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Protein

Pleckstrin homology domain-containing family M member 1

Gene

PLEKHM1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Proposed to act as a multivalent adapter protein that regulates Rab7-dependent and HOPS complex-dependent fusion events in the endolysosomal system and couples autophagic and the endocytic trafficking pathways. Required for late stages of endolysosomal maturation, facilitating both endocytosis-mediated degradation of growth factor receptors and autophagosome clearance. Seems to be involved in the terminal maturation of autophagosomes and to mediate autophagosome-lysosome fusion (PubMed:25498145). Positively regulates lysosome peripheral distribution and ruffled border formation in osteoclasts (By similarity). May be involved in negative regulation of endocytic transport from early endosome to late endosome/lysosome implicating its association with Rab7 (PubMed:20943950). May have a role in sialyl-lex-mediated transduction of apoptotic signals (PubMed:12820725). Involved in bone resorption (By similarity). In case of infection contributes to Salmonella typhimurium pathogenesis by supporting the integrity of the Salmonella-containing vacuole (SCV) probably in concert with the HOPS complex and Rab7 (PubMed:25500191).By similarityCurated4 Publications

Miscellaneous

Sialyl-lex is a carcinoma associated antigen.

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri986 – 1040Phorbol-ester/DAG-typePROSITE-ProRule annotationAdd BLAST55

GO - Molecular functioni

GO - Biological processi

Keywordsi

Biological processAutophagy, Protein transport, Transport
LigandMetal-binding, Zinc

Names & Taxonomyi

Protein namesi
Recommended name:
Pleckstrin homology domain-containing family M member 1
Short name:
PH domain-containing family M member 1
Alternative name(s):
162 kDa adapter protein
Short name:
AP162
Gene namesi
Name:PLEKHM1
Synonyms:KIAA0356
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 17

Organism-specific databases

EuPathDBiHostDB:ENSG00000225190.8
HGNCiHGNC:29017 PLEKHM1
MIMi611466 gene
neXtProtiNX_Q9Y4G2

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Endosome, Lysosome, Membrane

Pathology & Biotechi

Involvement in diseasei

Osteopetrosis, autosomal recessive 6 (OPTB6)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA rare genetic disease characterized by abnormally dense bone, due to defective resorption of immature bone. Osteopetrosis occurs in two forms: a severe autosomal recessive form occurring in utero, infancy, or childhood, and a benign autosomal dominant form occurring in adolescence or adulthood. Recessive osteopetrosis commonly manifests in early infancy with macrocephaly, feeding difficulties, evolving blindness and deafness, bone marrow failure, severe anemia, and hepatosplenomegaly. Deafness and blindness are generally thought to represent effects of pressure on nerves.
See also OMIM:611497

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi720 – 722Missing : Disrupts interaction with RAB7A. 1 Publication3
Mutagenesisi729E → A: Disrupts interaction with RAB7A. 1 Publication1
Mutagenesisi769R → A: Disrupts interaction with RAB7A. 1 Publication1
Mutagenesisi1021C → G: Disrupts interaction with Rab7 and no localization to endososmal membranes; when associated with G-1024, L-1029 and G-1032. 1 Publication1
Mutagenesisi1024C → G: Disrupts interaction with Rab7 and no localization to endososmal membranes; when associated with G-1021, L-1029 and G-1032. 1 Publication1
Mutagenesisi1029H → L: Disrupts interaction with Rab7 and no localization to endososmal membranes; when associated with G-1021, G-1024 and G-1032. 1 Publication1
Mutagenesisi1032C → G: Disrupts interaction with Rab7and no localization to endososmal membranes; when associated with G-1021, G-1024 and L-1029. 1 Publication1

Keywords - Diseasei

Osteopetrosis

Organism-specific databases

DisGeNETi9842
MalaCardsiPLEKHM1
MIMi611497 phenotype
OpenTargetsiENSG00000225190
Orphaneti210110 Intermediate osteopetrosis
PharmGKBiPA134906881

Polymorphism and mutation databases

BioMutaiPLEKHM1
DMDMi160419247

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00003093351 – 1056Pleckstrin homology domain-containing family M member 1Add BLAST1056

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei219PhosphoserineBy similarity1
Modified residuei432PhosphoserineCombined sources1
Modified residuei435PhosphoserineBy similarity1
Modified residuei490PhosphoserineBy similarity1

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ9Y4G2
MaxQBiQ9Y4G2
PaxDbiQ9Y4G2
PeptideAtlasiQ9Y4G2
PRIDEiQ9Y4G2
ProteomicsDBi86202

