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Protein

Phosphoenolpyruvate carboxykinase [GTP], mitochondrial

Gene

PCK2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

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

Mn2+By similarityNote: Binds 1 Mn2+ ion per subunit.By similarity

Pathway: gluconeogenesis

This protein is involved in the pathway gluconeogenesis, which is part of Carbohydrate biosynthesis.
View all proteins of this organism that are known to be involved in the pathway gluconeogenesis and in Carbohydrate biosynthesis.

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

GO - Biological processi

Complete GO annotation...

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 Componenti: Chromosome 14

Organism-specific databases

HGNCiHGNC:8725. PCK2.

Subcellular locationi

GO - Cellular componenti

  • extracellular exosome Source: UniProtKB
  • mitochondrial matrix Source: Reactome
  • mitochondrion Source: HPA
Complete GO annotation...

Keywords - Cellular componenti

Mitochondrion

Pathology & Biotechi

Involvement in diseasei

Mitochondrial phosphoenolpyruvate carboxykinase deficiency (M-PEPCKD)

The disease is caused by mutations affecting the gene represented in this entry.

Disease descriptionMetabolic 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.

See also OMIM:261650

Organism-specific databases

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

Polymorphism and mutation databases

BioMutaiPCK2.
DMDMi290457671.

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 residuei42 – 421Phosphothreonine1 Publication
Modified residuei88 – 881N6-acetyllysineBy similarity
Modified residuei115 – 1151Phosphoserine1 Publication
Modified residuei196 – 1961Phosphothreonine1 Publication
Modified residuei304 – 3041Phosphoserine1 Publication
Modified residuei457 – 4571N6-succinyllysineBy similarity

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

MaxQBiQ16822.
PaxDbiQ16822.
PRIDEiQ16822.

2D gel databases

SWISS-2DPAGEQ16822.

PTM databases

PhosphoSiteiQ16822.

Expressioni

Gene expression databases

BgeeiQ16822.
CleanExiHS_PCK2.
ExpressionAtlasiQ16822. baseline and differential.
GenevisibleiQ16822. HS.

Organism-specific databases

HPAiCAB018734.
HPA051162.
HPA053502.

Interactioni

Subunit structurei

Monomer.

Binary interactionsi

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

Protein-protein interaction databases

BioGridi111137. 27 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. AlignAdd to basket

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

        10         20         30         40         50
MAALYRPGLR LNWHGLSPLG WPSCRSIQTL RVLSGDLGQL PTGIRDFVEH
60 70 80 90 100
SARLCQPEGI HICDGTEAEN TATLTLLEQQ GLIRKLPKYN NCWLARTDPK
110 120 130 140 150
DVARVESKTV IVTPSQRDTV QLPPGGARGQ LGNWMSPADF QRAVDERFPG
160 170 180 190 200
CMQGRTMYVL PFSMGPVGSP LSRIGVQLTD SAYVVASMRI MTRLGTPVLQ
210 220 230 240 250
ALGDGDFVKC LHSVGQPLTG QGEPVSQWPC NPEKTLIGHV PDQREIISFG
260 270 280 290 300
SGYGGNSLLG KKCFALRIAS RLARDEGWLA EHMLILGITS PAGKKRYVAA
310 320 330 340 350
AFPSACGKTN LAMMRPALPG WKVECVGDDI AWMRFDSEGR LRAINPENGF
360 370 380 390 400
FGVAPGTSAT TNPNAMATIQ SNTIFTNVAE TSDGGVYWEG IDQPLPPGVT
410 420 430 440 450
VTSWLGKPWK PGDKEPCAHP NSRFCAPARQ CPIMDPAWEA PEGVPIDAII
460 470 480 490 500
FGGRRPKGVP LVYEAFNWRH GVFVGSAMRS ESTAAAEHKG KIIMHDPFAM
510 520 530 540 550
RPFFGYNFGH YLEHWLSMEG RKGAQLPRIF HVNWFRRDEA GHFLWPGFGE
560 570 580 590 600
NARVLDWICR RLEGEDSARE TPIGLVPKEG ALDLSGLRAI DTTQLFSLPK
610 620 630 640
DFWEQEVRDI RSYLTEQVNQ DLPKEVLAEL EALERRVHKM
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. Curated

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:
EMBLi
GenBanki
DDBJi
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.
GeneIDi5106.
KEGGihsa:5106.
UCSCiuc001wls.3. human. [Q16822-2]
uc001wlt.3. human. [Q16822-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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.

3D structure databases

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

Protein-protein interaction databases

BioGridi111137. 27 interactions.
IntActiQ16822. 7 interactions.
STRINGi9606.ENSP00000216780.

PTM databases

PhosphoSiteiQ16822.

Polymorphism and mutation databases

BioMutaiPCK2.
DMDMi290457671.

2D gel databases

SWISS-2DPAGEQ16822.

Proteomic databases

MaxQBiQ16822.
PaxDbiQ16822.
PRIDEiQ16822.

Protocols and materials databases

DNASUi5106.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi5106.
GeneCardsiGC14P024563.
HGNCiHGNC:8725. PCK2.
HPAiCAB018734.
HPA051162.
HPA053502.
MIMi261650. phenotype.
614095. gene.
neXtProtiNX_Q16822.
Orphaneti79317. Phosphoenolpyruvate carboxykinase 2 deficiency.
PharmGKBiPA33070.
GenAtlasiSearch...

Phylogenomic databases

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

Enzyme and pathway databases

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

Miscellaneous databases

GenomeRNAii5106.
NextBioi19706.
PROiQ16822.
SOURCEiSearch...

Gene expression databases

BgeeiQ16822.
CleanExiHS_PCK2.
ExpressionAtlasiQ16822. baseline and differential.
GenevisibleiQ16822. HS.

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]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  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].
  7. "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome."
    Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., Ye M., Zou H.
    J. Proteomics 96:253-262(2014) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-42; SER-115; THR-196 AND SER-304, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Liver.

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: June 24, 2015
This is version 159 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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.