PKM pyruvate kinase M1/2 [Homo sapiens (human)] - Gene

Summary

Official Symbol: PKMprovided by HGNC
Official Full Name: pyruvate kinase M1/2provided by HGNC
Primary source: HGNC:HGNC:9021
See related: Ensembl:ENSG00000067225 MIM:179050; AllianceGenome:HGNC:9021
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: PK3; TCB; p58; OIP3; PKM2; CTHBP; THBP1; HEL-S-30
Summary: This gene encodes a protein involved in glycolysis. The encoded protein is a pyruvate kinase that catalyzes the transfer of a phosphoryl group from phosphoenolpyruvate to ADP, generating ATP and pyruvate. This protein has been shown to interact with thyroid hormone and may mediate cellular metabolic effects induced by thyroid hormones. This protein has been found to bind Opa protein, a bacterial outer membrane protein involved in gonococcal adherence to and invasion of human cells, suggesting a role of this protein in bacterial pathogenesis. Several alternatively spliced transcript variants encoding a few distinct isoforms have been reported. [provided by RefSeq, May 2011]
Expression: Ubiquitous expression in brain (RPKM 155.4), esophagus (RPKM 151.3) and 24 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 15q23

Exon count:: 17

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	15	NC_000015.10 (72199029..72231591, complement)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	15	NC_060939.1 (70015755..70047883, complement)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	15	NC_000015.9 (72491370..72523531, complement)

Chromosome 15 - NC_000015.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

CircAGFG1 absence decreases PKM2 expression to enhance oxaliplatin sensitivity in colorectal cancer in a miR-7-5p-dependent manner.
Title: CircAGFG1 absence decreases PKM2 expression to enhance oxaliplatin sensitivity in colorectal cancer in a miR-7-5p-dependent manner.
CircPHGDH downregulation decreases papillary thyroid cancer progression through miR-122-5p/PKM2 axis.
Title: CircPHGDH downregulation decreases papillary thyroid cancer progression through miR-122-5p/PKM2 axis.
PKM2 is a Novel Osteoporosis-Associated Protein in Chinese.
Title: PKM2 is a Novel Osteoporosis-Associated Protein in Chinese.
Pyruvate Kinase Differentially Alters Metabolic Signatures during Head and Neck Carcinogenesis.
Title: Pyruvate Kinase Differentially Alters Metabolic Signatures during Head and Neck Carcinogenesis.
PP4R1 promotes glycolysis and gallbladder cancer progression through facilitating ERK1/2 mediated PKM2 nuclear translocation.
Title: PP4R1 promotes glycolysis and gallbladder cancer progression through facilitating ERK1/2 mediated PKM2 nuclear translocation.
Transcription factor LHX9 (LIM Homeobox 9) enhances pyruvate kinase PKM2 activity to induce glycolytic metabolic reprogramming in cancer stem cells, promoting gastric cancer progression.
Title: Transcription factor LHX9 (LIM Homeobox 9) enhances pyruvate kinase PKM2 activity to induce glycolytic metabolic reprogramming in cancer stem cells, promoting gastric cancer progression.
PKM2 promotes lymphatic metastasis of hypopharyngeal carcinoma via regulating epithelial-mesenchymal transition: an experimental research.
Title: PKM2 promotes lymphatic metastasis of hypopharyngeal carcinoma via regulating epithelial-mesenchymal transition: an experimental research.
LncRNA PWRN1 inhibits the progression of hepatocellular carcinoma by activating PKM2 activity.
Title: LncRNA PWRN1 inhibits the progression of hepatocellular carcinoma by activating PKM2 activity.
Long noncoding RNA TMPO-AS1 accelerates glycolysis by regulating the miR-1270/PKM2 axis in colorectal cancer.
Title: Long noncoding RNA TMPO-AS1 accelerates glycolysis by regulating the miR-1270/PKM2 axis in colorectal cancer.
The HIF-1alpha/PKM2 Feedback Loop in Relation to EGFR Mutational Status in Lung Adenocarcinoma.
Title: The HIF-1α/PKM2 Feedback Loop in Relation to EGFR Mutational Status in Lung Adenocarcinoma.

