PLEKHM2

Protein identityUniProt · HPA

UniProt accession

Q8IWE5

Gene

PLEKHM2

Ensembl

ENSG00000116786

Chromosome

1

Canonical length

1019 aa

Protein class

Predicted intracellular proteins

OverviewNCBI Gene

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]

Canonical amino-acid sequenceUniProt

1019 residues, UniProt reviewed canonical sequence.

>Q8IWE5|PLEKHM2
     1  MEPGEVKDRI LENISLSVKK LQSYFAACED EIPAIRNHDK VLQRLCEHLD HALLYGLQDL
    61  SSGYWVLVVH FTRREAIKQI EVLQHVATNL GRSRAWLYLA LNENSLESYL RLFQENLGLL
   121  HKYYVKNALV CSHDHLTLFL TLVSGLEFIR FELDLDAPYL DLAPYMPDYY KPQYLLDFED
   181  RLPSSVHGSD SLSLNSFNSV TSTNLEWDDS AIAPSSEDYD FGDVFPAVPS VPSTDWEDGD
   241  LTDTVSGPRS TASDLTSSKA STRSPTQRQN PFNEEPAETV SSSDTTPVHT TSQEKEEAQA
   301  LDPPDACTEL EVIRVTKKKK IGKKKKSRSD EEASPLHPAC SQKKCAKQGD GDSRNGSPSL
   361  GRDSPDTMLA SPQEEGEGPS STTESSERSE PGLLIPEMKD TSMERLGQPL SKVIDQLNGQ
   421  LDPSTWCSRA EPPDQSFRTG SPGDAPERPP LCDFSEGLSA PMDFYRFTVE SPSTVTSGGG
   481  HHDPAGLGQP LHVPSSPEAA GQEEEGGGGE GQTPRPLEDT TREAQELEAQ LSLVREGPVS
   541  EPEPGTQEVL CQLKRDQPSP CLSSAEDSGV DEGQGSPSEM VHSSEFRVDN NHLLLLMIHV
   601  FRENEEQLFK MIRMSTGHME GNLQLLYVLL TDCYVYLLRK GATEKPYLVE EAVSYNELDY
   661  VSVGLDQQTV KLVCTNRRKQ FLLDTADVAL AEFFLASLKS AMIKGCREPP YPSILTDATM
   721  EKLALAKFVA QESKCEASAV TVRFYGLVHW EDPTDESLGP TPCHCSPPEG TITKEGMLHY
   781  KAGTSYLGKE HWKTCFVVLS NGILYQYPDR TDVIPLLSVN MGGEQCGGCR RANTTDRPHA
   841  FQVILSDRPC LELSAESEAE MAEWMQHLCQ AVSKGVIPQG VAPSPCIPCC LVLTDDRLFT
   901  CHEDCQTSFF RSLGTAKLGD ISAVSTEPGK EYCVLEFSQD SQQLLPPWVI YLSCTSELDR
   961  LLSALNSGWK TIYQVDLPHT AIQEASNKKK FEDALSLIHS AWQRSDSLCR GRASRDPWC

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against PLEKHM2 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Other membrane

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.45

Highest tissue expression

159 nTPM

Expression across tissuesHPA

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.54

gnomAD pLI

0

gnomAD missense Z

2

DepMap mean gene effect

-0.07

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 5% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• Golgi organization
• lysosome localization
• natural killer cell mediated cytotoxicity
• regulation of protein localization

Molecular functions

• kinesin binding

Cellular components

• endosome membrane
• lysosomal membrane

Protein domainsUniProt · Pfam · InterPro

• Pleckstrin homology domain
• RUN domain
• PH-like domain superfamily
• RUN domain superfamily
• PLEKHM2, PH domain-like
• PH domain
• RUN domain
• PLEKHM2 PH domain-like
• PLEKHM2, RUN domain
• Pleckstrin homology domain-containing protein M2

KeywordsUniProt

• Acetylation
• Cytoplasm
• Lysosome
• Membrane
• Phosphoprotein

InteractionsUniProt · HPA

Protein binding partners of PLEKHM2 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• ARL8A
• BORCS5
• KIF5B
• KLC2
• VPS39