PCKGC_HUMAN
ID PCKGC_HUMAN Reviewed; 622 AA.
AC P35558; A8K437; B4DT64; Q8TCA3; Q9UJD2;
DT 01-JUN-1994, integrated into UniProtKB/Swiss-Prot.
DT 07-MAR-2006, sequence version 3.
DT 03-AUG-2022, entry version 214.
DE RecName: Full=Phosphoenolpyruvate carboxykinase, cytosolic [GTP] {ECO:0000305};
DE Short=PEPCK-C;
DE EC=4.1.1.32 {ECO:0000269|PubMed:24863970, ECO:0000269|PubMed:26971250, ECO:0000269|PubMed:28216384, ECO:0000269|PubMed:30193097};
DE AltName: Full=Serine-protein kinase PCK1 {ECO:0000305};
DE EC=2.7.11.- {ECO:0000269|PubMed:32322062};
GN Name=PCK1 {ECO:0000303|PubMed:8490617, ECO:0000312|HGNC:HGNC:8724};
GN Synonyms=PEPCK1 {ECO:0000303|PubMed:21726808};
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), TISSUE SPECIFICITY, AND VARIANTS
RP LEU-184 AND ASP-586.
RX PubMed=8490617; DOI=10.1093/hmg/2.1.1;
RA Stoffel M., Xiang K.S., Espinosa R. III, Cox N.J., le Beau M.M., Bell G.I.;
RT "cDNA sequence and localization of polymorphic human cytosolic
RT phosphoenolpyruvate carboxykinase gene (PCK1) to chromosome 20, band
RT q13.31: PCK1 is not tightly linked to maturity-onset diabetes of the
RT young.";
RL Hum. Mol. Genet. 2:1-4(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT LEU-184.
RC TISSUE=Liver;
RX PubMed=8325643; DOI=10.1006/geno.1993.1250;
RA Ting C.-N., Burgess D.L., Chamberlain J.S., Keith T.P., Falls K.,
RA Meisler M.H.;
RT "Phosphoenolpyruvate carboxykinase (GTP): characterization of the human
RT PCK1 gene and localization distal to MODY on chromosome 20.";
RL Genomics 16:698-706(1993).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS GLN-55; THR-60; ILE-138;
RP VAL-267; LYS-276; ILE-368 AND SER-427.
RG NIEHS SNPs program;
RL Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), AND VARIANT
RP LEU-184.
RC TISSUE=Kidney, and Pericardium;
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 [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=11780052; DOI=10.1038/414865a;
RA Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R.,
RA Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L.,
RA Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P.,
RA Bird C.P., Blakey S.E., Bridgeman A.M., Brown A.J., Buck D., Burrill W.D.,
RA Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G.,
RA Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E.,
RA Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D.,
RA Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P.,
RA Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E.,
RA Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J.,
RA Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D.,
RA Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S.,
RA Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D.,
RA Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A.,
RA Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T.,
RA Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I.,
RA Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M.,
RA Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D.,
RA Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M.,
RA Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A.,
RA Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L.,
RA Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L.,
RA Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 20.";
RL Nature 414:865-871(2001).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT LEU-184.
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANTS LEU-184
RP AND VAL-267.
RC TISSUE=Kidney;
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 [8]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-74.
RX PubMed=8547315; DOI=10.1016/0167-4781(95)00194-8;
RA O'Brien R.M., Printz R.L., Halmi N., Tiesinga J.J., Granner D.K.;
RT "Structural and functional analysis of the human phosphoenolpyruvate
RT carboxykinase gene promoter.";
RL Biochim. Biophys. Acta 1264:284-288(1995).
RN [9]
RP INDUCTION.
RX PubMed=1656199;
RA Liu J., Hanson R.W.;
RT "Regulation of phosphoenolpyruvate carboxykinase (GTP) gene
RT transcription.";
RL Mol. Cell. Biochem. 104:89-100(1991).
RN [10]
RP ACETYLATION AT LYS-70; LYS-71 AND LYS-594, ACTIVITY REGULATION, MUTAGENESIS
RP OF LYS-70; LYS-71 AND LYS-594, AND IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=20167786; DOI=10.1126/science.1179689;
RA Zhao S., Xu W., Jiang W., Yu W., Lin Y., Zhang T., Yao J., Zhou L.,
RA Zeng Y., Li H., Li Y., Shi J., An W., Hancock S.M., He F., Qin L., Chin J.,
RA Yang P., Chen X., Lei Q., Xiong Y., Guan K.L.;
RT "Regulation of cellular metabolism by protein lysine acetylation.";
RL Science 327:1000-1004(2010).
RN [11]
RP ACETYLATION AT LYS-70; LYS-71 AND LYS-594, DEACETYLATION BY SIRT2, AND
RP UBIQUITINATION BY UBR5.
RX PubMed=21726808; DOI=10.1016/j.molcel.2011.04.028;
RA Jiang W., Wang S., Xiao M., Lin Y., Zhou L., Lei Q., Xiong Y., Guan K.L.,
RA Zhao S.;
RT "Acetylation regulates gluconeogenesis by promoting PEPCK1 degradation via
RT recruiting the UBR5 ubiquitin ligase.";
RL Mol. Cell 43:33-44(2011).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-19, AND IDENTIFICATION BY
RP 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 [13]
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, PATHWAY,
RP BIOPHYSICOCHEMICAL PROPERTIES, ACETYLATION AT LYS-91 BY P300/EP300,
RP PHOSPHORYLATION, AND DEACETYLATION BY SIRT1.
RX PubMed=30193097; DOI=10.1016/j.molcel.2018.07.031;
RA Latorre-Muro P., Baeza J., Armstrong E.A., Hurtado-Guerrero R., Corzana F.,
RA Wu L.E., Sinclair D.A., Lopez-Buesa P., Carrodeguas J.A., Denu J.M.;
RT "Dynamic acetylation of phosphoenolpyruvate carboxykinase toggles enzyme
RT activity between gluconeogenic and anaplerotic reactions.";
RL Mol. Cell 71:718-732(2018).
