ID UFC1_HUMAN Reviewed; 167 AA. AC Q9Y3C8; A8K9R1; D3DVF9; Q549X0; Q5VTX1; Q9BS96; Q9P009; DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot. DT 17-OCT-2006, sequence version 3. DT 28-JAN-2026, entry version 201. DE RecName: Full=Ubiquitin-fold modifier-conjugating enzyme 1 {ECO:0000305}; DE Short=Ufm1-conjugating enzyme 1 {ECO:0000303|PubMed:15071506}; GN Name=UFC1 {ECO:0000303|PubMed:15071506, ECO:0000312|HGNC:HGNC:26941}; GN ORFNames=CGI-126 {ECO:0000303|PubMed:10810093}, HSPC155 GN {ECO:0000303|PubMed:11042152}; 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 [MRNA], FUNCTION, MUTAGENESIS OF CYS-116, AND ACTIVE RP SITE. RX PubMed=15071506; DOI=10.1038/sj.emboj.7600205; RA Komatsu M., Chiba T., Tatsumi K., Iemura S., Tanida I., Okazaki N., RA Ueno T., Kominami E., Natsume T., Tanaka K.; RT "A novel protein-conjugating system for Ufm1, a ubiquitin-fold modifier."; RL EMBO J. 23:1977-1986(2004). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RX PubMed=10810093; DOI=10.1101/gr.10.5.703; RA Lai C.-H., Chou C.-Y., Ch'ang L.-Y., Liu C.-S., Lin W.-C.; RT "Identification of novel human genes evolutionarily conserved in RT Caenorhabditis elegans by comparative proteomics."; RL Genome Res. 10:703-713(2000). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Umbilical cord blood; RX PubMed=11042152; DOI=10.1101/gr.140200; RA Zhang Q.-H., Ye M., Wu X.-Y., Ren S.-X., Zhao M., Zhao C.-J., Fu G., RA Shen Y., Fan H.-Y., Lu G., Zhong M., Xu X.-R., Han Z.-G., Zhang J.-W., RA Tao J., Huang Q.-H., Zhou J., Hu G.-X., Gu J., Chen S.-J., Chen Z.; RT "Cloning and functional analysis of cDNAs with open reading frames for 300 RT previously undefined genes expressed in CD34+ hematopoietic stem/progenitor RT cells."; RL Genome Res. 10:1546-1560(2000). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Trachea; 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 [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16710414; DOI=10.1038/nature04727; RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K., RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.; RT "The DNA sequence and biological annotation of human chromosome 1."; RL Nature 441:315-321(2006). RN [6] 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 [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT CYS-90. RC TISSUE=Urinary bladder; 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 [8] RP INTERACTION WITH UFL1. 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 [9] 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 [10] RP INTERACTION WITH KIRREL3. RX PubMed=25902260; DOI=10.1371/journal.pone.0123106; RA Liu Y.F., Sowell S.M., Luo Y., Chaubey A., Cameron R.S., Kim H.G., RA Srivastava A.K.; RT "Autism and intellectual disability-associated KIRREL3 interacts with RT neuronal proteins MAP1B and MYO16 with potential roles in RT neurodevelopment."; RL PLoS ONE 10:E0123106-E0123106(2015). RN [11] 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 [12] RP INTERACTION WITH UBA5. RX PubMed=27653677; DOI=10.1016/j.celrep.2016.08.067; RA Oweis W., Padala P., Hassouna F., Cohen-Kfir E., Gibbs D.R., Todd E.A., RA Berndsen C.E., Wiener R.; RT "Trans-binding mechanism of ubiquitin-like protein activation revealed by a RT UBA5-UFM1 Complex."; RL Cell Rep. 16:3113-3120(2016). RN [13] 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 [14] RP FUNCTION, INTERACTION WITH UFM1, INTERACTION WITH UBA5, MUTAGENESIS OF RP CYS-116, ACTIVE SITE, INVOLVEMENT IN NEDSG, VARIANTS NEDSG GLN-23 AND RP ILE-106, AND CHARACTERIZATION OF VARIANTS NEDSG GLN-23 AND ILE-106. RX PubMed=29868776; DOI=10.1093/brain/awy135; RA Nahorski M.S., Maddirevula S., Ishimura R., Alsahli S., Brady A.F., RA Begemann A., Mizushima T., Guzman-Vega F.J., Obata M., Ichimura Y., RA Alsaif H.S., Anazi S., Ibrahim N., Abdulwahab F., Hashem M., Monies D., RA Abouelhoda M., Meyer B.F., Alfadhel M., Eyaid W., Zweier M., Steindl K., RA Rauch A., Arold S.T., Woods C.G., Komatsu M., Alkuraya F.S.; RT "Biallelic UFM1 and UFC1 mutations expand the essential role of ufmylation RT in brain development."; RL Brain 141:1934-1945(2018). RN [15] RP INTERACTION WITH UFL1. 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 [16] 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 [17] RP FUNCTION. 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 [18] RP UFMYLATION AT LYS-122. RX PubMed=35926457; DOI=10.1016/j.celrep.2022.111168; RA Millrine D., Cummings T., Matthews S.P., Peter J.J., Magnussen H.M., RA Lange S.M., Macartney T., Lamoliatte F., Knebel A., Kulathu Y.; RT "Human UFSP1 is an active protease that regulates UFM1 maturation and RT UFMylation."; RL Cell Rep. 40:111168-111168(2022). RN [19] RP FUNCTION, MUTAGENESIS OF LYS-108, AND CHARACTERIZATION OF VARIANT NEDSG RP ILE-106. 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 [20] 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 [21] RP INTERACTION WITH UFL1, AND MUTAGENESIS OF LYS-47. 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 [22] 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 [23] RP PRELIMINARY STRUCTURE BY NMR. RX PubMed=16132835; DOI=10.1007/s10858-005-7941-9; RA Liu G., Aramini J., Atreya H.S., Eletsky A., Xiao R., Acton T., Ma L., RA Montelione G.T., Szyperski T.; RT "GFT NMR based resonance assignment for the 21 kDa human protein UFC1."; RL J. Biomol. NMR 32:261-261(2005). RN [24] RP X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS), INTERACTION WITH UBA5, AND RP MUTAGENESIS OF GLN-30 AND LYS-33. RX PubMed=17825256; DOI=10.1016/j.bbrc.2007.08.129; RA Mizushima T., Tatsumi K., Ozaki Y., Kawakami T., Suzuki A., Ogasahara K., RA Komatsu M., Kominami E., Tanaka K., Yamane T.; RT "Crystal structure of Ufc1, the Ufm1-conjugating enzyme."; RL Biochem. Biophys. Res. Commun. 362:1079-1084(2007). RN [25] RP X-RAY CRYSTALLOGRAPHY (2.54 ANGSTROMS), AND STRUCTURE BY NMR. RX PubMed=19101823; DOI=10.1007/s10969-008-9054-7; RA Liu G., Forouhar F., Eletsky A., Atreya H.S., Aramini J.M., Xiao R., RA Huang Y.J., Abashidze M., Seetharaman J., Liu J., Rost B., Acton T., RA Montelione G.T., Hunt J.F., Szyperski T.; RT "NMR and X-RAY structures of human E2-like ubiquitin-fold modifier RT conjugating enzyme 1 (UFC1) reveal structural and functional conservation RT in the metazoan UFM1-UBA5-UFC1 ubiquination pathway."; RL J. Struct. Funct. Genomics 