UFL1_MOUSE
ID UFL1_MOUSE Reviewed; 793 AA.
AC Q8CCJ3; A2RSP7; B1AXU5; B1AXU6; Q3V145; Q6ZQ50; Q8BT70; Q8C484; Q9D8I8;
DT 21-JUN-2005, integrated into UniProtKB/Swiss-Prot.
DT 21-JUN-2005, sequence version 2.
DT 03-AUG-2022, entry version 138.
DE RecName: Full=E3 UFM1-protein ligase 1 {ECO:0000305};
DE EC=2.3.2.- {ECO:0000250|UniProtKB:O94874};
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=Regulator of C53/LZAP and DDRGK1 {ECO:0000303|PubMed:25952549};
GN Name=Ufl1 {ECO:0000303|PubMed:25952549, ECO:0000312|MGI:MGI:1914740};
GN Synonyms=Kiaa0776 {ECO:0000303|PubMed:14621295},
GN Maxer {ECO:0000303|PubMed:20531390}, Rcad {ECO:0000303|PubMed:25952549};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3).
RC STRAIN=C57BL/6J; TISSUE=Cerebellum, Embryo, Pancreas, and Testis;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Embryonic tail;
RX PubMed=14621295; DOI=10.1093/dnares/10.4.167;
RA Okazaki N., Kikuno R., Ohara R., Inamoto S., Koseki H., Hiraoka S.,
RA Saga Y., Nagase T., Ohara O., Koga H.;
RT "Prediction of the coding sequences of mouse homologues of KIAA gene: III.
RT The complete nucleotide sequences of 500 mouse KIAA-homologous cDNAs
RT identified by screening of terminal sequences of cDNA clones randomly
RT sampled from size-fractionated libraries.";
RL DNA Res. 10:167-180(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
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=Liver;
RX PubMed=17208939; DOI=10.1074/mcp.m600218-mcp200;
RA Lee J., Xu Y., Chen Y., Sprung R., Kim S.C., Xie S., Zhao Y.;
RT "Mitochondrial phosphoproteome revealed by an improved IMAC method and
RT MS/MS/MS.";
RL Mol. Cell. Proteomics 6:669-676(2007).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-752 AND SER-753, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=17242355; DOI=10.1073/pnas.0609836104;
RA Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.;
RT "Large-scale phosphorylation analysis of mouse liver.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Heart, Kidney, Liver, Lung, Pancreas, Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [9]
RP TISSUE SPECIFICITY.
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 [10]
RP TISSUE SPECIFICITY.
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 [11]
RP INTERACTION WITH CDK5RAP3, AND TISSUE SPECIFICITY.
RX PubMed=21494687; DOI=10.1371/journal.pone.0018517;
RA Lemaire K., Moura R.F., Granvik M., Igoillo-Esteve M., Hohmeier H.E.,
RA Hendrickx N., Newgard C.B., Waelkens E., Cnop M., Schuit F.;
RT "Ubiquitin fold modifier 1 (UFM1) and its target UFBP1 protect pancreatic
RT beta cells from ER stress-induced apoptosis.";
RL PLoS ONE 6:E18517-E18517(2011).
RN [12]
RP METHYLATION [LARGE SCALE ANALYSIS] AT ARG-433, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain;
RX PubMed=24129315; DOI=10.1074/mcp.o113.027870;
RA Guo A., Gu H., Zhou J., Mulhern D., Wang Y., Lee K.A., Yang V., Aguiar M.,
RA Kornhauser J., Jia X., Ren J., Beausoleil S.A., Silva J.C., Vemulapalli V.,
RA Bedford M.T., Comb M.J.;
RT "Immunoaffinity enrichment and mass spectrometry analysis of protein
RT methylation.";
RL Mol. Cell. Proteomics 13:372-387(2014).
RN [13]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=25952549; DOI=10.1038/cdd.2015.51;
RA Zhang M., Zhu X., Zhang Y., Cai Y., Chen J., Sivaprakasam S., Gurav A.,
RA Pi W., Makala L., Wu J., Pace B., Tuan-Lo D., Ganapathy V., Singh N.,
RA Li H.;
RT "RCAD/Ufl1, a Ufm1 E3 ligase, is essential for hematopoietic stem cell
RT function and murine hematopoiesis.";
RL Cell Death Differ. 22:1922-1934(2015).
RN [14]
RP FUNCTION.
