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Q16822

- PCKGM_HUMAN

UniProt

Q16822 - PCKGM_HUMAN

Protein

Phosphoenolpyruvate carboxykinase [GTP], mitochondrial

Gene

PCK2

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 152 (01 Oct 2014)
      Sequence version 3 (02 Mar 2010)
      Previous versions | rss
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    Functioni

    Catalyzes the conversion of oxaloacetate (OAA) to phosphoenolpyruvate (PEP), the rate-limiting step in the metabolic pathway that produces glucose from lactate and other precursors derived from the citric acid cycle.By similarity

    Catalytic activityi

    GTP + oxaloacetate = GDP + phosphoenolpyruvate + CO2.

    Cofactori

    Manganese.By similarity
    Binds 1 manganese ion per subunit.By similarity

    Pathwayi

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei104 – 1041SubstrateBy similarity
    Binding sitei255 – 2551Substrate; via amide nitrogenBy similarity
    Metal bindingi262 – 2621ManganeseBy similarity
    Binding sitei262 – 2621SubstrateBy similarity
    Metal bindingi282 – 2821Manganese; via tele nitrogenBy similarity
    Binding sitei304 – 3041SubstrateBy similarity
    Active sitei306 – 3061By similarity
    Metal bindingi329 – 3291ManganeseBy similarity
    Binding sitei423 – 4231GTPBy similarity
    Binding sitei454 – 4541GTPBy similarity

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi305 – 3106GTPBy similarity
    Nucleotide bindingi548 – 5514GTPBy similarity

    GO - Molecular functioni

    1. GTP binding Source: UniProtKB-KW
    2. metal ion binding Source: UniProtKB-KW
    3. phosphoenolpyruvate carboxykinase (GTP) activity Source: UniProtKB-EC
    4. phosphoenolpyruvate carboxykinase activity Source: ProtInc
    5. protein binding Source: IntAct

    GO - Biological processi

    1. carbohydrate metabolic process Source: Reactome
    2. cellular response to glucose stimulus Source: Ensembl
    3. gluconeogenesis Source: Reactome
    4. glucose metabolic process Source: Reactome
    5. NADH oxidation Source: Ensembl
    6. oxaloacetate metabolic process Source: Ensembl
    7. positive regulation of insulin secretion Source: Ensembl
    8. pyruvate metabolic process Source: Ensembl
    9. response to glucocorticoid Source: Ensembl
    10. small molecule metabolic process Source: Reactome

    Keywords - Molecular functioni

    Decarboxylase, Lyase

    Keywords - Biological processi

    Gluconeogenesis

    Keywords - Ligandi

    GTP-binding, Manganese, Metal-binding, Nucleotide-binding

    Enzyme and pathway databases

    BioCyciMetaCyc:HS02160-MONOMER.
    ReactomeiREACT_1520. Gluconeogenesis.
    UniPathwayiUPA00138.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Phosphoenolpyruvate carboxykinase [GTP], mitochondrial (EC:4.1.1.32)
    Short name:
    PEPCK-M
    Gene namesi
    Name:PCK2
    Synonyms:PEPCK2
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 14

    Organism-specific databases

    HGNCiHGNC:8725. PCK2.

    Subcellular locationi

    GO - Cellular componenti

    1. extracellular vesicular exosome Source: UniProt
    2. mitochondrial matrix Source: Reactome
    3. mitochondrion Source: HPA

    Keywords - Cellular componenti

    Mitochondrion

    Pathology & Biotechi

    Involvement in diseasei

    Mitochondrial phosphoenolpyruvate carboxykinase deficiency (M-PEPCKD) [MIM:261650]: Metabolic disorder resulting from impaired gluconeogenesis. It is a rare disease with less than 10 cases reported in the literature. Clinical characteristics include hypotonia, hepatomegaly, failure to thrive, lactic acidosis and hypoglycemia. Autopsy reveals fatty infiltration of both the liver and kidneys. The disorder is transmitted as an autosomal recessive trait.
    Note: The disease is caused by mutations affecting the gene represented in this entry.

    Organism-specific databases

    MIMi261650. phenotype.
    Orphaneti79317. Phosphoenolpyruvate carboxykinase 2 deficiency.
    PharmGKBiPA33070.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transit peptidei1 – 3232MitochondrionBy similarityAdd
    BLAST
    Chaini33 – 640608Phosphoenolpyruvate carboxykinase [GTP], mitochondrialPRO_0000023568Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei457 – 4571N6-succinyllysineBy similarity

    Proteomic databases

    MaxQBiQ16822.
    PaxDbiQ16822.
    PRIDEiQ16822.

