Q13323 (BIK_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Bcl-2-interacting killer

Alternative name(s):
Apoptosis inducer NBK
BIP1
BP4

Gene names

Name:	BIK
Synonyms:	NBK

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	160 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Accelerates programmed cell death. Association to the apoptosis repressors Bcl-X(L), BHRF1, Bcl-2 or its adenovirus homolog E1B 19k protein suppresses this death-promoting activity. Does not interact with BAX. Ref.12
Subunit structure	Interacts with RHBDL4/RHBDD1. Ref.13
Subcellular location	Endomembrane system; Single-pass membrane protein. Mitochondrion membrane; Single-pass membrane protein By similarity. Note: Around the nuclear envelope, and in cytoplasmic membranes.
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.
Post-translational modification	Proteolytically cleaved by RHBDL4/RHBDD1. RHBDL4/RHBDD1-induced cleavage is a necessary step prior its degradation by the proteosome-dependent mechanism. Ref.13

Ontologies

Keywords
Biological process	Apoptosis
Cellular component	Membrane Mitochondrion
Coding sequence diversity	Polymorphism
Domain	Transmembrane Transmembrane helix
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	apoptotic process Inferred from electronic annotation. Source: UniProtKB-KW induction of apoptosis Traceable author statement PubMed 10381623. Source: UniProtKB male gonad development Inferred from electronic annotation. Source: Compara positive regulation of protein homooligomerization Inferred from direct assay PubMed 21041309. Source: BHF-UCL positive regulation of release of cytochrome c from mitochondria Inferred from direct assay PubMed 21041309. Source: BHF-UCL spermatogenesis Inferred from electronic annotation. Source: Compara
Cellular_component	endomembrane system Inferred from electronic annotation. Source: UniProtKB-SubCell integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW mitochondrial membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
BCL2	P10415	3	EBI-700794,EBI-77694
BCL2L1	Q07817	2	EBI-700794,EBI-78035
BCL2L1	Q07817-1	3	EBI-700794,EBI-287195
BCL2L2	Q92843	2	EBI-700794,EBI-707714

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 160	160	Bcl-2-interacting killer		PRO_0000143100
Regions
	Transmembrane	136 – 156	21	Helical; Potential
	Region	137 – 158	22	Leucine-zipper Potential
	Motif	57 – 71	15	BH3
Sites
	Site	153 – 154	2	Cleavage; by RHBDL4/RHBDD1 Probable
Natural variations
	Natural variant	19	1	E → K. Ref.7 Corresponds to variant rs4988415 [ dbSNP | Ensembl ].		VAR_029179
	Natural variant	26	1	T → I. Corresponds to variant rs11090143 [ dbSNP | Ensembl ].		VAR_048420
	Natural variant	148	1	L → P. Corresponds to variant rs11574527 [ dbSNP | Ensembl ].		VAR_029180
Experimental info
	Mutagenesis	153 – 154	2	GG → FF: Inhibits RHBDL4/RHBDD1-induced cleavage. Ref.13

Sequences

	Sequence		Length	Mass (Da)
	Q13323 [UniParc]. Last modified November 1, 1997. Version 2. Checksum: 89034F4443F5A136	FASTA	160	18,016
	10 20 30 40 50 60 MSEVRPLSRD ILMETLLYEQ LLEPPTMEVL GMTDSEEDLD PMEDFDSLEC MEGSDALALR 70 80 90 100 110 120 LACIGDEMDV SLRAPRLAQL SEVAMHSLGL AFIYDQTEDI RDVLRSFMDG FTTLKENIMR 130 140 150 160 FWRSPNPGSW VSCEQVLLAL LLLLALLLPL LSGGLHLLLK