10:127-136(2009). RN [26] {ECO:0007744|PDB:7OVC} RP STRUCTURE BY NMR. RX PubMed=34299007; DOI=10.3390/ijms22147390; RA Wesch N., Loehr F., Rogova N., Doetsch V., Rogov V.V.; RT "A concerted action of UBA5 C-terminal unstructured regions is important RT for transfer of activated UFM1 to UFC1."; RL Int. J. Mol. Sci. 22:0-0(2021). RN [27] {ECO:0007744|PDB:7NVJ, ECO:0007744|PDB:7NVK, ECO:0007744|PDB:7NW1} RP X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS) IN COMPLEX WITH UBA5, FUNCTION, RP INTERACTION WITH UBA5, ACTIVE SITE, AND MUTAGENESIS OF TYR-110 AND PHE-121. RX PubMed=34588452; DOI=10.1038/s41467-021-25994-6; RA Kumar M., Padala P., Fahoum J., Hassouna F., Tsaban T., Zoltsman G., RA Banerjee S., Cohen-Kfir E., Dessau M., Rosenzweig R., Isupov M.N., RA Schueler-Furman O., Wiener R.; RT "Structural basis for UFM1 transfer from UBA5 to UFC1."; RL Nat. Commun. 12:5708-5708(2021). RN [28] {ECO:0007744|PDB:8C0D} RP X-RAY CRYSTALLOGRAPHY (1.78 ANGSTROMS) IN COMPLEX WITH UFL1; UFM1 AND RP DDRGK1, FUNCTION, INTERACTION WITH UFL1, AND MUTAGENESIS OF LEU-32; ILE-40 RP AND ASP-50. 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). CC -!- FUNCTION: E2-like enzyme which specifically catalyzes the second step CC in ufmylation (PubMed:15071506, PubMed:29868776, PubMed:30626644, CC PubMed:34588452, PubMed:35394863, PubMed:36121123, PubMed:38383789). CC Accepts the ubiquitin-like modifier UFM1 from the E1 enzyme UBA5 and CC forms an intermediate with UFM1 via a thioester linkage CC (PubMed:15071506, PubMed:29868776, PubMed:34588452, PubMed:38383789). CC Ufmylation is involved in various processes, such as ribosome CC recycling, response to DNA damage, interferon response or reticulophagy CC (also called ER-phagy) (PubMed:27351204, PubMed:32160526, CC PubMed:35394863, PubMed:37036982, PubMed:38383789). CC {ECO:0000269|PubMed:15071506, ECO:0000269|PubMed:27351204, CC ECO:0000269|PubMed:29868776, ECO:0000269|PubMed:30626644, CC ECO:0000269|PubMed:32160526, ECO:0000269|PubMed:34588452, CC ECO:0000269|PubMed:35394863, ECO:0000269|PubMed:36121123, CC ECO:0000269|PubMed:37036982, ECO:0000269|PubMed:38383789}. CC -!- SUBUNIT: Interacts with UBA5 (via C-terminus) (PubMed:17825256, CC PubMed:27653677, PubMed:29868776, PubMed:34588452). Interacts with UFL1 CC (PubMed:20018847, PubMed:30886146, PubMed:37988244, PubMed:38383789). CC Interacts with UFM1 (PubMed:29868776). Interacts with KIRREL3 CC (PubMed:25902260). {ECO:0000269|PubMed:17825256, CC ECO:0000269|PubMed:20018847, ECO:0000269|PubMed:25902260, CC ECO:0000269|PubMed:27653677, ECO:0000269|PubMed:29868776, CC ECO:0000269|PubMed:30886146, ECO:0000269|PubMed:34588452, CC ECO:0000269|PubMed:37988244, ECO:0000269|PubMed:38383789}. CC -!- DOMAIN: In absence of UBA5, the active site is solvated by water CC molecules thereby reducing its nucleophilic activity (PubMed:34588452). CC A linker region of UBA5 is required to reduce the amount of water CC molecules in the vicinity of the active site and elevate its CC nucleophilic activity (PubMed:34588452). {ECO:0000269|PubMed:34588452}. CC -!- PTM: Ufmylated at Lys-122 (PubMed:35926457). Deufmylated by UFSP1 CC (PubMed:35926457). {ECO:0000269|PubMed:35926457}. CC -!