Reviewed, UniProtKB/Swiss-Prot Q16611 (BAK_HUMAN)

Names and origin

Protein names

Recommended name:
    Bcl-2 homologous antagonist/killer
Alternative name(s):
    Apoptosis regulator BAK
    Bcl-2-like 7 protein

Gene names

Name:	BAK1
Synonyms:	BAK, BCL2L7, CDN1

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	211 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
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 a. repressor BCL2 or its adenovirus homolog E1B 19k protein. Low micromolar levels of zinc ions inhibit the promotion of apoptosis.
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).
Subcellular location	Membrane; Single-pass membrane proteinPotential.
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
Coding sequence diversity	Polymorphism
Domain	Transmembrane
Ligand	Metal-binding Zinc
Technical term	3D-structure
Gene Ontology (GO)
Biological process	establishment or maintenance of transmembrane electrochemical gradient Inferred from direct assay. Source: HGNC induction of apoptosis Traceable author statement. Source: UniProtKB regulation of mitochondrial membrane permeability Inferred from direct assay. Source: HGNC regulation of mitochondrial membrane potential Inferred from direct assay. Source: HGNC regulation of protein heterodimerization activity Inferred from direct assay. Source: HGNC regulation of protein homodimerization activity Inferred from direct assay. Source: HGNC release of cytochrome c from mitochondria Inferred from direct assay. Source: HGNC
Cellular component	mitochondrial outer membrane Inferred from Experiment. Source: Reactome pore complex Inferred from direct assay. Source: HGNC
Molecular function	identical protein binding Inferred from physical interaction. Source: IntAct protein heterodimerization activity Inferred from physical interaction. Source: UniProtKB zinc ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
itself		1	EBI-519866,EBI-519866
ACTR2	P61160	1	EBI-519866,EBI-353580
AKAP13	Q12802	1	EBI-519866,EBI-1373806
BAX	Q07812	1	EBI-519866,EBI-516580
BCL2	P10415	1	EBI-519866,EBI-77694
BCL2L1	Q07817-1	5	EBI-519866,EBI-287195
BID	P55957	1	EBI-519866,EBI-519672
DFFA	O00273	1	EBI-519866,EBI-727171
FBL	P22087	1	EBI-519866,EBI-358318
KRT31	Q15323	1	EBI-519866,EBI-948001
MCL1	Q07820	3	EBI-519866,EBI-1003422
Mcl1	P97287	3	EBI-519866,EBI-707292	From a different organism.
MYCBP2	O75592	1	EBI-519866,EBI-1043774
SRRM2	Q9UQ35	1	EBI-519866,EBI-1050142
VDAC2	P45880	1	EBI-519866,EBI-354022

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

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: dbSNP rs4987115.

VAR_018829

Natural variant

69

1

S → R: dbSNP rs5745592.

VAR_018830

Experimental info

Mutagenesis

164

1

H → A: Strongly reduced zinc binding and homodimerization

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)
	Q16611-1 [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: 7715729] [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: 7715730] [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: 7715731] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[4]	"NIEHS-SNPs, environmental genome project, NIEHS ES15478, Department of Genome Sciences, Seattle, WA (URL: http://egp.gs.washington.edu)." Rieder M.J., Livingston R.J., Daniels M.R., Montoya M.A., Chung M.-W., Miyamoto K.E., Nguyen C.P., Nguyen D.A., Poel C.L., Robertson P.D., Schackwitz W.S., Sherwood J.K., Witrak L.A., Nickerson D.A. Submitted (MAR-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS VAL-28 AND ARG-69.
[5]	"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: 14574404] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"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]. Tissue: Lung.
[7]	"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.
[8]	"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: 8521816] [Abstract] Cited for: MUTAGENESIS, FUNCTION OF BH3 MOTIF.
[9]	"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: 9020082] [Abstract] Cited for: STRUCTURE BY NMR OF 72-87 IN COMPLEX WITH BCL2L1 ISOFORM BCL-X(L).
[10]	"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: 17157251] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.48 ANGSTROMS) OF 16-186, FUNCTION, SUBUNIT, MUTAGENESIS OF HIS-164, ZINC BINDING.
[11]	"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.

Cross-references

Sequence databases

EMBLGenBankDDBJ

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

PIR

S58873.

RefSeq

NP_001179.1.

UniGene

Hs.485139

3D structure databases

PDBMSD

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	[»]
2JCN	X-ray	1.80	A	21-190	[»]
2YV6	X-ray	2.50	A	1-211	[»]

ModBase

Search...

Protein-protein interaction databases

DIP

DIP:935N.

IntAct

Q16611.

Polymorphism databases

NIEHS-SNPs

Search...

Genome annotation databases

Ensembl

ENSG00000030110. Homo sapiens. [Contig view]

GeneID

578.

KEGG

hsa:578.

Organism-specific databases

H-InvDB

HIX0005780.
HIX0040824.
HIX0058969.

HGNC

HGNC:949. BAK1.

HPA

CAB005029.

MIM

600516. gene.

PharmGKB

PA25253.

GenAtlas

Search...

GeneCards

Search...

Phylogenomic databases

HOVERGEN

Q16611.

Enzyme and pathway databases

Reactome

REACT_578. Apoptosis.

Gene expression databases

CleanEx

HS_BAK1.

GermOnline

ENSG00000030110. Homo sapiens.

Family and domain databases

InterPro

IPR002475. BCL2_apoptsis.
IPR000712. Bcl2_BH.
[Graphical view]

Pfam

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

PRINTS

PR01862. BCL2FAMILY.

SMART

SM00337. BCL. 1 hit.
[Graphical view]

PROSITE

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

ProtoNet

Search...

Other Resources

LinkHub

Q16611.

NextBio

2359.

SOURCE

Search...

Entry information

Entry name

BAK_HUMAN

Accession

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

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	November 1, 1996
Last modified:	November 25, 2008
This is version 101 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)