ID   NBR1_MOUSE              Reviewed;         988 AA.
AC   P97432; Q9JIH9;
DT   30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT   01-MAY-1997, sequence version 1.
DT   02-SEP-2026, entry version 182.
DE   RecName: Full=Next to BRCA1 gene 1 protein;
DE   AltName: Full=Membrane component chromosome 17 surface marker 2 homolog;
DE   AltName: Full=Neighbor of BRCA1 gene 1 protein;
GN   Name=Nbr1; Synonyms=M17s2;
OS   Mus musculus (Mouse).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Mus; Mus.
OX   NCBI_TaxID=10090;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   STRAIN=ICR; TISSUE=Brain;
RX   PubMed=8975707; DOI=10.1006/geno.1996.0633;
RA   Chambers J.A., Solomon E.;
RT   "Isolation of the murine Nbr1 gene adjacent to the murine Brca1 gene.";
RL   Genomics 38:305-313(1996).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   STRAIN=129/Sv; TISSUE=Testis;
RX   PubMed=11179671; DOI=10.1016/s0378-1119(00)00549-7;
RA   Dimitrov S., Brennerova M., Forejt J.;
RT   "Expression profiles and intergenic structure of head-to-head oriented
RT   Brca1 and Nbr1 genes.";
RL   Gene 262:89-98(2001).
RN   [3]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Pancreas;
RX   PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA   Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA   Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT   "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL   Cell 143:1174-1189(2010).
RN   [4]
RP   FUNCTION, DISRUPTION PHENOTYPE, SUBCELLULAR LOCATION, INDUCTION BY
RP   OXIDATIVE STRESS, AND INTERACTION WITH SQSTM1.
RX   PubMed=31916398; DOI=10.15252/embr.201948902;
RA   Sanchez-Martin P., Sou Y.S., Kageyama S., Koike M., Waguri S., Komatsu M.;
RT   "NBR1-mediated p62-liquid droplets enhance the Keap1-Nrf2 system.";
RL   EMBO Rep. 21:e48902-e48902(2020).
RN   [5]
RP   FUNCTION, AND INTERACTION WITH IL12A AND IL12B.
RX   PubMed=34374750; DOI=10.1093/ecco-jcc/jjab144;
RA   Merkley S.D., Goodfellow S.M., Guo Y., Wilton Z.E.R., Byrum J.R.,
RA   Schwalm K.C., Dinwiddie D.L., Gullapalli R.R., Deretic V.,
RA   Jimenez Hernandez A., Bradfute S.B., In J.G., Castillo E.F.;
RT   "Non-autophagy Role of Atg5 and NBR1 in Unconventional Secretion of IL-12
RT   Prevents Gut Dysbiosis and Inflammation.";
RL   J. Crohns. Colitis. 16:259-274(2022).
CC   -!- FUNCTION: Ubiquitin-binding autophagy adapter that participates in
CC       different processes including host defense or intracellular homeostasis
CC       (PubMed:31916398, PubMed:34374750). Possesses a double function during
CC       the selective autophagy by acting as a shuttle bringing ubiquitinated
CC       proteins to autophagosomes and also by participating in the formation
CC       of protein aggregates. Plays a role in the regulation of the innate
CC       immune response by modulating type I interferon production and
CC       targeting ubiquitinated IRF3 for autophagic degradation (By
CC       similarity). In response to oxidative stress, promotes an increase in
CC       SQSTM1 levels, phosphorylation, and body formation by preventing its
CC       autophagic degradation (PubMed:31916398). In turn, activates the KEAP1-
CC       NRF2/NFE2L2 antioxidant pathway (PubMed:31916398). Also plays non-
CC       autophagy role by mediating the shuttle of IL-12 to late endosome for
CC       subsequent secretion (PubMed:34374750). {ECO:0000250|UniProtKB:Q14596,
CC       ECO:0000269|PubMed:31916398, ECO:0000269|PubMed:34374750}.
CC   -!- SUBUNIT: Homooligomer and heterooligomer. Interacts with TRIM55 (By
CC       similarity). Interacts with titin/TTN (By similarity). Interacts with
CC       RNF29, USP8, MAP1LC3A, MAP1LC3B, MAP1LC3C, GABARAP, GABARAPL1 and
CC       GABARAPL2. Binds to ubiquitin and ubiquitinated proteins. Interacts
CC       with SQSTM1. Interacts with TAX1BP1. Interacts with IRF3; this
CC       interaction mediates autophagic degradation of IRF3 (By similarity).
