Q86VI4 · LAP4B_HUMAN
- ProteinLysosomal-associated transmembrane protein 4B
- GeneLAPTM4B
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids317 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Required for optimal lysosomal function (PubMed:21224396).
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 (PubMed:25588945).
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 (PubMed:25998567).
Plays a role as negative regulator of TGFB1 production in regulatory T cells (PubMed:26126825).
Binds ceramide and facilitates its exit from late endosome in order to control cell death pathways (PubMed:26280656).
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 (PubMed:25588945).
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 (PubMed:25998567).
Plays a role as negative regulator of TGFB1 production in regulatory T cells (PubMed:26126825).
Binds ceramide and facilitates its exit from late endosome in order to control cell death pathways (PubMed:26280656).
GO annotations
all annotations | all molecular function | virus receptor activity | dna binding | rna binding | cytoskeletal motor activity | catalytic activity | gtpase activity | structural molecule activity | transporter activity | cytoskeletal protein binding | lipid binding | cyclase activity | antioxidant activity | oxidoreductase activity | transferase activity | hydrolase activity | lyase activity | isomerase activity | ligase activity | protein tag activity | cargo receptor activity | histone binding | protein folding chaperone | translation regulator activity | nutrient reservoir activity | receptor ligand activity | molecular transducer activity | molecular adaptor activity | toxin activity | cell adhesion mediator activity | molecular function regulator activity | virus coreceptor activity | catalytic activity, acting on a protein | catalytic activity, acting on dna | catalytic activity, acting on rna | molecular carrier activity | transcription regulator activity | general transcription initiation factor activity | molecular sensor activity | molecular sequestering activity | atp-dependent activity | other molecular function | all biological process | mitotic cell cycle | cytokinesis | cytoplasmic translation | immune system process | muscle system process | circulatory system process | renal system process | respiratory system process | carbohydrate metabolic process | generation of precursor metabolites and energy | dna replication | dna repair | dna recombination | chromatin organization | dna-templated transcription | regulation of dna-templated transcription | trna metabolic process | protein folding | protein glycosylation | amino acid metabolic process | modified amino acid metabolic process | lipid metabolic process | vitamin metabolic process | sulfur compound metabolic process | intracellular protein transport | nucleocytoplasmic transport | autophagy | inflammatory response | mitochondrion organization | cytoskeleton organization | microtubule-based movement | peroxisome organization | lysosome organization | chromosome segregation | cell adhesion | establishment or maintenance of cell polarity | programmed cell death | photosynthesis | mrna metabolic process | snrna metabolic process | vesicle-mediated transport | reproductive process | digestive system process | signaling | cell differentiation | protein catabolic process | extracellular matrix organization | regulatory ncrna-mediated gene silencing | telomere organization | cell junction organization | wound healing | ribosome biogenesis | cilium organization | anatomical structure development | cell motility | nervous system process | endocrine process | protein maturation | transmembrane transport | nucleobase-containing small molecule metabolic process | hepaticobiliary system process | membrane organization | protein-containing complex assembly | cell wall organization or biogenesis | nitrogen cycle metabolic process | protein localization to plasma membrane | defense response to other organism | detoxification | meiotic nuclear division | mitotic nuclear division | mitochondrial gene expression | carbohydrate derivative metabolic process | other biological process | all cellular component | nuclear chromosome | extracellular region | extracellular space | cell wall | nucleus | nuclear envelope | nucleoplasm | chromosome | nucleolus | mitochondrion | lysosome | endosome | vacuole | peroxisome | endoplasmic reticulum | golgi apparatus | lipid droplet | microtubule organizing center | cytosol | ribosome | cytoskeleton | plasma membrane | cilium | plastid | thylakoid | external encapsulating structure | extracellular matrix | cytoplasmic vesicle | organelle | other cellular component | |||
