NUCB2 (Nucleobindin 2)
A multifunctional protein involved in calcium homeostasis, feeding behavior, and cancer progression.
Gene Information Card
| Symbol | NUCB2 |
|---|---|
| Full Name | Nucleobindin 2 |
| Gene Type | Protein coding |
| Chromosomal Location | 11p15.1 |
| NCBI Gene ID | 4925 ncbi.nlm.nih.gov/gene/4925 |
| Ensembl ID | ENSG00000148773 |
| UniProt ID | P80303 |
| OMIM ID | 608020 |
| HGNC ID | 8044 |
| Aliases | NEFA, NUCB2A, NUCB2B, nesfatin-1 precursor |
Description
NUCB2 (nucleobindin 2) encodes a calcium-binding protein that is cleaved to produce nesfatin-1, a peptide involved in appetite regulation and energy homeostasis. The full-length protein also participates in intracellular calcium signaling, DNA binding, and may play roles in cell proliferation and differentiation. NUCB2 is widely expressed in brain, adipose tissue, and various cancers.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Obesity | Nesfatin-1 derived from NUCB2 regulates food intake and energy balance; altered expression linked to obesity | OMIM 608020, NCBI Gene |
| Breast cancer | NUCB2 overexpression promotes cell proliferation and migration; associated with poor prognosis | COSMIC, PubMed |
| Gastric cancer | Upregulated NUCB2 correlates with tumor invasion and metastasis | COSMIC, PubMed |
| Type 2 diabetes | Nesfatin-1 modulates insulin secretion and glucose metabolism; dysregulation contributes to diabetes | OMIM 608020, PubMed |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain (hypothalamus) | 12.5 | High |
| Adipose tissue | 8.3 | Medium |
| Pancreas | 6.7 | Medium |
| Stomach | 5.9 | Medium |
| Liver | 2.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| MCF7 (breast cancer) | 15.2 | High expression |
| HeLa (cervical cancer) | 10.8 | Medium expression |
| HepG2 (liver cancer) | 4.3 | Low expression |
| SH-SY5Y (neuroblastoma) | 9.1 | Medium expression |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.497C>T (p.Thr166Met) | Missense | <0.01% | Unknown significance; reported in ClinVar |
| c.1045G>A (p.Gly349Ser) | Missense | <0.01% | Likely benign |
| c.1234_1235insA | Frameshift | <0.01% | Loss of function; associated with cancer in COSMIC |
Mutation functional classification
Loss of Function (LOF)
Frameshift mutations (e.g., c.1234_1235insA) lead to truncated protein and loss of calcium-binding and signaling functions.
Gain of Function (GOF)
Not well documented; overexpression in cancers may act as a gain-of-function by promoting proliferation.
Dominant Negative (DN)
No known dominant-negative mutations reported.
View complete mutation data：
Gene Ontology (GO)
| • calcium ion binding | • DNA binding |
| • protein homodimerization activity | • regulation of feeding behavior |
| • negative regulation of appetite | • cellular response to glucose stimulus |
Pathways
• GPCR signaling (nesfatin-1 receptor)
• Calcium signaling pathway
• Energy homeostasis regulation
Protein Summary
NUCB2 encodes a 420-amino acid protein (nucleobindin 2) that contains a signal peptide, a DNA-binding domain, and two EF-hand calcium-binding domains. It is cleaved by prohormone convertases to generate nesfatin-1 (N-terminal 82 amino acids), which acts as an anorexigenic peptide. The full-length protein is involved in calcium-dependent intracellular signaling and transcriptional regulation. NUCB2 is expressed in multiple tissues and is implicated in metabolic disorders and cancer.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| NUCB2 Knockout HEK293 Cell Line | EDJ-KQ5367 | Human | 4925 | Details Get a Quote |
| NUCB2 Knockout A-549 Cell Line | EDJ-KQ28490 | Human | 4925 | Details Get a Quote |
| NUCB2 Knockout HCT 116 Cell Line | EDJ-KQ28491 | Human | 4925 | Details Get a Quote |
| NUCB2 Knockout HeLa Cell Line | EDJ-KQ28492 | Human | 4925 | Details Get a Quote |