RN [14]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, SUBCELLULAR
RP LOCATION, ACTIVITY REGULATION, PHOSPHORYLATION AT SER-90, AND MUTAGENESIS
RP OF SER-90 AND CYS-288.
RX PubMed=32322062; DOI=10.1038/s41586-020-2183-2;
RA Xu D., Wang Z., Xia Y., Shao F., Xia W., Wei Y., Li X., Qian X., Lee J.H.,
RA Du L., Zheng Y., Lv G., Leu J.S., Wang H., Xing D., Liang T., Hung M.C.,
RA Lu Z.;
RT "The gluconeogenic enzyme PCK1 phosphorylates INSIG1/2 for lipogenesis.";
RL Nature 580:530-535(2020).
RN [15]
RP X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS) IN COMPLEX WITH GTP ANALOG; PEP AND
RP MANGANESE, GTP-BINDING SITE, COFACTOR, SUBUNIT, AND ACTIVE SITE.
RX PubMed=11851336; DOI=10.1006/jmbi.2001.5364;
RA Dunten P., Belunis C., Crowther R., Hollfelder K., Kammlott U., Levin W.,
RA Michel H., Ramsey G.B., Swain A., Weber D., Wertheimer S.J.;
RT "Crystal structure of human cytosolic phosphoenolpyruvate carboxykinase
RT reveals a new GTP-binding site.";
RL J. Mol. Biol. 316:257-264(2002).
RN [16]
RP X-RAY CRYSTALLOGRAPHY (2.10 ANGSTROMS) IN COMPLEX WITH MANGANESE; GTP
RP ANALOG AND PEP, AND COFACTOR.
RX PubMed=14552798; DOI=10.1016/s0960-894x(03)00723-6;
RA Foley L.H., Wang P., Dunten P., Ramsey G., Gubler M.L., Wertheimer S.J.;
RT "X-ray structures of two xanthine inhibitors bound to PEPCK and N-3
RT modifications of substituted 1,8-dibenzylxanthines.";
RL Bioorg. Med. Chem. Lett. 13:3871-3874(2003).
RN [17]
RP X-RAY CRYSTALLOGRAPHY (2.30 ANGSTROMS) IN COMPLEX WITH MANGANESE; GTP
RP ANALOG AND PEP, COFACTOR, AND SUBUNIT.
RX PubMed=17532214; DOI=10.1016/j.bmcl.2007.05.013;
RA Pietranico S.L., Foley L.H., Huby N., Yun W., Dunten P., Vermeulen J.,
RA Wang P., Toth K., Ramsey G., Gubler M.L., Wertheimer S.J.;
RT "C-8 Modifications of 3-alkyl-1,8-dibenzylxanthines as inhibitors of human
RT cytosolic phosphoenolpyruvate carboxykinase.";
RL Bioorg. Med. Chem. Lett. 17:3835-3839(2007).
RN [18]
RP VARIANT PCKDC THR-45, CHARACTERIZATION OF VARIANT PCKDC THR-45, FUNCTION,
RP CATALYTIC ACTIVITY, AND PATHWAY.
RX PubMed=24863970; DOI=10.1016/j.ymgme.2014.04.001;
RA Adams D.R., Yuan H., Holyoak T., Arajs K.H., Hakimi P., Markello T.C.,
RA Wolfe L.A., Vilboux T., Burton B.K., Fajardo K.F., Grahame G., Holloman C.,
RA Sincan M., Smith A.C., Wells G.A., Huang Y., Vega H., Snyder J.P.,
RA Golas G.A., Tifft C.J., Boerkoel C.F., Hanson R.W., Traynelis S.F.,
RA Kerr D.S., Gahl W.A.;
RT "Three rare diseases in one sib pair: RAI1, PCK1, GRIN2B mutations
RT associated with Smith-Magenis Syndrome, cytosolic PEPCK deficiency and NMDA
RT receptor glutamate insensitivity.";
RL Mol. Genet. Metab. 113:161-170(2014).
RN [19]
RP VARIANT PCKDC 440-GLY--LEU-443 DEL, CHARACTERIZATION OF VARIANT PCKDC
RP 440-GLY--LEU-443 DEL, FUNCTION, CATALYTIC ACTIVITY, AND PATHWAY.
RX PubMed=26971250; DOI=10.1016/j.ymgme.2016.03.001;
RA Santra S., Cameron J.M., Shyr C., Zhang L., Droegemoeller B., Ross C.J.,
RA Wasserman W.W., Wevers R.A., Rodenburg R.J., Gupte G., Preece M.A.,
RA van Karnebeek C.D.;
RT "Cytosolic phosphoenolpyruvate carboxykinase deficiency presenting with
RT acute liver failure following gastroenteritis.";
RL Mol. Genet. Metab. 118:21-27(2016).
RN [20]
RP VARIANT PCKDC ARG-309, CHARACTERIZATION OF VARIANT PCKDC ARG-309, FUNCTION,
RP CATALYTIC ACTIVITY, AND PATHWAY.
RX PubMed=28216384; DOI=10.1016/j.ymgme.2017.02.003;
RA Vieira P., Cameron J., Rahikkala E., Keski-Filppula R., Zhang L.H.,
RA Santra S., Matthews A., Myllynen P., Nuutinen M., Moilanen J.S.,
RA Rodenburg R.J., Rolfs A., Uusimaa J., van Karnebeek C.D.;
RT "Novel homozygous PCK1 mutation causing cytosolic phosphoenolpyruvate
RT carboxykinase deficiency presenting as childhood hypoglycemia, an abnormal
RT pattern of urine metabolites and liver dysfunction.";
RL Mol. Genet. Metab. 120:337-341(2017).
CC -!- FUNCTION: Cytosolic phosphoenolpyruvate carboxykinase that catalyzes
CC the reversible decarboxylation and phosphorylation of oxaloacetate
CC (OAA) and acts as the rate-limiting enzyme in gluconeogenesis
CC (PubMed:30193097, PubMed:24863970, PubMed:26971250, PubMed:28216384).
