ID   PCKGM_HUMAN             Reviewed;         640 AA.
AC   Q16822; B4DW73; O43253; Q86U01; Q9BV62;
DT   15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT   28-MAR-2018, sequence version 4.
DT   27-MAR-2024, entry version 220.
DE   RecName: Full=Phosphoenolpyruvate carboxykinase [GTP], mitochondrial;
DE            Short=PEPCK-M;
DE            EC=4.1.1.32 {ECO:0000269|PubMed:28955899};
DE   AltName: Full=Phosphoenolpyruvate carboxykinase 2, mitochondrial {ECO:0000303|PubMed:9657976};
DE            Short=mtPCK2 {ECO:0000303|PubMed:9657976};
DE   Flags: Precursor;
GN   Name=PCK2 {ECO:0000312|HGNC:HGNC:8725}; Synonyms=PEPCK2;
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), AND SUBCELLULAR LOCATION.
RC   TISSUE=Liver;
RX   PubMed=8645161; DOI=10.1042/bj3150807;
RA   Modaressi S., Christ B., Bratke J., Zahn S., Heise T., Jungermann K.;
RT   "Molecular cloning, sequencing and expression of the cDNA of the
RT   mitochondrial form of phosphoenolpyruvate carboxykinase from human liver.";
RL   Biochem. J. 315:807-814(1996).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1), AND TISSUE SPECIFICITY.
RX   PubMed=9657976; DOI=10.1042/bj3330359;
RA   Modaressi S., Brechtel K., Christ B., Jungermann K.;
RT   "Human mitochondrial phosphoenolpyruvate carboxykinase 2 gene. Structure,
RT   chromosomal localization and tissue-specific expression.";
RL   Biochem. J. 333:359-366(1998).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC   TISSUE=Neuroblastoma;
RA   Li W.B., Gruber C., Jessee J., Polayes D.;
RT   "Full-length cDNA libraries and normalization.";
RL   Submitted (FEB-2003) to the EMBL/GenBank/DDBJ databases.
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RC   TISSUE=Kidney;
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=12508121; DOI=10.1038/nature01348;
RA   Heilig R., Eckenberg R., Petit J.-L., Fonknechten N., Da Silva C.,
RA   Cattolico L., Levy M., Barbe V., De Berardinis V., Ureta-Vidal A.,
RA   Pelletier E., Vico V., Anthouard V., Rowen L., Madan A., Qin S., Sun H.,
RA   Du H., Pepin K., Artiguenave F., Robert C., Cruaud C., Bruels T.,
RA   Jaillon O., Friedlander L., Samson G., Brottier P., Cure S., Segurens B.,
RA   Aniere F., Samain S., Crespeau H., Abbasi N., Aiach N., Boscus D.,
RA   Dickhoff R., Dors M., Dubois I., Friedman C., Gouyvenoux M., James R.,
RA   Madan A., Mairey-Estrada B., Mangenot S., Martins N., Menard M., Oztas S.,
RA   Ratcliffe A., Shaffer T., Trask B., Vacherie B., Bellemere C., Belser C.,
RA   Besnard-Gonnet M., Bartol-Mavel D., Boutard M., Briez-Silla S.,
RA   Combette S., Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C.,
RA   Muselet D., Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P.,
RA   Trybou A., Vega-Czarny N., Bataille E., Bluet E., Bordelais I., Dubois M.,
RA   Dumont C., Guerin T., Haffray S., Hammadi R., Muanga J., Pellouin V.,
RA   Robert D., Wunderle E., Gauguet G., Roy A., Sainte-Marthe L., Verdier J.,
RA   Verdier-Discala C., Hillier L.W., Fulton L., McPherson J., Matsuda F.,
RA   Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W., Quetier F.,
RA   Waterston R., Hood L., Weissenbach J.;
RT   "The DNA sequence and analysis of human chromosome 14.";
RL   Nature 421:601-607(2003).
RN   [6]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC   TISSUE=Placenta;
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA project:
RT   the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [7]
RP   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   [8]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-42; SER-115; THR-196 AND
RP   SER-304, AND 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   [9]
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   [10]
RP   FUNCTION, CATALYTIC ACTIVITY, COFACTOR, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX   PubMed=28955899; DOI=10.1016/j.bbrep.2016.06.007;
RA   Escos M., Latorre P., Hidalgo J., Hurtado-Guerrero R., Carrodeguas J.A.,
RA   Lopez-Buesa P.;
RT   "Kinetic and functional properties of human mitochondrial
RT   phosphoenolpyruvate carboxykinase.";
RL   Biochem. Biophys. Rep. 7:124-129(2016).
