Nuclear receptor-binding factor 2 (NRBF2)
The protein contains 287 amino acids for an estimated molecular weight of 32378 Da.
May modulate transcriptional activation by target nuclear receptors. Can act as transcriptional activator (in vitro).', 'Involved in starvation-induced autophagy probably by its association with PI3K complex I (PI3KC3-C1). However, effects has been described variably. Involved in the induction of starvation-induced autophagy (PubMed:24785657). Stabilzes PI3KC3-C1 assembly and enhances ATG14-linked lipid kinase activity of PIK3C3 (By similarity). Proposed to negatively regulate basal and starvation-induced autophagy and to inhibit PIK3C3 activity by modulating interactions in PI3KC3-C1 (PubMed:25086043). May be involved in autophagosome biogenesis (PubMed:25086043). May play a role in neural progenitor cell survival during differentiation (By similarity). (updated: Jan. 31, 2018)
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.
- Lange and co-workers. (2014) Annotating N termini for the human proteome project: N termini and Nα-acetylation status differentiate stable cleaved protein species from degradation remnants in the human erythrocyte proteome. J Proteome Res. 13(4), 2028-2044.
- 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.
- 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.
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Biological Process
Autophagy
Gene expression
Regulation of lipid kinase activity
Regulation of transcription, DNA-templated
Response to endoplasmic reticulum stress
Transcription initiation from RNA polymerase II promoter
Cellular Component
Autophagosome
Cytoplasm
Cytoplasmic vesicle
Nucleoplasm
Phosphatidylinositol 3-kinase complex, class III
Molecular Function
The reference OMIM entry for this protein is 616477
Nuclear receptor-binding factor 2; nrbf2
Comodulator of ppar and rxr; copr
DESCRIPTION
NRBF2 can regulate transactivation activity of nuclear hormone receptors (Flores et al., 2004) and also appears to regulate autophagy (Zhong et al., 2014).CLONING
By searching EST databases for sequences similar to rat Nrbf2, Yasumo et al. (2000) identified mouse and human NRBF2. All 3 proteins contain 287 amino acids and have a domain structure characteristic of a nuclear receptor, including an N-terminal AF1 domain for ligand-independent activation function, followed by a zinc finger domain involved in DNA binding, a hinge region, and a C-terminal AF2 domain for ligand-dependent activation function. All proteins also have a conserved LxxLL motif. Northern blot analysis detected a 1.9-kb transcript in all rat tissues and human cell lines examined. Epitope-tagged rat Nrbf2 was predominantly expressed in the nucleus of transfected HeLa cells. Using the ligand-binding domain of PPAR-alpha (PPARA; 170998) as bait in a yeast 2-hybrid screen of a human keratinocyte cDNA library, Flores et al. (2004) obtained a splice variant of NRBF2 that they called COPR1. The deduced 237-amino acid COPR1 protein differs from the sequence reported by Yasumo et al. (2000), which Flores et al. (2004) called COPR2, by lack of a 50-amino acid insertion immediately N-terminal to the LxxLL nuclear receptor box, which in COPR proteins is LLYLL. The insertion was predicted to alter the secondary structure of the N-terminal domain. RT-PCR analysis detected variable expression of COPR1 and COPR2 in liver, skeletal muscle, pancreas, lung, placenta, and heart, with little to no expression in kidney and brain. Cell type-specific expression of both variants was detected in keratinocytes, HaCaT keratinocyte cell lines, and MCF breast cancer cells. Zhong et al. (2014) reported that the N-terminal domain of full-length NRBF2 represents a microtubule-interacting and -trafficking (MIT) domain. They found that fluorescence-tagged NRBF2 colocalized to cytosolic punctae with autophagosome markers in human retinal pigment epithelial (RPE1) cells.GENE FUNCTION
Using a yeast 2-hybrid assay, Yasumo et al. (2000) found that rat Nrbf2 showed ligand-dependent binding to several nuclear receptors, including PPAR-alpha, THR-beta (THRB; 190160), RAR-alpha (RARA; 180240), and RXR-alpha (RXRA; 180245), but showed minimal ligand-dependent interaction with HNF4-alpha (HNF4A; 600281). Deletion analysis showed that the AF2 domain and the hinge region of rat Nrbf2 were required for binding to PPAR-alpha. Nrbf2 showed intrinsic transcriptional activity in yeast and activated a reporter following transfection into human cell lines. Flores et al. (2004) found that COPR1 and COPR2, which targeted AF2 domains in nuclear receptors, showed complex ligand-regulated and selective interactions with the receptors. Deletion and mutagenesis studies revealed that interaction with nuclear receptors was dependent on the proline- and acid-rich C terminus of COPR proteins and was facilitated by the LLYLL nuclear receptor box motif. Both COPR1 and COPR2 partially repressed endogenous RXR activity in HaCaT cells in the presence or absence of retinoic acid. Using reciprocal immunoprecipitation with HEK293 and RPE1 cells, Zhong et al. (2014) found that full-length NRBF2 interacted with beclin-1 (BECN1; 604378), VPS34 (PIK3C3; 602609), and VPS15 (PIK3R4; 602610), which are involved in lysosome-dependent autophagy. Knockdown of NRBF2 in RPE1 cells via small interfering RNA ... More on the omim web site
May 12, 2019: Protein entry updated
Automatic update: model status changed
Nov. 17, 2018: Protein entry updated
Automatic update: model status changed
Feb. 10, 2018: Protein entry updated
Automatic update: Entry updated from uniprot information.
Feb. 10, 2018: Protein entry updated
Automatic update: OMIM entry 616477 was added.
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 NRBF2
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