ID EI2BE_HUMAN Reviewed; 721 AA. AC Q13144; Q541Z1; Q96D04; DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot. DT 23-OCT-2007, sequence version 3. DT 27-MAR-2024, entry version 215. DE RecName: Full=Translation initiation factor eIF2B subunit epsilon; DE AltName: Full=eIF2B GDP-GTP exchange factor subunit epsilon; GN Name=EIF2B5; Synonyms=EIF2BE; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT VAL-587. RC TISSUE=Brain; 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 [2] 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 [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT VAL-587. 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 [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT VAL-587. 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 [5] RP NUCLEOTIDE SEQUENCE [MRNA] OF 81-721, AND VARIANT VAL-587. RX PubMed=8688466; DOI=10.1016/0167-4781(96)00054-1; RA Asuru A.I., Mellor H., Thomas N.S.B., Yu L., Chen J.-J., Crosby J.S., RA Hartson S.D., Kimball S.R., Jefferson L.S., Matts R.L.; RT "Cloning and characterization of cDNAs encoding the epsilon-subunit of RT eukaryotic initiation factor-2B from rabbit and human."; RL Biochim. Biophys. Acta 1307:309-317(1996). RN [6] RP PHOSPHORYLATION BY GSK3B. RX PubMed=8397507; DOI=10.1042/bj2940625; RA Welsh G.I., Proud C.G.; RT "Glycogen synthase kinase-3 is rapidly inactivated in response to insulin RT and phosphorylates eukaryotic initiation factor eIF-2B."; RL Biochem. J. 294:625-629(1993). RN [7] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-544, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Platelet; RX PubMed=18088087; DOI=10.1021/pr0704130; RA Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J., RA Schuetz C., Walter U., Gambaryan S., Sickmann A.; RT "Phosphoproteome of resting human platelets."; RL J. Proteome Res. 7:526-534(2008). RN [8] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-544, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007; RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., RA Greff Z., Keri G., Stemmann O., Mann M.; RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the RT kinome across the cell cycle."; RL Mol. Cell 31:438-448(2008). RN [9] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-544, AND IDENTIFICATION BY RP 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 [10] RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY RP [LARGE SCALE ANALYSIS]. RX PubMed=19413330; DOI=10.1021/ac9004309; RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.; RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a RT refined SCX-based approach."; RL Anal. Chem. 81:4493-4501(2009). RN [11] RP INTERACTION WITH RGS2. RX PubMed=19736320; DOI=10.1083/jcb.200811058; RA Nguyen C.H., Ming H., Zhao P., Hugendubler L., Gros R., Kimball S.R., RA Chidiac P.; RT "Translational control by RGS2."; RL J. Cell Biol. 186:755-765(2009). RN [12] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-717, 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 [13] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-544, 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 [14] 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 [15] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-544, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21406692; DOI=10.1126/scisignal.2001570; RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.; RT "System-wide temporal characterization of the proteome and phosphoproteome RT of human embryonic stem cell differentiation."; RL Sci. Signal. 