LAP4B_MACFA
ID LAP4B_MACFA Reviewed; 226 AA.
AC Q4R6E8;
DT 19-SEP-2006, integrated into UniProtKB/Swiss-Prot.
DT 19-JUL-2005, sequence version 1.
DT 03-AUG-2022, entry version 50.
DE RecName: Full=Lysosomal-associated transmembrane protein 4B {ECO:0000250|UniProtKB:Q86VI4};
GN Name=LAPTM4B {ECO:0000250|UniProtKB:Q86VI4}; ORFNames=QtsA-18169;
OS Macaca fascicularis (Crab-eating macaque) (Cynomolgus monkey).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini;
OC Cercopithecidae; Cercopithecinae; Macaca.
OX NCBI_TaxID=9541;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Testis;
RG International consortium for macaque cDNA sequencing and analysis;
RT "DNA sequences of macaque genes expressed in brain or testis and its
RT evolutionary implications.";
RL Submitted (JUN-2005) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Required for optimal lysosomal function. Blocks EGF-
CC stimulated EGFR intraluminal sorting and degradation. Conversely by
CC binding with the phosphatidylinositol 4,5-bisphosphate, regulates its
CC PIP5K1C interaction, inhibits HGS ubiquitination and relieves LAPTM4B
CC inhibition of EGFR degradation. Recruits SLC3A2 and SLC7A5 (the Leu
CC transporter) to the lysosome, promoting entry of leucine and other
CC essential amino acid (EAA) into the lysosome, stimulating activation of
CC proton-transporting vacuolar (V)-ATPase protein pump (V-ATPase) and
CC hence mTORC1 activation. Plays a role as negative regulator of TGFB1
CC production in regulatory T cells. Binds ceramide and facilitates its
CC exit from late endosome in order to control cell death pathways.
CC {ECO:0000250|UniProtKB:Q86VI4}.
CC -!- SUBUNIT: Homooligomer; upon reaching the lysosomes. Interacts with
CC MCOLN1. Interacts with NEDD4; may play a role in the lysosomal sorting
CC of LAPTM4B; enhances HGS association with NEDD4; mediates inhibition of
CC EGFR degradation. Interacts with PIP5K1C; promotes SNX5 association
CC with LAPTM4B; kinase activity of PIP5K1C is required; interaction is
CC regulated by phosphatidylinositol 4,5-bisphosphate generated by
CC PIP5K1C. Interacts with HGS; promotes HGS ubiquitination. Interacts
CC with SNX5. Interacts with SLC3A2 AND SLC7A5; recruits SLC3A2 and SLC7A5
CC to lysosomes to promote leucine uptake into these organelles and is
CC required for mTORC1 activation. Interacts with LRRC32; decreases TGFB1
CC production in regulatory T cells. Interacts with BECN1; competes with
CC EGFR for LAPTM4B binding; regulates EGFR activity. Interacts with EGFR;
CC positively correlates with EGFR activation.
CC {ECO:0000250|UniProtKB:Q86VI4}.
CC -!- SUBCELLULAR LOCATION: Endomembrane system
CC {ECO:0000250|UniProtKB:Q86VI4}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:Q86VI4}. Late endosome membrane
CC {ECO:0000250|UniProtKB:Q86VI4}. Cell membrane
CC {ECO:0000250|UniProtKB:Q86VI4}. Cell projection
CC {ECO:0000250|UniProtKB:Q86VI4}. Lysosome membrane
CC {ECO:0000250|UniProtKB:Q86VI4}. Endosome membrane
CC {ECO:0000250|UniProtKB:Q86VI4}. Endosome, multivesicular body membrane
CC {ECO:0000250|UniProtKB:Q86VI4}. Endosome, multivesicular body lumen
CC {ECO:0000250|UniProtKB:Q86VI4}.
CC -!- PTM: Undergoes proteolytic cleavage following delivery to the
CC lysosomes. {ECO:0000250|UniProtKB:Q86VI4}.
