ID UFL1_HUMAN Reviewed; 794 AA. AC O94874; A0PJ53; B4DJ57; C0H5X5; Q8N765; Q9NTQ0; DT 21-JUN-2005, integrated into UniProtKB/Swiss-Prot. DT 21-JUN-2005, sequence version 2. DT 28-JAN-2026, entry version 179. DE RecName: Full=E3 UFM1-protein ligase 1 {ECO:0000305}; DE EC=2.3.2.- {ECO:0000269|PubMed:20018847}; DE AltName: Full=E3 UFM1-protein transferase 1 {ECO:0000305}; DE AltName: Full=Multiple alpha-helix protein located at ER {ECO:0000303|PubMed:20531390}; DE AltName: Full=Novel LZAP-binding protein {ECO:0000303|PubMed:20164180}; DE AltName: Full=Regulator of C53/LZAP and DDRGK1 {ECO:0000303|PubMed:20228063}; GN Name=UFL1 {ECO:0000303|PubMed:30354401, ECO:0000312|HGNC:HGNC:23039}; GN Synonyms=KIAA0776 {ECO:0000303|PubMed:9872452}, MAXER GN {ECO:0000303|PubMed:20531390}, NLBP {ECO:0000303|PubMed:20164180}, GN RCAD {ECO:0000303|PubMed:20228063}; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Brain; RX PubMed=9872452; DOI=10.1093/dnares/5.5.277; RA Nagase T., Ishikawa K., Suyama M., Kikuno R., Miyajima N., Tanaka A., RA Kotani H., Nomura N., Ohara O.; RT "Prediction of the coding sequences of unidentified human genes. XI. The RT complete sequences of 100 new cDNA clones from brain which code for large RT proteins in vitro."; RL DNA Res. 5:277-286(1998). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC TISSUE=Substantia nigra; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=14574404; DOI=10.1038/nature02055; RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R., RA Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D., RA Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., RA Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H., RA Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J., RA Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P., RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V., RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J., RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E., RA Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J., RA French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J., RA Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C., RA Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A., RA Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R., RA Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., RA Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., RA Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., RA Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A., RA Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L., RA Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I., RA Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y., RA Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E., RA Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A., RA Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W., RA Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., RA West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J., RA Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M., RA Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I., RA Rogers J., Beck S.; RT "The DNA sequence and analysis of human chromosome 6."; RL Nature 425:805-811(2003). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3). RC TISSUE=Kidney, and Testis; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [6] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-458, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026; RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.; RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling RT networks."; RL Cell 127:635-648(2006). RN [7] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-458, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=18318008; DOI=10.1002/pmic.200700884; RA Han G., Ye M., Zhou H., Jiang X., Feng S., Jiang X., Tian R., Wan D., RA Zou H., Gu J.; RT "Large-scale phosphoproteome analysis of human liver tissue by enrichment RT and fractionation of phosphopeptides with strong anion exchange RT chromatography."; RL Proteomics 8:1346-1361(2008). RN [8] RP FUNCTION. RX PubMed=20531390; DOI=10.1038/emboj.2010.116; RA Shiwaku H., Yoshimura N., Tamura T., Sone M., Ogishima S., Watase K., RA Tagawa K., Okazawa H.; RT "Suppression of the novel ER protein Maxer by mutant ataxin-1 in Bergman RT glia contributes to non-cell-autonomous toxicity."; RL EMBO J. 29:2446-2460(2010). RN [9] RP IDENTIFICATION BY MASS SPECTROMETRY, FUNCTION, CATALYTIC ACTIVITY, RP SUBCELLULAR LOCATION, TISSUE SPECIFICITY, INTERACTION WITH DDRGK1 AND UFC1, RP AND REGION. RX PubMed=20018847; DOI=10.1074/jbc.m109.036814; RA Tatsumi K., Sou Y.S., Tada N., Nakamura E., Iemura S., Natsume T., RA Kang S.H., Chung C.H., Kasahara M., Kominami E., Yamamoto M., Tanaka K., RA Komatsu M.; RT "A novel type of E3 ligase for the Ufm1 conjugation system."; RL J. Biol. Chem. 285:5417-5427(2010). RN [10] RP IDENTIFICATION BY MASS