DHE3_HUMAN
ID DHE3_HUMAN Reviewed; 558 AA.
AC P00367; B3KV55; B4DGN5; Q5TBU3;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 01-JAN-1990, sequence version 2.
DT 03-AUG-2022, entry version 233.
DE RecName: Full=Glutamate dehydrogenase 1, mitochondrial;
DE Short=GDH 1;
DE EC=1.4.1.3 {ECO:0000269|PubMed:11032875, ECO:0000269|PubMed:11254391, ECO:0000269|PubMed:11903050, ECO:0000269|PubMed:16023112, ECO:0000269|PubMed:16959573};
DE Flags: Precursor;
GN Name=GLUD1; Synonyms=GLUD;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Brain, and Liver;
RX PubMed=3426581; DOI=10.1016/0006-291x(87)90381-0;
RA Nakatani Y., Banner C., von Herrat M., Schneider M.E., Smith H.H.,
RA Freese E.;
RT "Comparison of human brain and liver glutamate dehydrogenase cDNAs.";
RL Biochem. Biophys. Res. Commun. 149:405-410(1987).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Liver;
RX PubMed=3377777; DOI=10.1016/s0006-291x(88)80440-6;
RA Amuro N., Yamaura M., Goto Y., Okazaki T.;
RT "Molecular cloning and nucleotide sequence of the cDNA for human liver
RT glutamate dehydrogenase precursor.";
RL Biochem. Biophys. Res. Commun. 152:1395-1400(1988).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=3399399; DOI=10.1093/nar/16.13.6237;
RA Nakatani Y., Schneider M.E., Banner C., Freese E.;
RT "Complete nucleotide sequence of human glutamate dehydrogenase cDNA.";
RL Nucleic Acids Res. 16:6237-6237(1988).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Liver;
RX PubMed=3368458; DOI=10.1073/pnas.85.10.3494;
RA Mavrothalassitis G., Tzimagiorgis G., Mitsialis A., Zannis V.,
RA Plaitakis A., Papamatheakis J., Moschonas N.;
RT "Isolation and characterization of cDNA clones encoding human liver
RT glutamate dehydrogenase: evidence for a small gene family.";
RL Proc. Natl. Acad. Sci. U.S.A. 85:3494-3498(1988).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC TISSUE=Placenta;
RX PubMed=8486350; DOI=10.1006/geno.1993.1152;
RA Michaelidis T.M., Tzimagiorgis G., Moschonas N.K., Papamatheakis J.;
RT "The human glutamate dehydrogenase gene family: gene organization and
RT structural characterization.";
RL Genomics 16:150-160(1993).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 3).
RC TISSUE=Brain, and Brain cortex;
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 [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164054; DOI=10.1038/nature02462;
RA Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L.,
RA Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K.,
RA Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L.,
RA Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P.,
RA Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N.,
RA Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A.,
RA Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C.,
RA Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D.,
RA Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C.,
RA Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K.,
RA Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A.,
RA Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S.,
RA McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S.,
RA Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V.,
RA Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A.,
RA Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M.,
RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A.,
RA Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P.,
RA Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y.,
RA Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D.,
RA Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 10.";
RL Nature 429:375-381(2004).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton 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 [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Duodenum, and Eye;
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 [10]
RP PROTEIN SEQUENCE OF 54-558.
RC TISSUE=Liver;
RX PubMed=429360; DOI=10.1016/s0021-9258(18)50777-8;
RA Julliard J.H., Smith E.L.;
RT "Partial amino acid sequence of the glutamate dehydrogenase of human liver
RT and a revision of the sequence of the bovine enzyme.";
RL J. Biol. Chem. 254:3427-3438(1979).
RN [11]
RP PROTEIN SEQUENCE OF 54-69.
RC TISSUE=Liver;
RX PubMed=1286669; DOI=10.1002/elps.11501301201;
RA Hochstrasser D.F., Frutiger S., Paquet N., Bairoch A., Ravier F.,
RA Pasquali C., Sanchez J.-C., Tissot J.-D., Bjellqvist B., Vargas R.,
RA Appel R.D., Hughes G.J.;
RT "Human liver protein map: a reference database established by
RT microsequencing and gel comparison.";
RL Electrophoresis 13:992-1001(1992).
RN [12]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 301-558 (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=3585334; DOI=10.1111/j.1471-4159.1987.tb03422.x;
RA Banner C., Silverman S., Thomas J.W., Lampel K.A., Vitkovic L., Huie D.,
RA Wenthold R.J.;
RT "Isolation of a human brain cDNA for glutamate dehydrogenase.";
RL J. Neurochem. 49:246-252(1987).
RN [13]
RP PROTEIN SEQUENCE OF 481-496, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC TISSUE=Brain, and Cajal-Retzius cell;
RA Lubec G., Vishwanath V.;
RL Submitted (MAR-2007) to UniProtKB.
RN [14]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 540-558.
RX PubMed=8314555; DOI=10.1007/bf00217767;
RA Tzimagiorgis G., Leversha M.A., Chroniary K., Goulielmos G., Sargent C.A.,
RA Ferguson-Smith M., Moschonas N.K.;
RT "Structure and expression analysis of a member of the human glutamate
RT dehydrogenase (GLUD) gene family mapped to chromosome 10p11.2.";
RL Hum. Genet. 91:433-438(1993).
