Q12983 (BNIP3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
BCL2/adenovirus E1B 19 kDa protein-interacting protein 3

Gene names

Name:	BNIP3
Synonyms:	NIP3

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

General annotation (Comments)

Function	Apoptosis-inducing protein that can overcome BCL2 suppression. May play a role in repartitioning calcium between the two major intracellular calcium stores in association with BCL2. Involved in mitochondrial quality control via its interaction with SPATA18/MIEAP: in response to mitochondrial damage, participates to mitochondrial protein catabolic process (also named MALM) leading to the degradation of damaged proteins inside mitochondria. The physical interaction of SPATA18/MIEAP, BNIP3 and BNIP3L/NIX at the mitochondrial outer membrane regulates the opening of a pore in the mitochondrial double membrane in order to mediate the translocation of lysosomal proteins from the cytoplasm to the mitochondrial matrix. Plays an important role in the calprotectin (S100A8/A9)-induced cell death pathway. Ref.9 Ref.12
Subunit structure	Homodimer. Binds to BCL2. Interacts with BNIP3L and ACAA2. Also can interact with adenovirus E1B 19 kDa protein or Epstein-Barr virus BHRF1. Interacts (via BH3 domain) with SPATA18 (via coiled-coil domains). Ref.1 Ref.6 Ref.7 Ref.12
Subcellular location	Mitochondrion. Mitochondrion outer membrane; Single-pass membrane protein. Note: Coexpression with the EIB 19-kDa protein results in a shift in NIP3 localization pattern to the nuclear envelope. Colocalizes with ACAA2 in the mitochondria. Colocalizes with SPATA18 at the mitochondrion outer membrane. Ref.7 Ref.9 Ref.12
Sequence similarities	Belongs to the NIP3 family.

Ontologies

Keywords
Biological process	Apoptosis Host-virus interaction
Cellular component	Membrane Mitochondrion Mitochondrion outer membrane
Domain	Transmembrane Transmembrane helix
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	apoptotic DNA fragmentation Inferred from direct assay PubMed 10891486. Source: UniProtKB autophagic cell death Inferred from electronic annotation. Source: Compara brown fat cell differentiation Inferred from electronic annotation. Source: Compara cellular response to cobalt ion Inferred from mutant phenotype PubMed 20436456. Source: BHF-UCL cellular response to hydrogen peroxide Inferred from electronic annotation. Source: Compara cellular response to hypoxia Inferred from mutant phenotype PubMed 20436456. Source: BHF-UCL cellular response to mechanical stimulus Inferred from expression pattern PubMed 19593445. Source: UniProtKB chromatin remodeling Inferred from direct assay PubMed 10891486. Source: UniProtKB defense response to virus Inferred from direct assay PubMed 9973195. Source: UniProtKB induction of apoptosis Inferred from direct assay Ref.6Ref.2PubMed 9973195. Source: UniProtKB intrinsic apoptotic signaling pathway Inferred from electronic annotation. Source: Compara mitochondrial fragmentation involved in apoptotic process Inferred from direct assay PubMed 20436456. Source: BHF-UCL mitochondrial protein catabolic process Inferred from mutant phenotype Ref.12. Source: UniProtKB negative regulation of apoptotic process Traceable author statement Ref.1. Source: UniProtKB negative regulation of membrane potential Inferred from direct assay PubMed 10891486. Source: UniProtKB negative regulation of mitochondrial fusion Inferred from direct assay PubMed 20436456. Source: BHF-UCL neuron apoptotic process Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of mitochondrial fission Inferred from direct assay PubMed 20436456. Source: BHF-UCL positive regulation of protein complex disassembly Inferred from direct assay PubMed 20436456. Source: BHF-UCL positive regulation of release of cytochrome c from mitochondria Inferred from direct assay PubMed 20436456. Source: BHF-UCL reactive oxygen species metabolic process Inferred from direct assay PubMed 10891486. Source: UniProtKB regulation of mitochondrial membrane permeability Inferred from direct assay PubMed 10891486. Source: UniProtKB response to hyperoxia Inferred from electronic annotation. Source: Compara virus-host interaction Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	dendrite Inferred from sequence or structural similarity. Source: UniProtKB integral to mitochondrial outer membrane Inferred from direct assay PubMed 10891486. Source: UniProtKB nuclear envelope Inferred from direct assay Ref.1. Source: UniProtKB nucleoplasm Inferred from sequence or structural similarity. Source: UniProtKB
Molecular_function	protein heterodimerization activity Inferred from direct assay Ref.6. Source: UniProtKB protein homodimerization activity Inferred from direct assay Ref.6Ref.2. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
itself		2	EBI-749464,EBI-749464
BNIP3L	O60238	8	EBI-749464,EBI-849893
OPA1	O60313	10	EBI-749464,EBI-1054131
TMEM11	P17152	2	EBI-749464,EBI-723946