4:RS3-RS3(2011). RN [16] RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY RP [LARGE SCALE ANALYSIS]. RX PubMed=22223895; DOI=10.1074/mcp.m111.015131; RA Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T., RA Giglione C.; RT "Comparative large-scale characterisation of plant vs. mammal proteins RT reveals similar and idiosyncratic N-alpha acetylation features."; RL Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012). RN [17] RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY RP [LARGE SCALE ANALYSIS]. RX PubMed=22814378; DOI=10.1073/pnas.1210303109; RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.; RT "N-terminal acetylome analyses and functional insights of the N-terminal RT acetyltransferase NatB."; RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012). RN [18] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-544, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; 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 [19] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-450; SER-466; SER-469 AND RP SER-544, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [20] RP FUNCTION, ACTIVITY REGULATION, IDENTIFICATION BY MASS SPECTROMETRY, AND RP IDENTIFICATION IN THE EIF2B COMPLEX. RX PubMed=25858979; DOI=10.1126/science.aaa6986; RA Sekine Y., Zyryanova A., Crespillo-Casado A., Fischer P.M., Harding H.P., RA Ron D.; RT "Stress responses. Mutations in a translation initiation factor identify RT the target of a memory-enhancing compound."; RL Science 348:1027-1030(2015). RN [21] RP FUNCTION, AND IDENTIFICATION IN THE EIF2B COMPLEX. RX PubMed=27023709; DOI=10.1007/s10969-016-9203-3; RA Kashiwagi K., Shigeta T., Imataka H., Ito T., Yokoyama S.; RT "Expression, purification, and crystallization of Schizosaccharomyces pombe RT eIF2B."; RL J. Struct. Funct. Genomics 17:33-38(2016). RN [22] {ECO:0007744|PDB:6K71, ECO:0007744|PDB:6K72} RP STRUCTURE BY ELECTRON MICROSCOPY (4.30 ANGSTROMS) IN COMPLEX WITH THE EIF2 RP COMPLEX, FUNCTION, SUBUNIT, AND IDENTIFICATION IN THE EIF2B COMPLEX. RX PubMed=31048492; DOI=10.1126/science.aaw4104; RA Kashiwagi K., Yokoyama T., Nishimoto M., Takahashi M., Sakamoto A., RA Yonemochi M., Shirouzu M., Ito T.; RT "Structural basis for eIF2B inhibition in integrated stress response."; RL Science 364:495-499(2019). RN [23] RP VARIANTS VWM5 GLY-73; ALA-91; PHE-106; HIS-113; HIS-299; GLY-315; HIS-315; RP PRO-339; GLN-339; TRP-339; VAL-386; ALA-430; ARG-628 AND LYS-650, AND RP VARIANT VAL-587. RX PubMed=11704758; DOI=10.1038/ng764; RA Leegwater P.A.J., Vermeulen G., Koenst A.A.M., Naidu S., Mulders J., RA Visser A., Kersbergen P., Mobach D., Fonds D., van Berkel C.G.M., RA Lemmers R.J.L.F., Frants R.R., Oudejans C.B.M., Schutgens R.B.H., RA Pronk J.C., van der Knaap M.S.; RT "Subunits of the translation initiation factor eIF2B are mutant in RT leukoencephalopathy with vanishing white matter."; RL Nat. Genet. 29:383-388(2001). RN [24] RP VARIANT VWM5 HIS-195. RX PubMed=12325082; DOI=10.1002/ana.10339; RA Fogli A., Wong K., Eymard-Pierre E., Wenger J., Bouffard J.-P., Goldin E., RA Black D.N., Boespflug-Tanguy O., Schiffmann R.; RT "Cree leukoencephalopathy and CACH/VWM disease are allelic at the EIF2B5 RT locus."; RL Ann. Neurol. 52:506-510(2002). RN [25] RP VARIANTS VWM5 HIS-113 AND CYS-195. RX PubMed=12707859; DOI=10.1086/375404; RA Fogli A., Rodriguez D., Eymard-Pierre E., Bouhour F., Labauge P., RA Meaney B.F., Zeesman S., Kaneski C.R., Schiffmann R., Boespflug-Tanguy O.; RT "Ovarian failure related to eukaryotic initiation factor 2B mutations."; RL Am. J. Hum. Genet. 72:1544-1550(2003). RN [26] RP VARIANTS VWM5 SER-68; THR-74; HIS-113; GLY-269; PHE-310 AND ARG-335. RX PubMed=15776425; DOI=10.1002/humu.9325; RA Ohlenbusch A., Henneke M., Brockmann K., Goerg M., Hanefeld F., RA Kohlschutter A., Gartner J.; RT "Identification of ten novel mutations in patients with eIF2B-related RT disorders."; RL Hum. Mutat. 