RN [15]
RP CATALYTIC ACTIVITY, FUNCTION, AND ACTIVITY REGULATION.
RX PubMed=11032875; DOI=10.1046/j.1471-4159.2000.0751862.x;
RA Plaitakis A., Metaxari M., Shashidharan P.;
RT "Nerve tissue-specific (GLUD2) and housekeeping (GLUD1) human glutamate
RT dehydrogenases are regulated by distinct allosteric mechanisms:
RT implications for biologic function.";
RL J. Neurochem. 75:1862-1869(2000).
RN [16]
RP ADP-RIBOSYLATION AT CYS-172, CATALYTIC ACTIVITY, AND FUNCTION.
RX PubMed=16023112; DOI=10.1016/j.febslet.2005.06.041;
RA Choi M.M., Huh J.W., Yang S.J., Cho E.H., Choi S.Y., Cho S.W.;
RT "Identification of ADP-ribosylation site in human glutamate dehydrogenase
RT isozymes.";
RL FEBS Lett. 579:4125-4130(2005).
RN [17]
RP SUBCELLULAR LOCATION.
RX PubMed=19448744; DOI=10.1139/o09-008;
RA Mastorodemos V., Kotzamani D., Zaganas I., Arianoglou G., Latsoudis H.,
RA Plaitakis A.;
RT "Human GLUD1 and GLUD2 glutamate dehydrogenase localize to mitochondria and
RT endoplasmic reticulum.";
RL Biochem. Cell Biol. 87:505-516(2009).
RN [18]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-84; LYS-480 AND LYS-503, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C.,
RA Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [19]
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 [20]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-227; SER-384 AND TYR-512, AND
RP 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 [21]
RP CLEAVAGE OF TRANSIT PEPTIDE [LARGE SCALE ANALYSIS] AFTER TYR-53, AND
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 [22]
RP CHARACTERIZATION OF VARIANT TYR-507, ACTIVITY REGULATION, FUNCTION, AND
RP CATALYTIC ACTIVITY.
RX PubMed=11254391; DOI=10.1006/jmbi.2001.4499;
RA Smith T.J., Peterson P.E., Schmidt T., Fang J., Stanley C.A.;
RT "Structures of bovine glutamate dehydrogenase complexes elucidate the
RT mechanism of purine regulation.";
RL J. Mol. Biol. 307:707-720(2001).
RN [23]
RP MUTAGENESIS OF SER-501 AND ARG-516, CHARACTERIZATION OF VARIANT TYR-507,
RP AND ALLOSTERIC REGULATION.
RX PubMed=11903050; DOI=10.1042/0264-6021:3630081;
RA Fang J., Hsu B.Y.L., MacMullen C.M., Poncz M., Smith T.J., Stanley C.A.;
RT "Expression, purification and characterization of human glutamate
RT dehydrogenase (GDH) allosteric regulatory mutations.";
RL Biochem. J. 363:81-87(2002).
RN [24]
RP ADP-RIBOSYLATION, CATALYTIC ACTIVITY, FUNCTION, AND ACTIVITY REGULATION.
RX PubMed=16959573; DOI=10.1016/j.cell.2006.06.057;
RA Haigis M.C., Mostoslavsky R., Haigis K.M., Fahie K., Christodoulou D.C.,
RA Murphy A.J., Valenzuela D.M., Yancopoulos G.D., Karow M., Blander G.,
RA Wolberger C., Prolla T.A., Weindruch R., Alt F.W., Guarente L.;
RT "SIRT4 inhibits glutamate dehydrogenase and opposes the effects of calorie
RT restriction in pancreatic beta cells.";
RL Cell 126:941-954(2006).
RN [25]
RP HYDROXYBUTYRYLATION AT LYS-147.
RX PubMed=29192674; DOI=10.1038/cr.2017.149;
RA Huang H., Luo Z., Qi S., Huang J., Xu P., Wang X., Gao L., Li F., Wang J.,
RA Zhao W., Gu W., Chen Z., Dai L., Dai J., Zhao Y.;
RT "Landscape of the regulatory elements for lysine 2-hydroxyisobutyrylation
RT pathway.";
RL Cell Res. 28:111-125(2018).
RN [26]
RP X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 54-558.
RX PubMed=12054821; DOI=10.1016/s0022-2836(02)00161-4;
RA Smith T.J., Schmidt T., Fang J., Wu J., Siuzdak G., Stanley C.A.;
RT "The structure of apo human glutamate dehydrogenase details subunit
RT communication and allostery.";
RL J. Mol. Biol. 318:765-777(2002).
RN [27]
RP X-RAY CRYSTALLOGRAPHY (3.3 ANGSTROMS) OF 63-558 OF MUTANT ALA-516, AND
RP ALLOSTERIC REGULATION.
RX PubMed=12653548; DOI=10.1021/bi0206917;
RA Banerjee S., Schmidt T., Fang J., Stanley C.A., Smith T.J.;
RT "Structural studies on ADP activation of mammalian glutamate dehydrogenase
RT and the evolution of regulation.";
RL Biochemistry 42:3446-3456(2003).
RN [28]
RP VARIANTS HHF6 LEU-498; SER-499; ASP-499; PRO-501 AND TYR-507,
RP CHARACTERIZATION OF VARIANT TYR-507, FUNCTION, AND ACTIVITY REGULATION.
