ID UBA5_HUMAN Reviewed; 404 AA. AC Q9GZZ9; A6NJL3; D3DNC8; Q96ST1; DT 27-SEP-2005, integrated into UniProtKB/Swiss-Prot. DT 01-MAR-2001, sequence version 1. DT 28-JAN-2026, entry version 204. DE RecName: Full=Ubiquitin-like modifier-activating enzyme 5 {ECO:0000305}; DE Short=Ubiquitin-activating enzyme 5 {ECO:0000303|PubMed:15071506}; DE AltName: Full=ThiFP1 {ECO:0000303|PubMed:16328888}; DE AltName: Full=UFM1-activating enzyme {ECO:0000303|PubMed:15071506}; DE AltName: Full=Ubiquitin-activating enzyme E1 domain-containing protein 1 {ECO:0000303|PubMed:16328888}; GN Name=UBA5 {ECO:0000303|PubMed:15071506, ECO:0000312|HGNC:HGNC:23230}; GN Synonyms=UBE1DC1 {ECO:0000303|PubMed:16328888}; 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] (ISOFORM 1), FUNCTION, AND MUTAGENESIS OF RP CYS-250. 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 [MRNA] (ISOFORM 1), AND TISSUE SPECIFICITY. RX PubMed=16328888; DOI=10.1007/s11033-005-4822-y; RA Dou T., Gu S., Liu J., Chen F., Zeng L., Guo L., Xie Y., Mao Y.; RT "Isolation and characterization of ubiquitin-activating enzyme E1-domain RT containing 1, UBE1DC1."; RL Mol. Biol. Rep. 32:265-271(2005). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Testis; RX PubMed=11230166; DOI=10.1101/gr.gr1547r; RA Wiemann S., Weil B., Wellenreuther R., Gassenhuber J., Glassl S., RA Ansorge W., Boecher M., Bloecker H., Bauersachs S., Blum H., Lauber J., RA Duesterhoeft A., Beyer A., Koehrer K., Strack N., Mewes H.-W., RA Ottenwaelder B., Obermaier B., Tampe J., Heubner D., Wambutt R., Korn B., RA Klein M., Poustka A.; RT "Towards a catalog of human genes and proteins: sequencing and analysis of RT 500 novel complete protein coding human cDNAs."; RL Genome Res. 11:422-435(2001). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Colon, and Teratocarcinoma; 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=16641997; DOI=10.1038/nature04728; RA Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J., RA Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., RA Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A., RA Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L., RA Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G., RA Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W., RA Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., RA Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P., RA Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H., RA Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J., RA Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W., RA Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B., RA Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., RA Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B., RA Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H., RA Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J., RA Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X., RA Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R., RA Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A.; RT "The DNA sequence, annotation and analysis of human chromosome 3."; RL Nature 440:1194-1198(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]. RC TISSUE=Lung; 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 UFC1. 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 [9] RP FUNCTION, ALTERNATIVE SPLICING (ISOFORMS 1 AND 2), AND SUBCELLULAR RP LOCATION. RX PubMed=18442052; DOI=10.1002/jcb.21791; RA Zheng M., Gu X., Zheng D., Yang Z., Li F., Zhao J., Xie Y., Ji C., Mao Y.; RT "UBE1DC1, an ubiquitin-activating enzyme, activates two different RT ubiquitin-like proteins."; RL J. Cell. Biochem. 104:2324-2334(2008). RN [10] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [11] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-45, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Leukemic T-cell; RX PubMed=19690332; DOI=10.1126/scisignal.2000007; RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., RA Rodionov V., Han D.K.; RT "Quantitative phosphoproteomic analysis of T cell receptor signaling RT reveals system-wide modulation of protein-protein interactions."; RL Sci. Signal. 