NUCB1_RAT
ID NUCB1_RAT Reviewed; 459 AA.
AC Q63083; P97623; Q497A4;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1997, sequence version 1.
DT 03-AUG-2022, entry version 148.
DE RecName: Full=Nucleobindin-1;
DE AltName: Full=Bone 63 kDa calcium-binding protein;
DE AltName: Full=CALNUC;
DE Flags: Precursor;
GN Name=Nucb1; Synonyms=Nuc;
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], FUNCTION, SUBCELLULAR LOCATION, AND TISSUE
RP SPECIFICITY.
RC TISSUE=Bone;
RX PubMed=7890746; DOI=10.1074/jbc.270.11.6125;
RA Wendel M., Sommarin Y., Bergman T., Heinegaard D.;
RT "Isolation, characterization, and primary structure of a calcium-binding
RT 63-kDa bone protein.";
RL J. Biol. Chem. 270:6125-6133(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Sprague-Dawley;
RA Long X., Bigsby R.M., Nephew K.P.;
RT "Rat nucleobindin mRNA, complete cds and including 3' UTR.";
RL Submitted (JAN-2001) 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 NUCLEOTIDE SEQUENCE [MRNA] OF 351-425.
RC STRAIN=Wistar Kyoto; TISSUE=Aortic smooth muscle;
RA Adams L.A., Werny I., Schwartz S.M.;
RL Submitted (OCT-1996) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP SUBCELLULAR LOCATION.
RX PubMed=9647645; DOI=10.1083/jcb.141.7.1515;
RA Lin P., Le-Niculescu H., Hofmeister R., McCaffery J.M., Jin M.,
RA Hennemann H., McQuistan T., De Vries L., Farquhar M.G.;
RT "The mammalian calcium-binding protein, nucleobindin (CALNUC), is a Golgi
RT resident protein.";
RL J. Cell Biol. 141:1515-1527(1998).
RN [6]
RP SUBCELLULAR LOCATION, AND INTERACTION WITH GNAI3.
RX PubMed=10639138; DOI=10.1073/pnas.97.2.674;
RA Lin P., Fischer T., Weiss T., Farquhar M.G.;
RT "Calnuc, an EF-hand Ca(2+) binding protein, specifically interacts with the
RT C-terminal alpha5-helix of G(alpha)i3.";
RL Proc. Natl. Acad. Sci. U.S.A. 97:674-679(2000).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-368, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=16641100; DOI=10.1073/pnas.0600895103;
RA Hoffert J.D., Pisitkun T., Wang G., Shen R.-F., Knepper M.A.;
RT "Quantitative phosphoproteomics of vasopressin-sensitive renal cells:
RT regulation of aquaporin-2 phosphorylation at two sites.";
RL Proc. Natl. Acad. Sci. U.S.A. 103:7159-7164(2006).
RN [8]
RP FUNCTION, INTERACTION WITH GNAI1; GNAI2 AND GNAI3, GBA MOTIF, AND
RP MUTAGENESIS OF LEU-313; PHE-316 AND LEU-317.
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 [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-85 AND SER-368, AND
RP IDENTIFICATION BY 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: Major calcium-binding protein of the Golgi which may have a
CC role in calcium homeostasis (PubMed:7890746). Acts as a non-receptor
CC guanine nucleotide exchange factor which binds to and activates alpha
CC subunits of guanine nucleotide-binding proteins (G proteins)
CC (PubMed:21653697). {ECO:0000269|PubMed:21653697,
CC ECO:0000269|PubMed:7890746}.
CC -!- SUBUNIT: Interacts (via GBA motif) with guanine nucleotide-binding
CC protein G(i) alpha subunits GNAI1, GNAI2 and GNAI3 with higher affinity
CC for GNAI1 and GNAI3 than for GNAI2 (PubMed:10639138, PubMed:21653697).
CC Preferentially interacts with inactive rather than active GNAI3
CC (PubMed:21653697). Interaction with GNAI3 is inhibited when NUCB1 binds
CC calcium, probably due to a conformational change which renders the GBA
CC motif inaccessible (PubMed:21653697). {ECO:0000269|PubMed:10639138,
CC ECO:0000269|PubMed:21653697}.