RX PubMed=9571255; DOI=10.1056/nejm199805073381904;
RA Stanley C.A., Lieu Y.K., Hsu B.Y.L., Burlina A.B., Greenberg C.R.,
RA Hopwood N.J., Perlman K., Rich B.H., Zammarchi E., Poncz M.;
RT "Hyperinsulinism and hyperammonemia in infants with regulatory mutations of
RT the glutamate dehydrogenase gene.";
RL N. Engl. J. Med. 338:1352-1357(1998).
RN [29]
RP VARIANTS HHF6 LYS-318 AND ALA-349.
RX PubMed=10636977; DOI=10.1016/s0022-3476(00)90052-0;
RA Miki Y., Taki T., Ohura T., Kato H., Yanagisawa M., Hayashi Y.;
RT "Novel missense mutations in the glutamate dehydrogenase gene in the
RT congenital hyperinsulinism-hyperammonemia syndrome.";
RL J. Pediatr. 136:69-72(2000).
RN [30]
RP VARIANTS HHF6 CYS-274 AND HIS-322.
RX PubMed=11214910; DOI=10.1007/s004390000432;
RA Santer R., Kinner M., Passarge M., Superti-Furga A., Mayatepek E.,
RA Meissner T., Schneppenheim R., Schaub J.;
RT "Novel missense mutations outside the allosteric domain of glutamate
RT dehydrogenase are prevalent in European patients with the congenital
RT hyperinsulinism-hyperammonemia syndrome.";
RL Hum. Genet. 108:66-71(2001).
RN [31]
RP VARIANTS HHF6 CYS-270; CYS-274; THR-318; CYS-319; CYS-322 AND HIS-322,
RP CHARACTERIZATION OF VARIANTS HHF6 CYS-270; CYS-274; THR-318; CYS-322 AND
RP HIS-322, FUNCTION, AND ACTIVITY REGULATION.
RX PubMed=11297618; DOI=10.1210/jcem.86.4.7414;
RA MacMullen C., Fang J., Hsu B.Y.L., Kelly A., de Lonlay-Debeney P.,
RA Saudubray J.-M., Ganguly A., Smith T.J., Stanley C.A., Brown R., Buist N.,
RA Dasouki M., Fefferman R., Grange D., Karaviti L., Luedke C., Marriage B.,
RA McLaughlin J., Perlman K., Seashore M., van Vliet G.;
RT "Hyperinsulinism/hyperammonemia syndrome in children with regulatory
RT mutations in the inhibitory guanosine triphosphate-binding domain of
RT glutamate dehydrogenase.";
RL J. Clin. Endocrinol. Metab. 86:1782-1787(2001).
CC -!- FUNCTION: Mitochondrial glutamate dehydrogenase that catalyzes the
CC conversion of L-glutamate into alpha-ketoglutarate. Plays a key role in
CC glutamine anaplerosis by producing alpha-ketoglutarate, an important
CC intermediate in the tricarboxylic acid cycle (PubMed:11032875,
CC PubMed:16959573, PubMed:11254391, PubMed:16023112). Plays a role in
CC insulin homeostasis (PubMed:9571255, PubMed:11297618). May be involved
CC in learning and memory reactions by increasing the turnover of the
CC excitatory neurotransmitter glutamate (By similarity).
CC {ECO:0000250|UniProtKB:P10860, ECO:0000269|PubMed:11032875,
CC ECO:0000269|PubMed:11254391, ECO:0000269|PubMed:11297618,
CC ECO:0000269|PubMed:16023112, ECO:0000269|PubMed:16959573,
CC ECO:0000269|PubMed:9571255}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + L-glutamate + NAD(+) = 2-oxoglutarate + H(+) + NADH +
CC NH4(+); Xref=Rhea:RHEA:15133, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:16810, ChEBI:CHEBI:28938, ChEBI:CHEBI:29985,
CC ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; EC=1.4.1.3;
CC Evidence={ECO:0000269|PubMed:11254391, ECO:0000269|PubMed:11903050,
CC ECO:0000269|PubMed:16023112, ECO:0000269|PubMed:16959573};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H2O + L-glutamate + NADP(+) = 2-oxoglutarate + H(+) + NADPH +
CC NH4(+); Xref=Rhea:RHEA:11612, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:16810, ChEBI:CHEBI:28938, ChEBI:CHEBI:29985,
CC ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; EC=1.4.1.3;
CC Evidence={ECO:0000269|PubMed:11032875};
CC -!- ACTIVITY REGULATION: Subject to allosteric regulation. Activated by ADP
CC (PubMed:11903050). Inhibited by GTP and ATP (PubMed:11254391,
CC PubMed:11032875, PubMed:9571255, PubMed:11903050, PubMed:11297618). ADP
CC can occupy the NADH binding site and activate the enzyme
CC (PubMed:16023112). Inhibited by SIRT4 (PubMed:16959573). Inhibited by
CC HADH (By similarity). {ECO:0000250|UniProtKB:P26443,
CC ECO:0000269|PubMed:11032875, ECO:0000269|PubMed:11254391,
CC ECO:0000269|PubMed:11297618, ECO:0000269|PubMed:11903050,
CC ECO:0000269|PubMed:16023112, ECO:0000269|PubMed:16959573,
CC ECO:0000269|PubMed:9571255}.