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Aspect | Term | |
---|---|---|
Cellular Component | cell projection | |
Cellular Component | early endosome | |
Cellular Component | endosome | |
Cellular Component | late endosome membrane | |
Cellular Component | lysosomal membrane | |
Cellular Component | lysosome | |
Cellular Component | multivesicular body membrane | |
Cellular Component | multivesicular body, internal vesicle | |
Cellular Component | plasma membrane | |
Molecular Function | ceramide binding | |
Molecular Function | kinase binding | |
Molecular Function | phosphatidylinositol bisphosphate binding | |
Molecular Function | ubiquitin protein ligase binding | |
Biological Process | endosome organization | |
Biological Process | endosome transport via multivesicular body sorting pathway | |
Biological Process | negative regulation of lysosomal protein catabolic process | |
Biological Process | negative regulation of transforming growth factor beta1 production | |
Biological Process | regulation of lysosomal membrane permeability | |
Biological Process | regulation of lysosome organization |
Keywords
- Biological process
Enzyme and pathway databases
Protein family/group databases
Names & Taxonomy
Protein names
- Recommended nameLysosomal-associated transmembrane protein 4B
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionQ86VI4
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Features
Showing features for transmembrane.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Transmembrane | 117-137 | Helical | ||||
Sequence: ILLGVWYLIINAVVLLILLSA | ||||||
Transmembrane | 163-183 | Helical | ||||
Sequence: MCIAIAISLLMILICAMATYG | ||||||
Transmembrane | 191-211 | Helical | ||||
Sequence: WIIPFFCYQIFDFALNMLVAI | ||||||
Transmembrane | 244-264 | Helical | ||||
Sequence: CLVLIILLFISIILTFKGYLI |
Keywords
- Cellular component
Disease & Variants
Features
Showing features for mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 296 | Abolishes binding to NEDD4; when associated with A-312. Increases localization to cell membrane; when associated with A-312. Retains association with HGS and enhances PIP5K1C interaction; when associated with A-312. Does not affect EGFR degradation; when associated with A-312. | ||||
Sequence: P → A | ||||||
Mutagenesis | 312 | Abolishes binding to NEDD4; when associated with A-296. Increases localization to cell membrane; when associated with A-296. Retains association with HGS and enhances PIP5K1C interaction; when associated with A-296. Does not affect EGFR degradation; when associated with A-296. | ||||
Sequence: P → A |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 499 variants from UniProt as well as other sources including ClinVar and dbSNP.
Organism-specific databases
Miscellaneous
Genetic variation databases
PTM/Processing
Features
Showing features for chain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000249721 | 1-317 | Lysosomal-associated transmembrane protein 4B | |||
Sequence: MTSRTRVTWPSPPRPLPVPAAAAVAFGAKGTDPAEARSSRGIEEAGPRAHGRAGREPERRRSRQQRRGGLQARRSTLLKTCARARATAPGAMKMVAPWTRFYSNSCCLCCHVRTGTILLGVWYLIINAVVLLILLSALADPDQYNFSSSELGGDFEFMDDANMCIAIAISLLMILICAMATYGAYKQRAAWIIPFFCYQIFDFALNMLVAITVLIYPNSIQEYIRQLPPNFPYRDDVMSVNPTCLVLIILLFISIILTFKGYLISCVWNCYRYINGRNSSDVLVYVTSNDTTVLLPPYDDATVNGAAKEPPPPYVSA |
Post-translational modification
Undergoes proteolytic cleavage following delivery to the lysosomes.
Ubiquitinated by NEDD4.
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Interaction
Subunit
Homooligomer; upon reaching the lysosomes (PubMed:21224396).
Interacts with MCOLN1 (PubMed:21224396).
Interacts with NEDD4; may play a role in the lysosomal sorting of LAPTM4B; enhances HGS association with NEDD4; mediates inhibition of EGFR degradation (PubMed:22096579, PubMed:25588945).
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 (PubMed:25588945).
Interacts with HGS; promotes HGS ubiquitination (PubMed:25588945).
Interacts with SNX5 (PubMed:25588945).
Interacts with SLC3A2 and SLC7A5; recruits SLC3A2 and SLC7A5 to lysosomes to promote leucine uptake into these organelles and is required for mTORC1 activation (PubMed:25998567).
Interacts with LRRC32; decreases TGFB1 production in regulatory T cells (PubMed:26126825).
Interacts with BECN1; competes with EGFR for LAPTM4B binding; regulates EGFR activity (PubMed:28479384).