CC Regulates cataplerosis and anaplerosis, the processes that control the
CC levels of metabolic intermediates in the citric acid cycle
CC (PubMed:30193097, PubMed:24863970, PubMed:26971250, PubMed:28216384).
CC At low glucose levels, it catalyzes the cataplerotic conversion of
CC oxaloacetate to phosphoenolpyruvate (PEP), the rate-limiting step in
CC the metabolic pathway that produces glucose from lactate and other
CC precursors derived from the citric acid cycle (PubMed:30193097). At
CC high glucose levels, it catalyzes the anaplerotic conversion of
CC phosphoenolpyruvate to oxaloacetate (PubMed:30193097). Acts as a
CC regulator of formation and maintenance of memory CD8(+) T-cells: up-
CC regulated in these cells, where it generates phosphoenolpyruvate, via
CC gluconeogenesis (By similarity). The resultant phosphoenolpyruvate
CC flows to glycogen and pentose phosphate pathway, which is essential for
CC memory CD8(+) T-cells homeostasis (By similarity). In addition to the
CC phosphoenolpyruvate carboxykinase activity, also acts as a protein
CC kinase when phosphorylated at Ser-90: phosphorylation at Ser-90 by AKT1
CC reduces the binding affinity to oxaloacetate and promotes an atypical
CC serine protein kinase activity using GTP as donor (PubMed:32322062).
CC The protein kinase activity regulates lipogenesis: upon phosphorylation
CC at Ser-90, translocates to the endoplasmic reticulum and catalyzes
CC phosphorylation of INSIG proteins (INSIG1 and INSIG2), thereby
CC disrupting the interaction between INSIG proteins and SCAP and
CC promoting nuclear translocation of SREBP proteins (SREBF1/SREBP1 or
CC SREBF2/SREBP2) and subsequent transcription of downstream lipogenesis-
CC related genes (PubMed:32322062). {ECO:0000250|UniProtKB:Q9Z2V4,
CC ECO:0000269|PubMed:24863970, ECO:0000269|PubMed:26971250,
CC ECO:0000269|PubMed:28216384, ECO:0000269|PubMed:30193097,
CC ECO:0000269|PubMed:32322062}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=GTP + oxaloacetate = CO2 + GDP + phosphoenolpyruvate;
CC Xref=Rhea:RHEA:10388, ChEBI:CHEBI:16452, ChEBI:CHEBI:16526,
CC ChEBI:CHEBI:37565, ChEBI:CHEBI:58189, ChEBI:CHEBI:58702; EC=4.1.1.32;
CC Evidence={ECO:0000269|PubMed:24863970, ECO:0000269|PubMed:26971250,
CC ECO:0000269|PubMed:28216384, ECO:0000269|PubMed:30193097,
CC ECO:0000269|PubMed:32322062};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:10389;
CC Evidence={ECO:0000269|PubMed:30193097};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:10390;
CC Evidence={ECO:0000269|PubMed:30193097};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=GTP + L-seryl-[protein] = GDP + H(+) + O-phospho-L-seryl-
CC [protein]; Xref=Rhea:RHEA:64020, Rhea:RHEA-COMP:9863, Rhea:RHEA-
CC COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:37565,
CC ChEBI:CHEBI:58189, ChEBI:CHEBI:83421;
CC Evidence={ECO:0000269|PubMed:32322062};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:64021;
CC Evidence={ECO:0000269|PubMed:32322062};
CC -!- COFACTOR:
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000269|PubMed:11851336, ECO:0000269|PubMed:14552798,
CC ECO:0000269|PubMed:17532214};
CC Note=Binds 1 Mn(2+) ion per subunit. {ECO:0000269|PubMed:11851336,
CC ECO:0000269|PubMed:14552798, ECO:0000269|PubMed:17532214};
CC -!- ACTIVITY REGULATION: Phosphoenolpyruvate carboxykinase activity is
CC regulated by acetylation and glucose levels (PubMed:20167786,
CC PubMed:30193097). The anaplerotic conversion of phosphoenolpyruvate to
CC oxaloacetate is improved by PCK1 acetylation on Lys-91 (K91ac), Lys-473
CC (K473ac) and Lys-521 (K521ac) (By similarity). High glucose
CC concentrations favor PCK1 anaplerotic activity by triggering
CC acetylation on Lys-91 (K91ac). At low glucose levels, SIRT1-mediated
CC deacetylation of Lys-91 promotes the cataplerotic conversion of
CC oxaloacetate to phosphoenolpyruvate (PubMed:30193097). Phosphorylation
CC at Ser-90 reduces the binding affinity to oxaloacetate and converts the
CC enzyme into an atypical protein kinase using GTP as donor
CC (PubMed:32322062). {ECO:0000250|UniProtKB:P07379,
CC ECO:0000269|PubMed:20167786, ECO:0000269|PubMed:30193097,
CC ECO:0000269|PubMed:32322062}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=35 uM for oxaloacetate (for the enzyme purified from cells exposed
CC to 10 mM glucose) {ECO:0000269|PubMed:30193097};
CC KM=46 uM for oxaloacetate (for the enzyme purified from cells exposed
CC to 15 mM glucose) {ECO:0000269|PubMed:30193097};
CC KM=170 uM for GTP (for the enzyme purified from cells exposed to 10
CC mM glucose) {ECO:0000269|PubMed:30193097};
CC KM=151 uM for GTP (for the enzyme purified from cells exposed to 15
CC mM glucose) {ECO:0000269|PubMed:30193097};
CC KM=208 uM for phosphoenolpyruvate (for the enzyme purified from cells
CC exposed to 10 mM glucose) {ECO:0000269|PubMed:30193097};
CC KM=87 uM for phosphoenolpyruvate (for the enzyme purified from cells
CC exposed to 15 mM glucose) {ECO:0000269|PubMed:30193097};
CC KM=63 uM for GDP (for the enzyme purified from cells exposed to 10 mM
CC glucose) {ECO:0000269|PubMed:30193097};
CC KM=29 uM for GDP (for the enzyme purified from cells exposed to 15 mM
CC glucose) {ECO:0000269|PubMed:30193097};
CC KM=1.15 mM for GTP (in a protein kinase activity assay when not
CC phosphorylated at Ser-90) {ECO:0000269|PubMed:32322062};
CC KM=0.21 mM for GTP (in a protein kinase activity assay when using a
CC phosphomimetic mutant at Ser-90) {ECO:0000269|PubMed:32322062};
CC Note=kcat is 33 sec(-1) with oxaloacetate as substrate (for the
CC enzyme purified from cells exposed to 10 mM glucose)
CC (PubMed:30193097). kcat is 21 sec(-1) with oxaloacetate as substrate
CC (for the enzyme purified from cells exposed to 15 mM glucose)
CC (PubMed:30193097). kcat is 17 sec(-1) with phosphoenolpyruvate as
CC substrate (for the enzyme purified from cells exposed to 10 mM
CC glucose) (PubMed:30193097). kcat is 11 sec(-1)with
CC phosphoenolpyruvate as substrate (for the enzyme purified from cells
CC exposed to 15 mM glucose) (PubMed:30193097). kcat is 40 sec(-1) with
CC GTP as substrate (for the enzyme purified from cells exposed to 10 mM
CC glucose) (PubMed:30193097). kcat is 22 sec(-1) with GTP as substrate
CC (for the enzyme purified from cells exposed to 15 mM glucose)
CC (PubMed:30193097). kcat is 16 sec(-1) with GDP as substrate (for the
CC enzyme purified from cells exposed to 10 mM glucose)
CC (PubMed:30193097). kcat is 11 sec(-1) with GDP as substrate (for the
CC enzyme purified from cells exposed to 15 mM glucose)
CC (PubMed:30193097). {ECO:0000269|PubMed:30193097};
CC -!- PATHWAY: Carbohydrate biosynthesis; gluconeogenesis.