RN   [11]
RP   VARIANTS 23-SER--MET-640 DEL; LEU-170 AND 193-ARG--MET-640 DEL.
RX   PubMed=36845668; DOI=10.1016/j.xhgg.2023.100182;
RA   Sondheimer N., Aleman A., Cameron J., Gonorazky H., Sabha N., Oliveira P.,
RA   Amburgey K., Wahedi A., Wang D., Shy M., Dowling J.J.;
RT   "Biallelic pathogenic variants in the mitochondrial form of
RT   phosphoenolpyruvate carboxykinase cause peripheral neuropathy.";
RL   HGG Adv. 4:100182-100182(2023).
CC   -!- FUNCTION: Mitochondrial phosphoenolpyruvate carboxykinase that
CC       catalyzes the conversion of oxaloacetate (OAA) to phosphoenolpyruvate
CC       (PEP), the rate-limiting step in the metabolic pathway that produces
CC       glucose from lactate and other precursors derived from the citric acid
CC       cycle (PubMed:28955899). Can play an active role in glyceroneogenesis
CC       and gluconeogenesis (PubMed:28955899). {ECO:0000269|PubMed:28955899}.
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:28955899};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:10389;
CC         Evidence={ECO:0000305|PubMed:28955899};
CC   -!- COFACTOR:
CC       Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC         Evidence={ECO:0000269|PubMed:28955899};
CC       Note=Binds 1 Mn(2+) ion per subunit. {ECO:0000250|UniProtKB:P21642};
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       Kinetic parameters:
CC         KM=585 uM for phosphoenolpyruvate {ECO:0000269|PubMed:28955899};
CC         KM=8.7 uM for oxaloacetate {ECO:0000269|PubMed:28955899};
CC         KM=29 uM for GTP {ECO:0000269|PubMed:28955899};
CC         KM=200 uM for Mn(2+) {ECO:0000269|PubMed:28955899};
CC         KM=3.5 uM for Mn(2+) (in presence of Mg(2+))
CC         {ECO:0000269|PubMed:28955899};
CC         Note=kcat is 32 sec(-1) with oxaloacetate as substrate. kcat is 585
CC         sec(-1) with phosphoenolpyruvate as substrate.
CC         {ECO:0000269|PubMed:28955899};
CC   -!- PATHWAY: Carbohydrate biosynthesis; gluconeogenesis.
CC       {ECO:0000305|PubMed:28955899}.
CC   -!- SUBUNIT: Monomer. {ECO:0000250|UniProtKB:P21642}.
CC   -!- INTERACTION:
CC       Q16822; P84022: SMAD3; NbExp=2; IntAct=EBI-2825219, EBI-347161;
CC   -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000269|PubMed:8645161}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=3;
CC       Name=1;
CC         IsoId=Q16822-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=Q16822-2; Sequence=VSP_038783;
CC       Name=3;
CC         IsoId=Q16822-3; Sequence=VSP_059389;
CC   -!- TISSUE SPECIFICITY: Widely expressed. {ECO:0000269|PubMed:9657976}.
CC   -!- DISEASE: Mitochondrial phosphoenolpyruvate carboxykinase deficiency (M-
CC       PEPCKD) [MIM:261650]: Metabolic disorder resulting from impaired
CC       gluconeogenesis. It is a rare disease with less than 10 cases reported
CC       in the literature. Clinical characteristics include hypotonia,
CC       hepatomegaly, failure to thrive, lactic acidosis and hypoglycemia.
CC       Autopsy reveals fatty infiltration of both the liver and kidneys. The
CC       disorder is transmitted as an autosomal recessive trait. Note=The gene
CC       represented in this entry may be involved in disease pathogenesis.
CC   -!- MISCELLANEOUS: In eukaryotes there are two isozymes: a cytoplasmic one
CC       and a mitochondrial one.
CC   -!- SIMILARITY: Belongs to the phosphoenolpyruvate carboxykinase [GTP]
CC       family. {ECO:0000305}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=CAD62600.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR   EMBL; X92720; CAA63380.1; -; mRNA.
DR   EMBL; Y11484; CAA72272.1; -; Genomic_DNA.
DR   EMBL; BX248272; CAD62600.1; ALT_INIT; mRNA.
DR   EMBL; AK301400; BAG62935.1; -; mRNA.
DR   EMBL; AK316206; BAH14577.1; -; mRNA.
