ID   NUCB2_MOUSE             Reviewed;         420 AA.
AC   P81117;
DT   15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT   02-NOV-2001, sequence version 2.
DT   24-JAN-2024, entry version 178.
DE   RecName: Full=Nucleobindin-2;
DE   AltName: Full=DNA-binding protein NEFA;
DE   AltName: Full=Prepronesfatin;
DE   Contains:
DE     RecName: Full=Nesfatin-1;
DE   Flags: Precursor;
GN   Name=Nucb2; Synonyms=Nefa;
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], FUNCTION, SUBUNIT, SUBCELLULAR LOCATION, AND
RP   TISSUE SPECIFICITY.
RX   PubMed=10915798; DOI=10.1074/jbc.m005103200;
RA   Taniguchi N., Taniura H., Niinobe M., Takayama C., Tominaga-Yoshino K.,
RA   Ogura A., Yoshikawa K.;
RT   "The postmitotic growth suppressor necdin interacts with a calcium-binding
RT   protein (NEFA) in neuronal cytoplasm.";
RL   J. Biol. Chem. 275:31674-31681(2000).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   STRAIN=Swiss Webster / NIH; TISSUE=Embryo;
RA   Hoefig K., Barnikol-Watanabe S., Barnikol H.U., Hilschmann N.;
RT   "cDNA sequence analysis of mouse NEFA gene.";
RL   Submitted (NOV-1997) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=FVB/N; TISSUE=Mammary tumor;
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA project:
RT   the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [4]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Brown adipose tissue, Heart, Kidney, Lung, Pancreas, Spleen,
RC   and Testis;
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).
CC   -!- FUNCTION: Calcium-binding protein which may have a role in calcium
CC       homeostasis (PubMed:10915798). Acts as a non-receptor guanine
CC       nucleotide exchange factor which binds to and activates guanine
CC       nucleotide-binding protein (G-protein) alpha subunit GNAI3 (By
CC       similarity). {ECO:0000250|UniProtKB:Q9JI85,
CC       ECO:0000269|PubMed:10915798}.
CC   -!- FUNCTION: [Nesfatin-1]: Anorexigenic peptide, seems to play an
CC       important role in hypothalamic pathways regulating food intake and
CC       energy homeostasis, acting in a leptin-independent manner. May also
CC       exert hypertensive roles and modulate blood pressure through directly
CC       acting on peripheral arterial resistance.
CC       {ECO:0000250|UniProtKB:Q9JI85}.
CC   -!- SUBUNIT: Interacts (via GBA motif) with guanine nucleotide-binding
CC       protein G(i) alpha subunit GNAI3 (By similarity). Preferentially
CC       interacts with inactive rather than active GNAI3 (By similarity).
CC       Interaction with GNAI3 is inhibited when NUCB2 binds calcium, probably
CC       due to a conformational change which renders the GBA motif inaccessible
CC       (By similarity). Binds to the postmitotic growth suppressor NDN;
CC       coexpression abolishes NUCB2 secretion (PubMed:10915798).
CC       {ECO:0000250|UniProtKB:Q9JI85, ECO:0000269|PubMed:10915798}.
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:10915798}.
CC       Perikaryon {ECO:0000269|PubMed:10915798}. Endoplasmic reticulum
CC       {ECO:0000269|PubMed:10915798}. Golgi apparatus {ECO:0000250}. Nucleus
CC       envelope {ECO:0000269|PubMed:10915798}. Membrane {ECO:0000250};
CC       Peripheral membrane protein {ECO:0000250}. Secreted
CC       {ECO:0000269|PubMed:10915798}. Note=In dendrites and perikarya of brain
CC       neurons. Abundant in the ER cisternae and nuclear envelope, but not
CC       detected in Golgi, mitochondria or nucleoplasm in neurons. In cell
CC       culture, cytoplasmic and secreted.
CC   -!- SUBCELLULAR LOCATION: [Nesfatin-1]: Secreted {ECO:0000250}.
CC   -!- TISSUE SPECIFICITY: Found in liver, heart, thymus, muscle, intestine,
CC       kidney, lung, spleen and throughout the brain, in cerebral cortex,
CC       hippocampus, hypothalamus and medulla oblongata. Nucb2 and necdin
CC       levels were higher in postmitotic neurons.
CC       {ECO:0000269|PubMed:10915798}.
