O60238 (BNI3L_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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

Alternative name(s):
Adenovirus E1B19K-binding protein B5
BCL2/adenovirus E1B 19 kDa protein-interacting protein 3A
NIP3-like protein X
Short name=NIP3L

Gene names

Name:	BNIP3L
Synonyms:	BNIP3A, BNIP3H, NIX

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

General annotation (Comments)

Function	Induces apoptosis. Interacts with viral and cellular anti-apoptosis proteins. Can overcome the suppressors BCL-2 and BCL-XL, although high levels of BCL-XL expression will inhibit apoptosis. Inhibits apoptosis induced by BNIP3. 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. May function as a tumor suppressor. Ref.4 Ref.13
Subunit structure	Self-associates. Interacts with BNIP3 and STEAP3. Interacts with human adenovirus-2 E1B 19 kDa protein. Interacts (via BH3 domain) with SPATA18 (via coiled-coil domains). Ref.4 Ref.10 Ref.13
Subcellular location	Nucleus envelope. Endoplasmic reticulum. Mitochondrion outer membrane. Membrane; Single-pass membrane protein Potential. Note: Colocalizes with SPATA18 at the mitochondrion outer membrane. Ref.4 Ref.13
Post-translational modification	Undergoes progressive proteolysis to an 11 kDa C-terminal fragment, which is blocked by the proteasome inhibitor lactacystin.
Sequence similarities	Belongs to the NIP3 family.
Sequence caution	The sequence CAI46217.1 differs from that shown. Reason: Erroneous termination at position 122. Translated as Glu.

Ontologies

Keywords
Biological process	Apoptosis Host-virus interaction
Cellular component	Endoplasmic reticulum Membrane Mitochondrion Mitochondrion outer membrane Nucleus
Domain	Transmembrane Transmembrane helix
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	apoptotic process Inferred from electronic annotation. Source: UniProtKB-KW defense response to virus Inferred from direct assay PubMed 9973195. Source: UniProtKB induction of apoptosis Inferred from direct assay PubMed 9973195. Source: UniProtKB mitochondrial protein catabolic process Inferred from mutant phenotype Ref.13. Source: UniProtKB negative regulation of apoptotic process Inferred from direct assay Ref.4. Source: UniProtKB virus-host interaction Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	endoplasmic reticulum Inferred from direct assay Ref.4. Source: UniProtKB integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW intrinsic to membrane Traceable author statement Ref.4. Source: UniProtKB mitochondrial outer membrane Inferred from mutant phenotype Ref.13. Source: UniProtKB nuclear envelope Inferred from direct assay Ref.4. Source: UniProtKB
Molecular_function	lamin binding Inferred from direct assay Ref.4. Source: UniProtKB protein heterodimerization activity Inferred from direct assay Ref.4. Source: UniProtKB protein homodimerization activity Inferred from direct assay Ref.4. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
itself		7	EBI-849893,EBI-849893
ATP13A2	Q9NQ11	2	EBI-849893,EBI-6308763
BAD	Q92934	2	EBI-849893,EBI-700771
BCL2	P10415	2	EBI-849893,EBI-77694
BNIP3	Q12983	8	EBI-849893,EBI-749464
E1B	P03247	7	EBI-849893,EBI-849856	From a different organism.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 219	219	BCL2/adenovirus E1B 19 kDa protein-interacting protein 3-like		PRO_0000064957
Regions
	Transmembrane	188 – 208	21	Helical; Potential
	Motif	126 – 148	23	BH3
Amino acid modifications
	Modified residue	62	1	Phosphoserine By similarity
	Modified residue	63	1	Phosphoserine By similarity
	Modified residue	117	1	Phosphoserine By similarity
	Modified residue	118	1	Phosphoserine By similarity
	Modified residue	120	1	Phosphoserine Ref.12
Experimental info
	Sequence conflict	107	1	D → E in AAN04051. Ref.4
	Sequence conflict	150	1	N → S in CAI46217. Ref.8

Sequences

	Sequence		Length	Mass (Da)
	O60238 [UniParc]. Last modified August 1, 1998. Version 1. Checksum: 19372E897BC63609	FASTA	219	23,930
	10 20 30 40 50 60 MSSHLVEPPP PLHNNNNNCE ENEQSLPPPA GLNSSWVELP MNSSNGNDNG NGKNGGLEHV 70 80 90 100 110 120 PSSSSIHNGD MEKILLDAQH ESGQSSSRGS SHCDSPSPQE DGQIMFDVEM HTSRDHSSQS 130 140 150 160 170 180 EEEVVEGEKE VEALKKSADW VSDWSSRPEN IPPKEFHFRH PKRSVSLSMR KSGAMKKGGI 190 200 210 FSAEFLKVFI PSLFLSHVLA LGLGIYIGKR LSTPSASTY