Submit: New GeneRIF Correction See all GeneRIFs (454)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Protein interactions

Protein	Gene	Interaction	Pubs
Envelope surface glycoprotein gp120	env	Tandem affinity purification and mass spectrometry analysis identify pyruvate kinase of muscle (PKM), HIV-1 Gag, Gag/Pol, gp120, and Nef incorporated into staufen1 RNP complexes isolated from HIV-1-expressing cells	PubMed
Envelope surface glycoprotein gp160, precursor	env	HIV-1 gp160 is identified to have a physical interaction with pyruvate kinase, muscle (PKM2) in human HEK293 and/or Jurkat cell lines by using affinity tagging and purification mass spectrometry analyses	PubMed
Gag-Pol	gag-pol	Tandem affinity purification and mass spectrometry analysis identify pyruvate kinase of muscle (PKM), HIV-1 Gag, Gag/Pol, gp120, and Nef incorporated into staufen1 RNP complexes isolated from HIV-1-expressing cells	PubMed
Nef	nef	Tandem affinity purification and mass spectrometry analysis identify pyruvate kinase of muscle (PKM), HIV-1 Gag, Gag/Pol, gp120, and Nef incorporated into staufen1 RNP complexes isolated from HIV-1-expressing cells	PubMed
Pr55(Gag)	gag	Tandem affinity purification and mass spectrometry analysis identify pyruvate kinase of muscle (PKM), HIV-1 Gag, Gag/Pol, gp120, and Nef incorporated into staufen1 RNP complexes isolated from HIV-1-expressing cells	PubMed
Tat	tat	Expression of HIV-1 Tat upregulates the abundance of pyruvate kinase, muscle (PKM) in the nucleoli of Jurkat T-cells	PubMed
Vpr	vpr	A stable-isotope labeling by amino acids in cell culture coupled with mass spectrometry-based proteomics identifies upregulation of pyruvate kinase, muscle (PKM) expression by HIV-1 Vpr in Vpr transduced macrophages	PubMed
retropepsin	gag-pol	Positional proteomics analysis identifies the cleavage of human pyruvate kinase, muscle (PKM) at amino acid residues 306-307 and 359-361 by the HIV-1 protease	PubMed

Go to the HIV-1, Human Interaction Database

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

RH70518 (e-PCR)
- UniSTS:26704

GDB:451703 (e-PCR)
- UniSTS:99434

RH48501 (e-PCR)
- UniSTS:8057

SHGC-34981 (e-PCR)
- UniSTS:38540

RH68647 (e-PCR)
- UniSTS:50386

RH67936 (e-PCR)
- UniSTS:59617

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables ATP binding	IEA Inferred from Electronic Annotation more info
enables MHC class II protein complex binding	HDA more info	PubMed
enables RNA binding	HDA more info	PubMed
enables cadherin binding	HDA more info	PubMed
enables mRNA binding	ISS Inferred from Sequence or Structural Similarity more info
enables magnesium ion binding	IEA Inferred from Electronic Annotation more info
enables potassium ion binding	IEA Inferred from Electronic Annotation more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein tyrosine kinase activity	IEA Inferred from Electronic Annotation more info
enables pyruvate kinase activity	IBA Inferred from Biological aspect of Ancestor more info
enables pyruvate kinase activity	IDA Inferred from Direct Assay more info	PubMed
enables pyruvate kinase activity	TAS Traceable Author Statement more info	PubMed

Process	Evidence Code	Pubs
involved_in canonical glycolysis	IEA Inferred from Electronic Annotation more info
involved_in cellular response to insulin stimulus	IBA Inferred from Biological aspect of Ancestor more info
involved_in glycolytic process	IBA Inferred from Biological aspect of Ancestor more info
involved_in positive regulation of cytoplasmic translation	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of sprouting angiogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in programmed cell death	IDA Inferred from Direct Assay more info	PubMed

Component	Evidence Code	Pubs
located_in cilium	IEA Inferred from Electronic Annotation more info
located_in collagen-containing extracellular matrix	HDA more info	PubMed
is_active_in cytoplasm	IBA Inferred from Biological aspect of Ancestor more info
located_in cytoplasm	IDA Inferred from Direct Assay more info	PubMed
located_in cytosol	IDA Inferred from Direct Assay more info
located_in cytosol	NAS Non-traceable Author Statement more info	PubMed
located_in cytosol	TAS Traceable Author Statement more info
located_in extracellular exosome	HDA more info	PubMed
located_in extracellular region	TAS Traceable Author Statement more info
located_in extracellular vesicle	HDA more info	PubMed
located_in ficolin-1-rich granule lumen	TAS Traceable Author Statement more info
located_in mitochondrion	HDA more info	PubMed
located_in nucleus	HDA more info	PubMed
located_in nucleus	IDA Inferred from Direct Assay more info	PubMed
located_in rough endoplasmic reticulum	ISS Inferred from Sequence or Structural Similarity more info
located_in secretory granule lumen	TAS Traceable Author Statement more info
located_in vesicle	HDA more info	PubMed

