PPM1K protein phosphatase, Mg2+/Mn2+ dependent 1K [Homo sapiens (human)] - Gene

Summary

Official Symbol: PPM1Kprovided by HGNC
Official Full Name: protein phosphatase, Mg2+/Mn2+ dependent 1Kprovided by HGNC
Primary source: HGNC:HGNC:25415
See related: Ensembl:ENSG00000163644 MIM:611065; AllianceGenome:HGNC:25415
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: BDP; PTMP; BCKDH; PP2Cm; MSUDMV; PP2Ckappa; UG0882E07
Summary: This gene encodes a member of the PPM family of Mn2+/Mg2+-dependent protein phosphatases. The encoded protein, essential for cell survival and development, is targeted to the mitochondria where it plays a key role in regulation of the mitochondrial permeability transition pore. [provided by RefSeq, Sep 2012]
Expression: Broad expression in heart (RPKM 22.0), endometrium (RPKM 10.0) and 22 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 4q22.1

Exon count:: 11

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	4	NC_000004.12 (88257620..88284561, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	4	NC_060928.1 (91588591..91615539, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	4	NC_000004.11 (89178772..89205713, complement)

Chromosome 4 - NC_000004.12 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 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?

PPM1K-regulated impaired catabolism of branched-chain amino acids orchestrates polycystic ovary syndrome.
Title: PPM1K-regulated impaired catabolism of branched-chain amino acids orchestrates polycystic ovary syndrome.
The role of PP5 and PP2C in cardiac health and disease.
Title: The role of PP5 and PP2C in cardiac health and disease.
Effects of PPM1K rs1440581 and rs7678928 on serum branched-chain amino acid levels and risk of cardiovascular disease.
Title: Effects of PPM1K rs1440581 and rs7678928 on serum branched-chain amino acid levels and risk of cardiovascular disease.
three Mg(2+) were located in the active site of the PPM1K N94K instead of two Mg(2+) in the PPM1K wild type
Title: Crystal structure and catalytic activity of the PPM1K N94K mutant.
Branched chain amino acids related genetic variant rs1440581 was associated with an increased risk of incident T2 Diabetes in a Chinese population. This variant might modify effect of weight gain on development in Insulin resistance.
Title: Association of branched chain amino acids related variant rs1440581 with risk of incident diabetes and longitudinal changes in insulin resistance in Chinese.
PPM1K rs1440581 may affect changes in glucose metabolism during weight loss, and this effect is dependent on dietary fat and carbohydrate intakes.
Title: Effect of the interaction between diet composition and the PPM1K genetic variant on insulin resistance and β cell function markers during weight loss: results from the Nutrient Gene Interactions in Human Obesity: implications for dietary guidelines (NUGENOB) randomized trial.
miR-204 and miR-211 directly repress PPM1K expression via 3'UTR.
Title: Regulation of PP2Cm expression by miRNA-204/211 and miRNA-22 in mouse and human cells.
Overweight people with the C allele of the branched-chain amino acid/aromatic amino acid ratio-associated variant rs1440581 may benefit less in weight loss and improved insulin sensitivity than those without it on a energy-restricted high-fat diet.
Title: Genetic determinant for amino acid metabolites and changes in body weight and insulin resistance in response to weight-loss diets: the Preventing Overweight Using Novel Dietary Strategies (POUNDS LOST) trial.
The 2.4 A PP2Cm structure reveals a central beta-sandwich with two bound metal ions in the active-site cleft.
Title: Structural and biochemical characterization of human mitochondrial branched-chain α-ketoacid dehydrogenase phosphatase.
Observational study of gene-disease association. (HuGE Navigator)
Title: Genetic variants in nuclear-encoded mitochondrial genes influence AIDS progression.

Submit: New GeneRIF Correction See all GeneRIFs (13)

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

Associated conditions

Description	Tests
Maple syrup urine disease, mild variant MedGen: C3554575 OMIM: 615135 GeneReviews: Not available	not available

EBI GWAS Catalog

Description
An atlas of genetic influences on human blood metabolites. EBI GWAS Catalog EBI GWAS CatalogPubMed
Does parental expressed emotion moderate genetic effects in ADHD? An exploration using a genome wide association scan. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association study identifies multiple loci influencing human serum metabolite levels. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide meta-analysis identifies six novel loci associated with habitual coffee consumption. EBI GWAS Catalog EBI GWAS CatalogPubMed
Novel Loci for metabolic networks and multi-tissue expression studies reveal genes for atherosclerosis. EBI GWAS Catalog EBI GWAS CatalogPubMed

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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Replication interactions

Interaction	Pubs
Knockdown of protein phosphatase, Mg2+/Mn2+ dependent, 1K (PPM1K) by siRNA inhibits the early stages of HIV-1 replication in 293T cells infected with VSV-G pseudotyped HIV-1	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

