EI2BE_HUMAN
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 03-AUG-2022, entry version 206.
DE RecName: Full=Translation initiation factor eIF-2B subunit epsilon;
DE AltName: Full=eIF-2B 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 VARIANTS VWM 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 [21]
RP VARIANT VWM 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 [22]
RP VARIANTS VWM 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 [23]
RP VARIANTS VWM 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 [24]
RP VARIANTS VWM 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 [25]
RP VARIANT VWM 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: Catalyzes the exchange of eukaryotic initiation factor 2-
CC bound GDP for GTP.
CC -!- SUBUNIT: Complex of five different subunits; alpha, beta, gamma, delta
CC and epsilon. Interacts with RGS2. {ECO:0000269|PubMed:19736320}.
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 -!- 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: Leukodystrophy with vanishing white matter (VWM) [MIM:603896]:
CC A leukodystrophy that occurs mainly in children. Neurological signs
CC include progressive cerebellar ataxia, spasticity, inconstant optic
CC atrophy and relatively preserved mental abilities. The disease is
CC chronic-progressive with, in most individuals, additional episodes of
CC rapid deterioration following febrile infections or minor head trauma.
CC While childhood onset is the most common form of the disorder, some
CC severe forms are apparent at birth. A severe, early-onset form seen
CC among the Cree and Chippewayan populations of Quebec and Manitoba is
CC called Cree leukoencephalopathy. Milder forms may not become evident
CC until adolescence or adulthood. Some 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";
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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; 7VLK; EM; 2.27 A; I/J=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; 7VLK; -.
DR AlphaFoldDB; Q13144; -.
DR SMR; Q13144; -.
DR BioGRID; 114410; 173.
DR CORUM; Q13144; -.
DR IntAct; Q13144; 42.
DR MINT; Q13144; -.
DR STRING; 9606.ENSP00000273783; -.
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; Q13144; -.
DR PeptideAtlas; Q13144; -.
DR PRIDE; Q13144; -.
DR ProteomicsDB; 59187; -.
DR Antibodypedia; 4211; 170 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 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; 603896; phenotype.
DR MIM; 603945; gene.
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 OMA; HYLYDKD; -.
DR OrthoDB; 369837at2759; -.
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; 751 hits in 1084 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 202 other tissues.
DR ExpressionAtlas; Q13144; baseline and differential.
DR Genevisible; Q13144; HS.
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; IMP: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:0007568; P:aging; IEA:Ensembl.
DR GO; GO:0014002; P:astrocyte development; IMP:UniProtKB.
DR GO; GO:0048708; P:astrocyte differentiation; IMP: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:0010226; P:response to lithium ion; IEA:Ensembl.
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; cd11558; W2_eIF2B_epsilon; 1.
DR Gene3D; 3.90.550.10; -; 1.
DR InterPro; IPR016024; ARM-type_fold.
DR InterPro; IPR035543; eIF-2B_epsilon_N.
DR InterPro; IPR001451; Hexapep.
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 Pfam; PF00132; Hexapep; 1.
DR Pfam; PF02020; W2; 1.
DR SMART; SM00515; eIF5C; 1.
DR SUPFAM; SSF48371; SSF48371; 1.
DR SUPFAM; SSF51161; SSF51161; 1.
DR SUPFAM; SSF53448; SSF53448; 1.