RX PubMed=28575669; DOI=10.1016/j.cell.2017.05.022;
RA Simsek D., Tiu G.C., Flynn R.A., Byeon G.W., Leppek K., Xu A.F.,
RA Chang H.Y., Barna M.;
RT "The mammalian ribo-interactome reveals ribosome functional diversity and
RT heterogeneity.";
RL Cell 169:1051-1065(2017).
RN [15]
RP FUNCTION, TISSUE SPECIFICITY, INDUCTION, AND DISRUPTION PHENOTYPE.
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 [16]
RP FUNCTION.
RX PubMed=29461087; DOI=10.1089/dna.2017.4073;
RA Su M., Yue Z., Wang H., Jia M., Bai C., Qiu W., Chen J.;
RT "Ufmylation is activated in vascular remodeling and lipopolysaccharide-
RT induced endothelial cell injury.";
RL DNA Cell Biol. 37:426-431(2018).
RN [17]
RP FUNCTION, TISSUE SPECIFICITY, AND DISRUPTION PHENOTYPE.
RX PubMed=30701081; DOI=10.1038/s41421-018-0070-x;
RA Cai Y., Zhu G., Liu S., Pan Z., Quintero M., Poole C.J., Lu C., Zhu H.,
RA Islam B., Riggelen J.V., Browning D., Liu K., Blumberg R., Singh N., Li H.;
RT "Indispensable role of the ubiquitin-fold modifier 1-specific E3 ligase in
RT maintaining intestinal homeostasis and controlling gut inflammation.";
RL Cell Discov. 5:7-7(2019).
RN [18]
RP INTERACTION WITH CDK5RAP3.
RX PubMed=30635284; DOI=10.1242/dev.169235;
RA Yang R., Wang H., Kang B., Chen B., Shi Y., Yang S., Sun L., Liu Y.,
RA Xiao W., Zhang T., Yang J., Zhang Y., Zhu M., Xu P., Chang Y., Jia Y.,
RA Huang Y.;
RT "CDK5RAP3, a UFL1 substrate adaptor, is crucial for liver development.";
RL Development 146:0-0(2019).
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 (By similarity). In response to endoplasmic reticulum stress, recruited
CC 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 (By similarity).
CC Ufmylation-dependent reticulophagy inhibits the unfolded protein
CC response (UPR) via ERN1/IRE1-alpha (By similarity). Ufmylation in
CC response to endoplasmic reticulum stress is essential for processes
CC such as hematopoiesis, blood vessel morphogenesis or inflammatory
CC response (PubMed:25952549, PubMed:29461087, PubMed:30701081). Regulates
CC inflammation in response to endoplasmic reticulum stress by promoting
CC reticulophagy, leading to inhibit the activity of the NF-kappa-B
CC transcription factor (By similarity). Mediates ufmylation of DDRGK1 and
CC CDK5RAP3; the role of these modifications is however unclear: as both
CC DDRGK1 and CDK5RAP3 act as substrate adapters for ufmylation, it is
CC uncertain whether ufmylation of these proteins is a collateral effect
CC or is required for ufmylation (By similarity). 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
CC (PubMed:28575669). 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 (By
CC similarity). Also involved in the response to DNA damage: recruited to
CC double-strand break sites following DNA damage and mediates
CC monoufmylation of histone H4 (By similarity). Catalyzes ufmylation of
CC TRIP4, thereby playing a role in nuclear receptor-mediated
CC transcription (By similarity). Required for hematopoietic stem cell
CC function and hematopoiesis (PubMed:25952549). Required for cardiac
CC homeostasis (PubMed:30354401). {ECO:0000250|UniProtKB:A1A4I9,
CC ECO:0000250|UniProtKB:O94874, ECO:0000269|PubMed:25952549,
CC ECO:0000269|PubMed:28575669, ECO:0000269|PubMed:29461087,
CC ECO:0000269|PubMed:30354401, ECO:0000269|PubMed:30701081}.
CC -!- SUBUNIT: Interacts with DDRGK1 (via PCI domain) (By similarity).
CC Interacts with UFC1 (By similarity). Interacts with RELA (By
CC similarity). Interacts with TRIP4 (By similarity). Interacts with
CC CDK5RAP3; the interaction is direct (PubMed:21494687, PubMed:30635284).
CC Interacts with NBN; promoting recruitment to double-strand breaks
CC following DNA damage (By similarity). {ECO:0000250|UniProtKB:O94874,
CC ECO:0000269|PubMed:21494687, ECO:0000269|PubMed:30635284}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:O94874}. Cytoplasm, cytosol
CC {ECO:0000250|UniProtKB:O94874}. Nucleus {ECO:0000250|UniProtKB:O94874}.
