GUF1_HUMAN
ID GUF1_HUMAN Reviewed; 669 AA.
AC Q8N442; Q5XKM8; Q9H710; Q9H8U4;
DT 31-OCT-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2002, sequence version 1.
DT 03-AUG-2022, entry version 162.
DE RecName: Full=Translation factor GUF1, mitochondrial {ECO:0000255|HAMAP-Rule:MF_03137};
DE EC=3.6.5.-;
DE AltName: Full=Elongation factor 4 homolog {ECO:0000255|HAMAP-Rule:MF_03137};
DE Short=EF-4 {ECO:0000255|HAMAP-Rule:MF_03137};
DE AltName: Full=GTPase GUF1 {ECO:0000255|HAMAP-Rule:MF_03137};
DE AltName: Full=Ribosomal back-translocase {ECO:0000255|HAMAP-Rule:MF_03137};
DE Flags: Precursor;
GN Name=GUF1 {ECO:0000255|HAMAP-Rule:MF_03137};
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 PRO-58.
RC TISSUE=Colon, and Teratocarcinoma;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
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 [3]
RP INVOLVEMENT IN DEE40, AND VARIANT DEE40 SER-609.
RX PubMed=26486472; DOI=10.1038/ejhg.2015.227;
RA Alfaiz A.A., Mueller V., Boutry-Kryza N., Ville D., Guex N.,
RA de Bellescize J., Rivier C., Labalme A., des Portes V., Edery P., Till M.,
RA Xenarios I., Sanlaville D., Herrmann J.M., Lesca G., Reymond A.;
RT "West syndrome caused by homozygous variant in the evolutionary conserved
RT gene encoding the mitochondrial elongation factor GUF1.";
RL Eur. J. Hum. Genet. 24:1001-1008(2016).
CC -!- FUNCTION: Promotes mitochondrial protein synthesis. May act as a
CC fidelity factor of the translation reaction, by catalyzing a one-codon
CC backward translocation of tRNAs on improperly translocated ribosomes.
CC Binds to mitochondrial ribosomes in a GTP-dependent manner.
CC {ECO:0000255|HAMAP-Rule:MF_03137}.
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; Evidence={ECO:0000255|HAMAP-
CC Rule:MF_03137};
CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane {ECO:0000255|HAMAP-
CC Rule:MF_03137}; Peripheral membrane protein {ECO:0000255|HAMAP-
CC Rule:MF_03137}; Matrix side {ECO:0000255|HAMAP-Rule:MF_03137}.
CC -!- DISEASE: Developmental and epileptic encephalopathy 40 (DEE40)
CC [MIM:617065]: A form of epileptic encephalopathy, a heterogeneous group
CC of severe early-onset epilepsies characterized by refractory seizures,
CC neurodevelopmental impairment, and poor prognosis. Development is
CC normal prior to seizure onset, after which cognitive and motor delays
CC become apparent. DEE40 inheritance is autosomal recessive.
CC {ECO:0000269|PubMed:26486472}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the TRAFAC class translation factor GTPase
CC superfamily. Classic translation factor GTPase family. LepA subfamily.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAB15090.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; AK023282; BAB14507.1; -; mRNA.
DR EMBL; AK025248; BAB15090.1; ALT_SEQ; mRNA.
DR EMBL; BC036768; AAH36768.1; -; mRNA.
DR CCDS; CCDS3468.1; -.
DR RefSeq; NP_068746.2; NM_021927.2.
DR AlphaFoldDB; Q8N442; -.
DR SMR; Q8N442; -.
DR BioGRID; 121939; 102.
DR IntAct; Q8N442; 19.
DR MINT; Q8N442; -.
DR STRING; 9606.ENSP00000281543; -.
DR iPTMnet; Q8N442; -.
DR PhosphoSitePlus; Q8N442; -.
DR BioMuta; GUF1; -.
DR DMDM; 74728811; -.
DR EPD; Q8N442; -.
DR jPOST; Q8N442; -.
DR MassIVE; Q8N442; -.