2:RA46-RA46(2009). RN [12] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-358, 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-45, AND IDENTIFICATION BY RP 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 [15] RP FUNCTION. 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 [16] RP INTERACTION WITH UFC1, AND MUTAGENESIS OF CYS-250. 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 [17] RP FUNCTION, SUBUNIT, INTERACTION WITH UFM1, AND MUTAGENESIS OF ASP-290. RX PubMed=29295865; DOI=10.1096/fj.201701057r; RA Mashahreh B., Hassouna F., Soudah N., Cohen-Kfir E., Strulovich R., RA Haitin Y., Wiener R.; RT "Trans-binding of UFM1 to UBA5 stimulates UBA5 homodimerization and ATP RT binding."; RL FASEB J. 32:2794-2802(2018). RN [18] 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 [19] 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 [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] {ECO:0007744|PDB:3GUC, ECO:0007744|PDB:3H8V} RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 57-329 IN COMPLEX WITH ATP AND RP ZINC, FUNCTION, AND ACTIVE SITE. RX PubMed=20368332; DOI=10.1074/jbc.m110.102921; RA Bacik J.P., Walker J.R., Ali M., Schimmer A.D., Dhe-Paganon S.; RT "Crystal structure of the human ubiquitin-activating enzyme 5 (UBA5) bound RT to ATP: mechanistic insights into a minimalistic E1 enzyme."; RL J. Biol. Chem. 285:20273-20280(2010). RN [22] {ECO:0007744|PDB:5IAA, ECO:0007744|PDB:5L95} RP X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS) OF 57-346 IN COMPLEX WITH UFM1; AMP RP AND ZINC, FUNCTION, CATALYTIC ACTIVITY, SUBUNIT, INTERACTION WITH UFM1 AND RP UFC1, AND MUTAGENESIS OF ARG-188; 215-HIS--GLN-217; 230-ALA--LEU-233; RP CYS-250; LYS-271 AND ASP-290. 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 [23] {ECO:0007744|PDB:5HKH} RP X-RAY CRYSTALLOGRAPHY (2.55 ANGSTROMS) OF 338-346 IN COMPLEX WITH UFM1, RP FUNCTION, INTERACTION WITH UFM1; GABARAPL2; GABARAP AND GABARAPL1, DOMAIN, RP AND MUTAGENESIS OF TRP-341; GLY-342; ILE-343; LEU-345 AND VAL-346. RX PubMed=26929408; DOI=10.1074/jbc.m116.715474; RA Habisov S., Huber J., Ichimura Y., Akutsu M., Rogova N., Loehr F., RA McEwan D.G., Johansen T., Dikic I., Doetsch V., Komatsu M., Rogov V.V., RA Kirkin V.; RT "Structural and functional analysis of a novel interaction motif within RT UFM1-activating enzyme 5 (UBA5) required for binding to ubiquitin-like RT proteins and ufmylation."; RL J. Biol. Chem. 291:9025-9041(2016). RN [24] {ECO:0007744|PDB:5IA8} RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 334-346 AND 350-350 IN COMPLEX RP WITH UFM1, INTERACTION WITH UFM1, AND MUTAGENESIS OF HIS-336 AND RP 343-ILE--LEU-345. RX PubMed=28360427; DOI=10.1038/s41598-017-00610-0; RA Padala P., Oweis W., Mashahreh B., Soudah N., Cohen-Kfir E., Todd E.A., RA Berndsen C.E., Wiener R.; RT "Novel insights into the interaction of UBA5 with UFM1 via a UFM1- RT interacting sequence."; RL Sci. Rep. 7:508-508(2017). RN [25] {ECO:0007744|PDB:6H8C} RP STRUCTURE BY NMR OF 333-348 IN COMPLEX WITH GABARAPL2, INTERACTION WITH RP GABARAPL2, AND MUTAGENESIS OF TRP-341; ILE-343; LEU-345 AND VAL-346. RX PubMed=30990354; DOI=10.1080/15548627.2019.1606637; RA Huber J., Obata M., Gruber J., Akutsu M., Lohr F., Rogova N., Guntert P., RA Dikic I., Kirkin V., Komatsu M., Dotsch V., Rogov V.V.; RT "An atypical LIR motif within UBA5 (ubiquitin like modifier activating RT enzyme 5) interacts with GABARAP proteins and mediates membrane RT localization of UBA5."; RL Autophagy 16:256-270(2020). RN [26] {ECO:0007744|PDB:6H77, ECO:0007744|PDB:6H78} RP X-RAY CRYSTALLOGRAPHY (2.10 ANGSTROMS) OF 36-346 IN COMPLEX WITH UFM1; AMP RP AND ZINC, FUNCTION, AND INTERACTION WITH UFM1. RX PubMed=30412706; DOI=10.1016/j.jmb.2018.10.007; RA Soudah N., Padala P., Hassouna F., Kumar M., Mashahreh B., Lebedev A.A., RA Isupov M.N., Cohen-Kfir E., Wiener R.; RT "An N-terminal extension to UBA5 adenylation domain boosts UFM1 activation: RT isoform-specific differences in ubiquitin-like protein activation."; RL J. Mol. Biol. 431:463-478(2019). RN [27] {ECO:0007744|PDB:7OVC} RP STRUCTURE BY NMR OF 381-404 IN COMPLEX WITH UFC1, AND INTERACTION WITH RP UFC1; GABARAP AND GABARAPL2. 