General protein information

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Preferred Names: pyruvate kinase PKM

Names: OPA-interacting protein 3; PK, muscle type; cytosolic thyroid hormone-binding protein; epididymis secretory protein Li 30; pyruvate kinase 2/3; pyruvate kinase isozymes M1/M2; pyruvate kinase muscle isozyme; pyruvate kinase, muscle; threonine-protein kinase PKM2; thyroid hormone-binding protein 1; thyroid hormone-binding protein, cytosolic; tumor M2-PK; tyrosine-protein kinase PKM2

NP_001193725.1

EC 2.7.1.40

EC 2.7.10.2

EC 2.7.11.1

NP_001193726.1

EC 2.7.1.40

EC 2.7.10.2

EC 2.7.11.1

NP_001193727.1

EC 2.7.1.40

EC 2.7.10.2

EC 2.7.11.1

NP_001193728.1

EC 2.7.1.40

EC 2.7.10.2

EC 2.7.11.1

NP_001303247.1

EC 2.7.1.40

EC 2.7.10.2

EC 2.7.11.1

NP_001398010.1

EC 2.7.1.40

EC 2.7.10.2

EC 2.7.11.1

NP_002645.3

EC 2.7.1.40

EC 2.7.10.2

EC 2.7.11.1

NP_872270.1

EC 2.7.1.40

EC 2.7.10.2

EC 2.7.11.1

NP_872271.1

EC 2.7.1.40

EC 2.7.10.2

EC 2.7.11.1

XP_005254500.1

EC 2.7.1.40

EC 2.7.10.2

EC 2.7.11.1

XP_005254502.1

EC 2.7.1.40

EC 2.7.10.2

EC 2.7.11.1

XP_011519972.1

EC 2.7.1.40

EC 2.7.10.2

EC 2.7.11.1

XP_047288618.1

EC 2.7.1.40

EC 2.7.10.2

EC 2.7.11.1

XP_047288619.1

EC 2.7.1.40

EC 2.7.10.2

EC 2.7.11.1

XP_047288620.1

EC 2.7.1.40

EC 2.7.10.2

EC 2.7.11.1

XP_047288621.1

EC 2.7.1.40

EC 2.7.10.2

EC 2.7.11.1

XP_047288622.1

EC 2.7.1.40

EC 2.7.10.2

EC 2.7.11.1

XP_054234160.1

EC 2.7.1.40

EC 2.7.10.2

EC 2.7.11.1

XP_054234161.1

EC 2.7.1.40

EC 2.7.10.2

EC 2.7.11.1

XP_054234162.1

EC 2.7.1.40

EC 2.7.10.2

EC 2.7.11.1

XP_054234163.1

EC 2.7.1.40

EC 2.7.10.2

EC 2.7.11.1

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_052978.2 RefSeqGene

Range

5401..37562

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001206796.3 → NP_001193725.1 pyruvate kinase PKM isoform c

See identical proteins and their annotated locations for NP_001193725.1

Status: REVIEWED

Description

Transcript Variant: This variant (4) represents the longest transcript and encodes the longest isoform (c).

Source sequence(s)

AC020779

Consensus CDS

CCDS92037.1

UniProtKB/TrEMBL

A0A804F729, B4DRT3

Related

ENSP00000455901.2, ENST00000565154.6

Conserved Domains (2) summary

cd00288
Location:116 → 604

Pyruvate_Kinase; Pyruvate kinase (PK): Large allosteric enzyme that regulates glycolysis through binding of the substrate, phosphoenolpyruvate, and one or more allosteric effectors. Like other allosteric enzymes, PK has a high substrate affinity R state and a low ...

TIGR01064
Location:117 → 601

pyruv_kin; pyruvate kinase
NM_001206797.3 → NP_001193726.1 pyruvate kinase PKM isoform d

See identical proteins and their annotated locations for NP_001193726.1

Status: REVIEWED

Description

Transcript Variant: This variant (5) differs in the 5' UTR and coding sequence, lacks an alternate in-frame segment, and has an alternate in-frame coding exon compared to variant 4. The resulting isoform (d) is shorter at the N-terminus, lacks an alternate internal segment, and has a different internal segment compared to isoform c.

