Q16822 (PCKGM_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Phosphoenolpyruvate carboxykinase [GTP], mitochondrial
Short name=PEPCK-M
EC=4.1.1.32

Alternative name(s):
Phosphoenolpyruvate carboxylase

Gene names

Name:	PCK2
Synonyms:	PEPCK2

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	640 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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.
Catalytic activity	GTP + oxaloacetate = GDP + phosphoenolpyruvate + CO2.
Cofactor	Manganese By similarity. Binds 1 manganese ion per subunit By similarity.
Pathway	Carbohydrate biosynthesis; gluconeogenesis.
Subunit structure	Monomer.
Subcellular location	Mitochondrion.
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. Autoposy 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 process	Gluconeogenesis
Cellular component	Mitochondrion
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Transit peptide
Ligand	GTP-binding Manganese Metal-binding Nucleotide-binding
Molecular function	Decarboxylase Lyase
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	gluconeogenesis Traceable author statement. Source: Reactome small molecule metabolic process Traceable author statement. Source: Reactome
Cellular_component	mitochondrial matrix Traceable author statement. Source: Reactome
Molecular_function	GTP 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: EC phosphoenolpyruvate carboxykinase activity Traceable author statement Ref.1. Source: ProtInc
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
SMAD3	P84022	2	EBI-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 key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Transit peptide	1 – 32	32	Mitochondrion By similarity
	Chain	33 – 640	608	Phosphoenolpyruvate carboxykinase [GTP], mitochondrial		PRO_0000023568
Regions
	Nucleotide binding	305 – 310	6	GTP By similarity
	Nucleotide binding	548 – 551	4	GTP By similarity
	Region	421 – 423	3	Substrate binding By similarity
Sites
	Active site	306	1	By similarity
	Metal binding	262	1	Manganese By similarity
	Metal binding	282	1	Manganese By similarity
	Metal binding	329	1	Manganese By similarity
	Binding site	104	1	Substrate By similarity
	Binding site	255	1	Substrate; via amide nitrogen By similarity
	Binding site	262	1	Substrate By similarity
	Binding site	304	1	Substrate By similarity
	Binding site	423	1	GTP By similarity
	Binding site	454	1	GTP By similarity
Natural variations
	Alternative sequence	413 – 640	228	DKEPC…RVHKM → MCGGEGVAQPPGLSTLMVEK LSPQPPTIF in isoform 2.		VSP_038783
	Natural variant	31	1	R → Q. Corresponds to variant rs2229660 [ dbSNP | Ensembl ].		VAR_042445
	Natural variant	64	1	D → N. Corresponds to variant rs10132601 [ dbSNP | Ensembl ].		VAR_042446
	Natural variant	406	1	G → S. Corresponds to variant rs17101262 [ dbSNP | Ensembl ].		VAR_042447
	Natural variant	521	1	R → H. Corresponds to variant rs35618680 [ dbSNP | Ensembl ].		VAR_056662
Experimental info
	Sequence conflict	121	1	Q → P in CAA63380. Ref.1
	Sequence conflict	121	1	Q → P in CAA72272. Ref.2
	Sequence conflict	121	1	Q → P in AAH01454. Ref.5
	Sequence conflict	128	1	R → C in CAA63380. Ref.1
	Sequence conflict	296 – 298	3	RYV → ALC in CAA63380. Ref.1
	Sequence conflict	296 – 298	3	RYV → ALC in CAA72272. Ref.2
	Sequence conflict	476	1	S → R in CAA63380. Ref.1
	Sequence conflict	476	1	S → R in CAA72272. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified March 2, 2010. Version 3. Checksum: B8CAC4252EBF8871	FASTA	640	70,730
	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
	Isoform 2 [UniParc]. Checksum: 00FCF22C5C4053E5	FASTA	441	47,564
	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 PGMCGGEGVA 430 440 QPPGLSTLMV EKLSPQPPTI F

References

	« Hide 'large scale' referencesShow '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. , 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

GeneReviews

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.
IPI	IPI00384116. IPI00797038.
PIR	S69546.
RefSeq	NP_001018083.1. NM_001018073.1. NP_004554.2. NM_004563.2.
UniGene	Hs.75812.
3D structure databases
ProteinModelPortal	Q16822.
SMR	Q16822. Positions 31-640.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q16822. 7 interactions.
STRING	9606.ENSP00000216780.
PTM databases
PhosphoSite	Q16822.
Polymorphism databases
DMDM	290457671.
2D gel databases
SWISS-2DPAGE	Q16822.
Proteomic databases
PaxDb	Q16822.
PRIDE	Q16822.
Protocols and materials databases
DNASU	5106.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000216780; ENSP00000216780; ENSG00000100889. ENST00000396973; ENSP00000380171; ENSG00000100889.
GeneID	5106.
KEGG	hsa:5106.
UCSC	uc001wls.3. human. uc001wlt.3. human.
Organism-specific databases
CTD	5106.
GeneCards	GC14P024563.
HGNC	HGNC:8725. PCK2.
HPA	CAB018734.
MIM	261650. phenotype. 614095. gene.
neXtProt	NX_Q16822.
Orphanet	2880. Phosphoenolpyruvate carboxykinase deficiency.
PharmGKB	PA33070.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG1274.
HOGENOM	HOG000191700.
HOVERGEN	HBG053651.
InParanoid	Q16822.
KO	K01596.
OMA	KPWKPGD.
OrthoDB	EOG47SSD8.
PhylomeDB	Q16822.
Enzyme and pathway databases
Reactome	REACT_111217. Metabolism.
UniPathway	UPA00138.
Gene expression databases
ArrayExpress	Q16822.
Bgee	Q16822.
CleanEx	HS_PCK2.
Genevestigator	Q16822.
GermOnline	ENSG00000100889. Homo sapiens.
Family and domain databases
Gene3D	3.40.449.10. 1 hit. 3.90.228.20. 2 hits.
InterPro	IPR018091. PEP_carboxykin_GTP_CS. IPR013035. PEP_carboxykinase_C. IPR008209. PEP_carboxykinase_GTP. IPR008210. PEP_carboxykinase_N. [Graphical view]
PANTHER	PTHR11561. PTHR11561. 1 hit.
Pfam	PF00821. PEPCK. 1 hit. [Graphical view]
PIRSF	PIRSF001348. PEP_carboxykinase_GTP. 1 hit.
SUPFAM	SSF68923. PEP_carboxykinase_N. 1 hit.
PROSITE	PS00505. PEPCK_GTP. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChEMBL	CHEMBL3096.
GenomeRNAi	5106.
NextBio	19706.
SOURCE	Search...

Entry information

Entry name

PCKGM_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 138 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.