This gene encodes a protein with a suggested role in calcium level maintenance, eating regulation in the hypothalamus, and release of tumor necrosis factor from vascular endothelial cells. This protein binds calcium and has EF-folding domains. [provided by RefSeq, Oct 2011] See more...

Aliases for NUCB2 Gene

Aliases for NUCB2 Gene

  • Nucleobindin 2 2 3 5
  • NEFA 2 3 4
  • Novel DNA Binding/EF-Hand/Leucine Zipper Protein 2 3
  • Epididymis Secretory Protein Li 109 3 4
  • Gastric Cancer Antigen Zg4 3 4
  • DNA-Binding Protein NEFA 3 4
  • Nucleobindin-2 3 4
  • Prepronesfatin 3 4
  • Nucleobinding 2 3
  • Nesfatin 1 3
  • HEL-S-109 3
  • NUCB2 5

External Ids for NUCB2 Gene

Previous GeneCards Identifiers for NUCB2 Gene

  • GC11M018347
  • GC11P018224
  • GC11P017321
  • GC11P017262
  • GC11P017255
  • GC11P016982
  • GC11P017229
  • GC11P017212
  • GC11P017213
  • GC11P017218

Summaries for NUCB2 Gene

Entrez Gene Summary for NUCB2 Gene

  • This gene encodes a protein with a suggested role in calcium level maintenance, eating regulation in the hypothalamus, and release of tumor necrosis factor from vascular endothelial cells. This protein binds calcium and has EF-folding domains. [provided by RefSeq, Oct 2011]

GeneCards Summary for NUCB2 Gene

NUCB2 (Nucleobindin 2) is a Protein Coding gene. Gene Ontology (GO) annotations related to this gene include calcium ion binding. An important paralog of this gene is NUCB1.

UniProtKB/Swiss-Prot Summary for NUCB2 Gene

  • Calcium-binding protein which may have a role in calcium homeostasis (By similarity). Acts as a non-receptor guanine nucleotide exchange factor which binds to and activates guanine nucleotide-binding protein (G-protein) alpha subunit GNAI3 (By similarity).
  • [Nesfatin-1]: Anorexigenic peptide, seems to play an important role in hypothalamic pathways regulating food intake and energy homeostasis, acting in a leptin-independent manner. May also exert hypertensive roles and modulate blood pressure through directly acting on peripheral arterial resistance.

Gene Wiki entry for NUCB2 Gene

Additional gene information for NUCB2 Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for NUCB2 Gene

Genomics for NUCB2 Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for NUCB2 Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH11J017206 Promoter/Enhancer 2.4 EPDnew FANTOM5 Ensembl ENCODE CraniofacialAtlas 600.7 +0.3 279 4.9 CREB1 GATAD2A PRDM10 TFE3 ZNF512 SOX13 IKZF1 ZNF692 POLR2A BACH1 PIK3C2A NUCB2 lnc-PIK3C2A-1 lnc-NCR3LG1-4 lnc-NUCB2-4 SNORD14A SAAL1 OR7E14P SNORD14B RPS13
GH11J017273 Promoter/Enhancer 2.2 EPDnew Ensembl ENCODE CraniofacialAtlas dbSUPER 608.7 +68.8 68823 6.5 SP1 CREB1 GATAD2A PRDM10 RFX1 LEF1 IKZF1 KDM1A POLR2A FOS NUCB2 lnc-NCR3LG1-2 OR7E14P SAAL1 SNORD14A MN309336 NCR3LG1
GH11J017295 Promoter 0.5 EPDnew 600.2 +87.2 87163 0.1 FOXA2 FOXA3 NUCB2 MN309336 lnc-KCNJ11-5 lnc-NCR3LG1-2 NCR3LG1
GH11J017263 Enhancer 0.7 Ensembl 4.3 +56.7 56748 2.6 ZNF629 JUND PRDM1 ZNF600 CEBPB CTBP1 ZNF316 OSR2 JUN FOS OR7E14P RPS13 KCNJ11 ENSG00000260196 NUCB2 lnc-NCR3LG1-2 RF00017-876 NCR3LG1
GH11J017221 Enhancer 0.5 Ensembl 5 +14.2 14197 1.7 HMBOX1 POLR3A SPI1 ZBTB40 JUN ZNF384 OR7E14P RPS13 NCR3LG1 SNORD14B NUCB2 RPS2P40 piR-50444-057
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around NUCB2 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for NUCB2

