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 24-JAN-2024, entry version 139. 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}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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; 10116-ENSRNOP00000027753; -. DR Ensembl; ENSRNOT00055011151; ENSRNOP00055008730; ENSRNOG00055006787. DR Ensembl; ENSRNOT00060030920; ENSRNOP00060025035; ENSRNOG00060017872. DR Ensembl; ENSRNOT00065050545; ENSRNOP00065041535; ENSRNOG00065029150. DR GeneID; 59295; -. DR KEGG; rno:59295; -. DR UCSC; RGD:620888; rat. DR AGR; RGD:620888; -. DR CTD; 4925; -. DR RGD; 620888; Nucb2. DR eggNOG; KOG3866; Eukaryota. DR InParanoid; Q9JI85; -. DR OrthoDB; 2881246at2759; -. DR PhylomeDB; Q9JI85; -. DR PRO; PR:Q9JI85; -. DR Proteomes; UP000002494; Unplaced. DR GO; GO:0005737; C:cytoplasm; ISO: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 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. 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 //