DR   EMBL; AL136295; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; KF455834; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BC001454; AAH01454.1; -; mRNA.
DR   CCDS; CCDS41928.1; -. [Q16822-2]
DR   CCDS; CCDS76660.1; -. [Q16822-3]
DR   CCDS; CCDS9609.1; -. [Q16822-1]
DR   PIR; S69546; S69546.
DR   RefSeq; NP_001018083.2; NM_001018073.2. [Q16822-2]
DR   RefSeq; NP_001278485.1; NM_001291556.1. [Q16822-3]
DR   RefSeq; NP_001294983.1; NM_001308054.1. [Q16822-3]
DR   RefSeq; NP_004554.3; NM_004563.3. [Q16822-1]
DR   AlphaFoldDB; Q16822; -.
DR   SMR; Q16822; -.
DR   BioGRID; 111137; 106.
DR   IntAct; Q16822; 57.
DR   MINT; Q16822; -.
DR   STRING; 9606.ENSP00000216780; -.
DR   ChEMBL; CHEMBL3096; -.
DR   DrugBank; DB00787; Acyclovir.
DR   GlyGen; Q16822; 1 site, 1 O-linked glycan (1 site).
DR   iPTMnet; Q16822; -.
DR   PhosphoSitePlus; Q16822; -.
DR   SwissPalm; Q16822; -.
DR   BioMuta; PCK2; -.
DR   DMDM; 290457671; -.
DR   EPD; Q16822; -.
DR   jPOST; Q16822; -.
DR   MassIVE; Q16822; -.
DR   MaxQB; Q16822; -.
DR   PaxDb; 9606-ENSP00000216780; -.
DR   PeptideAtlas; Q16822; -.
DR   ProteomicsDB; 5315; -.
DR   ProteomicsDB; 61082; -. [Q16822-1]
DR   ProteomicsDB; 61083; -. [Q16822-2]
DR   Pumba; Q16822; -.
DR   TopDownProteomics; Q16822-2; -. [Q16822-2]
DR   Antibodypedia; 8846; 341 antibodies from 36 providers.
DR   DNASU; 5106; -.
DR   Ensembl; ENST00000216780.9; ENSP00000216780.4; ENSG00000100889.12. [Q16822-1]
DR   Ensembl; ENST00000396973.8; ENSP00000380171.4; ENSG00000100889.12. [Q16822-2]
DR   Ensembl; ENST00000545054.6; ENSP00000441826.2; ENSG00000100889.12. [Q16822-3]
DR   Ensembl; ENST00000561286.5; ENSP00000454011.1; ENSG00000100889.12. [Q16822-3]
DR   Ensembl; ENST00000644679.1; ENSP00000496102.1; ENSG00000285241.2. [Q16822-3]
DR   Ensembl; ENST00000645217.2; ENSP00000494919.1; ENSG00000285241.2. [Q16822-1]
DR   Ensembl; ENST00000645536.1; ENSP00000496343.1; ENSG00000285241.2. [Q16822-3]
DR   Ensembl; ENST00000645709.1; ENSP00000494029.1; ENSG00000285241.2. [Q16822-2]
DR   GeneID; 5106; -.
DR   KEGG; hsa:5106; -.
DR   MANE-Select; ENST00000216780.9; ENSP00000216780.4; NM_004563.4; NP_004554.3.
DR   UCSC; uc001wlt.4; human. [Q16822-1]
DR   UCSC; uc010tnw.3; human.
DR   AGR; HGNC:8725; -.
DR   CTD; 5106; -.
DR   DisGeNET; 5106; -.
DR   GeneCards; PCK2; -.
DR   HGNC; HGNC:8725; PCK2.
DR   HPA; ENSG00000100889; Group enriched (intestine, kidney, liver).
DR   MalaCards; PCK2; -.
DR   MIM; 261650; phenotype.
DR   MIM; 614095; gene.
DR   neXtProt; NX_Q16822; -.
DR   OpenTargets; ENSG00000100889; -.
DR   Orphanet; 2880; Phosphoenolpyruvate carboxykinase deficiency.
DR   PharmGKB; PA33070; -.
DR   VEuPathDB; HostDB:ENSG00000100889; -.
DR   eggNOG; KOG3749; Eukaryota.
DR   GeneTree; ENSGT00390000001912; -.
DR   HOGENOM; CLU_028872_1_0_1; -.
DR   InParanoid; Q16822; -.
DR   OMA; SEHMFIT; -.
DR   OrthoDB; 5471652at2759; -.
