IF2G_HUMAN
ID IF2G_HUMAN Reviewed; 472 AA.
AC P41091; A0A024RBY4; A8K2Y2; B2R5N2; B5BTZ4; Q53HK3;
DT 01-FEB-1995, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 203.
DE RecName: Full=Eukaryotic translation initiation factor 2 subunit 3;
DE EC=3.6.5.3;
DE AltName: Full=Eukaryotic translation initiation factor 2 subunit gamma X;
DE Short=eIF-2-gamma X;
DE Short=eIF-2gX;
GN Name=EIF2S3; Synonyms=EIF2G;
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], AND PARTIAL PROTEIN SEQUENCE.
RC TISSUE=Leukemia;
RX PubMed=8106381; DOI=10.1016/s0021-9258(17)41878-3;
RA Gaspar N.J., Kinzy T.G., Scherer B.J., Huembelin M., Hershey J.W.B.,
RA Merrick W.C.;
RT "Translation initiation factor eIF-2. Cloning and expression of the human
RT cDNA encoding the gamma-subunit.";
RL J. Biol. Chem. 269:3415-3422(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Astrocyte, and Umbilical cord blood;
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=19054851; DOI=10.1038/nmeth.1273;
RA Goshima N., Kawamura Y., Fukumoto A., Miura A., Honma R., Satoh R.,
RA Wakamatsu A., Yamamoto J., Kimura K., Nishikawa T., Andoh T., Iida Y.,
RA Ishikawa K., Ito E., Kagawa N., Kaminaga C., Kanehori K., Kawakami B.,
RA Kenmochi K., Kimura R., Kobayashi M., Kuroita T., Kuwayama H., Maruyama Y.,
RA Matsuo K., Minami K., Mitsubori M., Mori M., Morishita R., Murase A.,
RA Nishikawa A., Nishikawa S., Okamoto T., Sakagami N., Sakamoto Y.,
RA Sasaki Y., Seki T., Sono S., Sugiyama A., Sumiya T., Takayama T.,
RA Takayama Y., Takeda H., Togashi T., Yahata K., Yamada H., Yanagisawa Y.,
RA Endo Y., Imamoto F., Kisu Y., Tanaka S., Isogai T., Imai J., Watanabe S.,
RA Nomura N.;
RT "Human protein factory for converting the transcriptome into an in vitro-
RT expressed proteome.";
RL Nat. Methods 5:1011-1017(2008).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Endothelial cell;
RA Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y.,
RA Tanaka A., Yokoyama S.;
RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
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 (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Lymph;
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 [7]
RP PROTEIN SEQUENCE OF 2-17.
RC TISSUE=Platelet;
RX PubMed=12665801; DOI=10.1038/nbt810;
RA Gevaert K., Goethals M., Martens L., Van Damme J., Staes A., Thomas G.R.,
RA Vandekerckhove J.;
RT "Exploring proteomes and analyzing protein processing by mass spectrometric
RT identification of sorted N-terminal peptides.";
RL Nat. Biotechnol. 21:566-569(2003).
RN [8]
RP PROTEIN SEQUENCE OF 2-54; 60-75; 182-191; 242-255; 276-285; 290-303;
RP 318-342; 401-416; 453-460 AND 462-472, CLEAVAGE OF INITIATOR METHIONINE,
RP ACETYLATION AT ALA-2, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC TISSUE=Colon carcinoma, Hepatoma, Lung carcinoma, and Ovarian carcinoma;
RA Bienvenut W.V., Boldt K., von Kriegsheim A., Kolch W., Heiserich L.,
RA Gottlieb E., Vousden K.H., Lukashchuk N., Lilla S., Lempens A.;
RL Submitted (DEC-2008) to UniProtKB.
RN [9]
RP TISSUE SPECIFICITY, LACK OF HOMOLOG ON CHROMOSOME Y, AND ESCAPE FROM
RP X-INACTIVATION.
RX PubMed=9736774; DOI=10.1093/hmg/7.11.1725;
RA Ehrmann I.E., Ellis P.S., Mazeyrat S., Duthie S., Brockdorff N.,
RA Mattei M.-G., Gavin M.A., Affara N.A., Brown G.M., Simpson E.,
RA Mitchell M.J., Scott D.M.;
RT "Characterization of genes encoding translation initiation factor eIF-
RT 2gamma in mouse and human: sex chromosome localization, escape from X-
RT inactivation and evolution.";
RL Hum. Mol. Genet. 7:1725-1737(1998).
