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

    Gene ID: 23207, updated on 2-Nov-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
    mouse all
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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_2024_08 current GRCh38.p14 (GCF_000001405.40) 1 NC_000001.11 (15681506..15734769)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 1 NC_060925.1 (15125588..15179507)
    RS_2024_09 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 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. 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
    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. 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
    5. Two germline mutations can serve as genetic susceptibility screening makers for a lung adenocarcinoma family. Xiao N, et al. J Cancer Res Clin Oncol, 2023 Aug. PMID 36781503

    See all (30) 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_2024_08

    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

      Related
      ENSP00000520714.1, ENST00000718276.1
      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

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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