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 194

194

BCL2/adenovirus E1B 19 kDa protein-interacting protein 3

PRO_0000064964

Regions

Transmembrane

164 – 184

21

Helical; Potential

Motif

100 – 125

26

BH3

Amino acid modifications

Modified residue

86

1

Phosphoserine Ref.10

Modified residue

92

1

Phosphoserine By similarity

Modified residue

95

1

Phosphoserine By similarity

Experimental info

Sequence conflict

3

1

Q → E in AAC00022. Ref.1

Secondary structure

1

.

.

.

194

Helix Strand Turn

Details...

Helix

159 – 188

30

Sequences

	Sequence		Length	Mass (Da)
	Q12983 [UniParc]. Last modified May 10, 2002. Version 2. Checksum: 6D79E68F146D25EB	FASTA	194	21,541
	10 20 30 40 50 60 MSQNGAPGMQ EESLQGSWVE LHFSNNGNGG SVPASVSIYN GDMEKILLDA QHESGRSSSK 70 80 90 100 110 120 SSHCDSPPRS QTPQDTNRAS ETDTHSIGEK NSSQSEEDDI ERRKEVESIL KKNSDWIWDW 130 140 150 160 170 180 SSRPENIPPK EFLFKHPKRT ATLSMRNTSV MKKGGIFSAE FLKVFLPSLL LSHLLAIGLG 190 IYIGRRLTTS TSTF

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Adenovirus E1B 19 kDa and Bcl-2 proteins interact with a common set of cellular proteins." Boyd J.M., Malstrom S., Subramanian T., Venkatesh L.K., Schaeper U., Elangovan B., D'Sa-Eipper C., Chinnadurai G. Cell 79:341-351(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], INTERACTION WITH BCL2. Tissue: B-cell.
[2]	"The E1B 19K/Bcl-2-binding protein Nip3 is a dimeric mitochondrial protein that activates apoptosis." Chen G., Ray R., Dubik D., Shi L., Cizeau J., Bleackley R.C., Saxena S., Gietz R.D., Greenberg A.H. J. Exp. Med. 186:1975-1983(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: B-cell.
[3]	NIEHS SNPs program Submitted (JAN-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]	"The DNA sequence and comparative analysis of human chromosome 10." Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L., Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K., Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L., Taylor A., Battles J. , Bird C.P., Ainscough R., Almeida J.P., Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A., Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P., Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D., Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J. Nature 429:375-381(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"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: Brain.
[6]	"A novel adenovirus E1B19K-binding protein B5 inhibits apoptosis induced by Nip3 by forming a heterodimer through the C-terminal hydrophobic region." Ohi N., Tokunaga A., Tsunoda H., Nakano K., Haraguchi K., Oda K., Motoyama N., Nakajima T. Cell Death Differ. 6:314-325(1999) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH BNIP3L.
[7]	"Acetyl-Coenzyme A acyltransferase 2 attenuates the apoptotic effects of BNIP3 in two human cell lines." Cao W., Liu N., Tang S., Bao L., Shen L., Yuan H., Zhao X., Lu H. Biochim. Biophys. Acta 1780:873-880(2008) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION, INTERACTION WITH ACAA2.
[8]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: Cervix carcinoma.
[9]	"S100A8/A9 induces autophagy and apoptosis via ROS-mediated cross-talk between mitochondria and lysosomes that involves BNIP3." Ghavami S., Eshragi M., Ande S.R., Chazin W.J., Klonisch T., Halayko A.J., McNeill K.D., Hashemi M., Kerkhoff C., Los M. Cell Res. 20:314-331(2010) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION.
[10]	"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis." Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M. Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-86, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[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]	"BNIP3 and NIX mediate Mieap-induced accumulation of lysosomal proteins within mitochondria." Nakamura Y., Kitamura N., Shinogi D., Yoshida M., Goda O., Murai R., Kamino H., Arakawa H. PLoS ONE 7:E30767-E30767(2012) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH SPATA18, SUBCELLULAR LOCATION.
+	Additional computationally mapped references.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