CC Chromosome {ECO:0000250|UniProtKB:O94874}. Note=Recruited to double-
CC strand breaks by the MRE11-RAD50-NBN (MRN) complex following DNA
CC damage. {ECO:0000250|UniProtKB:O94874}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q8CCJ3-3; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8CCJ3-1; Sequence=VSP_014250, VSP_014251;
CC Name=3;
CC IsoId=Q8CCJ3-2; Sequence=VSP_014249;
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed with higher expression in
CC pancreatic islets and other secretory tissues (PubMed:20228063,
CC PubMed:21494687). In the embryonic brain at 17 dpc, detected in Sox2-
CC positive neural stem cells and in Slc1a3/GLAST-positive radial glia
CC (PubMed:20531390). In perinatal brain, highly expressed in Slc1a3-
CC positive Bergmann glia of the cerebellum (PubMed:20531390). Continues
CC to be expressed in Bergmann glia of adult brain at 16 weeks
CC (PubMed:20531390). Expressed in adult heart (PubMed:30354401). Highly
CC expressed in the intestinal exocrine cells (PubMed:30701081).
CC {ECO:0000269|PubMed:20228063, ECO:0000269|PubMed:20531390,
CC ECO:0000269|PubMed:21494687, ECO:0000269|PubMed:30354401,
CC ECO:0000269|PubMed:30701081}.
CC -!- INDUCTION: Up-regulated in hypertrophic hearts (at protein level).
CC {ECO:0000269|PubMed:30354401}.
CC -!- PTM: Ubiquitinated, leading to its degradation by the proteasome.
CC Interaction with CDK5RAP3 protects both proteins against ubiquitination
CC and degradation via the proteasome. {ECO:0000250|UniProtKB:O94874}.
CC -!- PTM: Phosphorylated at Ser-462 by ATM, enhancing protein ligase
CC activity and promoting ATM activation in a positive feedback loop.
CC {ECO:0000250|UniProtKB:O94874}.
CC -!- DISRUPTION PHENOTYPE: Embryonic lethality caused by impaired erythroid
CC development (PubMed:25952549). Conditional deletion in adult mice
CC results in severe anemia and cytopenia (PubMed:25952549). Cells show
CC elevated endoplasmic reticulum stress and unfolded protein response in
CC bone marrow cells and impaired autophagic degradation
CC (PubMed:25952549). Conditional knockout in cardiomyocytes causes age-
CC dependent cardiomyopathy and heart failure, characterized by elevated
CC cardiac fetal gene expression, increased fibrosis, and impaired cardiac
CC contractility (PubMed:30354401). When challenged with pressure
CC overload, cardiac-specific knockout mice display greater hypertrophy,
CC exacerbated fibrosis, and worsened cardiac contractility compared to
CC wild-type mice counterparts (PubMed:30354401). Conditional knockout in
CC adults causes a significant loss of both Paneth and goblet cells in
CC intestine, which in turn results in dysbiotic microbiota and increased
CC susceptibility to experimentally induced colitis (PubMed:30701081).
CC {ECO:0000269|PubMed:25952549, ECO:0000269|PubMed:30354401,
CC ECO:0000269|PubMed:30701081}.
CC -!- SIMILARITY: Belongs to the UFL1 family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAC98021.1; 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; AK007993; BAB25395.1; -; mRNA.
DR EMBL; AK013382; BAC25404.1; -; mRNA.
DR EMBL; AK032663; BAC27976.1; -; mRNA.
DR EMBL; AK082785; BAC38618.1; -; mRNA.
DR EMBL; AK129211; BAC98021.1; ALT_INIT; mRNA.
DR EMBL; AK132697; BAE21308.1; -; mRNA.
DR EMBL; AL831754; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL935267; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH466538; EDL05527.1; -; Genomic_DNA.
DR EMBL; BC138153; AAI38154.1; -; mRNA.
DR EMBL; BC132195; AAI32196.1; -; mRNA.
DR CCDS; CCDS18010.1; -. [Q8CCJ3-3]
DR RefSeq; NP_080470.2; NM_026194.4. [Q8CCJ3-3]
DR RefSeq; XP_006538266.1; XM_006538203.3.
DR AlphaFoldDB; Q8CCJ3; -.
DR BioGRID; 212226; 61.
DR IntAct; Q8CCJ3; 60.
DR MINT; Q8CCJ3; -.
DR STRING; 10090.ENSMUSP00000100059; -.
DR iPTMnet; Q8CCJ3; -.
