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

Summary

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

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_000001.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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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?

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.
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.
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.
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.
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.

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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

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 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

SHGC-74261 (e-PCR)
- UniSTS:80208

MARC_16951-16952:1020776560:5 (e-PCR)
- UniSTS:268161

D1S3097 (e-PCR)
- UniSTS:154565

SHGC-74256 (e-PCR)
- UniSTS:13006

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

NG_053033.1 RefSeqGene

Range

7815..58264

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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
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

NC_000001.11 Reference GRCh38.p14 Primary Assembly

Range

15681506..15734769

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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

UniProtKB/TrEMBL

A0A2R8Y575
XM_017000758.1 → XP_016856247.1 pleckstrin homology domain-containing family M member 2 isoform X2

UniProtKB/TrEMBL

A0A2R8Y575
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

NC_060925.1 Alternate T2T-CHM13v2.0

Range

15125588..15179507

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_054335373.1 → XP_054191348.1 pleckstrin homology domain-containing family M member 2 isoform X1
XM_054335374.1 → XP_054191349.1 pleckstrin homology domain-containing family M member 2 isoform X2
XM_054335375.1 → XP_054191350.1 pleckstrin homology domain-containing family M member 2 isoform X3