Interacts with EGFR; positively correlates with EGFR activation (PubMed:28479384).
Interacts with MCOLN1 (PubMed:21224396).
Interacts with NEDD4; may play a role in the lysosomal sorting of LAPTM4B; enhances HGS association with NEDD4; mediates inhibition of EGFR degradation (PubMed:22096579, PubMed:25588945).
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 (PubMed:25588945).
Interacts with HGS; promotes HGS ubiquitination (PubMed:25588945).
Interacts with SNX5 (PubMed:25588945).
Interacts with SLC3A2 and SLC7A5; recruits SLC3A2 and SLC7A5 to lysosomes to promote leucine uptake into these organelles and is required for mTORC1 activation (PubMed:25998567).
Interacts with LRRC32; decreases TGFB1 production in regulatory T cells (PubMed:26126825).
Interacts with BECN1; competes with EGFR for LAPTM4B binding; regulates EGFR activity (PubMed:28479384).
Interacts with EGFR; positively correlates with EGFR activation (PubMed:28479384).
Binary interactions
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for region, compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 25-73 | Disordered | ||||
Sequence: AFGAKGTDPAEARSSRGIEEAGPRAHGRAGREPERRRSRQQRRGGLQAR | ||||||
Compositional bias | 36-65 | Basic and acidic residues | ||||
Sequence: ARSSRGIEEAGPRAHGRAGREPERRRSRQQ | ||||||
Region | 205-221 | Required for NEDD4 interaction | ||||
Sequence: LNMLVAITVLIYPNSIQ |
Sequence similarities
Belongs to the LAPTM4/LAPTM5 transporter family.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence & Isoform
- Sequence statusComplete
This entry describes 2 isoforms produced by Alternative splicing.
Q86VI4-3
This isoform has been chosen as the canonical sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
- Name1
- Length317
- Mass (Da)35,123
- Last updated2018-10-10 v2
- Checksum4E93093E066BE948
Q86VI4-2
- Name2
- Differences from canonical
- 1-91: Missing
Computationally mapped potential isoform sequences
There is 1 potential isoform mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
H0YBN1 | H0YBN1_HUMAN | LAPTM4B | 152 |
Sequence caution
Features
Showing features for alternative sequence, sequence conflict, compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Alternative sequence | VSP_059831 | 1-91 | in isoform 2 | |||
Sequence: Missing | ||||||
Sequence conflict | 32 | in Ref. 5; CAB66876 | ||||
Sequence: D → R | ||||||
Compositional bias | 36-65 | Basic and acidic residues | ||||
Sequence: ARSSRGIEEAGPRAHGRAGREPERRRSRQQ | ||||||
Sequence conflict | 85 | in Ref. 4; AAH38117 | ||||
Sequence: R → S | ||||||
Sequence conflict | 179 | in Ref. 4; AAH38117 | ||||
Sequence: M → T |
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AF527412 EMBL· GenBank· DDBJ | AAP14034.1 EMBL· GenBank· DDBJ | mRNA | ||
AY057051 EMBL· GenBank· DDBJ | AAL17908.2 EMBL· GenBank· DDBJ | mRNA | ||
AY261384 EMBL· GenBank· DDBJ | AAO84265.1 EMBL· GenBank· DDBJ | mRNA | Sequence problems. | |
AF317417 EMBL· GenBank· DDBJ | AAK69595.1 EMBL· GenBank· DDBJ | mRNA | ||
AK075326 EMBL· GenBank· DDBJ | BAC11549.1 EMBL· GenBank· DDBJ | mRNA | ||
BC014129 EMBL· GenBank· DDBJ | AAH14129.1 EMBL· GenBank· DDBJ | mRNA | ||
BC031021 EMBL· GenBank· DDBJ | AAH31021.1 EMBL· GenBank· DDBJ | mRNA | ||
BC038117 EMBL· GenBank· DDBJ | AAH38117.1 EMBL· GenBank· DDBJ | mRNA | ||
AL136942 EMBL· GenBank· DDBJ | CAB66876.2 EMBL· GenBank· DDBJ | mRNA |