Markedly increases the anti-cell death function of BCL2 induced by various stimuli. |
| Subunit structure | Binds to the ATPase domain of HSP70/HSC chaperones. Binds to BCL2 and NR3C1. Interacts with N-terminal region of STK19. Interacts with PPP1R15A. Isoform 2 doesn't interact with HSP70/HSC or BCL2. |
| Subcellular location | Isoform 2: Cytoplasm. Nucleus. Note= Isoform2 localizes to the cytoplasm and shuttles into the nucleus in response to heat shock. |
| Post-translational modification | Ubiquitinated; mediated by SIAH1 or SIAH2 and leading to its subsequent proteasomal degradation Probable. |
| Involvement in disease | May be linked to the cryptophthalmos syndrome (Fraser syndrome), an autosomal recessive disorder characterized by the failure of eyes fissures to form during embryogenesis, webbed fingers, and atresia of ear canals, anus, vagina, alimentary tract, or larynx. All these developmental processes require cell death. |
| Sequence similarities | Contains 1 BAG domain. Contains 1 ubiquitin-like domain. |
Ontologies
Keywords | |
|---|---|
| Biological process | Apoptosis |
| Cellular component | Cytoplasm Nucleus |
| Coding sequence diversity | Alternative splicing |
| Domain | Repeat |
| Molecular function | Chaperone |
| PTM | Ubl conjugation |
| Technical term | 3D-structure |
Gene Ontology (GO) | |
| Biological process | anti-apoptosis Traceable author statement. Source: ProtInc cell surface receptor linked signal transductionTraceable author statement. Source: ProtInc |
| Cellular component | cytoplasm Traceable author statement. Source: ProtInc nucleusInferred from direct assay. Source: LIFEdb |
| Molecular function | protein binding Ref.10 Inferred from physical interaction. Source: IntAct receptor signaling protein activityTraceable author statement. Source: ProtInc |
| Complete GO annotation... | |
Binary interactions
With | Entry | #Exp. | IntAct | Notes |
|---|---|---|---|---|
| HSPA8 | P19120 | 1 | EBI-1030678,EBI-907802 | From a different organism. |
Alternative products
| This entry describes 2 isoforms produced by alternative splicing. [Align] [Select] | |||||
| Isoform 1 (identifier: Q99933-1) 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. | |||||
| Isoform 2 (identifier: Q99933-2) Also known as: BAG1V; HAPV; The sequence of this isoform differs from the canonical sequence as follows: 302-345: KDSRLKRKGLVKKVQAFLAECDTVEQNICQETERLQSTNFALAE → PTLTLVLNEK | |||||
| Notes: Isoform2 localizes to the cytoplasm and shuttles into the nucleus in response to heat shock. |
Sequence annotation (Features)
| Feature key | Position(s) | Length | Description | Graphical view | |||||||||||||||||||||||||||||||
Molecule processing | |||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Chain | 1 – 345 | 345 | BAG family molecular chaperone regulator 1 | ||||||||||||||||||||||||||||||||
Regions | |||||||||||||||||||||||||||||||||||
| Repeat | 96 – 101 | 6 | 1 | ||||||||||||||||||||||||||||||||
| Repeat | 102 – 107 | 6 | 2 | ||||||||||||||||||||||||||||||||
| Repeat | 108 – 113 | 6 | 3 | ||||||||||||||||||||||||||||||||
| Repeat | 114 – 119 | 6 | 4 | ||||||||||||||||||||||||||||||||
| Repeat | 120 – 125 | 6 | 5 | ||||||||||||||||||||||||||||||||
| Repeat | 126 – 131 | 6 | 6 | ||||||||||||||||||||||||||||||||
| Repeat | 132 – 137 | 6 | 7 | ||||||||||||||||||||||||||||||||
| Domain | 144 – 224 | 81 | Ubiquitin-like | ||||||||||||||||||||||||||||||||
| Domain | 246 – 326 | 81 | BAG | ||||||||||||||||||||||||||||||||
| Region | 96 – 137 | 42 | 7 X 6 AA tandem repeat of E-E-X(4) | ||||||||||||||||||||||||||||||||
| Region | 216 – 345 | 130 | Interaction with PPP1R15A | ||||||||||||||||||||||||||||||||
| Compositional bias | 4 – 82 | 79 | Arg-rich | ||||||||||||||||||||||||||||||||