DR MaxQB; Q8N442; -.
DR PaxDb; Q8N442; -.
DR PeptideAtlas; Q8N442; -.
DR PRIDE; Q8N442; -.
DR ProteomicsDB; 71880; -.
DR Antibodypedia; 1337; 140 antibodies from 26 providers.
DR DNASU; 60558; -.
DR Ensembl; ENST00000281543.6; ENSP00000281543.5; ENSG00000151806.14.
DR GeneID; 60558; -.
DR KEGG; hsa:60558; -.
DR MANE-Select; ENST00000281543.6; ENSP00000281543.5; NM_021927.3; NP_068746.2.
DR UCSC; uc003gww.5; human.
DR CTD; 60558; -.
DR DisGeNET; 60558; -.
DR GeneCards; GUF1; -.
DR HGNC; HGNC:25799; GUF1.
DR HPA; ENSG00000151806; Low tissue specificity.
DR MalaCards; GUF1; -.
DR MIM; 617064; gene.
DR MIM; 617065; phenotype.
DR neXtProt; NX_Q8N442; -.
DR OpenTargets; ENSG00000151806; -.
DR Orphanet; 3451; Infantile spasms syndrome.
DR PharmGKB; PA143485485; -.
DR VEuPathDB; HostDB:ENSG00000151806; -.
DR eggNOG; KOG0462; Eukaryota.
DR GeneTree; ENSGT00550000074940; -.
DR HOGENOM; CLU_009995_3_3_1; -.
DR InParanoid; Q8N442; -.
DR OMA; MVQIAIQ; -.
DR OrthoDB; 165663at2759; -.
DR PhylomeDB; Q8N442; -.
DR TreeFam; TF314751; -.
DR PathwayCommons; Q8N442; -.
DR SignaLink; Q8N442; -.
DR BioGRID-ORCS; 60558; 11 hits in 1077 CRISPR screens.
DR ChiTaRS; GUF1; human.
DR GenomeRNAi; 60558; -.
DR Pharos; Q8N442; Tbio.
DR PRO; PR:Q8N442; -.
DR Proteomes; UP000005640; Chromosome 4.
DR RNAct; Q8N442; protein.
DR Bgee; ENSG00000151806; Expressed in ventricular zone and 182 other tissues.
DR ExpressionAtlas; Q8N442; baseline and differential.
DR Genevisible; Q8N442; HS.
DR GO; GO:0005743; C:mitochondrial inner membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005759; C:mitochondrial matrix; IEA:UniProtKB-UniRule.
DR GO; GO:0005739; C:mitochondrion; IBA:GO_Central.
DR GO; GO:0005525; F:GTP binding; IEA:UniProtKB-UniRule.
DR GO; GO:0003924; F:GTPase activity; IEA:UniProtKB-UniRule.
DR GO; GO:0097177; F:mitochondrial ribosome binding; IBA:GO_Central.
DR GO; GO:0043022; F:ribosome binding; IBA:GO_Central.
DR GO; GO:0045727; P:positive regulation of translation; IBA:GO_Central.
DR GO; GO:0006412; P:translation; IEA:UniProtKB-KW.
DR CDD; cd03709; lepA_C; 1.
DR Gene3D; 3.30.70.2570; -; 1.
DR Gene3D; 3.40.50.300; -; 1.
DR HAMAP; MF_00071; LepA; 1.
DR InterPro; IPR006297; EF-4.
DR InterPro; IPR035647; EFG_III/V.
DR InterPro; IPR000640; EFG_V-like.
DR InterPro; IPR004161; EFTu-like_2.
DR InterPro; IPR031157; G_TR_CS.
DR InterPro; IPR038363; LepA_C_sf.
DR InterPro; IPR013842; LepA_CTD.
DR InterPro; IPR035654; LepA_IV.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR005225; Small_GTP-bd_dom.
DR InterPro; IPR000795; T_Tr_GTP-bd_dom.
DR InterPro; IPR009000; Transl_B-barrel_sf.
