Q16611 (BAK_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Bcl-2 homologous antagonist/killer

Alternative name(s):
Apoptosis regulator BAK
Bcl-2-like protein 7
Short name=Bcl2-L-7

Gene names

Name:	BAK1
Synonyms:	BAK, BCL2L7, CDN1

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	211 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	In the presence of an appropriate stimulus, accelerates programmed cell death by binding to, and antagonizing the anti-apoptotic action of BCL2 or its adenovirus homolog E1B 19k protein. Low micromolar levels of zinc ions inhibit the promotion of apoptosis. Ref.10 Ref.14
Subunit structure	Interacts with BCL2A1 By similarity. Homodimer. Formation of the homodimer is zinc-dependent. Forms heterodimers with BCL2, E1B 19k protein, and BCL2L1 isoform Bcl-X(L). Interacts with myxoma virus protein M11L. Interacts with BOP/C22orf29. Ref.12 Ref.14
Subcellular location	Mitochondrion membrane; Single-pass membrane protein Potential.
Tissue specificity	Expressed in a wide variety of tissues, with highest levels in the heart and skeletal muscle.
Domain	Intact BH3 motif is required by BIK, BID, BAK, BAD and BAX for their pro-apoptotic activity and for their interaction with anti-apoptotic members of the Bcl-2 family.
Sequence similarities	Belongs to the Bcl-2 family.

Ontologies

Keywords
Biological process	Apoptosis
Cellular component	Membrane Mitochondrion
Coding sequence diversity	Polymorphism
Domain	Transmembrane Transmembrane helix
Ligand	Metal-binding Zinc
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	B cell apoptotic process Inferred from electronic annotation. Source: Compara B cell homeostasis Inferred from electronic annotation. Source: Compara B cell negative selection Inferred from electronic annotation. Source: Compara activation of cysteine-type endopeptidase activity Inferred from direct assay PubMed 18387192. Source: BHF-UCL activation of cysteine-type endopeptidase activity involved in apoptotic process by cytochrome c Inferred from electronic annotation. Source: Compara aging Inferred from electronic annotation. Source: Compara blood vessel remodeling Inferred from electronic annotation. Source: Compara brain development Inferred from electronic annotation. Source: Compara cell proliferation Inferred from electronic annotation. Source: Compara cellular response to UV Inferred from mutant phenotype PubMed 15901672. Source: UniProtKB cellular response to mechanical stimulus Inferred from expression pattern PubMed 19593445. Source: UniProtKB endocrine pancreas development Inferred from electronic annotation. Source: Compara establishment or maintenance of transmembrane electrochemical gradient Inferred from direct assay PubMed 9843949. Source: HGNC intrinsic apoptotic signaling pathway Traceable author statement. Source: Reactome intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress Inferred from electronic annotation. Source: Compara limb morphogenesis Inferred from electronic annotation. Source: Compara mitochondrial fusion Inferred from electronic annotation. Source: Compara myeloid cell homeostasis Inferred from electronic annotation. Source: Compara negative regulation of cell proliferation Inferred from electronic annotation. Source: Compara negative regulation of gene expression Inferred from electronic annotation. Source: Compara negative regulation of peptidyl-serine phosphorylation Inferred from electronic annotation. Source: Compara organ regeneration Inferred from electronic annotation. Source: Compara positive regulation of apoptotic process Inferred from mutant phenotype PubMed 17289999. Source: UniProtKB positive regulation of calcium ion transport into cytosol Inferred from electronic annotation. Source: Compara positive regulation of endoplasmic reticulum unfolded protein response Inferred from mutant phenotype PubMed 16645094. Source: UniProtKB positive regulation of mitochondrial outer membrane permeabilization Traceable author statement. Source: Reactome positive regulation of proteolysis Inferred from direct assay PubMed 18387192. Source: BHF-UCL positive regulation of release of cytochrome c from mitochondria Inferred from electronic annotation. Source: Compara post-embryonic camera-type eye morphogenesis Inferred from electronic annotation. Source: Compara reduction of endoplasmic reticulum calcium ion concentration Inferred from electronic annotation. Source: Compara regulation of cell cycle Inferred from electronic annotation. Source: Compara regulation of mitochondrial membrane permeability Inferred from direct assay PubMed 21041309. Source: BHF-UCL regulation of mitochondrial membrane potential Inferred from direct assay PubMed 9843949. Source: HGNC regulation of protein heterodimerization activity Inferred from direct assay PubMed 9111042. Source: HGNC regulation of protein homodimerization activity Inferred from direct assay PubMed 9111042. Source: HGNC release of cytochrome c from mitochondria Inferred from direct assay PubMed 9843949. Source: HGNC response to UV-C Inferred from electronic annotation. Source: Compara response to drug Inferred from electronic annotation. Source: Compara response to ethanol Inferred from electronic annotation. Source: Compara response to fungus Inferred from electronic annotation. Source: Compara response to gamma radiation Inferred from electronic annotation. Source: Compara response to hydrogen peroxide Inferred from electronic annotation. Source: Compara response to mycotoxin Inferred from electronic annotation. Source: Compara response to organic cyclic compound Inferred from electronic annotation. Source: Compara vagina development Inferred from electronic annotation. Source: Compara
Cellular_component	cytosol Inferred from electronic annotation. Source: Compara endoplasmic reticulum Inferred from electronic annotation. Source: Compara integral to mitochondrial outer membrane Inferred from sequence or structural similarity. Source: BHF-UCL pore complex Inferred from direct assay PubMed 9843949. Source: HGNC
Molecular_function	metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
itself		2	EBI-519866,EBI-519866
BAX	Q07812	3	EBI-519866,EBI-516580
BCL2L1	Q07817	3	EBI-519866,EBI-78035
BCL2L1	Q07817-1	8	EBI-519866,EBI-287195
MCL1	Q07820	6	EBI-519866,EBI-1003422
Mcl1	P97287	3	EBI-519866,EBI-707292	From a different organism.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 211

