BNIP3_CAEEL
ID BNIP3_CAEEL Reviewed; 221 AA.
AC Q09969; Q95QW5; Q9UB15;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 03-OCT-2012, sequence version 2.
DT 03-AUG-2022, entry version 140.
DE RecName: Full=NIP3 homolog;
DE Short=CeBNIP3;
DE AltName: Full=Daf-16/FOXO controlled germline tumor affecting-1 {ECO:0000312|WormBase:C14F5.1a};
GN Name=dct-1 {ECO:0000312|WormBase:C14F5.1a};
GN ORFNames=C14F5.1 {ECO:0000312|WormBase:C14F5.1a};
OS Caenorhabditis elegans.
OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC Caenorhabditis.
OX NCBI_TaxID=6239;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM A), FUNCTION, HOMODIMER, SUBCELLULAR
RP LOCATION, INTERACTION WITH CED-3 AND CED-9, UBIQUITINATION, AND PROTEASOMAL
RP DEGRADATION.
RX PubMed=11114722; DOI=10.1038/sj.onc.1203929;
RA Cizeau J., Ray R., Chen G., Gietz R.D., Greenberg A.H.;
RT "The C. elegans orthologue ceBNIP3 interacts with CED-9 and CED-3 but kills
RT through a BH3- and caspase-independent mechanism.";
RL Oncogene 19:5453-5463(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Bristol N2;
RX PubMed=9851916; DOI=10.1126/science.282.5396.2012;
RG The C. elegans sequencing consortium;
RT "Genome sequence of the nematode C. elegans: a platform for investigating
RT biology.";
RL Science 282:2012-2018(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 12-221 (ISOFORM A), AND INTERACTION WITH
RP CED-3 AND CED-9.
RX PubMed=9824163; DOI=10.1038/sj.onc.1202467;
RA Yasuda M., D'Sa-Eipper C., Gong X.L., Chinnadurai G.;
RT "Regulation of apoptosis by a Caenorhabditis elegans BNIP3 homolog.";
RL Oncogene 17:2525-2530(1998).
RN [4]
RP FUNCTION.
RX PubMed=16380712; DOI=10.1038/ng1723;
RA Oh S.W., Mukhopadhyay A., Dixit B.L., Raha T., Green M.R., Tissenbaum H.A.;
RT "Identification of direct DAF-16 targets controlling longevity, metabolism
RT and diapause by chromatin immunoprecipitation.";
RL Nat. Genet. 38:251-257(2006).
RN [5]
RP FUNCTION.
RX PubMed=17934462; DOI=10.1038/ng.2007.1;
RA Pinkston-Gosse J., Kenyon C.;
RT "DAF-16/FOXO targets genes that regulate tumor growth in Caenorhabditis
RT elegans.";
RL Nat. Genet. 39:1403-1409(2007).
RN [6]
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE,
RP UBIQUITINATION AT LYS-26, AND DISRUPTION PHENOTYPE.
RX PubMed=25896323; DOI=10.1038/nature14300;
RA Palikaras K., Lionaki E., Tavernarakis N.;
RT "Coordination of mitophagy and mitochondrial biogenesis during ageing in C.
RT elegans.";
RL Nature 521:525-528(2015).
CC -!- FUNCTION: Initiates apoptosis in a BH3-independent mechanism possibly
CC by recruiting ced-3 to mitochondria and other cytoplasmic membranes
CC (PubMed:11114722). Has a role in lifespan and tumor growth
CC (PubMed:16380712, PubMed:17934462). Required for the induction of
CC mitophagy under stress conditions (PubMed:25896323).
CC {ECO:0000269|PubMed:11114722, ECO:0000269|PubMed:16380712,
CC ECO:0000269|PubMed:17934462, ECO:0000269|PubMed:25896323}.
CC -!- SUBUNIT: Homodimer; via transmembrane domain (PubMed:11114722,
CC PubMed:9824163). Interacts with ced-3 and ced-9 (PubMed:9824163).
CC {ECO:0000269|PubMed:11114722, ECO:0000269|PubMed:9824163}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion outer membrane
CC {ECO:0000269|PubMed:25896323}; Single-pass membrane protein
CC {ECO:0000305}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=a;
CC IsoId=Q09969-1; Sequence=Displayed;
CC Name=b;
CC IsoId=Q09969-2; Sequence=VSP_037301;
CC -!- TISSUE SPECIFICITY: Expressed in all somatic tissues including neurons,
CC pharynx, intestine, body wall muscles and vulva muscles.
CC {ECO:0000269|PubMed:25896323}.
CC -!- DEVELOPMENTAL STAGE: Expressed in the embryo and throughout all stages
CC of development to adulthood. {ECO:0000269|PubMed:25896323}.
CC -!- PTM: Ubiquitinated and degraded by the proteasome (PubMed:11114722).
CC Under oxidative stress conditions, ubiquitinated at Lys-26 in a pink-1
CC dependent manner. Colocalizes with pdr-1 and may be ubiquitinated by it
CC (PubMed:25896323). {ECO:0000269|PubMed:11114722,
CC ECO:0000269|PubMed:25896323}.
