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Protein

Lysosomal-associated transmembrane protein 4B

Gene

LAPTM4B

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

Functioni

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).5 Publications

GO - Molecular functioni

  • ceramide binding Source: UniProtKB
  • kinase binding Source: UniProtKB
  • phosphatidylinositol bisphosphate binding Source: UniProtKB
  • ubiquitin protein ligase binding Source: UniProtKB

GO - Biological processi

Keywordsi

Biological processTransport

Protein family/group databases

TCDBi2.A.74.1.3 the 4 tms multidrug endosomal transporter (met) family

Names & Taxonomyi

Protein namesi
Recommended name:
Lysosomal-associated transmembrane protein 4BCurated
Alternative name(s):
Lysosome-associated transmembrane protein 4-beta1 Publication
Gene namesi
Name:LAPTM4BImported
ORF Names:PSEC0001
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 8

Organism-specific databases

EuPathDBiHostDB:ENSG00000104341.16
HGNCiHGNC:13646 LAPTM4B
MIMi613296 gene
neXtProtiNX_Q86VI4

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
Transmembranei117 – 137HelicalSequence analysisAdd BLAST21
Transmembranei163 – 183HelicalSequence analysisAdd BLAST21
Transmembranei191 – 211HelicalSequence analysisAdd BLAST21
Transmembranei244 – 264HelicalSequence analysisAdd BLAST21

Keywords - Cellular componenti

Cell membrane, Cell projection, Endosome, Lysosome, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi296P → A: 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. 2 Publications1
Mutagenesisi312P → A: 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. 2 Publications1

Organism-specific databases

DisGeNETi55353
OpenTargetsiENSG00000104341
PharmGKBiPA128395785

Polymorphism and mutation databases

BioMutaiLAPTM4B
DMDMi74714056

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002497211 – 317Lysosomal-associated transmembrane protein 4BAdd BLAST317

Post-translational modificationi

Undergoes proteolytic cleavage following delivery to the lysosomes.1 Publication
Ubiquitinated by NEDD4.1 Publication

Keywords - PTMi

Ubl conjugation

Proteomic databases

EPDiQ86VI4
MaxQBiQ86VI4
PaxDbiQ86VI4
PeptideAtlasiQ86VI4
PRIDEiQ86VI4
ProteomicsDBi70024
70025 [Q86VI4-2]
70026 [Q86VI4-3]

PTM databases

iPTMnetiQ86VI4
PhosphoSitePlusiQ86VI4

Expressioni

Gene expression databases

BgeeiENSG00000104341 Expressed in 238 organ(s), highest expression level in metanephros
CleanExiHS_LAPTM4B
ExpressionAtlasiQ86VI4 baseline and differential
GenevisibleiQ86VI4 HS

Organism-specific databases

HPAiCAB020782
HPA068830

Interactioni

Subunit structurei

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).6 Publications

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi120633, 19 interactors
IntActiQ86VI4, 19 interactors
STRINGi9606.ENSP00000402301

Structurei

3D structure databases

ProteinModelPortaliQ86VI4
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni205 – 221Required for NEDD4 interaction1 PublicationAdd BLAST17

Sequence similaritiesi

Belongs to the LAPTM4/LAPTM5 transporter family.Curated

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410IGWG Eukaryota
ENOG4111K1Z LUCA
GeneTreeiENSGT00390000013359
HOGENOMiHOG000007698
HOVERGENiHBG000908
InParanoidiQ86VI4
KOiK12387
OMAiTEVLVYV
OrthoDBiEOG091G0MA5
PhylomeDBiQ86VI4
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

Sequences (2+)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 2 described isoforms and 1 potential isoform that is computationally mapped.Show allAlign All

Isoform 1 (identifier: Q86VI4-3) [UniParc]FASTAAdd to basket

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.

« Hide
        10         20         30         40         50
MTSRTRVTWP SPPRPLPVPA AAAVAFGAKG TDPAEARSSR GIEEAGPRAH
60 70 80 90 100
GRAGREPERR RSRQQRRGGL QARRSTLLKT CARARATAPG AMKMVAPWTR
110 120 130 140 150
FYSNSCCLCC HVRTGTILLG VWYLIINAVV LLILLSALAD PDQYNFSSSE
160 170 180 190 200
LGGDFEFMDD ANMCIAIAIS LLMILICAMA TYGAYKQRAA WIIPFFCYQI
210 220 230 240 250
FDFALNMLVA ITVLIYPNSI QEYIRQLPPN FPYRDDVMSV NPTCLVLIIL
260 270 280 290 300
LFISIILTFK GYLISCVWNC YRYINGRNSS DVLVYVTSND TTVLLPPYDD
310
ATVNGAAKEP PPPYVSA
Length:317
Mass (Da):35,123
Last modified:October 10, 2018 - v2
Checksum:i4E93093E066BE948
GO
Isoform 2 (identifier: Q86VI4-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-91: Missing.

