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 27-MAR-2024, entry version 242. 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: Hyperinsulinemic hypoglycemia, familial, 6 (HHF6) CC [MIM:606762]: A form of hyperinsulinemic hypoglycemia, a clinically and CC genetically heterogeneous disorder characterized by inappropriate CC insulin secretion from the pancreatic beta-cells in the presence of low CC blood glucose levels. HHF6 is an autosomal dominant form characterized CC by hypoglycemia due to congenital hyperinsulinism combined with CC persistent hyperammonemia. Clinical features include loss of CC consciousness due to hypoglycemia, hypoglycemic seizures, and mental CC retardation. {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"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; 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 CCDS; CCDS91291.1; -. [P00367-2] 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 PDB; 7UZM; EM; 3.24 A; A/B/C/D/E/F=1-558. DR PDB; 8KGY; EM; 2.59 A; A/B/C/D/E/F=1-558. DR PDB; 8W4J; EM; 3.06 A; A/B/C/D/E/F=1-558. DR PDBsum; 1L1F; -. DR PDBsum; 1NR1; -. DR PDBsum; 6DQG; -. DR PDBsum; 7UZM; -. DR PDBsum; 8KGY; -. DR PDBsum; 8W4J; -. DR AlphaFoldDB; P00367; -. DR EMDB; EMD-26915; -. DR EMDB; EMD-37235; -. DR EMDB; EMD-37266; -. DR SMR; P00367; -. DR BioGRID; 109008; 239. DR IntAct; P00367; 95. 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 CPTAC; CPTAC-2725; -. DR CPTAC; CPTAC-2726; -. DR EPD; P00367; -. DR jPOST; P00367; -. DR MassIVE; P00367; -. DR MaxQB; P00367; -. DR PaxDb; 9606-ENSP00000277865; -. DR PeptideAtlas; P00367; -. DR ProteomicsDB; 3743; -. DR ProteomicsDB; 4147; -. DR ProteomicsDB; 51236; -. [P00367-1] DR Pumba; P00367; -. DR Antibodypedia; 16023; 281 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 AGR; HGNC:4335; -. DR CTD; 2746; -. DR DisGeNET; 2746; -. DR GeneCards; GLUD1; -. DR GeneReviews; GLUD1; -. DR HGNC; HGNC:4335; GLUD1. DR HPA; ENSG00000148672; Group enriched (brain, kidney, 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; MIMGWMM; -. DR OrthoDB; 45283at2759; -. DR PhylomeDB; P00367; -. DR TreeFam; TF313945; -. DR BioCyc; MetaCyc:HS07548-MONOMER; -. 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; 20 hits in 1163 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 202 other cell types or tissues. DR ExpressionAtlas; P00367; baseline and differential. 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:HPA. 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:0070728; F:leucine binding; IDA:BHF-UCL. DR GO; GO:0070403; F:NAD+ binding; IDA:BHF-UCL. DR GO; GO:0042803; F:protein homodimerization activity; IPI: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 Gene3D; 1.10.287.140; -; 1. DR Gene3D; 3.40.50.10860; Leucine Dehydrogenase, chain A, domain 1; 1. DR Gene3D; 3.40.50.720; NAD(P)-binding Rossmann-like Domain; 1. DR InterPro; IPR046346; Aminoacid_DH-like_N_sf. DR InterPro; IPR006095; Glu/Leu/Phe/Val/Trp_DH. DR InterPro; IPR006096; Glu/Leu/Phe/Val/Trp_DH_C. DR InterPro; IPR006097; Glu/Leu/Phe/Val/Trp_DH_dimer. DR InterPro; IPR033524; Glu/Leu/Phe/Val_DH_AS. DR InterPro; IPR036291; NAD(P)-bd_dom_sf. DR InterPro; IPR033922; NAD_bind_Glu_DH. DR PANTHER; PTHR11606; GLUTAMATE DEHYDROGENASE; 1. DR PANTHER; PTHR11606:SF13; GLUTAMATE DEHYDROGENASE 1, MITOCHONDRIAL; 1. 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; SSF53223; Aminoacid dehydrogenase-like, N-terminal domain; 1. DR SUPFAM; SSF51735; NAD(P)-binding Rossmann-fold domains; 1. DR PROSITE; PS00074; GLFV_DEHYDROGENASE; 1. DR SWISS-2DPAGE; P00367; -. DR UCD-2DPAGE; P00367; -. DR Genevisible; P00367; HS. 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 STRAND 254..257 FT /evidence="ECO:0007829|PDB:7UZM" 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 //