Top Transcription factor binding sites by QIAGEN in the NUCB2 gene promoter:
  • AML1a
  • HNF-4alpha1
  • HNF-4alpha2
  • NF-kappaB
  • NF-kappaB1
  • Pax-5
  • PPAR-alpha
  • SREBP-1a
  • SREBP-1b
  • SREBP-1c

Genomic Locations for NUCB2 Gene

Genomic Locations for NUCB2 Gene
chr11:17,208,153-17,349,980
(GRCh38/hg38)
Size:
141,828 bases
Orientation:
Plus strand
chr11:17,229,700-17,371,521
(GRCh37/hg19)
Size:
141,822 bases
Orientation:
Plus strand

Genomic View for NUCB2 Gene

Genes around NUCB2 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
NUCB2 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for NUCB2 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for NUCB2 Gene

Proteins for NUCB2 Gene

  • Protein details for NUCB2 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    P80303-NUCB2_HUMAN
    Recommended name:
    Nucleobindin-2
    Protein Accession:
    P80303
    Secondary Accessions:
    • A8K642
    • D3DQX5
    • Q8NFT5
    • V9HW75

    Protein attributes for NUCB2 Gene

    Size:
    420 amino acids
    Molecular mass:
    50223 Da
    Quaternary structure:
    • Interacts (via GBA motif) with guanine nucleotide-binding protein G(i) alpha subunit GNAI3 (By similarity). Preferentially interacts with inactive rather than active GNAI3 (By similarity). Interaction with GNAI3 is inhibited when NUCB2 binds calcium, probably due to a conformational change which renders the GBA motif inaccessible (By similarity). Binds to the postmitotic growth suppressor NDN; coexpression abolishes NUCB2 secretion (By similarity).
    Miscellaneous:
    • NEFA stands for N=DNA-binding; EF=EF-hand; A=Acidic region.

    Alternative splice isoforms for NUCB2 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for NUCB2 Gene

Post-translational modifications for NUCB2 Gene

  • Glycosylation at Ser42, Ser96, Thr163, Thr172, Thr314, Thr322, Tyr389, and Ser408
  • Ubiquitination at Lys90 and Lys247
  • Modification sites at PhosphoSitePlus

No data available for DME Specific Peptides for NUCB2 Gene

Domains & Families for NUCB2 Gene

Gene Families for NUCB2 Gene

HGNC:
Human Protein Atlas (HPA):
  • Predicted intracellular proteins
  • Predicted secreted proteins

Protein Domains for NUCB2 Gene

Suggested Antigen Peptide Sequences for NUCB2 Gene

GenScript: Design optimal peptide antigens:
  • Nucleobindin 2 (A7LNF3_HUMAN)
  • Nucleobindin 2 (A7LNF4_HUMAN)
  • Nucleobindin 2 (A7LNF5_HUMAN)
  • Nucleobinding 2 (D3DQX5_HUMAN)
  • Gastric cancer antigen Zg4 (NUCB2_HUMAN)

Graphical View of Domain Structure for InterPro Entry

P80303

UniProtKB/Swiss-Prot:

NUCB2_HUMAN :
  • The GBA (G-alpha binding and activating) motif mediates binding to the alpha subunits of guanine nucleotide-binding proteins (G proteins).
  • Belongs to the nucleobindin family.
Domain:
  • The GBA (G-alpha binding and activating) motif mediates binding to the alpha subunits of guanine nucleotide-binding proteins (G proteins).
Family:
  • Belongs to the nucleobindin family.
genes like me logo Genes that share domains with NUCB2: view

Function for NUCB2 Gene

Molecular function for NUCB2 Gene

UniProtKB/Swiss-Prot Function:
Calcium-binding protein which may have a role in calcium homeostasis (By similarity). Acts as a non-receptor guanine nucleotide exchange factor which binds to and activates guanine nucleotide-binding protein (G-protein) alpha subunit GNAI3 (By similarity).
UniProtKB/Swiss-Prot Function:
[Nesfatin-1]: Anorexigenic peptide, seems to play an important role in hypothalamic pathways regulating food intake and energy homeostasis, acting in a leptin-independent manner. May also exert hypertensive roles and modulate blood pressure through directly acting on peripheral arterial resistance.