211

Bcl-2 homologous antagonist/killer

PRO_0000143059

Regions

Transmembrane

188 – 205

18

Helical; Potential

Motif

74 – 88

15

BH3

Motif

117 – 136

20

BH1

Motif

169 – 184

16

BH2

Sites

Metal binding

160

1

Zinc; shared with dimeric partner

Metal binding

164

1

Zinc; shared with dimeric partner

Natural variations

Natural variant

28

1

A → V. Ref.4
Corresponds to variant rs4987115 [ dbSNP | Ensembl ].

VAR_018829

Natural variant

42

1

R → H.
Corresponds to variant rs1051911 [ dbSNP | Ensembl ].

VAR_048417

Natural variant

69

1

S → R. Ref.4
Corresponds to variant rs5745592 [ dbSNP | Ensembl ].

VAR_018830

Experimental info

Mutagenesis

164

1

H → A: Strongly reduced zinc binding and homodimerization. Ref.14

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

211

Helix Strand Turn

Details...

Helix

24 – 50

27

Helix

51 – 53

3

Helix

59 – 62

4

Helix

70 – 85

16

Helix

87 – 97

11

Helix

104 – 118

15

Turn

119 – 121

3

Helix

125 – 144

20

Helix

151 – 164

14

Helix

167 – 173

7

Helix

177 – 180

4

Sequences

	Sequence		Length	Mass (Da)
	Q16611 [UniParc]. Last modified November 1, 1996. Version 1. Checksum: A2200FE72A46D04E	FASTA	211	23,409
	10 20 30 40 50 60 MASGQGPGPP RQECGEPALP SASEEQVAQD TEEVFRSYVF YRHQQEQEAE GVAAPADPEM 70 80 90 100 110 120 VTLPLQPSST MGQVGRQLAI IGDDINRRYD SEFQTMLQHL QPTAENAYEY FTKIATSLFE 130 140 150 160 170 180 SGINWGRVVA LLGFGYRLAL HVYQHGLTGF LGQVTRFVVD FMLHHCIARW IAQRGGWVAA 190 200 210 LNLGNGPILN VLVVLGVVLL GQFVVRRFFK S