- DISEASE: Neurodevelopmental disorder with spasticity and poor growth CC (NEDSG) [MIM:618076]: An autosomal recessive disorder apparent soon CC after birth or in early infancy. NEDSG is characterized by axial CC hypotonia, delayed psychomotor development, poor feeding, failure to CC thrive, peripheral spasticity with hyperreflexia, poor overall growth, CC and microcephaly in most patients. Additional variable features include CC contractures, facial dysmorphisms, and ocular movement abnormalities. CC {ECO:0000269|PubMed:29868776, ECO:0000269|PubMed:36121123}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- SIMILARITY: Belongs to the ubiquitin-conjugating enzyme family. UFC1 CC subfamily. {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; AB154405; BAD15374.1; -; mRNA. DR EMBL; AF151884; AAD34121.1; -; mRNA. DR EMBL; AF161504; AAF29119.1; -; mRNA. DR EMBL; AK292776; BAF85465.1; -; mRNA. DR EMBL; AL590714; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471121; EAW52646.1; -; Genomic_DNA. DR EMBL; CH471121; EAW52647.1; -; Genomic_DNA. DR EMBL; BC005187; AAH05187.1; -; mRNA. DR CCDS; CCDS1220.1; -. DR RefSeq; NP_057490.2; NM_016406.4. DR RefSeq; XP_054192944.1; XM_054336969.1. DR RefSeq; XP_054192945.1; XM_054336970.1. DR RefSeq; XP_054192946.1; XM_054336971.1. DR RefSeq; XP_054192947.1; XM_054336972.1. DR PDB; 2K07; NMR; -; A=1-167. DR PDB; 2Z6O; X-ray; 1.60 A; A=1-167. DR PDB; 2Z6P; X-ray; 1.80 A; A=1-167. DR PDB; 3EVX; X-ray; 2.54 A; A/B/C/D=1-167. DR PDB; 7NVJ; X-ray; 2.20 A; AAA=1-167. DR PDB; 7NVK; X-ray; 2.65 A; AAA=1-167. DR PDB; 7NW1; X-ray; 1.95 A; AAA/BBB=1-167. DR PDB; 7OVC; NMR; -; A=1-167. DR PDB; 8BZR; X-ray; 1.78 A; A=1-167. DR PDB; 8C0D; X-ray; 2.56 A; C/F=1-167. DR PDB; 9GLH; X-ray; 1.11 A; AAA=1-167. DR PDB; 9GLI; X-ray; 1.43 A; AAA=1-167. DR PDB; 9GLJ; X-ray; 1.21 A; AAA=1-167. DR PDB; 9GLK; X-ray; 2.03 A; AAA=1-167. DR PDB; 9GLL; X-ray; 1.65 A; AAA=1-167. DR PDB; 9GLM; X-ray; 1.79 A; AAA=1-167. DR PDB; 9GLN; X-ray; 1.92 A; AAA=1-167. DR PDB; 9GLO; X-ray; 1.53 A; AAA=1-167. DR PDB; 9GLP; X-ray; 1.77 A; AAA=1-167. DR PDB; 9GMM; X-ray; 1.35 A; AAA=1-167. DR PDB; 9GMN; X-ray; 2.00 A; AAA=1-167. DR PDB; 9GN8; X-ray; 1.96 A; AAA=1-167. DR PDB; 9I9M; X-ray; 1.54 A; AAA=1-167. DR PDB; 9I9N; X-ray; 1.88 A; AAA=1-167. DR PDB; 9I9O; X-ray; 2.05 A; AAA=1-167. DR PDB; 9I9P; X-ray; 2.02 A; AAA=1-167. DR PDB; 9IA8; X-ray; 1.90 A; AAA=1-167. DR PDBsum; 2K07; -. DR PDBsum; 2Z6O; -. DR PDBsum; 2Z6P; -. DR PDBsum; 3EVX; -. DR PDBsum; 7NVJ; -. DR PDBsum; 7NVK; -. DR PDBsum; 7NW1; -. DR PDBsum; 7OVC; -. DR PDBsum; 8BZR; -. DR PDBsum; 8C0D; -. DR PDBsum; 9GLH; -. DR PDBsum; 9GLI; -. DR PDBsum; 9GLJ; -. DR PDBsum; 9GLK; -. DR PDBsum; 9GLL; -. DR PDBsum; 9GLM; -. DR PDBsum; 9GLN; -. DR PDBsum; 9GLO; -. DR PDBsum; 9GLP; -. DR PDBsum; 9GMM; -. DR PDBsum; 9GMN; -. DR PDBsum; 9GN8; -. DR PDBsum; 9I9M; -. DR PDBsum; 9I9N; -. DR PDBsum; 9I9O; -. DR PDBsum; 9I9P; -. DR PDBsum; 9IA8; -. DR AlphaFoldDB; Q9Y3C8; -. DR BMRB; Q9Y3C8; -. DR SMR; Q9Y3C8; -. DR BioGRID; 119577; 72. DR FunCoup; Q9Y3C8; 567. DR STRING; 9606.ENSP00000356982; -. DR GlyGen; Q9Y3C8; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; Q9Y3C8; -. DR