CC {ECO:0000269|PubMed:24863970, ECO:0000269|PubMed:26971250,
CC ECO:0000269|PubMed:28216384, ECO:0000269|PubMed:30193097}.
CC -!- SUBUNIT: Monomer. {ECO:0000269|PubMed:11851336,
CC ECO:0000269|PubMed:17532214}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000269|PubMed:32322062}.
CC Endoplasmic reticulum {ECO:0000269|PubMed:32322062}.
CC Note=Phosphorylation at Ser-90 promotes translocation to the
CC endoplasmic reticulum. {ECO:0000269|PubMed:32322062}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P35558-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P35558-2; Sequence=VSP_057073, VSP_057074;
CC -!- TISSUE SPECIFICITY: Major sites of expression are liver, kidney and
CC adipocytes. {ECO:0000269|PubMed:8490617}.
CC -!- INDUCTION: Regulated by cAMP and insulin. {ECO:0000269|PubMed:1656199}.
CC -!- PTM: Acetylated. Lysine acetylation by p300/EP300 is increased on high
CC glucose conditions (PubMed:20167786, PubMed:21726808, PubMed:30193097).
CC Lysine acetylation promotes ubiquitination by UBR5 (PubMed:21726808).
CC Acetylation is enhanced in the presence of BAG6. Deacetylated by SIRT2.
CC Deacetylation of Lys-91 is carried out by SIRT1 and depends on PCK1
CC phosphorylation levels (PubMed:30193097). {ECO:0000269|PubMed:20167786,
CC ECO:0000269|PubMed:21726808, ECO:0000269|PubMed:30193097}.
CC -!- PTM: Phosphorylated in a GSK3B-mediated pathway; phosphorylation
CC affects the efficiency of SIRT1-mediated deacetylation, and regulates
CC PCK1 ubiquitination and degradation (PubMed:30193097). Phosphorylation
CC at Ser-90 by AKT1 reduces the binding affinity to oxaloacetate and
CC promotes the protein kinase activity: phosphorylated PCK1 translocates
CC to the endoplasmic reticulum, where it phosphorylates INSIG1 and INSIG2
CC (PubMed:32322062). {ECO:0000269|PubMed:30193097,
CC ECO:0000269|PubMed:32322062}.
CC -!- PTM: Ubiquitination by UBR5 leads to proteasomal degradation.
CC {ECO:0000269|PubMed:21726808}.
CC -!- DISEASE: Phosphoenolpyruvate carboxykinase deficiency, cytosolic
CC (PCKDC) [MIM:261680]: An autosomal recessive metabolic disorder
CC characterized by impaired gluconeogenesis, hypoglycemia, hypotonia,
CC hepatomegaly, hepatic dysfunction, failure to thrive, lactic acidosis,
CC and elevated tricarboxylic acid intermediates, particularly fumarate,
CC in urine. {ECO:0000269|PubMed:24863970, ECO:0000269|PubMed:26971250,
CC ECO:0000269|PubMed:28216384}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- MISCELLANEOUS: In eukaryotes there are two isozymes: a cytoplasmic one
CC and a mitochondrial one. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the phosphoenolpyruvate carboxykinase [GTP]
CC family. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/pck1/";
CC -!- WEB RESOURCE: Name=Protein Spotlight; Note=On a tangent - Issue 233 of
CC February 2021;
CC URL="https://web.expasy.org/spotlight/back_issues/233/";
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DR EMBL; L05144; AAA60084.1; -; mRNA.
DR EMBL; L12760; AAA02558.1; -; Genomic_DNA.
DR EMBL; AY794987; AAV50001.1; -; Genomic_DNA.
DR EMBL; AK290802; BAF83491.1; -; mRNA.
DR EMBL; AK300072; BAG61876.1; -; mRNA.
DR EMBL; AL035541; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471077; EAW75514.1; -; Genomic_DNA.
DR EMBL; BC023978; AAH23978.1; -; mRNA.
DR EMBL; U31519; AAA91026.1; -; Genomic_DNA.
DR CCDS; CCDS13460.1; -. [P35558-1]
DR PIR; A45746; A45746.
DR RefSeq; NP_002582.3; NM_002591.3. [P35558-1]
DR PDB; 1KHB; X-ray; 1.85 A; A=1-622.
DR PDB; 1KHE; X-ray; 2.40 A; A=1-622.