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 [28] {ECO:0007744|PDB:7NVK, ECO:0007744|PDB:7NW1} RP X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS) OF 389-404 IN COMPLEX WITH UFC1, RP FUNCTION, INTERACTION WITH UFC1, DOMAIN, ACTIVE SITE, AND MUTAGENESIS OF RP CYS-250; TYR-372; LEU-397 AND MET-401. 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 [29] RP VARIANTS DEE44 VAL-57; GLU-168; MET-260; THR-371 AND TYR-389, RP CHARACTERIZATION OF VARIANTS DEE44 VAL-57; GLU-168; MET-260; THR-371 AND RP TYR-389, FUNCTION, AND INVOLVEMENT IN DEE44. RX PubMed=27545681; DOI=10.1016/j.ajhg.2016.06.030; RG FREX Consortium; RA Colin E., Daniel J., Ziegler A., Wakim J., Scrivo A., Haack T.B., RA Khiati S., Denomme A.S., Amati-Bonneau P., Charif M., Procaccio V., RA Reynier P., Aleck K.A., Botto L.D., Herper C.L., Kaiser C.S., Nabbout R., RA N'Guyen S., Mora-Lorca J.A., Assmann B., Christ S., Meitinger T., RA Strom T.M., Prokisch H., Miranda-Vizuete A., Hoffmann G.F., Lenaers G., RA Bomont P., Liebau E., Bonneau D.; RT "Biallelic variants in UBA5 reveal that disruption of the UFM1 cascade can RT result in early-onset encephalopathy."; RL Am. J. Hum. Genet. 99:695-703(2016). RN [30] RP VARIANTS SCAR24 GLU-310 AND 246-ARG--MET-404 DEL, CHARACTERIZATION OF RP VARIANTS SCAR24 GLU-310 AND 246-ARG--MET-404 DEL, INTERACTION WITH UFM1, RP SUBCELLULAR LOCATION, AND INVOLVEMENT IN SCAR24. RX PubMed=26872069; DOI=10.1371/journal.pone.0149039; RA Duan R., Shi Y., Yu L., Zhang G., Li J., Lin Y., Guo J., Wang J., Shen L., RA Jiang H., Wang G., Tang B.; RT "UBA5 mutations cause a new form of autosomal recessive cerebellar RT ataxia."; RL PLoS ONE 11:E0149039-E0149039(2016). RN [31] RP VARIANTS DEE44 HIS-55 AND THR-371, CHARACTERIZATION OF VARIANTS DEE44 RP HIS-55 AND THR-371, MUTAGENESIS OF CYS-250, AND FUNCTION. RX PubMed=27545674; DOI=10.1016/j.ajhg.2016.06.020; RG DDD Study; RA Muona M., Ishimura R., Laari A., Ichimura Y., Linnankivi T., RA Keski-Filppula R., Herva R., Rantala H., Paetau A., Poeyhoenen M., RA Obata M., Uemura T., Karhu T., Bizen N., Takebayashi H., McKee S., RA Parker M.J., Akawi N., McRae J., Hurles M.E., Kuismin O., Kurki M.I., RA Anttonen A.K., Tanaka K., Palotie A., Waguri S., Lehesjoki A.E., RA Komatsu M.; RT "Biallelic variants in UBA5 link dysfunctional UFM1 ubiquitin-like modifier RT pathway to severe infantile-onset encephalopathy."; RL Am. J. Hum. Genet. 99:683-694(2016). CC -!- FUNCTION: E1-like enzyme which specifically catalyzes the first step in CC ufmylation (PubMed:15071506, PubMed:18442052, PubMed:20368332, CC PubMed:25219498, PubMed:26929408, PubMed:27545674, PubMed:27545681, CC PubMed:27653677, PubMed:30412706, PubMed:30626644, PubMed:34588452). CC Activates UFM1 by first adenylating its C-terminal glycine residue with CC ATP, and thereafter linking this residue to the side chain of a CC cysteine residue in E1, yielding a UFM1-E1 thioester and free AMP CC (PubMed:20368332, PubMed:26929408, PubMed:27653677, PubMed:30412706). CC Activates UFM1 via a trans-binding mechanism, in which UFM1 interacts CC with distinct sites in both subunits of the UBA5 homodimer CC (PubMed:27653677). Trans-binding also promotes stabilization of the CC UBA5 homodimer, and enhances ATP-binding (PubMed:29295865). Transfer of CC UFM1 from UBA5 to the E2-like enzyme UFC1 also takes place using a CC trans mechanism (PubMed:27653677, PubMed:34588452). Ufmylation plays a CC key role in various processes, such as ribosome recycling, response to CC DNA damage, interferon response or reticulophagy (also called ER-phagy) CC (PubMed:30412706, PubMed:32160526, PubMed:35394863). Ufmylation is CC essential for erythroid differentiation of both megakaryocytes and CC erythrocytes (By similarity). {ECO:0000250|UniProtKB:Q8VE47, CC ECO:0000269|PubMed:15071506, ECO:0000269|PubMed:18442052, CC ECO:0000269|PubMed:20368332, ECO:0000269|PubMed:25219498, CC ECO:0000269|PubMed:26929408, ECO:0000269|PubMed:27545674, CC ECO:0000269|PubMed:27545681, ECO:0000269|PubMed:27653677, CC ECO:0000269|PubMed:29295865, ECO:0000269|PubMed:30412706, CC ECO:0000269|PubMed:30626644, ECO:0000269|PubMed:32160526, CC ECO:0000269|PubMed:34588452, ECO:0000269|PubMed:35394863}. CC -!