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Q12983 (BNIP3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 136. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
BCL2/adenovirus E1B 19 kDa protein-interacting protein 3
Gene names
Name:BNIP3
Synonyms:NIP3
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length194 AA.
Sequence statusComplete.
Protein existenceEvidence 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 processApoptosis
Host-virus interaction
   Cellular componentMembrane
Mitochondrion
Mitochondrion outer membrane
   DomainTransmembrane
Transmembrane helix
   PTMPhosphoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processapoptotic process

Inferred from physical interaction Ref.1. Source: MGI

autophagic cell death

Inferred from electronic annotation. Source: Ensembl

brown fat cell differentiation

Inferred from electronic annotation. Source: Ensembl

cell death

Inferred from sequence or structural similarity. Source: UniProtKB

cellular response to cobalt ion

Inferred from mutant phenotype PubMed 20436456. Source: BHF-UCL

cellular response to hydrogen peroxide

Inferred from electronic annotation. Source: Ensembl

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

defense response to virus

Inferred from direct assay PubMed 9973195. Source: UniProtKB

granzyme-mediated apoptotic signaling pathway

Inferred from direct assay Ref.2. Source: UniProtKB

intrinsic apoptotic signaling pathway in response to hypoxia

Inferred from mutant phenotype PubMed 20436456. Source: BHF-UCL

mitochondrial fragmentation involved in apoptotic process

Inferred from direct assay PubMed 20436456. Source: BHF-UCL

mitochondrial outer membrane permeabilization

Inferred from direct assay Ref.7. Source: UniProtKB

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 apoptotic process

Inferred from direct assay Ref.6PubMed 9973195. Source: UniProtKB

positive regulation of autophagy

Traceable author statement PubMed 18309324. Source: UniProtKB

positive regulation of mitochondrial fission

Inferred from direct assay PubMed 20436456. Source: BHF-UCL

positive regulation of programmed cell death

Inferred from direct assay PubMed 10891486. Source: UniProtKB

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: Ensembl

response to hypoxia

Inferred from sequence or structural similarity. Source: UniProtKB

viral process

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componentcytoplasm

Inferred from sequence or structural similarity. Source: UniProtKB

dendrite

Inferred from sequence or structural similarity. Source: UniProtKB

endoplasmic reticulum

Inferred from Biological aspect of Ancestor. Source: RefGenome

integral component of mitochondrial outer membrane

Inferred from direct assay PubMed 10891486. Source: UniProtKB

mitochondrial membrane

Inferred from direct assay PubMed 10891486. Source: UniProtKB

mitochondrial outer membrane

Inferred from direct assay Ref.12. Source: UniProtKB

mitochondrion

Inferred from direct assay Ref.7Ref.1Ref.2. Source: UniProtKB

nuclear envelope

Inferred from direct assay Ref.1. Source: UniProtKB

nucleoplasm

Inferred from sequence or structural similarity. Source: UniProtKB

nucleus

Inferred from sequence or structural similarity. Source: UniProtKB

   Molecular_functionGTPase binding

Inferred from physical interaction PubMed 20436456. Source: BHF-UCL

identical protein binding

Inferred from physical interaction Ref.6PubMed 16189514. Source: IntAct

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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 194194BCL2/adenovirus E1B 19 kDa protein-interacting protein 3
PRO_0000064964

Regions

Transmembrane164 – 18421Helical; Potential
Motif100 – 12526BH3

Amino acid modifications

Modified residue861Phosphoserine Ref.10
Modified residue921Phosphoserine By similarity
Modified residue951Phosphoserine By similarity

Experimental info

Sequence conflict31Q → E in AAC00022. Ref.1

Secondary structure

... 194
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q12983 [UniParc].

Last modified May 10, 2002. Version 2.
Checksum: 6D79E68F146D25EB

FASTA19421,541
        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 

« Hide

References

« Hide '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. expand/collapse author list , 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, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
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.

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.
PIRI38865.
RefSeqNP_004043.2. NM_004052.2.
UniGeneHs.144873.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2J5DNMR-A/B146-190[»]
2KA1NMR-A/B154-188[»]
2KA2NMR-A/B154-188[»]
ProteinModelPortalQ12983.
SMRQ12983. Positions 146-190.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid107132. 15 interactions.
IntActQ12983. 8 interactions.
MINTMINT-1475327.
STRING9606.ENSP00000357625.

Protein family/group databases

TCDB1.A.20.1.1. the bcl2/adenovirus e1b-interacting protein 3 (bnip3) family.

PTM databases

PhosphoSiteQ12983.

Polymorphism databases

DMDM20532402.

Proteomic databases

PaxDbQ12983.
PRIDEQ12983.

Protocols and materials databases

DNASU664.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000368636; ENSP00000357625; ENSG00000176171.
GeneID664.
KEGGhsa:664.
UCSCuc001lkv.1. human.

Organism-specific databases

CTD664.
GeneCardsGC10M133781.
H-InvDBHIX0037770.
HGNCHGNC:1084. BNIP3.
HPACAB011676.
HPA003015.
MIM603293. gene.
neXtProtNX_Q12983.
PharmGKBPA25394.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG68335.
HOVERGENHBG050707.
InParanoidQ12983.
KOK15464.
OMAMKKNADW.
OrthoDBEOG74N5J4.
PhylomeDBQ12983.
TreeFamTF315424.

Gene expression databases

ArrayExpressQ12983.
BgeeQ12983.
CleanExHS_BNIP3.
GenevestigatorQ12983.

Family and domain databases

InterProIPR010548. BNIP3.
[Graphical view]
PfamPF06553. BNIP3. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceQ12983.
GeneWikiBNIP3.
GenomeRNAi664.
NextBio2708.
PROQ12983.
SOURCESearch...

Entry information

Entry nameBNIP3_HUMAN
AccessionPrimary (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: April 16, 2014
This is version 136 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human chromosome 10

Human chromosome 10: entries, gene names and cross-references to MIM