D11S2921 (e-PCR)
- UniSTS:152074

GDB:434012 (e-PCR)
- UniSTS:157204

SHGC-24822 (e-PCR)
- UniSTS:27674

20 (e-PCR), detects polymorphism
- UniSTS:24357

L17705 (e-PCR)
- UniSTS:66091

D4S905 (e-PCR)
- UniSTS:81712

D8S2278 (e-PCR)
- UniSTS:473906

D8S2279 (e-PCR)
- UniSTS:473907

STS-N22865 (e-PCR)
- UniSTS:57943

STS-M61964 (e-PCR)
- UniSTS:49766

D10S16 (e-PCR)
- UniSTS:155756

D1S1423 (e-PCR)
- UniSTS:149619

D1S1425 (e-PCR)
- UniSTS:149621

STS-AA017240 (e-PCR)
- UniSTS:74366

D11S3732 (e-PCR)
- UniSTS:152962

L18441 (e-PCR)
- UniSTS:71348

GDB:631802 (e-PCR)
- UniSTS:158429

D3S1673 (e-PCR)
- UniSTS:148450

SHGC-36508 (e-PCR)
- UniSTS:7148

STS-F04960 (e-PCR)
- UniSTS:37359

D11S2875 (e-PCR)
- UniSTS:152053

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables [3-methyl-2-oxobutanoate dehydrogenase (lipoamide)]-phosphatase activity	IEA Inferred from Electronic Annotation more info
enables manganese ion binding	IDA Inferred from Direct Assay more info	PubMed
enables myosin phosphatase activity	IEA Inferred from Electronic Annotation more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein serine/threonine phosphatase activity	IBA Inferred from Biological aspect of Ancestor more info
enables protein serine/threonine phosphatase activity	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
involved_in branched-chain amino acid catabolic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in protein dephosphorylation	IEA Inferred from Electronic Annotation more info
involved_in regulation of intracellular signal transduction	IBA Inferred from Biological aspect of Ancestor more info
involved_in regulation of mitochondrial membrane permeability involved in apoptotic process	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
located_in mitochondrial matrix	ISS Inferred from Sequence or Structural Similarity more info
located_in mitochondrial matrix	TAS Traceable Author Statement more info
located_in mitochondrion	HTP more info	PubMed
is_active_in mitochondrion	IBA Inferred from Biological aspect of Ancestor more info
located_in mitochondrion	IDA Inferred from Direct Assay more info

General protein information

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Preferred Names: protein phosphatase Mn(2+)-dependent 1K

Names: PP2C domain-containing protein phosphatase 1K; PP2C-kappa; PP2C-type mitochondrial phosphoprotein phosphatase; [3-methyl-2-oxobutanoate dehydrogenase (2-methylpropanoyl-transferring)]-phosphatase, mitochondrial; branched-chain I+/--ketoacid dehydrogenase phosphatase; branched-chain alpha-ketoacid dehydrogenase phosphatase; protein phosphatase 1K, mitochondrial; protein phosphatase 2C family member; protein phosphatase 2C kappa

NP_689755.3

EC 3.1.3.16

EC 3.1.3.52

XP_005262832.1

EC 3.1.3.16

EC 3.1.3.52

XP_006714174.1

EC 3.1.3.16

EC 3.1.3.52

XP_016863292.1

EC 3.1.3.16

EC 3.1.3.52

XP_016863295.1

EC 3.1.3.16

EC 3.1.3.52

XP_047305628.1

EC 3.1.3.16

EC 3.1.3.52

XP_047305629.1

EC 3.1.3.16

EC 3.1.3.52

XP_047305630.1

EC 3.1.3.16

EC 3.1.3.52

XP_047305631.1

EC 3.1.3.16

EC 3.1.3.52

XP_054205018.1

EC 3.1.3.16

EC 3.1.3.52

XP_054205019.1

EC 3.1.3.16

EC 3.1.3.52

XP_054205020.1

EC 3.1.3.16

EC 3.1.3.52

XP_054205021.1

EC 3.1.3.16

EC 3.1.3.52

XP_054205022.1

EC 3.1.3.16

EC 3.1.3.52

XP_054205023.1

EC 3.1.3.16

EC 3.1.3.52

XP_054205024.1

EC 3.1.3.16

EC 3.1.3.52

XP_054205025.1

EC 3.1.3.16

EC 3.1.3.52

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_032931.1 RefSeqGene

Range

5271..32212

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_152542.5 → NP_689755.3 protein phosphatase Mn(2+)-dependent 1K

See identical proteins and their annotated locations for NP_689755.3

Status: REVIEWED

Source sequence(s)

AC097484, AC108213, AY435431

Consensus CDS

CCDS3629.1

UniProtKB/Swiss-Prot

B2RAZ1, Q05CT5, Q49AB5, Q4W5E6, Q56AN8, Q8IUZ7, Q8IXG7, Q8N3J5, Q8ND70, Q96NT4

UniProtKB/TrEMBL

A0A0A0MQZ4

Related

ENSP00000477341.1, ENST00000608933.6

Conserved Domains (1) summary

cd00143
Location:95 → 346

PP2Cc; Serine/threonine phosphatases, family 2C, catalytic domain; The protein architecture and deduced catalytic mechanism of PP2C phosphatases are similar to the PP1, PP2A, PP2B family of protein Ser/Thr phosphatases, with which PP2C shares no sequence ...

