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 [+]

Source	Domain Name	Start	End
PFAM A	Bcl-2	78	177

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 *

Information from other databases [+]

Gene related links:

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

Protein related links:

Uniprot protein info: Q16611
PIR protein info: Q16611
Protein interactions from IntAct: Q16611

Gene and disease information from OMIM: (For a full disease description table, click here.)

OMIM gene information: 600516
OMIM disease information:

Other links

entrezgene: 578
refseq_dna: NM_001188
refseq_peptide: NP_001179

Click on [?] for more information.