25:411-411(2005). RN [27] RP VARIANTS VWM5 VAL-62; CYS-113; GLN-269; CYS-315; SER-335; PRO-339; ASP-376; RP VAL-386 AND LEU-447. RX PubMed=19158808; DOI=10.1038/jhg.2008.10; RA Wu Y., Pan Y., Du L., Wang J., Gu Q., Gao Z., Li J., Leng X., Qin J., RA Wu X., Jiang Y.; RT "Identification of novel EIF2B mutations in Chinese patients with vanishing RT white matter disease."; RL J. Hum. Genet. 54:74-77(2009). RN [28] RP VARIANT VWM5 HIS-270. RX PubMed=21484434; DOI=10.1007/s10048-011-0284-7; RA Matsukawa T., Wang X., Liu R., Wortham N.C., Onuki Y., Kubota A., Hida A., RA Kowa H., Fukuda Y., Ishiura H., Mitsui J., Takahashi Y., Aoki S., RA Takizawa S., Shimizu J., Goto J., Proud C.G., Tsuji S.; RT "Adult-onset leukoencephalopathies with vanishing white matter with novel RT missense mutations in EIF2B2, EIF2B3, and EIF2B5."; RL Neurogenetics 12:259-261(2011). CC -!- FUNCTION: Acts as a component of the translation initiation factor 2B CC (eIF2B) complex, which catalyzes the exchange of GDP for GTP on CC eukaryotic initiation factor 2 (eIF2) gamma subunit (PubMed:25858979, CC PubMed:27023709, PubMed:31048492). Its guanine nucleotide exchange CC factor activity is repressed when bound to eIF2 complex phosphorylated CC on the alpha subunit, thereby limiting the amount of methionyl- CC initiator methionine tRNA available to the ribosome and consequently CC global translation is repressed (PubMed:25858979, PubMed:31048492). CC {ECO:0000269|PubMed:25858979, ECO:0000269|PubMed:27023709, CC ECO:0000269|PubMed:31048492}. CC -!- ACTIVITY REGULATION: Activated by the chemical integrated stress CC response (ISR) inhibitor ISRIB which stimulates guanine nucleotide CC exchange factor activity for both phosphorylated and unphosphorylated CC eIF2. {ECO:0000269|PubMed:25858979}. CC -!- SUBUNIT: Component of the translation initiation factor 2B (eIF2B) CC complex which is a heterodecamer of two sets of five different CC subunits: alpha, beta, gamma, delta and epsilon. Subunits alpha, beta CC and delta comprise a regulatory subcomplex and subunits epsilon and CC gamma comprise a catalytic subcomplex (PubMed:25858979, CC PubMed:27023709, PubMed:31048492). Within the complex, the hexameric CC regulatory complex resides at the center, with the two heterodimeric CC catalytic subcomplexes bound on opposite sides (PubMed:31048492). CC {ECO:0000269|PubMed:25858979, ECO:0000269|PubMed:27023709, CC ECO:0000269|PubMed:31048492}. CC -!- INTERACTION: CC Q13144; Q14204: DYNC1H1; NbExp=3; IntAct=EBI-4401110, EBI-356015; CC Q13144; P49841: GSK3B; NbExp=2; IntAct=EBI-4401110, EBI-373586; CC Q13144; Q92876: KLK6; NbExp=3; IntAct=EBI-4401110, EBI-2432309; CC Q13144; O75558: STX11; NbExp=3; IntAct=EBI-4401110, EBI-714135; CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol CC {ECO:0000250|UniProtKB:P56287}. CC -!- PTM: Phosphorylated at Ser-544 by DYRK2; this is required for CC subsequent phosphorylation by GSK3B (By similarity). Phosphorylated on CC serine and threonine residues by GSK3B; phosphorylation inhibits its CC function. {ECO:0000250, ECO:0000269|PubMed:8397507}. CC -!- PTM: Polyubiquitinated, probably by NEDD4. {ECO:0000250}. CC -!