- SUBUNIT: Homodimer; homodimerization is required for UFM1 activation CC (PubMed:27653677, PubMed:29295865). Interacts (via UIS motif) with CC UFM1; binds UFM1 via a trans-binding mechanism in which UFM1 interacts CC with distinct sites in both subunits of the UBA5 homodimer CC (PubMed:26872069, PubMed:26929408, PubMed:27653677, PubMed:28360427, CC PubMed:29295865, PubMed:30412706). Interacts (via C-terminus) with UFC1 CC (PubMed:17825256, PubMed:27653677, PubMed:29868776, PubMed:34299007, CC PubMed:34588452). Interacts (via UIS motif) with GABARAPL2 and, with CC lower affinity, with GABARAP and GABARAPL1 (PubMed:26929408, CC PubMed:30990354, PubMed:34299007). {ECO:0000269|PubMed:17825256, CC ECO:0000269|PubMed:26872069, ECO:0000269|PubMed:26929408, CC ECO:0000269|PubMed:27653677, ECO:0000269|PubMed:28360427, CC ECO:0000269|PubMed:29295865, ECO:0000269|PubMed:29868776, CC ECO:0000269|PubMed:30412706, ECO:0000269|PubMed:30990354, CC ECO:0000269|PubMed:34299007, ECO:0000269|PubMed:34588452}. CC -!- INTERACTION: CC Q9GZZ9; O95166: GABARAP; NbExp=2; IntAct=EBI-747805, EBI-712001; CC Q9GZZ9; Q9H0R8: GABARAPL1; NbExp=3; IntAct=EBI-747805, EBI-746969; CC Q9GZZ9; P60520: GABARAPL2; NbExp=20; IntAct=EBI-747805, EBI-720116; CC Q9GZZ9; Q9GZQ8: MAP1LC3B; NbExp=2; IntAct=EBI-747805, EBI-373144; CC Q9GZZ9; Q9BXW4: MAP1LC3C; NbExp=2; IntAct=EBI-747805, EBI-2603996; CC Q9GZZ9; P61960: UFM1; NbExp=8; IntAct=EBI-747805, EBI-1045061; CC Q9GZZ9; P10823: GPA2; Xeno; NbExp=3; IntAct=EBI-747805, EBI-7382; CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:18442052, CC ECO:0000269|PubMed:26872069}. Nucleus {ECO:0000269|PubMed:18442052}. CC Endoplasmic reticulum membrane {ECO:0000269|PubMed:30990354}. Golgi CC apparatus {ECO:0000269|PubMed:26872069}. Note=Localizes mainly in the CC cytoplasm, while it localizes to the nucleus in presence of SUMO2 CC (PubMed:18442052). Interaction with GABARAPL2 promotes localization to CC the endoplasmic reticulum membrane (PubMed:30990354). CC {ECO:0000269|PubMed:18442052, ECO:0000269|PubMed:30990354}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; Synonyms=UBE1DC1A {ECO:0000303|PubMed:18442052}; CC IsoId=Q9GZZ9-1; Sequence=Displayed; CC Name=2; Synonyms=UBE1DC1B {ECO:0000303|PubMed:18442052}; CC IsoId=Q9GZZ9-2; Sequence=VSP_038528; CC -!- TISSUE SPECIFICITY: Widely expressed. {ECO:0000269|PubMed:16328888}. CC -!- DOMAIN: The UFC1-binding sequence (UFC) motif mediates interaction with CC UFC1. {ECO:0000269|PubMed:34588452}. CC -!- DOMAIN: The linker region is required to activate the active site of CC UFC1: it region moves next to active site of UFC1 to reduce the amount CC of water molecules in the vicinity of UFC1's active site and thereby CC elevate the nucleophilic activity of UFC1 active site. CC {ECO:0000269|PubMed:34588452}. CC -!- DOMAIN: The UFM1-interacting sequence (UIS) motif mediates interaction CC with both UFM1 and LC3/GABARAP proteins (GABARAP, GABARAPL1 and CC GABARAPL2). {ECO:0000269|PubMed:26929408}. CC -!- DOMAIN: [Isoform 1]: The N-terminus (1-56) contributes to the transfer CC of UFM1 from UBA5 to UFC1. {ECO:0000269|PubMed:30412706}. CC -!