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PLEKHM2 pleckstrin homology and RUN domain containing M2 [ Homo sapiens (human) ]

Gene ID: 23207, updated on 3-Apr-2024

Summary

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Official Symbol
PLEKHM2provided by HGNC
Official Full Name
pleckstrin homology and RUN domain containing M2provided by HGNC
Primary source
HGNC:HGNC:29131
See related
Ensembl:ENSG00000116786 MIM:609613; AllianceGenome:HGNC:29131
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
SKIP
Summary
This gene encodes a protein that binds the plus-end directed microtubule motor protein kinesin, together with the lysosomal GTPase Arl8, and is required for lysosomes to distribute away from the microtubule-organizing center. The encoded protein belongs to the multisubunit BLOC-one-related complex that regulates lysosome positioning. It binds a Salmonella effector protein called Salmonella induced filament A and is a critical host determinant in Salmonella pathogenesis. It has a domain architecture consisting of an N-terminal RPIP8, UNC-14, and NESCA (RUN) domain that binds kinesin-1 as well as the lysosomal GTPase Arl8, and a C-terminal pleckstrin homology domain that binds the Salmonella induced filament A effector protein. Naturally occurring mutations in this gene lead to abnormal localization of lysosomes, impaired autophagy flux and are associated with recessive dilated cardiomyopathy and left ventricular noncompaction. [provided by RefSeq, Feb 2017]
Expression
Ubiquitous expression in bone marrow (RPKM 21.8), testis (RPKM 21.5) and 25 other tissues See more
Orthologs
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Genomic context

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See PLEKHM2 in Genome Data Viewer
Location:
1p36.21
Exon count:
22
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 1 NC_000001.11 (15681506..15734769)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 1 NC_060925.1 (15125588..15179507)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 1 NC_000001.10 (16010815..16061264)

Chromosome 1 - NC_000001.11Genomic Context describing neighboring genes Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 309 Neighboring gene CD24 molecule pseudogene 1 Neighboring gene DNA damage inducible 1 homolog 2 Neighboring gene MPRA-validated peak82 silencer Neighboring gene regulator of solute carriers 1 Neighboring gene ReSE screen-validated silencer GRCh37_chr1:16005129-16005676 Neighboring gene H3K27ac hESC enhancer GRCh37_chr1:16006379-16006879 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 310 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 311 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 312 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 240 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 242 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 241 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 243 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 244 Neighboring gene ReSE screen-validated silencer GRCh37_chr1:16051023-16051299 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:16051819-16052339 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr1:16061087-16061852 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr1:16061853-16062619 Neighboring gene SLC25A34 and TMEM82 antisense RNA 1 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 245 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:16068575-16069355 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr1:16070316-16070829 Neighboring gene solute carrier family 25 member 34 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr1:16070830-16071342 Neighboring gene transmembrane protein 82

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • 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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Related articles in PubMed

  1. Functional defects in hiPSCs-derived cardiomyocytes from patients with a PLEKHM2-mutation associated with dilated cardiomyopathy and left ventricular non-compaction. Korover N, et al. Biol Res, 2023 Jun 23. PMID 37349842, Free PMC Article
  2. PLEKHM2 mutation leads to abnormal localization of lysosomes, impaired autophagy flux and associates with recessive dilated cardiomyopathy and left ventricular noncompaction. Muhammad E, et al. Hum Mol Genet, 2015 Dec 20. PMID 26464484, Free PMC Article
  3. Salmonella inhibits retrograde trafficking of mannose-6-phosphate receptors and lysosome function. McGourty K, et al. Science, 2012 Nov 16. PMID 23162002, Free PMC Article
  4. SKIP, the host target of the Salmonella virulence factor SifA, promotes kinesin-1-dependent vacuolar membrane exchanges. Dumont A, et al. Traffic, 2010 Jul 1. PMID 20406420
  5. Structural basis for kinesin-1:cargo recognition. Pernigo S, et al. Science, 2013 Apr 19. PMID 23519214, Free PMC Article

See all (27) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Two germline mutations can serve as genetic susceptibility screening makers for a lung adenocarcinoma family.
    Title: Two germline mutations can serve as genetic susceptibility screening makers for a lung adenocarcinoma family.
  2. Functional defects in hiPSCs-derived cardiomyocytes from patients with a PLEKHM2-mutation associated with dilated cardiomyopathy and left ventricular non-compaction.
    Title: Functional defects in hiPSCs-derived cardiomyocytes from patients with a PLEKHM2-mutation associated with dilated cardiomyopathy and left ventricular non-compaction.
  3. BORC complex specific components and Kinesin-1 mediate autophagy evasion by the autophagy-resistant Mycobacterium tuberculosis Beijing strain.
    Title: BORC complex specific components and Kinesin-1 mediate autophagy evasion by the autophagy-resistant Mycobacterium tuberculosis Beijing strain.
  4. The association of PLEKHM2 mutation with dilated cardiomyopathy and left ventricular noncompaction supports the importance of autophagy for normal cardiac function.
    Title: PLEKHM2 mutation leads to abnormal localization of lysosomes, impaired autophagy flux and associates with recessive dilated cardiomyopathy and left ventricular noncompaction.
  5. A dynamic process of kinesin recruitment in Salmonella-infected cells is down-regulated by the SifA-mediated recruitment of SKIP on membranes [SKIP]
    Title: The intracellular fate of Salmonella depends on the recruitment of kinesin.
Submit: New GeneRIF Correction