CC -!- DISRUPTION PHENOTYPE: RNAi-mediated knockdown causes an increased
CC sensitivity to stress and inhibits mitophagy which leads to an
CC accumulation of defective mitochondria that have increased mass,
CC altered network morphology, decreased ATP levels, increased reactive
CC oxygen species (ROS) generation, membrane depolarization, increased
CC oxygen consumption and increased cytoplasmic Ca(2+) that intensifies
CC under stress conditions. RNAi-mediated knockdown in daf-2, isp-1, or
CC clk-1 mutant backgrounds suppresses their increased lifespan phenotype.
CC {ECO:0000269|PubMed:25896323}.
CC -!- SIMILARITY: Belongs to the NIP3 family. {ECO:0000305}.
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DR EMBL; AF133832; AAD32265.1; -; mRNA.
DR EMBL; FO080456; CCD63843.2; -; Genomic_DNA.
DR EMBL; FO080456; CCD63844.2; -; Genomic_DNA.
DR EMBL; AF080583; AAC31574.1; -; mRNA.
DR PIR; T43338; T43338.
DR RefSeq; NP_509339.4; NM_076938.4. [Q09969-1]
DR RefSeq; NP_509340.2; NM_076939.3. [Q09969-2]
DR AlphaFoldDB; Q09969; -.
DR BioGRID; 45977; 5.
DR DIP; DIP-26299N; -.
DR STRING; 6239.C14F5.1a; -.
DR TCDB; 1.A.20.2.1; the bcl2/adenovirus e1b-interacting protein 3 (bnip3) family.
DR iPTMnet; Q09969; -.
DR EPD; Q09969; -.
DR PaxDb; Q09969; -.
DR PeptideAtlas; Q09969; -.
DR EnsemblMetazoa; C14F5.1a.1; C14F5.1a.1; WBGene00015776. [Q09969-1]
DR EnsemblMetazoa; C14F5.1b.1; C14F5.1b.1; WBGene00015776. [Q09969-2]
DR GeneID; 181053; -.
DR KEGG; cel:CELE_C14F5.1; -.
DR UCSC; C14F5.1a; c. elegans.
DR CTD; 181053; -.
DR WormBase; C14F5.1a; CE47388; WBGene00015776; dct-1. [Q09969-1]
DR WormBase; C14F5.1b; CE47263; WBGene00015776; dct-1. [Q09969-2]
DR eggNOG; ENOG502SF13; Eukaryota.
DR GeneTree; ENSGT00390000013415; -.
DR HOGENOM; CLU_1251645_0_0_1; -.
DR InParanoid; Q09969; -.
DR OMA; SPHVEFE; -.
DR OrthoDB; 1250566at2759; -.
DR PRO; PR:Q09969; -.
DR Proteomes; UP000001940; Chromosome X.
DR Bgee; WBGene00015776; Expressed in pharyngeal muscle cell (C elegans) and 3 other tissues.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0031966; C:mitochondrial membrane; IDA:UniProtKB.
DR GO; GO:0005741; C:mitochondrial outer membrane; IDA:WormBase.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0032991; C:protein-containing complex; IPI:WormBase.
DR GO; GO:0002020; F:protease binding; IPI:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB.
DR GO; GO:0006915; P:apoptotic process; IMP:UniProtKB.
DR GO; GO:0000422; P:autophagy of mitochondrion; IMP:WormBase.
DR GO; GO:0008340; P:determination of adult lifespan; IMP:UniProtKB.
DR GO; GO:0097345; P:mitochondrial outer membrane permeabilization; IBA:GO_Central.
DR GO; GO:0043065; P:positive regulation of apoptotic process; IEA:InterPro.
DR GO; GO:2001272; P:positive regulation of cysteine-type endopeptidase activity involved in execution phase of apoptosis; IDA:WormBase.
DR GO; GO:0051726; P:regulation of cell cycle; IGI:UniProtKB.
DR GO; GO:0043067; P:regulation of programmed cell death; IBA:GO_Central.
DR InterPro; IPR010548; BNIP3.
DR PANTHER; PTHR15186; PTHR15186; 1.
DR Pfam; PF06553; BNIP3; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Apoptosis; Autophagy; Isopeptide bond; Membrane;
KW Mitochondrion; Mitochondrion outer membrane; Reference proteome;
KW Transmembrane; Transmembrane helix; Ubl conjugation.
FT CHAIN 1..221
FT /note="NIP3 homolog"
FT /id="PRO_0000064963"
FT TRANSMEM 189..209
FT /note="Helical"
FT /evidence="ECO:0000255"
FT REGION 24..55
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 189..209
FT /note="Required for initiation of apoptosis"
FT COMPBIAS 25..55
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CROSSLNK 26
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000269|PubMed:25896323"
FT VAR_SEQ 66..68
FT /note="Missing (in isoform b)"
FT /evidence="ECO:0000305"
FT /id="VSP_037301"
SQ SEQUENCE 221 AA; 24843 MW; A915F512EA06ADFE CRC64;
MSSFLEFAKP KMLDIKRKIN FASGEKTDES VQPQQQTEQS SAQQTTPSAK AVSNPFITPL
TESTPGMSES WVELAPSRTS LCSSVDINMV IIDEKDKDSR LSPVSIAQSP HVEFESLEQV
KYKLVREMLP PGKNTDWIWD WSSRPENTPP KTVRMVQYGS NLTTPPNSPE PELYQYLPCE
SDSLFNVRVV FGFLVTNIFS FVVGAAVGFA VCRKLIKHHR Q