Show »
Length:226
Mass (Da):25,419
Checksum:iA3156D2F2C0DCF0B
GO

Computationally mapped potential isoform sequencesi

There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
H0YBN1H0YBN1_HUMAN
Lysosomal-associated transmembrane ...
LAPTM4B
152Annotation score:

Sequence cautioni

The sequence AAO84265 differs from that shown. Probable cloning artifact.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti32D → R in CAB66876 (PubMed:11230166).Curated1
Sequence conflicti85R → S in AAH38117 (PubMed:15489334).Curated1
Sequence conflicti179M → T in AAH38117 (PubMed:15489334).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0598311 – 91Missing in isoform 2. Add BLAST91

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF527412 mRNA Translation: AAP14034.1
AY057051 mRNA Translation: AAL17908.2
AY261384 mRNA Translation: AAO84265.1 Sequence problems.
AF317417 mRNA Translation: AAK69595.1
AK075326 mRNA Translation: BAC11549.1
BC014129 mRNA Translation: AAH14129.1
BC031021 mRNA Translation: AAH31021.1
BC038117 mRNA Translation: AAH38117.1
AL136942 mRNA Translation: CAB66876.2
CCDSiCCDS6275.1 [Q86VI4-2]
RefSeqiNP_060877.3, NM_018407.4 [Q86VI4-2]
UniGeneiHs.492314

Genome annotation databases

EnsembliENST00000445593; ENSP00000402301; ENSG00000104341 [Q86VI4-3]
ENST00000521545; ENSP00000428409; ENSG00000104341 [Q86VI4-2]
ENST00000619747; ENSP00000482533; ENSG00000104341 [Q86VI4-3]
GeneIDi55353
KEGGihsa:55353
UCSCiuc003yia.4 human [Q86VI4-3]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF527412 mRNA Translation: AAP14034.1
AY057051 mRNA Translation: AAL17908.2
AY261384 mRNA Translation: AAO84265.1 Sequence problems.
AF317417 mRNA Translation: AAK69595.1
AK075326 mRNA Translation: BAC11549.1
BC014129 mRNA Translation: AAH14129.1
BC031021 mRNA Translation: AAH31021.1
BC038117 mRNA Translation: AAH38117.1
AL136942 mRNA Translation: CAB66876.2
CCDSiCCDS6275.1 [Q86VI4-2]
RefSeqiNP_060877.3, NM_018407.4 [Q86VI4-2]
UniGeneiHs.492314

3D structure databases

ProteinModelPortaliQ86VI4
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi120633, 19 interactors
IntActiQ86VI4, 19 interactors
STRINGi9606.ENSP00000402301

Protein family/group databases

TCDBi2.A.74.1.3 the 4 tms multidrug endosomal transporter (met) family

PTM databases

iPTMnetiQ86VI4
PhosphoSitePlusiQ86VI4

Polymorphism and mutation databases

BioMutaiLAPTM4B
DMDMi74714056

Proteomic databases

EPDiQ86VI4
MaxQBiQ86VI4
PaxDbiQ86VI4
PeptideAtlasiQ86VI4
PRIDEiQ86VI4
ProteomicsDBi70024
70025 [Q86VI4-2]
70026 [Q86VI4-3]

Protocols and materials databases

DNASUi55353
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000445593; ENSP00000402301; ENSG00000104341 [Q86VI4-3]
ENST00000521545; ENSP00000428409; ENSG00000104341 [Q86VI4-2]
ENST00000619747; ENSP00000482533; ENSG00000104341 [Q86VI4-3]
GeneIDi55353
KEGGihsa:55353
UCSCiuc003yia.4 human [Q86VI4-3]

Organism-specific databases

CTDi55353
DisGeNETi55353
EuPathDBiHostDB:ENSG00000104341.16
GeneCardsiLAPTM4B
HGNCiHGNC:13646 LAPTM4B
HPAiCAB020782
HPA068830
MIMi613296 gene
neXtProtiNX_Q86VI4
OpenTargetsiENSG00000104341
PharmGKBiPA128395785
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IGWG Eukaryota
ENOG4111K1Z LUCA
GeneTreeiENSGT00390000013359
HOGENOMiHOG000007698
HOVERGENiHBG000908
InParanoidiQ86VI4
KOiK12387
OMAiTEVLVYV
OrthoDBiEOG091G0MA5
PhylomeDBiQ86VI4
TreeFamiTF330843

Miscellaneous databases

GeneWikiiLAPTM4B
GenomeRNAii55353
PROiPR:Q86VI4
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000104341 Expressed in 238 organ(s), highest expression level in metanephros
CleanExiHS_LAPTM4B
ExpressionAtlasiQ86VI4 baseline and differential
GenevisibleiQ86VI4 HS

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_HUMAN
AccessioniPrimary (citable) accession number: Q86VI4
Secondary accession number(s): Q3ZCV5
, Q7L909, Q86VH8, Q9H060
Entry historyiIntegrated into UniProtKB/Swiss-Prot: September 19, 2006
Last sequence update: October 10, 2018
Last modified: November 7, 2018
This is version 115 of the entry and version 2 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

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. Human chromosome 8
    Human chromosome 8: entries, gene names and cross-references to MIM
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Main funding by: National Institutes of Health

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