CC -!- SUBUNIT: Homohexamer (By similarity). Interacts with HADH; this
CC interaction inhibits the activation of GLUD1 (By similarity).
CC {ECO:0000250|UniProtKB:P00366, ECO:0000250|UniProtKB:P26443}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000269|PubMed:19448744}.
CC Endoplasmic reticulum {ECO:0000269|PubMed:19448744}. Note=Mostly
CC translocates into the mitochondria, only a small amount of the protein
CC localizes to the endoplasmic reticulum. {ECO:0000269|PubMed:19448744}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=P00367-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P00367-2; Sequence=VSP_056244;
CC Name=3;
CC IsoId=P00367-3; Sequence=VSP_056523, VSP_056524;
CC -!- PTM: ADP-ribosylated by SIRT4, leading to inactivate glutamate
CC dehydrogenase activity (PubMed:16959573). Stoichiometry shows that ADP-
CC ribosylation occurs in one subunit per catalytically active homohexamer
CC (PubMed:16023112). {ECO:0000269|PubMed:16023112,
CC ECO:0000269|PubMed:16959573}.
CC -!- DISEASE: Familial hyperinsulinemic hypoglycemia 6 (HHF6) [MIM:606762]:
CC Familial hyperinsulinemic hypoglycemia [MIM:256450], also referred to
CC as congenital hyperinsulinism, nesidioblastosis, or persistent
CC hyperinsulinemic hypoglycemia of infancy (PPHI), is the most common
CC cause of persistent hypoglycemia in infancy and is due to defective
CC negative feedback regulation of insulin secretion by low glucose
CC levels. In HHF6 elevated oxidation rate of glutamate to alpha-
CC ketoglutarate stimulates insulin secretion in the pancreatic beta
CC cells, while they impair detoxification of ammonium in the liver.
CC {ECO:0000269|PubMed:10636977, ECO:0000269|PubMed:11214910,
CC ECO:0000269|PubMed:11297618, ECO:0000269|PubMed:9571255}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- SIMILARITY: Belongs to the Glu/Leu/Phe/Val dehydrogenases family.
CC {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Wikipedia; Note=Glutamate dehydrogenase 1 entry;
CC URL="https://en.wikipedia.org/wiki/Glutamate_dehydrogenase_1";
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DR EMBL; X07674; CAA30521.1; -; mRNA.
DR EMBL; M20867; AAA52526.1; -; mRNA.
DR EMBL; M37154; AAA52525.1; -; mRNA.
DR EMBL; X07769; CAA30598.1; -; mRNA.
DR EMBL; J03248; AAA52523.1; -; mRNA.
DR EMBL; X66300; CAA46994.2; -; Genomic_DNA.
DR EMBL; X66301; CAA46994.2; JOINED; Genomic_DNA.
DR EMBL; X66302; CAA46994.2; JOINED; Genomic_DNA.
DR EMBL; X66303; CAA46994.2; JOINED; Genomic_DNA.
DR EMBL; X66304; CAA46994.2; JOINED; Genomic_DNA.
DR EMBL; X66305; CAA46994.2; JOINED; Genomic_DNA.
DR EMBL; X66306; CAA46994.2; JOINED; Genomic_DNA.
DR EMBL; X66307; CAA46994.2; JOINED; Genomic_DNA.
DR EMBL; X66308; CAA46994.2; JOINED; Genomic_DNA.
DR EMBL; X66309; CAA46994.2; JOINED; Genomic_DNA.
DR EMBL; X66311; CAA46994.2; JOINED; Genomic_DNA.
DR EMBL; X66312; CAA46994.2; JOINED; Genomic_DNA.
DR EMBL; AK122685; BAG53667.1; -; mRNA.
DR EMBL; AK294685; BAG57846.1; -; mRNA.
DR EMBL; AL136982; CAI17120.1; -; Genomic_DNA.
DR EMBL; CH471142; EAW80300.1; -; Genomic_DNA.
DR EMBL; CH471142; EAW80302.1; -; Genomic_DNA.
DR EMBL; BC040132; AAH40132.1; -; mRNA.
DR EMBL; BC112946; AAI12947.1; -; mRNA.
DR EMBL; X67491; CAA47830.1; -; Genomic_DNA.
DR CCDS; CCDS7382.1; -. [P00367-1]
DR PIR; A28208; DEHUE.
DR PIR; I37424; I37424.
DR PIR; S29331; S29331.
DR PIR; S60192; S60192.
DR RefSeq; NP_001305829.1; NM_001318900.1. [P00367-3]
DR RefSeq; NP_001305830.1; NM_001318901.1. [P00367-2]
DR RefSeq; NP_001305831.1; NM_001318902.1. [P00367-2]
DR RefSeq; NP_001305833.1; NM_001318904.1. [P00367-2]
DR RefSeq; NP_001305834.1; NM_001318905.1. [P00367-2]
DR RefSeq; NP_001305835.1; NM_001318906.1. [P00367-2]
DR RefSeq; NP_005262.1; NM_005271.4. [P00367-1]
DR PDB; 1L1F; X-ray; 2.70 A; A/B/C/D/E/F=54-558.