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Bik, a novel death-inducing protein shares a distinct sequence motif with Bcl-2 family proteins and interacts with viral and cellular survival-promoting proteins." Boyd J.M., Gallo G.J., Elangovan B., Houghton A.B., Malstrom S., Avery B.J., Ebb R.G., Subramanian T., Chittenden T., Lutz R.J., Chinnadurai G. Oncogene 11:1921-1928(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: B-cell.
[2]	"Induction of apoptosis by human Nbk/Bik, a BH3-containing protein that interacts with E1B 19K." Han J., Sabbatini P., White E. Mol. Cell. Biol. 16:5857-5864(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	"E1B-19K interacts with a novel apoptotic inducer, NBK." Pun K.-T., Farrow S.N., Raven T., Wride C.J., White J.H.M., Brown R. Submitted (JUL-1995) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Lymphoid tissue.
[4]	"Mapping of a target region of allelic loss to a 0.5-cM interval on chromosome 22q13 in human colorectal cancer." Castells A., Ino Y., Louis D.N., Ramesh V., Gusella J.F., Rustgi A.K. Gastroenterology 117:831-837(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[5]	"A genome annotation-driven approach to cloning the human ORFeome." Collins J.E., Wright C.L., Edwards C.A., Davis M.P., Grinham J.A., Cole C.G., Goward M.E., Aguado B., Mallya M., Mokrab Y., Huckle E.J., Beare D.M., Dunham I. Genome Biol. 5:R84.1-R84.11(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[6]	"Cloning of human full-length CDSs in BD Creator(TM) system donor vector." Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A. Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[7]	NIEHS SNPs program Submitted (FEB-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT LYS-19.
[8]	"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].
[9]	"The DNA sequence of human chromosome 22." Dunham I., Hunt A.R., Collins J.E., Bruskiewich R., Beare D.M., Clamp M., Smink L.J., Ainscough R., Almeida J.P., Babbage A.K., Bagguley C., Bailey J., Barlow K.F., Bates K.N., Beasley O.P., Bird C.P., Blakey S.E., Bridgeman A.M. , Buck D., Burgess J., Burrill W.D., Burton J., Carder C., Carter N.P., Chen Y., Clark G., Clegg S.M., Cobley V.E., Cole C.G., Collier R.E., Connor R., Conroy D., Corby N.R., Coville G.J., Cox A.V., Davis J., Dawson E., Dhami P.D., Dockree C., Dodsworth S.J., Durbin R.M., Ellington A.G., Evans K.L., Fey J.M., Fleming K., French L., Garner A.A., Gilbert J.G.R., Goward M.E., Grafham D.V., Griffiths M.N.D., Hall C., Hall R.E., Hall-Tamlyn G., Heathcott R.W., Ho S., Holmes S., Hunt S.E., Jones M.C., Kershaw J., Kimberley A.M., King A., Laird G.K., Langford C.F., Leversha M.A., Lloyd C., Lloyd D.M., Martyn I.D., Mashreghi-Mohammadi M., Matthews L.H., Mccann O.T., Mcclay J., Mclaren S., McMurray A.A., Milne S.A., Mortimore B.J., Odell C.N., Pavitt R., Pearce A.V., Pearson D., Phillimore B.J.C.T., Phillips S.H., Plumb R.W., Ramsay H., Ramsey Y., Rogers L., Ross M.T., Scott C.E., Sehra H.K., Skuce C.D., Smalley S., Smith M.L., Soderlund C., Spragon L., Steward C.A., Sulston J.E., Swann R.M., Vaudin M., Wall M., Wallis J.M., Whiteley M.N., Willey D.L., Williams L., Williams S.A., Williamson H., Wilmer T.E., Wilming L., Wright C.L., Hubbard T., Bentley D.R., Beck S., Rogers J., Shimizu N., Minoshima S., Kawasaki K., Sasaki T., Asakawa S., Kudoh J., Shintani A., Shibuya K., Yoshizaki Y., Aoki N., Mitsuyama S., Roe B.A., Chen F., Chu L., Crabtree J., Deschamps S., Do A., Do T., Dorman A., Fang F., Fu Y., Hu P., Hua A., Kenton S., Lai H., Lao H.I., Lewis J., Lewis S., Lin S.-P., Loh P., Malaj E., Nguyen T., Pan H., Phan S., Qi S., Qian Y., Ray L., Ren Q., Shaull S., Sloan D., Song L., Wang Q., Wang Y., Wang Z., White J., Willingham D., Wu H., Yao Z., Zhan M., Zhang G., Chissoe S., Murray J., Miller N., Minx P., Fulton R., Johnson D., Bemis G., Bentley D., Bradshaw H., Bourne S., Cordes M., Du Z., Fulton L., Goela D., Graves T., Hawkins J., Hinds K., Kemp K., Latreille P., Layman D., Ozersky P., Rohlfing T., Scheet P., Walker C., Wamsley A., Wohldmann P., Pepin K., Nelson J., Korf I., Bedell J.A., Hillier L.W., Mardis E., Waterston R., Wilson R., Emanuel B.S., Shaikh T., Kurahashi H., Saitta S., Budarf M.L., McDermid H.E., Johnson A., Wong A.C.C., Morrow B.E., Edelmann L., Kim U.J., Shizuya H., Simon M.I., Dumanski J.P., Peyrard M., Kedra D., Seroussi E., Fransson I., Tapia I., Bruder C.E., O'Brien K.P., Wilkinson P., Bodenteich A., Hartman K., Hu X., Khan A.S., Lane L., Tilahun Y., Wright H. Nature 402:489-495(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[10]	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].
[11]	"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: Lymph.
[12]	"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.
[13]	"A novel member of the Rhomboid family, RHBDD1, regulates BIK-mediated apoptosis." Wang Y., Guan X., Fok K.L., Li S., Zhang X., Miao S., Zong S., Koide S.S., Chan H.C., Wang L. Cell. Mol. Life Sci. 65:3822-3829(2008) [PubMed] [Europe PMC] [Abstract] Cited for: CLEAVAGE BY RHBDD1, INTERACTION WITH RHBDD1, MUTAGENESIS OF 153-GLY-PHE-154.
+	Additional computationally mapped references.