CC       Interacts with IL12A and IL12B (PubMed:34374750). Interacts with SRBD1;
CC       this interaction clears SRBD1 through the autophagic-lysosomal pathway
CC       (By similarity). {ECO:0000250|UniProtKB:Q501R9,
CC       ECO:0000269|PubMed:34374750}.
CC   -!- INTERACTION:
CC       P97432; Q9GZQ8: MAP1LC3B; Xeno; NbExp=2; IntAct=EBI-642554, EBI-373144;
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:31916398}.
CC       Cytoplasmic vesicle, autophagosome {ECO:0000250|UniProtKB:Q14596}.
CC       Lysosome {ECO:0000250|UniProtKB:Q14596}. Cytoplasm, myofibril,
CC       sarcomere, M line {ECO:0000250|UniProtKB:Q501R9}. Note=In cardiac
CC       muscles localizes to the sarcomeric M line (By similarity). Is targeted
CC       to lysosomes for degradation (By similarity).
CC       {ECO:0000250|UniProtKB:Q14596, ECO:0000250|UniProtKB:Q501R9,
CC       ECO:0000269|PubMed:31916398}.
CC   -!- TISSUE SPECIFICITY: Expressed in brain.
CC   -!- INDUCTION: In response to oxidative stress.
CC       {ECO:0000269|PubMed:31916398}.
CC   -!- DOMAIN: The PB1 domain mediates interaction with SQSTM1. {ECO:0000250}.
CC   -!- PTM: Phosphorylated by GSK3A; this phosphorylation inhibits NBR1
CC       involvement in the formation of ubiquitinated protein aggregates.
CC       {ECO:0000250|UniProtKB:Q14596}.
CC   -!- DISRUPTION PHENOTYPE: NBR1-conditional knockout mice are not affected
CC       concerning general autophagy. However, the deletion results in a slight
CC       but significant reduction on the number and size of SQSTM1 liquid
CC       droplets. {ECO:0000269|PubMed:34374750}.
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DR   EMBL; U73039; AAC53025.1; -; mRNA.
DR   EMBL; AF227188; AAF74118.1; -; mRNA.
DR   CCDS; CCDS25475.1; -.
DR   RefSeq; NP_001239149.1; NM_001252220.1.
DR   RefSeq; NP_032702.1; NM_008676.3.
DR   AlphaFoldDB; P97432; -.
DR   SMR; P97432; -.
DR   BioGRID; 201698; 17.
DR   FunCoup; P97432; 3281.
DR   IntAct; P97432; 8.
DR   MINT; P97432; -.
DR   STRING; 10090.ENSMUSP00000099388; -.
DR   iPTMnet; P97432; -.
DR   PhosphoSitePlus; P97432; -.
DR   PaxDb; 10090-ENSMUSP00000099388; -.
DR   ProteomicsDB; 252646; -.
DR   Pumba; P97432; -.
DR   Antibodypedia; 8116; 316 antibodies from 35 providers.
DR   DNASU; 17966; -.
DR   Ensembl; ENSMUST00000103098.9; ENSMUSP00000099387.3; ENSMUSG00000017119.21.
DR   Ensembl; ENSMUST00000103099.8; ENSMUSP00000099388.2; ENSMUSG00000017119.21.
DR   Ensembl; ENSMUST00000107218.10; ENSMUSP00000102836.4; ENSMUSG00000017119.21.
DR   GeneID; 17966; -.
DR   KEGG; mmu:17966; -.
DR   UCSC; uc007lpg.2; mouse.
DR   AGR; MGI:108498; -.
DR   CTD; 4077; -.
DR   MGI; MGI:108498; Nbr1.
DR   VEuPathDB; HostDB:ENSMUSG00000017119; -.
DR   eggNOG; KOG4351; Eukaryota.
DR   eggNOG; KOG4582; Eukaryota.
DR   GeneTree; ENSGT00390000016335; -.
DR   InParanoid; P97432; -.
DR   OMA; SHWRLTQ; -.
DR   OrthoDB; 661148at2759; -.
DR   PhylomeDB; P97432; -.
DR   Reactome; R-MMU-9664873; Pexophagy.
DR   BioGRID-ORCS; 17966; 12 hits in 76 CRISPR screens.
DR   PRO; PR:P97432; -.
DR   Proteomes; UP000000589; Chromosome 11.