SPECTROMETRY, UBIQUITINATION, FUNCTION, SUBCELLULAR RP LOCATION, INTERACTION WITH CDK5RAP3; DDRGK1 AND RELA, AND REGION. RX PubMed=20164180; DOI=10.1074/jbc.m109.065920; RA Kwon J., Cho H.J., Han S.H., No J.G., Kwon J.Y., Kim H.; RT "A novel LZAP-binding protein, NLBP, inhibits cell invasion."; RL J. Biol. Chem. 285:12232-12240(2010). RN [11] RP FUNCTION, INTERACTION WITH CDK5RAP3, AND SUBCELLULAR LOCATION. RX PubMed=20228063; DOI=10.1074/jbc.m110.110619; RA Wu J., Lei G., Mei M., Tang Y., Li H.; RT "A novel C53/LZAP-interacting protein regulates stability of C53/LZAP and RT DDRGK domain-containing Protein 1 (DDRGK1) and modulates NF-kappaB RT signaling."; RL J. Biol. Chem. 285:15126-15136(2010). RN [12] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-458, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=20068231; DOI=10.1126/scisignal.2000475; RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.; RT "Quantitative phosphoproteomics reveals widespread full phosphorylation RT site occupancy during mitosis."; RL Sci. Signal. 3:RA3-RA3(2010). RN [13] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [14] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-458, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21406692; DOI=10.1126/scisignal.2001570; RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.; RT "System-wide temporal characterization of the proteome and phosphoproteome RT of human embryonic stem cell differentiation."; RL Sci. Signal. 4:RS3-RS3(2011). RN [15] RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY RP [LARGE SCALE ANALYSIS]. RX PubMed=22223895; DOI=10.1074/mcp.m111.015131; RA Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T., RA Giglione C.; RT "Comparative large-scale characterisation of plant vs. mammal proteins RT reveals similar and idiosyncratic N-alpha acetylation features."; RL Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012). RN [16] RP FUNCTION, AND INDUCTION. RX PubMed=23152784; DOI=10.1371/journal.pone.0048587; RA Zhang Y., Zhang M., Wu J., Lei G., Li H.; RT "Transcriptional regulation of the Ufm1 conjugation system in response to RT disturbance of the endoplasmic reticulum homeostasis and inhibition of RT vesicle trafficking."; RL PLoS ONE 7:E48587-E48587(2012). RN [17] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [18] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-458, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [19] RP FUNCTION, INTERACTION WITH DDRGK1, AND REGION. RX PubMed=25219498; DOI=10.1016/j.molcel.2014.08.007; RA Yoo H.M., Kang S.H., Kim J.Y., Lee J.E., Seong M.W., Lee S.W., Ka S.H., RA Sou Y.S., Komatsu M., Tanaka K., Lee S.T., Noh D.Y., Baek S.H., Jeon Y.J., RA Chung C.H.; RT "Modification of ASC1 by UFM1 is crucial for ERalpha transactivation and RT breast cancer development."; RL Mol. Cell 56:261-274(2014). RN [20] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25944712; DOI=10.1002/pmic.201400617; RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D., RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.; RT "N-terminome analysis of the human mitochondrial proteome."; RL Proteomics 15:2519-2524(2015). RN [21] RP FUNCTION. RX PubMed=27351204; DOI=10.7554/elife.17290; RA DeJesus R., Moretti F., McAllister G., Wang Z., Bergman P., Liu S., RA Frias E., Alford J., Reece-Hoyes J.S., Lindeman A., Kelliher J., Russ C., RA Knehr J., Carbone W., Beibel M., Roma G., Ng A., Tallarico J.A., RA Porter J.A., Xavier R.J., Mickanin C., Murphy L.O., Hoffman G.R., RA Nyfeler B.; RT "Functional CRISPR screening identifies the ufmylation pathway as a RT regulator of SQSTM1/p62."; RL Elife 5:0-0(2016). RN [22] RP INDUCTION. RX PubMed=30354401; DOI=10.1161/circheartfailure.118.004917; RA Li J., Yue G., Ma W., Zhang A., Zou J., Cai Y., Tang X., Wang J., Liu J., RA Li H., Su H.; RT "Ufm1-specific ligase Ufl1 regulates endoplasmic reticulum homeostasis and RT protects against heart failure."; RL Circ. Heart Fail. 11:e004917-e004917(2018). RN [23] RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH NBN AND UFC1, RP PHOSPHORYLATION AT SER-462, AND MUTAGENESIS OF 125-GLU--VAL-127 AND RP SER-462. RX PubMed=30886146; DOI=10.1038/s41467-019-09175-0; RA Qin B., Yu J., Nowsheen S., Wang M., Tu X., Liu T., Li H., Wang L., Lou Z.; RT "UFL1 promotes histone H4 ufmylation and ATM activation."; RL Nat. Commun. 