Web resources

NIEHS-SNPs

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

U34584 mRNA. Translation: AAC50413.1.
U49730 mRNA. Translation: AAC79124.1.
X89986 mRNA. Translation: CAA62013.1.
AF174424 , AF174421, AF174422, AF174423 Genomic DNA. Translation: AAF01156.1.
CR456390 mRNA. Translation: CAG30276.1.
BT006728 mRNA. Translation: AAP35374.1.
AY245248 Genomic DNA. Translation: AAO61089.1.
CR541863 mRNA. Translation: CAG46661.1.
CR541883 mRNA. Translation: CAG46681.1.
AL022237 Genomic DNA. Translation: CAA18260.2.
CH471138 Genomic DNA. Translation: EAW73282.1.
BC001599 mRNA. Translation: AAH01599.1.

IPI

IPI00012753.

PIR

S58214.

RefSeq

NP_001188.1. NM_001197.4.

UniGene

Hs.475055.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2IPE	model	-	@	1-160	[»]

ProteinModelPortal

Q13323.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-928N.

IntAct

Q13323. 9 interactions.

MINT

MINT-1457938.

STRING

9606.ENSP00000216115.

PTM databases

PhosphoSite

Q13323.

Polymorphism databases

DMDM

2493284.

Proteomic databases

PaxDb

Q13323.

PRIDE

Q13323.

Protocols and materials databases

DNASU

638.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000216115; ENSP00000216115; ENSG00000100290.

GeneID

638.

KEGG

hsa:638.

UCSC

uc003bdk.3. human.

Organism-specific databases

CTD

638.

GeneCards

GC22P043506.

HGNC

HGNC:1051. BIK.

MIM

603392. gene.

neXtProt

NX_Q13323.

PharmGKB

PA25354.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG39366.

HOGENOM

HOG000095229.

HOVERGEN

HBG001515.

InParanoid

Q13323.

OMA

EPPTMEV.

OrthoDB

EOG4TB4D0.

PhylomeDB

Q13323.

Gene expression databases

Bgee

Q13323.

CleanEx

HS_BIK.

Genevestigator

Q13323.

Family and domain databases

InterPro

IPR024579. Bcl2-int_killer.
IPR020728. Bcl2_BH3_motif_CS.
[Graphical view]

PANTHER

PTHR15018. PTHR15018. 1 hit.

Pfam

PF12201. bcl-2I13. 1 hit.
[Graphical view]

ProDom

PD032623. PD032623. 1 hit.
[Graphical view] [Entries sharing at least one domain]

PROSITE

PS01259. BH3. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

GenomeRNAi

638.

NextBio

2586.

SOURCE

Search...

Entry information

Entry name

BIK_HUMAN

Accession

Primary (citable) accession number: Q13323
Secondary accession number(s): Q16582, Q6FH93

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	November 1, 1997
Last modified:	April 3, 2013
This is version 113 of the entry and version 2 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.