Phenotypes From GWAS Catalog for NUCB2 Gene

Gene Ontology (GO) - Molecular Function for NUCB2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0001965 G-protein alpha-subunit binding ISS --
GO:0003677 DNA binding TAS,IEA --
GO:0005085 guanyl-nucleotide exchange factor activity ISS --
GO:0005509 calcium ion binding IEA,IBA 21873635
GO:0005515 protein binding IPI 21988832
genes like me logo Genes that share ontologies with NUCB2: view
genes like me logo Genes that share phenotypes with NUCB2: view

Animal Model Products

  • Taconic Biosciences Mouse Models for NUCB2

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for NUCB2

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , Animal Models , Transcription Factor Targets and HOMER Transcription for NUCB2 Gene

Localization for NUCB2 Gene

Subcellular locations from UniProtKB/Swiss-Prot for NUCB2 Gene

Golgi apparatus. Membrane. Peripheral membrane protein. Cytoplasm. Secreted. Endoplasmic reticulum. Nucleus envelope. Note=Golgi retention is mediated by its N-terminal region.
[Nesfatin-1]: Secreted.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for NUCB2 gene
Compartment Confidence
extracellular 5
plasma membrane 4
endoplasmic reticulum 4
cytosol 4
golgi apparatus 4
nucleus 3
cytoskeleton 1
mitochondrion 1
peroxisome 1
lysosome 1

Subcellular locations from the

Human Protein Atlas (HPA)
  • Golgi apparatus (4)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for NUCB2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005576 extracellular region IEA --
GO:0005615 extracellular space TAS,HDA 16502470
GO:0005634 nucleus IEA --
GO:0005635 nuclear envelope IEA --
GO:0005640 nuclear outer membrane IEA --
genes like me logo Genes that share ontologies with NUCB2: view

Pathways & Interactions for NUCB2 Gene

PathCards logo

SuperPathways for NUCB2 Gene

No Data Available

Gene Ontology (GO) - Biological Process for NUCB2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0007264 small GTPase mediated signal transduction ISS --
GO:0032099 negative regulation of appetite IEA --
genes like me logo Genes that share ontologies with NUCB2: view

No data available for Pathways by source and SIGNOR curated interactions for NUCB2 Gene

Drugs & Compounds for NUCB2 Gene

(5) Drugs for NUCB2 Gene - From: DrugBank, PharmGKB, and HMDB

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Calcium citrate Approved, Investigational Pharma Target, ligand 0
Calcium Phosphate Approved Pharma Target, ligand 0
Calcium phosphate dihydrate Approved Pharma Target 0
Hydrochlorothiazide Approved, Vet_approved Pharma Inhibitor, Inhibition 453
Calcium Nutra 6556
genes like me logo Genes that share compounds with NUCB2: view

Transcripts for NUCB2 Gene

mRNA/cDNA for NUCB2 Gene

14 REFSEQ mRNAs :
17 NCBI additional mRNA sequence :
21 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

CRISPR Products

Inhibitory RNA Products

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for NUCB2

Alternative Splicing Database (ASD) splice patterns (SP) for NUCB2 Gene

No ASD Table

Relevant External Links for NUCB2 Gene

GeneLoc Exon Structure for
NUCB2

Expression for NUCB2 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for NUCB2 Gene

Protein differential expression in normal tissues from HIPED for NUCB2 Gene

This gene is overexpressed in Skin (23.8) and Salivary gland (12.4).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for NUCB2 Gene



Protein tissue co-expression partners for NUCB2 Gene

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for NUCB2

SOURCE GeneReport for Unigene cluster for NUCB2 Gene:

Hs.654599

mRNA Expression by UniProt/SwissProt for NUCB2 Gene:

P80303-NUCB2_HUMAN
Tissue specificity: Predominantly expressed in spleen, testis and normal stomach.