Natural variations | |||||||||||||||||||||||||||||||||||
| Alternative sequence | 302 – 345 | 44 | KDSRL…FALAE → PTLTLVLNEK in isoform 2. | ||||||||||||||||||||||||||||||||
Experimental info | |||||||||||||||||||||||||||||||||||
| Sequence conflict | 79 | 1 | R → F in AAD11467. Ref.2 | ||||||||||||||||||||||||||||||||
| Sequence conflict | 84 | 1 | E → K in AAD11467. Ref.2 | ||||||||||||||||||||||||||||||||
| Sequence conflict | 90 | 1 | E → K in AAD11467. Ref.2 | ||||||||||||||||||||||||||||||||
| Sequence conflict | 245 | 1 | D → N in AAD11467. Ref.2 | ||||||||||||||||||||||||||||||||
| Sequence conflict | 293 | 1 | D → H in AAD11467. Ref.2 | ||||||||||||||||||||||||||||||||
Secondary structure | |||||||||||||||||||||||||||||||||||
Helix Strand Turn | |||||||||||||||||||||||||||||||||||
| Beta strand | 72 – 78 | 7 | |||||||||||||||||||||||||||||||||
| Beta strand | 80 – 88 | 9 | |||||||||||||||||||||||||||||||||
| Beta strand | 92 – 96 | 5 | |||||||||||||||||||||||||||||||||
| Helix | 99 – 109 | 11 | |||||||||||||||||||||||||||||||||
| Turn | 114 – 116 | 3 | |||||||||||||||||||||||||||||||||
| Beta strand | 118 – 121 | 4 | |||||||||||||||||||||||||||||||||
| Beta strand | 124 – 126 | 3 | |||||||||||||||||||||||||||||||||
| Beta strand | 129 – 132 | 4 | |||||||||||||||||||||||||||||||||
| Helix | 133 – 136 | 4 | |||||||||||||||||||||||||||||||||
| Beta strand | 140 – 148 | 9 | |||||||||||||||||||||||||||||||||
| Helix | 224 – 259 | 36 | |||||||||||||||||||||||||||||||||
| Helix | 264 – 272 | 9 | |||||||||||||||||||||||||||||||||
| Helix | 275 – 292 | 18 | |||||||||||||||||||||||||||||||||
| Helix | 302 – 326 | 25 | |||||||||||||||||||||||||||||||||
Sequences
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References
| « Hide 'large scale' references | |
| [1] | "A protein that interacts with members of the nuclear hormone receptor family: identification and cDNA cloning." Zeiner M., Gehring U. Proc. Natl. Acad. Sci. U.S.A. 92:11465-11469(1995) [PubMed: 8524784] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Liver. |
| [2] | "Cloning of cDNAs encoding the human BAG1 protein and localization of the human BAG1 gene to chromosome 9p12." Takayama S., Kochel K., Irie S., Inazawa J., Abe T., Sato T., Druck T., Huebner K., Reed J.C. Genomics 35:494-498(1996) [PubMed: 8812483] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Mammary gland. |
| [3] | Takayama S. Submitted (SEP-1997) to the EMBL/GenBank/DDBJ databases Cited for: SEQUENCE REVISION TO N-TERMINUS; 79; 84; 90; 245 AND 293. |
| [4] | "Characterization of Hap/BAG-1 variants as RP1 binding proteins with antiapoptotic activity." Wadle A., Mischo A., Henrich P.P., Stenner-Lieven F., Scherer C., Imig J., Petersen G., Pfreundschuh M., Renner C. Int. J. Cancer 117:896-904(2005) [PubMed: 15986447] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), ANTI-APOPTOTIC ACTIVITY, SUBCELLULAR LOCATION, INTERACTION WITH STK19. Tissue: T-cell. |
| [5] | "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Cervix and Lung. |
| [6] | "p53-inducible human homologue of Drosophila seven in absentia (Siah) inhibits cell growth: suppression by BAG-1." Matsuzawa S., Takayama S., Froesch B.A., Zapata J.M., Reed J.C. EMBO J. 17:2736-2747(1998) [PubMed: 9582267] [Abstract] Cited for: INTERACTION WITH SIAH1. |
| [7] | "An evolutionarily conserved family of Hsp70/Hsc70 molecular chaperone regulators." Takayama S., Xie Z., Reed J.C. J. Biol. Chem. 274:781-786(1999) [PubMed: 9873016] [Abstract] Cited for: FUNCTION. |
| [8] | "A nuclear action of the eukaryotic cochaperone RAP46 in downregulation of glucocorticoid receptor activity." Schneikert J., Huebner S., Martin E., Cato A.B.C. J. Cell Biol. 146:929-940(1999) [PubMed: 10477749] [Abstract] Cited for: INTERACTION WITH NR3C1. |