10:1242-1242(2019). RN [24] RP FUNCTION. RX PubMed=30783677; DOI=10.1093/nar/gkz110; RA Wang Z., Gong Y., Peng B., Shi R., Fan D., Zhao H., Zhu M., Zhang H., RA Lou Z., Zhou J., Zhu W.G., Cong Y.S., Xu X.; RT "MRE11 UFMylation promotes ATM activation."; RL Nucleic Acids Res. 47:4124-4135(2019). RN [25] RP FUNCTION. RX PubMed=30626644; DOI=10.1073/pnas.1816202116; RA Walczak C.P., Leto D.E., Zhang L., Riepe C., Muller R.Y., DaRosa P.A., RA Ingolia N.T., Elias J.E., Kopito R.R.; RT "Ribosomal protein RPL26 is the principal target of UFMylation."; RL Proc. Natl. Acad. Sci. U.S.A. 116:1299-1308(2019). RN [26] RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH DDRGK1. RX PubMed=32160526; DOI=10.1016/j.cell.2020.02.017; RA Liang J.R., Lingeman E., Luong T., Ahmed S., Muhar M., Nguyen T., RA Olzmann J.A., Corn J.E.; RT "A genome-wide ER-phagy screen highlights key roles of mitochondrial RT metabolism and ER-Resident UFMylation."; RL Cell 180:1160-1177(2020). RN [27] RP FUNCTION. RX PubMed=32050156; DOI=10.1016/j.intimp.2020.106278; RA Yang G., Wang Y., Chen Y., Huang R.; RT "UFL1 attenuates IL-1beta-induced inflammatory response in human RT osteoarthritis chondrocytes."; RL Int. Immunopharmacol. 81:106278-106278(2020). RN [28] RP FUNCTION. RX PubMed=32807901; DOI=10.1038/s41556-020-0559-z; RA Liu J., Guan D., Dong M., Yang J., Wei H., Liang Q., Song L., Xu L., RA Bai J., Liu C., Mao J., Zhang Q., Zhou J., Wu X., Wang M., Cong Y.S.; RT "UFMylation maintains tumour suppressor p53 stability by antagonizing its RT ubiquitination."; RL Nat. Cell Biol. 22:1056-1063(2020). RN [29] RP FUNCTION, IDENTIFICATION IN THE UREL COMPLEX, AND MUTAGENESIS OF CYS-32; RP CYS-143; CYS-300 AND CYS-372. RX PubMed=36121123; DOI=10.15252/embj.2022111015; RA Peter J.J., Magnussen H.M., DaRosa P.A., Millrine D., Matthews S.P., RA Lamoliatte F., Sundaramoorthy R., Kopito R.R., Kulathu Y.; RT "A non-canonical scaffold-type E3 ligase complex mediates protein RT UFMylation."; RL EMBO J. 41:e111015-e111015(2022). RN [30] RP FUNCTION. RX PubMed=35753586; DOI=10.1016/j.freeradbiomed.2022.06.237; RA Zhu J., Ma X., Jing Y., Zhang G., Zhang D., Mao Z., Ma X., Liu H., Chen F.; RT "P4HB UFMylation regulates mitochondrial function and oxidative stress."; RL Free Radic. Biol. Med. 188:277-286(2022). RN [31] RP FUNCTION, SUBCELLULAR LOCATION, AND IDENTIFICATION IN THE UREL COMPLEX. RX PubMed=36543799; DOI=10.1038/s41467-022-35501-0; RA Ishimura R., El-Gowily A.H., Noshiro D., Komatsu-Hirota S., Ono Y., RA Shindo M., Hatta T., Abe M., Uemura T., Lee-Okada H.C., Mohamed T.M., RA Yokomizo T., Ueno T., Sakimura K., Natsume T., Sorimachi H., Inada T., RA Waguri S., Noda N.N., Komatsu M.; RT "The UFM1 system regulates ER-phagy through the ufmylation of CYB5R3."; RL Nat. Commun. 13:7857-7857(2022). RN [32] RP FUNCTION. RX PubMed=35394863; DOI=10.1073/pnas.2119531119; RA Snider D.L., Park M., Murphy K.A., Beachboard D.C., Horner S.M.; RT "Signaling from the RNA sensor RIG-I is regulated by ufmylation."; RL Proc. Natl. Acad. Sci. U.S.A. 119:e2119531119-e2119531119(2022). RN [33] RP FUNCTION, AND INTERACTION WITH EPSTEIN-BARR VIRUS PROTEIN BILF1 (MICROBIAL RP INFECTION). RX PubMed=37311461; DOI=10.1016/j.molcel.2023.05.018; RA Yiu S.P.T., Zerbe C., Vanderwall D., Huttlin E.L., Weekes M.P., RA Gewurz B.E.; RT "An Epstein-Barr virus protein interaction map reveals NLRP3 inflammasome RT evasion via MAVS UFMylation."; RL Mol. Cell 0:0-0(2023). RN [34] RP FUNCTION. RX PubMed=37795761; DOI=10.1096/fj.202300004rrrr; RA Luo H., Jiao Q.B., Shen C.B., Gong W.Y., Yuan J.H., Liu Y.Y., Chen Z., RA Liu J., Xu X.L., Cong Y.S., Zhang X.W.; RT "UFMylation of HRD1 regulates endoplasmic reticulum homeostasis."; RL FASEB J. 37:e23221-e23221(2023). RN [35] RP FUNCTION. RX PubMed=36893266; DOI=10.1073/pnas.2215732120; RA Zhou J., Ma X., He X., Chen B., Yuan J., Jin Z., Li L., Wang Z., Xiao Q., RA Cai Y., Zou Y., Cong Y.S.; RT "Dysregulation of PD-L1 by UFMylation imparts tumor immune evasion and RT identified as a potential therapeutic target."; RL Proc. Natl. Acad. Sci. U.S.A. 120:e2215732120-e2215732120(2023). RN [36] RP FUNCTION. RX PubMed=37036982; DOI=10.1073/pnas.2220340120; RA Scavone F., Gumbin S.C., Da Rosa P.A., Kopito R.R.; RT "RPL26/uL24 UFMylation is essential for ribosome-associated quality control RT at the endoplasmic reticulum."; RL Proc. Natl. Acad. Sci. U.S.A. 120:e2220340120-e2220340120(2023). RN [37] RP FUNCTION, IDENTIFICATION IN THE UREL COMPLEX, AND MUTAGENESIS OF LEU-27; RP 32-CYS--LEU-39; ASP-129; ARG-185; ARG-191; ARG-199 AND ARG-251. RX PubMed=37595036; DOI=10.1126/sciadv.adh3635; RA Ishimura R., Ito S., Mao G., Komatsu-Hirota S., Inada T., Noda N.N., RA Komatsu M.; RT "Mechanistic insights into the roles of the UFM1 E3 ligase complex in RT ufmylation and ribosome-associated protein quality control."; RL Sci. Adv. 9:eadh3635-eadh3635(2023). RN [38] RP FUNCTION, INTERACTION WITH YWHAG, PHOSPHORYLATION AT THR-536, AND RP MUTAGENESIS OF THR-536. RX PubMed=38377992; DOI=10.1016/j.molcel.2024.01.024; RA He C., Xing X., Chen H.Y., Gao M., Shi J., Xiang B., Xiao X., Sun Y., RA Yu H., Xu G., Yao Y., Xie Z., Xing Y., Budiarto B.R., Chen S.Y., Gao Y., RA Lee Y.R., Zhang J.; RT "UFL1 ablation in T cells suppresses PD-1 UFMylation to enhance anti-tumor RT immunity."; RL Mol. Cell 0:0-0(2024). RN [39] {ECO:0007744|PDB:8B9X} RP X-RAY CRYSTALLOGRAPHY (3.07 ANGSTROMS) OF 27-200 IN COMPLEX WITH DDRGK1, RP INTERACTION WITH UFC1, AND MUTAGENESIS OF 11-LEU--PHE-15. RX PubMed=37988244; DOI=10.15252/embr.202356920; RA