DR PROSITE; PS51363; W2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; 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 eIF-2B subunit
FT 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 VWM; dbSNP:rs1560105986)"
FT /evidence="ECO:0000269|PubMed:19158808"
FT /id="VAR_068457"
FT VARIANT 68
FT /note="L -> S (in VWM; dbSNP:rs113994044)"
FT /evidence="ECO:0000269|PubMed:15776425"
FT /id="VAR_068458"
FT VARIANT 73
FT /note="V -> G (in VWM; dbSNP:rs113994045)"
FT /evidence="ECO:0000269|PubMed:11704758"
FT /id="VAR_012323"
FT VARIANT 74
FT /note="A -> T (in VWM; dbSNP:rs113994046)"
FT /evidence="ECO:0000269|PubMed:15776425"
FT /id="VAR_068459"
FT VARIANT 91
FT /note="T -> A (in VWM; dbSNP:rs28939717)"
FT /evidence="ECO:0000269|PubMed:11704758"
FT /id="VAR_012291"
FT VARIANT 106
FT /note="L -> F (in VWM; dbSNP:rs113994048)"
FT /evidence="ECO:0000269|PubMed:11704758"
FT /id="VAR_012324"
FT VARIANT 113
FT /note="R -> C (in VWM; dbSNP:rs113994050)"
FT /evidence="ECO:0000269|PubMed:19158808"
FT /id="VAR_068460"
FT VARIANT 113
FT /note="R -> H (in VWM; 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 VWM; with ovarian failure;
FT dbSNP:rs113994055)"
FT /evidence="ECO:0000269|PubMed:12707859"
FT /id="VAR_016845"
FT VARIANT 195
FT /note="R -> H (in VWM; 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 VWM; dbSNP:rs113994058)"
FT /evidence="ECO:0000269|PubMed:15776425"
FT /id="VAR_068461"
FT VARIANT 269
FT /note="R -> Q (in VWM; dbSNP:rs113994057)"
FT /evidence="ECO:0000269|PubMed:19158808"
FT /id="VAR_068462"
FT VARIANT 270
FT /note="D -> H (in VWM; dbSNP:rs397514646)"
FT /evidence="ECO:0000269|PubMed:21484434"
FT /id="VAR_068463"
FT VARIANT 299
FT /note="R -> H (in VWM; dbSNP:rs113994060)"
FT /evidence="ECO:0000269|PubMed:11704758"
FT /id="VAR_012325"
FT VARIANT 310
FT /note="C -> F (in VWM; dbSNP:rs113994062)"
FT /evidence="ECO:0000269|PubMed:15776425"
FT /id="VAR_068464"
FT VARIANT 315
FT /note="R -> C (in VWM; dbSNP:rs113994063)"
FT /evidence="ECO:0000269|PubMed:19158808"
FT /id="VAR_068465"
FT VARIANT 315
FT /note="R -> G (in VWM; dbSNP:rs113994063)"
FT /evidence="ECO:0000269|PubMed:11704758"
FT /id="VAR_012326"
FT VARIANT 315
FT /note="R -> H (in VWM; dbSNP:rs113994064)"
FT /evidence="ECO:0000269|PubMed:11704758"
FT /id="VAR_012327"
FT VARIANT 335
FT /note="C -> R (in VWM; dbSNP:rs113994067)"
FT /evidence="ECO:0000269|PubMed:15776425"
FT /id="VAR_068466"
FT VARIANT 335
FT /note="C -> S (in VWM)"
FT /evidence="ECO:0000269|PubMed:19158808"
FT /id="VAR_068467"
FT VARIANT 339
FT /note="R -> P (in VWM; 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 VWM; dbSNP:rs113994069)"
FT /evidence="ECO:0000269|PubMed:11704758"
FT /id="VAR_012329"
FT VARIANT 339
FT /note="R -> W (in VWM; dbSNP:rs113994068)"
FT /evidence="ECO:0000269|PubMed:11704758"
FT /id="VAR_012330"
FT VARIANT 376
FT /note="N -> D (in VWM)"
FT /evidence="ECO:0000269|PubMed:19158808"
FT /id="VAR_068468"
FT VARIANT 386
FT /note="G -> V (in VWM; 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 VWM; dbSNP:rs113994079)"
FT /evidence="ECO:0000269|PubMed:11704758"
FT /id="VAR_012331"
FT VARIANT 447
FT /note="S -> L (in VWM; 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 VWM; dbSNP:rs28937596)"
FT /evidence="ECO:0000269|PubMed:11704758"
FT /id="VAR_012294"
FT VARIANT 650
FT /note="E -> K (in VWM; 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