- DISEASE: Developmental and epileptic encephalopathy 44 (DEE44) CC [MIM:617132]: A form of epileptic encephalopathy, a heterogeneous group CC of severe early-onset epilepsies characterized by refractory seizures, CC neurodevelopmental impairment, and poor prognosis. Development is CC normal prior to seizure onset, after which cognitive and motor delays CC become apparent. DEE44 transmission pattern is consistent with CC autosomal recessive inheritance. {ECO:0000269|PubMed:27545674, CC ECO:0000269|PubMed:27545681}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- DISEASE: Spinocerebellar ataxia, autosomal recessive, 24 (SCAR24) CC [MIM:617133]: A form of spinocerebellar ataxia, a clinically and CC genetically heterogeneous group of cerebellar disorders due to CC degeneration of the cerebellum with variable involvement of the CC brainstem and spinal cord. SCAR24 patients manifest gait instability CC and speech difficulties with onset in childhood. Clinical features CC include gait and limb ataxia, dysarthria, nystagmus, cataracts, and CC cerebellar atrophy on brain imaging. {ECO:0000269|PubMed:26872069}. CC Note=The disease is caused by variants affecting the gene represented CC in this entry. CC -!- SIMILARITY: Belongs to the ubiquitin-activating E1 family. UBA5 CC subfamily. {ECO:0000305}. CC -!- CAUTION: Was initially reported to mediate activation of SUMO2 in CC addition to UFM1 (PubMed:18442052). However, it was later shown that it CC is specific for UFM1 (By similarity). {ECO:0000250|UniProtKB:Q8VE47, CC ECO:0000269|PubMed:18442052}. 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; AB154406; BAD15375.1; -; mRNA. DR EMBL; AY253672; AAP79600.1; -; mRNA. DR EMBL; AL136757; CAB66691.1; -; mRNA. DR EMBL; AK026904; BAB15587.1; -; mRNA. DR EMBL; AK027563; BAB55199.1; -; mRNA. DR EMBL; AC020632; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471052; EAW79192.1; -; Genomic_DNA. DR EMBL; CH471052; EAW79189.1; -; Genomic_DNA. DR EMBL; CH471052; EAW79191.1; -; Genomic_DNA. DR EMBL; BC009737; AAH09737.1; -; mRNA. DR CCDS; CCDS3076.1; -. [Q9GZZ9-1] DR CCDS; CCDS3077.1; -. [Q9GZZ9-2] DR RefSeq; NP_001307139.1; NM_001320210.2. [Q9GZZ9-2] DR RefSeq; NP_001308167.1; NM_001321238.1. DR RefSeq; NP_001308168.1; NM_001321239.1. DR RefSeq; NP_079094.1; NM_024818.6. [Q9GZZ9-1] DR RefSeq; NP_938143.1; NM_198329.4. [Q9GZZ9-2] DR PDB; 3GUC; X-ray; 2.25 A; A/B=57-329. DR PDB; 3H8V; X-ray; 2.00 A; A/B=57-329. DR PDB; 5HKH; X-ray; 2.55 A; B=338-346. DR PDB; 5IA8; X-ray; 2.00 A; A/B=334-346, A/B=349-374. DR PDB; 5IAA; X-ray; 1.85 A; A/B=57-346. DR PDB; 5L95; X-ray; 2.10 A; A/B=68-346. DR PDB; 6H77; X-ray; 2.10 A; A/B/C/D=36-346. DR PDB; 6H78; X-ray; 2.70 A; A/B/C/D/E/F/G/H/I/J/K/L/M/N/O/P=36-335. DR PDB; 6H8C; NMR; -; B=333-348. DR PDB; 7NVK; X-ray; 2.65 A; AAA=347-404. DR PDB; 7NW1; X-ray; 1.95 A; CCC/FFF=389-404. DR PDB; 7OVC; NMR; -; B=381-404. DR PDBsum; 3GUC; -. DR PDBsum; 3H8V; -. DR PDBsum; 5HKH; -. DR PDBsum; 5IA8; -. DR PDBsum; 5IAA; -. DR PDBsum; 5L95; -. DR PDBsum; 6H77; -. DR PDBsum; 6H78; -. DR PDBsum; 6H8C; -. DR PDBsum; 7NVK; -. DR PDBsum; 7NW1; -. DR PDBsum; 7OVC; -. DR AlphaFoldDB; Q9GZZ9; -. DR SASBDB; Q9GZZ9; -. DR SMR; Q9GZZ9; -. DR BioGRID; 122964; 137. DR ELM; Q9GZZ9; -. DR FunCoup; Q9GZZ9; 3968. DR IntAct; Q9GZZ9; 96. DR MINT; Q9GZZ9; -. DR STRING; 9606.ENSP00000348565; -. DR ChEMBL; CHEMBL2016429; -. DR GlyGen; Q9GZZ9; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; Q9GZZ9; -. DR MetOSite; Q9GZZ9; -. DR PhosphoSitePlus; Q9GZZ9; -. DR SwissPalm; Q9GZZ9; -. DR BioMuta; UBA5; -. DR DMDM; 74733510; -. DR jPOST; Q9GZZ9; -. DR MassIVE; Q9GZZ9; -. DR PaxDb; 9606-ENSP00000348565; -. DR PeptideAtlas; Q9GZZ9; -. DR ProteomicsDB; 80189; -. [Q9GZZ9-1] DR ProteomicsDB; 80190; -. [Q9GZZ9-2] DR Pumba; Q9GZZ9; -. DR Antibodypedia; 2258; 164 antibodies from 31 providers. DR DNASU; 79876; -. DR Ensembl; ENST00000264991.8; ENSP00000264991.4; ENSG00000081307.16. [Q9GZZ9-2] DR Ensembl; ENST00000356232.10; ENSP00000348565.4; ENSG00000081307.16. [Q9GZZ9-1] DR Ensembl; ENST00000494238.6; ENSP00000418807.2; ENSG00000081307.16. [Q9GZZ9-2] DR GeneID; 79876; -. DR KEGG; hsa:79876; -. DR MANE-Select; ENST00000356232.10; ENSP00000348565.4; NM_024818.6; NP_079094.1. DR UCSC; uc003epa.5; human. [Q9GZZ9-1] DR AGR; HGNC:23230; -. DR ClinPGx; PA162407661; -. DR CTD; 79876; -. DR DisGeNET; 79876; -. DR GeneCards; UBA5; -. DR HGNC; HGNC:23230; UBA5. DR HPA; ENSG00000081307; Low tissue specificity. DR MalaCards; UBA5; -. DR MIM; 610552; gene. DR MIM; 617132; phenotype. DR MIM; 617133; phenotype. DR OpenTargets; ENSG00000081307; -. DR Orphanet; 442835; Non-specific early-onset epileptic encephalopathy. DR