Banerjee S., Varga J.K., Kumar M., Zoltsman G., Rotem-Bamberger S., RA Cohen-Kfir E., Isupov M.N., Rosenzweig R., Schueler-Furman O., Wiener R.; RT "Structural study of UFL1-UFC1 interaction uncovers the role of UFL1 N- RT terminal helix in ufmylation."; RL EMBO Rep. 24:e56920-e56920(2023). RN [40] {ECO:0007744|PDB:8C0D, ECO:0007744|PDB:8QFC, ECO:0007744|PDB:8QFD} RP STRUCTURE BY ELECTRON MICROSCOPY (3.2 ANGSTROMS) IN COMPLEX WITH CDK5RAP3 RP AND RIBOSOME, X-RAY CRYSTALLOGRAPHY (2.56 ANGSTROMS) OF 1-179 IN COMPLEX RP WITH DDRGK1 AND UFC1, FUNCTION, SUBCELLULAR LOCATION, IDENTIFICATION IN THE RP UREL COMPLEX, INTERACTION WITH UFC1, AND MUTAGENESIS OF ILE-8; PHE-15 AND RP GLN-19. RX PubMed=38383789; DOI=10.1038/s41586-024-07093-w; RA Makhlouf L., Peter J.J., Magnussen H.M., Thakur R., Millrine D., RA Minshull T.C., Harrison G., Varghese J., Lamoliatte F., Foglizzo M., RA Macartney T., Calabrese A.N., Zeqiraj E., Kulathu Y.; RT "The UFM1 E3 ligase recognizes and releases 60S ribosomes from ER RT translocons."; RL Nature 627:437-444(2024). RN [41] {ECO:0007744|PDB:8OJ0, ECO:0007744|PDB:8OJ8} RP STRUCTURE BY ELECTRON MICROSCOPY (2.9 ANGSTROMS) OF THE UREL COMPLEX IN RP COMPLEX WITH THE 60S RIBOSOME, FUNCTION, SUBCELLULAR LOCATION, AND RP IDENTIFICATION IN THE UREL COMPLEX. RX PubMed=38383785; DOI=10.1038/s41586-024-07073-0; RA DaRosa P.A., Penchev I., Gumbin S.C., Scavone F., Wachalska M., Paulo J.A., RA Ordureau A., Peter J.J., Kulathu Y., Harper J.W., Becker T., Beckmann R., RA Kopito R.R.; RT "UFM1 E3 ligase promotes recycling of 60S ribosomal subunits from the ER."; RL Nature 627:445-452(2024). CC -!- FUNCTION: E3 protein ligase that mediates ufmylation, the covalent CC attachment of the ubiquitin-like modifier UFM1 to lysine residues on CC target proteins, and which plays a key role in various processes, such CC as ribosome recycling, response to DNA damage, interferon response or CC reticulophagy (also called ER-phagy) (PubMed:20018847, PubMed:20164180, CC PubMed:20228063, PubMed:25219498, PubMed:27351204, PubMed:30626644, CC PubMed:30783677, PubMed:32160526, PubMed:32807901, PubMed:35394863, CC PubMed:36121123, PubMed:36543799, PubMed:36893266, PubMed:37036982, CC PubMed:37311461, PubMed:37595036, PubMed:37795761, PubMed:38377992, CC PubMed:38383785, PubMed:38383789). Catalyzes ufmylation of many CC protein, such as CD274/PD-L1, CDK5RAP3, CYB5R3, DDRGK1, EIF6, histone CC H4, MRE11, P4HB, PDCD1/PD-1, TRIP4, RPN1, RPS20/uS10, RPL10/uL16, CC RPL26/uL24, SYVN1/HRD1 and TP53/p53 (PubMed:20018847, PubMed:20531390, CC PubMed:25219498, PubMed:30783677, PubMed:30886146, PubMed:32160526, CC PubMed:35753586, PubMed:36543799, PubMed:36893266, PubMed:37036982, CC PubMed:37595036, PubMed:37795761, PubMed:38383785, PubMed:38383789). As CC part of the UREL complex, plays a key role in ribosome recycling by CC catalyzing mono-ufmylation of RPL26/uL24 subunit of the 60S ribosome CC (PubMed:38383785, PubMed:38383789). Ufmylation of RPL26/uL24 occurs on CC free 60S ribosomes following ribosome dissociation: it weakens the CC junction between post-termination 60S subunits and SEC61 translocons, CC promoting release and recycling of the large ribosomal subunit from the CC endoplasmic reticulum membrane (PubMed:38383785, PubMed:38383789). CC Ufmylation of RPL26/uL24 and subsequent 60S ribosome recycling either CC take place after normal termination of translation or after ribosome CC stalling during cotranslational translocation at the endoplasmic CC reticulum (PubMed:37036982, PubMed:37595036, PubMed:38383785, CC PubMed:38383789). Involved in reticulophagy in response to endoplasmic CC reticulum stress by mediating ufmylation of proteins such as CYB5R3 and CC RPN1, thereby promoting lysosomal degradation of ufmylated proteins CC (PubMed:23152784, PubMed:32160526, PubMed:36543799). Ufmylation in CC response to endoplasmic reticulum stress is essential for processes CC such as hematopoiesis, blood vessel morphogenesis or inflammatory CC response (PubMed:32050156). Mediates ufmylation of DDRGK1 and CDK5RAP3; CC the role of these modifications is however unclear: as both DDRGK1 and CC CDK5RAP3 act as substrate adapters for ufmylation, it is uncertain CC whether ufmylation of these proteins is, a collateral effect or is CC required for ufmylation (PubMed:20018847, PubMed:20531390). Acts as a CC negative regulator of T-cell activation by mediating ufmylation and CC stabilization of PDCD1/PD-1 (PubMed:38377992). Also involved in the CC response to DNA damage: recruited to double-strand break sites CC following DNA damage and mediates monoufmylation of histone H4 and CC ufmylation of MRE11 (PubMed:30783677, PubMed:30886146). Mediates CC ufmylation of TP53/p53, promoting its stability (PubMed:32807901). CC Catalyzes ufmylation of TRIP4, thereby playing a role in nuclear CC receptor-mediated transcription (PubMed:25219498). Required for CC hematopoietic