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Protein

Pleckstrin homology domain-containing family M member 1

Gene

Plekhm1

Organism
Mus musculus (Mouse)
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 (PubMed:27777970). May be involved in negative regulation of endocytic transport from early endosome to late endosome/lysosome implicating its association with Rab7 (By similarity). May have a role in sialyl-lex-mediated transduction of apoptotic signals (By similarity). Involved in bone resorption (PubMed:27777970).By similarityCurated2 Publications

Miscellaneous

Sialyl-lex is a carcinoma associated antigen.

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri1004 – 1058Phorbol-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
Gene namesi
Name:Plekhm1
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 11

Organism-specific databases

MGIiMGI:2443207 Plekhm1

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

Disruption phenotypei

Osteoclast-specific conditional knockout mice show normal tooth eruption, developed normally and are fertile, but trabecular bone mass in long bones and vertebrae is increased (PubMed:27777970). Osteoclast differentiation and number are normal, but bone resorption is decreased (PubMed:27777970). Show mislocalization of osteoclast lysosomes at the perinuclear area, instead at the cell periphery, and decreased ruffled border formation (PubMed:27777970).1 Publication

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi714R → C: No change in osteoclast formation and bone resorption. 1 Publication1
Mutagenesisi949 – 950YL → AA: Decreases interaction with RAB7A. 1 Publication2

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00003093361 – 1074Pleckstrin homology domain-containing family M member 1Add BLAST1074

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei218PhosphoserineCombined sources1
Modified residuei433PhosphoserineBy similarity1
Modified residuei436PhosphoserineCombined sources1
Modified residuei491PhosphoserineCombined sources1

Keywords - PTMi

Phosphoprotein

Proteomic databases

MaxQBiQ7TSI1
PaxDbiQ7TSI1
PeptideAtlasiQ7TSI1
PRIDEiQ7TSI1

PTM databases

iPTMnetiQ7TSI1
PhosphoSitePlusiQ7TSI1

Expressioni

Gene expression databases

BgeeiENSMUSG00000034247 Expressed in 198 organ(s), highest expression level in mesenteric lymph node
ExpressionAtlasiQ7TSI1 baseline and differential
GenevisibleiQ7TSI1 MM

Interactioni

Subunit structurei

Interacts with VPS41, VPS11 and VPS39; indicative for an association with the HOPS complex; the interaction with VPS41 seems to require RAB7A. Interacts with GABARAP, GABARAPL, GABARAPL2, MAP1LC3A, MAP1LC3B and MAP1LC3C (By similarity). Interacts with PAFAH1B1; detected in osteoblasts (PubMed:22073305). Interacts (via N- and C-terminus) with NDEL1 (PubMed:27777970). Interacts (via C-terminus) with MAP3K7 (PubMed:27777970). Interacts (via N- and C-terminus) with FAM98A (PubMed:27777970). Interacts (via C-terminus) with DEF8; this interaction is weak but increased in a RAB7A-dependent manner (PubMed:27777970). Interacts (via N- and C-terminus) with RAB7A (GTP-bound form) (PubMed:27777970). May interact with sialyl-lex positive protein (By similarity).By similarity2 Publications

Protein-protein interaction databases

IntActiQ7TSI1, 1 interactor
STRINGi10090.ENSMUSP00000047327

Structurei

3D structure databases

ProteinModelPortaliQ7TSI1
SMRiQ7TSI1
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini40 – 182RUNPROSITE-ProRule annotationAdd BLAST143
Domaini551 – 642PH 1PROSITE-ProRule annotationAdd BLAST92
Domaini701 – 795PH 2PROSITE-ProRule annotationAdd BLAST95

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni672 – 1074Interaction with RAB7ABy similarityAdd BLAST403

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi649 – 655LIRBy similarity7

Domaini

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

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri1004 – 1058Phorbol-ester/DAG-typePROSITE-ProRule annotationAdd BLAST55

Keywords - Domaini

Repeat, Zinc-finger

Phylogenomic databases

eggNOGiENOG410KDQT Eukaryota
ENOG4111EZ2 LUCA
GeneTreeiENSGT00550000074570
HOGENOMiHOG000247013
HOVERGENiHBG056799
InParanoidiQ7TSI1
OMAiNHGLLEC
OrthoDBiEOG091G013Y
PhylomeDBiQ7TSI1
TreeFamiTF317067

Family and domain databases

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, 2 hits
PS50826 RUN, 1 hit
PS50081 ZF_DAG_PE_2, 1 hit

Sequence (1+)i

Sequence statusi: Complete.

This entry has 1 described isoform and 1 potential isoform that is computationally mapped.Show allAlign All