CC   -!- DOMAIN: The GBA (G-alpha binding and activating) motif mediates binding
CC       to the alpha subunits of guanine nucleotide-binding proteins (G
CC       proteins). {ECO:0000250|UniProtKB:Q9JI85}.
CC   -!- SIMILARITY: Belongs to the nucleobindin family. {ECO:0000305}.
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DR   EMBL; AJ222586; CAA10858.1; -; mRNA.
DR   EMBL; BC010459; AAH10459.1; -; mRNA.
DR   CCDS; CCDS52372.1; -.
DR   RefSeq; NP_001123951.1; NM_001130479.2.
DR   RefSeq; XP_006508087.1; XM_006508024.2.
DR   RefSeq; XP_006508088.1; XM_006508025.2.
DR   AlphaFoldDB; P81117; -.
DR   SMR; P81117; -.
DR   BioGRID; 207285; 8.
DR   STRING; 10090.ENSMUSP00000032895; -.
DR   GlyGen; P81117; 1 site, 1 O-linked glycan (1 site).
DR   iPTMnet; P81117; -.
DR   PhosphoSitePlus; P81117; -.
DR   EPD; P81117; -.
DR   jPOST; P81117; -.
DR   MaxQB; P81117; -.
DR   PaxDb; 10090-ENSMUSP00000032895; -.
DR   PeptideAtlas; P81117; -.
DR   ProteomicsDB; 291921; -.
DR   Pumba; P81117; -.
DR   Antibodypedia; 1610; 416 antibodies from 30 providers.
DR   DNASU; 53322; -.
DR   Ensembl; ENSMUST00000032895.15; ENSMUSP00000032895.8; ENSMUSG00000030659.15.
DR   GeneID; 53322; -.
DR   KEGG; mmu:53322; -.
DR   UCSC; uc009jjk.3; mouse.
DR   AGR; MGI:1858179; -.
DR   CTD; 4925; -.
DR   MGI; MGI:1858179; Nucb2.
DR   VEuPathDB; HostDB:ENSMUSG00000030659; -.
DR   eggNOG; KOG3866; Eukaryota.
DR   GeneTree; ENSGT00390000001927; -.
DR   HOGENOM; CLU_031153_1_0_1; -.
DR   InParanoid; P81117; -.
DR   OMA; QETDTNH; -.
DR   OrthoDB; 2881246at2759; -.
DR   PhylomeDB; P81117; -.
DR   TreeFam; TF323218; -.
DR   BioGRID-ORCS; 53322; 1 hit in 76 CRISPR screens.
DR   ChiTaRS; Nucb2; mouse.
DR   PRO; PR:P81117; -.
DR   Proteomes; UP000000589; Chromosome 7.
DR   RNAct; P81117; Protein.
DR   Bgee; ENSMUSG00000030659; Expressed in seminal vesicle and 240 other cell types or tissues.
DR   ExpressionAtlas; P81117; baseline and differential.
DR   GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR   GO; GO:0005783; C:endoplasmic reticulum; IDA:MGI.
DR   GO; GO:0005793; C:endoplasmic reticulum-Golgi intermediate compartment; ISO:MGI.
DR   GO; GO:0005615; C:extracellular space; ISO:MGI.
DR   GO; GO:0005794; C:Golgi apparatus; ISO:MGI.
DR   GO; GO:0005797; C:Golgi medial cisterna; ISO:MGI.
DR   GO; GO:0005640; C:nuclear outer membrane; IDA:MGI.
DR   GO; GO:0005634; C:nucleus; IDA:MGI.
DR   GO; GO:0043204; C:perikaryon; IEA:UniProtKB-SubCell.
DR   GO; GO:0005509; F:calcium ion binding; IDA:MGI.
DR   GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
DR   GO; GO:0001965; F:G-protein alpha-subunit binding; ISS:UniProtKB.
DR   GO; GO:0005085; F:guanyl-nucleotide exchange factor activity; ISS:UniProtKB.
DR   GO; GO:0005164; F:tumor necrosis factor receptor binding; ISO:MGI.
DR   GO; GO:1901142; P:insulin metabolic process; ISO:MGI.
DR   GO; GO:0006874; P:intracellular calcium ion homeostasis; TAS:MGI.
DR   GO; GO:0032099; P:negative regulation of appetite; ISO:MGI.