stem cell function and hematopoiesis (By similarity). CC {ECO:0000250|UniProtKB:Q8CCJ3, ECO:0000269|PubMed:20018847, CC ECO:0000269|PubMed:20164180, ECO:0000269|PubMed:20228063, CC ECO:0000269|PubMed:20531390, ECO:0000269|PubMed:23152784, CC ECO:0000269|PubMed:25219498, ECO:0000269|PubMed:27351204, CC ECO:0000269|PubMed:30626644, ECO:0000269|PubMed:30783677, CC ECO:0000269|PubMed:30886146, ECO:0000269|PubMed:32050156, CC ECO:0000269|PubMed:32160526, ECO:0000269|PubMed:32807901, CC ECO:0000269|PubMed:35394863, ECO:0000269|PubMed:35753586, CC ECO:0000269|PubMed:36121123, ECO:0000269|PubMed:36543799, CC ECO:0000269|PubMed:36893266, ECO:0000269|PubMed:37036982, CC ECO:0000269|PubMed:37311461, ECO:0000269|PubMed:37595036, CC ECO:0000269|PubMed:37795761, ECO:0000269|PubMed:38377992, CC ECO:0000269|PubMed:38383785, ECO:0000269|PubMed:38383789}. CC -!- SUBUNIT: Catalytic component of the UFM1 ribosome E3 ligase (UREL) CC complex, composed of UFL1, DDRGK1 and CDK5RAP3 (PubMed:20018847, CC PubMed:20164180, PubMed:20228063, PubMed:25219498, PubMed:32160526, CC PubMed:36121123, PubMed:36543799, PubMed:37595036, PubMed:38383785, CC PubMed:38383789). Interacts with E2-like enzyme UFC1 (PubMed:20018847, CC PubMed:30886146, PubMed:37988244, PubMed:38383789). Interacts with RELA CC (PubMed:20164180). Interacts with NBN; promoting recruitment to double- CC strand breaks following DNA damage (PubMed:30886146). Interacts (when CC phosphorylated) with YWHAG/14-3-3-gamma; sequestering UFL1 and CC preventing its association with PDCD1/PD-1 substrate (PubMed:38377992). CC {ECO:0000269|PubMed:20018847, ECO:0000269|PubMed:20164180, CC ECO:0000269|PubMed:20228063, ECO:0000269|PubMed:25219498, CC ECO:0000269|PubMed:30886146, ECO:0000269|PubMed:32160526, CC ECO:0000269|PubMed:36121123, ECO:0000269|PubMed:36543799, CC ECO:0000269|PubMed:37595036, ECO:0000269|PubMed:37988244, CC ECO:0000269|PubMed:38377992, ECO:0000269|PubMed:38383785, CC ECO:0000269|PubMed:38383789}. CC -!- SUBUNIT: (Microbial infection) Interacts with Epstein-Barr virus CC protein BILF1; this interaction mediates MAVS UFMylation and subsequent CC routing from mitochondria to lysosomes. {ECO:0000269|PubMed:37311461}. CC -!- INTERACTION: CC O94874; Q96JB5: CDK5RAP3; NbExp=13; IntAct=EBI-1048088, EBI-718818; CC O94874; Q96HY6: DDRGK1; NbExp=10; IntAct=EBI-1048088, EBI-1054024; CC O94874; Q9Y3C8: UFC1; NbExp=9; IntAct=EBI-1048088, EBI-1045733; CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane CC {ECO:0000269|PubMed:20018847, ECO:0000269|PubMed:20164180, CC ECO:0000269|PubMed:20228063, ECO:0000269|PubMed:32160526, CC ECO:0000269|PubMed:36543799, ECO:0000269|PubMed:38383785, CC ECO:0000269|PubMed:38383789}. Cytoplasm, cytosol CC {ECO:0000269|PubMed:20228063, ECO:0000269|PubMed:30886146}. Nucleus CC {ECO:0000269|PubMed:30886146}. Chromosome CC {ECO:0000269|PubMed:30886146}. Note=Recruited to double-strand breaks CC by the MRE11-RAD50-NBN (MRN) complex following DNA damage. CC {ECO:0000269|PubMed:30886146}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; CC IsoId=O94874-1; Sequence=Displayed; CC Name=2; CC IsoId=O94874-2; Sequence=VSP_038759; CC Name=3; CC IsoId=O94874-3; Sequence=VSP_038760, VSP_038761; CC -!- TISSUE SPECIFICITY: Ubiquitously expressed, with a high expression in CC liver (at protein level) (PubMed:20018847). Low expression in several CC invasive hepatocellular carcinomas, such Hep-G2, Hep 3B2.1-7, HLE and CC PLC (PubMed:20018847). {ECO:0000269|PubMed:20018847}. CC -!- INDUCTION: Up-regulated by thapsigargin (PubMed:23152784). Down- CC regulated in the failing hearts of patients with dilated cardiomyopathy CC (PubMed:23152784). {ECO:0000269|PubMed:23152784}. CC -!- PTM: Ubiquitinated, leading to its degradation by the proteasome CC (PubMed:20164180). Interaction with CDK5RAP3 protects both proteins CC against ubiquitination and degradation via the proteasome CC (PubMed:20164180). {ECO:0000269|PubMed:20164180}. CC -!- PTM: Phosphorylated at Ser-462 by ATM, enhancing protein ligase CC activity and promoting ATM activation in a positive feedback loop CC (PubMed:30886146). Phosphorylation at Thr-536 by AMPK promotes its CC interaction with YWHAG/14-3-3-gamma, thereby preventing UFL1 CC association with PDCD1/PD-1 substrate (PubMed:38377992). CC {ECO:0000269|PubMed:30886146, ECO:0000269|PubMed:38377992}. CC -!- SIMILARITY: Belongs to the UFL1 family. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=AAH15377.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Potential poly-A sequence.; Evidence={ECO:0000305}; CC Sequence=BAA34496.