DR PDB; 1NR1; X-ray; 3.30 A; A/B/C/D/E/F=63-558.
DR PDB; 6DQG; X-ray; 2.70 A; A/B/C/D/E/F=63-558.
DR PDBsum; 1L1F; -.
DR PDBsum; 1NR1; -.
DR PDBsum; 6DQG; -.
DR AlphaFoldDB; P00367; -.
DR SMR; P00367; -.
DR BioGRID; 109008; 174.
DR IntAct; P00367; 81.
DR MINT; P00367; -.
DR STRING; 9606.ENSP00000277865; -.
DR DrugBank; DB11081; Aluminum chloride.
DR DrugBank; DB00142; Glutamic acid.
DR DrugBank; DB04137; Guanosine-5'-Triphosphate.
DR DrugBank; DB00756; Hexachlorophene.
DR DrugBank; DB00157; NADH.
DR DrugCentral; P00367; -.
DR GlyGen; P00367; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P00367; -.
DR MetOSite; P00367; -.
DR PhosphoSitePlus; P00367; -.
DR SwissPalm; P00367; -.
DR BioMuta; GLUD1; -.
DR DMDM; 118541; -.
DR REPRODUCTION-2DPAGE; IPI00016801; -.
DR SWISS-2DPAGE; P00367; -.
DR UCD-2DPAGE; P00367; -.
DR EPD; P00367; -.
DR jPOST; P00367; -.
DR MassIVE; P00367; -.
DR MaxQB; P00367; -.
DR PaxDb; P00367; -.
DR PeptideAtlas; P00367; -.
DR PRIDE; P00367; -.
DR ProteomicsDB; 3743; -.
DR ProteomicsDB; 4147; -.
DR ProteomicsDB; 51236; -. [P00367-1]
DR Antibodypedia; 16023; 259 antibodies from 38 providers.
DR DNASU; 2746; -.
DR Ensembl; ENST00000277865.5; ENSP00000277865.4; ENSG00000148672.10. [P00367-1]
DR Ensembl; ENST00000681988.1; ENSP00000507316.1; ENSG00000148672.10. [P00367-2]
DR Ensembl; ENST00000682507.1; ENSP00000508098.1; ENSG00000148672.10. [P00367-2]
DR Ensembl; ENST00000683256.1; ENSP00000507901.1; ENSG00000148672.10. [P00367-2]
DR Ensembl; ENST00000683269.1; ENSP00000508107.1; ENSG00000148672.10. [P00367-2]
DR Ensembl; ENST00000683783.1; ENSP00000507881.1; ENSG00000148672.10. [P00367-2]
DR Ensembl; ENST00000684372.1; ENSP00000508244.1; ENSG00000148672.10. [P00367-2]
DR Ensembl; ENST00000684546.1; ENSP00000507729.1; ENSG00000148672.10. [P00367-2]
DR GeneID; 2746; -.
DR KEGG; hsa:2746; -.
DR MANE-Select; ENST00000277865.5; ENSP00000277865.4; NM_005271.5; NP_005262.1.
DR UCSC; uc001keh.4; human. [P00367-1]
DR CTD; 2746; -.
DR DisGeNET; 2746; -.
DR GeneCards; GLUD1; -.
DR GeneReviews; GLUD1; -.
DR HGNC; HGNC:4335; GLUD1.
DR HPA; ENSG00000148672; Tissue enhanced (liver).
DR MalaCards; GLUD1; -.
DR MIM; 138130; gene.
DR MIM; 606762; phenotype.
DR neXtProt; NX_P00367; -.
DR OpenTargets; ENSG00000148672; -.
DR Orphanet; 35878; Hyperinsulinism-hyperammonemia syndrome.
DR PharmGKB; PA28737; -.
DR VEuPathDB; HostDB:ENSG00000148672; -.
DR eggNOG; KOG2250; Eukaryota.
DR GeneTree; ENSGT00390000000854; -.
DR HOGENOM; CLU_025763_1_0_1; -.
DR InParanoid; P00367; -.
DR OMA; PCFAAFP; -.
DR PhylomeDB; P00367; -.
DR TreeFam; TF313945; -.
DR BioCyc; MetaCyc:HS07548-MON; -.
DR BRENDA; 1.4.1.3; 2681.
DR PathwayCommons; P00367; -.
DR Reactome; R-HSA-2151201; Transcriptional activation of mitochondrial biogenesis.
DR Reactome; R-HSA-8964539; Glutamate and glutamine metabolism.
DR SABIO-RK; P00367; -.
DR SignaLink; P00367; -.
DR SIGNOR; P00367; -.
DR BioGRID-ORCS; 2746; 19 hits in 1085 CRISPR screens.
DR ChiTaRS; GLUD1; human.
DR EvolutionaryTrace; P00367; -.
DR GeneWiki; Glutamate_dehydrogenase_1; -.
DR GenomeRNAi; 2746; -.
DR Pharos; P00367; Tbio.
DR PRO; PR:P00367; -.
DR Proteomes; UP000005640; Chromosome 10.
DR RNAct; P00367; protein.
DR Bgee; ENSG00000148672; Expressed in right lobe of liver and 200 other tissues.
DR ExpressionAtlas; P00367; baseline and differential.
DR Genevisible; P00367; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:BHF-UCL.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:UniProtKB.