RN [10]
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 [11]
RP INVOLVEMENT IN MEHMO, VARIANT MEHMO THR-222, CHARACTERIZATION OF VARIANT
RP MEHMO THR-222, AND SUBUNIT.
RX PubMed=23063529; DOI=10.1016/j.molcel.2012.09.005;
RA Borck G., Shin B.S., Stiller B., Mimouni-Bloch A., Thiele H., Kim J.R.,
RA Thakur M., Skinner C., Aschenbach L., Smirin-Yosef P., Har-Zahav A.,
RA Nuernberg G., Altmueller J., Frommolt P., Hofmann K., Konen O.,
RA Nuernberg P., Munnich A., Schwartz C.E., Gothelf D., Colleaux L.,
RA Dever T.E., Kubisch C., Basel-Vanagaite L.;
RT "eIF2gamma mutation that disrupts eIF2 complex integrity links intellectual
RT disability to impaired translation initiation.";
RL Mol. Cell 48:641-646(2012).
RN [12]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [13] {ECO:0007744|PDB:6FEC}
RP STRUCTURE BY ELECTRON MICROSCOPY (6.30 ANGSTROMS) OF 39-460.
RX PubMed=29401259; DOI=10.1093/nar/gky054;
RA Eliseev B., Yeramala L., Leitner A., Karuppasamy M., Raimondeau E.,
RA Huard K., Alkalaeva E., Aebersold R., Schaffitzel C.;
RT "Structure of a human cap-dependent 48S translation pre-initiation
RT complex.";
RL Nucleic Acids Res. 46:2678-2689(2018).
RN [14] {ECO:0007744|PDB:6O81, ECO:0007744|PDB:6O85}
RP STRUCTURE BY ELECTRON MICROSCOPY (3.03 ANGSTROMS).
RX PubMed=31048491; DOI=10.1126/science.aaw2922;
RA Kenner L.R., Anand A.A., Nguyen H.C., Myasnikov A.G., Klose C.J.,
RA McGeever L.A., Tsai J.C., Miller-Vedam L.E., Walter P., Frost A.;
RT "eIF2B-catalyzed nucleotide exchange and phosphoregulation by the
RT integrated stress response.";
RL Science 364:491-495(2019).
RN [15] {ECO:0007744|PDB:6K71, ECO:0007744|PDB:6K72}
RP STRUCTURE BY ELECTRON MICROSCOPY (4.30 ANGSTROMS).
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 [16]
RP INVOLVEMENT IN MEHMO, AND VARIANT MEHMO MET-259.
RX PubMed=27333055; DOI=10.1002/ajmg.a.37792;
RA Moortgat S., Desir J., Benoit V., Boulanger S., Pendeville H.,
RA Nassogne M.C., Lederer D., Maystadt I.;
RT "Two novel EIF2S3 mutations associated with syndromic intellectual
RT disability with severe microcephaly, growth retardation, and epilepsy.";
RL Am. J. Med. Genet. A 170:2927-2933(2016).
RN [17]
RP INVOLVEMENT IN MEHMO, AND VARIANT MEHMO ARG-108.
RX PubMed=28055140; DOI=10.1002/humu.23170;
RA Skopkova M., Hennig F., Shin B.S., Turner C.E., Stanikova D.,
RA Brennerova K., Stanik J., Fischer U., Henden L., Mueller U.,
RA Steinberger D., Leshinsky-Silver E., Bottani A., Kurdiova T., Ukropec J.,
RA Nyitrayova O., Kolnikova M., Klimes I., Borck G., Bahlo M., Haas S.A.,
RA Kim J.R., Lotspeich-Cole L.E., Gasperikova D., Dever T.E., Kalscheuer V.M.;
RT "EIF2S3 mutations associated with severe X-linked intellectual disability
RT syndrome MEHMO.";
RL Hum. Mutat. 38:409-425(2017).