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AB018319; BAA34496.1; ALT_INIT; mRNA. DR EMBL; AK295934; BAG58719.1; -; mRNA. DR EMBL; AL132776; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL590404; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471051; EAW48507.1; -; Genomic_DNA. DR EMBL; BC015377; AAH15377.1; ALT_SEQ; mRNA. DR EMBL; BC028608; AAH28608.1; -; mRNA. DR EMBL; BC036379; AAH36379.1; -; mRNA. DR CCDS; CCDS5034.1; -. [O94874-1] DR RefSeq; NP_056138.1; NM_015323.5. [O94874-1] DR PDB; 8B9X; X-ray; 3.07 A; A/B=27-200. DR PDB; 8C0D; X-ray; 2.56 A; A/D=1-179. DR PDB; 8OHD; EM; 3.10 A; A=1-794. DR PDB; 8OJ0; EM; 3.30 A; A=1-794. DR PDB; 8OJ5; EM; 2.90 A; A=1-794. DR PDB; 8OJ8; EM; 3.30 A; A=1-794. DR PDB; 8QFC; EM; 3.20 A; B=1-794. DR PDB; 8QFD; EM; 2.20 A; s=1-794. DR PDB; 9GY4; EM; 3.00 A; E=1-794. DR PDBsum; 8B9X; -. DR PDBsum; 8C0D; -. DR PDBsum; 8OHD; -. DR PDBsum; 8OJ0; -. DR PDBsum; 8OJ5; -. DR PDBsum; 8OJ8; -. DR PDBsum; 8QFC; -. DR PDBsum; 8QFD; -. DR PDBsum; 9GY4; -. DR AlphaFoldDB; O94874; -. DR EMDB; EMD-16880; -. DR EMDB; EMD-16902; -. DR EMDB; EMD-16905; -. DR EMDB; EMD-16908; -. DR EMDB; EMD-18381; -. DR EMDB; EMD-18382; -. DR EMDB; EMD-51681; -. DR SMR; O94874; -. DR BioGRID; 116953; 1082. DR ComplexPortal; CPX-8304; UFM1 ribosome E3 ligase complex. DR FunCoup; O94874; 3588. DR IntAct; O94874; 104. DR MINT; O94874; -. DR STRING; 9606.ENSP00000358283; -. DR GlyGen; O94874; 2 sites, 1 O-linked glycan (1 site). DR iPTMnet; O94874; -. DR MetOSite; O94874; -. DR PhosphoSitePlus; O94874; -. DR SwissPalm; O94874; -. DR BioMuta; UFL1; -. DR jPOST; O94874; -. DR MassIVE; O94874; -. DR PaxDb; 9606-ENSP00000358283; -. DR PeptideAtlas; O94874; -. DR ProteomicsDB; 50509; -. [O94874-1] DR ProteomicsDB; 50510; -. [O94874-2] DR ProteomicsDB; 50511; -. [O94874-3] DR Pumba; O94874; -. DR Antibodypedia; 31948; 110 antibodies from 23 providers. DR DNASU; 23376; -. DR Ensembl; ENST00000369278.5; ENSP00000358283.4; ENSG00000014123.11. [O94874-1] DR GeneID; 23376; -. DR KEGG; hsa:23376; -. DR MANE-Select; ENST00000369278.5; ENSP00000358283.4; NM_015323.5; NP_056138.1. DR UCSC; uc003por.4; human. [O94874-1] DR AGR; HGNC:23039; -. DR ClinPGx; PA134937763; -. DR CTD; 23376; -. DR DisGeNET; 23376; -. DR GeneCards; UFL1; -. DR HGNC; HGNC:23039; UFL1. DR HPA; ENSG00000014123; Low tissue specificity. DR MIM; 613372; gene. DR OpenTargets; ENSG00000014123; -. DR VEuPathDB; HostDB:ENSG00000014123; -. DR eggNOG; KOG2235; Eukaryota. DR GeneTree; ENSGT00390000002112; -. DR HOGENOM; CLU_012417_1_0_1; -. DR InParanoid; O94874; -. DR OMA; CILHASG; -. DR OrthoDB; 10258297at2759; -. DR PAN-GO; O94874; 5 GO annotations based on evolutionary models. DR PhylomeDB; O94874; -. DR PathwayCommons; O94874; -. DR Reactome; R-HSA-983168; Antigen processing: Ubiquitination & Proteasome degradation. DR SignaLink; O94874; -. DR SIGNOR; O94874; -. DR Agora; ENSG00000014123; -. DR BioGRID-ORCS; 23376; 295 hits in 1174 CRISPR screens. DR CD-CODE; FB4E32DD; Presynaptic clusters and postsynaptic densities. DR ChiTaRS; UFL1; human. DR GenomeRNAi; 23376; -. DR Pharos; O94874; Tbio. DR PRO; PR:O94874; -. DR Proteomes; UP000005640; Chromosome 6. DR RNAct; O94874; protein. DR Bgee; ENSG00000014123; Expressed in caput epididymis and 212 other cell types or tissues. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0005829; C:cytosol; IEA:UniProtKB-SubCell. DR GO; GO:0005783; C:endoplasmic reticulum; IDA:HPA. DR GO; GO:0005789; C:endoplasmic reticulum membrane; IDA:UniProtKB. DR GO; GO:0016020; C:membrane; HDA:UniProtKB. DR GO; GO:0005741; C:mitochondrial outer membrane; IDA:UniProt. DR GO; GO:0043005; C:neuron projection; IEA:Ensembl. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0032991; C:protein-containing complex; IDA:MGI. DR GO; GO:0035861; C:site of double-strand break; IDA:UniProtKB. DR GO; GO:0019901; F:protein kinase binding; IPI:UniProtKB. DR GO; GO:0061666; F:UFM1 ligase activity; IDA:UniProtKB. DR GO; GO:0071568; F:UFM1 transferase activity; IBA:GO_Central. DR GO; GO:0000077; P:DNA damage checkpoint signaling; IDA:UniProtKB. DR GO; GO:0006974; P:DNA damage response; IDA:UniProtKB. DR GO; GO:0006281; P:DNA repair; IEA:UniProtKB-KW. DR GO; GO:0030218; P:erythrocyte differentiation; ISS:UniProtKB. DR GO; GO:0060218; P:hematopoietic stem cell differentiation; ISS:UniProtKB. DR GO; GO:1903895; P:negative regulation of IRE1-mediated unfolded protein response; IDA:UniProtKB. DR GO; GO:0032088; P:negative regulation of NF-kappaB transcription factor activity; IMP:UniProtKB. DR GO; GO:0031397; P:negative regulation of protein ubiquitination; IDA:UniProtKB. DR GO; GO:0050868; P:negative regulation of T cell activation; IDA:UniProtKB. DR GO; GO:0002841; P:negative regulation of T cell mediated immune response to tumor cell; IDA:UniProtKB. DR GO; GO:0001649; P:osteoblast differentiation; HDA:UniProtKB. DR GO; GO:0010508; P:positive regulation of autophagy; ISS:UniProtKB. DR GO; GO:0008284; P:positive regulation of cell population proliferation; IMP:MGI. DR GO; GO:0060252; P:positive regulation of glial cell proliferation; IEA:Ensembl. DR GO; GO:1903052; P:positive regulation of proteolysis involved in protein catabolic process; IDA:UniProt. DR GO; GO:0140501; P:positive regulation of reticulophagy; IDA:UniProtKB. DR