PMVK phosphomevalonate kinase [Homo sapiens (human)] - Gene

Summary

Official Symbol: PMVKprovided by HGNC
Official Full Name: phosphomevalonate kinaseprovided by HGNC
Primary source: HGNC:HGNC:9141
See related: Ensembl:ENSG00000163344 MIM:607622; AllianceGenome:HGNC:9141
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: PMK; PMKA; PMKASE; POROK1; HUMPMKI
Summary: This gene encodes a peroxisomal enzyme that is a member of the galactokinase, homoserine kinase, mevalonate kinase, and phosphomevalonate kinase (GHMP) family of ATP-dependent enzymes. The encoded protein catalyzes the conversion of mevalonate 5-phosphate to mevalonate 5-diphosphate, which is the fifth step in the mevalonate pathway of isoprenoid biosynthesis. Mutations in this gene are linked to certain types of porokeratosis including disseminated superficial porokeratosis. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2017]
Expression: Ubiquitous expression in kidney (RPKM 26.9), liver (RPKM 17.8) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 1q21.3

Exon count:: 6

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	1	NC_000001.11 (154924740..154942658, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	1	NC_060925.1 (154064101..154082019, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	1	NC_000001.10 (154897216..154915134, complement)

Chromosome 1 - NC_000001.11 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?

CaMKK2 and CHK1 phosphorylate human STN1 in response to replication stress to protect stalled forks from aberrant resection.
Title: CaMKK2 and CHK1 phosphorylate human STN1 in response to replication stress to protect stalled forks from aberrant resection.
CELF1 Selectively Regulates Alternative Splicing of DNA Repair Genes Associated With Cataract in Human Lens Cell Line.
Title: CELF1 Selectively Regulates Alternative Splicing of DNA Repair Genes Associated With Cataract in Human Lens Cell Line.
Data indicate that exome sequencing revealed disseminated superficial porokeratosis (DSP)-associated mutations in phosphomevalonate kinase gene (PMVK).
Title: Loss-of-function Mutation in PMVK Causes Autosomal Dominant Disseminated Superficial Porokeratosis.
Observational study of gene-disease association, gene-environment interaction, and pharmacogenomic / toxicogenomic. (HuGE Navigator)
Title: Variation at the NFATC2 locus increases the risk of thiazolidinedione-induced edema in the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) study.
Binding of mevalonate 5-phosphate causes the phosphomevalonate kinase structure to compress (tau(c) = 13.5 nsec), whereas subsequent binding of Mg-ADP opens the structure up (tau(c) = 15.6 nsec).
Title: Substrate induced structural and dynamics changes in human phosphomevalonate kinase and implications for mechanism.
This is the first report of hPMK crystal structure that suggests a potential substrate binding site and a possible enzyme catalytic mechanism.
Title: Crystal structure of human phosphomevalonate kinase at 1.8 A resolution.
Observational study of gene-disease association. (HuGE Navigator)
Title: Gene-centric association signals for lipids and apolipoproteins identified via the HumanCVD BeadChip.
Functional evaluation of conserved basic residues in PMVK is reported.
Title: Functional evaluation of conserved basic residues in human phosphomevalonate kinase.
found an exclusive cytosolic localization of both endogenously expressed PMVK(in human fibroblasts, human liver, and HEK293 cells) and overexpressed PMVK. No indication of a peroxisomal localization was obtained.
Title: Phosphomevalonate kinase is a cytosolic protein in humans.