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)

Genotypes

HIV-1 interactions

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Replication interactions

Interaction Pubs
Knockdown of pleckstrin homology domain containing, family M (with RUN domain) member 2 (PLEKHM2) by shRNA library screening inhibits HIV-1 replication in cultured Jurkat T-cells 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

Homology

Clone Names

  • KIAA0842

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables kinesin binding IBA
Inferred from Biological aspect of Ancestor
more info
  
enables kinesin binding IDA
Inferred from Direct Assay
more info
 PubMed 
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
Process Evidence Code Pubs
involved_in Golgi organization IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in Golgi organization IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in lysosome localization IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in lysosome localization IDA
Inferred from Direct Assay
more info
 PubMed 
involved_in lysosome localization IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in natural killer cell mediated cytotoxicity IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in regulation of protein localization IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in regulation of protein localization IMP
Inferred from Mutant Phenotype
more info
 PubMed 
Component Evidence Code Pubs
is_active_in endosome membrane IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in endosome membrane IDA
Inferred from Direct Assay
more info
 PubMed 
located_in lysosomal membrane IDA
Inferred from Direct Assay
more info
 PubMed 

General protein information

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Preferred Names
pleckstrin homology domain-containing family M member 2
Names
PH domain-containing family M member 2
SifA (Salmonella-induced filaments A) and kinesin-interacting protein
novel RUN and PH domain-containing protein
pleckstrin homology domain containing, family M (with RUN domain) member 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

  1. NG_053033.1 RefSeqGene

    Range
    7815..58264
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_001410755.1 → NP_001397684.1  pleckstrin homology domain-containing family M member 2 isoform 2

    Status: REVIEWED

    Source sequence(s)
    AL121992, AL450998, AL606758
    Consensus CDS
    CCDS90868.1
    Related
    ENSP00000364950.2, ENST00000375793.2

  2. NM_015164.4 → NP_055979.2  pleckstrin homology domain-containing family M member 2 isoform 1

    See identical proteins and their annotated locations for NP_055979.2

    Status: REVIEWED

    Source sequence(s)
    AB020649, AL121992, BC040441, HY056873
    Consensus CDS
    CCDS44063.1
    UniProtKB/Swiss-Prot
    O94928, Q5VT65, Q5VVD7, Q6NUH9, Q7L8G1, Q8IVT7, Q8IWE5, Q8N2T4, Q96AY0, Q9NTF7
    UniProtKB/TrEMBL
    A0A2R8Y575
    Related
    ENSP00000364956.3, ENST00000375799.8
    Conserved Domains (3) summary
    smart00593
    Location:93 → 156
    RUN; domain involved in Ras-like GTPase signaling
    cd13309
    Location:773 → 875
    PH_SKIP; SifA and kinesin-interacting protein Pleckstrin homology (PH) domain
    pfam00169
    Location:772 → 873
    PH; PH domain

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

  1. NC_000001.11 Reference GRCh38.p14 Primary Assembly

    Range
    15681506..15734769
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_017000757.1 → XP_016856246.1  pleckstrin homology domain-containing family M member 2 isoform X1

    UniProtKB/TrEMBL
    A0A2R8Y575

  2. XM_017000758.1 → XP_016856247.1  pleckstrin homology domain-containing family M member 2 isoform X2

    UniProtKB/TrEMBL
    A0A2R8Y575

  3. XM_005245791.5 → XP_005245848.1  pleckstrin homology domain-containing family M member 2 isoform X3

    Conserved Domains (2) summary
    cd13309
    Location:570 → 672
    PH_SKIP; SifA and kinesin-interacting protein Pleckstrin homology (PH) domain
    pfam00169
    Location:569 → 670
    PH; PH domain

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060925.1 Alternate T2T-CHM13v2.0

    Range
    15125588..15179507
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054335373.1 → XP_054191348.1  pleckstrin homology domain-containing family M member 2 isoform X1

  2. XM_054335374.1 → XP_054191349.1  pleckstrin homology domain-containing family M member 2 isoform X2

  3. XM_054335375.1 → XP_054191350.1  pleckstrin homology domain-containing family M member 2 isoform X3

RNA

  1. XR_008485964.1 RNA Sequence

Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q8IWE5.2 GenPept UniProtKB/Swiss-Prot:Q8IWE5

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