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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

Pathwayi: 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)DescriptionActionsGraphical viewLength
Binding sitei104SubstrateBy similarity1
Metal bindingi262ManganeseBy similarity1
Metal bindingi282Manganese; via tele nitrogenBy similarity1
Binding sitei304SubstrateBy similarity1
Active sitei306By similarity1
Metal bindingi329ManganeseBy similarity1
Binding sitei423GTPBy similarity1
Binding sitei454GTPBy similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi305 – 310GTPBy similarity6
Nucleotide bindingi548 – 551GTPBy similarity4

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.
ZFISH:HS02160-MONOMER.
ReactomeiR-HSA-70263. 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
Proteomesi
  • UP000005640 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

DisGeNETi5106.
MalaCardsiPCK2.
MIMi261650. phenotype.
Orphaneti79317. Phosphoenolpyruvate carboxykinase 2 deficiency.
PharmGKBiPA33070.

Polymorphism and mutation databases

BioMutaiPCK2.
DMDMi290457671.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Transit peptidei1 – 32MitochondrionBy similarityAdd BLAST32
ChainiPRO_000002356833 – 640Phosphoenolpyruvate carboxykinase [GTP], mitochondrialAdd BLAST608

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei42PhosphothreonineCombined sources1
Modified residuei88N6-acetyllysineBy similarity1
Modified residuei115PhosphoserineCombined sources1
Modified residuei196PhosphothreonineCombined sources1
Modified residuei304PhosphoserineCombined sources1
Modified residuei457N6-succinyllysineBy similarity1

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiQ16822.
MaxQBiQ16822.
PaxDbiQ16822.
PeptideAtlasiQ16822.
PRIDEiQ16822.
TopDownProteomicsiQ16822-2. [Q16822-2]

2D gel databases

SWISS-2DPAGEQ16822.

PTM databases

iPTMnetiQ16822.
PhosphoSitePlusiQ16822.

Expressioni

Gene expression databases

BgeeiENSG00000100889.
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. 34 interactors.
IntActiQ16822. 17 interactors.
STRINGi9606.ENSP00000216780.

Structurei

3D structure databases

ProteinModelPortaliQ16822.
SMRiQ16822.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni253 – 255Substrate bindingBy similarity3
Regioni421 – 423Substrate bindingBy similarity3

Sequence similaritiesi

Keywords - Domaini

Transit peptide

Phylogenomic databases

eggNOGiKOG3749. Eukaryota.
COG1274. LUCA.
HOGENOMiHOG000191700.
HOVERGENiHBG053651.
InParanoidiQ16822.
KOiK01596.
OrthoDBiEOG091G02YK.
PhylomeDBiQ16822.
TreeFamiTF314402.

Family and domain databases

Gene3Di3.40.449.10. 1 hit.
3.90.228.20. 2 hits.
HAMAPiMF_00452. PEPCK_GTP. 1 hit.
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 differs from that shown. Reason: Erroneous initiation.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti121Q → P in CAA63380 (PubMed:8645161).Curated1
Sequence conflicti121Q → P in CAA72272 (PubMed:9657976).Curated1
Sequence conflicti121Q → P in AAH01454 (PubMed:15489334).Curated1
Sequence conflicti128R → C in CAA63380 (PubMed:8645161).Curated1
Sequence conflicti296 – 298RYV → ALC in CAA63380 (PubMed:8645161).Curated3
Sequence conflicti296 – 298RYV → ALC in CAA72272 (PubMed:9657976).Curated3
Sequence conflicti476S → R in CAA63380 (PubMed:8645161).Curated1
Sequence conflicti476S → R in CAA72272 (PubMed:9657976).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_04244531R → Q.Corresponds to variant rs2229660dbSNPEnsembl.1
Natural variantiVAR_04244664D → N.Corresponds to variant rs10132601dbSNPEnsembl.1
Natural variantiVAR_042447406G → S.Corresponds to variant rs17101262dbSNPEnsembl.1
Natural variantiVAR_056662521R → H.Corresponds to variant rs35618680dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_038783413 – 640DKEPC…RVHKM → MCGGEGVAQPPGLSTLMVEK LSPQPPTIF in isoform 2. 1 PublicationAdd BLAST228

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.
UCSCiuc001wlt.4. 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.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi111137. 34 interactors.
IntActiQ16822. 17 interactors.
STRINGi9606.ENSP00000216780.

PTM databases

iPTMnetiQ16822.
PhosphoSitePlusiQ16822.

Polymorphism and mutation databases

BioMutaiPCK2.
DMDMi290457671.

2D gel databases

SWISS-2DPAGEQ16822.

Proteomic databases

EPDiQ16822.
MaxQBiQ16822.
PaxDbiQ16822.
PeptideAtlasiQ16822.
PRIDEiQ16822.
TopDownProteomicsiQ16822-2. [Q16822-2]

Protocols and materials databases

DNASUi5106.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000216780; ENSP00000216780; ENSG00000100889.
GeneIDi5106.
KEGGihsa:5106.
UCSCiuc001wlt.4. human. [Q16822-1]

Organism-specific databases

CTDi5106.
DisGeNETi5106.
GeneCardsiPCK2.
HGNCiHGNC:8725. PCK2.
HPAiCAB018734.
HPA051162.
HPA053502.
MalaCardsiPCK2.
MIMi261650. phenotype.
614095. gene.
neXtProtiNX_Q16822.
Orphaneti79317. Phosphoenolpyruvate carboxykinase 2 deficiency.
PharmGKBiPA33070.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3749. Eukaryota.
COG1274. LUCA.
HOGENOMiHOG000191700.
HOVERGENiHBG053651.
InParanoidiQ16822.
KOiK01596.
OrthoDBiEOG091G02YK.
PhylomeDBiQ16822.
TreeFamiTF314402.

Enzyme and pathway databases

UniPathwayiUPA00138.
BioCyciMetaCyc:HS02160-MONOMER.
ZFISH:HS02160-MONOMER.
ReactomeiR-HSA-70263. Gluconeogenesis.

Miscellaneous databases

GenomeRNAii5106.
PROiQ16822.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000100889.
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. 1 hit.
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...

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: November 30, 2016
This is version 173 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

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 one 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.