CC -!- FUNCTION: As a subunit of eukaryotic initiation factor 2 (eIF-2),
CC involved in the early steps of protein synthesis. In the presence of
CC GTP, eIF-2 forms a ternary complex with initiator tRNA Met-tRNAi and
CC then recruits the 40S ribosomal complex and initiation factors eIF-1,
CC eIF-1A and eIF-3 to form the 43S pre-initiation complex (43S PIC), a
CC step that determines the rate of protein translation. The 43S PIC binds
CC to mRNA and scans downstream to the initiation codon, where it forms a
CC 48S initiation complex by codon-anticodon base pairing. This leads to
CC the displacement of eIF-1 to allow GTPase-activating protein (GAP) eIF-
CC 5-mediated hydrolysis of eIF2-bound GTP. Hydrolysis of GTP and release
CC of Pi, which makes GTP hydrolysis irreversible, causes the release of
CC the eIF-2-GDP binary complex from the 40S subunit, an event that is
CC essential for the subsequent joining of the 60S ribosomal subunit to
CC form an elongation-competent 80S ribosome. In order for eIF-2 to
CC recycle and catalyze another round of initiation, the GDP bound to eIF-
CC 2 must be exchanged with GTP by way of a reaction catalyzed by GDP-GTP
CC exchange factor (GEF) eIF-2B (By similarity). Along with its paralog on
CC chromosome Y, may contribute to spermatogenesis up to the round
CC spermatid stage (By similarity). {ECO:0000250|UniProtKB:P32481,
CC ECO:0000250|UniProtKB:Q9Z0N1}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=GTP + H2O = GDP + H(+) + phosphate; Xref=Rhea:RHEA:19669,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:37565,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:58189; EC=3.6.5.3;
CC Evidence={ECO:0000250|UniProtKB:P32481};
CC -!- SUBUNIT: The eukaryotic translation initiation factor 2 complex/eIF2 is
CC a heterotrimer composed of an alpha subunit, also called subunit 1
CC (encoded by EIF2S1), a beta subunit, also called subunit 2 (encoded by
CC EIF2S2) and a gamma subunit, also called subunit 3 (encoded by EIF2S3).
CC {ECO:0000269|PubMed:23063529}.
CC -!- INTERACTION:
CC P41091; Q6DHV7-2: ADAL; NbExp=3; IntAct=EBI-1054228, EBI-18899653;
CC P41091; Q96FT7-4: ASIC4; NbExp=3; IntAct=EBI-1054228, EBI-9089489;
CC P41091; Q8TBE0: BAHD1; NbExp=3; IntAct=EBI-1054228, EBI-742750;
CC P41091; P38936: CDKN1A; NbExp=3; IntAct=EBI-1054228, EBI-375077;
CC P41091; A0A024RCP2: DOM3Z; NbExp=3; IntAct=EBI-1054228, EBI-25847826;
CC P41091; Q92782-2: DPF1; NbExp=3; IntAct=EBI-1054228, EBI-23669343;
CC P41091; P05198: EIF2S1; NbExp=4; IntAct=EBI-1054228, EBI-1056162;
CC P41091; P20042: EIF2S2; NbExp=4; IntAct=EBI-1054228, EBI-711977;
CC P41091; Q53R41: FASTKD1; NbExp=3; IntAct=EBI-1054228, EBI-3957005;
CC P41091; Q06547-2: GABPB1; NbExp=3; IntAct=EBI-1054228, EBI-618189;
CC P41091; Q06547-3: GABPB1; NbExp=3; IntAct=EBI-1054228, EBI-9088619;
CC P41091; P42858: HTT; NbExp=3; IntAct=EBI-1054228, EBI-466029;
CC P41091; Q0VD86: INCA1; NbExp=3; IntAct=EBI-1054228, EBI-6509505;
CC P41091; Q92615: LARP4B; NbExp=3; IntAct=EBI-1054228, EBI-1052558;
