BAK1 (Homo sapiens)
Description [+]
- Synonyms: BAK1, BAK2
- Species: Metazoa;Bilateria;Deuterostoma;Chordata;Vertebrata;Mammalia;Primates;Hominidae; Homo sapiens
- Short gene description: Bcl-2 homologous antagonist/killer (Apoptosis regulator BAK)(Bcl-2-like 7 protein) [Source:UniProtKB/Swiss-Prot;Acc:Q16611]
- Family: Bcl-2 family : multidomain Bcl-2
- Process: apoptosis,
- Pathways: intrinsic pathway, pre-mitochondrial signaling events,
- Criteria: manually curated
- Curator comment:
- Mouse ortholog(s): Bak1
- WIKI: BAK1-H_sapiens
References [+]
- Induction of apoptosis by the Bcl-2 homologue Bak.
- Chittenden T, Harrington EA, O'Connor R, Flemington C, Lutz RJ, Evan GI, Guild BC
- Cells are eliminated in a variety of physiological settings by apoptosis, a genetically encoded process of cellular suicide. Apoptosis comprises an intrinsic cellular defence against tumorigenesis, which, when suppressed, may contribute to the development of malignancies. The bcl-2 oncogene, which is activated in follicular lymphomas, functions as a potent suppressor of apoptosis under diverse conditions. Here we describe the complementary DNA cloning and functional analysis of a new Bcl-2 homologue, Bak, which promotes cell death and counteracts the protection from apoptosis provided by Bcl-2. Moreover, enforced expression of Bak induces rapid and extensive apoptosis of serum-deprived fibroblasts. This raises the possibility that Bak is directly involved in activating the cell death machinery. Nature. 1995 Apr 20;374(6524):733-6.
- References from Mouse ortholog(s):
- Proapoptotic BAX and BAK: a requisite gateway to mitochondrial dysfunction and death.
- Wei MC, Zong WX, Cheng EH, Lindsten T, Panoutsakopoulou V, Ross AJ, Roth KA, MacGregor GR, Thompson CB, Korsmeyer SJ
- Multiple death signals influence mitochondria during apoptosis, yet the critical initiating event for mitochondrial dysfunction in vivo has been unclear. tBID, the caspase-activated form of a "BH3-domain-only" BCL-2 family member, triggers the homooligomerization of "multidomain" conserved proapoptotic family members BAK or BAX, resulting in the release of cytochrome c from mitochondria. We find that cells lacking both Bax and Bak, but not cells lacking only one of these components, are completely resistant to tBID-induced cytochrome c release and apoptosis. Moreover, doubly deficient cells are resistant to multiple apoptotic stimuli that act through disruption of mitochondrial function: staurosporine, ultraviolet radiation, growth factor deprivation, etoposide, and the endoplasmic reticulum stress stimuli thapsigargin and tunicamycin. Thus, activation of a "multidomain" proapoptotic member, BAX or BAK, appears to be an essential gateway to mitochondrial dysfunction required for cell death in response to diverse stimuli. Science. 2001 Apr 27;292(5517):727-30.
- Gene structure, cDNA sequence, and expression of murine Bak, a proapoptotic Bcl-2 family member.
- Ulrich E, Kauffmann-Zeh A, Hueber AO, Williamson J, Chittenden T, Ma A, Evan G
- To facilitate the creation of Bak knockout mice and the further analysis of this Bcl-2 family member, we have isolated and sequenced the complete mouse Bak cDNA. The cDNA is 2 kb long and shares an overall nucleotide identity to the human Bak cDNA of 62%. The mouse Bak protein is 208 amino acids long with a predicted molecular weight of 23 kDa. The mouse Bak mRNA could be detected in all mouse tissues examined. In addition we mapped the murine bak gene. It consists of six exons spanning about 10 kb on chromosome 17B. The 5' region of the murine bak gene is unmethylated on the dinucleotide CpG in the area around exon 1. Furthermore, it contains potential binding sites for transcription factors such as Sp1 and c-Myb. Genomics. 1997 Sep 1;44(2):195-200.
Structure & Sequence [+]
Pfam domains:
(Pfam is a large collection of protein families.)