DR GO; GO:0005759; C:mitochondrial matrix; TAS:Reactome.
DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB.
DR GO; GO:0043531; F:ADP binding; IDA:BHF-UCL.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004352; F:glutamate dehydrogenase (NAD+) activity; IDA:UniProtKB.
DR GO; GO:0004354; F:glutamate dehydrogenase (NADP+) activity; IEA:RHEA.
DR GO; GO:0004353; F:glutamate dehydrogenase [NAD(P)+] activity; IDA:BHF-UCL.
DR GO; GO:0005525; F:GTP binding; IDA:BHF-UCL.
DR GO; GO:0042802; F:identical protein binding; TAS:BHF-UCL.
DR GO; GO:0070728; F:leucine binding; IDA:BHF-UCL.
DR GO; GO:0070403; F:NAD+ binding; IDA:BHF-UCL.
DR GO; GO:0006537; P:glutamate biosynthetic process; IDA:BHF-UCL.
DR GO; GO:0006538; P:glutamate catabolic process; IDA:UniProtKB.
DR GO; GO:0006541; P:glutamine metabolic process; ISS:UniProtKB.
DR GO; GO:0032024; P:positive regulation of insulin secretion; IMP:BHF-UCL.
DR GO; GO:0021762; P:substantia nigra development; HEP:UniProtKB.
DR GO; GO:0072350; P:tricarboxylic acid metabolic process; ISS:UniProtKB.
DR CDD; cd01076; NAD_bind_1_Glu_DH; 1.
DR InterPro; IPR046346; Aminiacid_DH-like_N_sf.
DR InterPro; IPR006095; Glu/Leu/Phe/Val_DH.
DR InterPro; IPR033524; Glu/Leu/Phe/Val_DH_AS.
DR InterPro; IPR006096; Glu/Leu/Phe/Val_DH_C.
DR InterPro; IPR006097; Glu/Leu/Phe/Val_DH_dimer_dom.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR InterPro; IPR033922; NAD_bind_Glu_DH.
DR Pfam; PF00208; ELFV_dehydrog; 1.
DR Pfam; PF02812; ELFV_dehydrog_N; 1.
DR PRINTS; PR00082; GLFDHDRGNASE.
DR SMART; SM00839; ELFV_dehydrog; 1.
DR SUPFAM; SSF51735; SSF51735; 1.
DR SUPFAM; SSF53223; SSF53223; 1.
DR PROSITE; PS00074; GLFV_DEHYDROGENASE; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; ADP-ribosylation; Alternative splicing;
KW ATP-binding; Direct protein sequencing; Disease variant;
KW Endoplasmic reticulum; GTP-binding; Hydroxylation; Mitochondrion; NADP;
KW Nucleotide-binding; Oxidoreductase; Phosphoprotein; Reference proteome;
KW Transit peptide.
FT TRANSIT 1..53
FT /note="Mitochondrion"
FT /evidence="ECO:0000269|PubMed:1286669,
FT ECO:0000269|PubMed:429360, ECO:0007744|PubMed:25944712"
FT CHAIN 54..558
FT /note="Glutamate dehydrogenase 1, mitochondrial"
FT /id="PRO_0000007206"
FT ACT_SITE 183
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10011"
FT BINDING 141..143
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P00366"
FT BINDING 147
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P00366"
FT BINDING 171
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P00366"
FT BINDING 176
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P00366"
FT BINDING 252
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P00366"
FT BINDING 266
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:P00366"
FT BINDING 270
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:P00366"
FT BINDING 319
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:P00366"
FT BINDING 322
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250|UniProtKB:P00366"
FT BINDING 438
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P00366"
FT BINDING 444
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000250|UniProtKB:P00366"
FT BINDING 450
FT /ligand="ADP"
FT /ligand_id="ChEBI:CHEBI:456216"
FT /evidence="ECO:0000250|UniProtKB:P00366"
FT BINDING 516
FT /ligand="ADP"
FT /ligand_id="ChEBI:CHEBI:456216"
FT /evidence="ECO:0000250|UniProtKB:P00366"
FT MOD_RES 68
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:P26443"
FT MOD_RES 79
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P26443"
FT MOD_RES 84
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 84
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P00366"
FT MOD_RES 110
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P00366"
FT MOD_RES 110
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P00366"
FT MOD_RES 128
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P26443"
FT MOD_RES 135
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P26443"
FT MOD_RES 147
FT /note="N6-(2-hydroxyisobutyryl)lysine"
FT /evidence="ECO:0000269|PubMed:29192674"
FT MOD_RES 162
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P00366"
FT MOD_RES 162
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P00366"
FT MOD_RES 171
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P26443"
FT MOD_RES 172
FT /note="ADP-ribosylcysteine"
FT /evidence="ECO:0000269|PubMed:16023112"
FT MOD_RES 183
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P00366"
FT MOD_RES 183
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P26443"
FT MOD_RES 187
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P26443"
FT MOD_RES 191
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P00366"
FT MOD_RES 191
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P26443"
FT MOD_RES 200
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:P26443"
FT MOD_RES 211
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P26443"
FT MOD_RES 227