    2D gel databases

    SWISS-2DPAGEQ16822.

    PTM databases

    PhosphoSiteiQ16822.

    Expressioni

    Gene expression databases

    ArrayExpressiQ16822.
    BgeeiQ16822.
    CleanExiHS_PCK2.
    GenevestigatoriQ16822.

    Organism-specific databases

    HPAiCAB018734.
    HPA051162.
    HPA053502.

    Interactioni

    Subunit structurei

    Monomer.

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    SMAD3P840222EBI-2825219,EBI-347161

    Protein-protein interaction databases

    BioGridi111137. 6 interactions.
    IntActiQ16822. 7 interactions.
    STRINGi9606.ENSP00000216780.

    Structurei

    3D structure databases

    ProteinModelPortaliQ16822.
    SMRiQ16822. Positions 31-640.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni421 – 4233Substrate bindingBy similarity

    Sequence similaritiesi

    Keywords - Domaini

    Transit peptide

    Phylogenomic databases

    eggNOGiCOG1274.
    HOGENOMiHOG000191700.
    HOVERGENiHBG053651.
    InParanoidiQ16822.
    KOiK01596.
    OMAiQAVDERF.
    OrthoDBiEOG7KSX81.
    PhylomeDBiQ16822.
    TreeFamiTF314402.

    Family and domain databases

    Gene3Di3.40.449.10. 1 hit.
    3.90.228.20. 2 hits.
    HAMAPiMF_00452. PEPCK_GTP.
    InterProiIPR018091. PEP_carboxykin_GTP_CS.
    IPR013035. PEP_carboxykinase_C.
    IPR008209. PEP_carboxykinase_GTP.
    IPR008210. PEP_carboxykinase_N.
    [Graphical view]
    PANTHERiPTHR11561. PTHR11561. 1 hit.
    PfamiPF00821. PEPCK. 1 hit.
    [Graphical view]
    PIRSFiPIRSF001348. PEP_carboxykinase_GTP. 1 hit.
    SUPFAMiSSF68923. SSF68923. 1 hit.
    PROSITEiPS00505. PEPCK_GTP. 1 hit.
    [Graphical view]

    Sequences (2)i

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    This entry describes 2 isoformsi produced by alternative splicing. Align

    Isoform 1 (identifier: Q16822-1) [UniParc]FASTAAdd to Basket

    This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

    « Hide

    MAALYRPGLR LNWHGLSPLG WPSCRSIQTL RVLSGDLGQL PTGIRDFVEH    50
    SARLCQPEGI HICDGTEAEN TATLTLLEQQ GLIRKLPKYN NCWLARTDPK 100
    DVARVESKTV IVTPSQRDTV QLPPGGARGQ LGNWMSPADF QRAVDERFPG 150
    CMQGRTMYVL PFSMGPVGSP LSRIGVQLTD SAYVVASMRI MTRLGTPVLQ 200
    ALGDGDFVKC LHSVGQPLTG QGEPVSQWPC NPEKTLIGHV PDQREIISFG 250
    SGYGGNSLLG KKCFALRIAS RLARDEGWLA EHMLILGITS PAGKKRYVAA 300
    AFPSACGKTN LAMMRPALPG WKVECVGDDI AWMRFDSEGR LRAINPENGF 350
    FGVAPGTSAT TNPNAMATIQ SNTIFTNVAE TSDGGVYWEG IDQPLPPGVT 400
    VTSWLGKPWK PGDKEPCAHP NSRFCAPARQ CPIMDPAWEA PEGVPIDAII 450
    FGGRRPKGVP LVYEAFNWRH GVFVGSAMRS ESTAAAEHKG KIIMHDPFAM 500
    RPFFGYNFGH YLEHWLSMEG RKGAQLPRIF HVNWFRRDEA GHFLWPGFGE 550
    NARVLDWICR RLEGEDSARE TPIGLVPKEG ALDLSGLRAI DTTQLFSLPK 600
    DFWEQEVRDI RSYLTEQVNQ DLPKEVLAEL EALERRVHKM 640
    Length:640
    Mass (Da):70,730
    Last modified:March 2, 2010 - v3
    Checksum:iB8CAC4252EBF8871
    GO
    Isoform 2 (identifier: Q16822-2) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         413-640: DKEPCAHPNS...EALERRVHKM → MCGGEGVAQPPGLSTLMVEKLSPQPPTIF

    Show »
    Length:441
    Mass (Da):47,564
    Checksum:i00FCF22C5C4053E5
    GO

    Sequence cautioni

    The sequence CAD62600.1 differs from that shown. Reason: Erroneous initiation.