PhosphoSitePlus; Q9Y3C8; -. DR SwissPalm; Q9Y3C8; -. DR BioMuta; UFC1; -. DR DMDM; 116242840; -. DR jPOST; Q9Y3C8; -. DR MassIVE; Q9Y3C8; -. DR PaxDb; 9606-ENSP00000356982; -. DR PeptideAtlas; Q9Y3C8; -. DR ProteomicsDB; 86017; -. DR Pumba; Q9Y3C8; -. DR Antibodypedia; 34296; 225 antibodies from 28 providers. DR DNASU; 51506; -. DR Ensembl; ENST00000368003.6; ENSP00000356982.5; ENSG00000143222.13. DR GeneID; 51506; -. DR KEGG; hsa:51506; -. DR MANE-Select; ENST00000368003.6; ENSP00000356982.5; NM_016406.4; NP_057490.2. DR UCSC; uc001fyd.5; human. DR AGR; HGNC:26941; -. DR ClinPGx; PA142670644; -. DR CTD; 51506; -. DR DisGeNET; 51506; -. DR GeneCards; UFC1; -. DR HGNC; HGNC:26941; UFC1. DR HPA; ENSG00000143222; Low tissue specificity. DR MalaCards; UFC1; -. DR MIM; 610554; gene. DR MIM; 618076; phenotype. DR OpenTargets; ENSG00000143222; -. DR VEuPathDB; HostDB:ENSG00000143222; -. DR eggNOG; KOG3357; Eukaryota. DR GeneTree; ENSGT00390000008196; -. DR HOGENOM; CLU_101170_0_0_1; -. DR InParanoid; Q9Y3C8; -. DR OMA; LWQKNVP; -. DR OrthoDB; 10256182at2759; -. DR PAN-GO; Q9Y3C8; 2 GO annotations based on evolutionary models. DR PhylomeDB; Q9Y3C8; -. DR PathwayCommons; Q9Y3C8; -. DR SignaLink; Q9Y3C8; -. DR Agora; ENSG00000143222; -. DR BioGRID-ORCS; 51506; 236 hits in 1169 CRISPR screens. DR ChiTaRS; UFC1; human. DR EvolutionaryTrace; Q9Y3C8; -. DR GenomeRNAi; 51506; -. DR Pharos; Q9Y3C8; Tbio. DR PRO; PR:Q9Y3C8; -. DR Proteomes; UP000005640; Chromosome 1. DR RNAct; Q9Y3C8; protein. DR Bgee; ENSG00000143222; Expressed in bronchial epithelial cell and 208 other cell types or tissues. DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB. DR GO; GO:0061657; F:UFM1 conjugating enzyme activity; IDA:UniProtKB. DR GO; GO:0071568; F:UFM1 transferase activity; IBA:GO_Central. DR GO; GO:0007420; P:brain development; IMP:UniProtKB. DR GO; GO:1990592; P:protein K69-linked ufmylation; IDA:UniProtKB. DR GO; GO:0071569; P:protein ufmylation; IDA:UniProtKB. DR GO; GO:0032649; P:regulation of type II interferon production; ISS:UniProtKB. DR GO; GO:0034976; P:response to endoplasmic reticulum stress; IDA:MGI. DR GO; GO:0061709; P:reticulophagy; IMP:UniProtKB. DR CDD; cd11686; UBCc_UFC1; 1. DR FunFam; 3.10.110.10:FF:000042; Ubiquitin-fold modifier-conjugating enzyme 1; 1. DR Gene3D; 3.10.110.10; Ubiquitin Conjugating Enzyme; 1. DR InterPro; IPR016135; UBQ-conjugating_enzyme/RWD. DR InterPro; IPR014806; Ufc1. DR PANTHER; PTHR12921; UBIQUITIN-FOLD MODIFIER-CONJUGATING ENZYME 1; 1. DR PANTHER; PTHR12921:SF0; UBIQUITIN-FOLD MODIFIER-CONJUGATING ENZYME 1; 1. DR Pfam; PF08694; UFC1; 1. DR PIRSF; PIRSF008716; DUF1782; 1. DR SUPFAM; SSF54495; UBC-like; 1. PE 1: Evidence at protein level; KW 3D-structure; Disease variant; Isopeptide bond; Proteomics identification; KW Reference proteome; Ubl conjugation; Ubl conjugation pathway. FT CHAIN 1..167 FT /note="Ubiquitin-fold modifier-conjugating enzyme 1" FT /id="PRO_0000082613" FT ACT_SITE 116 FT /note="Glycyl thioester intermediate" FT /evidence="ECO:0000269|PubMed:15071506, FT ECO:0000269|PubMed:29868776, ECO:0000269|PubMed:34588452" FT CROSSLNK 122 