Source | Domain Name | Start | End |
---|---|---|---|
PFAM A | Bcl-2 | 78 | 177 |
Protein sequence [+]
BAK1 | Homo sapiens | 9606 | length:211
MASGQGPGPPRQECGEPALPSASEEQVAQDTEEVFRSYVFYRHQQEQEAEGVAAPADPEM
VTLPLQPSSTMGQVGRQLAIIGDDINRRYDSEFQTMLQHLQPTAENAYEYFTKIATSLFE
SGINWGRVVALLGFGYRLALHVYQHGLTGFLGQVTRFVVDFMLHHCIARWIAQRGGWVAA
LNLGNGPILNVLVVLGVVLLGQFVVRRFFKS
VTLPLQPSSTMGQVGRQLAIIGDDINRRYDSEFQTMLQHLQPTAENAYEYFTKIATSLFE
SGINWGRVVALLGFGYRLALHVYQHGLTGFLGQVTRFVVDFMLHHCIARWIAQRGGWVAA
LNLGNGPILNVLVVLGVVLLGQFVVRRFFKS
Structure links:
- Smartdomain prediction information: SM00337
- Prosite motif and domain information: PS01080
- Prosite motif and domain information: PS01258
- Prosite motif and domain information: PS01259
- Profile motif and domain profile information: PS50062
- Interpro domain information: Q16611
- PFAM domain and domain family information: Q16611
- Protein 3D structures from PDB: 2JBY 1BXL
Evolution [+]
View protein alignment and tree with Jalview:  
Explore tree at phylomeDB:   Click here.
Homologs list [+]
Name | Relationship | Species |
---|---|---|
NP_001026091.1 | orthology | Chicken |
XR_024448.1 | orthology | Chimpanzee |
NP_001071386.1 | orthology | Cow |
NP_001018644.1 | orthology | Dog |
BAK1 | orthology | Gorilla |
BAK1 | orthology | Horse |
BAK1 | orthology | Lyzard |
BAK1 | orthology | Macaca |
BAK1 | orthology | Monodelphis |
Bak1 | orthology | Mouse |
P_pygmaeus_ENSPPYP00000018457 | orthology | Orangutan |
BAK1 | orthology | Rabbit |
Bak1 | orthology | Rat |
BAK1 | orthology | Xenopus |
BAK1 | orthology | Zebra finch |
A_aegypti_AAEL001521-PA | paralogy | Aedes |
BOK_CHICK | paralogy | Chicken |
BCLX_CHICK | paralogy | Chicken |
BCL2_CHICK | paralogy | Chicken |
MCL1 | paralogy | Chimpanzee |
BCL2L2 | paralogy | Chimpanzee |
BCL2 | paralogy | Chimpanzee |
BAX | paralogy | Chimpanzee |
BCL2L1 | paralogy | Chimpanzee |
C_intestinalis_ENSCINP00000024813 | paralogy | Ciona |
NP_001070954.1 | paralogy | Cow |
BAX_BOVIN | paralogy | Cow |
NP_001092676.1 | paralogy | Cow |
Q462R3_BOVIN | paralogy | Cow |
BCLW_BOVIN | paralogy | Cow |
BCL2 | paralogy | Dog |
NP_001003072.1 | paralogy | Dog |
MCL1_CANFA | paralogy | Dog |
T_rubripes_ENSTRUP00000006891 | paralogy | Fugu |
BCL2 | paralogy | Fugu |
BCL2L1 (1 of 6) | paralogy | Fugu |
BCL2L1 (2 of 6) | paralogy | Fugu |
BAX | paralogy | Fugu |
BCL2L1 (1 of 2) | paralogy | Gasterosteus |
BOK (1 of 2) | paralogy | Gasterosteus |
BCL2L1 (2 of 2) | paralogy | Gasterosteus |
BCL2 | paralogy | Gasterosteus |
BOK (2 of 2) | paralogy | Gasterosteus |
BAX | paralogy | Gasterosteus |
G_aculeatus_ENSGACP00000018978 | paralogy | Gasterosteus |
BCL2 | paralogy | Gorilla |
BCL2L2 | paralogy | Gorilla |
BAX | paralogy | Gorilla |
MCL1 | paralogy | Gorilla |
BCL2L2 | paralogy | Horse |
BCL2L1 | paralogy | Horse |
MCL1 | paralogy | Horse |
BCL2 | paralogy | Horse |
BCL2L2 | paralogy | Human |
BAX | paralogy | Human |
MCL1 | paralogy | Human |
BCL2L1 | paralogy | Human |
BCL2 | paralogy | Human |
BOK | paralogy | Lyzard |
A_carolinensis_ENSACAP00000004550 | paralogy | Lyzard |
BCL2L1 | paralogy | Lyzard |
BAX | paralogy | Lyzard |
BCL2 | paralogy | Lyzard |
BAX | paralogy | Macaca |
BCL2L1 | paralogy | Macaca |
BCL2 | paralogy | Macaca |
MCL1 | paralogy | Macaca |
BCL2L2 | paralogy | Macaca |
BAX | paralogy | Medaka |
BCL2L1 | paralogy | Medaka |
BCL2 | paralogy | Medaka |
BCL2 | paralogy | Monodelphis |
BAX | paralogy | Monodelphis |
MCL1 | paralogy | Monodelphis |
BCL2A1 | paralogy | Monodelphis |
BCL2L1 | paralogy | Monodelphis |
M_domestica_ENSMODP00000005598 | paralogy | Monodelphis |
Bcl2l2 | paralogy | Mouse |