Source sequence(s)

AC020779

Consensus CDS

CCDS73752.1

UniProtKB/TrEMBL

B4DNK4, B4DRT3

Related

ENSP00000373745.4, ENST00000389093.7

Conserved Domains (1) summary

cd00288
Location:42 → 456

Pyruvate_Kinase; Pyruvate kinase (PK): Large allosteric enzyme that regulates glycolysis through binding of the substrate, phosphoenolpyruvate, and one or more allosteric effectors. Like other allosteric enzymes, PK has a high substrate affinity R state and a low ...
NM_001206798.3 → NP_001193727.1 pyruvate kinase PKM isoform e

See identical proteins and their annotated locations for NP_001193727.1

Status: REVIEWED

Description

Transcript Variant: This variant (6) differs in the 5' UTR and coding sequence, lacks an alternate exon, and has an alternate in-frame coding exon compared to variant 4. The resulting isoform (e) has a shorter and distinct N-terminus, lacks an alternate internal segment, and has a different internal segment compared to isoform c.

Source sequence(s)

AC020779

UniProtKB/TrEMBL

B4DRT3

Conserved Domains (2) summary

cd00288
Location:68 → 515

Pyruvate_Kinase; Pyruvate kinase (PK): Large allosteric enzyme that regulates glycolysis through binding of the substrate, phosphoenolpyruvate, and one or more allosteric effectors. Like other allosteric enzymes, PK has a high substrate affinity R state and a low ...

TIGR01064
Location:68 → 512

pyruv_kin; pyruvate kinase
NM_001206799.2 → NP_001193728.1 pyruvate kinase PKM isoform f

See identical proteins and their annotated locations for NP_001193728.1

Status: REVIEWED

Description

Transcript Variant: This variant (7) differs in the 5' UTR and coding sequence compared to variant 4. The resulting isoform (f) has a shorter and distinct N-terminus compared to isoform c.

Source sequence(s)

AC020779, AK294315, AK309781, BC000481, BC035198

UniProtKB/TrEMBL

B4DRT3

Conserved Domains (2) summary

cd00288
Location:47 → 535

Pyruvate_Kinase; Pyruvate kinase (PK): Large allosteric enzyme that regulates glycolysis through binding of the substrate, phosphoenolpyruvate, and one or more allosteric effectors. Like other allosteric enzymes, PK has a high substrate affinity R state and a low ...

TIGR01064
Location:48 → 532

pyruv_kin; pyruvate kinase
NM_001316318.2 → NP_001303247.1 pyruvate kinase PKM isoform g

Status: REVIEWED

Description

Transcript Variant: This variant (8) lacks an alternate in-frame exon in the 5' end of the coding sequence compared to variant 4. The resulting isoform (g) has the same N- and C-termini but is shorter compared to isoform c.

Source sequence(s)

AC020779

Consensus CDS

CCDS92035.1

UniProtKB/TrEMBL

A0A804F6T5, B4DRT3

Related

ENSP00000455736.2, ENST00000565184.6

Conserved Domains (2) summary

cd00288
Location:77 → 565

Pyruvate_Kinase; Pyruvate kinase (PK): Large allosteric enzyme that regulates glycolysis through binding of the substrate, phosphoenolpyruvate, and one or more allosteric effectors. Like other allosteric enzymes, PK has a high substrate affinity R state and a low ...

TIGR01064
Location:78 → 562

pyruv_kin; pyruvate kinase
NM_001411081.1 → NP_001398010.1 pyruvate kinase PKM isoform h

Status: REVIEWED

Source sequence(s)

AC020779

Consensus CDS

CCDS92036.1

UniProtKB/TrEMBL

A0A8V8TNX9

Related

ENSP00000513903.1, ENST00000698741.1
NM_002654.6 → NP_002645.3 pyruvate kinase PKM isoform a

See identical proteins and their annotated locations for NP_002645.3

Status: REVIEWED

Description

Transcript Variant: This variant (1) differs in the 5' UTR and coding sequence and has an alternate in-frame coding exon compared to variant 4. The resulting isoform (a, also called M2) is shorter at the N-terminus and has a different internal segment compared to isoform c.

Source sequence(s)

AC020779

Consensus CDS

CCDS32284.1

UniProtKB/Swiss-Prot

A6NFK3, B2R5N8, B3KRY0, B4DFX8, B4DUU6, P14618, P14786, Q53GK4, Q96E76, Q9BWB5, Q9UCV6, Q9UPF2

UniProtKB/TrEMBL

B4DRT3, V9HWB8

Related

ENSP00000334983.5, ENST00000335181.10

Conserved Domains (1) summary

cd00288
Location:42 → 530

Pyruvate_Kinase; Pyruvate kinase (PK): Large allosteric enzyme that regulates glycolysis through binding of the substrate, phosphoenolpyruvate, and one or more allosteric effectors. Like other allosteric enzymes, PK has a high substrate affinity R state and a low ...
NM_182470.4 → NP_872270.1 pyruvate kinase PKM isoform b

See identical proteins and their annotated locations for NP_872270.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) differs in the 5' UTR and coding sequence compared to variant 4. The resulting isoform (b, also called M1) is shorter at the N-terminus compared to isoform c.

