Primary Information |
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| BoMiProt ID | Bomi5389 |
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| Protein Name | E3 UFM1-protein ligase 1 |
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| Organism | Bos taurus |
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| Uniprot ID | A1A4I9 |
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| Milk Fraction | Whey |
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| Ref Sequence ID | NP_001073745.1 |
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| Aminoacid Length | 792 |
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| Molecular Weight | 89383 |
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| FASTA Sequence |
Download |
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| Gene Name | UFL1 |
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| Gene ID | 515894 |
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| Protein Existence Status | reviewed |
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Secondary Information |
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| Protein Function | is enriched in the endoplasmic reticulum (ER),participate in Ufmylation,a type of PTM which deals with complex and fine-tuned cellular activities,such as protein synthesis, folding, and secretion, compounding lipids or sterols, and maintaining calcium homeostasis. Also it is important for ATM activation. UFL1 is recruited to double strand breaks by the MRE11/RAD50/NBS1 complex, and monoufmylates histone H4 following DNA damage. UFL1 can serve as a positive regulator of cell proliferation, and probably plays roles in milk lactation. |
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| Biochemical Properties | 794 AA residues with a calculated molecular weight of 89.5 kDa .Ufl1 does not contain any well-characterized functional domains, such as the RING and HECT domain.the N-terminal region of UFL1 is highly conserved among different species to ensure that Ufm1 is transferred to its target proteins from Ufc1. |
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| PTMs | Phospphorylation on Ser,Ubl conjugation |
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Site(s) of PTM(s)
N-glycosylation,
O-glycosylation,
Phosphorylation
| >sp|A1A4I9|UFL1_BOVIN E3 UFM1-protein ligase 1 OS=Bos taurus OX=9913 GN=UFL1 PE=2 SV=1
MADAWEEIRRLAADFQRAQFAEATQRLSERNCIEIVNKLIAQKQLEVVHTLDGKEYITPA
QISKEMRDELHVRGGRVNIVDLQQAINVDLTHIENRIGDIVKSEKHVQLVLGQLIDENYL
DRLAEEVNDKLQESGQVTIAELCKTYDLPGNFLTQALTQRLGRIINGHIDLDNRGVIFTE
AFVSRHKARIRGLFSAITRPTAVNSLISRYGFQEQLLYSVLEELVNDGRLRGTVVGGRQD
KAVFIPDIYSRTQSTWVDSFLRQNGYLEFDALSRLGIPDAMSYIKKRYKTTQLLFLKAAC
VGQGLVDQVEASVEEAISSGTWVDIAPLLPSSLSVEDAAILLQHVMRALSKQASAVVFSD
TIVVSEKFINDCTDLFSELMHQKAEKEMKNNPVHLITEEDLKQISILESINTSKKDKKDE
RRRKATEGSGSVRGGGGSNAREYKIKKTKKKGRKDDDS*458DDESSHTGKKKPEITFMFQDEI
EDFLRKHLQDAPEEFISELAEYLIKPLNKTYLEVVHSVYMSSTSSASGTGRKRTIKDLQE
EVSNLYNNIRLFEKGMKFFTDDTQAALTKHLLKTVCTDITNLVFNFLASDLMMAVDDPAT
ITSEVRKKILSKLSEETKVALTKLHNSLNEKSIEDFLACLDSAAEACDIMLKKGDKKRER
QVLFQHRQALVEQLKVTEDPALTLHLTSVLLFQFSTHSMLHAPGRCVPQIIAFLSSKIPE
DQHALLVKYQGLVVKHLVSQNKKTGQGEDPLS*752DELDKEQEDIINTTRKELQELSSSIKDL
VLKSRKSSVTEE |
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| Predicted Disorder Regions | 410-467, 742-759, 782-791 |
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| DisProt Annotation | |
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| TM Helix Prediction | No TM helices |
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| Significance of PTMs | Phosphorylation-ATM phosphorylates UFL1 at serine 462, enhancing UFL1 E3 ligase activity and promoting ATM activation in a positive feedback loop. UFL1 S462 is major ATM phosphorylation site. Because the interaction between NBS1 and UFL1 requires the FHA and BRCT1/2 domains of NBS1, which recognize phospho-residues and this phosphorylation is important for interaction between NBS1 and UFL1. |
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| Additional Comments | Ufl1 and its target protein Ufbp1 are transcriptionally upregulated in pancreatic acini and resulted in Bip upregulation, thereby protecting the exocrine pancreas from the negative effects of alcohol. |
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| Bibliography | 1.Qin B, Yu J, Nowsheen S, Wang M, Tu X, Liu T, Li H, Wang L, Lou Z. UFL1 promotes histone H4 ufmylation and ATM activation. Nat Commun. 2019 Mar 18;10(1):1242. doi: 10.1038/s41467-019-09175-0. PMID: 30886146; PMCID: PMC6423285. 2.Xie Z, Fang Z, Pan Z. Ufl1/RCAD, a Ufm1 E3 ligase, has an intricate connection with ER stress. Int J Biol Macromol. 2019 Aug 15;135:760-767. doi: 10.1016/j.ijbiomac.2019.05.170. Epub 2019 May 23. PMID: 31129212. 3.Li, C., Li, L., Ali, I. et al. UFL1 regulates milk protein and fat synthesis–related gene expression of bovine mammary epithelial cells probably via the mTOR signaling pathway. In Vitro Cell.Dev.Biol.-Animal 57, 550–559 (2021). https://doi.org/10.1007/s11626-021-00587-1 |
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