DR PDB; 1KHF; X-ray; 2.02 A; A=1-622.
DR PDB; 1KHG; X-ray; 2.34 A; A=1-622.
DR PDB; 1M51; X-ray; 2.25 A; A=1-622.
DR PDB; 1NHX; X-ray; 2.10 A; A=1-622.
DR PDB; 2GMV; X-ray; 2.30 A; A/B=1-622.
DR PDBsum; 1KHB; -.
DR PDBsum; 1KHE; -.
DR PDBsum; 1KHF; -.
DR PDBsum; 1KHG; -.
DR PDBsum; 1M51; -.
DR PDBsum; 1NHX; -.
DR PDBsum; 2GMV; -.
DR AlphaFoldDB; P35558; -.
DR SMR; P35558; -.
DR BioGRID; 111136; 135.
DR IntAct; P35558; 5.
DR MINT; P35558; -.
DR STRING; 9606.ENSP00000319814; -.
DR BindingDB; P35558; -.
DR ChEMBL; CHEMBL2911; -.
DR DrugBank; DB02008; 1-(2-Fluorobenzyl)-3-Butyl-8-(N-Acetyl-4-Aminobenzyl)-Xanthine.
DR DrugBank; DB03267; 1-Allyl-3-Butyl-8-(N-Acetyl-4-Aminobenzyl)-Xanthine.
DR DrugBank; DB03725; 5'-Guanylylmethylenebisphosphonate.
DR DrugBank; DB00787; Acyclovir.
DR DrugBank; DB09338; Mersalyl.
DR DrugBank; DB01819; Phosphoenolpyruvate.
DR iPTMnet; P35558; -.
DR PhosphoSitePlus; P35558; -.
DR BioMuta; PCK1; -.
DR DMDM; 93138710; -.
DR EPD; P35558; -.
DR jPOST; P35558; -.
DR MassIVE; P35558; -.
DR MaxQB; P35558; -.
DR PaxDb; P35558; -.
DR PeptideAtlas; P35558; -.
DR PRIDE; P35558; -.
DR ProteomicsDB; 5077; -.
DR ProteomicsDB; 55087; -. [P35558-1]
DR Antibodypedia; 1643; 613 antibodies from 40 providers.
DR DNASU; 5105; -.
DR Ensembl; ENST00000319441.6; ENSP00000319814.4; ENSG00000124253.11. [P35558-1]
DR GeneID; 5105; -.
DR KEGG; hsa:5105; -.
DR MANE-Select; ENST00000319441.6; ENSP00000319814.4; NM_002591.4; NP_002582.3.
DR UCSC; uc002xyn.5; human. [P35558-1]
DR CTD; 5105; -.
DR DisGeNET; 5105; -.
DR GeneCards; PCK1; -.
DR HGNC; HGNC:8724; PCK1.
DR HPA; ENSG00000124253; Tissue enhanced (kidney, liver).
DR MalaCards; PCK1; -.
DR MIM; 261680; phenotype.
DR MIM; 614168; gene.
DR neXtProt; NX_P35558; -.
DR OpenTargets; ENSG00000124253; -.
DR Orphanet; 2880; Phosphoenolpyruvate carboxykinase deficiency.
DR PharmGKB; PA33069; -.
DR VEuPathDB; HostDB:ENSG00000124253; -.
DR eggNOG; KOG3749; Eukaryota.
DR GeneTree; ENSGT00390000001912; -.
DR HOGENOM; CLU_028872_1_1_1; -.
DR InParanoid; P35558; -.
DR OMA; GPTNNWV; -.
DR OrthoDB; 286671at2759; -.
DR PhylomeDB; P35558; -.
DR TreeFam; TF314402; -.
DR BioCyc; MetaCyc:HS04751-MON; -.
DR BRENDA; 4.1.1.32; 2681.
DR PathwayCommons; P35558; -.
DR Reactome; R-HSA-2161541; Abacavir metabolism.
DR Reactome; R-HSA-381340; Transcriptional regulation of white adipocyte differentiation.
DR Reactome; R-HSA-70263; Gluconeogenesis.
DR Reactome; R-HSA-9615017; FOXO-mediated transcription of oxidative stress, metabolic and neuronal genes.
DR Reactome; R-HSA-9632974; NR1H2 & NR1H3 regulate gene expression linked to gluconeogenesis.
DR SABIO-RK; P35558; -.
DR SignaLink; P35558; -.
DR SIGNOR; P35558; -.
DR UniPathway; UPA00138; -.
DR BioGRID-ORCS; 5105; 14 hits in 1071 CRISPR screens.
DR ChiTaRS; PCK1; human.
DR EvolutionaryTrace; P35558; -.
DR GeneWiki; PCK1; -.
DR GenomeRNAi; 5105; -.
DR Pharos; P35558; Tbio.
DR PRO; PR:P35558; -.
DR Proteomes; UP000005640; Chromosome 20.
DR RNAct; P35558; protein.
DR Bgee; ENSG00000124253; Expressed in jejunal mucosa and 144 other tissues.
DR Genevisible; P35558; HS.
DR GO; GO:0005737; C:cytoplasm; ISS:BHF-UCL.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:UniProtKB.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; IBA:GO_Central.
DR GO; GO:0031406; F:carboxylic acid binding; IDA:BHF-UCL.
DR GO; GO:0005525; F:GTP binding; IDA:BHF-UCL.
DR GO; GO:0000287; F:magnesium ion binding; IDA:BHF-UCL.
DR GO; GO:0030145; F:manganese ion binding; IDA:BHF-UCL.
DR GO; GO:0004613; F:phosphoenolpyruvate carboxykinase (GTP) activity; IDA:UniProtKB.
DR GO; GO:0106264; F:protein serine kinase activity (using GTP as donor); IDA:UniProtKB.
DR GO; GO:0071549; P:cellular response to dexamethasone stimulus; IBA:GO_Central.
DR GO; GO:0071333; P:cellular response to glucose stimulus; IDA:UniProtKB.
DR GO; GO:0032869; P:cellular response to insulin stimulus; IDA:UniProtKB.