| [9] | "Human BAG-1 proteins bind to the cellular stress response protein GADD34 and interfere with GADD34 functions." Hung W.J., Roberson R.S., Taft J., Wu D.Y. Mol. Cell. Biol. 23:3477-3486(2003) [PubMed: 12724406] [Abstract] Cited for: INTERACTION WITH PPP1R15A, FUNCTION. |
| [10] | "Structure of a Bag/Hsc70 complex: convergent functional evolution of Hsp70 nucleotide exchange factors." Sondermann H., Scheufler C., Schneider C., Hohfeld J., Hartl F.U., Moarefi I. Science 291:1553-1557(2001) [PubMed: 11222862] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 222-334 IN COMPLEX WITH HSC70. |
| [11] | "Solution structure of the ubiquitin domain of Bcl-2 binding athanogene-1." RIKEN structural genomics initiative (RSGI) Submitted (AUG-2005) to the PDB data bank Cited for: STRUCTURE BY NMR OF 72-152. |
| + | Additional computationally mapped references. |
Cross-references
Sequence databases | |||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. BC001936 mRNA. Translation: AAH01936.2. BC014774 mRNA. Translation: AAH14774.2. | |||||||||||||||||||
| UniGene | Hs.377484 | ||||||||||||||||||
3D structure databases | |||||||||||||||||||
| |||||||||||||||||||
| SMR | Q99933. Positions 216-345. | ||||||||||||||||||
| ModBase | Search... | ||||||||||||||||||
Protein-protein interaction databases | |||||||||||||||||||
| DIP | DIP:3341N. | ||||||||||||||||||
| IntAct | Q99933. | ||||||||||||||||||
Genome annotation databases | |||||||||||||||||||
| Ensembl | ENSG00000107262. Homo sapiens. [Contig view] | ||||||||||||||||||
Organism-specific databases | |||||||||||||||||||
| H-InvDB | HIX0007978. HIX0080318. | ||||||||||||||||||
| HGNC | HGNC:937. BAG1. | ||||||||||||||||||
| HPA | CAB002486. | ||||||||||||||||||
| MIM | 601497. gene. | ||||||||||||||||||
| PharmGKB | PA25237. | ||||||||||||||||||
| GenAtlas | Search... | ||||||||||||||||||
| GeneCards | Search... | ||||||||||||||||||
Phylogenomic databases | |||||||||||||||||||
| HOVERGEN | Q99933. | ||||||||||||||||||
Gene expression databases | |||||||||||||||||||
| ArrayExpress | Q99933. | ||||||||||||||||||
| CleanEx | HS_BAG1. | ||||||||||||||||||
| GermOnline | ENSG00000107262. Homo sapiens. | ||||||||||||||||||
Family and domain databases | |||||||||||||||||||
| InterPro | IPR003103. BAG. IPR017093. Molecular_chp_reg_BAG_1. IPR000626. Ubiquitin. [Graphical view] | ||||||||||||||||||
| Pfam | PF02179. BAG. 1 hit. PF00240. ubiquitin. 1 hit. [Graphical view] | ||||||||||||||||||
| PIRSF | PIRSF037029. BAG_1. 1 hit. | ||||||||||||||||||
| SMART | SM00264. BAG. 1 hit. SM00213. UBQ. 1 hit. [Graphical view] | ||||||||||||||||||
| PROSITE | PS51035. BAG. 1 hit. PS00299. UBIQUITIN_1. False negative. PS50053. UBIQUITIN_2. 1 hit. [Graphical view] | ||||||||||||||||||
| ProDom | Q99933. [Graphical view] [Entries sharing at least one domain] | ||||||||||||||||||
| BLOCKS | Search... | ||||||||||||||||||
Other Resources | |||||||||||||||||||
| LinkHub | Q99933. | ||||||||||||||||||
| SOURCE | Search... | ||||||||||||||||||
| ProtoNet | Search... | ||||||||||||||||||
Entry information
| Entry name | BAG1_HUMAN | ||||||||
| Accession | Primary (citable) accession number: Q99933 Secondary accession number(s): O75315 Q9Y2V4 | ||||||||
| Entry history |
| ||||||||
| Entry status | Reviewed (UniProtKB/Swiss-Prot) | ||||||||
| Annotation project | HPI (Human Proteome Initiative) | ||||||||
Relevant documents
| Human chromosome 9 Human chromosome 9: entries, gene names and cross-references to MIM |
| MIM cross-references Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot |
| PDB cross-references Index of Protein Data Bank (PDB) cross-references |
| UniProtKB secondary accession numbers Index of UniProtKB secondary accession numbers |
| SIMILARITY comments Index of protein domains and families |

Clusters with


