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Protein

Phosphoenolpyruvate carboxykinase [GTP], mitochondrial

Gene

PCK2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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

Miscellaneous

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

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

Keywordsi

Molecular functionDecarboxylase, Lyase
Biological processGluconeogenesis
LigandGTP-binding, Manganese, Metal-binding, Nucleotide-binding

Enzyme and pathway databases

BioCyciMetaCyc:HS02160-MONOMER
ReactomeiR-HSA-70263 Gluconeogenesis
SIGNORiQ16822
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

EuPathDBiHostDB:ENSG00000100889.11
HGNCiHGNC:8725 PCK2
MIMi614095 gene
neXtProtiNX_Q16822

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

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
OpenTargetsiENSG00000100889
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
ProteomicsDBi61082
61083 [Q16822-2]
TopDownProteomicsiQ16822-2 [Q16822-2]

2D gel databases

SWISS-2DPAGEiQ16822

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, 37 interactors
IntActiQ16822, 19 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
GeneTreeiENSGT00390000001912
HOGENOMiHOG000191700
HOVERGENiHBG053651
InParanoidiQ16822
KOiK01596
OrthoDBiEOG091G02YK
PhylomeDBiQ16822
TreeFamiTF314402

Family and domain databases

CDDicd00819 PEPCK_GTP, 1 hit
Gene3Di3.40.449.10, 2 hits
3.90.228.20, 2 hits
HAMAPiMF_00452 PEPCK_GTP, 1 hit
InterProiView protein in InterPro
IPR018091 PEP_carboxykin_GTP_CS
IPR013035 PEP_carboxykinase_C
IPR008209 PEP_carboxykinase_GTP
IPR035077 PEP_carboxykinase_GTP_C
IPR035078 PEP_carboxykinase_GTP_N
IPR008210 PEP_carboxykinase_N
PANTHERiPTHR11561 PTHR11561, 1 hit
PfamiView protein in Pfam
PF00821 PEPCK_C, 1 hit
PF17297 PEPCK_N, 1 hit
PIRSFiPIRSF001348 PEP_carboxykinase_GTP, 1 hit
SUPFAMiSSF68923 SSF68923, 1 hit
PROSITEiView protein in PROSITE
PS00505 PEPCK_GTP, 1 hit

Sequences (3)i

Sequence statusi: Complete.

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

This entry describes 3 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 PLPPGGARGQ 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):70,699
Last modified:March 28, 2018 - v4
Checksum:iDCE561252EBF8871
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):47,533
Checksum:i9E79995C37AED6E5
GO
Isoform 3 (identifier: Q16822-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-134: Missing.

Show »
Length:506
Mass (Da):55,953
Checksum:iFE493E8F66C42DAE
GO

Sequence cautioni

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

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti121P → Q in CAD62600 (Ref. 3) 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 dbSNP:rs2229660Ensembl.1
Natural variantiVAR_04244664D → N. Corresponds to variant dbSNP:rs10132601Ensembl.1
Natural variantiVAR_042447406G → S. Corresponds to variant dbSNP:rs17101262Ensembl.1
Natural variantiVAR_056662521R → H. Corresponds to variant dbSNP:rs35618680Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0593891 – 134Missing in isoform 3. Add BLAST134
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.
AK301400 mRNA Translation: BAG62935.1
AK316206 mRNA Translation: BAH14577.1
AL136295 Genomic DNA No translation available.
KF455834 Genomic DNA No translation available.
BC001454 mRNA Translation: AAH01454.1
CCDSiCCDS41928.1 [Q16822-2]
CCDS76660.1 [Q16822-3]
CCDS9609.1 [Q16822-1]
PIRiS69546
RefSeqiNP_001018083.2, NM_001018073.2 [Q16822-2]
NP_001278485.1, NM_001291556.1 [Q16822-3]
NP_001294983.1, NM_001308054.1 [Q16822-3]
NP_004554.3, NM_004563.3 [Q16822-1]
UniGeneiHs.75812

Genome annotation databases

EnsembliENST00000216780; ENSP00000216780; ENSG00000100889 [Q16822-1]
ENST00000396973; ENSP00000380171; ENSG00000100889 [Q16822-2]
ENST00000545054; ENSP00000441826; ENSG00000100889 [Q16822-3]
ENST00000561286; ENSP00000454011; ENSG00000100889 [Q16822-3]
ENST00000644679; ENSP00000496102; ENSG00000285241 [Q16822-3]
ENST00000645217; ENSP00000494919; ENSG00000285241 [Q16822-1]
ENST00000645536; ENSP00000496343; ENSG00000285241 [Q16822-3]
ENST00000645709; ENSP00000494029; ENSG00000285241 [Q16822-2]
GeneIDi5106
KEGGihsa:5106
UCSCiuc001wlt.4 human [Q16822-1]
uc010tnw.3 human

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Entry informationi

Entry nameiPCKGM_HUMAN
AccessioniPrimary (citable) accession number: Q16822
Secondary accession number(s): B4DW73
, O43253, Q86U01, Q9BV62
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 15, 1998
Last sequence update: March 28, 2018
Last modified: June 20, 2018
This is version 184 of the entry and version 4 of the sequence. See 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

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

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