UFL1_HUMAN
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 03-AUG-2022, entry version 162.
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:0000312|HGNC:HGNC:23039};
GN Synonyms=KIAA0776 {ECO:0000303|PubMed:9872452},
GN MAXER {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 TRIP4, 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 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 [22]
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 [23]
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 [24]
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).
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 reticulophagy (also
CC called ER-phagy) induced in response to endoplasmic reticulum stress
CC (PubMed:20018847, PubMed:20164180, PubMed:20228063, PubMed:25219498,
CC PubMed:32160526). In response to endoplasmic reticulum stress,
CC recruited to the endoplasmic reticulum membrane by DDRGK1, and mediates
CC ufmylation of proteins such as RPN1 and RPL26/uL24, thereby promoting
CC reticulophagy of endoplasmic reticulum sheets (PubMed:32160526).
CC Ufmylation-dependent reticulophagy inhibits the unfolded protein
CC response (UPR) via ERN1/IRE1-alpha (PubMed:23152784, PubMed:32160526).
CC Ufmylation in response to endoplasmic reticulum stress is essential for
CC processes such as hematopoiesis, blood vessel morphogenesis or
CC inflammatory response (PubMed:32050156). Regulates inflammation in
CC response to endoplasmic reticulum stress by promoting reticulophagy,
CC leading to inhibit the activity of the NF-kappa-B transcription factor
CC (By similarity). Mediates ufmylation of DDRGK1 and CDK5RAP3; the role
CC of these modifications is however unclear: as both DDRGK1 and CDK5RAP3
CC act as substrate adapters for ufmylation, it is uncertain whether
CC ufmylation of these proteins is a collateral effect or is required for
CC ufmylation (PubMed:20531390, PubMed:20018847). Catalyzes ufmylation of
CC various subunits of the ribosomal complex or associated components,
CC such as RPS3/uS3, RPS20/uS10, RPL10/uL16, RPL26/uL24 and EIF6 (By
CC similarity). Anchors CDK5RAP3 in the cytoplasm, preventing its
CC translocation to the nucleus which allows expression of the CCND1
CC cyclin and progression of cells through the G1/S transition
CC (PubMed:20531390). Also involved in the response to DNA damage:
CC recruited to double-strand break sites following DNA damage and
CC mediates monoufmylation of histone H4 (PubMed:30886146). Catalyzes
CC ufmylation of TRIP4, thereby playing a role in nuclear receptor-
CC mediated transcription (PubMed:25219498). Required for hematopoietic
CC stem cell function and hematopoiesis (By similarity). Required for
CC cardiac homeostasis (By similarity). {ECO:0000250|UniProtKB:A1A4I9,
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:30886146,
CC ECO:0000269|PubMed:32050156, ECO:0000269|PubMed:32160526}.
CC -!- SUBUNIT: Interacts with DDRGK1 (via PCI domain) (PubMed:20018847,
CC PubMed:20164180, PubMed:25219498, PubMed:32160526). Interacts with UFC1
CC (PubMed:20018847, PubMed:30886146). Interacts with RELA
CC (PubMed:20164180). Interacts with TRIP4 (PubMed:25219498). Interacts
CC with CDK5RAP3; the interaction is direct (PubMed:20164180,
CC PubMed:20228063). Interacts with NBN; promoting recruitment to double-
CC strand breaks following DNA damage (PubMed:30886146).
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 -!- INTERACTION:
CC O94874; Q96JB5: CDK5RAP3; NbExp=3; IntAct=EBI-1048088, EBI-718818;
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:20018847, ECO:0000269|PubMed:20164180,
CC ECO:0000269|PubMed:20228063, ECO:0000269|PubMed:32160526}. Cytoplasm,
CC cytosol {ECO:0000269|PubMed:20228063, ECO:0000269|PubMed:30886146}.
CC Nucleus {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 {ECO:0000269|PubMed:30886146}.
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};
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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_015323.4. [O94874-1]
DR AlphaFoldDB; O94874; -.
DR BioGRID; 116953; 1032.
DR IntAct; O94874; 33.
DR MINT; O94874; -.
DR STRING; 9606.ENSP00000358283; -.
DR GlyGen; O94874; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; O94874; -.
DR MetOSite; O94874; -.
DR PhosphoSitePlus; O94874; -.
DR SwissPalm; O94874; -.
DR BioMuta; UFL1; -.
DR EPD; O94874; -.
DR jPOST; O94874; -.
DR MassIVE; O94874; -.
DR MaxQB; O94874; -.
DR PaxDb; O94874; -.
DR PeptideAtlas; O94874; -.
DR PRIDE; O94874; -.
DR ProteomicsDB; 50509; -. [O94874-1]
DR ProteomicsDB; 50510; -. [O94874-2]
DR ProteomicsDB; 50511; -. [O94874-3]
DR Antibodypedia; 31948; 113 antibodies from 21 providers.
DR DNASU; 23376; -.
DR Ensembl; ENST00000369278.5; ENSP00000358283.4; ENSG00000014123.10. [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 CTD; 23376; -.
DR DisGeNET; 23376; -.
DR GeneCards; UFL1; -.
DR HGNC; HGNC:23039; UFL1.
DR HPA; ENSG00000014123; Low tissue specificity.
DR MIM; 613372; gene.
DR neXtProt; NX_O94874; -.
DR OpenTargets; ENSG00000014123; -.
DR PharmGKB; PA134937763; -.
DR VEuPathDB; HostDB:ENSG00000014123; -.
DR eggNOG; KOG2235; Eukaryota.
DR GeneTree; ENSGT00390000002112; -.
DR HOGENOM; CLU_012417_1_0_1; -.
DR InParanoid; O94874; -.
DR OMA; NECSATK; -.
DR OrthoDB; 289380at2759; -.
DR PhylomeDB; O94874; -.
DR TreeFam; TF319116; -.
DR PathwayCommons; O94874; -.
DR Reactome; R-HSA-983168; Antigen processing: Ubiquitination & Proteasome degradation.
DR SignaLink; O94874; -.
DR SIGNOR; O94874; -.
DR BioGRID-ORCS; 23376; 287 hits in 1096 CRISPR screens.
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 210 other tissues.
DR Genevisible; O94874; HS.
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:UniProtKB.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IDA:UniProtKB.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
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:0006974; P:cellular response to DNA damage stimulus; 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:0016570; P:histone modification; IDA:UniProtKB.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IEA:Ensembl.
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: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:1990592; P:protein K69-linked ufmylation; IDA:UniProtKB.
DR GO; GO:0071569; P:protein ufmylation; IDA:UniProtKB.
DR GO; GO:0043122; P:regulation of I-kappaB kinase/NF-kappaB signaling; 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: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 InterPro; IPR018611; Ufl1.
DR PANTHER; PTHR31057; PTHR31057; 1.
DR Pfam; PF09743; E3_UFM1_ligase; 1.
PE 1: Evidence at protein level;
KW Acetylation; Alternative splicing; Chromosome; Cytoplasm; DNA damage;
KW DNA repair; Endoplasmic reticulum; Membrane; Methylation; Nucleus;
KW Phosphoprotein; Reference proteome; Transferase; Ubl conjugation;
KW 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 COMPBIAS 411..428
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 449..473
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 755..769
FT /note="Basic and acidic residues"
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 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 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 462
FT /note="S->A: Impaired recruitment to double-strand break
FT sites."
FT /evidence="ECO:0000269|PubMed:30886146"
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