DR GO; GO:0051365; P:cellular response to potassium ion starvation; IEA:Ensembl.
DR GO; GO:0006094; P:gluconeogenesis; IMP:UniProtKB.
DR GO; GO:0042593; P:glucose homeostasis; ISS:BHF-UCL.
DR GO; GO:0006006; P:glucose metabolic process; IMP:BHF-UCL.
DR GO; GO:0046327; P:glycerol biosynthetic process from pyruvate; ISS:BHF-UCL.
DR GO; GO:0070365; P:hepatocyte differentiation; IBA:GO_Central.
DR GO; GO:0006107; P:oxaloacetate metabolic process; IDA:UniProtKB.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; IDA:UniProtKB.
DR GO; GO:0043382; P:positive regulation of memory T cell differentiation; ISS:UniProtKB.
DR GO; GO:0061402; P:positive regulation of transcription from RNA polymerase II promoter in response to acidic pH; IEA:Ensembl.
DR GO; GO:0019543; P:propionate catabolic process; IBA:GO_Central.
DR GO; GO:0046890; P:regulation of lipid biosynthetic process; IDA:UniProtKB.
DR GO; GO:0009617; P:response to bacterium; IEA:Ensembl.
DR GO; GO:0032868; P:response to insulin; IDA:BHF-UCL.
DR GO; GO:0033993; P:response to lipid; IBA:GO_Central.
DR GO; GO:0042594; P:response to starvation; IBA:GO_Central.
DR CDD; cd00819; PEPCK_GTP; 1.
DR Gene3D; 3.40.449.10; -; 1.
DR Gene3D; 3.90.228.20; -; 1.
DR HAMAP; MF_00452; PEPCK_GTP; 1.
DR InterPro; IPR018091; PEP_carboxykin_GTP_CS.
DR InterPro; IPR013035; PEP_carboxykinase_C.
DR InterPro; IPR008209; PEP_carboxykinase_GTP.
DR InterPro; IPR035077; PEP_carboxykinase_GTP_C.
DR InterPro; IPR035078; PEP_carboxykinase_GTP_N.
DR InterPro; IPR008210; PEP_carboxykinase_N.
DR PANTHER; PTHR11561; PTHR11561; 1.
DR Pfam; PF00821; PEPCK_GTP; 1.
DR Pfam; PF17297; PEPCK_N; 1.
DR PIRSF; PIRSF001348; PEP_carboxykinase_GTP; 1.
DR SUPFAM; SSF68923; SSF68923; 1.
DR PROSITE; PS00505; PEPCK_GTP; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Cytoplasm; Decarboxylase;
KW Endoplasmic reticulum; Gluconeogenesis; GTP-binding; Kinase; Lyase;
KW Manganese; Metal-binding; Nucleotide-binding; Phosphoprotein;
KW Reference proteome; Transferase; Ubl conjugation.
FT CHAIN 1..622
FT /note="Phosphoenolpyruvate carboxykinase, cytosolic [GTP]"
FT /id="PRO_0000103627"
FT REGION 457..487
FT /note="Omega-loop"
FT /evidence="ECO:0000250|UniProtKB:P07379"
FT ACT_SITE 288
FT /evidence="ECO:0000269|PubMed:11851336,
FT ECO:0000305|PubMed:32322062"
FT BINDING 87
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:11851336,
FT ECO:0000269|PubMed:14552798, ECO:0000269|PubMed:17532214"
FT BINDING 235..237
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:11851336,
FT ECO:0000269|PubMed:14552798, ECO:0000269|PubMed:17532214"
FT BINDING 244
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /evidence="ECO:0000269|PubMed:11851336,
FT ECO:0000269|PubMed:14552798, ECO:0000269|PubMed:17532214"
FT BINDING 264
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /evidence="ECO:0000269|PubMed:11851336,
FT ECO:0000269|PubMed:14552798, ECO:0000269|PubMed:17532214"
FT BINDING 286
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:P07379"
FT BINDING 287..292
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000269|PubMed:11851336"
FT BINDING 311
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /evidence="ECO:0000269|PubMed:11851336,
FT ECO:0000269|PubMed:14552798, ECO:0000269|PubMed:17532214"
FT BINDING 403..405
FT /ligand="substrate"
FT /evidence="ECO:0000269|PubMed:11851336,
FT ECO:0000269|PubMed:14552798, ECO:0000269|PubMed:17532214"
FT BINDING 405
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000269|PubMed:11851336"
FT BINDING 436
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000269|PubMed:11851336"
FT BINDING 530..533
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000269|PubMed:11851336,
FT ECO:0000269|PubMed:14552798, ECO:0000269|PubMed:17532214"
FT MOD_RES 19
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT MOD_RES 70
FT /note="N6-acetyllysine; by p300/EP300"
FT /evidence="ECO:0000269|PubMed:20167786,
FT ECO:0000269|PubMed:21726808"
FT MOD_RES 71
FT /note="N6-acetyllysine; by p300/EP300"
FT /evidence="ECO:0000269|PubMed:20167786,
FT ECO:0000269|PubMed:21726808"
FT MOD_RES 90
FT /note="Phosphoserine; by PKB/AKT1"
FT /evidence="ECO:0000269|PubMed:32322062"
FT MOD_RES 91
FT /note="N6-acetyllysine; by p300/EP300"