CC P41091; Q99683: MAP3K5; NbExp=3; IntAct=EBI-1054228, EBI-476263;
CC P41091; A6NJ78-4: METTL15; NbExp=3; IntAct=EBI-1054228, EBI-10174029;
CC P41091; Q6GQQ9-2: OTUD7B; NbExp=3; IntAct=EBI-1054228, EBI-25830200;
CC P41091; Q8N2H9-4: PELI3; NbExp=3; IntAct=EBI-1054228, EBI-25852006;
CC P41091; O15534: PER1; NbExp=3; IntAct=EBI-1054228, EBI-2557276;
CC P41091; Q9H1D9: POLR3F; NbExp=3; IntAct=EBI-1054228, EBI-710067;
CC P41091; Q9HD47-3: RANGRF; NbExp=3; IntAct=EBI-1054228, EBI-9089733;
CC P41091; Q9NS23-4: RASSF1; NbExp=3; IntAct=EBI-1054228, EBI-438710;
CC P41091; Q7Z6I5: SPATA12; NbExp=3; IntAct=EBI-1054228, EBI-10696971;
CC P41091; Q496A3: SPATS1; NbExp=3; IntAct=EBI-1054228, EBI-3923692;
CC P41091; O60506-4: SYNCRIP; NbExp=3; IntAct=EBI-1054228, EBI-11123832;
CC P41091; Q7Z7C8-2: TAF8; NbExp=3; IntAct=EBI-1054228, EBI-9089028;
CC P41091; P49459: UBE2A; NbExp=3; IntAct=EBI-1054228, EBI-2339348;
CC P41091; Q9NX94: WBP1L; NbExp=3; IntAct=EBI-1054228, EBI-10316321;
CC P41091; Q9BRR0: ZKSCAN3; NbExp=3; IntAct=EBI-1054228, EBI-1965777;
CC P41091; Q3KNS6-3: ZNF829; NbExp=3; IntAct=EBI-1054228, EBI-18036029;
CC -!- TISSUE SPECIFICITY: Expressed in testis, brain, liver and muscle.
CC {ECO:0000269|PubMed:9736774}.
CC -!- DISEASE: MEHMO syndrome (MEHMO) [MIM:300148]: An X-linked recessive
CC syndrome characterized by intellectual disability, epileptic seizures,
CC hypogonadism and hypogenitalism, microcephaly, and obesity.
CC {ECO:0000269|PubMed:23063529, ECO:0000269|PubMed:27333055,
CC ECO:0000269|PubMed:28055140}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- MISCELLANEOUS: Encoded by an chromosome X-linked gene which escapes
CC inactivation. Does not have any homolog on chromosome Y.
CC {ECO:0000269|PubMed:9736774}.
CC -!- SIMILARITY: Belongs to the TRAFAC class translation factor GTPase
CC superfamily. Classic translation factor GTPase family. EIF2G subfamily.
CC {ECO:0000255|PROSITE-ProRule:PRU01059}.
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DR EMBL; L19161; AAA19696.1; -; mRNA.
DR EMBL; AK290397; BAF83086.1; -; mRNA.
DR EMBL; AK312247; BAG35179.1; -; mRNA.
DR EMBL; AB451230; BAG70044.1; -; mRNA.
DR EMBL; AB451353; BAG70167.1; -; mRNA.
DR EMBL; AK222577; BAD96297.1; -; mRNA.
DR EMBL; CH471074; EAW99010.1; -; Genomic_DNA.
DR EMBL; CH471074; EAW99011.1; -; Genomic_DNA.
DR EMBL; CH471074; EAW99012.1; -; Genomic_DNA.
DR EMBL; BC019906; AAH19906.1; -; mRNA.
DR CCDS; CCDS14210.1; -.
DR PIR; A53048; A53048.
DR RefSeq; NP_001406.1; NM_001415.3.
DR PDB; 6FEC; EM; 6.30 A; S=39-460.
DR PDB; 6K71; EM; 4.30 A; P=1-472.
DR PDB; 6K72; EM; 4.60 A; P=1-472.
DR PDB; 6O81; EM; 3.21 A; S/T=1-472.
DR PDB; 6O85; EM; 3.03 A; S=1-472.
DR PDB; 6YBV; EM; 3.80 A; t=1-472.
DR PDB; 6ZMW; EM; 3.70 A; t=1-472.
DR PDB; 6ZP4; EM; 2.90 A; Y=1-472.
DR PDB; 7A09; EM; 3.50 A; Y=1-472.
DR PDB; 7D43; EM; 4.30 A; P=1-472.
DR PDB; 7F66; EM; 2.76 A; S=1-472.
DR PDB; 7F67; EM; 3.59 A; S/T=1-472.
DR PDBsum; 6FEC; -.
DR PDBsum; 6K71; -.
DR PDBsum; 6K72; -.
DR PDBsum; 6O81; -.
DR PDBsum; 6O85; -.
DR PDBsum; 6YBV; -.