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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
Porokeratosis 1, Mibelli type MedGen: CN297066 OMIM: 175800 GeneReviews: Not available	Compare labs

EBI GWAS Catalog

Description
Discovery and refinement of loci associated with lipid levels. EBI GWAS Catalog EBI GWAS CatalogPubMed
Identification of 23 new prostate cancer susceptibility loci using the iCOGS custom genotyping array. EBI GWAS Catalog EBI GWAS CatalogPubMed
Meta-analysis identifies six new susceptibility loci for atrial fibrillation. 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)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables ATP binding	IDA Inferred from Direct Assay more info	PubMed
enables phosphomevalonate kinase activity	IBA Inferred from Biological aspect of Ancestor more info
enables phosphomevalonate kinase activity	IDA Inferred from Direct Assay more info	PubMed
enables phosphomevalonate kinase activity	TAS Traceable Author Statement more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in cholesterol biosynthetic process	IBA Inferred from Biological aspect of Ancestor more info
involved_in cholesterol biosynthetic process	IDA Inferred from Direct Assay more info	PubMed
involved_in cholesterol biosynthetic process	TAS Traceable Author Statement more info
involved_in isopentenyl diphosphate biosynthetic process, mevalonate pathway	IBA Inferred from Biological aspect of Ancestor more info
involved_in isopentenyl diphosphate biosynthetic process, mevalonate pathway	IEA Inferred from Electronic Annotation more info
involved_in response to cholesterol	IEP Inferred from Expression Pattern more info	PubMed
involved_in sterol biosynthetic process	IDA Inferred from Direct Assay more info	PubMed

Component	Evidence Code	Pubs
located_in cytosol	IDA Inferred from Direct Assay more info	PubMed
located_in cytosol	TAS Traceable Author Statement more info
located_in extracellular exosome	HDA more info	PubMed
located_in membrane	HDA more info	PubMed
NOT located_in peroxisome	IDA Inferred from Direct Assay more info	PubMed
located_in peroxisome	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: phosphomevalonate kinase

Names: testis tissue sperm-binding protein Li 95mP

NP_001309940.1

EC 2.7.4.2

NP_001309941.1

EC 2.7.4.2

NP_001335625.1

EC 2.7.4.2

NP_006547.1

EC 2.7.4.2

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_053028.1 RefSeqGene

Range

10932..22911

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001323011.3 → NP_001309940.1 phosphomevalonate kinase isoform 2

Status: REVIEWED

Description

Transcript Variant: This variant (2) differs in the 5' UTR and initiates translation at an alternate start codon, compared to variant 1. The encoded isoform (2) is shorter and has a distinct N-terminus, compared to isoform 1.

Source sequence(s)

AL451085, CN344384, HM005718

UniProtKB/TrEMBL

Q6FGV9

Conserved Domains (1) summary

pfam04275
Location:16 → 109

P-mevalo_kinase; Phosphomevalonate kinase
NM_001323012.3 → NP_001309941.1 phosphomevalonate kinase isoform 3

Status: REVIEWED

Description

Transcript Variant: This variant (3) contains an alternate exon in the 5' UTR and initiates translation at a downstream start codon, compared to variant 1. The encoded isoform (3) has a shorter N-terminus, compared to isoform 1.

Source sequence(s)

AL451085, BQ057770, HM005718

UniProtKB/TrEMBL

Q6FGV9

Conserved Domains (1) summary

cl04466
Location:1 → 111

P-mevalo_kinase; Phosphomevalonate kinase
NM_001348696.2 → NP_001335625.1 phosphomevalonate kinase isoform 4

Status: REVIEWED

Description

Transcript Variant: This variant (4) uses an alternate splice site in the coding region and initiates translation at an alternate start codon compared to variant 1. The encoded isoform (4) has a shorter and distinct N-terminus, compared to isoform 1.

Source sequence(s)

BM793483, BQ057770, HM005718

UniProtKB/TrEMBL

Q6FGV9

Conserved Domains (1) summary

cl04466
Location:18 → 111

P-mevalo_kinase; Phosphomevalonate kinase
NM_006556.4 → NP_006547.1 phosphomevalonate kinase isoform 1

See identical proteins and their annotated locations for NP_006547.1

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (1).

Source sequence(s)

BC007694

Consensus CDS

CCDS1073.1

UniProtKB/Swiss-Prot

Q15126, Q5TZW9

UniProtKB/TrEMBL

D3DV77, Q6FGV9

Related

ENSP00000357452.3, ENST00000368467.4

Conserved Domains (1) summary

pfam04275
Location:14 → 123

P-mevalo_kinase; Phosphomevalonate kinase