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Q16822 (PCKGM_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 147. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Phosphoenolpyruvate carboxykinase [GTP], mitochondrial

Short name=PEPCK-M
EC=4.1.1.32
Gene names
Name:PCK2
Synonyms:PEPCK2
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length640 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. HAMAP-Rule MF_00452

Catalytic activity

GTP + oxaloacetate = GDP + phosphoenolpyruvate + CO2. HAMAP-Rule MF_00452

Cofactor

Manganese By similarity. HAMAP-Rule MF_00452

Binds 1 manganese ion per subunit By similarity. HAMAP-Rule MF_00452

Pathway

Carbohydrate biosynthesis; gluconeogenesis. HAMAP-Rule MF_00452

Subunit structure

Monomer.

Subcellular location

Mitochondrion HAMAP-Rule MF_00452.

Involvement in disease

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.

Miscellaneous

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

Sequence similarities

Belongs to the phosphoenolpyruvate carboxykinase [GTP] family.

Sequence caution

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

Ontologies

Keywords
   Biological processGluconeogenesis
   Cellular componentMitochondrion
   Coding sequence diversityAlternative splicing
Polymorphism
   DomainTransit peptide
   LigandGTP-binding
Manganese
Metal-binding
Nucleotide-binding
   Molecular functionDecarboxylase
Lyase
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processNADH oxidation

Inferred from electronic annotation. Source: Ensembl

carbohydrate metabolic process

Traceable author statement. Source: Reactome

cellular response to glucose stimulus

Inferred from electronic annotation. Source: Ensembl

gluconeogenesis

Traceable author statement. Source: Reactome

glucose metabolic process

Traceable author statement. Source: Reactome

oxaloacetate metabolic process

Inferred from electronic annotation. Source: Ensembl

positive regulation of insulin secretion

Inferred from electronic annotation. Source: Ensembl

pyruvate metabolic process

Inferred from electronic annotation. Source: Ensembl

response to glucocorticoid

Inferred from electronic annotation. Source: Ensembl

small molecule metabolic process

Traceable author statement. Source: Reactome

   Cellular_componentmitochondrial matrix

Traceable author statement. Source: Reactome

mitochondrion

Inferred from direct assay. Source: HPA

   Molecular_functionGTP binding

Inferred from electronic annotation. Source: UniProtKB-KW

metal ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

phosphoenolpyruvate carboxykinase (GTP) activity

Inferred from electronic annotation. Source: UniProtKB-EC

phosphoenolpyruvate carboxykinase activity

Traceable author statement Ref.1. Source: ProtInc

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

SMAD3P840222EBI-2825219,EBI-347161

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q16822-1)

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.
Isoform 2 (identifier: Q16822-2)

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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Transit peptide1 – 3232Mitochondrion By similarity
Chain33 – 640608Phosphoenolpyruvate carboxykinase [GTP], mitochondrial HAMAP-Rule MF_00452
PRO_0000023568

Regions

Nucleotide binding305 – 3106GTP By similarity
Nucleotide binding548 – 5514GTP By similarity
Region421 – 4233Substrate binding By similarity

Sites

Active site3061 By similarity
Metal binding2621Manganese By similarity
Metal binding2821Manganese; via tele nitrogen By similarity
Metal binding3291Manganese By similarity
Binding site1041Substrate By similarity
Binding site2551Substrate; via amide nitrogen By similarity
Binding site2621Substrate By similarity
Binding site3041Substrate By similarity
Binding site4231GTP By similarity
Binding site4541GTP By similarity

Amino acid modifications

Modified residue4571N6-succinyllysine By similarity

Natural variations

Alternative sequence413 – 640228DKEPC…RVHKM → MCGGEGVAQPPGLSTLMVEK LSPQPPTIF in isoform 2.
VSP_038783
Natural variant311R → Q.
Corresponds to variant rs2229660 [ dbSNP | Ensembl ].
VAR_042445
Natural variant641D → N.
Corresponds to variant rs10132601 [ dbSNP | Ensembl ].
VAR_042446
Natural variant4061G → S.
Corresponds to variant rs17101262 [ dbSNP | Ensembl ].
VAR_042447
Natural variant5211R → H.
Corresponds to variant rs35618680 [ dbSNP | Ensembl ].
VAR_056662

Experimental info

Sequence conflict1211Q → P in CAA63380. Ref.1
Sequence conflict1211Q → P in CAA72272. Ref.2
Sequence conflict1211Q → P in AAH01454. Ref.5
Sequence conflict1281R → C in CAA63380. Ref.1
Sequence conflict296 – 2983RYV → ALC in CAA63380. Ref.1
Sequence conflict296 – 2983RYV → ALC in CAA72272. Ref.2
Sequence conflict4761S → R in CAA63380. Ref.1
Sequence conflict4761S → R in CAA72272. Ref.2

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified March 2, 2010. Version 3.
Checksum: B8CAC4252EBF8871

FASTA64070,730
        10         20         30         40         50         60 
MAALYRPGLR LNWHGLSPLG WPSCRSIQTL RVLSGDLGQL PTGIRDFVEH SARLCQPEGI 