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti121 – 1211Q → P in CAA63380. (PubMed:8645161)Curated
    Sequence conflicti121 – 1211Q → P in CAA72272. (PubMed:9657976)Curated
    Sequence conflicti121 – 1211Q → P in AAH01454. (PubMed:15489334)Curated
    Sequence conflicti128 – 1281R → C in CAA63380. (PubMed:8645161)Curated
    Sequence conflicti296 – 2983RYV → ALC in CAA63380. (PubMed:8645161)Curated
    Sequence conflicti296 – 2983RYV → ALC in CAA72272. (PubMed:9657976)Curated
    Sequence conflicti476 – 4761S → R in CAA63380. (PubMed:8645161)Curated
    Sequence conflicti476 – 4761S → R in CAA72272. (PubMed:9657976)Curated

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti31 – 311R → Q.
    Corresponds to variant rs2229660 [ dbSNP | Ensembl ].
    VAR_042445
    Natural varianti64 – 641D → N.
    Corresponds to variant rs10132601 [ dbSNP | Ensembl ].
    VAR_042446
    Natural varianti406 – 4061G → S.
    Corresponds to variant rs17101262 [ dbSNP | Ensembl ].
    VAR_042447
    Natural varianti521 – 5211R → H.
    Corresponds to variant rs35618680 [ dbSNP | Ensembl ].
    VAR_056662

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei413 – 640228DKEPC…RVHKM → MCGGEGVAQPPGLSTLMVEK LSPQPPTIF in isoform 2. 1 PublicationVSP_038783Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    X92720 mRNA. Translation: CAA63380.1.
    Y11484 Genomic DNA. Translation: CAA72272.1.
    BX248272 mRNA. Translation: CAD62600.1. Different initiation.
    AL136295 Genomic DNA. No translation available.
    BC001454 mRNA. Translation: AAH01454.1.
    CCDSiCCDS41928.1. [Q16822-2]
    CCDS9609.1. [Q16822-1]
    PIRiS69546.
    RefSeqiNP_001018083.2. NM_001018073.2.
    NP_004554.3. NM_004563.3.
    UniGeneiHs.75812.

    Genome annotation databases

    EnsembliENST00000216780; ENSP00000216780; ENSG00000100889. [Q16822-1]
    ENST00000396973; ENSP00000380171; ENSG00000100889. [Q16822-2]
    GeneIDi5106.
    KEGGihsa:5106.
    UCSCiuc001wls.3. human. [Q16822-2]
    uc001wlt.3. human. [Q16822-1]

    Polymorphism databases

    DMDMi290457671.

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    X92720 mRNA. Translation: CAA63380.1 .
    Y11484 Genomic DNA. Translation: CAA72272.1 .
    BX248272 mRNA. Translation: CAD62600.1 . Different initiation.
    AL136295 Genomic DNA. No translation available.
    BC001454 mRNA. Translation: AAH01454.1 .
    CCDSi CCDS41928.1. [Q16822-2 ]
    CCDS9609.1. [Q16822-1 ]
    PIRi S69546.
    RefSeqi NP_001018083.2. NM_001018073.2.
    NP_004554.3. NM_004563.3.
    UniGenei Hs.75812.

    3D structure databases

    ProteinModelPortali Q16822.
    SMRi Q16822. Positions 31-640.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 111137. 6 interactions.
    IntActi Q16822. 7 interactions.
    STRINGi 9606.ENSP00000216780.

    PTM databases

    PhosphoSitei Q16822.

    Polymorphism databases

    DMDMi 290457671.

    2D gel databases

    SWISS-2DPAGE Q16822.

    Proteomic databases

    MaxQBi Q16822.
    PaxDbi Q16822.
    PRIDEi Q16822.

    Protocols and materials databases

    DNASUi 5106.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000216780 ; ENSP00000216780 ; ENSG00000100889 . [Q16822-1 ]
    ENST00000396973 ; ENSP00000380171 ; ENSG00000100889 . [Q16822-2 ]
    GeneIDi 5106.
    KEGGi hsa:5106.
    UCSCi uc001wls.3. human. [Q16822-2 ]
    uc001wlt.3. human. [Q16822-1 ]

    Organism-specific databases

    CTDi 5106.
    GeneCardsi GC14P024563.
    HGNCi HGNC:8725. PCK2.
    HPAi CAB018734.
    HPA051162.
    HPA053502.
    MIMi 261650. phenotype.
    614095. gene.
    neXtProti NX_Q16822.
    Orphaneti 79317. Phosphoenolpyruvate carboxykinase 2 deficiency.
    PharmGKBi PA33070.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi COG1274.
    HOGENOMi HOG000191700.
    HOVERGENi HBG053651.
    InParanoidi Q16822.
    KOi K01596.
    OMAi QAVDERF.
    OrthoDBi EOG7KSX81.
    PhylomeDBi Q16822.
    TreeFami TF314402.