DR PhosphoSitePlus; Q8CCJ3; -.
DR EPD; Q8CCJ3; -.
DR jPOST; Q8CCJ3; -.
DR MaxQB; Q8CCJ3; -.
DR PaxDb; Q8CCJ3; -.
DR PeptideAtlas; Q8CCJ3; -.
DR PRIDE; Q8CCJ3; -.
DR ProteomicsDB; 297806; -. [Q8CCJ3-3]
DR ProteomicsDB; 297807; -. [Q8CCJ3-1]
DR ProteomicsDB; 297808; -. [Q8CCJ3-2]
DR Antibodypedia; 31948; 113 antibodies from 21 providers.
DR Ensembl; ENSMUST00000038705; ENSMUSP00000042118; ENSMUSG00000040359. [Q8CCJ3-1]
DR Ensembl; ENSMUST00000102994; ENSMUSP00000100059; ENSMUSG00000040359. [Q8CCJ3-3]
DR GeneID; 67490; -.
DR KEGG; mmu:67490; -.
DR UCSC; uc008seg.2; mouse. [Q8CCJ3-3]
DR UCSC; uc012dbb.1; mouse. [Q8CCJ3-1]
DR CTD; 23376; -.
DR MGI; MGI:1914740; Ufl1.
DR VEuPathDB; HostDB:ENSMUSG00000040359; -.
DR eggNOG; KOG2235; Eukaryota.
DR GeneTree; ENSGT00390000002112; -.
DR HOGENOM; CLU_012417_1_0_1; -.
DR InParanoid; Q8CCJ3; -.
DR OMA; NECSATK; -.
DR OrthoDB; 289380at2759; -.
DR PhylomeDB; Q8CCJ3; -.
DR TreeFam; TF319116; -.
DR Reactome; R-MMU-983168; Antigen processing: Ubiquitination & Proteasome degradation.
DR BioGRID-ORCS; 67490; 25 hits in 76 CRISPR screens.
DR ChiTaRS; Cdh4; mouse.
DR PRO; PR:Q8CCJ3; -.
DR Proteomes; UP000000589; Chromosome 4.
DR RNAct; Q8CCJ3; protein.
DR Bgee; ENSMUSG00000040359; Expressed in spermatocyte and 227 other tissues.
DR Genevisible; Q8CCJ3; MM.
DR GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR GO; GO:0005829; C:cytosol; IEA:UniProtKB-SubCell.
DR GO; GO:0005783; C:endoplasmic reticulum; ISS:UniProtKB.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; ISS:UniProtKB.
DR GO; GO:0043005; C:neuron projection; IDA:MGI.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0032991; C:protein-containing complex; ISO:MGI.
DR GO; GO:0035861; C:site of double-strand break; ISS:UniProtKB.
DR GO; GO:0019901; F:protein kinase binding; ISO:MGI.
DR GO; GO:0061666; F:UFM1 ligase activity; ISS:UniProtKB.
DR GO; GO:0071568; F:UFM1 transferase activity; IBA:GO_Central.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; ISS:UniProtKB.
DR GO; GO:0006281; P:DNA repair; IEA:UniProtKB-KW.
DR GO; GO:0030218; P:erythrocyte differentiation; IMP:UniProtKB.
DR GO; GO:0060218; P:hematopoietic stem cell differentiation; IMP:UniProtKB.
DR GO; GO:0016570; P:histone modification; ISS:UniProtKB.
DR GO; GO:0043066; P:negative regulation of apoptotic process; ISO:MGI.
DR GO; GO:1903895; P:negative regulation of IRE1-mediated unfolded protein response; ISS:UniProtKB.
DR GO; GO:0032088; P:negative regulation of NF-kappaB transcription factor activity; ISS:UniProtKB.
DR GO; GO:0031397; P:negative regulation of protein ubiquitination; ISS:UniProtKB.
DR GO; GO:0010508; P:positive regulation of autophagy; IMP:UniProtKB.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; ISO:MGI.
DR GO; GO:0060252; P:positive regulation of glial cell proliferation; IDA:MGI.
DR GO; GO:0032092; P:positive regulation of protein binding; TAS:ParkinsonsUK-UCL.
DR GO; GO:1990592; P:protein K69-linked ufmylation; ISS:UniProtKB.
DR GO; GO:0071569; P:protein ufmylation; ISS:UniProtKB.
DR GO; GO:0010468; P:regulation of gene expression; IMP:MGI.
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; ISS:UniProtKB.
DR GO; GO:0032434; P:regulation of proteasomal ubiquitin-dependent protein catabolic process; ISO:MGI.