DR PANTHER; PTHR43512; PTHR43512; 1.
DR Pfam; PF00679; EFG_C; 1.
DR Pfam; PF00009; GTP_EFTU; 1.
DR Pfam; PF03144; GTP_EFTU_D2; 1.
DR Pfam; PF06421; LepA_C; 1.
DR PRINTS; PR00315; ELONGATNFCT.
DR SUPFAM; SSF50447; SSF50447; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
DR SUPFAM; SSF54980; SSF54980; 2.
DR TIGRFAMs; TIGR01393; lepA; 1.
DR TIGRFAMs; TIGR00231; small_GTP; 1.
DR PROSITE; PS00301; G_TR_1; 1.
DR PROSITE; PS51722; G_TR_2; 1.
PE 1: Evidence at protein level;
KW Disease variant; Epilepsy; GTP-binding; Hydrolase; Membrane; Mitochondrion;
KW Mitochondrion inner membrane; Nucleotide-binding; Protein biosynthesis;
KW Reference proteome; Transit peptide.
FT TRANSIT 1..49
FT /note="Mitochondrion"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03137"
FT CHAIN 50..669
FT /note="Translation factor GUF1, mitochondrial"
FT /id="PRO_0000256251"
FT DOMAIN 66..247
FT /note="tr-type G"
FT BINDING 75..82
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03137"
FT BINDING 140..144
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03137"
FT BINDING 194..197
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03137"
FT VARIANT 58
FT /note="L -> P (in dbSNP:rs6447368)"
FT /evidence="ECO:0000269|PubMed:14702039"
FT /id="VAR_028895"
FT VARIANT 329
FT /note="T -> I (in dbSNP:rs10470742)"
FT /id="VAR_028896"
FT VARIANT 609
FT /note="A -> S (in DEE40; dbSNP:rs879255631)"
FT /evidence="ECO:0000269|PubMed:26486472"
FT /id="VAR_077804"
FT CONFLICT 85
FT /note="A -> T (in Ref. 1; BAB14507)"
FT /evidence="ECO:0000305"
FT CONFLICT 417
FT /note="L -> P (in Ref. 1; BAB14507)"
FT /evidence="ECO:0000305"
FT CONFLICT 625
FT /note="Y -> C (in Ref. 1; BAB14507)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 669 AA; 74328 MW; 428892437C91ED36 CRC64;
MWTLVGRGWG CARALAPRAT GAALLVAPGP RSAPTLGAAP ESWATDRLYS SAEFKEKLDM
SRFPVENIRN FSIVAHVDHG KSTLADRLLE LTGTIDKTKN NKQVLDKLQV ERERGITVKA
QTASLFYNCE GKQYLLNLID TPGHVDFSYE VSRSLSACQG VLLVVDANEG IQAQTVANFF
LAFEAQLSVI PVINKIDLKN ADPERVENQI EKVFDIPSDE CIKISAKLGT NVESVLQAII
ERIPPPKVHR KNPLRALVFD STFDQYRGVI ANVALFDGVV SKGDKIVSAH TQKTYEVNEV
GVLNPNEQPT HKLYAGQVGY LIAGMKDVTE AQIGDTLCLH KQPVEPLPGF KSAKPMVFAG
MYPLDQSEYN NLKSAIEKLT LNDSSVTVHR DSSLALGAGW RLGFLGLLHM EVFNQRLEQE
YNASVILTTP TVPYKAVLSS SKLIKEHREK EITIINPAQF PDKSKVTEYL EPVVLGTIIT
PDEYTGKIMM LCEARRAVQK NMIFIDQNRV MLKYLFPLNE IVVDFYDSLK SLSSGYASFD
YEDAGYQTAE LVKMDILLNG NTVEELVTVV HKDKAHSIGK AICERLKDSL PRQLFEIAIQ
AAIGSKIIAR ETVKAYRKNV LAKCYGGDIT RKMKLLKRQA EGKKKLRKIG NVEVPKDAFI
KVLKTQSSK
