NUCB2_MOUSE
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 03-AUG-2022, entry version 170.
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, and
RC 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 iPTMnet; P81117; -.
DR PhosphoSitePlus; P81117; -.
DR EPD; P81117; -.
DR jPOST; P81117; -.
DR MaxQB; P81117; -.
DR PaxDb; P81117; -.
DR PeptideAtlas; P81117; -.
DR PRIDE; P81117; -.
DR ProteomicsDB; 291921; -.
DR Antibodypedia; 1610; 314 antibodies from 29 providers.
DR DNASU; 53322; -.
DR Ensembl; ENSMUST00000032895; ENSMUSP00000032895; ENSMUSG00000030659.
DR GeneID; 53322; -.
DR KEGG; mmu:53322; -.
DR UCSC; uc009jjk.3; mouse.
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; KMCWSRA; -.
DR OrthoDB; 1339224at2759; -.
DR PhylomeDB; P81117; -.
DR TreeFam; TF323218; -.
DR BioGRID-ORCS; 53322; 1 hit in 71 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 236 other tissues.
DR ExpressionAtlas; P81117; baseline and differential.
DR Genevisible; P81117; MM.
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:0006874; P:cellular calcium ion homeostasis; TAS:MGI.
DR GO; GO:1901142; P:insulin metabolic process; ISO: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 InterPro; IPR011992; EF-hand-dom_pair.
DR InterPro; IPR018247; EF_Hand_1_Ca_BS.
DR InterPro; IPR002048; EF_hand_dom.
DR InterPro; IPR028813; NUCB2.
DR InterPro; IPR040250; Nucleobindin.
DR PANTHER; PTHR19237; PTHR19237; 1.
DR PANTHER; PTHR19237:SF22; PTHR19237:SF22; 1.
DR Pfam; PF13499; EF-hand_7; 1.
DR SMART; SM00054; EFh; 2.
DR SUPFAM; SSF47473; SSF47473; 1.
DR PROSITE; PS00018; EF_HAND_1; 2.
DR PROSITE; PS50222; EF_HAND_2; 2.
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