DR PDBsum; 6ZMW; -.
DR PDBsum; 6ZP4; -.
DR PDBsum; 7A09; -.
DR PDBsum; 7D43; -.
DR PDBsum; 7F66; -.
DR PDBsum; 7F67; -.
DR AlphaFoldDB; P41091; -.
DR SMR; P41091; -.
DR BioGRID; 108287; 130.
DR CORUM; P41091; -.
DR IntAct; P41091; 73.
DR MINT; P41091; -.
DR STRING; 9606.ENSP00000253039; -.
DR DrugBank; DB04315; Guanosine-5'-Diphosphate.
DR GlyGen; P41091; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P41091; -.
DR MetOSite; P41091; -.
DR PhosphoSitePlus; P41091; -.
DR SwissPalm; P41091; -.
DR BioMuta; EIF2S3; -.
DR DMDM; 729816; -.
DR EPD; P41091; -.
DR jPOST; P41091; -.
DR MassIVE; P41091; -.
DR MaxQB; P41091; -.
DR PaxDb; P41091; -.
DR PeptideAtlas; P41091; -.
DR PRIDE; P41091; -.
DR ProteomicsDB; 55399; -.
DR Antibodypedia; 10229; 217 antibodies from 27 providers.
DR DNASU; 1968; -.
DR Ensembl; ENST00000253039.9; ENSP00000253039.4; ENSG00000130741.11.
DR GeneID; 1968; -.
DR KEGG; hsa:1968; -.
DR MANE-Select; ENST00000253039.9; ENSP00000253039.4; NM_001415.4; NP_001406.1.
DR UCSC; uc004dbc.5; human.
DR CTD; 1968; -.
DR DisGeNET; 1968; -.
DR GeneCards; EIF2S3; -.
DR HGNC; HGNC:3267; EIF2S3.
DR HPA; ENSG00000130741; Low tissue specificity.
DR MalaCards; EIF2S3; -.
DR MIM; 300148; phenotype.
DR MIM; 300161; gene.
DR neXtProt; NX_P41091; -.
DR OpenTargets; ENSG00000130741; -.
DR Orphanet; 85282; MEHMO syndrome.
DR PharmGKB; PA27697; -.
DR VEuPathDB; HostDB:ENSG00000130741; -.
DR eggNOG; KOG0466; Eukaryota.
DR GeneTree; ENSGT00550000074801; -.
DR HOGENOM; CLU_027154_0_1_1; -.
DR InParanoid; P41091; -.
DR OMA; NIGMVGH; -.
DR OrthoDB; 903135at2759; -.
DR PhylomeDB; P41091; -.
DR TreeFam; TF101513; -.
DR BRENDA; 3.6.5.3; 2681.
DR PathwayCommons; P41091; -.
DR Reactome; R-HSA-156827; L13a-mediated translational silencing of Ceruloplasmin expression.
DR Reactome; R-HSA-381042; PERK regulates gene expression.
DR Reactome; R-HSA-382556; ABC-family proteins mediated transport.
DR Reactome; R-HSA-72649; Translation initiation complex formation.
DR Reactome; R-HSA-72695; Formation of the ternary complex, and subsequently, the 43S complex.
DR Reactome; R-HSA-72702; Ribosomal scanning and start codon recognition.
DR Reactome; R-HSA-72706; GTP hydrolysis and joining of the 60S ribosomal subunit.
DR Reactome; R-HSA-72731; Recycling of eIF2:GDP.
DR Reactome; R-HSA-9633012; Response of EIF2AK4 (GCN2) to amino acid deficiency.
DR Reactome; R-HSA-9648895; Response of EIF2AK1 (HRI) to heme deficiency.
DR SignaLink; P41091; -.
DR BioGRID-ORCS; 1968; 420 hits in 704 CRISPR screens.
DR ChiTaRS; EIF2S3; human.
DR GeneWiki; EIF2S3; -.
DR GenomeRNAi; 1968; -.
DR Pharos; P41091; Tbio.
DR PRO; PR:P41091; -.
DR Proteomes; UP000005640; Chromosome X.
DR RNAct; P41091; protein.
DR Bgee; ENSG00000130741; Expressed in germinal epithelium of ovary and 188 other tissues.
DR ExpressionAtlas; P41091; baseline and differential.