DR   GO; GO:0043951; P:negative regulation of cAMP-mediated signaling; ISO:MGI.
DR   GO; GO:0045599; P:negative regulation of fat cell differentiation; ISO:MGI.
DR   GO; GO:0070093; P:negative regulation of glucagon secretion; ISO:MGI.
DR   GO; GO:0046627; P:negative regulation of insulin receptor signaling pathway; ISO:MGI.
DR   GO; GO:0046321; P:positive regulation of fatty acid oxidation; ISO:MGI.
DR   GO; GO:2000845; P:positive regulation of testosterone secretion; ISO:MGI.
DR   GO; GO:0007264; P:small GTPase mediated signal transduction; ISS:UniProtKB.
DR   Gene3D; 1.10.238.10; EF-hand; 1.
DR   InterPro; IPR011992; EF-hand-dom_pair.
DR   InterPro; IPR018247; EF_Hand_1_Ca_BS.
DR   InterPro; IPR002048; EF_hand_dom.
DR   InterPro; IPR040250; Nucleobindin.
DR   PANTHER; PTHR19237; NUCLEOBINDIN; 1.
DR   PANTHER; PTHR19237:SF22; NUCLEOBINDIN-2; 1.
DR   Pfam; PF13499; EF-hand_7; 1.
DR   SMART; SM00054; EFh; 2.
DR   SUPFAM; SSF47473; EF-hand; 1.
DR   PROSITE; PS00018; EF_HAND_1; 2.
DR   PROSITE; PS50222; EF_HAND_2; 2.
DR   Genevisible; P81117; MM.
PE   1: Evidence at protein level;
KW   Calcium; Cleavage on pair of basic residues; Cytoplasm; DNA-binding;
KW   Endoplasmic reticulum; Golgi apparatus;
KW   Guanine-nucleotide releasing factor; Membrane; Metal-binding; Nucleus;
KW   Phosphoprotein; Reference proteome; Repeat; Secreted; Signal.
FT   SIGNAL          1..24
FT                   /evidence="ECO:0000255"
FT   CHAIN           25..420
FT                   /note="Nucleobindin-2"
FT                   /id="PRO_0000004166"
FT   CHAIN           25..106
FT                   /note="Nesfatin-1"
FT                   /id="PRO_0000419820"
FT   DOMAIN          241..276
FT                   /note="EF-hand 1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT   DOMAIN          293..328
FT                   /note="EF-hand 2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT   DNA_BIND        171..223
FT                   /evidence="ECO:0000250"
FT   REGION          193..225
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          213..420
FT                   /note="Binds to necdin"
FT   REGION          365..420
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOTIF           304..334
FT                   /note="GBA"
FT                   /evidence="ECO:0000250|UniProtKB:P80303"
FT   COMPBIAS        365..395
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   BINDING         254
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT   BINDING         256
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT   BINDING         258
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT   BINDING         265
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT   BINDING         306
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT   BINDING         308
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT   BINDING         310
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT   BINDING         317
FT                   /ligand="Ca(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29108"
FT                   /ligand_label="2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT   MOD_RES         332
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:P80303"
FT   CONFLICT        18
FT                   /note="M -> T (in Ref. 2; CAA10858)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   420 AA;  50304 MW;  0DEBD51724CB7E72 CRC64;
     MRWRIIQVQY CFLLVPCMLT ALEAVPIDVD KTKVHNTEPV ENARIEPPDT GLYYDEYLKQ
     VIEVLETDPH FREKLQKADI EEIRSGRLSQ ELDLVSHKVR TRLDELKRQE VGRLRMLIKA
     KLDALQDTGM NHHLLLKQFE HLNHQNPNTF ESRDLDMLIK AATADLEQYD RTRHEEFKKY
     EMMKEHERRE YLKTLSEEKR KEEESKFEEM KRKHEDHPKV NHPGSKDQLK EVWEETDGLD
     PNDFDPKTFF KLHDVNNDGF LDEQELEALF TRELEKVYNP QNAEDDMIEM EEERLRMREH
     VMSEIDNNKD RLVTLEEFLR ATEKKEFLEP DSWETLDQQQ LFTEDELKEY ESIIAIQENE
     LKKRAEELQK QKEDLQRQHD HLEAQKQEYH QAVQHLEQKK LQQGIAPSGP AGELKFEPHT
//