CC -!- SUBCELLULAR LOCATION: Golgi apparatus, cis-Golgi network membrane
CC {ECO:0000269|PubMed:10639138, ECO:0000269|PubMed:9647645}; Peripheral
CC membrane protein {ECO:0000269|PubMed:9647645}; Lumenal side
CC {ECO:0000269|PubMed:9647645}. Cytoplasm {ECO:0000269|PubMed:10639138,
CC ECO:0000269|PubMed:9647645}. Secreted {ECO:0000269|PubMed:7890746}.
CC Note=A small fraction of the protein may be cytoplasmic. In bone at
CC least part of it is found in the extracellular matrix and in the
CC culture medium of calvaria explants. {ECO:0000269|PubMed:7890746,
CC ECO:0000269|PubMed:9647645}.
CC -!- TISSUE SPECIFICITY: Minor constituent of the mineralized matrix of
CC bone. Detected in calvaria, rib cartilage, liver, kidney, spleen,
CC brain, lung, skeletal and heart muscle with highest expression in
CC calvaria and approximately half the amount in kidney, liver and brain.
CC {ECO:0000269|PubMed:7890746}.
CC -!- DOMAIN: The EF-hand domains are unfolded in the absence of Ca(2+) and
CC fold upon Ca(2+) addition. {ECO:0000250|UniProtKB:Q02818}.
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: Discovered as DNA-binding protein in the serum of lupus-
CC prone mice.
CC -!- SIMILARITY: Belongs to the nucleobindin family. {ECO:0000305}.
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DR EMBL; Z36277; CAA85285.1; -; mRNA.
DR EMBL; U75409; AAB19111.1; -; mRNA.
DR EMBL; BC100643; AAI00644.1; -; mRNA.
DR EMBL; AF336828; AAK21297.1; -; mRNA.
DR PIR; I55472; I55472.
DR RefSeq; NP_445915.1; NM_053463.1.
DR RefSeq; XP_006229227.1; XM_006229165.1.
DR AlphaFoldDB; Q63083; -.
DR BMRB; Q63083; -.
DR SMR; Q63083; -.
DR BioGRID; 250025; 2.
DR IntAct; Q63083; 3.
DR STRING; 10116.ENSRNOP00000028390; -.
DR iPTMnet; Q63083; -.
DR PhosphoSitePlus; Q63083; -.
DR jPOST; Q63083; -.
DR PaxDb; Q63083; -.
DR PRIDE; Q63083; -.
DR GeneID; 84595; -.
DR KEGG; rno:84595; -.
DR UCSC; RGD:620030; rat.
DR CTD; 4924; -.
DR RGD; 620030; Nucb1.
DR VEuPathDB; HostDB:ENSRNOG00000020889; -.
DR eggNOG; KOG3866; Eukaryota.
DR HOGENOM; CLU_031153_1_0_1; -.
DR InParanoid; Q63083; -.
DR OMA; QETDTNH; -.
DR OrthoDB; 1445357at2759; -.
DR PhylomeDB; Q63083; -.
DR TreeFam; TF323218; -.
DR Reactome; R-RNO-381426; Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs).
DR Reactome; R-RNO-8957275; Post-translational protein phosphorylation.
DR PRO; PR:Q63083; -.
DR Proteomes; UP000002494; Chromosome 1.
DR Bgee; ENSRNOG00000020889; Expressed in cerebellum and 19 other tissues.
DR Genevisible; Q63083; RN.
DR GO; GO:0005801; C:cis-Golgi network; IDA:RGD.
DR GO; GO:0005737; C:cytoplasm; IDA:RGD.
DR GO; GO:0005769; C:early endosome; IDA:RGD.
DR GO; GO:0005793; C:endoplasmic reticulum-Golgi intermediate compartment; ISO:RGD.
DR GO; GO:0005576; C:extracellular region; IDA:RGD.
DR GO; GO:0005615; C:extracellular space; IDA:RGD.
DR GO; GO:0090498; C:extrinsic component of Golgi membrane; IDA:RGD.
DR GO; GO:0005794; C:Golgi apparatus; IDA:RGD.
DR GO; GO:0032580; C:Golgi cisterna membrane; IDA:RGD.