        70         80         90        100        110        120 
HICDGTEAEN TATLTLLEQQ GLIRKLPKYN NCWLARTDPK DVARVESKTV IVTPSQRDTV 

       130        140        150        160        170        180 
QLPPGGARGQ LGNWMSPADF QRAVDERFPG CMQGRTMYVL PFSMGPVGSP LSRIGVQLTD 

       190        200        210        220        230        240 
SAYVVASMRI MTRLGTPVLQ ALGDGDFVKC LHSVGQPLTG QGEPVSQWPC NPEKTLIGHV 

       250        260        270        280        290        300 
PDQREIISFG SGYGGNSLLG KKCFALRIAS RLARDEGWLA EHMLILGITS PAGKKRYVAA 

       310        320        330        340        350        360 
AFPSACGKTN LAMMRPALPG WKVECVGDDI AWMRFDSEGR LRAINPENGF FGVAPGTSAT 

       370        380        390        400        410        420 
TNPNAMATIQ SNTIFTNVAE TSDGGVYWEG IDQPLPPGVT VTSWLGKPWK PGDKEPCAHP 

       430        440        450        460        470        480 
NSRFCAPARQ CPIMDPAWEA PEGVPIDAII FGGRRPKGVP LVYEAFNWRH GVFVGSAMRS 

       490        500        510        520        530        540 
ESTAAAEHKG KIIMHDPFAM RPFFGYNFGH YLEHWLSMEG RKGAQLPRIF HVNWFRRDEA 

       550        560        570        580        590        600 
GHFLWPGFGE NARVLDWICR RLEGEDSARE TPIGLVPKEG ALDLSGLRAI DTTQLFSLPK 

       610        620        630        640 
DFWEQEVRDI RSYLTEQVNQ DLPKEVLAEL EALERRVHKM 

« Hide

Isoform 2 [UniParc].

Checksum: 00FCF22C5C4053E5
Show »

FASTA44147,564

References

« Hide 'large scale' references
[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. expand/collapse author list , 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]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
+Additional computationally mapped references.

Web resources

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
PIRS69546.
RefSeqNP_001018083.1. NM_001018073.1.
NP_004554.2. NM_004563.2.
UniGeneHs.75812.

3D structure databases

ProteinModelPortalQ16822.
SMRQ16822. Positions 31-640.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid111137. 4 interactions.
IntActQ16822. 7 interactions.
STRING9606.ENSP00000216780.

PTM databases

PhosphoSiteQ16822.

Polymorphism databases

DMDM290457671.

2D gel databases

SWISS-2DPAGEQ16822.

Proteomic databases

PaxDbQ16822.
PRIDEQ16822.

Protocols and materials databases

DNASU5106.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000216780; ENSP00000216780; ENSG00000100889. [Q16822-1]
ENST00000396973; ENSP00000380171; ENSG00000100889. [Q16822-2]
GeneID5106.
KEGGhsa:5106.
UCSCuc001wls.3. human. [Q16822-2]
uc001wlt.3. human. [Q16822-1]

Organism-specific databases

CTD5106.
GeneCardsGC14P024563.
HGNCHGNC:8725. PCK2.
HPACAB018734.
HPA051162.
HPA053502.
MIM261650. phenotype.
614095. gene.
neXtProtNX_Q16822.
Orphanet79317. Phosphoenolpyruvate carboxykinase 2 deficiency.
PharmGKBPA33070.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG1274.
HOGENOMHOG000191700.
HOVERGENHBG053651.
InParanoidQ16822.
KOK01596.
OMAQAVDERF.
OrthoDBEOG7KSX81.
PhylomeDBQ16822.
TreeFamTF314402.

Enzyme and pathway databases

BioCycMetaCyc:HS02160-MONOMER.
ReactomeREACT_111217. Metabolism.
UniPathwayUPA00138.

Gene expression databases

ArrayExpressQ16822.
BgeeQ16822.
CleanExHS_PCK2.
GenevestigatorQ16822.

Family and domain databases

Gene3D3.40.449.10. 1 hit.
3.90.228.20. 2 hits.
HAMAPMF_00452. PEPCK_GTP.
InterProIPR018091. PEP_carboxykin_GTP_CS.
IPR013035. PEP_carboxykinase_C.
IPR008209. PEP_carboxykinase_GTP.
IPR008210. PEP_carboxykinase_N.
[Graphical view]
PANTHERPTHR11561. PTHR11561. 1 hit.
PfamPF00821. PEPCK. 1 hit.
[Graphical view]
PIRSFPIRSF001348. PEP_carboxykinase_GTP. 1 hit.
SUPFAMSSF68923. SSF68923. 1 hit.
PROSITEPS00505. PEPCK_GTP. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GenomeRNAi5106.
NextBio19706.
PROQ16822.
SOURCESearch...

Entry information

Entry namePCKGM_HUMAN
AccessionPrimary (citable) accession number: Q16822
Secondary accession number(s): O43253, Q86U01, Q9BV62
Entry history
Integrated into UniProtKB/Swiss-Prot: July 15, 1998
Last sequence update: March 2, 2010
Last modified: April 16, 2014
This is version 147 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PATHWAY comments

Index of metabolic and biosynthesis pathways

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 14

Human chromosome 14: entries, gene names and cross-references to MIM