DR   PhylomeDB; Q16822; -.
DR   TreeFam; TF314402; -.
DR   BioCyc; MetaCyc:HS02160-MONOMER; -.
DR   BRENDA; 4.1.1.32; 2681.
DR   PathwayCommons; Q16822; -.
DR   Reactome; R-HSA-70263; Gluconeogenesis.
DR   SignaLink; Q16822; -.
DR   SIGNOR; Q16822; -.
DR   UniPathway; UPA00138; -.
DR   BioGRID-ORCS; 5106; 21 hits in 1157 CRISPR screens.
DR   ChiTaRS; PCK2; human.
DR   GenomeRNAi; 5106; -.
DR   Pharos; Q16822; Tbio.
DR   PRO; PR:Q16822; -.
DR   Proteomes; UP000005640; Chromosome 14.
DR   RNAct; Q16822; Protein.
DR   Bgee; ENSG00000100889; Expressed in right lobe of liver and 105 other cell types or tissues.
DR   ExpressionAtlas; Q16822; baseline and differential.
DR   GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR   GO; GO:0005759; C:mitochondrial matrix; TAS:Reactome.
DR   GO; GO:0005739; C:mitochondrion; IDA:HPA.
DR   GO; GO:0005525; F:GTP binding; IEA:UniProtKB-KW.
DR   GO; GO:0030145; F:manganese ion binding; IDA:UniProtKB.
DR   GO; GO:0004613; F:phosphoenolpyruvate carboxykinase (GTP) activity; IDA:UniProtKB.
DR   GO; GO:0004611; F:phosphoenolpyruvate carboxykinase activity; TAS:ProtInc.
DR   GO; GO:0071549; P:cellular response to dexamethasone stimulus; IBA:GO_Central.
DR   GO; GO:0071333; P:cellular response to glucose stimulus; IBA:GO_Central.
DR   GO; GO:0032869; P:cellular response to insulin stimulus; IBA:GO_Central.
DR   GO; GO:0071356; P:cellular response to tumor necrosis factor; IEA:Ensembl.
DR   GO; GO:0006094; P:gluconeogenesis; IBA:GO_Central.
DR   GO; GO:0046327; P:glycerol biosynthetic process from pyruvate; IBA:GO_Central.
DR   GO; GO:0070365; P:hepatocyte differentiation; IBA:GO_Central.
DR   GO; GO:0006116; P:NADH oxidation; IEA:Ensembl.
DR   GO; GO:0006107; P:oxaloacetate metabolic process; IEA:Ensembl.
DR   GO; GO:0032024; P:positive regulation of insulin secretion; IEA:Ensembl.
DR   GO; GO:0019543; P:propionate catabolic process; IBA:GO_Central.
DR   GO; GO:0032496; P:response to lipopolysaccharide; IEA:Ensembl.
DR   GO; GO:0042594; P:response to starvation; IBA:GO_Central.
DR   CDD; cd00819; PEPCK_GTP; 1.
DR   Gene3D; 3.90.228.20; -; 1.
DR   Gene3D; 3.40.449.10; Phosphoenolpyruvate Carboxykinase, domain 1; 1.
DR   Gene3D; 2.170.8.10; Phosphoenolpyruvate Carboxykinase, domain 2; 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; PHOSPHOENOLPYRUVATE CARBOXYKINASE; 1.
DR   PANTHER; PTHR11561:SF11; PHOSPHOENOLPYRUVATE CARBOXYKINASE [GTP], MITOCHONDRIAL; 1.
DR   Pfam; PF00821; PEPCK_GTP; 1.
DR   Pfam; PF17297; PEPCK_N; 1.
DR   PIRSF; PIRSF001348; PEP_carboxykinase_GTP; 1.
DR   SUPFAM; SSF68923; PEP carboxykinase N-terminal domain; 1.
DR   SUPFAM; SSF53795; PEP carboxykinase-like; 1.
DR   PROSITE; PS00505; PEPCK_GTP; 1.
DR   SWISS-2DPAGE; Q16822; -.
DR   Genevisible; Q16822; HS.
PE   1: Evidence at protein level;
KW   Acetylation; Alternative splicing; Decarboxylase; Disease variant;
KW   Gluconeogenesis; GTP-binding; Lyase; Manganese; Metal-binding;
KW   Mitochondrion; Nucleotide-binding; Phosphoprotein; Reference proteome;
KW   Transit peptide.
