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Protein

Lysosomal-associated transmembrane protein 4B

Gene

Laptm4b

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: -Experimental evidence at transcript leveli

Functioni

Required for optimal lysosomal function. Blocks EGF-stimulated EGFR intraluminal sorting and degradation. Conversely by binding with the phosphatidylinositol 4,5-bisphosphate, regulates its PIP5K1C interaction, inhibits HGS ubiquitination and relieves LAPTM4B inhibition of EGFR degradation. Recruits SLC3A2 and SLC7A5 (the Leu transporter) to the lysosome, promoting entry of leucine and other essential amino acid (EAA) into the lysosome, stimulating activation of proton-transporting vacuolar (V)-ATPase protein pump (V-ATPase) and hence mTORC1 activation. Plays a role as negative regulator of TGFB1 production in regulatory T cells. Binds ceramide and facilitates its exit from late endosome in order to control cell death pathways.By similarity

GO - Molecular functioni

GO - Biological processi

Keywordsi

Biological processTransport

Names & Taxonomyi

Protein namesi
Recommended name:
Lysosomal-associated transmembrane protein 4BBy similarity
Gene namesi
Name:Laptm4bImported
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 7

Organism-specific databases

RGDi1311853 Laptm4b

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

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Transmembranei26 – 46HelicalSequence analysisAdd BLAST21
Transmembranei72 – 92HelicalSequence analysisAdd BLAST21
Transmembranei100 – 120HelicalSequence analysisAdd BLAST21
Transmembranei153 – 173HelicalSequence analysisAdd BLAST21

Keywords - Cellular componenti

Cell membrane, Cell projection, Endosome, Lysosome, Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002497241 – 227Lysosomal-associated transmembrane protein 4BAdd BLAST227

Post-translational modificationi

Undergoes proteolytic cleavage following delivery to the lysosomes.By similarity
Ubiquitinated by NEDD4.By similarity

Keywords - PTMi

Ubl conjugation

Proteomic databases

PaxDbiQ5U1W4
PRIDEiQ5U1W4

Expressioni

Gene expression databases

BgeeiENSRNOG00000006766 Expressed in 10 organ(s), highest expression level in testis
GenevisibleiQ5U1W4 RN

Interactioni

Subunit structurei

Homooligomer; upon reaching the lysosomes. Interacts with MCOLN1. Interacts with NEDD4; may play a role in the lysosomal sorting of LAPTM4B; enhances HGS association with NEDD4; mediates inhibition of EGFR degradation. Interacts with PIP5K1C; promotes SNX5 association with LAPTM4B; kinase activity of PIP5K1C is required; interaction is regulated by phosphatidylinositol 4,5-bisphosphate generated by PIP5K1C. Interacts with HGS; promotes HGS ubiquitination. Interacts with SNX5. Interacts with SLC3A2 AND SLC7A5; recruits SLC3A2 and SLC7A5 to lysosomes to promote leucine uptake into these organelles and is required for mTORC1 activation. Interacts with LRRC32; decreases TGFB1 production in regulatory T cells. Interacts with BECN1; competes with EGFR for LAPTM4B binding; regulates EGFR activity. Interacts with EGFR; positively correlates with EGFR activation.By similarity

GO - Molecular functioni

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000008969

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni205 – 222Required for NEDD4 interactionBy similarityAdd BLAST18

Sequence similaritiesi

Belongs to the LAPTM4/LAPTM5 transporter family.Curated

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410IGWG Eukaryota
ENOG4111K1Z LUCA
GeneTreeiENSGT00390000013359
HOGENOMiHOG000007698
HOVERGENiHBG000908
InParanoidiQ5U1W4
KOiK12387
OMAiTEVLVYV
OrthoDBiEOG091G0MA5
PhylomeDBiQ5U1W4
TreeFamiTF330843

Family and domain databases

InterProiView protein in InterPro
IPR004687 LAPTM4/5
IPR018401 Lysosomal-assoc_TM_prot4B
PANTHERiPTHR12479:SF6 PTHR12479:SF6, 1 hit
PfamiView protein in Pfam
PF03821 Mtp, 1 hit

Sequencei

Sequence statusi: Complete.

Q5U1W4-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MKMVAPWTRF YSHSCCLCCH VRTGTILLGI WYLIINAVVL LILLSALADP
60 70 80 90 100
DQYHFSGSEL GGEFEFMDDA NMCIAIAISL LMILICAMAT YGAYKQHAAW
110 120 130 140 150
IIPFFCYQIF DFALNTLVAI TVLVYPNSIQ EYIRQLPPSF PYRDDIMSVN
160 170 180 190 200
PTCLVLVILL FIGIILTFKG YLISCVWSCY RYINGRNSSD VLVYVTSNDT
210 220
TVLLPPYDDA TAVTGTAKEP PPPYVSA
Length:227
Mass (Da):25,404
Last modified:December 7, 2004 - v1
Checksum:i502B649C22D1C421
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
BC086442 mRNA Translation: AAH86442.1
RefSeqiNP_001013192.1, NM_001013174.1
UniGeneiRn.8123

Genome annotation databases

EnsembliENSRNOT00000008969; ENSRNOP00000008969; ENSRNOG00000006766
GeneIDi315047
KEGGirno:315047
UCSCiRGD:1311853 rat

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
BC086442 mRNA Translation: AAH86442.1
RefSeqiNP_001013192.1, NM_001013174.1
UniGeneiRn.8123

3D structure databases

ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000008969

Proteomic databases

PaxDbiQ5U1W4
PRIDEiQ5U1W4

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSRNOT00000008969; ENSRNOP00000008969; ENSRNOG00000006766
GeneIDi315047
KEGGirno:315047
UCSCiRGD:1311853 rat

Organism-specific databases

CTDi55353
RGDi1311853 Laptm4b

Phylogenomic databases

eggNOGiENOG410IGWG Eukaryota
ENOG4111K1Z LUCA
GeneTreeiENSGT00390000013359
HOGENOMiHOG000007698
HOVERGENiHBG000908
InParanoidiQ5U1W4
KOiK12387
OMAiTEVLVYV
OrthoDBiEOG091G0MA5
PhylomeDBiQ5U1W4
TreeFamiTF330843

Miscellaneous databases

PROiPR:Q5U1W4

Gene expression databases

BgeeiENSRNOG00000006766 Expressed in 10 organ(s), highest expression level in testis
GenevisibleiQ5U1W4 RN

Family and domain databases

InterProiView protein in InterPro
IPR004687 LAPTM4/5
IPR018401 Lysosomal-assoc_TM_prot4B
PANTHERiPTHR12479:SF6 PTHR12479:SF6, 1 hit
PfamiView protein in Pfam
PF03821 Mtp, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiLAP4B_RAT
AccessioniPrimary (citable) accession number: Q5U1W4
Entry historyiIntegrated into UniProtKB/Swiss-Prot: September 19, 2006
Last sequence update: December 7, 2004
Last modified: November 7, 2018
This is version 87 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. SIMILARITY comments
    Index of protein domains and families
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Main funding by: National Institutes of Health

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