Evidence on tissue expression from TISSUES for NUCB2 Gene

  • Liver(4.6)
  • Blood(4.5)
  • Pancreas(3.2)
  • Nervous system(3.1)
  • Stomach(2.9)
  • Heart(2.9)
  • Intestine(2.5)
  • Muscle(2.5)
  • Adrenal gland(2.4)
  • Thyroid gland(2.4)
  • Kidney(2.4)
  • Bone marrow(2.4)
  • Lymph node(2.2)
  • Skin(2)
genes like me logo Genes that share expression patterns with NUCB2: view

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery , mRNA differential expression in normal tissues and Phenotype-based relationships between genes and organs from Gene ORGANizer for NUCB2 Gene

Orthologs for NUCB2 Gene

This gene was present in the common ancestor of animals.

Orthologs for NUCB2 Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia NUCB2 30 31
  • 99.84 (n)
OneToOne
Dog
(Canis familiaris)
Mammalia NUCB2 30 31
  • 93.24 (n)
OneToOne
Cow
(Bos Taurus)
Mammalia NUCB2 30 31
  • 91.73 (n)
OneToOne
Oppossum
(Monodelphis domestica)
Mammalia NUCB2 31
  • 86 (a)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Nucb2 30
  • 83.85 (n)
Mouse
(Mus musculus)
Mammalia Nucb2 30 17 31
  • 83.77 (n)
OneToOne
Platypus
(Ornithorhynchus anatinus)
Mammalia NUCB2 31
  • 79 (a)
OneToOne
Chicken
(Gallus gallus)
Aves NUCB2 30 31
  • 79.82 (n)
OneToOne
Lizard
(Anolis carolinensis)
Reptilia NUCB2 31
  • 72 (a)
OneToOne
Tropical Clawed Frog
(Silurana tropicalis)
Amphibia nucb2 30
  • 68.16 (n)
Zebrafish
(Danio rerio)
Actinopterygii nucb2a 30 31
  • 68.26 (n)
OneToMany
nucb2b 31
  • 63 (a)
OneToMany
Dr.85 30
Rainbow Trout
(Oncorhynchus mykiss)
Actinopterygii Omy.7060 30
Fruit Fly
(Drosophila melanogaster)
Insecta NUCB1 30 31
  • 50.92 (n)
OneToMany
African malaria mosquito
(Anopheles gambiae)
Insecta AgaP_AGAP005608 30
  • 50.65 (n)
Worm
(Caenorhabditis elegans)
Secernentea nucb-1 30 31
  • 53.69 (n)
OneToMany
Sea Squirt
(Ciona savignyi)
Ascidiacea CSA.6711 31
  • 36 (a)
OneToMany
Sea Vase
(Ciona intestinalis)
Ascidiacea Cin.12858 30
Species where no ortholog for NUCB2 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • Alicante grape (Vitis vinifera)
  • Alpha proteobacteria (Wolbachia pipientis)
  • Amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • Baker's yeast (Saccharomyces cerevisiae)
  • Barley (Hordeum vulgare)
  • Beta proteobacteria (Neisseria meningitidis)
  • Bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • Common water flea (Daphnia pulex)
  • Corn (Zea mays)
  • E. coli (Escherichia coli)
  • Filamentous fungi (Aspergillus nidulans)
  • Firmicute Bacteria (Streptococcus pneumoniae)
  • Fission Yeast (Schizosaccharomyces pombe)
  • Green Algae (Chlamydomonas reinhardtii)
  • Honey Bee (Apis mellifera)
  • K. Lactis Yeast (Kluyveromyces lactis)
  • Loblloly Pine (Pinus taeda)
  • Malaria Parasite (Plasmodium falciparum)
  • Medicago Trunc (Medicago Truncatula)
  • Moss (Physcomitrella patens)
  • Orangutan (Pongo pygmaeus)
  • Pig (Sus scrofa)
  • Rice (Oryza sativa)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Urchin (Strongylocentrotus purpuratus)
  • Sorghum (Sorghum bicolor)
  • Soybean (Glycine max)
  • Stem Rust Fungus (Puccinia graminis)
  • Sugarcane (Saccharum officinarum)
  • Thale Cress (Arabidopsis thaliana)
  • Tomato (Lycopersicon esculentum)
  • Toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • Wheat (Triticum aestivum)