FT /evidence="ECO:0000269|PubMed:30193097"
FT MOD_RES 118
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9Z2V4"
FT MOD_RES 178
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q16822"
FT MOD_RES 286
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q16822"
FT MOD_RES 473
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P07379"
FT MOD_RES 521
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P07379"
FT MOD_RES 524
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P07379"
FT MOD_RES 594
FT /note="N6-acetyllysine; by p300/EP300"
FT /evidence="ECO:0000269|PubMed:20167786,
FT ECO:0000269|PubMed:21726808"
FT VAR_SEQ 1..3
FT /note="MPP -> MTT (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_057073"
FT VAR_SEQ 4..320
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_057074"
FT VARIANT 45
FT /note="I -> T (in PCKDC; decreased stability; no effect on
FT phosphoenolpyruvate carboxykinase activity;
FT dbSNP:rs202197769)"
FT /evidence="ECO:0000269|PubMed:24863970"
FT /id="VAR_079633"
FT VARIANT 55
FT /note="R -> Q (in dbSNP:rs28383585)"
FT /evidence="ECO:0000269|Ref.3"
FT /id="VAR_021072"
FT VARIANT 60
FT /note="M -> T (in dbSNP:rs28383586)"
FT /evidence="ECO:0000269|Ref.3"
FT /id="VAR_021073"
FT VARIANT 138
FT /note="T -> I (in dbSNP:rs28359542)"
FT /evidence="ECO:0000269|Ref.3"
FT /id="VAR_021074"
FT VARIANT 184
FT /note="V -> L (in dbSNP:rs707555)"
FT /evidence="ECO:0000269|PubMed:14702039,
FT ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:8325643,
FT ECO:0000269|PubMed:8490617, ECO:0000269|Ref.6"
FT /id="VAR_021075"
FT VARIANT 267
FT /note="I -> V (in dbSNP:rs8192708)"
FT /evidence="ECO:0000269|PubMed:15489334, ECO:0000269|Ref.3"
FT /id="VAR_015575"
FT VARIANT 276
FT /note="E -> K (in dbSNP:rs11552145)"
FT /evidence="ECO:0000269|Ref.3"
FT /id="VAR_021076"
FT VARIANT 309
FT /note="G -> R (in PCKDC; unknown pathological significance;
FT decreased phosphoenolpyruvate carboxykinase activity;
FT dbSNP:rs201186470)"
FT /evidence="ECO:0000269|PubMed:28216384"
FT /id="VAR_079634"
FT VARIANT 368
FT /note="V -> I (in dbSNP:rs1804160)"
FT /evidence="ECO:0000269|Ref.3"
FT /id="VAR_021077"
FT VARIANT 427
FT /note="P -> S (in dbSNP:rs28359550)"
FT /evidence="ECO:0000269|Ref.3"
FT /id="VAR_021078"
FT VARIANT 440..443
FT /note="Missing (in PCKDC; decreased phosphoenolpyruvate
FT carboxykinase activity)"
FT /evidence="ECO:0000269|PubMed:26971250"
FT /id="VAR_079635"
FT VARIANT 586
FT /note="E -> D (in dbSNP:rs1042529)"
FT /evidence="ECO:0000269|PubMed:8490617"
FT /id="VAR_042444"
FT MUTAGEN 70
FT /note="K->R: Abolishes acetylation and increases protein
FT stability; when associated with R-71 and R-594."
FT /evidence="ECO:0000269|PubMed:20167786"
FT MUTAGEN 71
FT /note="K->R: Abolishes acetylation and increases protein
FT stability; when associated with R-70 and R-594."
FT /evidence="ECO:0000269|PubMed:20167786"
FT MUTAGEN 90
FT /note="S->A: Abolished phosphorylation by AKT1, interaction
FT with INSIG proteins (INSIG1 and INSIG2) and ability to
FT regulate lipogenesis."
FT /evidence="ECO:0000269|PubMed:32322062"
FT MUTAGEN 90
FT /note="S->E: Phosphomimetic mutant, promotes the serine
FT protein kinase activity by reducing the binding affinity to
FT oxaloacetate."
FT /evidence="ECO:0000269|PubMed:32322062"
FT MUTAGEN 288
FT /note="C->S: Abolished both phosphoenolpyruvate
FT carboxykinase and protein kinase activities."
FT /evidence="ECO:0000269|PubMed:32322062"
FT MUTAGEN 594
FT /note="K->R: Abolishes acetylation and increases protein
FT stability; when associated with R-70 and R-71."
FT /evidence="ECO:0000269|PubMed:20167786"
FT CONFLICT 250
FT /note="M -> N (in Ref. 2; AAA02558)"
FT /evidence="ECO:0000305"
FT CONFLICT 256
FT /note="K -> E (in Ref. 1; AAA60084)"
FT /evidence="ECO:0000305"
FT CONFLICT 291
FT /note="T -> S (in Ref. 2; AAA02558)"
FT /evidence="ECO:0000305"
FT CONFLICT 551..552
FT /note="KL -> NV (in Ref. 1; AAA60084)"
FT /evidence="ECO:0000305"
FT CONFLICT 597
FT /note="E -> V (in Ref. 1; AAA60084)"
FT /evidence="ECO:0000305"
FT HELIX 11..14
FT /evidence="ECO:0007829|PDB:1KHB"
FT STRAND 15..18
FT /evidence="ECO:0007829|PDB:1KHB"
FT HELIX 20..22
FT /evidence="ECO:0007829|PDB:1KHB"