DR Genevisible; P41091; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005850; C:eukaryotic translation initiation factor 2 complex; IDA:UniProtKB.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0045296; F:cadherin binding; HDA:BHF-UCL.
DR GO; GO:0005525; F:GTP binding; IEA:UniProtKB-KW.
DR GO; GO:0003924; F:GTPase activity; TAS:ProtInc.
DR GO; GO:0008135; F:translation factor activity, RNA binding; IDA:UniProtKB.
DR GO; GO:0003743; F:translation initiation factor activity; IDA:UniProtKB.
DR GO; GO:0000049; F:tRNA binding; IEA:InterPro.
DR GO; GO:0001731; P:formation of translation preinitiation complex; IBA:GO_Central.
DR GO; GO:0045903; P:positive regulation of translational fidelity; IBA:GO_Central.
DR GO; GO:0006413; P:translational initiation; IDA:UniProtKB.
DR CDD; cd01888; eIF2_gamma; 1.
DR CDD; cd03688; eIF2_gamma_II; 1.
DR CDD; cd15490; eIF2_gamma_III; 1.
DR Gene3D; 3.40.50.300; -; 1.
DR InterPro; IPR004161; EFTu-like_2.
DR InterPro; IPR015256; eIF2g_C.
DR InterPro; IPR044127; eIF2g_dom_2.
DR InterPro; IPR044128; eIF2g_GTP-bd.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR000795; T_Tr_GTP-bd_dom.
DR InterPro; IPR009000; Transl_B-barrel_sf.
DR InterPro; IPR009001; Transl_elong_EF1A/Init_IF2_C.
DR Pfam; PF09173; eIF2_C; 1.
DR Pfam; PF00009; GTP_EFTU; 1.
DR Pfam; PF03144; GTP_EFTU_D2; 1.
DR PRINTS; PR00315; ELONGATNFCT.
DR SUPFAM; SSF50447; SSF50447; 1.
DR SUPFAM; SSF50465; SSF50465; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
DR PROSITE; PS51722; G_TR_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Direct protein sequencing; Disease variant;
KW Epilepsy; GTP-binding; Hydrolase; Initiation factor;
KW Intellectual disability; Nucleotide-binding; Obesity; Phosphoprotein;
KW Protein biosynthesis; Reference proteome.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|PubMed:12665801, ECO:0000269|Ref.8"
FT CHAIN 2..472
FT /note="Eukaryotic translation initiation factor 2 subunit
FT 3"
FT /id="PRO_0000137438"
FT DOMAIN 39..248
FT /note="tr-type G"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01059"
FT REGION 48..55
FT /note="G1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01059"
FT REGION 76..80
FT /note="G2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01059"
FT REGION 134..137
FT /note="G3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01059"
FT REGION 190..193
FT /note="G4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01059"
FT REGION 225..227
FT /note="G5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01059"
FT BINDING 51..56
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:P32481"
FT BINDING 190..193
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:P32481"
FT BINDING 225..227
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:P32481"
FT MOD_RES 2
FT /note="N-acetylalanine; partial"
FT /evidence="ECO:0000269|Ref.8"
FT MOD_RES 16
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9Z0N1"
FT VARIANT 108
FT /note="S -> R (in MEHMO; unknown pathological significance;
FT dbSNP:rs1057515578)"
FT /evidence="ECO:0000269|PubMed:28055140"