NIEHS-SNPs

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

U15174 mRNA. Translation: AAC00022.1.
AF002697 mRNA. Translation: AAC16738.1.
AY886764 Genomic DNA. Translation: AAW62256.1.
AL162274 Genomic DNA. Translation: CAD13201.1.
BC009342 mRNA. No translation available.
BC021989 mRNA. Translation: AAH21989.1.

IPI

IPI00290409.

PIR

I38865.

RefSeq

NP_004043.2. NM_004052.2.

UniGene

Hs.144873.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2J5D	NMR	-	A/B	146-190	[»]
2KA1	NMR	-	A/B	154-188	[»]
2KA2	NMR	-	A/B	154-188	[»]

ProteinModelPortal

Q12983.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q12983. 7 interactions.

MINT

MINT-1475327.

STRING

9606.ENSP00000357625.

Protein family/group databases

TCDB

1.A.20.1.1. BCL2/adenovirus E1B-interacting protein 3 (BNip3) family.

PTM databases

PhosphoSite

Q12983.

Polymorphism databases

DMDM

20532402.

Proteomic databases

PaxDb

Q12983.

PRIDE

Q12983.

Protocols and materials databases

DNASU

664.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000368636; ENSP00000357625; ENSG00000176171.

GeneID

664.

KEGG

hsa:664.

UCSC

uc001lkv.1. human.

Organism-specific databases

CTD

664.

GeneCards

GC10M133781.

H-InvDB

HIX0037770.

HGNC

HGNC:1084. BNIP3.

HPA

CAB011676.
HPA003015.

MIM

603293. gene.

neXtProt

NX_Q12983.

PharmGKB

PA25394.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG68335.

HOVERGEN

HBG050707.

InParanoid

Q12983.

KO

K15464.

OMA

MKKNADW.

OrthoDB

EOG4T784H.

Enzyme and pathway databases

Pathway_Interaction_DB

hif1_tfpathway. HIF-1-alpha transcription factor network.

Gene expression databases

ArrayExpress

Q12983.

Bgee

Q12983.

CleanEx

HS_BNIP3.

Genevestigator

Q12983.

GermOnline

ENSG00000176171. Homo sapiens.

Family and domain databases

InterPro

IPR010548. BNIP3.
[Graphical view]

Pfam

PF06553. BNIP3. 1 hit.
[Graphical view]

PROSITE

PS01259. BH3. False negative.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

Q12983.

GenomeRNAi

664.

NextBio

2708.

SOURCE

Search...

Entry information

Entry name

BNIP3_HUMAN

Accession

Primary (citable) accession number: Q12983
Secondary accession number(s): O14620, Q96GP0

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 15, 1999
Last sequence update:	May 10, 2002
Last modified:	May 1, 2013
This is version 127 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.