GO; GO:1990592; P:protein K69-linked ufmylation; IDA:UniProtKB. DR GO; GO:0050821; P:protein stabilization; IDA:UniProt. DR GO; GO:0071569; P:protein ufmylation; IDA:UniProtKB. DR GO; GO:0043122; P:regulation of canonical NF-kappaB signal transduction; ISS:UniProtKB. DR GO; GO:0050727; P:regulation of inflammatory response; ISS:UniProtKB. DR GO; GO:0033146; P:regulation of intracellular estrogen receptor signaling pathway; IDA:UniProtKB. DR GO; GO:0032434; P:regulation of proteasomal ubiquitin-dependent protein catabolic process; IMP:MGI. DR GO; GO:0032880; P:regulation of protein localization; IMP:MGI. DR GO; GO:0072344; P:rescue of stalled ribosome; IDA:UniProtKB. DR GO; GO:0034976; P:response to endoplasmic reticulum stress; IDA:UniProtKB. DR GO; GO:1902065; P:response to L-glutamate; IEA:Ensembl. DR GO; GO:0061709; P:reticulophagy; IDA:UniProtKB. DR GO; GO:0032790; P:ribosome disassembly; IDA:UniProtKB. DR InterPro; IPR018611; Ufl1. DR InterPro; IPR056761; Ufl1-like_C. DR InterPro; IPR056580; Ufl1_dom. DR InterPro; IPR056579; Ufl1_N. DR PANTHER; PTHR31057; E3 UFM1-PROTEIN LIGASE 1; 1. DR PANTHER; PTHR31057:SF0; E3 UFM1-PROTEIN LIGASE 1; 1. DR Pfam; PF09743; E3_UFM1_ligase; 1. DR Pfam; PF23659; UFL1; 1. DR Pfam; PF25041; UFL1_C; 1. DR Pfam; PF25870; WHD_UFL1_5th; 1. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Alternative splicing; Chromosome; Cytoplasm; KW DNA damage; DNA repair; Endoplasmic reticulum; Membrane; Methylation; KW Nucleus; Phosphoprotein; Proteomics identification; Reference proteome; KW Transferase; Ubl conjugation; Ubl conjugation pathway. FT INIT_MET 1 FT /note="Removed" FT /evidence="ECO:0007744|PubMed:22223895" FT CHAIN 2..794 FT /note="E3 UFM1-protein ligase 1" FT /id="PRO_0000050771" FT REGION 2..212 FT /note="Required for E3 UFM1-protein ligase activity" FT /evidence="ECO:0000269|PubMed:20018847" FT REGION 2..200 FT /note="Mediates interaction with DDRGK1" FT /evidence="ECO:0000269|PubMed:25219498" FT REGION 121..250 FT /note="Involved in CDK5RAP3-binding" FT /evidence="ECO:0000269|PubMed:20164180" FT REGION 200..400 FT /note="Mediates interaction with TRIP4" FT /evidence="ECO:0000269|PubMed:25219498" FT REGION 407..473 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 490..684 FT /note="Mediates interaction with CDK5RAP3" FT /evidence="ECO:0000250|UniProtKB:B2GV24" FT REGION 745..770 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 2 FT /note="N-acetylalanine" FT /evidence="ECO:0007744|PubMed:22223895" FT MOD_RES 433 FT /note="Omega-N-methylarginine" FT /evidence="ECO:0000250|UniProtKB:Q8CCJ3" FT MOD_RES 458 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:17081983, FT ECO:0007744|PubMed:18318008, ECO:0007744|PubMed:20068231, FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:24275569" FT MOD_RES 462 FT /note="Phosphoserine; by ATM" FT /evidence="ECO:0000269|PubMed:30886146" FT MOD_RES 536 FT /note="Phosphothreonine; by AMPK" FT /evidence="ECO:0000269|PubMed:38377992" FT VAR_SEQ 1..65 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_038759" FT VAR_SEQ 508..509 FT /note="PL -> QV (in isoform 3)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_038760" FT VAR_SEQ 510..794 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_038761" FT VARIANT 137 FT /note="V -> F (in dbSNP:rs28372909)" FT /id="VAR_034037" FT MUTAGEN 8 FT /note="I->R: Abolished interaction with E2-like enzyme FT UFC1." FT /evidence="ECO:0000269|PubMed:38383789" FT MUTAGEN 11..15 FT /note="LAADF->RAADR: Abolished interaction with E2-like FT enzyme UFC1." FT /evidence="ECO:0000269|PubMed:37988244" FT MUTAGEN 15 FT /note="F->R: Abolished interaction with E2-like enzyme FT UFC1." FT /evidence="ECO:0000269|PubMed:38383789" FT MUTAGEN 19 FT /note="Q->R: Abolished interaction with E2-like enzyme FT UFC1." FT /evidence="ECO:0000269|PubMed:38383789" FT MUTAGEN 27 FT /note="L->A: Abolished interaction with DDRGK1; when FT associated with A-32--A-39." FT /evidence="ECO:0000269|PubMed:37595036" FT MUTAGEN 32..39 FT /note="CIEIVNKL->AIEAVNKA: Abolished interaction with FT DDRGK1; when associated with A-27." FT /evidence="ECO:0000269|PubMed:37595036" FT MUTAGEN 32 FT /note="C->A: Does not affect UFM1 ligase activity." FT /evidence="ECO:0000269|PubMed:36121123" FT MUTAGEN 125..127 FT /note="Missing: Abolished interaction with UFC1, impairing FT E3 protein ligase activity and ability to regulate ATM FT activation." FT /evidence="ECO:0000269|PubMed:30886146" FT MUTAGEN 129 FT /note="D->A: Abolished interaction with CDK5RAP3; when FT associated with A-185, A-191, A-199 and A-251." FT /evidence="ECO:0000269|PubMed:37595036" FT MUTAGEN 143 FT /note="C->A: Does not affect UFM1 ligase activity." FT /evidence="ECO:0000269|PubMed:36121123" FT MUTAGEN 185 FT /note="R->A: Abolished interaction with CDK5RAP3; when FT associated with A-129, A-191, A-199 and A-251." FT /evidence="ECO:0000269|PubMed:37595036" FT MUTAGEN 191 FT /note="R->A: Abolished interaction