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in UFM1)" FT /evidence="ECO:0000269|PubMed:35926457" FT VARIANT 23 FT /note="R -> Q (in NEDSG; decreased ability to form FT thioester bond with UFM1; decreased protein ufmylation; FT dbSNP:rs1181612302)" FT /evidence="ECO:0000269|PubMed:29868776" FT /id="VAR_081216" FT VARIANT 90 FT /note="Y -> C (in dbSNP:rs17849932)" FT /evidence="ECO:0000269|PubMed:15489334" FT /id="VAR_028312" FT VARIANT 106 FT /note="T -> I (in NEDSG; decreased ability to form FT thioester bond with UFM1; decreased protein ufmylation; FT dbSNP:rs1553232770)" FT /evidence="ECO:0000269|PubMed:29868776, FT ECO:0000269|PubMed:36121123" FT /id="VAR_081217" FT MUTAGEN 30 FT /note="Q->A: Does not affect neither UBA5-binding nor FT thioester formation with UFM1." FT /evidence="ECO:0000269|PubMed:17825256" FT MUTAGEN 32 FT /note="L->R: Abolished interaction with UFL1." FT /evidence="ECO:0000269|PubMed:38383789" FT MUTAGEN 33 FT /note="K->A: Impairs binding to UBA5 and thioester FT formation with UFM1." FT /evidence="ECO:0000269|PubMed:17825256" FT MUTAGEN 40 FT /note="I->R: Abolished interaction with UFL1." FT /evidence="ECO:0000269|PubMed:38383789" FT MUTAGEN 47 FT /note="K->E: Decreased interaction with UFL1." FT /evidence="ECO:0000269|PubMed:37988244" FT MUTAGEN 50 FT /note="D->A: Decreased ribosome ufmylation." FT /evidence="ECO:0000269|PubMed:38383789" FT MUTAGEN 108 FT /note="K->A: Abolished ufmylation." FT /evidence="ECO:0000269|PubMed:36121123" FT MUTAGEN 110 FT /note="Y->A: Decreased UFM1 transfer." FT /evidence="ECO:0000269|PubMed:34588452" FT MUTAGEN 116 FT /note="C->S: Instead of the formation of an intermediate FT complex with a thiol ester bond between UFC1 (E2-like FT enzyme) and UFM1 (substrate), a stable complex with an FT O-ester bond is formed." FT /evidence="ECO:0000269|PubMed:15071506, FT ECO:0000269|PubMed:29868776" FT MUTAGEN 121 FT /note="F->A: Decreased UFM1 transfer." FT /evidence="ECO:0000269|PubMed:34588452" FT CONFLICT 159 FT /note="I -> N (in Ref. 4; BAF85465)" FT /evidence="ECO:0000305" FT CONFLICT 160 FT /note="Q -> H (in Ref. 1; BAD15374 and 3; AAF29119)" FT /evidence="ECO:0000305" FT HELIX 2..10 FT /evidence="ECO:0007829|PDB:2Z6O" FT HELIX 22..24 FT /evidence="ECO:0007829|PDB:8BZR" FT HELIX 26..48 FT /evidence="ECO:0007829|PDB:2Z6O" FT STRAND 54..58 FT /evidence="ECO:0007829|PDB:2Z6O" FT STRAND 64..73 FT /evidence="ECO:0007829|PDB:2Z6O" FT STRAND 76..85 FT /evidence="ECO:0007829|PDB:2Z6O" FT TURN 88..92 FT /evidence="ECO:0007829|PDB:2Z6O" FT HELIX 100..102 FT /evidence="ECO:0007829|PDB:2Z6O" FT TURN 103..105 FT /evidence="ECO:0007829|PDB:2Z6O" FT STRAND 107..109 FT /evidence="ECO:0007829|PDB:2Z6O" FT STRAND 113..115 FT /evidence="ECO:0007829|PDB:2Z6O" FT HELIX 121..128 FT /evidence="ECO:0007829|PDB:2Z6O" FT HELIX 134..140 FT /evidence="ECO:0007829|PDB:2Z6O" FT HELIX 142..156 FT /evidence="ECO:0007829|PDB:2Z6O" FT STRAND 162..164 FT /evidence="ECO:0007829|PDB:2Z6O" SQ SEQUENCE 167 AA; 19458 MW; 1675D9187DC43E14 CRC64; MADEATRRVV SEIPVLKTNA GPRDRELWVQ RLKEEYQSLI RYVENNKNAD NDWFRLESNK EGTRWFGKCW YIHDLLKYEF DIEFDIPITY PTTAPEIAVP ELDGKTAKMY RGGKICLTDH FKPLWARNVP KFGLAHLMAL GLGPWLAVEI PDLIQKGVIQ HKEKCNQ //