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 326
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P26443"
FT MOD_RES 346
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P26443"
FT MOD_RES 346
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P26443"
FT MOD_RES 352
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P26443"
FT MOD_RES 352
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P26443"
FT MOD_RES 363
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P00366"
FT MOD_RES 363
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P00366"
FT MOD_RES 365
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P00366"
FT MOD_RES 365
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P26443"
FT MOD_RES 384
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 386
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P00366"
FT MOD_RES 390
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P26443"
FT MOD_RES 390
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P26443"
FT MOD_RES 399
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P00366"
FT MOD_RES 410
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P10860"
FT MOD_RES 415
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P00366"
FT MOD_RES 415
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P00366"
FT MOD_RES 457
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P00366"
FT MOD_RES 457
FT /note="N6-malonyllysine; alternate"
FT /evidence="ECO:0000250"
FT MOD_RES 457
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P00366"
FT MOD_RES 477
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P26443"
FT MOD_RES 477
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P26443"
FT MOD_RES 480
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 480
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P26443"
FT MOD_RES 503
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 503
FT /note="N6-malonyllysine; alternate"
FT /evidence="ECO:0000250"
FT MOD_RES 503
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P00366"
FT MOD_RES 512
FT /note="Phosphotyrosine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 527
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P00366"
FT MOD_RES 527
FT /note="N6-malonyllysine; alternate"
FT /evidence="ECO:0000250"
FT MOD_RES 527
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P00366"
FT MOD_RES 545
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P00366"
FT MOD_RES 545
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P00366"
FT MOD_RES 548
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P26443"
FT VAR_SEQ 1..167
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_056244"
FT VAR_SEQ 1..16
FT /note="MYRYLGEALLLSRAGP -> MTCPCDNASSVFLGFC (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_056523"
FT VAR_SEQ 17..149
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_056524"
FT VARIANT 270
FT /note="S -> C (in HHF6; diminished sensitivity to GTP)"
FT /evidence="ECO:0000269|PubMed:11297618"
FT /id="VAR_016760"
FT VARIANT 274
FT /note="R -> C (in HHF6; diminished sensitivity to GTP;
FT dbSNP:rs56275071)"
FT /evidence="ECO:0000269|PubMed:11214910,
FT ECO:0000269|PubMed:11297618"
FT /id="VAR_016761"
FT VARIANT 318
FT /note="R -> K (in HHF6; dbSNP:rs121909736)"
FT /evidence="ECO:0000269|PubMed:10636977"
FT /id="VAR_009270"
FT VARIANT 318
FT /note="R -> T (in HHF6; diminished sensitivity to GTP)"
FT /evidence="ECO:0000269|PubMed:11297618"
FT /id="VAR_016762"
FT VARIANT 319
FT /note="Y -> C (in HHF6; dbSNP:rs1554906133)"
FT /evidence="ECO:0000269|PubMed:11297618"
FT /id="VAR_016763"
FT VARIANT 322
FT /note="R -> C (in HHF6; diminished sensitivity to GTP)"
FT /evidence="ECO:0000269|PubMed:11297618"
FT /id="VAR_016764"
FT VARIANT 322
FT /note="R -> H (in HHF6; diminished sensitivity to GTP;
FT dbSNP:rs121909737)"
FT /evidence="ECO:0000269|PubMed:11214910,
FT ECO:0000269|PubMed:11297618"
FT /id="VAR_016765"
FT VARIANT 349
FT /note="E -> A (in HHF6; dbSNP:rs121909735)"
FT /evidence="ECO:0000269|PubMed:10636977"
FT /id="VAR_009271"
FT VARIANT 498
FT /note="S -> L (in HHF6; dbSNP:rs121909731)"
FT /evidence="ECO:0000269|PubMed:9571255"
FT /id="VAR_008666"
FT VARIANT 499
FT /note="G -> D (in HHF6; dbSNP:rs121909734)"
FT /evidence="ECO:0000269|PubMed:9571255"
FT /id="VAR_008667"
FT VARIANT 499
FT /note="G -> S (in HHF6; dbSNP:rs121909733)"
FT /evidence="ECO:0000269|PubMed:9571255"
FT /id="VAR_008668"
FT VARIANT 501
FT /note="S -> P (in HHF6; dbSNP:rs121909732)"
FT /evidence="ECO:0000269|PubMed:9571255"
FT /id="VAR_008669"
FT VARIANT 507
FT /note="H -> Y (in HHF6; abolishes inhibition by ATP; no
FT effect on activation by ADP; Strongly reduces inhibition by
FT GTP; dbSNP:rs121909730)"
FT /evidence="ECO:0000269|PubMed:11254391,
FT ECO:0000269|PubMed:11903050, ECO:0000269|PubMed:9571255"
FT /id="VAR_008670"
FT MUTAGEN 501
FT /note="S->A: Reduces activity and inhibition by GTP."
FT /evidence="ECO:0000269|PubMed:11903050"
FT MUTAGEN 516
FT /note="R->A: Abolishes activation by ADP."