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

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

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000004.12 Reference GRCh38.p14 Primary Assembly

Range

88257620..88284561 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_017007803.3 → XP_016863292.1 protein phosphatase Mn(2+)-dependent 1K isoform X1

UniProtKB/Swiss-Prot

B2RAZ1, Q05CT5, Q49AB5, Q4W5E6, Q56AN8, Q8IUZ7, Q8IXG7, Q8N3J5, Q8ND70, Q96NT4

UniProtKB/TrEMBL

A0A0A0MQZ4

Conserved Domains (1) summary

cd00143
Location:95 → 346

PP2Cc; Serine/threonine phosphatases, family 2C, catalytic domain; The protein architecture and deduced catalytic mechanism of PP2C phosphatases are similar to the PP1, PP2A, PP2B family of protein Ser/Thr phosphatases, with which PP2C shares no sequence ...
XM_006714111.5 → XP_006714174.1 protein phosphatase Mn(2+)-dependent 1K isoform X1

See identical proteins and their annotated locations for XP_006714174.1

UniProtKB/Swiss-Prot

B2RAZ1, Q05CT5, Q49AB5, Q4W5E6, Q56AN8, Q8IUZ7, Q8IXG7, Q8N3J5, Q8ND70, Q96NT4

UniProtKB/TrEMBL

A0A0A0MQZ4

Conserved Domains (1) summary

cd00143
Location:95 → 346

PP2Cc; Serine/threonine phosphatases, family 2C, catalytic domain; The protein architecture and deduced catalytic mechanism of PP2C phosphatases are similar to the PP1, PP2A, PP2B family of protein Ser/Thr phosphatases, with which PP2C shares no sequence ...
XM_017007806.3 → XP_016863295.1 protein phosphatase Mn(2+)-dependent 1K isoform X2
XM_047449672.1 → XP_047305628.1 protein phosphatase Mn(2+)-dependent 1K isoform X3
XM_047449675.1 → XP_047305631.1 protein phosphatase Mn(2+)-dependent 1K isoform X6
XM_047449674.1 → XP_047305630.1 protein phosphatase Mn(2+)-dependent 1K isoform X5
XM_005262775.5 → XP_005262832.1 protein phosphatase Mn(2+)-dependent 1K isoform X4

UniProtKB/TrEMBL

V9GYZ5

Conserved Domains (1) summary

cl00120
Location:95 → 184

PP2Cc; Serine/threonine phosphatases, family 2C, catalytic domain; The protein architecture and deduced catalytic mechanism of PP2C phosphatases are similar to the PP1, PP2A, PP2B family of protein Ser/Thr phosphatases, with which PP2C shares no sequence ...
XM_047449673.1 → XP_047305629.1 protein phosphatase Mn(2+)-dependent 1K isoform X4

Alternate T2T-CHM13v2.0

Genomic

NC_060928.1 Alternate T2T-CHM13v2.0

Range

91588591..91615539 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_054349044.1 → XP_054205019.1 protein phosphatase Mn(2+)-dependent 1K isoform X1

UniProtKB/Swiss-Prot

B2RAZ1, Q05CT5, Q49AB5, Q4W5E6, Q56AN8, Q8IUZ7, Q8IXG7, Q8N3J5, Q8ND70, Q96NT4
XM_054349043.1 → XP_054205018.1 protein phosphatase Mn(2+)-dependent 1K isoform X1

UniProtKB/Swiss-Prot

B2RAZ1, Q05CT5, Q49AB5, Q4W5E6, Q56AN8, Q8IUZ7, Q8IXG7, Q8N3J5, Q8ND70, Q96NT4
XM_054349045.1 → XP_054205020.1 protein phosphatase Mn(2+)-dependent 1K isoform X2
XM_054349046.1 → XP_054205021.1 protein phosphatase Mn(2+)-dependent 1K isoform X3
XM_054349050.1 → XP_054205025.1 protein phosphatase Mn(2+)-dependent 1K isoform X6
XM_054349049.1 → XP_054205024.1 protein phosphatase Mn(2+)-dependent 1K isoform X5
XM_054349047.1 → XP_054205022.1 protein phosphatase Mn(2+)-dependent 1K isoform X4
XM_054349048.1 → XP_054205023.1 protein phosphatase Mn(2+)-dependent 1K isoform X4