EP300-interacting inhibitor of differentiation 1 is a protein that in humans is encoded by the EID1 gene.[5][6][7]
| EID1 | |||||||||||||||||||||||||||||||||||||||||||||||||||
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| Identifiers | |||||||||||||||||||||||||||||||||||||||||||||||||||
| Aliases | EID1, C15orf3, CRI1, EID-1, IRO45620, PTD014, RBP21, PNAS-22, EP300 interacting inhibitor of differentiation 1 | ||||||||||||||||||||||||||||||||||||||||||||||||||
| External IDs | OMIM: 605894; MGI: 1889651; HomoloGene: 49376; GeneCards: EID1; OMA:EID1 - orthologs | ||||||||||||||||||||||||||||||||||||||||||||||||||
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Interactions
editEID1 has been shown to interact with EP300[6][8] and retinoblastoma protein.[6][8] Represses MYOD1 transactivation, and inhibits histone acetyltransferase activity of EP300 and CBP. [9]
Function
editEID1 encodes a transcriptional regulatory protein that has been implicated in cell differentiation and negative regulation of transcription. It enables histone acetyltransferase binding activity and acting upstream of or within the negative regulation of transcription by RNA polymerase II. [9][10]
Structure
editEID1 is a protein-coding gene whose product is assigned to the EID family. [9]
Isoforms
editEID1 undergoes alternative splicing. There are multiple isoforms. [10]
Expression
editEID1 is a broadly expressed human gene that does not show strong restriction to a single tissue. Its RNA expression pattern is classified as low tissue specificity, placing it among genes detected across many tissue contexts such as the heart, skeletal muscle, pancreas, brain, testis, etc. [11][9][12]
EID1 is also grouped with predicted intracellular proteins, which is consistent with its assignment as a non-secreted cellular regulatory protein. [12]
Subcellular localization
editThe EID1 protein is in both the nucleus and the cytoplasm. It is further localized to the nucleoplasm and to cytoplasmic ribonucleoprotein granules. [9]
Post-translational regulation
editEID1 is subject to post-translational regulation through ubiquitin-dependent proteolysis. [13] The protein contains a modular peptidic degron that is recognized by an SCF ubiquitin ligase complex whose substrate-recognition component is FBOX21. [13]
This complex mediates polyubiquitylation of EID1 and is necessary for efficient degradation of the protein in both proliferating and quiescent cells. [13]
EID1 is described as unstable and short-lived, also that its degradation is especially pronounced in G0 cells. [13] It was further reported that the degron overlaps in part with the RB1-binding domain of EID1, raising the possibility that binding interactions and protein turnover are automatically connected. [13]
Myoblast differentiation
editStudies have implicated EID1 as in control of myogenic differentiation. A study of the Prader-Willi syndrome protein necdin identified a direct interaction between necdin and EID1. In that study, EID1 was described as suppressing transcriptional activation of genes required for myoblast differentiation, while necdin promoted differentiation by binding EID1 and relieving its repression of MyoD-dependent transcription. It was also reported that EID1 is degraded in myoblasts as cells exit the cell cycle, which further links the regulation of EID1 abundance to the progression of muscle differentiation. [14]
Studies in mice
editThe role of EID1 in the brain has been investigated using Eid1-knockout mouse models. In one transcriptomic study, RNA sequencing of the Eid1-knockout mouse brain identified 2,531 genes with altered expression compared to the wild-type brain, and a follow-up qRT-PCR was used to confirm the reliability of the sequencing data. Based on the changes, it was proposed that EID1 links cell proliferation in the brain. [15]
Orthologs of EID1 have been identified in other mammals, including the rat gene Eid1, indicating that the gene is conserved across species.[15]
Relations
editEID3 shares homology with a region of EID1 implicated in CBP/p300 binding. EID1 and EID3 both function as inhibitors of CBP/p300-dependent transcription in a tissue-specific manner. [16]
EID2 was identified as a second family member and was described as a homolog of EID1 with inhibitory effects on MyoD-dependent transcription and muscle differentiation. [17]
Nuclear receptor interactions
editEID1 has been identified as an interacting partner of the orphan nuclear receptor SF-1. EID1 was reported to suppress SF-1 mediated transactivation, indicating that EID1 can modulate transcriptional output downstream of steroidogenic factor signaling. The same study found that the inhibitory effect was not reproduced with several other nuclear receptors, including LRH-1, ERRy, and mCAR, which suggests a degree of specificity in the interaction between EID1 and SF-1. [18]
References
edit- 1 2 3 GRCh38: Ensembl release 89: ENSG00000255302 – Ensembl, May 2017
- 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000091337 – Ensembl, May 2017
- ↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ↑ Carim L, Sumoy L, Andreu N, Estivill X, Escarceller M (June 2000). "Identification and expression analysis of C15orf3, a novel gene on chromosome 15q21.1→q21.2". Cytogenetics and Cell Genetics. 88 (3–4): 330–332. doi:10.1159/000015523. PMID 10828624. S2CID 27139235.
- 1 2 3 MacLellan WR, Xiao G, Abdellatif M, Schneider MD (December 2000). "A novel Rb- and p300-binding protein inhibits transactivation by MyoD". Molecular and Cellular Biology. 20 (23): 8903–8915. doi:10.1128/MCB.20.23.8903-8915.2000. PMC 86545. PMID 11073990.
- ↑ "Entrez Gene: EID1 EP300 interacting inhibitor of differentiation 1".