DR   RNAct; P97432; protein.
DR   Bgee; ENSMUSG00000017119; Expressed in ciliary body and 267 other cell types or tissues.
DR   ExpressionAtlas; P97432; baseline and differential.
DR   GO; GO:0005776; C:autophagosome; IEA:UniProtKB-SubCell.
DR   GO; GO:0005737; C:cytoplasm; EXP:UniProtKB.
DR   GO; GO:0005829; C:cytosol; ISS:UniProtKB.
DR   GO; GO:0005770; C:late endosome; IDA:UniProtKB.
DR   GO; GO:0005764; C:lysosome; ISS:UniProtKB.
DR   GO; GO:0031430; C:M band; IEA:UniProtKB-SubCell.
DR   GO; GO:0005758; C:mitochondrial intermembrane space; IDA:MGI.
DR   GO; GO:0016604; C:nuclear body; ISO:GO_Central.
DR   GO; GO:0005654; C:nucleoplasm; ISO:GO_Central.
DR   GO; GO:0005778; C:peroxisomal membrane; TAS:Reactome.
DR   GO; GO:0000407; C:phagophore assembly site; IDA:MGI.
DR   GO; GO:0043235; C:signaling receptor complex; ISS:UniProtKB.
DR   GO; GO:0051019; F:mitogen-activated protein kinase binding; IDA:BHF-UCL.
DR   GO; GO:0043130; F:ubiquitin binding; ISS:UniProtKB.
DR   GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR   GO; GO:0016236; P:macroautophagy; ISS:UniProtKB.
DR   GO; GO:0045668; P:negative regulation of osteoblast differentiation; IMP:BHF-UCL.
DR   GO; GO:0030500; P:regulation of bone mineralization; IMP:BHF-UCL.
DR   GO; GO:0032872; P:regulation of stress-activated MAPK cascade; IMP:BHF-UCL.
DR   CDD; cd14947; NBR1_like; 1.
DR   CDD; cd06396; PB1_NBR1; 1.
DR   CDD; cd14319; UBA_NBR1; 1.
DR   CDD; cd02340; ZZ_NBR1_like; 1.
DR   FunFam; 1.10.8.10:FF:000033; Next to BRCA1 gene 1 protein; 1.
DR   FunFam; 3.10.20.90:FF:000292; Next to BRCA1 gene 1 protein; 1.
DR   FunFam; 3.30.60.90:FF:000007; Next to BRCA1 gene 1 protein; 1.
DR   FunFam; 2.60.40.10:FF:000199; next to BRCA1 gene 1 protein-like; 1.
DR   Gene3D; 3.30.60.90; -; 1.
DR   Gene3D; 1.10.8.10; DNA helicase RuvA subunit, C-terminal domain; 1.
DR   Gene3D; 2.60.40.10; Immunoglobulins; 1.
DR   Gene3D; 3.10.20.90; Phosphatidylinositol 3-kinase Catalytic Subunit, Chain A, domain 1; 1.
DR   InterPro; IPR013783; Ig-like_fold.
DR   InterPro; IPR032350; Nbr1_FW.
DR   InterPro; IPR053793; PB1-like.
DR   InterPro; IPR000270; PB1_dom.
DR   InterPro; IPR034852; PB1_Nbr1.
DR   InterPro; IPR015940; UBA.
DR   InterPro; IPR009060; UBA-like_sf.
DR   InterPro; IPR056893; UBA_Nbr1_C.
DR   InterPro; IPR000433; Znf_ZZ.
DR   InterPro; IPR043145; Znf_ZZ_sf.
DR   PANTHER; PTHR20930:SF2; NEXT TO BRCA1 GENE 1 PROTEIN; 1.
DR   PANTHER; PTHR20930; OVARIAN CARCINOMA ANTIGEN CA125-RELATED; 1.
DR   Pfam; PF16158; N_BRCA1_IG; 1.
DR   Pfam; PF00564; PB1; 1.
DR   Pfam; PF24932; UBA_NBR1_C; 1.
DR   Pfam; PF00569; ZZ; 1.
DR   SMART; SM00666; PB1; 1.
DR   SMART; SM00291; ZnF_ZZ; 1.
DR   SUPFAM; SSF54277; CAD & PB1 domains; 1.
DR   SUPFAM; SSF57850; RING/U-box; 1.
DR   SUPFAM; SSF46934; UBA-like; 1.
DR   PROSITE; PS51745; PB1; 1.