DR GO; GO:0032880; P:regulation of protein localization; ISO:MGI.
DR GO; GO:0034976; P:response to endoplasmic reticulum stress; IMP:UniProtKB.
DR GO; GO:1902065; P:response to L-glutamate; IMP:MGI.
DR GO; GO:0061709; P:reticulophagy; ISS: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:0000250|UniProtKB:O94874"
FT CHAIN 2..793
FT /note="E3 UFM1-protein ligase 1"
FT /id="PRO_0000050772"
FT REGION 2..212
FT /note="Required for E3 UFM1-protein ligase activity"
FT /evidence="ECO:0000250|UniProtKB:O94874"
FT REGION 2..200
FT /note="Mediates interaction with DDRGK1"
FT /evidence="ECO:0000250|UniProtKB:O94874"
FT REGION 121..250
FT /note="Involved in CDK5RAP3-binding"
FT /evidence="ECO:0000250|UniProtKB:O94874"
FT REGION 200..400
FT /note="Mediates interaction with TRIP4"
FT /evidence="ECO:0000250|UniProtKB:O94874"
FT REGION 410..473
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 490..683
FT /note="Mediates interaction with CDK5RAP3"
FT /evidence="ECO:0000250|UniProtKB:B2GV24"
FT REGION 742..765
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 748..765
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0000250|UniProtKB:O94874"
FT MOD_RES 433
FT /note="Omega-N-methylarginine"
FT /evidence="ECO:0007744|PubMed:24129315"
FT MOD_RES 458
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17208939"
FT MOD_RES 462
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O94874"
FT MOD_RES 752
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17242355"
FT MOD_RES 753
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17242355"
FT VAR_SEQ 1..476
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_014249"
FT VAR_SEQ 1..80
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14621295"
FT /id="VSP_014250"
FT VAR_SEQ 81..84
FT /note="DLQQ -> MSEV (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14621295"
FT /id="VSP_014251"
FT CONFLICT 122
FT /note="Q -> R (in Ref. 2; BAC98021 and 5; AAI38154/
FT AAI32196)"
FT /evidence="ECO:0000305"
FT CONFLICT 389
FT /note="K -> N (in Ref. 1; BAC27976)"
FT /evidence="ECO:0000305"
FT CONFLICT 408
FT /note="E -> G (in Ref. 1; BAB25395)"
FT /evidence="ECO:0000305"
FT CONFLICT 409
FT /note="S -> C (in Ref. 1; BAC38618)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 793 AA; 89520 MW; 182930A83D1F7155 CRC64;
MADAWEEIRR LAADFQRAQF AESTQRLSER NCIEIVNKLI SQKQLEVVHT LDGKEYITPA
QISKEMRDEL HVRGGRVNIV DLQQVINVDL THIESRVSDI IKSEKHVQMV LGQLIDENYL
DQLSEEVNDK LQESGQVTVS ELCKAYDLPG DFLTQALTQR LGRIINGHLD LDNRGVIFTE
AFVARHKARI RGLFSAITRP TPVNSLVSKY GFQEQLLYSV LEDLVSTGRL RGTVVGGRQD
KAVFVPDIYS RTQSTWVDSF FRQNGYLEFD ALSRLGIPDA VNYIKKRYKN TQLLFLKATC
VGQGLVDQVE ASVEEAISSG TWVDISPLLP SSLSVEDAAM LLQQVMRPFG KLASAIVFSD
TVVVSEKFIT DCTGLFSERM HQKAEKEMKN NPVHLITEED LKQISILESV NTSKKDKKDE
RRKKATEGSG SVRGGGGGNA REYKIKKTKK KGRKDEDSDD ESQSSHGGKK KPDITFMFQD
EIEDCLRKHI QDAPEEFISE LAEYLIKPLN KMYLEVVRSV FMSSTSASGT GRKRTIKDLQ
EEVSNLYNNI RLFEKGMKYF ADDTQTALTK HLLKTVCTDI TNLMFNFLAS DFLMAVEEPA
AITSDIRKKI LSKLTEETKV ALTKLHNSLN EKSIEDFLSC LDSATEACDI MVKKGDKKRE
RQILFQHRQA LCEQLKVTED PALILHLTAV LLFQLSTHSM LHAPGRCVPQ IIAFLHSKIP
EDQHTLLVKY QGLVVKQLVS QNKKTGQGED PSSDELDKEQ HDVTNATRKE LQELSLSIKD
LVLKSRKSSV TEE