VEuPathDB; HostDB:ENSG00000081307; -. DR eggNOG; KOG2336; Eukaryota. DR GeneTree; ENSGT00940000156177; -. DR InParanoid; Q9GZZ9; -. DR OMA; MNIVKDY; -. DR OrthoDB; 206053at2759; -. DR PAN-GO; Q9GZZ9; 4 GO annotations based on evolutionary models. DR PhylomeDB; Q9GZZ9; -. DR BRENDA; 6.2.1.45; 2681. DR PathwayCommons; Q9GZZ9; -. DR Reactome; R-HSA-983168; Antigen processing: Ubiquitination & Proteasome degradation. DR SignaLink; Q9GZZ9; -. DR Agora; ENSG00000081307; -. DR BioGRID-ORCS; 79876; 456 hits in 1174 CRISPR screens. DR ChiTaRS; UBA5; human. DR EvolutionaryTrace; Q9GZZ9; -. DR GeneWiki; UBE1DC1; -. DR GenomeRNAi; 79876; -. DR Pharos; Q9GZZ9; Tbio. DR PRO; PR:Q9GZZ9; -. DR Proteomes; UP000005640; Chromosome 3. DR RNAct; Q9GZZ9; protein. DR Bgee; ENSG00000081307; Expressed in body of pancreas and 196 other cell types or tissues. DR ExpressionAtlas; Q9GZZ9; baseline and differential. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:0005789; C:endoplasmic reticulum membrane; IDA:UniProtKB. DR GO; GO:0005794; C:Golgi apparatus; IEA:UniProtKB-SubCell. DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB. DR GO; GO:0071566; F:UFM1 activating enzyme activity; IDA:UniProtKB. DR GO; GO:0008270; F:zinc ion binding; IDA:UniProtKB. DR GO; GO:0030218; P:erythrocyte differentiation; ISS:UniProtKB. DR GO; GO:0030219; P:megakaryocyte differentiation; ISS:UniProtKB. DR GO; GO:0050905; P:neuromuscular process; IGI:UniProtKB. DR GO; GO:1990592; P:protein K69-linked ufmylation; IDA:UniProtKB. DR GO; GO:0071569; P:protein ufmylation; IDA:UniProtKB. DR GO; GO:0033146; P:regulation of intracellular estrogen receptor signaling pathway; IMP:UniProtKB. DR GO; GO:0032649; P:regulation of type II interferon production; IEA:Ensembl. DR GO; GO:0034976; P:response to endoplasmic reticulum stress; IDA:MGI. DR GO; GO:0061709; P:reticulophagy; IMP:UniProtKB. DR CDD; cd00757; ThiF_MoeB_HesA_family; 1. DR DisProt; DP03487; -. DR FunFam; 3.40.50.720:FF:000066; Putative ubiquitin-like modifier-activating enzyme 5; 1. DR Gene3D; 3.40.50.720; NAD(P)-binding Rossmann-like Domain; 1. DR InterPro; IPR029752; D-isomer_DH_CS1. DR InterPro; IPR045886; ThiF/MoeB/HesA. DR InterPro; IPR000594; ThiF_NAD_FAD-bd. DR InterPro; IPR035985; Ubiquitin-activating_enz. DR PANTHER; PTHR10953; UBIQUITIN-ACTIVATING ENZYME E1; 1. DR PANTHER; PTHR10953:SF9; UBIQUITIN-LIKE MODIFIER-ACTIVATING ENZYME 5; 1. DR Pfam; PF00899; ThiF; 1. DR SUPFAM; SSF69572; Activating enzymes of the ubiquitin-like proteins; 1. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; ATP-binding; Cytoplasm; KW Disease variant; Endoplasmic reticulum; Epilepsy; Golgi apparatus; KW Intellectual disability; Membrane; Metal-binding; Neurodegeneration; KW Nucleotide-binding; Nucleus; Phosphoprotein; Proteomics identification; KW Reference proteome; Ubl conjugation pathway; Zinc. FT CHAIN 1..404 FT /note="Ubiquitin-like modifier-activating enzyme 5" FT /id="PRO_0000194970" FT REGION 347..377 FT /note="Linker" FT /evidence="ECO:0000269|PubMed:34588452" FT MOTIF 334..346 FT /note="UFM1-interacting sequence (UIS)" FT /evidence="ECO:0000269|PubMed:26929408, FT ECO:0000269|PubMed:27653677" FT MOTIF 389..404 FT /note="UFC1-binding sequence (UFC)" FT /evidence="ECO:0000269|PubMed:34588452" FT ACT_SITE 250 FT /note="Glycyl thioester intermediate" FT /evidence="ECO:0000269|PubMed:20368332, FT ECO:0000269|PubMed:27545674, ECO:0000269|PubMed:27653677, FT ECO:0000269|PubMed:34588452" FT BINDING 83 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000269|PubMed:20368332, FT ECO:0000269|PubMed:27653677, ECO:0000269|PubMed:30412706, FT ECO:0007744|PDB:5L95, ECO:0007744|PDB:6H77, FT ECO:0007744|PDB:6H78" FT BINDING 104 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000269|PubMed:20368332, FT ECO:0000269|PubMed:27653677, ECO:0000269|PubMed:30412706, FT ECO:0007744|PDB:5L95, ECO:0007744|PDB:6H78" FT BINDING 127 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000269|PubMed:20368332, FT ECO:0000269|PubMed:27653677, ECO:0000269|PubMed:30412706, FT ECO:0007744|PDB:5L95, ECO:0007744|PDB:6H77, FT