- DISEASE: Leukoencephalopathy with vanishing white matter 5 (VWM5) CC [MIM:620315]: An autosomal recessive brain disease characterized by CC neurological features including progressive cerebellar ataxia, CC spasticity, and cognitive deficits. Brain imaging shows abnormal white CC matter that vanishes over time and is replaced by cerebrospinal fluid. CC Disease severity ranges from fatal infantile forms to adult forms CC without neurological deterioration. The disease is progressive with, in CC most individuals, additional episodes of rapid deterioration following CC febrile infections or minor head trauma. Death may occurs after a CC variable period after disease onset, usually following an episode of CC fever and coma. A subset of affected females with milder forms of the CC disease who survive to adolescence exhibit ovarian dysfunction. This CC variant of the disorder is called ovarioleukodystrophy. CC {ECO:0000269|PubMed:11704758, ECO:0000269|PubMed:12325082, CC ECO:0000269|PubMed:12707859, ECO:0000269|PubMed:15776425, CC ECO:0000269|PubMed:19158808, ECO:0000269|PubMed:21484434}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- SIMILARITY: Belongs to the eIF-2B gamma/epsilon subunits family. CC {ECO:0000305}. CC -!- WEB RESOURCE: Name=Mendelian genes eukaryotic translation initiation CC factor 2B, subunit 5 epsilon, 82kDa (EIF2B5); Note=Leiden Open CC Variation Database (LOVD); CC URL="https://databases.lovd.nl/shared/genes/EIF2B5"; 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; AK091646; BAC03712.1; -; mRNA. DR EMBL; AC131235; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471052; EAW78299.1; -; Genomic_DNA. DR EMBL; BC013590; AAH13590.1; -; mRNA. DR EMBL; U23028; AAC50646.1; -; mRNA. DR CCDS; CCDS3252.1; -. DR RefSeq; NP_003898.2; NM_003907.2. DR PDB; 3JUI; X-ray; 2.00 A; A=548-721. DR PDB; 6CAJ; EM; 2.80 A; A/B=1-721. DR PDB; 6EZO; EM; 4.10 A; I/J=1-721. DR PDB; 6K71; EM; 4.30 A; I/J=1-721. DR PDB; 6K72; EM; 4.60 A; I/J=1-721. DR PDB; 6O81; EM; 3.21 A; A/B=1-721. DR PDB; 6O85; EM; 3.03 A; A/B=1-721. DR PDB; 6O9Z; EM; 3.03 A; A/B=1-721. DR PDB; 7D43; EM; 4.30 A; I/J=1-721. DR PDB; 7D44; EM; 4.00 A; I/J=1-721. DR PDB; 7D45; EM; 3.80 A; I/J=1-721. DR PDB; 7D46; EM; 4.00 A; I/J=1-721. DR PDB; 7F64; EM; 2.42 A; I/J=1-721. DR PDB; 7F66; EM; 2.76 A; I/J=1-721. DR PDB; 7F67; EM; 3.59 A; I/J=1-721. DR PDB; 7KMF; EM; 2.91 A; B/I=1-721. DR PDB; 7L70; EM; 2.80 A; A/B=1-721. DR PDB; 7L7G; EM; 3.00 A; A/B=1-721. DR PDB; 7RLO; EM; 2.60 A; A/B=1-721. DR PDB; 7TRJ; EM; 2.80 A; A/B=1-721. DR PDB; 7VLK; EM; 2.27 A; I/J=1-721. DR PDB; 8TQO; EM; 3.10 A; A=1-721. DR PDB; 8TQZ; EM; 2.90 A; A/B=1-721. DR PDBsum; 3JUI; -. DR PDBsum; 6CAJ; -. DR PDBsum; 6EZO; -. DR PDBsum; 6K71; -. DR PDBsum; 6K72; -. DR PDBsum; 6O81; -. DR PDBsum; 6O85; -. DR PDBsum; 6O9Z; -. DR PDBsum; 7D43; -. DR PDBsum; 7D44; -. DR PDBsum; 7D45; -. DR PDBsum; 7D46; -. DR PDBsum; 7F64; -. DR PDBsum; 7F66; -. DR PDBsum; 7F67; -. DR PDBsum; 7KMF; -. DR PDBsum; 7L70; -. DR PDBsum; 7L7G; -. DR PDBsum; 7RLO; -. DR PDBsum; 7TRJ; -. DR PDBsum; 7VLK; -. DR PDBsum; 8TQO; -. DR PDBsum; 8TQZ; -. DR AlphaFoldDB; Q13144; -. DR EMDB; EMD-0649; -. DR EMDB; EMD-0651; -. DR EMDB; EMD-0664; -. DR EMDB; EMD-22924; -. DR EMDB; EMD-23209; -. DR EMDB; EMD-24535; -. DR EMDB; EMD-26098; -. DR EMDB; EMD-30568; -. DR EMDB; EMD-30569; -. DR EMDB; EMD-30570; -. DR EMDB; EMD-30571; -. DR EMDB; EMD-31472; -. DR EMDB; EMD-31474; -. DR EMDB; EMD-31475; -. DR EMDB; EMD-32023; -. DR EMDB; EMD-4162; -. DR EMDB; EMD-7442; -. DR EMDB; EMD-9840; -. DR EMDB; EMD-9841; -. DR EMDB; EMD-9842; -. DR SMR; Q13144; -. DR BioGRID; 114410; 191. DR CORUM; Q13144; -. DR IntAct; Q13144; 44. DR MINT; Q13144; -. DR STRING; 9606.ENSP00000497160; -. DR GlyGen; Q13144; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; Q13144; -. DR PhosphoSitePlus; Q13144; -. DR SwissPalm; Q13144; -. DR BioMuta; EIF2B5; -. DR DMDM; 160359049; -. DR EPD; Q13144; -. DR jPOST; Q13144; -. DR MassIVE; Q13144; -. DR MaxQB; Q13144; -. DR PaxDb; 9606-ENSP00000273783; -. DR PeptideAtlas; Q13144; -. DR ProteomicsDB; 59187; -. DR Pumba; Q13144; -. DR Antibodypedia; 4211; 203 