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning of a bcl-2 homologue by interaction with adenovirus E1B 19K." Farrow S.N., White J.H.M., Martinou I., Raven T., Pun K.-T., Grinham C.J., Martinou J.-C., Brown R. Nature 374:731-733(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: B-cell.
[2]	"Induction of apoptosis by the Bcl-2 homologue Bak." Chittenden T., Harrington E.A., O'Connor R., Flemington C., Lutz R.J., Evan G.I., Guild B.C. Nature 374:733-736(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	"Modulation of apoptosis by the widely distributed Bcl-2 homologue Bak." Kiefer M.C., Brauer M.J., Powers V.C., Wu J.J., Umansky S.R., Tomei L.D., Barr P.J. Nature 374:736-739(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[4]	NIEHS SNPs program Submitted (MAR-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS VAL-28 AND ARG-69.
[5]	"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)." Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B. Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[6]	"The DNA sequence and analysis of human chromosome 6." Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D., Andrews T.D. , Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H., Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V., Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J., Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E., Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J., French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J., Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C., Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A., Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R., Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A., Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L., Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I., Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y., Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E., Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A., Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W., Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J., Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M., Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I., Rogers J., Beck S. Nature 425:805-811(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Lung.
[9]	"Estrogen alters expression of apoptosis-regulators, Bcl-2, Bcl-xL and Bak, as well as susceptibility to therapeutic agents of human breast cancer cells." Eguchi H., Hayashi S. Submitted (NOV-1996) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 96-206.
[10]	"A conserved domain in Bak, distinct from BH1 and BH2, mediates cell death and protein binding functions." Chittenden T., Flemington C., Houghton A.B., Ebb R.G., Gallo G.J., Elangovan B., Chinnadurai G., Lutz R.J. EMBO J. 14:5589-5596(1995) [PubMed] [Europe PMC] [Abstract] Cited for: MUTAGENESIS, FUNCTION OF BH3 MOTIF.
[11]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[12]	"Human Bop is a novel BH3-only member of the Bcl-2 protein family." Zhang X., Weng C., Li Y., Wang X., Jiang C., Li X., Xu Y., Chen Q., Pan L., Tang H. Protein Cell 3:790-801(2012) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH BOP/C22ORF29.
[13]	"Structure of Bcl-xL-Bak peptide complex: recognition between regulators of apoptosis." Sattler M., Liang H., Nettesheim D., Meadows R.P., Harlan J.E., Eberstadt M., Yoon H.S., Shuker S.B., Chang B.S., Minn A.J., Thompson C.B., Fesik S.W. Science 275:983-986(1997) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR OF 72-87 IN COMPLEX WITH BCL2L1 ISOFORM BCL-X(L).
[14]	"The X-ray structure of a BAK homodimer reveals an inhibitory zinc binding site." Moldoveanu T., Liu Q., Tocilj A., Watson M., Shore G., Gehring K. Mol. Cell 24:677-688(2006) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.48 ANGSTROMS) OF 16-186, FUNCTION, SUBUNIT, MUTAGENESIS OF HIS-164, ZINC-BINDING.
[15]	"A structural viral mimic of prosurvival Bcl-2: a pivotal role for sequestering proapoptotic Bax and Bak." Kvansakul M., van Delft M.F., Lee E.F., Gulbis J.M., Fairlie W.D., Huang D.C.S., Colman P.M. Mol. Cell 25:933-942(2007) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.41 ANGSTROMS) OF 67-92 IN COMPLEX WITH MYXOMA VIRUS PROTEIN M11L.
[16]	"Crystal structure of MS0836." RIKEN structural genomics initiative (RSGI) Submitted (APR-2008) to the PDB data bank Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS).
+	Additional computationally mapped references.