ECO:0007744|PDB:6H78" FT BINDING 150 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000269|PubMed:20368332, FT ECO:0000269|PubMed:27653677, ECO:0000269|PubMed:30412706, FT ECO:0007744|PDB:5L95, ECO:0007744|PDB:6H77, FT ECO:0007744|PDB:6H78" FT BINDING 184 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000269|PubMed:20368332, FT ECO:0000269|PubMed:27653677, ECO:0000269|PubMed:30412706, FT ECO:0007744|PDB:5L95, ECO:0007744|PDB:6H77, FT ECO:0007744|PDB:6H78" FT BINDING 226 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000269|PubMed:20368332, FT ECO:0000269|PubMed:27653677, ECO:0000269|PubMed:30412706, FT ECO:0007744|PDB:5IAA, ECO:0007744|PDB:5L95, FT ECO:0007744|PDB:6H77, ECO:0007744|PDB:6H78" FT BINDING 229 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000269|PubMed:20368332, FT ECO:0000269|PubMed:27653677, ECO:0000269|PubMed:30412706, FT ECO:0007744|PDB:5IAA, ECO:0007744|PDB:5L95, FT ECO:0007744|PDB:6H77, ECO:0007744|PDB:6H78" FT BINDING 303 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000269|PubMed:20368332, FT ECO:0000269|PubMed:27653677, ECO:0000269|PubMed:30412706, FT ECO:0007744|PDB:5IAA, ECO:0007744|PDB:5L95, FT ECO:0007744|PDB:6H77, ECO:0007744|PDB:6H78" FT BINDING 308 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000269|PubMed:20368332, FT ECO:0000269|PubMed:27653677, ECO:0000269|PubMed:30412706, FT ECO:0007744|PDB:5IAA, ECO:0007744|PDB:5L95, FT ECO:0007744|PDB:6H77, ECO:0007744|PDB:6H78" FT MOD_RES 45 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:19690332, FT ECO:0007744|PubMed:23186163" FT MOD_RES 358 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:20068231" FT MOD_RES 393 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q8VE47" FT VAR_SEQ 1..56 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000305" FT /id="VSP_038528" FT VARIANT 55 FT /note="R -> H (in DEE44; reduces UFM1 activating enzyme FT activity; dbSNP:rs774318611)" FT /evidence="ECO:0000269|PubMed:27545674" FT /id="VAR_077153" FT VARIANT 57 FT /note="M -> V (in DEE44; reduces UFM1 activating enzyme FT activity; reduces UFM1-DDRGK1 formation; FT dbSNP:rs532178791)" FT /evidence="ECO:0000269|PubMed:27545681" FT /id="VAR_077154" FT VARIANT 168 FT /note="G -> E (in DEE44; abolishes UFM1 activating enzyme FT activity; dbSNP:rs886039761)" FT /evidence="ECO:0000269|PubMed:27545681" FT /id="VAR_077155" FT VARIANT 246..404 FT /note="Missing (in SCAR24; delocalizes protein to the FT nucleus; activates degradation through the ubiquitin FT proteasome pathway; decreases protein stability; disrupts FT interaction with UFM1)" FT /evidence="ECO:0000269|PubMed:26872069" FT /id="VAR_080409" FT VARIANT 260 FT /note="V -> M (in DEE44; reduces UFM1 activating enzyme FT activity; dbSNP:rs886039759)" FT /evidence="ECO:0000269|PubMed:27545681" FT /id="VAR_077156" FT VARIANT 310 FT /note="K -> E (in SCAR24; does not affect cytoplasm FT localization; decreases protein stability; does not affect FT interaction with UFM1; dbSNP:rs886039762)" FT /evidence="ECO:0000269|PubMed:26872069" FT /id="VAR_077157" FT VARIANT 371 FT /note="A -> T (in DEE44; reduces UFM1 activating enzyme FT activity; reduces UFM1 activating enzyme activity; reduces FT UFM1-DDRGK1 formation; dbSNP:rs114925667)" FT /evidence="ECO:0000269|PubMed:27545674, FT ECO:0000269|PubMed:27545681" FT /id="VAR_077158" FT VARIANT 389 FT /note="D -> Y (in DEE44; no effect on UFM1 activating FT enzyme activity; dbSNP:rs886039760)" FT /evidence="ECO:0000269|PubMed:27545681" FT /id="VAR_077159" FT MUTAGEN 188 FT /note="R->A: Abolished ability to activate UFM1." FT /evidence="ECO:0000269|PubMed:27653677" FT MUTAGEN 215..217 FT /note="HIQ->AQA: Abolished ability to activate UFM1." FT /evidence="ECO:0000269|PubMed:27653677" FT MUTAGEN 230..233 FT /note="APPL->RPPA,FPPA: Abolished interaction with UFM1." FT /evidence="ECO:0000269|PubMed:27653677" FT MUTAGEN 250 FT /note="C->A: Abolished ability to activate UFM1." FT /evidence="ECO:0000269|PubMed:27653677, FT ECO:0000269|PubMed:34588452" FT MUTAGEN 250 FT /note="C->S: Forms a stable intermediate