FT /id="VAR_078100"
FT VARIANT 125
FT /note="K -> R (in dbSNP:rs16997659)"
FT /id="VAR_002352"
FT VARIANT 222
FT /note="I -> T (in MEHMO; decreased interaction with the
FT other eIF2 complex subunits EIF2S1 and EIF2S2;
FT dbSNP:rs886040855)"
FT /evidence="ECO:0000269|PubMed:23063529"
FT /id="VAR_077139"
FT VARIANT 259
FT /note="I -> M (in MEHMO; unknown pathological significance;
FT dbSNP:rs886040856)"
FT /evidence="ECO:0000269|PubMed:27333055"
FT /id="VAR_077140"
FT CONFLICT 43
FT /note="N -> D (in Ref. 2; BAF83086)"
FT /evidence="ECO:0000305"
FT CONFLICT 292
FT /note="Q -> R (in Ref. 2; BAG35179)"
FT /evidence="ECO:0000305"
FT CONFLICT 407
FT /note="N -> S (in Ref. 4; BAD96297)"
FT /evidence="ECO:0000305"
FT TURN 35..37
FT /evidence="ECO:0007829|PDB:7F66"
FT STRAND 42..45
FT /evidence="ECO:0007829|PDB:7F66"
FT HELIX 54..61
FT /evidence="ECO:0007829|PDB:7F66"
FT STRAND 64..66
FT /evidence="ECO:0007829|PDB:7F66"
FT STRAND 77..80
FT /evidence="ECO:0007829|PDB:7F66"
FT STRAND 83..90
FT /evidence="ECO:0007829|PDB:7F66"
FT STRAND 125..133
FT /evidence="ECO:0007829|PDB:7F66"
FT HELIX 138..145
FT /evidence="ECO:0007829|PDB:7F66"
FT STRAND 147..151
FT /evidence="ECO:0007829|PDB:7F66"
FT STRAND 153..159
FT /evidence="ECO:0007829|PDB:6O85"
FT HELIX 166..178
FT /evidence="ECO:0007829|PDB:7F66"
FT STRAND 185..189
FT /evidence="ECO:0007829|PDB:6O85"
FT HELIX 196..213
FT /evidence="ECO:0007829|PDB:7F66"
FT TURN 214..216
FT /evidence="ECO:0007829|PDB:7F66"
FT HELIX 229..242
FT /evidence="ECO:0007829|PDB:7F66"
FT STRAND 256..259
FT /evidence="ECO:0007829|PDB:6O85"
FT STRAND 270..273
FT /evidence="ECO:0007829|PDB:7F66"
FT STRAND 278..283
FT /evidence="ECO:0007829|PDB:6O85"
FT STRAND 293..302
FT /evidence="ECO:0007829|PDB:7F66"
FT STRAND 306..308
FT /evidence="ECO:0007829|PDB:7F66"
FT STRAND 310..318
FT /evidence="ECO:0007829|PDB:7F66"
FT STRAND 329..331
FT /evidence="ECO:0007829|PDB:7F66"
FT STRAND 333..336
FT /evidence="ECO:0007829|PDB:7F66"
FT STRAND 340..342
FT /evidence="ECO:0007829|PDB:7F66"
FT TURN 345..347
FT /evidence="ECO:0007829|PDB:7F66"
FT STRAND 357..361
FT /evidence="ECO:0007829|PDB:7F66"
FT STRAND 367..374
FT /evidence="ECO:0007829|PDB:7F66"
FT STRAND 390..393
FT /evidence="ECO:0007829|PDB:7F66"
FT STRAND 403..408
FT /evidence="ECO:0007829|PDB:7F66"
FT STRAND 415..420
FT /evidence="ECO:0007829|PDB:7F66"
FT STRAND 425..433
FT /evidence="ECO:0007829|PDB:7F66"
FT STRAND 442..455
FT /evidence="ECO:0007829|PDB:7F66"
FT STRAND 458..465
FT /evidence="ECO:0007829|PDB:7F66"
SQ SEQUENCE 472 AA; 51109 MW; 7A292A6AAF6DF983 CRC64;
MAGGEAGVTL GQPHLSRQDL TTLDVTKLTP LSHEVISRQA TINIGTIGHV AHGKSTVVKA
ISGVHTVRFK NELERNITIK LGYANAKIYK LDDPSCPRPE CYRSCGSSTP DEFPTDIPGT
KGNFKLVRHV SFVDCPGHDI LMATMLNGAA VMDAALLLIA GNESCPQPQT SEHLAAIEIM
KLKHILILQN KIDLVKESQA KEQYEQILAF VQGTVAEGAP IIPISAQLKY NIEVVCEYIV
KKIPVPPRDF TSEPRLIVIR SFDVNKPGCE VDDLKGGVAG GSILKGVLKV GQEIEVRPGI
VSKDSEGKLM CKPIFSKIVS LFAEHNDLQY AAPGGLIGVG TKIDPTLCRA DRMVGQVLGA
VGALPEIFTE LEISYFLLRR LLGVRTEGDK KAAKVQKLSK NEVLMVNIGS LSTGGRVSAV
KADLGKIVLT NPVCTEVGEK IALSRRVEKH WRLIGWGQIR RGVTIKPTVD DD