DR   PROSITE; PS50030; UBA; 1.
DR   PROSITE; PS01357; ZF_ZZ_1; 1.
DR   PROSITE; PS50135; ZF_ZZ_2; 1.
PE   1: Evidence at protein level;
KW   Cytoplasm; Cytoplasmic vesicle; Lysosome; Metal-binding; Phosphoprotein;
KW   Reference proteome; Ubl conjugation; Zinc; Zinc-finger.
FT   CHAIN           1..988
FT                   /note="Next to BRCA1 gene 1 protein"
FT                   /id="PRO_0000096747"
FT   DOMAIN          4..86
FT                   /note="PB1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01081"
FT   DOMAIN          935..979
FT                   /note="UBA"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00212"
FT   ZN_FING         213..265
FT                   /note="ZZ-type"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00228"
FT   REGION          126..150
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          543..637
FT                   /note="ATG8 family proteins-binding"
FT                   /evidence="ECO:0000250"
FT   REGION          611..644
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          745..756
FT                   /note="ATG8 family proteins-binding"
FT                   /evidence="ECO:0000250"
FT   REGION          768..822
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          841..900
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        795..807
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        808..822
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   BINDING         218
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00228"
FT   BINDING         221
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00228"
FT   BINDING         232
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00228"
FT   BINDING         235
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00228"
FT   BINDING         241
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00228"
FT   BINDING         244
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00228"
FT   BINDING         251
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00228"
FT   BINDING         255
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00228"
FT   MOD_RES         117
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q14596"
FT   MOD_RES         587
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0000250|UniProtKB:Q14596"
FT   MOD_RES         591
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q501R9"
FT   MOD_RES         597
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q501R9"
FT   MOD_RES         626
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q14596"
FT   MOD_RES         860
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q501R9"
FT   CONFLICT        807
FT                   /note="Q -> R (in Ref. 2; AAF74118)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   988 AA;  109958 MW;  E5BB4B281FE33CE0 CRC64;
     MEPQVTLNVT FKNETQSFLV SDPENTTWAD VEAMVKVSFD LNTIQIKYLD EENEEISINS
     QGEYEEALKM ANIKQGNQLQ MQVHEGYHVV DEALPKNVVE NQAAARTGKK PLAHYSSLVR
     VLGSDMKTTE EPAPEQCSSA PCDTDQPQDK PPDWFTSYLE MFREQVVKET VEKLEQRLQE
     KLVLQKPLLS SSPTEVSMPI SEETLFLPEN QFSWHIACSH CQKRIVGVRY QCSLCPSYNI
     CEDCEAGPYT HDTNHVLLKL RRPVVISSEP FFYSKYSAPR LPAALEQVRL QKQVDKNFVK
     AEKQRLRAEK KQRKAEVKEL KKQLKLHRKI HLWNSIHGLQ SPKSPLGRPE SLLQSNTLML
     PLQPCAPVMP TLSAAFVDEN LPDGTHLQPG TKFIKHWRMK NTGNVKWNTD TKLKFMWGNL
     TLASTEKKDV LVPCLKAGHV GVVSVEFIAP TLEGTYTSHW RLSHKGQQFG PRVWCSIIVD
     PFPSSESPDN VEGDRISSSK ADDFSCEQEE AFLLAEEEIP LGEVTKQTEG TGASASQKTR
     RAASERELYI PSVDLLTAQD LLSFELLDIN IVQELERVPH NTPVDMTPCM SPLPHDSPLI
     EKPGLGQIQE ESEGAGFKAP PDSTVSAKRK AETPASVEET EEDLSGTQFV CETVIRSLTL
     DAAPDHNPPC RQRSPQRELQ LYSTEGQQPL VLPGFCRKDS SLKFALPEEG PRGDEREEIV
     HIVEEEVVEE EEEVQDEEVQ SQSSASSEDY IIILPECFDT SRPLGDSMYS SALSQPGLER
     GAEGEPGIES GLEPTEARER LPERESQPQE QSISDILTTS QPLDTVPLVP EVAGLPAALS
     RSAPCGQCES SGVDSPGVDS PATMHEVPPA PDDIRGEPRG STGLANSRQR SCDHSRHHNG
     SSIAGGLVKG ALSVAASAYK ALFSGPPVTA QPIVSEDQTT ALMAHLFEMG FCDRQLNLRL
     LRKHNYNILQ VVTELLQVNN NDWYSHRY
//