complex." FT /evidence="ECO:0000269|PubMed:15071506, FT ECO:0000269|PubMed:27545674, ECO:0000269|PubMed:29868776" FT MUTAGEN 271 FT /note="K->D: Impaired ability to activate UFM1 via a FT trans-binding mechanism." FT /evidence="ECO:0000269|PubMed:27653677" FT MUTAGEN 290 FT /note="D->K: Impaired homodimerization and ability to FT activate UFM1 via a trans-binding mechanism." FT /evidence="ECO:0000269|PubMed:27653677, FT ECO:0000269|PubMed:29295865" FT MUTAGEN 336 FT /note="H->A,D: Impaired ability to activate UFM1." FT /evidence="ECO:0000269|PubMed:28360427" FT MUTAGEN 341 FT /note="W->A: Abolished interaction with UFM1 and FT GABARAPL2." FT /evidence="ECO:0000269|PubMed:26929408, FT ECO:0000269|PubMed:30990354" FT MUTAGEN 342 FT /note="G->A: Decreased interaction with UFM1 without FT affecting interaction with GABARAPL2." FT /evidence="ECO:0000269|PubMed:26929408" FT MUTAGEN 343..345 FT /note="IEL->AEA: Impaired ability to activate UFM1." FT /evidence="ECO:0000269|PubMed:28360427" FT MUTAGEN 343 FT /note="I->A: Abolished interaction with UFM1 and decreased FT interaction with GABARAPL2." FT /evidence="ECO:0000269|PubMed:26929408, FT ECO:0000269|PubMed:30990354" FT MUTAGEN 345 FT /note="L->A: Abolished interaction with UFM1 and decreased FT interaction with GABARAPL2." FT /evidence="ECO:0000269|PubMed:26929408, FT ECO:0000269|PubMed:30990354" FT MUTAGEN 346 FT /note="V->A: Abolished interaction with UFM1 and decreased FT interaction with GABARAPL2." FT /evidence="ECO:0000269|PubMed:26929408, FT ECO:0000269|PubMed:30990354" FT MUTAGEN 372 FT /note="Y->A,E: Strongly decreased ability to transfer UFM1 FT to UFC1." FT /evidence="ECO:0000269|PubMed:34588452" FT MUTAGEN 372 FT /note="Y->F: Does not affect ability to transfer UFM1 to FT UFC1." FT /evidence="ECO:0000269|PubMed:34588452" FT MUTAGEN 397 FT /note="L->R: Abolished interaction with UFC1." FT /evidence="ECO:0000269|PubMed:34588452" FT MUTAGEN 401 FT /note="M->R: Abolished interaction with UFC1." FT /evidence="ECO:0000269|PubMed:34588452" FT CONFLICT 403 FT /note="N -> S (in Ref. 4; BAB55199)" FT /evidence="ECO:0000305" FT HELIX 54..61 FT /evidence="ECO:0007829|PDB:6H77" FT HELIX 70..73 FT /evidence="ECO:0007829|PDB:3H8V" FT STRAND 75..79 FT /evidence="ECO:0007829|PDB:3H8V" FT HELIX 83..95 FT /evidence="ECO:0007829|PDB:3H8V" FT STRAND 98..103 FT /evidence="ECO:0007829|PDB:3H8V" FT HELIX 110..112 FT /evidence="ECO:0007829|PDB:6H77" FT STRAND 115..117 FT /evidence="ECO:0007829|PDB:6H77" FT HELIX 120..122 FT /evidence="ECO:0007829|PDB:6H77" FT HELIX 127..138 FT /evidence="ECO:0007829|PDB:3H8V" FT STRAND 142..147 FT /evidence="ECO:0007829|PDB:3H8V" FT HELIX 154..166 FT /evidence="ECO:0007829|PDB:3H8V" FT STRAND 167..170 FT /evidence="ECO:0007829|PDB:3H8V" FT STRAND 176..180 FT /evidence="ECO:0007829|PDB:3H8V" FT HELIX 185..198 FT /evidence="ECO:0007829|PDB:3H8V" FT STRAND 202..207 FT /evidence="ECO:0007829|PDB:3H8V" FT STRAND 211..219 FT /evidence="ECO:0007829|PDB:3H8V" FT TURN 221..223 FT /evidence="ECO:0007829|PDB:3H8V" FT STRAND 229..231 FT /evidence="ECO:0007829|PDB:3H8V" FT HELIX 233..236 FT /evidence="ECO:0007829|PDB:6H77" FT HELIX 241..244 FT /evidence="ECO:0007829|PDB:6H77" FT HELIX 247..274 FT /evidence="ECO:0007829|PDB:3H8V" FT STRAND 281..286 FT /evidence="ECO:0007829|PDB:3H8V" FT TURN 287..290 FT /evidence="ECO:0007829|PDB:3H8V" FT HELIX 306..317 FT /evidence="ECO:0007829|PDB:3H8V" FT STRAND 342..345 FT /evidence="ECO:0007829|PDB:6H8C" FT STRAND 382..384 FT /evidence="ECO:0007829|PDB:7OVC" FT HELIX 394..404 FT /evidence="ECO:0007829|PDB:7OVC" SQ SEQUENCE 404 AA; 44863 MW; 02F0F64FEAA1E880 CRC64; MAESVERLQQ RVQELERELA QERSLQVPRS GDGGGGRVRI EKMSSEVVDS NPYSRLMALK RMGIVSDYEK IRTFAVAIVG VGGVGSVTAE MLTRCGIGKL LLFDYDKVEL ANMNRLFFQP HQAGLSKVQA AEHTLRNINP DVLFEVHNYN ITTVENFQHF MDRISNGGLE EGKPVDLVLS CVDNFEARMT INTACNELGQ TWMESGVSEN AVSGHIQLII PGESACFACA PPLVVAANID EKTLKREGVC AASLPTTMGV VAGILVQNVL KFLLNFGTVS FYLGYNAMQD FFPTMSMKPN PQCDDRNCRK QQEEYKKKVA ALPKQEVIQE EEEIIHEDNE WGIELVSEVS EEELKNFSGP VPDLPEGITV AYTIPKKQED SVTELTVEDS GESLEDLMAK MKNM //