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Isolation, mapping, and functional analysis of a novel human cDNA (BNIP3L) encoding a protein homologous to human NIP3." Matsushima M., Fujiwara T., Takahashi E., Minaguchi T., Eguchi Y., Tsujimoto Y., Suzumori K., Nakamura Y. Genes Chromosomes Cancer 21:230-235(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"BNIP3a, a human homolog of pro-apoptotic protein BNIP3, promotes apoptosis and interacts with viral and cellular anti-apoptosis proteins." Yasuda M., Han J.-W., Dionne C.A., Boyd J.M., Chinnadurai G. Submitted (JUL-1998) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	"Nix and Nip3 form a subfamily of pro-apoptotic mitochondrial proteins." Chen G., Cizeau J., Vande Velde C., Park J.H., Bozek G., Bolton J., Shi L., Dubik D., Greenberg A. J. Biol. Chem. 274:7-10(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Fetal liver.
[4]	"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: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, SELF-ASSOCIATION, INTERACTION WITH BNIP3 AND HUMAN ADENOVIRUS-2 E1B 19 KDA PROTEIN.
[5]	"The proapoptotic factor Nix is coexpressed with Bcl-xL during terminal erythroid differentiation." Aerbajinai W., Giattina M., Lee Y.T., Raffeld M., Miller J.L. Blood 102:712-717(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[6]	"A catalog of genes in the human dermal papilla cells as identified by expressed sequence tags." Farooq M., Kim M.K., Kim Y.H., Seo J.M., Lee H.M., Sohn M.Y., Hwang S.Y., Chung H.J., Im S.U., Jung E.J., Kim J.C. Submitted (APR-2000) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Tissue: Hair follicle dermal papilla.
[7]	"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].
[8]	"The full-ORF clone resource of the German cDNA consortium." Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I. BMC Genomics 8:399-399(2007) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Kidney.
[9]	"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: Bone marrow and Cervix.
[10]	"The p53-inducible TSAP6 gene product regulates apoptosis and the cell cycle and interacts with Nix and the Myt1 kinase." Passer B.J., Nancy-Portebois V., Amzallag N., Prieur S., Cans C., Roborel de Climens A., Fiucci G., Bouvard V., Tuynder M., Susini L., Morchoisne S., Crible V., Lespagnol A., Dausset J., Oren M., Amson R., Telerman A. Proc. Natl. Acad. Sci. U.S.A. 100:2284-2289(2003) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH STEAP3.
[11]	"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks." Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M. Cell 127:635-648(2006) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: Cervix carcinoma.
[12]	"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-120, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[13]	"Mieap, a p53-inducible protein, controls mitochondrial quality by repairing or eliminating unhealthy mitochondria." Kitamura N., Nakamura Y., Miyamoto Y., Miyamoto T., Kabu K., Yoshida M., Futamura M., Ichinose S., Arakawa H. PLoS ONE 6:E16060-E16060(2011) [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

Cross-references

Sequence databases
EMBL GenBank DDBJ	AB004788 mRNA. Translation: BAA28692.1. AF079221 mRNA. Translation: AAC27723.1. AF067396 mRNA. Translation: AAD03589.1. AF536326 mRNA. Translation: AAN04051.1. AF452712 mRNA. Translation: AAL50978.1. AF255051 Genomic DNA. Translation: AAF70290.1. BT019501 mRNA. Translation: AAV38308.1. AL132665 mRNA. Translation: CAI46217.1. Sequence problems. BC001559 mRNA. Translation: AAH01559.1. BC009603 mRNA. Translation: AAH09603.1.
IPI	IPI00028419.
PIR	T34523.
RefSeq	NP_004322.1. NM_004331.2.
UniGene	Hs.131226.
3D structure databases
ProteinModelPortal	O60238.
ModBase	Search...
Protein-protein interaction databases
IntAct	O60238. 20 interactions.
MINT	MINT-1429960.
STRING	9606.ENSP00000370003.
Protein family/group databases
TCDB	1.A.20.1.2. BCL2/adenovirus E1B-interacting protein 3 (BNip3) family.
PTM databases
PhosphoSite	O60238.
Proteomic databases
PaxDb	O60238.
PRIDE	O60238.
Protocols and materials databases
DNASU	665.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000380629; ENSP00000370003; ENSG00000104765.
GeneID	665.
KEGG	hsa:665.
UCSC	uc003xex.1. human.
Organism-specific databases
CTD	665.
GeneCards	GC08P026240.
HGNC	HGNC:1085. BNIP3L.
HPA	CAB025371. HPA015652.
MIM	605368. gene.
neXtProt	NX_O60238.
PharmGKB	PA25395.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG83470.
HOVERGEN	HBG050707.
InParanoid	O60238.
KO	K15465.
OrthoDB	EOG4Q2DGM.
PhylomeDB	O60238.
Gene expression databases
ArrayExpress	O60238.
Bgee	O60238.
CleanEx	HS_BNIP3L.
Genevestigator	O60238.
GermOnline	ENSG00000104765. 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
ChiTaRS	BNIP3L. human.
GenomeRNAi	665.
NextBio	2712.
SOURCE	Search...

Entry information

Entry name

BNI3L_HUMAN

Accession

Primary (citable) accession number: O60238
Secondary accession number(s): Q5JW63, Q8NF87

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 15, 1999
Last sequence update:	August 1, 1998
Last modified:	May 29, 2013
This is version 119 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.