FT /evidence="ECO:0000269|PubMed:11903050"
FT HELIX 66..90
FT /evidence="ECO:0007829|PDB:1L1F"
FT HELIX 91..93
FT /evidence="ECO:0007829|PDB:1L1F"
FT HELIX 95..97
FT /evidence="ECO:0007829|PDB:1L1F"
FT HELIX 99..102
FT /evidence="ECO:0007829|PDB:1L1F"
FT HELIX 104..109
FT /evidence="ECO:0007829|PDB:1L1F"
FT STRAND 113..123
FT /evidence="ECO:0007829|PDB:1L1F"
FT STRAND 125..127
FT /evidence="ECO:0007829|PDB:1L1F"
FT STRAND 129..138
FT /evidence="ECO:0007829|PDB:1L1F"
FT STRAND 142..152
FT /evidence="ECO:0007829|PDB:1L1F"
FT HELIX 158..174
FT /evidence="ECO:0007829|PDB:1L1F"
FT STRAND 180..186
FT /evidence="ECO:0007829|PDB:1L1F"
FT HELIX 190..192
FT /evidence="ECO:0007829|PDB:1L1F"
FT HELIX 195..211
FT /evidence="ECO:0007829|PDB:1L1F"
FT TURN 217..219
FT /evidence="ECO:0007829|PDB:1L1F"
FT STRAND 220..223
FT /evidence="ECO:0007829|PDB:1L1F"
FT HELIX 230..242
FT /evidence="ECO:0007829|PDB:1L1F"
FT TURN 243..247
FT /evidence="ECO:0007829|PDB:1L1F"
FT HELIX 251..253
FT /evidence="ECO:0007829|PDB:1L1F"
FT HELIX 260..262
FT /evidence="ECO:0007829|PDB:1L1F"
FT HELIX 271..284
FT /evidence="ECO:0007829|PDB:1L1F"
FT HELIX 287..293
FT /evidence="ECO:0007829|PDB:1L1F"
FT STRAND 298..300
FT /evidence="ECO:0007829|PDB:1L1F"
FT STRAND 303..307
FT /evidence="ECO:0007829|PDB:1L1F"
FT HELIX 311..322
FT /evidence="ECO:0007829|PDB:1L1F"
FT STRAND 326..331
FT /evidence="ECO:0007829|PDB:1L1F"
FT STRAND 336..338
FT /evidence="ECO:0007829|PDB:6DQG"
FT HELIX 345..354
FT /evidence="ECO:0007829|PDB:1L1F"
FT STRAND 355..358
FT /evidence="ECO:0007829|PDB:1L1F"
FT STRAND 364..366
FT /evidence="ECO:0007829|PDB:6DQG"
FT TURN 371..373
FT /evidence="ECO:0007829|PDB:1L1F"
FT STRAND 377..381
FT /evidence="ECO:0007829|PDB:1L1F"
FT STRAND 383..386
FT /evidence="ECO:0007829|PDB:1L1F"
FT TURN 390..392
FT /evidence="ECO:0007829|PDB:1L1F"
FT HELIX 393..395
FT /evidence="ECO:0007829|PDB:1L1F"
FT STRAND 399..402
FT /evidence="ECO:0007829|PDB:1L1F"
FT STRAND 405..407
FT /evidence="ECO:0007829|PDB:1L1F"
FT HELIX 411..419
FT /evidence="ECO:0007829|PDB:1L1F"
FT STRAND 423..425
FT /evidence="ECO:0007829|PDB:1L1F"
FT HELIX 427..430
FT /evidence="ECO:0007829|PDB:1L1F"
FT HELIX 433..447
FT /evidence="ECO:0007829|PDB:1L1F"
FT TURN 451..455
FT /evidence="ECO:0007829|PDB:1L1F"
FT HELIX 456..475
FT /evidence="ECO:0007829|PDB:1L1F"
FT TURN 476..479
FT /evidence="ECO:0007829|PDB:1L1F"
FT STRAND 481..483
FT /evidence="ECO:0007829|PDB:6DQG"
FT HELIX 491..498
FT /evidence="ECO:0007829|PDB:1L1F"
FT HELIX 502..527
FT /evidence="ECO:0007829|PDB:1L1F"
FT HELIX 534..551
FT /evidence="ECO:0007829|PDB:1L1F"
SQ SEQUENCE 558 AA; 61398 MW; A7319A840F57FBB2 CRC64;
MYRYLGEALL LSRAGPAALG SASADSAALL GWARGQPAAA PQPGLALAAR RHYSEAVADR
EDDPNFFKMV EGFFDRGASI VEDKLVEDLR TRESEEQKRN RVRGILRIIK PCNHVLSLSF
PIRRDDGSWE VIEGYRAQHS QHRTPCKGGI RYSTDVSVDE VKALASLMTY KCAVVDVPFG
GAKAGVKINP KNYTDNELEK ITRRFTMELA KKGFIGPGID VPAPDMSTGE REMSWIADTY
ASTIGHYDIN AHACVTGKPI SQGGIHGRIS ATGRGVFHGI ENFINEASYM SILGMTPGFG
DKTFVVQGFG NVGLHSMRYL HRFGAKCIAV GESDGSIWNP DGIDPKELED FKLQHGSILG
FPKAKPYEGS ILEADCDILI PAASEKQLTK SNAPRVKAKI IAEGANGPTT PEADKIFLER
NIMVIPDLYL NAGGVTVSYF EWLKNLNHVS YGRLTFKYER DSNYHLLMSV QESLERKFGK
HGGTIPIVPT AEFQDRISGA SEKDIVHSGL AYTMERSARQ IMRTAMKYNL GLDLRTAAYV
NAIEKVFKVY NEAGVTFT