Q7TSI1-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MLSVENGLDP RAAIQVIKKK LVGSVKALQK QHVSLDTVVT SEDGDANTMC
60 70 80 90 100
SALEAVFIHG LHAKHIRAEA GGKRKKHTHQ KALPQPVFWP LLKAITHRHI
110 120 130 140 150
VSDLEHLVFI NTDVGRCRAW LRLALNDGLM ECYLKLLLQE PARLCEYYQP
160 170 180 190 200
TALLRDAEEA EFLLSFLQGL TSLSFELSYK SAILNEWTLT PLSLSGLCPL
210 220 230 240 250
SELDPLTTSG AELQRKESLD SISHSSGSED IEVQHSGHKI RRNRKLTASS
260 270 280 290 300
LSLDTASSSQ LSCSLNSDSC LLQENGPKSP DHSEEPMSYD SDLGMANTDD
310 320 330 340 350
PDRSLQEVLS EFSKAQVNSA PSSGPNQEPD TPMFQTPLSL HSLATSTHLH
360 370 380 390 400
FEGSEELFPA HKSSGTSSGG HKHQLLPQET PDEKQLGTAQ AGPAQSTSDQ
410 420 430 440 450
QPSSPVGGAA GQGSGPWKAL EYGRVGPKLV VSSPTSPKGK SWISEDDFCR
460 470 480 490 500
PPQEPALKSA AGLCTSPVQD TPESRAALHG PFSQGPRKSC SLGALDKACV
510 520 530 540 550
PSQACGNAQP APAPAPAPAP APAPAPGVTQ DHKNFCVVHR RQMGLSNPFR
560 570 580 590 600
GLMKLGTVAR RGAMGIWKEF FCELSPLEFR LYLSDEERTC VESCSLLRCE
610 620 630 640 650
AVGPAHSDGR FELVFSGKKL ALRASSQDEA EDWLDRVREA LQKVRPQQED
660 670 680 690 700
EWVNIQYPDQ AEDAPEAPPD SLPPYSTLLP EPAGAQGMQL DWTSAQVPEP
710 720 730 740 750
DAIKESLLYL YADRTWVPYI FSLSLESLKC FRVRNNEKML SDSHGVETIR
760 770 780 790 800
DILPDTSLGG PAFFKIITAK AVLKLQAKNT EEATHWRDLV RKVLASYLES
810 820 830 840 850
AEEAVTLGGS LDEKCQEVLK FATRENGFLL QYLVAIPTEK GLDSQGCFCA
860 870 880 890 900
GCSRQIGFSF VRPKLCAFSG LYYCDFCHQD DASVIPARII HNWDLTKRPV
910 920 930 940 950
CRQALKFLAQ IRAQPLINLQ LVNASLYEHV ERMHLIGRSR EQLKLLGDYL
960 970 980 990 1000
GLCRSGALKE LCKRLSHRNY LLESPHRFSV ADLQQIAEGV YEGFLKALIE
1010 1020 1030 1040 1050
FASQHVYHCD LCTQRGFICQ ICHHQDIIFP FEFDTTVRCA ECRTVFHQSC
1060 1070
QAVVRKGCPR CARRRKYQEQ NVVS
Length:1,074
Mass (Da):118,535
Last modified:October 1, 2003 - v1
Checksum:i56EDA05514E4B9F9
GO

Computationally mapped potential isoform sequencesi

There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
V9GWX7V9GWX7_MOUSE
Pleckstrin homology domain-containi...
Plekhm1
47Annotation score:

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti742 – 744DSH → TRP in AAH38943 (PubMed:15489334).Curated3
Sequence conflicti768T → S in BAE32773 (PubMed:16141072).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK154703 mRNA Translation: BAE32773.1
AL772325, AL929552 Genomic DNA Translation: CAM16600.1
AL929552, AL772325 Genomic DNA Translation: CAM17476.1
BC038943 mRNA Translation: AAH38943.1
BC053079 mRNA Translation: AAH53079.1
CCDSiCCDS25518.1
RefSeqiNP_898855.1, NM_183034.1
UniGeneiMm.383308
Mm.444201

Genome annotation databases

EnsembliENSMUST00000041272; ENSMUSP00000047327; ENSMUSG00000034247
GeneIDi353047
KEGGimmu:353047
UCSCiuc007lug.1 mouse

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK154703 mRNA Translation: BAE32773.1
AL772325, AL929552 Genomic DNA Translation: CAM16600.1
AL929552, AL772325 Genomic DNA Translation: CAM17476.1
BC038943 mRNA Translation: AAH38943.1
BC053079 mRNA Translation: AAH53079.1
CCDSiCCDS25518.1
RefSeqiNP_898855.1, NM_183034.1
UniGeneiMm.383308
Mm.444201

3D structure databases

ProteinModelPortaliQ7TSI1
SMRiQ7TSI1
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiQ7TSI1, 1 interactor
STRINGi10090.ENSMUSP00000047327

PTM databases

iPTMnetiQ7TSI1
PhosphoSitePlusiQ7TSI1

Proteomic databases

MaxQBiQ7TSI1
PaxDbiQ7TSI1
PeptideAtlasiQ7TSI1
PRIDEiQ7TSI1

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000041272; ENSMUSP00000047327; ENSMUSG00000034247
GeneIDi353047
KEGGimmu:353047
UCSCiuc007lug.1 mouse

Organism-specific databases

CTDi9842
MGIiMGI:2443207 Plekhm1

Phylogenomic databases

eggNOGiENOG410KDQT Eukaryota
ENOG4111EZ2 LUCA
GeneTreeiENSGT00550000074570
HOGENOMiHOG000247013
HOVERGENiHBG056799
InParanoidiQ7TSI1
OMAiNHGLLEC
OrthoDBiEOG091G013Y
PhylomeDBiQ7TSI1
TreeFamiTF317067

Miscellaneous databases

ChiTaRSiPlekhm1 mouse
PROiPR:Q7TSI1
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000034247 Expressed in 198 organ(s), highest expression level in mesenteric lymph node
ExpressionAtlasiQ7TSI1 baseline and differential
GenevisibleiQ7TSI1 MM

Family and domain databases

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, 2 hits
PS50826 RUN, 1 hit
PS50081 ZF_DAG_PE_2, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiPKHM1_MOUSE
AccessioniPrimary (citable) accession number: Q7TSI1
Secondary accession number(s): Q3U3L2, Q8CHU5
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 13, 2007
Last sequence update: October 1, 2003
Last modified: November 7, 2018
This is version 116 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
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Main funding by: National Institutes of Health

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