CC -!- PTM: Ubiquitinated by NEDD4. {ECO:0000250|UniProtKB:Q86VI4}.
CC -!- SIMILARITY: Belongs to the LAPTM4/LAPTM5 transporter family.
CC {ECO:0000305}.
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DR EMBL; AB169236; BAE01327.1; -; mRNA.
DR AlphaFoldDB; Q4R6E8; -.
DR Ensembl; ENSMFAT00000004002; ENSMFAP00000029799; ENSMFAG00000042049.
DR VEuPathDB; HostDB:ENSMFAG00000042049; -.
DR GeneTree; ENSGT00940000153446; -.
DR OMA; YDDPANG; -.
DR Proteomes; UP000233100; Chromosome 8.
DR Bgee; ENSMFAG00000042049; Expressed in heart and 13 other tissues.
DR GO; GO:0042995; C:cell projection; ISS:UniProtKB.
DR GO; GO:0005769; C:early endosome; ISS:UniProtKB.
DR GO; GO:0005768; C:endosome; ISS:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0031902; C:late endosome membrane; ISS:UniProtKB.
DR GO; GO:0005765; C:lysosomal membrane; ISS:UniProtKB.
DR GO; GO:0005764; C:lysosome; ISS:UniProtKB.
DR GO; GO:0032585; C:multivesicular body membrane; ISS:UniProtKB.
DR GO; GO:0097487; C:multivesicular body, internal vesicle; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0097001; F:ceramide binding; ISS:UniProtKB.
DR GO; GO:1902936; F:phosphatidylinositol bisphosphate binding; ISS:UniProtKB.
DR GO; GO:0007032; P:endosome organization; ISS:UniProtKB.
DR GO; GO:0032509; P:endosome transport via multivesicular body sorting pathway; ISS:UniProtKB.
DR GO; GO:1905166; P:negative regulation of lysosomal protein catabolic process; ISS:UniProtKB.
DR GO; GO:0032911; P:negative regulation of transforming growth factor beta1 production; ISS:UniProtKB.
DR GO; GO:0097213; P:regulation of lysosomal membrane permeability; ISS:UniProtKB.
DR GO; GO:1905671; P:regulation of lysosome organization; ISS:UniProtKB.
DR InterPro; IPR004687; LAPTM4/5.
DR InterPro; IPR018401; Lysosomal-assoc_TM_prot4B.
DR PANTHER; PTHR12479:SF6; PTHR12479:SF6; 1.
DR Pfam; PF03821; Mtp; 1.
PE 2: Evidence at transcript level;
KW Cell membrane; Cell projection; Endosome; Lysosome; Membrane;
KW Reference proteome; Transmembrane; Transmembrane helix; Transport;
KW Ubl conjugation.
FT CHAIN 1..226
FT /note="Lysosomal-associated transmembrane protein 4B"
FT /id="PRO_0000249722"
FT TRANSMEM 26..46
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 72..92
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 100..120
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 153..173
FT /note="Helical"
FT /evidence="ECO:0000255"
FT REGION 205..221
FT /note="Required for NEDD4 interaction"
FT /evidence="ECO:0000250|UniProtKB:Q86VI4"
SQ SEQUENCE 226 AA; 25398 MW; 1F395DE8BBBE5081 CRC64;
MKMVAPWTRF YSNSCCLCCH VRTGTILLGV WYLIINAVVL LILLSALADP DQYHFSSSEL
GGDFEFMDDA NMCIAIAISL LMILICAMAT YGAYKQRAAW IIPFFCYQIF DFALNTLVAI
TVLVYPNSIQ EYIRQLPPNF PYRDDVMSVN PTCLVLIILL FISIILTFKG YLISCVWNCY
RYINGRNSSD VLVYVTSNDT TVLLPPYDDA TVNGAAKEPP PPYVSA