PTM databases

iPTMnetiQ9Y4G2
PhosphoSitePlusiQ9Y4G2

Expressioni

Tissue specificityi

Expressed in placenta, liver, prostate, thymus, spleen, ovary, colon, colon carcinoma and peripheral blood lymphocytes (PBL). Weakly expressed in brain, lung, kidney, and testis. No expression in heart, skeletal muscle, pancreas and small intestine. Predominantly expressed in the breast carcinoma cell line MCF-7.2 Publications

Gene expression databases

BgeeiENSG00000225190
CleanExiHS_PLEKHM1
ExpressionAtlasiQ9Y4G2 baseline and differential
GenevisibleiQ9Y4G2 HS

Organism-specific databases

HPAiHPA025018
HPA039473

Interactioni

Subunit structurei

Interacts (via N- and C-terminus) with RAB7A (GTP-bound form) (PubMed:20943950, PubMed:25500191). Interacts with VPS41, VPS11 and VPS39; indicative for an association with the HOPS complex; the interaction with VPS41 seems to require RAB7A (PubMed:25500191, PubMed:25498145). Interacts with GABARAP, GABARAPL, GABARAPL2, MAP1LC3A, MAP1LC3B and MAP1LC3C (PubMed:25498145). Interacts with PAFAH1B (By similarity). Interacts with Salmonella typhimurium sifA (PubMed:25500191). Interacts (via N- and C-terminus) with NDEL1 (By similarity). Interacts (via C-terminus) with MAP3K7 (By similarity). Interacts (via N- and C-terminus) with FAM98A (By similarity). Interacts (via C-terminus) with DEF8; this interaction is weak but increased in a RAB7A-dependent manner (By similarity). In colon carcinoma and breast carcinoma cells, it interacts with sialyl-lex-positive protein (PubMed:12820725).By similarity4 Publications

Protein-protein interaction databases

BioGridi115178, 8 interactors
IntActiQ9Y4G2, 8 interactors
MINTiQ9Y4G2
STRINGi9606.ENSP00000389913

Structurei

Secondary structure

11056
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi635 – 637Combined sources3

3D structure databases

ProteinModelPortaliQ9Y4G2
SMRiQ9Y4G2
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini41 – 183RUNPROSITE-ProRule annotationAdd BLAST143
Domaini534 – 625PH 1PROSITE-ProRule annotationAdd BLAST92
Domaini683 – 777PH 2PROSITE-ProRule annotationAdd BLAST95

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni654 – 1056Interaction with RAB7A1 PublicationAdd BLAST403

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi632 – 638LIRCurated7

Domaini

The LIR (LC3-interacting region) motif mediates the interaction with ATG8 family proteins GABARAP, GABARAPL, GABARAPL2, and LC3A/B/C.1 Publication

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri986 – 1040Phorbol-ester/DAG-typePROSITE-ProRule annotationAdd BLAST55

Keywords - Domaini

Repeat, Zinc-finger

Phylogenomic databases

eggNOGiENOG410ITGM Eukaryota
ENOG4111EZ2 LUCA
GeneTreeiENSGT00550000074570
HOGENOMiHOG000247013
HOVERGENiHBG056799
InParanoidiQ9Y4G2
OMAiPAFFKII
OrthoDBiEOG091G013Y
PhylomeDBiQ9Y4G2
TreeFamiTF317067

Family and domain databases

CDDicd00029 C1, 1 hit
Gene3Di2.30.29.30, 1 hit
InterProiView protein in InterPro
IPR002219 PE/DAG-bd
IPR011993 PH-like_dom_sf
IPR001849 PH_domain
IPR004012 Run_dom
IPR037213 Run_dom_sf
IPR025258 Zf-RING_9
PfamiView protein in Pfam
PF02759 RUN, 1 hit
PF13901 zf-RING_9, 1 hit
SMARTiView protein in SMART
SM00109 C1, 1 hit
SM01175 DUF4206, 1 hit
SM00233 PH, 2 hits
SM00593 RUN, 1 hit
SUPFAMiSSF140741 SSF140741, 1 hit
PROSITEiView protein in PROSITE
PS50003 PH_DOMAIN, 1 hit
PS50826 RUN, 1 hit
PS50081 ZF_DAG_PE_2, 1 hit

Sequencei

Sequence statusi: Complete.