Source sequence(s)

AC020779

Consensus CDS

CCDS32285.1

UniProtKB/TrEMBL

B4DRT3

Related

ENSP00000320171.6, ENST00000319622.10

Conserved Domains (1) summary

cd00288
Location:42 → 530

Pyruvate_Kinase; Pyruvate kinase (PK): Large allosteric enzyme that regulates glycolysis through binding of the substrate, phosphoenolpyruvate, and one or more allosteric effectors. Like other allosteric enzymes, PK has a high substrate affinity R state and a low ...
NM_182471.4 → NP_872271.1 pyruvate kinase PKM isoform b

See identical proteins and their annotated locations for NP_872271.1

Status: REVIEWED

Description

Transcript Variant: This variant (3) differs in the 5' UTR and coding sequence compared to variant 4. The resulting isoform (b, also called M1) is shorter at the N-terminus compared to isoform c.

Source sequence(s)

AC020779

Consensus CDS

CCDS32285.1

UniProtKB/TrEMBL

B4DRT3

Related

ENSP00000456970.1, ENST00000568459.5

Conserved Domains (1) summary

cd00288
Location:42 → 530

Pyruvate_Kinase; Pyruvate kinase (PK): Large allosteric enzyme that regulates glycolysis through binding of the substrate, phosphoenolpyruvate, and one or more allosteric effectors. Like other allosteric enzymes, PK has a high substrate affinity R state and a low ...

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000015.10 Reference GRCh38.p14 Primary Assembly

Range

72199029..72231591 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_005254445.6 → XP_005254502.1 pyruvate kinase PKM isoform X7

See identical proteins and their annotated locations for XP_005254502.1

UniProtKB/Swiss-Prot

A6NFK3, B2R5N8, B3KRY0, B4DFX8, B4DUU6, P14618, P14786, Q53GK4, Q96E76, Q9BWB5, Q9UCV6, Q9UPF2

UniProtKB/TrEMBL

B4DRT3, V9HWB8

Conserved Domains (1) summary

cd00288
Location:42 → 530

Pyruvate_Kinase; Pyruvate kinase (PK): Large allosteric enzyme that regulates glycolysis through binding of the substrate, phosphoenolpyruvate, and one or more allosteric effectors. Like other allosteric enzymes, PK has a high substrate affinity R state and a low ...
XM_011521670.2 → XP_011519972.1 pyruvate kinase PKM isoform X4

See identical proteins and their annotated locations for XP_011519972.1

UniProtKB/TrEMBL

B4DRT3

Conserved Domains (1) summary

cd00288
Location:77 → 565

Pyruvate_Kinase; Pyruvate kinase (PK): Large allosteric enzyme that regulates glycolysis through binding of the substrate, phosphoenolpyruvate, and one or more allosteric effectors. Like other allosteric enzymes, PK has a high substrate affinity R state and a low ...
XM_047432666.1 → XP_047288622.1 pyruvate kinase PKM isoform X7

UniProtKB/Swiss-Prot

A6NFK3, B2R5N8, B3KRY0, B4DFX8, B4DUU6, P14618, P14786, Q53GK4, Q96E76, Q9BWB5, Q9UCV6, Q9UPF2

UniProtKB/TrEMBL

V9HWB8
XM_047432664.1 → XP_047288620.1 pyruvate kinase PKM isoform X5
XM_047432665.1 → XP_047288621.1 pyruvate kinase PKM isoform X6
XM_005254443.2 → XP_005254500.1 pyruvate kinase PKM isoform X3

UniProtKB/TrEMBL

B4DRT3

Conserved Domains (2) summary

cd00288
Location:102 → 590

Pyruvate_Kinase; Pyruvate kinase (PK): Large allosteric enzyme that regulates glycolysis through binding of the substrate, phosphoenolpyruvate, and one or more allosteric effectors. Like other allosteric enzymes, PK has a high substrate affinity R state and a low ...

TIGR01064
Location:103 → 587

pyruv_kin; pyruvate kinase
XM_047432662.1 → XP_047288618.1 pyruvate kinase PKM isoform X1
XM_047432663.1 → XP_047288619.1 pyruvate kinase PKM isoform X2