Bax | paralogy | Mouse |
Mcl1 | paralogy | Mouse |
Bcl2l1 | paralogy | Mouse |
Bcl2 | paralogy | Mouse |
MCL1 | paralogy | Orangutan |
P_pygmaeus_ENSPPYP00000006150 | paralogy | Orangutan |
BCL2 | paralogy | Orangutan |
BCL2L1 | paralogy | Orangutan |
BOK | paralogy | Ornithorhynchus |
BCL2L2 | paralogy | Ornithorhynchus |
Q9MYW4_RABIT | paralogy | Rabbit |
BAX | paralogy | Rabbit |
MCL1 | paralogy | Rabbit |
Bcl2 | paralogy | Rat |
Bax | paralogy | Rat |
BCLX_RAT | paralogy | Rat |
RGD1565822_predicted | paralogy | Rat |
BCL2 | paralogy | Tetraodon |
BOK (1 of 2) | paralogy | Tetraodon |
BCL2L1 (1 of 3) | paralogy | Tetraodon |
BCL2L1 (2 of 3) | paralogy | Tetraodon |
T_nigroviridis_ENSTNIP00000017211 | paralogy | Tetraodon |
BOK (2 of 2) | paralogy | Tetraodon |
bcl2l2 | paralogy | Xenopus |
bax | paralogy | Xenopus |
BCL2 | paralogy | Xenopus |
BCL2L1 | paralogy | Xenopus |
BCL2 | paralogy | Zebra finch |
BOK | paralogy | Zebra finch |
BCL2L1 | paralogy | Zebra finch |
BAX | paralogy | Zebra finch |
baxa | paralogy | Zebrafish |
BAXB | paralogy | Zebrafish |
zgc:153993 | paralogy | Zebrafish |
bcl2l | paralogy | Zebrafish |
bcl2 | paralogy | Zebrafish |
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Gene Ontology [+]
GO id | Name | Ontology type | Evidence |
---|---|---|---|
GO:0042981 | regulation of apoptosis | biological_proccess | IEA |
GO:0001782 | B cell homeostasis | biological_proccess | IEA |
GO:0008283 | cell proliferation | biological_proccess | IEA |
GO:0051726 | regulation of cell cycle | biological_proccess | IEA |
GO:0006919 | activation of caspase activity | biological_proccess | IEA |
GO:0048872 | homeostasis of number of cells | biological_proccess | IEA |
GO:0043065 | positive regulation of apoptosis | biological_proccess | IEA |
GO:0010332 | response to gamma radiation | biological_proccess | IEA |
GO:0001974 | blood vessel remodeling | biological_proccess | IEA |
GO:0002262 | myeloid cell homeostasis | biological_proccess | IEA |
GO:0001783 | B cell apoptosis | biological_proccess | IEA |
GO:0009620 | response to fungus | biological_proccess | IEA |
GO:0008053 | mitochondrial fusion | biological_proccess | IEA |
GO:0035108 | limb morphogenesis | biological_proccess | IEA |
GO:0048597 | post-embryonic camera-type eye morphogenesis | biological_proccess | IEA |
GO:0001776 | leukocyte homeostasis | biological_proccess | IEA |
GO:0033137 | negative regulation of peptidyl-serine phosphorylation | biological_proccess | IEA |
GO:0070059 | apoptosis in response to endoplasmic reticulum stress | biological_proccess | IEA |
GO:0002352 | B cell negative selection | biological_proccess | IEA |
GO:0008635 | activation of caspase activity by cytochrome c | biological_proccess | IEA |
GO:0010046 | response to mycotoxin | biological_proccess | IEA |
GO:0010524 | positive regulation of calcium ion transport into cytosol | biological_proccess | IEA |
GO:0032471 | reduction of endoplasmic reticulum calcium ion concentration | biological_proccess | IEA |
GO:0060068 | vagina development | biological_proccess | IEA |
GO:0006917 | induction of apoptosis | biological_proccess | NAS |
GO:0001836 | release of cytochrome c from mitochondria | biological_proccess | IDA |
GO:0010248 | establishment or maintenance of transmembrane electrochemical gradient | biological_proccess | IDA |
GO:0046902 | regulation of mitochondrial membrane permeability | biological_proccess | IDA |
GO:0051881 | regulation of mitochondrial membrane potential | biological_proccess | IDA |
GO:0043496 | regulation of protein homodimerization activity | biological_proccess | IDA |