FT   TRANSIT         1..32
FT                   /note="Mitochondrion"
FT                   /evidence="ECO:0000250|UniProtKB:P21642"
FT   CHAIN           33..640
FT                   /note="Phosphoenolpyruvate carboxykinase [GTP],
FT                   mitochondrial"
FT                   /id="PRO_0000023568"
FT   BINDING         104
FT                   /ligand="phosphoenolpyruvate"
FT                   /ligand_id="ChEBI:CHEBI:58702"
FT                   /evidence="ECO:0000250|UniProtKB:P21642"
FT   BINDING         255
FT                   /ligand="phosphoenolpyruvate"
FT                   /ligand_id="ChEBI:CHEBI:58702"
FT                   /evidence="ECO:0000250|UniProtKB:P21642"
FT   BINDING         262
FT                   /ligand="Mn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29035"
FT                   /evidence="ECO:0000250|UniProtKB:P21642"
FT   BINDING         282
FT                   /ligand="Mn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29035"
FT                   /evidence="ECO:0000250|UniProtKB:P21642"
FT   BINDING         305
FT                   /ligand="GDP"
FT                   /ligand_id="ChEBI:CHEBI:58189"
FT                   /evidence="ECO:0000250|UniProtKB:P21642"
FT   BINDING         306
FT                   /ligand="GDP"
FT                   /ligand_id="ChEBI:CHEBI:58189"
FT                   /evidence="ECO:0000250|UniProtKB:P21642"
FT   BINDING         306
FT                   /ligand="Mn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29035"
FT                   /evidence="ECO:0000250|UniProtKB:P21642"
FT   BINDING         307
FT                   /ligand="GDP"
FT                   /ligand_id="ChEBI:CHEBI:58189"
FT                   /evidence="ECO:0000250|UniProtKB:P21642"
FT   BINDING         308
FT                   /ligand="GDP"
FT                   /ligand_id="ChEBI:CHEBI:58189"
FT                   /evidence="ECO:0000250|UniProtKB:P21642"
FT   BINDING         309
FT                   /ligand="GDP"
FT                   /ligand_id="ChEBI:CHEBI:58189"
FT                   /evidence="ECO:0000250|UniProtKB:P21642"
FT   BINDING         310
FT                   /ligand="GDP"
FT                   /ligand_id="ChEBI:CHEBI:58189"
FT                   /evidence="ECO:0000250|UniProtKB:P21642"
FT   BINDING         329
FT                   /ligand="Mn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29035"
FT                   /evidence="ECO:0000250|UniProtKB:P21642"
FT   BINDING         355
FT                   /ligand="GDP"
FT                   /ligand_id="ChEBI:CHEBI:58189"
FT                   /evidence="ECO:0000250|UniProtKB:P21642"
FT   BINDING         421
FT                   /ligand="phosphoenolpyruvate"
FT                   /ligand_id="ChEBI:CHEBI:58702"
FT                   /evidence="ECO:0000250|UniProtKB:P21642"
FT   BINDING         423
FT                   /ligand="phosphoenolpyruvate"
FT                   /ligand_id="ChEBI:CHEBI:58702"
FT                   /evidence="ECO:0000250|UniProtKB:P21642"
FT   BINDING         454
FT                   /ligand="GDP"
FT                   /ligand_id="ChEBI:CHEBI:58189"
FT                   /evidence="ECO:0000250|UniProtKB:P21642"
FT   BINDING         534
FT                   /ligand="GDP"
FT                   /ligand_id="ChEBI:CHEBI:58189"
FT                   /evidence="ECO:0000250|UniProtKB:P21642"
FT   BINDING         543
FT                   /ligand="GDP"
FT                   /ligand_id="ChEBI:CHEBI:58189"
FT                   /evidence="ECO:0000250|UniProtKB:P21642"
FT   BINDING         548
FT                   /ligand="GDP"
FT                   /ligand_id="ChEBI:CHEBI:58189"
FT                   /evidence="ECO:0000250|UniProtKB:P21642"
FT   BINDING         551
FT                   /ligand="GDP"
FT                   /ligand_id="ChEBI:CHEBI:58189"
FT                   /evidence="ECO:0000250|UniProtKB:P21642"
FT   MOD_RES         42