Q9Y4G2-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MLSVVENGLD PQAAIPVIKK KLVGSVKALQ KQYVSLDTVV TSEDGDANTM
60 70 80 90 100
CSALEAVFIH GLHAKHIRAE AGGKRKKSAH QKPLPQPVFW PLLKAVTHKH
110 120 130 140 150
IISELEHLTF VNTDVGRCRA WLRLALNDGL MECYLKLLLQ EQARLHEYYQ
160 170 180 190 200
PTALLRDAEE GEFLLSFLQG LTSLSFELSY KSAILNEWTL TPLALSGLCP
210 220 230 240 250
LSELDPLSTS GAELQRKESL DSISHSSGSE DIEVHHSGHK IRRNQKLTAS
260 270 280 290 300
SLSLDTASSS QLSCSLNSDS CLLQENGSKS PDHCEEPMSC DSDLGTANAE
310 320 330 340 350
DSDRSLQEVL LEFSKAQVNS VPTNGLSQET EIPTPQASLS LHGLNTSTYL
360 370 380 390 400
HCEAPAEPLP AQAASGTQDG VHVQEPRPQA PSPLDLQQPV ESTSGQQPSS
410 420 430 440 450
TVSETAREVG QGNGLQKAQA HDGAGLKLVV SSPTSPKNKS WISEDDFYRP
460 470 480 490 500
SREQPLESAS DHPIASYRGT PGSRPGLHRH FSQEPRKNCS LGALDQACVP
510 520 530 540 550
SPGRRQAQAA PSQGHKSFRV VHRRQMGLSN PFRGLMKLGT VERRGAMGIW
560 570 580 590 600
KELFCELSPL EFRLYLSNEE HTCVENCSLL RCESVGPAHS DGRFELVFSG
610 620 630 640 650
KKLALRASSQ DEAEDWLDRV REALQKVRPQ QEDEWVNVQY PDQPEEPPEA
660 670 680 690 700
PQGCLSPSDL LSEPAALQGT QFDWSSAQVP EPDAIKESLL YLYMDRTWMP
710 720 730 740 750
YIFSLSLEAL KCFRIRNNEK MLSDSHGVET IRDILPDTSL GGPSFFKIIT
760 770 780 790 800
AKAVLKLQAG NAEEAALWRD LVRKVLASYL ETAEEAVTLG GSLDENCQEV
810 820 830 840 850
LKFATRENGF LLQYLVAIPM EKGLDSQGCF CAGCSRQIGF SFVRPKLCAF
860 870 880 890 900
SGLYYCDICH QDDASVIPAR IIHNWDLTKR PICRQALKFL TQIRAQPLIN
910 920 930 940 950
LQMVNASLYE HVERMHLIGR RREQLKLLGD YLGLCRSGAL KELSKRLNHR
960 970 980 990 1000
NYLLESPHRF SVADLQQIAD GVYEGFLKAL IEFASQHVYH CDLCTQRGFI
1010 1020 1030 1040 1050
CQICQHHDII FPFEFDTTVR CAECKTVFHQ SCQAVVKKGC PRCARRRKYQ

EQNIFA
Length:1,056
Mass (Da):117,443
Last modified:November 13, 2007 - v3
Checksum:i24004093CFA89079
GO

Sequence cautioni

The sequence BAA20813 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated
The sequence CAB91652 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti429 – 436VVSSPTSP → GLRPVSAR in BAB84929 (Ref. 4) Curated8
Sequence conflicti817A → G in BAB84929 (Ref. 4) Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_036932377R → H. Corresponds to variant dbSNP:rs1859059Ensembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB002354 mRNA Translation: BAA20813.2 Different initiation.
BC064361 mRNA Translation: AAH64361.1
AJ002220 mRNA Translation: CAB91652.1 Different initiation.
AK074103 mRNA Translation: BAB84929.1
AL389948 mRNA Translation: CAB97526.1
CCDSiCCDS32671.1
RefSeqiNP_055613.1, NM_014798.2
XP_006722264.1, XM_006722201.3
XP_011523825.1, XM_011525523.2
XP_011523826.1, XM_011525524.1
XP_016880940.1, XM_017025451.1
XP_016880942.1, XM_017025453.1
UniGeneiHs.514242

Genome annotation databases

EnsembliENST00000430334; ENSP00000389913; ENSG00000225190
ENST00000613787; ENSP00000479066; ENSG00000277111
ENST00000617688; ENSP00000483820; ENSG00000276358
GeneIDi9842
KEGGihsa:9842
UCSCiuc002ija.4 human

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Entry informationi

Entry nameiPKHM1_HUMAN
AccessioniPrimary (citable) accession number: Q9Y4G2
Secondary accession number(s): Q6P2R5
, Q8TEL9, Q9NPP5, Q9NYA0
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 13, 2007
Last sequence update: November 13, 2007
Last modified: July 18, 2018
This is version 137 of the entry and version 3 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 17
    Human chromosome 17: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references

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