Evolution for NUCB2 Gene

ENSEMBL:
Gene Tree for NUCB2 (if available)
TreeFam:
Gene Tree for NUCB2 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for NUCB2: view image

Paralogs for NUCB2 Gene

Paralogs for NUCB2 Gene

(2) SIMAP similar genes for NUCB2 Gene using alignment to 14 proteins:

  • NUCB2_HUMAN
  • A7LNF3_HUMAN
  • A7LNF4_HUMAN
  • A7LNF5_HUMAN
  • E9PJP3_HUMAN
  • E9PKG6_HUMAN
  • E9PLE9_HUMAN
  • E9PLR0_HUMAN
  • E9PLR5_HUMAN
  • E9PM22_HUMAN
  • E9PRQ3_HUMAN
  • H0YD18_HUMAN
  • H0YEG8_HUMAN
  • J3KQU0_HUMAN
genes like me logo Genes that share paralogs with NUCB2: view

Variants for NUCB2 Gene

Polymorphic Variants from UniProtKB/Swiss-Prot for NUCB2 Gene

NUCB2_HUMAN-P80303
Deletion of Gln-402 is frequent.

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for NUCB2 Gene

SNP ID Clinical significance and condition Chr 11 pos Variation AA Info Type
rs182903196 Not Provided: not provided 17,276,676(+) G/A
rs186174 Not Provided: not provided 17,276,557(+) A/C
rs214087 Not Provided: not provided 17,276,818(+) G/C FIVE_PRIME_UTR_VARIANT
rs214088 Uncertain Significance: not provided 17,276,578(+) C/G
rs4757506 Not Provided: not provided 17,276,730(+) A/G FIVE_PRIME_UTR_VARIANT

Additional dbSNP identifiers (rs#s) for NUCB2 Gene

Structural Variations from Database of Genomic Variants (DGV) for NUCB2 Gene

Variant ID Type Subtype PubMed ID
esv3625473 CNV loss 21293372
esv3625474 CNV loss 21293372
nsv467711 CNV gain 19166990
nsv469762 CNV gain 16826518
nsv524611 CNV loss 19592680
nsv553567 CNV gain 21841781
nsv553568 CNV gain 21841781
nsv553582 CNV loss 21841781
nsv7692 CNV insertion 18451855

Variation tolerance for NUCB2 Gene

Residual Variation Intolerance Score: 45.3% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 13.14; 95.14% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for NUCB2 Gene

Human Gene Mutation Database (HGMD)
NUCB2
SNPedia medical, phenotypic, and genealogical associations of SNPs for
NUCB2

SNP Genotyping and Copy Number Assay Products

Disorders for NUCB2 Gene

Additional Disease Information for NUCB2

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
Open Targets Platform

No disorders were found for NUCB2 Gene.

No data available for MalaCards , UniProtKB/Swiss-Prot and Genatlas for NUCB2 Gene

Publications for NUCB2 Gene

  1. Troglitazone, a ligand of peroxisome proliferator-activated receptor-{gamma}, stabilizes NUCB2 (Nesfatin) mRNA by activating the ERK1/2 pathway: isolation and characterization of the human NUCB2 gene. (PMID: 20427483) Yamada M … Mori M (Endocrinology 2010) 3 4 23
  2. Human protein NEFA, a novel DNA binding/EF-hand/leucine zipper protein. Molecular cloning and sequence analysis of the cDNA, isolation and characterization of the protein. (PMID: 7811391) Barnikol-Watanabe S … Hilschmann N (Biological chemistry Hoppe-Seyler 1994) 2 3 4
  3. Nucleobindin-2/nesfatin in the endocrine pancreas: distribution and relationship to glycaemic state. (PMID: 20032201) Foo KS … Broberger C (The Journal of endocrinology 2010) 3 23
  4. Variation at the NFATC2 locus increases the risk of thiazolidinedione-induced edema in the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) study. (PMID: 20628086) Bailey SD … DREAM investigators (Diabetes care 2010) 3 41
  5. [Influence of AML1 and AML1-ETO on transcriptional regulation of nucb2 gene]. (PMID: 20030931) Zou B … Wang KK (Zhongguo shi yan xue ye xue za zhi 2009) 3 23

Products for NUCB2 Gene

Sources for NUCB2 Gene