DR GO; GO:0005798; C:Golgi-associated vesicle; IDA:RGD.
DR GO; GO:0098547; C:lumenal side of Golgi membrane; IDA:RGD.
DR GO; GO:0005634; C:nucleus; IDA:RGD.
DR GO; GO:0005791; C:rough endoplasmic reticulum; IDA:RGD.
DR GO; GO:0005802; C:trans-Golgi network; IDA:RGD.
DR GO; GO:0005509; F:calcium ion binding; IDA: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:1903533; P:regulation of protein targeting; IDA:RGD.
DR GO; GO:0072718; P:response to cisplatin; 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; IPR040253; NUCB1.
DR InterPro; IPR040250; Nucleobindin.
DR PANTHER; PTHR19237; PTHR19237; 1.
DR PANTHER; PTHR19237:SF21; PTHR19237:SF21; 1.
DR Pfam; PF13499; EF-hand_7; 1.
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; Coiled coil; Cytoplasm; DNA-binding; Golgi apparatus;
KW Guanine-nucleotide releasing factor; Membrane; Metal-binding;
KW Phosphoprotein; Reference proteome; Repeat; Secreted; Signal.
FT SIGNAL 1..25
FT /evidence="ECO:0000250|UniProtKB:Q0P569"
FT CHAIN 26..459
FT /note="Nucleobindin-1"
FT /id="PRO_0000004164"
FT DOMAIN 239..274
FT /note="EF-hand 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT DOMAIN 291..326
FT /note="EF-hand 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT DNA_BIND 171..217
FT /evidence="ECO:0000255"
FT REGION 192..220
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 227..320
FT /note="Binds to GNAI2 and GNAI3"
FT REGION 393..459
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 149..217
FT /evidence="ECO:0000255"
FT COILED 340..407
FT /evidence="ECO:0000255"
FT MOTIF 302..332
FT /note="GBA"
FT /evidence="ECO:0000250|UniProtKB:Q02818"
FT COMPBIAS 192..218
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 393..417
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 252
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
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 263
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT BINDING 304
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
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 315
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT MOD_RES 85
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 147
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q02818"
FT MOD_RES 368
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:16641100,
FT ECO:0007744|PubMed:22673903"
FT MOD_RES 456
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q02819"
FT MUTAGEN 313
FT /note="L->A: Decreased binding to GNAI3. Further decrease
FT in binding to GNAI3 and loss of GNAI3 activation; when
FT associated with A-317."
FT /evidence="ECO:0000269|PubMed:21653697"
FT MUTAGEN 316
FT /note="F->A: Decreased binding to GNAI3 and impaired GNAI3
FT activation."
FT /evidence="ECO:0000269|PubMed:21653697"
FT MUTAGEN 317
FT /note="L->A: Decreased binding to GNAI3. Further decrease
FT in binding to GNAI3 and loss of GNAI3 activation; when
FT associated with A-313."
FT /evidence="ECO:0000269|PubMed:21653697"
SQ SEQUENCE 459 AA; 53507 MW; 862BC82673002949 CRC64;
MPTSVPRGAP FLLLPPLLML SAVLAVPVDR AAPHQEDNQA TETPDTGLYY HRYLQEVINV
LETDGHFREK LQAANAEDIK SGKLSQELDF VSHNVRTKLD ELKRQEVSRL RMLLKAKMDA
KQEPNLQVDH MNLLKQFEHL DPQNQHTFEA RDLELLIQTA TRDLAQYDAA HHEEFKRYEM
LKEHERRRYL ESLGEEQRKE AERKLQEQQR RHREHPKVNV PGSQAQLKEV WEELDGLDPN
RFNPKTFFIL HDINSDGVLD EQELEALFTK ELEKVYDPKN EEDDMREMEE ERLRMREHVM
KNVDTNQDRL VTLEEFLAST QRKEFGETAE GWKTVEMYPA YTEEELKRFE EELAAREAEL
NARAQRLSQE TEALGRSQDR LEAQKRELQQ AVLQMEQRKQ QQQEQSAPPS QPDGQLQFRA
DTGDAPVPAP AGDQKDVPAS EKKVPEQPPV LPQLDSQHL