GO:0043497 | regulation of protein heterodimerization activity | biological_proccess | IDA |
GO:0031072 | heat shock protein binding | mollecular_function | IEA |
GO:0051087 | chaperone binding | mollecular_function | IEA |
GO:0003674 | molecular_function | mollecular_function | ND |
GO:0042802 | identical protein binding | mollecular_function | IPI |
GO:0046872 | metal ion binding | mollecular_function | IEA |
GO:0046982 | protein heterodimerization activity | mollecular_function | IPI |
GO:0008270 | zinc ion binding | mollecular_function | IEA |
GO:0005622 | intracellular | cell_component | IEA |
GO:0005783 | endoplasmic reticulum | cell_component | IEA |
GO:0005829 | cytosol | cell_component | IEA |
GO:0005739 | mitochondrion | cell_component | IEA |
GO:0031966 | mitochondrial membrane | cell_component | IEA |
GO:0016021 | integral to membrane | cell_component | IEA |
GO:0016020 | membrane | cell_component | NAS |
GO:0046930 | pore complex | cell_component | IDA |
GO:0005739 | mitochondrion | cell_component | IDA |
GO:0005741 | mitochondrial outer membrane | cell_component | EXP |
Check GO Evidence Codes here
miRNAs [+]
miRNA | Regulation | Description | Pubmed |
---|---|---|---|
hsa-miR-125b | overexpression by mature mRNA mimics transfection | By using a 2.0-fold difference as the cut-off, there were 60 differentially expressed genes: 13 were up-regulated and 47 were down-regulated (SI Tables 1 and 2). | Ref. |
hsa-miR-125b | overexpression by mature mRNA mimics transfection | We therefore evaluated the effect of miR-125b on the expression of this gene. RT-PCR analysis of RNA extracted from miR-125bm-treated LNCaP cells exhibited a marked decrease in the expression of BAK1 (Fig. 6A), thus validating the microarray results. | Ref. |
hsa-miR-125b | overexpression by mature mRNA mimics transfection | Next, we examined the level of Bak1 protein in miR-125bm- and antimiR-125b-treated LNCaP and/or cds1 cells. Transfection with miR-125bm led to _70% down-regulation of Bak1 in both cell lines (Fig. 6B), whereas treatment with anti-miR-125b induced 200% increase in the Bak1 in LNCaP cells (Fig. 6C). | Ref. |
hsa-miR-125b | downreguation by anti-miRNA | Next, we examined the level of Bak1 protein in miR-125bm- and antimiR-125b-treated LNCaP and/or cds1 cells. Transfection with miR-125bm led to _70% down-regulation of Bak1 in both cell lines (Fig. 6B), whereas treatment with anti-miR-125b induced 200% increase in the Bak1 in LNCaP cells (Fig. 6C). | Ref. |
hsa-miR-125b | overexpression by mature mRNA mimics transfection | As shown in Fig. 6E, miR-125bm transfection did not alter luciferase activity in DU145 cells cotransfected with either pMIR-REPORT Luciferase vector or BAK1 3_ UTR antisense-inserted vector. However, transfection of miR-125bm at concentrations of 25–100 nM resulted in _50–60% reduction of the reporter in the sense vectortransfected DU145 cells. These results indicate that the 3_ UTR of BAK1 transcript is a miR-125b target. | Ref. |
Curated Isoforms [+]
Transcript | Translation |
---|---|
OTTHUMT00000040202 * | OTTHUMP00000016211 * |
Info from The Vertebrate Genome Annotation (VEGA) database.
(*) Canonical transcript and translation forms.
Information from other databases [+]
- Gene info from HGNC [?] :996
- Gene related info from GeneCards [?] : BAK1
- Ensembl genome browser [?] : ENSG00000030110
- Expression info from Arrayexpress [?] : ENSG00000030110
- Protein expression from Protein Atlas: [?] ENSG00000030110
- Community gene edition from Wikigenes: [?] 578
- OMIM gene information: 600516
- OMIM disease information:
Click on [?] for more information.