Nucleobindin-2 (NUCB2)
The protein contains 420 amino acids for an estimated molecular weight of 50196 Da.
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).', '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. (updated: Dec. 11, 2019)
Protein identification was indicated in the following studies:
- Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
- Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
- D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
- Chu and co-workers. (2018) Quantitative mass spectrometry of human reticulocytes reveal proteome-wide modifications during maturation. Br J Haematol. 180(1), 118-133.
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
This protein is annotated as membranous in Gene Ontology.
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| Variant | Description |
|---|---|
| dbSNP:rs2521998 | |
| dbSNP:rs757081 |
The reference OMIM entry for this protein is 608020
Nucleobindin 2; nucb2
Nefa
DESCRIPTION
Nucleobindin-2 is a calcium-binding EF-hand protein.CLONING
By screening cDNA libraries constructed from a human acute lymphoblastic leukemia cell line with an anti-CALLA (120520) monoclonal antibody, Barnikol-Watanabe et al. (1994) isolated a partial NUCB2 cDNA clone. They assembled a full-length clone encoding a deduced 420-amino acid protein, which they called NEFA, with a calculated molecular mass of 48 kD. The protein contains a basic amino acid-rich putative DNA-binding domain with a potential nuclear targeting signal, 2 helix-loop-helix motif regions, 2 concurrent EF-hand motifs, an acidic amino acid region between the EF-hands, and a leucine zipper motif. The protein shares high homology with human NUCB1 (601323). Isoelectric focusing demonstrated the presence of NUCB2 on the plasma membrane, in the cytosol, and in the culture supernatant. NUCB2 is a highly charged protein with a relative molecular mass of 55 kD by SDS-PAGE, despite the lack of N- or O-glycosylation sites.GENE FUNCTION
To determine whether NUCB2 binds Ca(2+) via its EF-hand domains, Kroll et al. (1999) used heterologous overexpression of recombinant NUCB2 analogous to the mature protein and mutants with deletions in the EF-hand domain in yeast. Experiments with the expression products suggested that 1 mol of NUCB2 binds 2 mol of Ca(2+) ions. Fluorescence titration exhibited 2 classes of Ca(2+)-binding sites with Kd values of 0.08 microM and 0.2 microM. Circular dichroism spectroscopy showed an increase from 30% to 43% in the amount of alpha-helix in NUCB2 after addition of calcium ions. Limited proteolytic digestion indicated a Ca(2+)-dependent conformational change accompanied by an altered accessibility to the enzyme. Oh-I et al. (2006) demonstrated that the secreted protein nesfatin, corresponding to NEFA/nucleobindin-2 (NUCB2), is expressed in the appetite control hypothalamic nuclei in rats. Intracerebroventricular injection of NUCB2 reduced feeding. Rat cerebrospinal fluid contains nesfatin-1, an amino-terminal fragment derived from NUCB2, and its expression is decreased in the hypothalamic paraventricular nucleus under starved conditions. Intracerebroventricular injection of nesfatin-1 decreased food intake in a dose-dependent manner, whereas injection of an antibody neutralizing nesfatin-1 stimulated appetite. In contrast, intracerebroventricular injection of other possible fragments processed from NUCB2 did not promote satiety, and conversion of NUCB2 to nesfatin-1 was necessary to induce feeding suppression. Chronic intracerebroventricular injection of nesfatin-1 reduced body weight, whereas rats gained body weight after chronic intracerebroventricular injection of antisense morpholino oligonucleotide against the gene encoding NUCB2. Nesfatin-1 induced anorexia occurs in Zucker rats with a leptin receptor (601007) mutation, and an anti-nesfatin-1 antibody did not block leptin (164160)-induced anorexia. In contrast, central injection of alpha-melanocyte-stimulating hormone (176830) elevated NUCB2 gene expression in the paraventricular nucleus, and satiety by nesfatin-1 is abolished by an antagonist of the melanocortin-3/4 receptor (see 155540). Oh-I et al. (2006) concluded that nesfatin-1 is a satiety molecule that is associated with melanocortin signaling in the hypothalamus.GENE STRUCTURE
By sequence analysis, Caldwell et al. (2001) determined that the NUCB2 gene contains at least 14 exons and ... More on the omim web site
Jan. 22, 2020: Protein entry updated
Automatic update: Entry updated from uniprot information.
May 12, 2019: Protein entry updated
Automatic update: model status changed
Nov. 17, 2018: Protein entry updated
Automatic update: model status changed
Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated
Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated
Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated
Oct. 27, 2017: Protein entry updated
Automatic update: model status changed
March 25, 2017: Additional information
No protein expression data in P. Mayeux work for NUCB2
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 608020 was added.
Feb. 25, 2016: Protein entry updated
Automatic update: model status changed
Feb. 24, 2016: Protein entry updated
Automatic update: model status changed
Jan. 24, 2016: Protein entry updated
Automatic update: model status changed