antibodies from 27 providers. DR DNASU; 8893; -. DR Ensembl; ENST00000648915.2; ENSP00000497160.1; ENSG00000145191.15. DR GeneID; 8893; -. DR KEGG; hsa:8893; -. DR MANE-Select; ENST00000648915.2; ENSP00000497160.1; NM_003907.3; NP_003898.2. DR UCSC; uc003fmp.4; human. DR AGR; HGNC:3261; -. DR CTD; 8893; -. DR DisGeNET; 8893; -. DR GeneCards; EIF2B5; -. DR GeneReviews; EIF2B5; -. DR HGNC; HGNC:3261; EIF2B5. DR HPA; ENSG00000145191; Low tissue specificity. DR MalaCards; EIF2B5; -. DR MIM; 603945; gene. DR MIM; 620315; phenotype. DR neXtProt; NX_Q13144; -. DR OpenTargets; ENSG00000145191; -. DR Orphanet; 157713; Congenital or early infantile CACH syndrome. DR Orphanet; 99854; Cree leukoencephalopathy. DR Orphanet; 157719; Juvenile or adult CACH syndrome. DR Orphanet; 157716; Late infantile CACH syndrome. DR Orphanet; 99853; Ovarioleukodystrophy. DR PharmGKB; PA27692; -. DR VEuPathDB; HostDB:ENSG00000145191; -. DR eggNOG; KOG1461; Eukaryota. DR GeneTree; ENSGT00510000047568; -. DR HOGENOM; CLU_012507_2_0_1; -. DR InParanoid; Q13144; -. DR OrthoDB; 5474157at2759; -. DR PhylomeDB; Q13144; -. DR TreeFam; TF101509; -. DR PathwayCommons; Q13144; -. DR Reactome; R-HSA-72731; Recycling of eIF2:GDP. DR SignaLink; Q13144; -. DR SIGNOR; Q13144; -. DR BioGRID-ORCS; 8893; 787 hits in 1160 CRISPR screens. DR ChiTaRS; EIF2B5; human. DR EvolutionaryTrace; Q13144; -. DR GeneWiki; EIF2B5; -. DR GenomeRNAi; 8893; -. DR Pharos; Q13144; Tbio. DR PRO; PR:Q13144; -. DR Proteomes; UP000005640; Chromosome 3. DR RNAct; Q13144; Protein. DR Bgee; ENSG00000145191; Expressed in sural nerve and 204 other cell types or tissues. DR ExpressionAtlas; Q13144; baseline and differential. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:0005851; C:eukaryotic translation initiation factor 2B complex; IDA:UniProtKB. DR GO; GO:0005634; C:nucleus; ISS:UniProtKB. DR GO; GO:0005085; F:guanyl-nucleotide exchange factor activity; IDA:UniProtKB. DR GO; GO:0003743; F:translation initiation factor activity; NAS:UniProtKB. DR GO; GO:0031369; F:translation initiation factor binding; ISS:UniProtKB. DR GO; GO:0014002; P:astrocyte development; IMP:UniProtKB. DR GO; GO:0048708; P:astrocyte differentiation; IMP:UniProtKB. DR GO; GO:0002183; P:cytoplasmic translational initiation; IDA:UniProtKB. DR GO; GO:0021766; P:hippocampus development; IEA:Ensembl. DR GO; GO:0042552; P:myelination; IMP:UniProtKB. DR GO; GO:0014003; P:oligodendrocyte development; IMP:UniProtKB. DR GO; GO:0001541; P:ovarian follicle development; IMP:UniProtKB. DR GO; GO:0043065; P:positive regulation of apoptotic process; IEA:Ensembl. DR GO; GO:0045948; P:positive regulation of translational initiation; ISS:UniProtKB. DR GO; GO:0034976; P:response to endoplasmic reticulum stress; IMP:UniProtKB. DR GO; GO:0009749; P:response to glucose; ISS:UniProtKB. DR GO; GO:0009408; P:response to heat; IMP:UniProtKB. DR GO; GO:0043434; P:response to peptide hormone; ISS:UniProtKB. DR GO; GO:0050852; P:T cell receptor signaling pathway; IDA:UniProtKB. DR GO; GO:0006413; P:translational initiation; IDA:UniProtKB. DR CDD; cd04197; eIF-2B_epsilon_N; 1. DR CDD; cd05787; LbH_eIF2B_epsilon; 1. DR CDD; cd11558; W2_eIF2B_epsilon; 1. DR Gene3D; 1.25.40.180; -; 1. DR Gene3D; 2.160.10.10; Hexapeptide repeat proteins; 2. DR InterPro; IPR016024; ARM-type_fold. DR InterPro; IPR035543; eIF-2B_epsilon_N. DR InterPro; IPR029044; Nucleotide-diphossugar_trans. DR InterPro; IPR011004; Trimer_LpxA-like_sf. DR InterPro; IPR003307; W2_domain. DR InterPro; IPR044123; W2_eIF2B_epsilon. DR PANTHER; PTHR45887; TRANSLATION INITIATION FACTOR EIF-2B SUBUNIT EPSILON; 1. DR PANTHER; PTHR45887:SF1; TRANSLATION INITIATION FACTOR EIF-2B SUBUNIT EPSILON; 1. DR Pfam; PF02020; W2; 1. DR SMART; SM00515; eIF5C; 1. DR SUPFAM; SSF48371; ARM repeat; 1. DR SUPFAM; SSF53448; Nucleotide-diphospho-sugar transferases; 1. DR SUPFAM; SSF51161; Trimeric LpxA-like enzymes; 1. DR PROSITE; PS51363; W2; 1. DR Genevisible; Q13144; HS. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Cytoplasm; Disease variant; Initiation factor; KW Isopeptide bond; Leukodystrophy; Methylation; Phosphoprotein; KW Protein biosynthesis; Reference proteome; Ubl conjugation. FT INIT_MET 1 FT /note="Removed" FT /evidence="ECO:0007744|PubMed:19413330, FT ECO:0007744|PubMed:22223895, ECO:0007744|PubMed:22814378" FT CHAIN 2..721 FT /note="Translation initiation factor eIF2B subunit epsilon" FT /id="PRO_0000156073" FT DOMAIN 543..720 FT /note="W2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00695" FT REGION 1..40 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 444..483 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 523..547 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 455..469 FT /note="Acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 2 FT /note="N-acetylalanine" FT /evidence="ECO:0007744|PubMed:19413330, FT ECO:0007744|PubMed:22223895, ECO:0007744|PubMed:22814378" FT MOD_RES 19 FT /note="Omega-N-methylarginine" FT /evidence="ECO:0000250|UniProtKB:Q8CHW4" FT MOD_RES 27 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q64350" FT MOD_RES 130 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q64350" FT MOD_RES 322 FT /note="Phosphothreonine" FT /evidence="ECO:0000250|UniProtKB:Q64350" FT MOD_RES 450 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:24275569" FT MOD_RES 466 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:24275569" FT MOD_RES 469 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:24275569" FT MOD_RES 532 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q64350" FT MOD_RES 540 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q64350" FT MOD_RES 544 FT /note="Phosphoserine; by DYRK2" FT /evidence="ECO:0007744|PubMed:18088087, FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:18691976, FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692, FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569" FT MOD_RES 717 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:19690332" FT CROSSLNK 61 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in ubiquitin)" FT /evidence="ECO:0000250|UniProtKB:Q64350" FT CROSSLNK 103 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in ubiquitin)" FT /evidence="ECO:0000250|UniProtKB:Q64350" FT CROSSLNK 141 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in ubiquitin)" FT /evidence="ECO:0000250|UniProtKB:Q64350" FT CROSSLNK 217 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in ubiquitin)" FT /evidence="ECO:0000250|UniProtKB:Q64350" FT VARIANT 62 FT /note="D -> V (in VWM5; dbSNP:rs1560105986)" FT /evidence="ECO:0000269|PubMed:19158808" FT /id="VAR_068457" FT VARIANT 68 FT /note="L -> S (in VWM5; dbSNP:rs113994044)" FT /evidence="ECO:0000269|PubMed:15776425" FT /id="VAR_068458" FT VARIANT 73 FT /note="V -> G (in VWM5; dbSNP:rs113994045)" FT /evidence="ECO:0000269|PubMed:11704758" FT /id="VAR_012323" FT VARIANT 74 FT /note="A -> T (in VWM5; dbSNP:rs113994046)" FT /evidence="ECO:0000269|PubMed:15776425" FT /id="VAR_068459" FT VARIANT 91 FT /note="T -> A (in VWM5; dbSNP:rs28939717)" FT /evidence="ECO:0000269|PubMed:11704758" FT /id="VAR_012291" FT VARIANT 106 FT /note="L -> F (in VWM5; dbSNP:rs113994048)" FT /evidence="ECO:0000269|PubMed:11704758" FT /id="VAR_012324" FT VARIANT 113 FT /note="R -> C (in VWM5; dbSNP:rs113994050)" FT /evidence="ECO:0000269|PubMed:19158808" FT /id="VAR_068460" FT VARIANT 113 FT /note="R -> H (in VWM5; with ovarian failure; FT dbSNP:rs113994049)" FT /evidence="ECO:0000269|PubMed:11704758, FT ECO:0000269|PubMed:12707859, ECO:0000269|PubMed:15776425" FT /id="VAR_012292" FT VARIANT 195 FT /note="R -> C (in VWM5; with ovarian failure; FT dbSNP:rs113994055)" FT /evidence="ECO:0000269|PubMed:12707859" FT /id="VAR_016845" FT VARIANT 195 FT /note="R -> H (in VWM5; Cree leukoencephalopathy type; FT dbSNP:rs113994054)" FT /evidence="ECO:0000269|PubMed:12325082" FT /id="VAR_016846" FT VARIANT 200 FT /note="N -> T (in dbSNP:rs2971409)" FT /id="VAR_048919" FT VARIANT 269 FT /note="R -> G (in VWM5; dbSNP:rs113994058)" FT /evidence="ECO:0000269|PubMed:15776425" FT /id="VAR_068461" FT VARIANT 269 FT /note="R -> Q (in VWM5; dbSNP:rs113994057)" FT /evidence="ECO:0000269|PubMed:19158808" FT /id="VAR_068462" FT VARIANT 270 FT /note="D -> H (in VWM5; dbSNP:rs397514646)" FT /evidence="ECO:0000269|PubMed:21484434" FT /id="VAR_068463" FT VARIANT 299 FT /note="R -> H (in VWM5; dbSNP:rs113994060)" FT /evidence="ECO:0000269|PubMed:11704758" FT /id="VAR_012325" FT VARIANT 310 FT /note="C -> F (in VWM5; dbSNP:rs113994062)" FT /evidence="ECO:0000269|PubMed:15776425" FT /id="VAR_068464" FT VARIANT 315 FT /note="R -> C (in VWM5; dbSNP:rs113994063)" FT /evidence="ECO:0000269|PubMed:19158808" FT /id="VAR_068465" FT VARIANT 315 FT /note="R -> G (in VWM5; dbSNP:rs113994063)" FT /evidence="ECO:0000269|PubMed:11704758" FT /id="VAR_012326" FT VARIANT 315 FT /note="R -> H (in VWM5; dbSNP:rs113994064)" FT /evidence="ECO:0000269|PubMed:11704758" FT /id="VAR_012327" FT VARIANT 335 FT /note="C -> R (in VWM5; dbSNP:rs113994067)" FT /evidence="ECO:0000269|PubMed:15776425" FT /id="VAR_068466" FT VARIANT 335 FT /note="C -> S (in VWM5)" FT /evidence="ECO:0000269|PubMed:19158808" FT /id="VAR_068467" FT VARIANT 339 FT /note="R -> P (in VWM5; dbSNP:rs113994069)" FT /evidence="ECO:0000269|PubMed:11704758, FT ECO:0000269|PubMed:19158808" FT /id="VAR_012328" FT VARIANT 339 FT /note="R -> Q (in VWM5; dbSNP:rs113994069)" FT /evidence="ECO:0000269|PubMed:11704758" FT /id="VAR_012329" FT VARIANT 339 FT /note="R -> W (in VWM5; dbSNP:rs113994068)" FT /evidence="ECO:0000269|PubMed:11704758" FT /id="VAR_012330" FT VARIANT 376 FT /note="N -> D (in VWM5)" FT /evidence="ECO:0000269|PubMed:19158808" FT /id="VAR_068468" FT VARIANT 386 FT /note="G -> V (in VWM5; dbSNP:rs113994074)" FT /evidence="ECO:0000269|PubMed:11704758, FT ECO:0000269|PubMed:19158808" FT /id="VAR_012293" FT VARIANT 430 FT /note="V -> A (in VWM5; dbSNP:rs113994079)" FT /evidence="ECO:0000269|PubMed:11704758" FT /id="VAR_012331" FT VARIANT 447 FT /note="S -> L (in VWM5; dbSNP:rs113994080)" FT /evidence="ECO:0000269|PubMed:19158808" FT /id="VAR_068469" FT VARIANT 587 FT /note="I -> V (in dbSNP:rs843358)" FT /evidence="ECO:0000269|PubMed:11704758, FT ECO:0000269|PubMed:14702039, ECO:0000269|PubMed:15489334, FT ECO:0000269|PubMed:8688466, ECO:0000269|Ref.3" FT /id="VAR_012332" FT VARIANT 628 FT /note="W -> R (in VWM5; dbSNP:rs28937596)" FT /evidence="ECO:0000269|PubMed:11704758" FT /id="VAR_012294" FT VARIANT 650 FT /note="E -> K (in VWM5; dbSNP:rs113994085)" FT /evidence="ECO:0000269|PubMed:11704758" FT /id="VAR_012333" FT STRAND 44..48 FT /evidence="ECO:0007829|PDB:7VLK" FT TURN 55..58 FT /evidence="ECO:0007829|PDB:7VLK" FT HELIX 59..61 FT /evidence="ECO:0007829|PDB:7VLK" FT HELIX 65..67 FT /evidence="ECO:0007829|PDB:7VLK" FT STRAND 69..74 FT /evidence="ECO:0007829|PDB:7VLK" FT HELIX 75..85 FT /evidence="ECO:0007829|PDB:7VLK" FT STRAND 90..95 FT /evidence="ECO:0007829|PDB:7VLK" FT HELIX 99..107 FT /evidence="ECO:0007829|PDB:7VLK" FT HELIX 110..112 FT /evidence="ECO:0007829|PDB:7VLK" FT STRAND 117..124 FT /evidence="ECO:0007829|PDB:7VLK" FT HELIX 131..141 FT /evidence="ECO:0007829|PDB:7VLK" FT STRAND 149..152 FT /evidence="ECO:0007829|PDB:7VLK" FT STRAND 155..157 FT /evidence="ECO:0007829|PDB:7VLK" FT HELIX 162..174 FT /evidence="ECO:0007829|PDB:7VLK" FT TURN 175..177 FT /evidence="ECO:0007829|PDB:7VLK" FT STRAND 181..187 FT /evidence="ECO:0007829|PDB:7VLK" FT HELIX 193..195 FT /evidence="ECO:0007829|PDB:7RLO" FT TURN 197..199 FT /evidence="ECO:0007829|PDB:7F64" FT STRAND 201..206 FT /evidence="ECO:0007829|PDB:7VLK" FT TURN 207..210 FT /evidence="ECO:0007829|PDB:7VLK" FT STRAND 211..217 FT /evidence="ECO:0007829|PDB:7VLK" FT STRAND 222..226 FT /evidence="ECO:0007829|PDB:7VLK" FT HELIX 230..232 FT /evidence="ECO:0007829|PDB:7VLK" FT STRAND 238..241 FT /evidence="ECO:0007829|PDB:7VLK" FT STRAND 244..251 FT /evidence="ECO:0007829|PDB:7VLK" FT HELIX 254..262 FT /evidence="ECO:0007829|PDB:7VLK" FT HELIX 269..278 FT /evidence="ECO:0007829|PDB:7VLK" FT STRAND 281..283 FT /evidence="ECO:0007829|PDB:7VLK" FT STRAND 287..295 FT /evidence="ECO:0007829|PDB:7VLK" FT STRAND 297..299 FT /evidence="ECO:0007829|PDB:7VLK" FT HELIX 303..314 FT /evidence="ECO:0007829|PDB:7VLK" FT TURN 315..320 FT /evidence="ECO:0007829|PDB:7VLK" FT HELIX 323..325 FT /evidence="ECO:0007829|PDB:7VLK" FT HELIX 331..333 FT /evidence="ECO:0007829|PDB:7VLK" FT STRAND 336..338 FT /evidence="ECO:0007829|PDB:7VLK" FT TURN 339..341 FT /evidence="ECO:0007829|PDB:7VLK" FT STRAND 342..344 FT /evidence="ECO:0007829|PDB:7VLK" FT STRAND 358..362 FT /evidence="ECO:0007829|PDB:7VLK" FT STRAND 373..376 FT /evidence="ECO:0007829|PDB:7VLK" FT STRAND 384..387 FT /evidence="ECO:0007829|PDB:7KMF" FT STRAND 390..393 FT /evidence="ECO:0007829|PDB:7VLK" FT STRAND 400..405 FT /evidence="ECO:0007829|PDB:7KMF" FT STRAND 407..413 FT /evidence="ECO:0007829|PDB:7VLK" FT STRAND 421..425 FT /evidence="ECO:0007829|PDB:7VLK" FT STRAND 427..434 FT /evidence="ECO:0007829|PDB:7VLK" FT STRAND 439..442 FT /evidence="ECO:0007829|PDB:7VLK" FT STRAND 448..452 FT /evidence="ECO:0007829|PDB:7VLK" FT TURN 453..455 FT /evidence="ECO:0007829|PDB:7VLK" FT STRAND 456..458 FT /evidence="ECO:0007829|PDB:7F64" FT STRAND 462..464 FT /evidence="ECO:0007829|PDB:6O85" FT HELIX 548..567 FT /evidence="ECO:0007829|PDB:3JUI" FT HELIX 571..584 FT /evidence="ECO:0007829|PDB:3JUI" FT HELIX 589..602 FT /evidence="ECO:0007829|PDB:3JUI" FT HELIX 603..607 FT /evidence="ECO:0007829|PDB:3JUI" FT STRAND 608..610 FT /evidence="ECO:0007829|PDB:7F66" FT HELIX 614..635 FT /evidence="ECO:0007829|PDB:3JUI" FT HELIX 639..655 FT /evidence="ECO:0007829|PDB:3JUI" FT HELIX 657..662 FT /evidence="ECO:0007829|PDB:3JUI" FT HELIX 663..672 FT /evidence="ECO:0007829|PDB:3JUI" FT HELIX 678..685 FT /evidence="ECO:0007829|PDB:3JUI" FT HELIX 693..697 FT /evidence="ECO:0007829|PDB:3JUI" FT HELIX 701..714 FT /evidence="ECO:0007829|PDB:3JUI" SQ SEQUENCE 721 AA; 80380 MW; 08B39D3A5EE7D905 CRC64; MAAPVVAPPG VVVSRANKRS GAGPGGSGGG GARGAEEEPP PPLQAVLVAD SFDRRFFPIS KDQPRVLLPL ANVALIDYTL EFLTATGVQE TFVFCCWKAA QIKEHLLKSK WCRPTSLNVV RIITSELYRS LGDVLRDVDA KALVRSDFLL VYGDVISNIN ITRALEEHRL RRKLEKNVSV MTMIFKESSP SHPTRCHEDN VVVAVDSTTN RVLHFQKTQG LRRFAFPLSL FQGSSDGVEV RYDLLDCHIS ICSPQVAQLF TDNFDYQTRD DFVRGLLVNE EILGNQIHMH VTAKEYGARV SNLHMYSAVC ADVIRRWVYP LTPEANFTDS TTQSCTHSRH NIYRGPEVSL GHGSILEENV LLGSGTVIGS NCFITNSVIG PGCHIGDNVV LDQTYLWQGV RVAAGAQIHQ SLLCDNAEVK ERVTLKPRSV LTSQVVVGPN ITLPEGSVIS LHPPDAEEDE DDGEFSDDSG ADQEKDKVKM KGYNPAEVGA AGKGYLWKAA GMNMEEEEEL QQNLWGLKIN MEEESESESE QSMDSEEPDS RGGSPQMDDI KVFQNEVLGT LQRGKEENIS CDNLVLEINS LKYAYNISLK EVMQVLSHVV LEFPLQQMDS PLDSSRYCAL LLPLLKAWSP VFRNYIKRAA DHLEALAAIE DFFLEHEALG ISMAKVLMAF YQLEILAEET ILSWFSQRDT TDKGQQLRKN QQLQRFIQWL KEAEEESSED D //