    Enzyme and pathway databases

    UniPathwayi UPA00138 .
    BioCyci MetaCyc:HS02160-MONOMER.
    Reactomei REACT_1520. Gluconeogenesis.

    Miscellaneous databases

    GenomeRNAii 5106.
    NextBioi 19706.
    PROi Q16822.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi Q16822.
    Bgeei Q16822.
    CleanExi HS_PCK2.
    Genevestigatori Q16822.

    Family and domain databases

    Gene3Di 3.40.449.10. 1 hit.
    3.90.228.20. 2 hits.
    HAMAPi MF_00452. PEPCK_GTP.
    InterProi IPR018091. PEP_carboxykin_GTP_CS.
    IPR013035. PEP_carboxykinase_C.
    IPR008209. PEP_carboxykinase_GTP.
    IPR008210. PEP_carboxykinase_N.
    [Graphical view ]
    PANTHERi PTHR11561. PTHR11561. 1 hit.
    Pfami PF00821. PEPCK. 1 hit.
    [Graphical view ]
    PIRSFi PIRSF001348. PEP_carboxykinase_GTP. 1 hit.
    SUPFAMi SSF68923. SSF68923. 1 hit.
    PROSITEi PS00505. PEPCK_GTP. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Molecular cloning, sequencing and expression of the cDNA of the mitochondrial form of phosphoenolpyruvate carboxykinase from human liver."
      Modaressi S., Christ B., Bratke J., Zahn S., Heise T., Jungermann K.
      Biochem. J. 315:807-814(1996) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
      Tissue: Liver.
    2. "Human mitochondrial phosphoenolpyruvate carboxykinase 2 gene. Structure, chromosomal localization and tissue-specific expression."
      Modaressi S., Brechtel K., Christ B., Jungermann K.
      Biochem. J. 333:359-366(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1).
    3. "Full-length cDNA libraries and normalization."
      Li W.B., Gruber C., Jessee J., Polayes D.
      Submitted (FEB-2003) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
      Tissue: Neuroblastoma.
    4. "The DNA sequence and analysis of human chromosome 14."
      Heilig R., Eckenberg R., Petit J.-L., Fonknechten N., Da Silva C., Cattolico L., Levy M., Barbe V., De Berardinis V., Ureta-Vidal A., Pelletier E., Vico V., Anthouard V., Rowen L., Madan A., Qin S., Sun H., Du H.
      , Pepin K., Artiguenave F., Robert C., Cruaud C., Bruels T., Jaillon O., Friedlander L., Samson G., Brottier P., Cure S., Segurens B., Aniere F., Samain S., Crespeau H., Abbasi N., Aiach N., Boscus D., Dickhoff R., Dors M., Dubois I., Friedman C., Gouyvenoux M., James R., Madan A., Mairey-Estrada B., Mangenot S., Martins N., Menard M., Oztas S., Ratcliffe A., Shaffer T., Trask B., Vacherie B., Bellemere C., Belser C., Besnard-Gonnet M., Bartol-Mavel D., Boutard M., Briez-Silla S., Combette S., Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C., Muselet D., Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P., Trybou A., Vega-Czarny N., Bataille E., Bluet E., Bordelais I., Dubois M., Dumont C., Guerin T., Haffray S., Hammadi R., Muanga J., Pellouin V., Robert D., Wunderle E., Gauguet G., Roy A., Sainte-Marthe L., Verdier J., Verdier-Discala C., Hillier L.W., Fulton L., McPherson J., Matsuda F., Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W., Quetier F., Waterston R., Hood L., Weissenbach J.
      Nature 421:601-607(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    5. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
      Tissue: Placenta.
    6. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].

    Entry informationi

    Entry nameiPCKGM_HUMAN
    AccessioniPrimary (citable) accession number: Q16822
    Secondary accession number(s): O43253, Q86U01, Q9BV62
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: July 15, 1998
    Last sequence update: March 2, 2010
    Last modified: October 1, 2014
    This is version 152 of the entry and version 3 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Miscellaneous

    In eukaryotes there are two isozymes: a cytoplasmic one and a mitochondrial one.

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. Human chromosome 14
      Human chromosome 14: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. PATHWAY comments
      Index of metabolic and biosynthesis pathways
    6. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3