FT HELIX 25..38
FT /evidence="ECO:0007829|PDB:1KHB"
FT STRAND 41..45
FT /evidence="ECO:0007829|PDB:1KHB"
FT HELIX 50..62
FT /evidence="ECO:0007829|PDB:1KHB"
FT STRAND 65..68
FT /evidence="ECO:0007829|PDB:1KHF"
FT STRAND 72..74
FT /evidence="ECO:0007829|PDB:1KHB"
FT STRAND 76..78
FT /evidence="ECO:0007829|PDB:1KHB"
FT STRAND 84..86
FT /evidence="ECO:0007829|PDB:1KHB"
FT HELIX 89..91
FT /evidence="ECO:0007829|PDB:1KHB"
FT STRAND 92..95
FT /evidence="ECO:0007829|PDB:1KHB"
FT HELIX 99..102
FT /evidence="ECO:0007829|PDB:1KHB"
FT STRAND 107..109
FT /evidence="ECO:0007829|PDB:1KHB"
FT HELIX 119..129
FT /evidence="ECO:0007829|PDB:1KHB"
FT TURN 131..136
FT /evidence="ECO:0007829|PDB:1KHB"
FT STRAND 137..150
FT /evidence="ECO:0007829|PDB:1KHB"
FT STRAND 155..162
FT /evidence="ECO:0007829|PDB:1KHB"
FT HELIX 164..173
FT /evidence="ECO:0007829|PDB:1KHB"
FT STRAND 174..177
FT /evidence="ECO:0007829|PDB:1KHB"
FT HELIX 178..184
FT /evidence="ECO:0007829|PDB:1KHB"
FT STRAND 190..195
FT /evidence="ECO:0007829|PDB:1KHB"
FT HELIX 214..216
FT /evidence="ECO:0007829|PDB:1KHB"
FT STRAND 218..222
FT /evidence="ECO:0007829|PDB:1KHB"
FT HELIX 223..225
FT /evidence="ECO:0007829|PDB:1KHB"
FT STRAND 227..232
FT /evidence="ECO:0007829|PDB:1KHB"
FT HELIX 236..239
FT /evidence="ECO:0007829|PDB:1KHB"
FT HELIX 242..248
FT /evidence="ECO:0007829|PDB:1KHB"
FT HELIX 249..258
FT /evidence="ECO:0007829|PDB:1KHB"
FT STRAND 261..264
FT /evidence="ECO:0007829|PDB:1KHB"
FT STRAND 266..271
FT /evidence="ECO:0007829|PDB:1KHB"
FT STRAND 277..283
FT /evidence="ECO:0007829|PDB:1KHB"
FT HELIX 290..294
FT /evidence="ECO:0007829|PDB:1KHB"
FT STRAND 304..311
FT /evidence="ECO:0007829|PDB:1KHB"
FT STRAND 313..317
FT /evidence="ECO:0007829|PDB:1KHB"
FT STRAND 321..326
FT /evidence="ECO:0007829|PDB:1KHB"
FT STRAND 330..335
FT /evidence="ECO:0007829|PDB:1KHB"
FT TURN 341..343
FT /evidence="ECO:0007829|PDB:1KHB"
FT HELIX 345..350
FT /evidence="ECO:0007829|PDB:1KHB"
FT STRAND 356..359
FT /evidence="ECO:0007829|PDB:1KHB"
FT STRAND 361..363
FT /evidence="ECO:0007829|PDB:1KHB"
FT STRAND 388..391
FT /evidence="ECO:0007829|PDB:1KHB"
FT STRAND 395..397
FT /evidence="ECO:0007829|PDB:1KHB"
FT STRAND 405..409
FT /evidence="ECO:0007829|PDB:1KHB"
FT HELIX 410..412
FT /evidence="ECO:0007829|PDB:1KHB"
FT TURN 418..421
FT /evidence="ECO:0007829|PDB:1KHB"
FT STRAND 426..434
FT /evidence="ECO:0007829|PDB:1KHB"
FT STRAND 438..440
FT /evidence="ECO:0007829|PDB:1KHB"
FT STRAND 443..446
FT /evidence="ECO:0007829|PDB:1KHB"
FT HELIX 450..458
FT /evidence="ECO:0007829|PDB:1KHB"
FT STRAND 461..463
FT /evidence="ECO:0007829|PDB:1KHB"
FT STRAND 475..477
FT /evidence="ECO:0007829|PDB:1KHB"
FT HELIX 479..481
FT /evidence="ECO:0007829|PDB:1KHB"
FT TURN 483..485
FT /evidence="ECO:0007829|PDB:1KHB"
FT HELIX 490..499
FT /evidence="ECO:0007829|PDB:1KHB"
FT HELIX 500..502
FT /evidence="ECO:0007829|PDB:1KHB"
FT STRAND 510..514
FT /evidence="ECO:0007829|PDB:1KHB"
FT STRAND 525..527
FT /evidence="ECO:0007829|PDB:1KHB"
FT HELIX 530..533
FT /evidence="ECO:0007829|PDB:1KHB"
FT HELIX 534..544
FT /evidence="ECO:0007829|PDB:1KHB"
FT STRAND 550..553
FT /evidence="ECO:0007829|PDB:1KHB"
FT STRAND 556..559
FT /evidence="ECO:0007829|PDB:1KHB"
FT TURN 561..563
FT /evidence="ECO:0007829|PDB:1KHF"
FT HELIX 574..577
FT /evidence="ECO:0007829|PDB:1KHB"
FT HELIX 582..600
FT /evidence="ECO:0007829|PDB:1KHB"
FT HELIX 601..603
FT /evidence="ECO:0007829|PDB:1KHB"
FT HELIX 606..620
FT /evidence="ECO:0007829|PDB:1KHB"
SQ SEQUENCE 622 AA; 69195 MW; 78D309E0845CC181 CRC64;
MPPQLQNGLN LSAKVVQGSL DSLPQAVREF LENNAELCQP DHIHICDGSE EENGRLLGQM
EEEGILRRLK KYDNCWLALT DPRDVARIES KTVIVTQEQR DTVPIPKTGL SQLGRWMSEE
DFEKAFNARF PGCMKGRTMY VIPFSMGPLG SPLSKIGIEL TDSPYVVASM RIMTRMGTPV
LEAVGDGEFV KCLHSVGCPL PLQKPLVNNW PCNPELTLIA HLPDRREIIS FGSGYGGNSL
LGKKCFALRM ASRLAKEEGW LAEHMLILGI TNPEGEKKYL AAAFPSACGK TNLAMMNPSL
PGWKVECVGD DIAWMKFDAQ GHLRAINPEN GFFGVAPGTS VKTNPNAIKT IQKNTIFTNV
AETSDGGVYW EGIDEPLASG VTITSWKNKE WSSEDGEPCA HPNSRFCTPA SQCPIIDAAW
ESPEGVPIEG IIFGGRRPAG VPLVYEALSW QHGVFVGAAM RSEATAAAEH KGKIIMHDPF
AMRPFFGYNF GKYLAHWLSM AQHPAAKLPK IFHVNWFRKD KEGKFLWPGF GENSRVLEWM
FNRIDGKAST KLTPIGYIPK EDALNLKGLG HINMMELFSI SKEFWEKEVE DIEKYLEDQV
NADLPCEIER EILALKQRIS QM