Web resources

NIEHS-SNPs

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

X84213 mRNA. Translation: CAA58997.1.
U23765 mRNA. Translation: AAA93066.1.
U16811 mRNA. Translation: AAA74466.1.
AY260471 Genomic DNA. Translation: AAO74828.1.
CR457419 mRNA. Translation: CAG33700.1.
Z93017 Genomic DNA. Translation: CAB65626.1.
CH471081 Genomic DNA. Translation: EAX03742.1.
BC004431 mRNA. Translation: AAH04431.1.
D88397 Genomic DNA. Translation: BAA13606.1.

IPI

IPI00924856.

PIR

S58873.

RefSeq

NP_001179.1. NM_001188.3.

UniGene

Hs.485139.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1BXL	NMR	-	B	72-87	[»]
2IMS	X-ray	1.48	A	16-186	[»]
2IMT	X-ray	1.49	A	16-186	[»]
2JBY	X-ray	2.41	B	67-92	[»]
2JCN	X-ray	1.80	A	21-190	[»]
2XPX	X-ray	2.05	B	67-92	[»]
2YV6	X-ray	2.50	A	23-185	[»]
3I1H	X-ray	2.20	B	72-87	[»]
3QBR	X-ray	2.60	B/Y	63-96	[»]

ProteinModelPortal

Q16611.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-935N.

IntAct

Q16611. 9 interactions.

MINT

MINT-96576.

STRING

9606.ENSP00000363591.

Protein family/group databases

TCDB

1.A.21.1.3. bcl-2 (Bcl-2) family.

PTM databases

PhosphoSite

Q16611.

Polymorphism databases

DMDM

2493274.

Proteomic databases

PaxDb

Q16611.

PRIDE

Q16611.

Protocols and materials databases

DNASU

578.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000360661; ENSP00000353878; ENSG00000030110.
ENST00000374467; ENSP00000363591; ENSG00000030110.

GeneID

578.

KEGG

hsa:578.

UCSC

uc003oer.3. human.

Organism-specific databases

CTD

578.

GeneCards

GC06M033541.

HGNC

HGNC:949. BAK1.

HPA

CAB005029.

MIM

600516. gene.

neXtProt

NX_Q16611.

PharmGKB

PA25253.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG145601.

HOGENOM

HOG000006521.

HOVERGEN

HBG002674.

InParanoid

Q16611.

KO

K14021.

OMA

INWGRVI.

OrthoDB

EOG4XWFZW.

PhylomeDB

Q16611.

Enzyme and pathway databases

Reactome

REACT_578. Apoptosis.

Gene expression databases

ArrayExpress

Q16611.

Bgee

Q16611.

CleanEx

HS_BAK1.

Genevestigator

Q16611.

GermOnline

ENSG00000030110. Homo sapiens.

Family and domain databases

InterPro

IPR026308. BAK.
IPR002475. Bcl2-like.
IPR020717. Bcl2_BH1_motif_CS.
IPR020726. Bcl2_BH2_motif_CS.
IPR020728. Bcl2_BH3_motif_CS.
IPR026298. Blc2_fam.
[Graphical view]

PANTHER

PTHR11256. PTHR11256. 1 hit.
PTHR11256:SF8. PTHR11256:SF8. 1 hit.

Pfam

PF00452. Bcl-2. 1 hit.
[Graphical view]

PRINTS

PR01862. BCL2FAMILY.

PROSITE

PS50062. BCL2_FAMILY. 1 hit.
PS01080. BH1. 1 hit.
PS01258. BH2. 1 hit.
PS01259. BH3. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

Q16611.

ChEMBL

CHEMBL5609.

EvolutionaryTrace

Q16611.

GenomeRNAi

578.

NextBio

2359.

SOURCE

Search...

Entry information

Entry name

BAK_HUMAN

Accession

Primary (citable) accession number: Q16611
Secondary accession number(s): Q6I9T6, Q92533

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	November 1, 1996
Last modified:	May 29, 2013
This is version 152 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.