NUCB2_RAT
ID NUCB2_RAT Reviewed; 420 AA.
AC Q9JI85;
DT 02-NOV-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 03-AUG-2022, entry version 134.
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 Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Sprague-Dawley; TISSUE=Ovary;
RA Hirschfeld G., Heiden I., Barnikol-Watanabe S., Barnikol H.U.,
RA Hilschmann N.;
RT "Rat NEFA mRNA.";
RL Submitted (MAR-2000) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Hauge X., Neve K.A.;
RT "Characterization of rat NEFA protein.";
RL Submitted (FEB-2000) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Prostate;
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 FUNCTION OF NESFATIN.
RX PubMed=17036007; DOI=10.1038/nature05162;
RA Oh-I S., Shimizu H., Satoh T., Okada S., Adachi S., Inoue K., Eguchi H.,
RA Yamamoto M., Imaki T., Hashimoto K., Tsuchiya T., Monden T., Horiguchi K.,
RA Yamada M., Mori M.;
RT "Identification of nesfatin-1 as a satiety molecule in the hypothalamus.";
RL Nature 443:709-712(2006).
RN [5]
RP FUNCTION, INTERACTION WITH GNAI3, GBA MOTIF, AND MUTAGENESIS OF LEU-315;
RP PHE-318 AND LEU-319.
RX PubMed=21653697; DOI=10.1074/jbc.m110.204099;
RA Garcia-Marcos M., Kietrsunthorn P.S., Wang H., Ghosh P., Farquhar M.G.;
RT "G Protein binding sites on Calnuc (nucleobindin 1) and NUCB2 (nucleobindin
RT 2) define a new class of G(alpha)i-regulatory motifs.";
RL J. Biol. Chem. 286:28138-28149(2011).
RN [6]
RP FUNCTION OF NESFATIN.
RX PubMed=22293188; DOI=10.1016/j.bbrc.2012.01.076;
RA Yamawaki H., Takahashi M., Mukohda M., Morita T., Okada M., Hara Y.;
RT "A novel adipocytokine, nesfatin-1 modulates peripheral arterial
RT contractility and blood pressure in rats.";
RL Biochem. Biophys. Res. Commun. 418:676-681(2012).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-332, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
CC -!- FUNCTION: Calcium-binding protein which may have a role in calcium
CC homeostasis (By similarity). Acts as a non-receptor guanine nucleotide
CC exchange factor which binds to and activates guanine nucleotide-binding
CC protein (G-protein) alpha subunit GNAI3 (PubMed:21653697).
CC {ECO:0000250|UniProtKB:P81117, ECO:0000269|PubMed:21653697}.
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. {ECO:0000269|PubMed:17036007,
CC ECO:0000269|PubMed:22293188}.
CC -!- SUBUNIT: Interacts (via GBA motif) with guanine nucleotide-binding
CC protein G(i) alpha subunit GNAI3 (PubMed:21653697). Preferentially
CC interacts with inactive rather than active GNAI3 (PubMed:21653697).
CC Interaction with GNAI3 is inhibited when NUCB2 binds calcium, probably
CC due to a conformational change which renders the GBA motif inaccessible
CC (PubMed:21653697). Binds to the postmitotic growth suppressor NDN;
CC coexpression abolishes NUCB2 secretion (By similarity).
CC {ECO:0000250|UniProtKB:P81117, ECO:0000269|PubMed:21653697}.
CC -!- SUBCELLULAR LOCATION: Golgi apparatus {ECO:0000250}. Endoplasmic
CC reticulum {ECO:0000250}. Nucleus envelope {ECO:0000250}. Membrane
CC {ECO:0000250}; Peripheral membrane protein {ECO:0000250}. Cytoplasm
CC {ECO:0000250}. Secreted {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: [Nesfatin-1]: Secreted.
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:0000269|PubMed:21653697}.
CC -!- MISCELLANEOUS: NEFA stands for N=DNA-binding; EF=EF-hand; A=Acidic
CC region.
CC -!- SIMILARITY: Belongs to the nucleobindin family. {ECO:0000305}.
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DR EMBL; AF250142; AAF75993.1; -; mRNA.
DR EMBL; AF238223; AAK66864.1; -; mRNA.
DR EMBL; BC061778; AAH61778.1; -; mRNA.
DR RefSeq; NP_067695.1; NM_021663.2.
DR AlphaFoldDB; Q9JI85; -.
DR SMR; Q9JI85; -.
DR IntAct; Q9JI85; 2.
DR STRING; 10116.ENSRNOP00000027753; -.
DR iPTMnet; Q9JI85; -.
DR PhosphoSitePlus; Q9JI85; -.
DR jPOST; Q9JI85; -.
DR PaxDb; Q9JI85; -.
DR PRIDE; Q9JI85; -.