with CDK5RAP3; when FT associated with A-129, A-185, A-199 and A-251." FT /evidence="ECO:0000269|PubMed:37595036" FT MUTAGEN 199 FT /note="R->A: Abolished interaction with CDK5RAP3; when FT associated with A-129, A-185, A-191 and A-251." FT /evidence="ECO:0000269|PubMed:37595036" FT MUTAGEN 251 FT /note="R->A: Abolished interaction with CDK5RAP3; when FT associated with A-129, A-185, A-191 and A-199." FT /evidence="ECO:0000269|PubMed:37595036" FT MUTAGEN 300 FT /note="C->A: Does not affect UFM1 ligase activity." FT /evidence="ECO:0000269|PubMed:36121123" FT MUTAGEN 372 FT /note="C->A: Does not affect UFM1 ligase activity." FT /evidence="ECO:0000269|PubMed:36121123" FT MUTAGEN 462 FT /note="S->A: Impaired recruitment to double-strand break FT sites." FT /evidence="ECO:0000269|PubMed:30886146" FT MUTAGEN 536 FT /note="T->A: Abolished phosphorylation by AMPK, preventing FT interaction with YWHAG/14-3-3-gamma and promoting FT PDCD1/PD-1 ufmylation." FT /evidence="ECO:0000269|PubMed:38377992" FT MUTAGEN 536 FT /note="T->E: Mimics phosphorylation; leading to decreased FT PDCD1/PD-1 ufmylation." FT /evidence="ECO:0000269|PubMed:38377992" FT HELIX 2..20 FT /evidence="ECO:0007829|PDB:8C0D" FT HELIX 29..41 FT /evidence="ECO:0007829|PDB:8C0D" FT STRAND 53..57 FT /evidence="ECO:0007829|PDB:8C0D" FT HELIX 59..73 FT /evidence="ECO:0007829|PDB:8C0D" FT STRAND 75..78 FT /evidence="ECO:0007829|PDB:8C0D" FT HELIX 79..81 FT /evidence="ECO:0007829|PDB:8C0D" FT HELIX 82..86 FT /evidence="ECO:0007829|PDB:8C0D" FT HELIX 90..94 FT /evidence="ECO:0007829|PDB:8C0D" FT HELIX 97..104 FT /evidence="ECO:0007829|PDB:8C0D" FT STRAND 105..110 FT /evidence="ECO:0007829|PDB:8C0D" FT STRAND 113..116 FT /evidence="ECO:0007829|PDB:8C0D" FT HELIX 117..131 FT /evidence="ECO:0007829|PDB:8C0D" FT STRAND 135..138 FT /evidence="ECO:0007829|PDB:8B9X" FT HELIX 139..145 FT /evidence="ECO:0007829|PDB:8C0D" FT HELIX 150..158 FT /evidence="ECO:0007829|PDB:8C0D" FT TURN 162..164 FT /evidence="ECO:0007829|PDB:8B9X" FT STRAND 167..180 FT /evidence="ECO:0007829|PDB:8B9X" FT HELIX 203..210 FT /evidence="ECO:0007829|PDB:8QFC" FT HELIX 214..226 FT /evidence="ECO:0007829|PDB:8QFC" FT STRAND 232..235 FT /evidence="ECO:0007829|PDB:8QFC" FT STRAND 243..246 FT /evidence="ECO:0007829|PDB:8QFC" FT HELIX 247..264 FT /evidence="ECO:0007829|PDB:8QFC" FT STRAND 265..267 FT /evidence="ECO:0007829|PDB:8QFC" FT HELIX 271..274 FT /evidence="ECO:0007829|PDB:8QFC" FT HELIX 280..287 FT /evidence="ECO:0007829|PDB:8QFC" FT STRAND 293..295 FT /evidence="ECO:0007829|PDB:8QFC" FT STRAND 300..302 FT /evidence="ECO:0007829|PDB:8QFC" FT HELIX 305..319 FT /evidence="ECO:0007829|PDB:8QFC" FT STRAND 322..324 FT /evidence="ECO:0007829|PDB:8QFC" FT HELIX 326..328 FT /evidence="ECO:0007829|PDB:8QFC" FT HELIX 335..346 FT /evidence="ECO:0007829|PDB:8QFC" FT STRAND 350..352 FT /evidence="ECO:0007829|PDB:8QFC" FT STRAND 356..358 FT /evidence="ECO:0007829|PDB:8QFC" FT TURN 359..361 FT /evidence="ECO:0007829|PDB:8QFC" FT STRAND 362..364 FT /evidence="ECO:0007829|PDB:8QFC" FT HELIX 366..387 FT /evidence="ECO:0007829|PDB:8QFC" FT HELIX 479..489 FT /evidence="ECO:0007829|PDB:8QFC" FT HELIX 495..523 FT /evidence="ECO:0007829|PDB:8QFC" FT TURN 524..527 FT /evidence="ECO:0007829|PDB:8QFC" FT HELIX 528..534 FT /evidence="ECO:0007829|PDB:8QFC" FT HELIX 537..560 FT /evidence="ECO:0007829|PDB:8QFC" FT HELIX 563..593 FT /evidence="ECO:0007829|PDB:8QFC" FT HELIX 600..602 FT /evidence="ECO:0007829|PDB:8QFC" FT HELIX 605..612 FT /evidence="ECO:0007829|PDB:8QFC" FT HELIX 617..628 FT /evidence="ECO:0007829|PDB:8QFC" FT HELIX 629..631 FT /evidence="ECO:0007829|PDB:8QFC" FT HELIX 636..648 FT /evidence="ECO:0007829|PDB:8QFC" FT HELIX 658..678 FT /evidence="ECO:0007829|PDB:8QFC" FT HELIX 682..698 FT /evidence="ECO:0007829|PDB:8QFC" FT HELIX 709..716 FT /evidence="ECO:0007829|PDB:8QFC" FT TURN 717..719 FT /evidence="ECO:0007829|PDB:8QFC" FT HELIX 722..732 FT /evidence="ECO:0007829|PDB:8QFC" FT HELIX 774..785 FT /evidence="ECO:0007829|PDB:8QFC" SQ SEQUENCE 794 AA; 89595 MW; C6C1777455551991 CRC64; MADAWEEIRR LAADFQRAQF AEATQRLSER NCIEIVNKLI AQKQLEVVHT LDGKEYITPA QISKEMRDEL HVRGGRVNIV DLQQVINVDL IHIENRIGDI IKSEKHVQLV LGQLIDENYL DRLAEEVNDK LQESGQVTIS ELCKTYDLPG NFLTQALTQR LGRIISGHID LDNRGVIFTE AFVARHKARI RGLFSAITRP TAVNSLISKY GFQEQLLYSV LEELVNSGRL RGTVVGGRQD KAVFVPDIYS RTQSTWVDSF FRQNGYLEFD ALSRLGIPDA VSYIKKRYKT TQLLFLKAAC VGQGLVDQVE ASVEEAISSG TWVDIAPLLP TSLSVEDAAI LLQQVMRAFS KQASTVVFSD TVVVSEKFIN DCTELFRELM HQKAEKEMKN NPVHLITEED LKQISTLESV STSKKDKKDE RRRKATEGSG SMRGGGGGNA REYKIKKVKK KGRKDDDSDD ESQSSHTGKK KPEISFMFQD EIEDFLRKHI QDAPEEFISE LAEYLIKPLN KTYLEVVRSV FMSSTTSASG TGRKRTIKDL QEEVSNLYNN IRLFEKGMKF FADDTQAALT KHLLKSVCTD ITNLIFNFLA SDLMMAVDDP AAITSEIRKK ILSKLSEETK VALTKLHNSL NEKSIEDFIS CLDSAAEACD IMVKRGDKKR ERQILFQHRQ ALAEQLKVTE DPALILHLTS VLLFQFSTHS MLHAPGRCVP QIIAFLNSKI PEDQHALLVK YQGLVVKQLV SQSKKTGQGD YPLNNELDKE QEDVASTTRK ELQELSSSIK DLVLKSRKSS VTEE //