- 1 2 Miyake S, Sellers WR, Safran M, Li X, Zhao W, Grossman SR, et al. (December 2000). "Cells degrade a novel inhibitor of differentiation with E1A-like properties upon exiting the cell cycle". Molecular and Cellular Biology. 20 (23): 8889–8902. doi:10.1128/MCB.20.23.8889-8902.2000. PMC 86544. PMID 11073989.
- 1 2 3 4 5 "GeneCards". GeneCards.
- 1 2 "UniProt". UniProt. Retrieved 2026-04-22.
- ↑ "Alliance of Genome Resources". www.alliancegenome.org. Retrieved 2026-04-22.
- 1 2 "EID1 protein expression summary - The Human Protein Atlas". www.proteinatlas.org. Retrieved 2026-04-29.
- 1 2 3 4 5 Zhang C, Li X, Adelmant G, Dobbins J, Geisen C, Oser MG, et al. (December 2015). "Peptidic degron in EID1 is recognized by an SCF E3 ligase complex containing the orphan F-box protein FBXO21". Proceedings of the National Academy of Sciences of the United States of America. 112 (50): 15372–15377. doi:10.1073/pnas.1522006112. PMC 4687553. PMID 26631746.
- ↑ Bush JR, Wevrick R (November 2008). "The Prader-Willi syndrome protein necdin interacts with the E1A-like inhibitor of differentiation EID-1 and promotes myoblast differentiation". Differentiation; Research in Biological Diversity. 76 (9): 994–1005. doi:10.1111/j.1432-0436.2008.00281.x. PMID 18557765.
- 1 2 Fu X, Luo L, Yi R, Ding B, Wang C, Zhang W, et al. (October 2019). "Transcriptome profiling in Eid1-KO mice brain shows that Eid1 links cell proliferation in the brain". Gene. 717 143998. doi:10.1016/j.gene.2019.143998. PMID 31381951.
- ↑ Båvner A, Matthews J, Sanyal S, Gustafsson JA, Treuter E (2005-06-16). "EID3 is a novel EID family member and an inhibitor of CBP-dependent co-activation". Nucleic Acids Research. 33 (11): 3561–3569. doi:10.1093/nar/gki667. PMC 1159117. PMID 15987788. Archived from the original on 2022-06-20.
- ↑ Miyake S, Yanagisawa Y, Yuasa Y (May 2003). "A novel EID-1 family member, EID-2, associates with histone deacetylases and inhibits muscle differentiation". The Journal of Biological Chemistry. 278 (19): 17060–17065. doi:10.1074/jbc.M212212200. PMID 12586827.
- ↑ Park YY, Park KC, Shong M, Lee SJ, Lee YH, Choi HS (December 2007). "EID-1 interacts with orphan nuclear receptor SF-1 and represses its transactivation". Molecules and Cells. 24 (3): 372–377. doi:10.1016/S1016-8478(23)07353-3. PMID 18182853.
Further reading
edit- Ghosh AK, Varga J (2007). "The transcriptional coactivator and acetyltransferase p300 in fibroblast biology and fibrosis". Journal of Cellular Physiology. 213 (3): 663–671. doi:10.1002/jcp.21162. PMID 17559085. S2CID 41744258.
- Margottin F, Bour SP, Durand H, Selig L, Benichou S, Richard V, et al. (March 1998). "A novel human WD protein, h-beta TrCp, that interacts with HIV-1 Vpu connects CD4 to the ER degradation pathway through an F-box motif". Molecular Cell. 1 (4): 565–574. doi:10.1016/S1097-2765(00)80056-8. PMID 9660940.
- Miyake S, Sellers WR, Safran M, Li X, Zhao W, Grossman SR, et al. (December 2000). "Cells degrade a novel inhibitor of differentiation with E1A-like properties upon exiting the cell cycle". Molecular and Cellular Biology. 20 (23): 8889–8902. doi:10.1128/MCB.20.23.8889-8902.2000. PMC 86544. PMID 11073989.
- Wen H, Ao S (2001). "Identification and characterization of a novel human cDNA encoding a 21 kDa pRb-associated protein". Gene. 263 (1–2): 85–92. doi:10.1016/S0378-1119(00)00585-0. PMID 11223246.
- Båvner A, Johansson L, Toresson G, Gustafsson JA, Treuter E (May 2002). "A transcriptional inhibitor targeted by the atypical orphan nuclear receptor SHP". EMBO Reports. 3 (5): 478–484. doi:10.1093/embo-reports/kvf087. PMC 1084100. PMID 11964378.
- Ledl A, Schmidt D, Müller S (2005). "Viral oncoproteins E1A and E7 and cellular LxCxE proteins repress SUMO modification of the retinoblastoma tumor suppressor". Oncogene. 24 (23): 3810–3818. doi:10.1038/sj.onc.1208539. PMID 15806172.
- Krützfeldt M, Ellis M, Weekes DB, Bull JJ, Eilers M, Vivanco MD, et al. (April 2005). "Selective ablation of retinoblastoma protein function by the RET finger protein". Molecular Cell. 18 (2): 213–224. doi:10.1016/j.molcel.2005.03.009. PMID 15837424.
- Benevolenskaya EV, Murray HL, Branton P, Young RA, Kaelin WG (June 2005). "Binding of pRB to the PHD protein RBP2 promotes cellular differentiation". Molecular Cell. 18 (6): 623–635. doi:10.1016/j.molcel.2005.05.012. PMID 15949438.
- Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, et al. (October 2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature. 437 (7062): 1173–1178. Bibcode:2005Natur.437.1173R. doi:10.1038/nature04209. PMID 16189514. S2CID 4427026.