DR GeneID; 59295; -.
DR KEGG; rno:59295; -.
DR UCSC; RGD:620888; rat.
DR CTD; 4925; -.
DR RGD; 620888; Nucb2.
DR eggNOG; KOG3866; Eukaryota.
DR InParanoid; Q9JI85; -.
DR OrthoDB; 1339224at2759; -.
DR PhylomeDB; Q9JI85; -.
DR PRO; PR:Q9JI85; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0005737; C:cytoplasm; IDA:RGD.
DR GO; GO:0005783; C:endoplasmic reticulum; ISO:RGD.
DR GO; GO:0005793; C:endoplasmic reticulum-Golgi intermediate compartment; ISO:RGD.
DR GO; GO:0005615; C:extracellular space; IDA:RGD.
DR GO; GO:0005797; C:Golgi medial cisterna; IDA:RGD.
DR GO; GO:0005640; C:nuclear outer membrane; ISO:RGD.
DR GO; GO:0005634; C:nucleus; ISO:RGD.
DR GO; GO:0005509; F:calcium ion binding; ISO:RGD.
DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
DR GO; GO:0001965; F:G-protein alpha-subunit binding; IDA:UniProtKB.
DR GO; GO:0005085; F:guanyl-nucleotide exchange factor activity; IDA:UniProtKB.
DR GO; GO:0005164; F:tumor necrosis factor receptor binding; IPI:RGD.
DR GO; GO:1901142; P:insulin metabolic process; IDA:RGD.
DR GO; GO:0032099; P:negative regulation of appetite; IMP:RGD.
DR GO; GO:0043951; P:negative regulation of cAMP-mediated signaling; IDA:RGD.
DR GO; GO:0045599; P:negative regulation of fat cell differentiation; IDA:RGD.
DR GO; GO:0070093; P:negative regulation of glucagon secretion; IDA:RGD.
DR GO; GO:0046627; P:negative regulation of insulin receptor signaling pathway; IDA:RGD.
DR GO; GO:0046321; P:positive regulation of fatty acid oxidation; IDA:RGD.
DR GO; GO:2000845; P:positive regulation of testosterone secretion; IDA:RGD.
DR GO; GO:0009749; P:response to glucose; IEP:RGD.
DR GO; GO:0044752; P:response to human chorionic gonadotropin; IEP:RGD.
DR GO; GO:1990680; P:response to melanocyte-stimulating hormone; IEP:RGD.
DR GO; GO:0042594; P:response to starvation; IEP:RGD.
DR GO; GO:0007264; P:small GTPase mediated signal transduction; IDA: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_0000004167"
FT CHAIN 25..106
FT /note="Nesfatin-1"
FT /id="PRO_0000419821"
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 194..225
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 213..420
FT /note="Binds to necdin"
FT /evidence="ECO:0000250"
FT REGION 366..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 366..386
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 387..402
FT /note="Polar 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:0007744|PubMed:22673903"
FT MUTAGEN 315
FT /note="L->A: Abolishes binding to and activation of GNAI3;
FT when associated with A-319."
FT /evidence="ECO:0000269|PubMed:21653697"
FT MUTAGEN 318
FT /note="F->A: Abolishes binding to and activation of GNAI3."
FT /evidence="ECO:0000269|PubMed:21653697"
FT MUTAGEN 319
FT /note="L->A: Abolishes binding to and activation of GNAI3;
FT when associated with A-315."
FT /evidence="ECO:0000269|PubMed:21653697"
FT CONFLICT 38
FT /note="E -> D (in Ref. 2; AAK66864)"
FT /evidence="ECO:0000305"
FT CONFLICT 352
FT /note="S -> G (in Ref. 2; AAK66864)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 420 AA; 50090 MW; E7684E6C835F98FB CRC64;
MRWRTIQARY CFLLVPCVLT ALEAVPIDVD KTKVHNVEPV ESARIEPPDT GLYYDEYLKQ
VIEVLETDPH FREKLQKADI EEIRSGRLSQ ELDLVSHKVR TRLDELKRQE VGRLRMLIKA
KLDALQDTGM NHHLLLKQFE HLNHQNPDTF ESKDLDMLIK AATADLEQYD RTRHEEFKKY
EMMKEHERRE YLKTLSEEKR KEEEAKFAEM KRKHEDHPKV NHPGSKDQLK EVWEETDGLD
PNDFDPKTFF KLHDVNNDGF LDEQELEALF TKELDKVYNP QNAEDDMIEM EEERLRMREH
VMNEIDNNKD RLVTLEEFLR ATEKKEFLEP DSWETLDQQQ LFTEEELKEY ESIIAIQESE
LKKKADELQK QKEELQRQHD HLEAQKQEYQ QAVQQLEQKK FQQGIAPSGP AGELKFEPHT
