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Protein

Pleckstrin homology domain-containing family M member 1

Gene

PLEKHM1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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). Involved in vesicular transport in the osteoclast (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). 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

Regions

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

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Biological processi

Autophagy, Protein transport, Transport

Keywords - Ligandi

Metal-binding, Zinc

Enzyme and pathway databases

BioCyciZFISH:G66-33478-MONOMER.

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

HGNCiHGNC:29017. PLEKHM1.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

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.
ENSG00000276358.
ENSG00000277111.
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.

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.
HPA041005.

Interactioni

Subunit structurei

In colon carcinoma and breast carcinoma cells, it interacts with sialyl-lex-positive protein (PubMed:12820725). Interacts 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).By similarity4 Publications

Protein-protein interaction databases

BioGridi115178. 7 interactors.
IntActiQ9Y4G2. 8 interactors.
MINTiMINT-1400097.
STRINGi9606.ENSP00000389913.

Structurei

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
5DPRX-ray2.50A/B/C/D627-638[»]
A/B/C/D641-779[»]
5DPWX-ray2.19B/D/F/H/J/L/N/P629-642[»]
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

Sequence similaritiesi

Contains 2 PH domains.PROSITE-ProRule annotation
Contains 1 phorbol-ester/DAG-type zinc finger.PROSITE-ProRule annotation
Contains 1 RUN domain.PROSITE-ProRule annotation

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. 2 hits.
InterProiIPR002219. PE/DAG-bd.
IPR011993. PH_dom-like.
IPR001849. PH_domain.
IPR004012. Run_dom.
IPR025258. Zf-RING_9.
[Graphical view]
PfamiPF02759. RUN. 1 hit.
PF13901. zf-RING_9. 1 hit.
[Graphical view]
SMARTiSM00109. C1. 1 hit.
SM01175. DUF4206. 1 hit.
SM00233. PH. 2 hits.
SM00593. RUN. 1 hit.
[Graphical view]
SUPFAMiSSF50729. SSF50729. 2 hits.
PROSITEiPS50003. PH_DOMAIN. 1 hit.
PS50826. RUN. 1 hit.
PS50081. ZF_DAG_PE_2. 1 hit.
[Graphical view]

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 rs1859059dbSNPEnsembl.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

Cross-referencesi

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.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
5DPRX-ray2.50A/B/C/D627-638[»]
A/B/C/D641-779[»]
5DPWX-ray2.19B/D/F/H/J/L/N/P629-642[»]
ProteinModelPortaliQ9Y4G2.
SMRiQ9Y4G2.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi115178. 7 interactors.
IntActiQ9Y4G2. 8 interactors.
MINTiMINT-1400097.
STRINGi9606.ENSP00000389913.

PTM databases

iPTMnetiQ9Y4G2.
PhosphoSitePlusiQ9Y4G2.

Polymorphism and mutation databases

BioMutaiPLEKHM1.
DMDMi160419247.

Proteomic databases

EPDiQ9Y4G2.
MaxQBiQ9Y4G2.
PaxDbiQ9Y4G2.
PeptideAtlasiQ9Y4G2.
PRIDEiQ9Y4G2.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi9842.
DisGeNETi9842.
GeneCardsiPLEKHM1.
H-InvDBHIX0014106.
HIX0174141.
HGNCiHGNC:29017. PLEKHM1.
HPAiHPA025018.
HPA039473.
HPA041005.
MalaCardsiPLEKHM1.
MIMi611466. gene.
611497. phenotype.
neXtProtiNX_Q9Y4G2.
OpenTargetsiENSG00000225190.
ENSG00000276358.
ENSG00000277111.
Orphaneti210110. Intermediate osteopetrosis.
PharmGKBiPA134906881.
HUGEiSearch...
GenAtlasiSearch...

Phylogenomic databases

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

Enzyme and pathway databases

BioCyciZFISH:G66-33478-MONOMER.

Miscellaneous databases

ChiTaRSiPLEKHM1. human.
GeneWikiiPLEKHM1.
GenomeRNAii9842.
PROiQ9Y4G2.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000225190.
CleanExiHS_PLEKHM1.
ExpressionAtlasiQ9Y4G2. baseline and differential.
GenevisibleiQ9Y4G2. HS.

Family and domain databases

CDDicd00029. C1. 1 hit.
Gene3Di2.30.29.30. 2 hits.
InterProiIPR002219. PE/DAG-bd.
IPR011993. PH_dom-like.
IPR001849. PH_domain.
IPR004012. Run_dom.
IPR025258. Zf-RING_9.
[Graphical view]
PfamiPF02759. RUN. 1 hit.
PF13901. zf-RING_9. 1 hit.
[Graphical view]
SMARTiSM00109. C1. 1 hit.
SM01175. DUF4206. 1 hit.
SM00233. PH. 2 hits.
SM00593. RUN. 1 hit.
[Graphical view]
SUPFAMiSSF50729. SSF50729. 2 hits.
PROSITEiPS50003. PH_DOMAIN. 1 hit.
PS50826. RUN. 1 hit.
PS50081. ZF_DAG_PE_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiPKHM1_HUMAN
AccessioniPrimary (citable) accession number: Q9Y4G2
Secondary accession number(s): Q6P2R5
, Q8TEL9, Q9NPP5, Q9NYA0
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 13, 2007
Last sequence update: November 13, 2007
Last modified: November 30, 2016
This is version 124 of the entry and version 3 of the sequence. [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

Miscellaneous

Sialyl-lex is a carcinoma associated antigen.

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
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.