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0007744|PubMed:24275569"
FT   MOD_RES         88
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:P35558"
FT   MOD_RES         115
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:24275569"
FT   MOD_RES         196
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0007744|PubMed:24275569"
FT   MOD_RES         304
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:24275569"
FT   MOD_RES         457
FT                   /note="N6-succinyllysine"
FT                   /evidence="ECO:0000250|UniProtKB:Q8BH04"
FT   VAR_SEQ         1..134
FT                   /note="Missing (in isoform 3)"
FT                   /id="VSP_059389"
FT   VAR_SEQ         413..640
FT                   /note="DKEPCAHPNSRFCAPARQCPIMDPAWEAPEGVPIDAIIFGGRRPKGVPLVYE
FT                   AFNWRHGVFVGSAMRSESTAAAEHKGKIIMHDPFAMRPFFGYNFGHYLEHWLSMEGRKG
FT                   AQLPRIFHVNWFRRDEAGHFLWPGFGENARVLDWICRRLEGEDSARETPIGLVPKEGAL
FT                   DLSGLRAIDTTQLFSLPKDFWEQEVRDIRSYLTEQVNQDLPKEVLAELEALERRVHKM
FT                   -> MCGGEGVAQPPGLSTLMVEKLSPQPPTIF (in isoform 2)"
FT                   /evidence="ECO:0000303|Ref.3"
FT                   /id="VSP_038783"
FT   VARIANT         23..640
FT                   /note="Missing (found in a patient with abnormal gait and
FT                   demyelinating peripheral neuropathy; uncertain
FT                   significance)"
FT                   /evidence="ECO:0000269|PubMed:36845668"
FT                   /id="VAR_088520"
FT   VARIANT         31
FT                   /note="R -> Q (in dbSNP:rs2229660)"
FT                   /id="VAR_042445"
FT   VARIANT         64
FT                   /note="D -> N (in dbSNP:rs10132601)"
FT                   /id="VAR_042446"
FT   VARIANT         170
FT                   /note="P -> L (found in a patient with abnormal gait and
FT                   demyelinating peripheral neuropathy; uncertain
FT                   significance)"
FT                   /evidence="ECO:0000269|PubMed:36845668"
FT                   /id="VAR_088521"
FT   VARIANT         193..640
FT                   /note="Missing (found in a patient with abnormal gait and
FT                   demyelinating peripheral neuropathy; likely pathogenic)"
FT                   /evidence="ECO:0000269|PubMed:36845668"
FT                   /id="VAR_088522"
FT   VARIANT         406
FT                   /note="G -> S (in dbSNP:rs17101262)"
FT                   /id="VAR_042447"
FT   VARIANT         521
FT                   /note="R -> H (in dbSNP:rs35618680)"
FT                   /id="VAR_056662"
FT   CONFLICT        121
FT                   /note="P -> Q (in Ref. 3; CAD62600)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        128
FT                   /note="R -> C (in Ref. 1; CAA63380)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        296..298
FT                   /note="RYV -> ALC (in Ref. 1; CAA63380 and 2; CAA72272)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        476
FT                   /note="S -> R (in Ref. 1; CAA63380 and 2; CAA72272)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   640 AA;  70699 MW;  DCE561252EBF8871 CRC64;
     MAALYRPGLR LNWHGLSPLG WPSCRSIQTL RVLSGDLGQL PTGIRDFVEH SARLCQPEGI
     HICDGTEAEN TATLTLLEQQ GLIRKLPKYN NCWLARTDPK DVARVESKTV IVTPSQRDTV
     PLPPGGARGQ LGNWMSPADF QRAVDERFPG CMQGRTMYVL PFSMGPVGSP LSRIGVQLTD
     SAYVVASMRI MTRLGTPVLQ ALGDGDFVKC LHSVGQPLTG QGEPVSQWPC NPEKTLIGHV
     PDQREIISFG SGYGGNSLLG KKCFALRIAS RLARDEGWLA EHMLILGITS PAGKKRYVAA
     AFPSACGKTN LAMMRPALPG WKVECVGDDI AWMRFDSEGR LRAINPENGF FGVAPGTSAT
     TNPNAMATIQ SNTIFTNVAE TSDGGVYWEG IDQPLPPGVT VTSWLGKPWK PGDKEPCAHP
     NSRFCAPARQ CPIMDPAWEA PEGVPIDAII FGGRRPKGVP LVYEAFNWRH GVFVGSAMRS
     ESTAAAEHKG KIIMHDPFAM RPFFGYNFGH YLEHWLSMEG RKGAQLPRIF HVNWFRRDEA
     GHFLWPGFGE NARVLDWICR RLEGEDSARE TPIGLVPKEG ALDLSGLRAI DTTQLFSLPK
     DFWEQEVRDI RSYLTEQVNQ DLPKEVLAEL EALERRVHKM
//