ID   LAP4B_MOUSE             Reviewed;         227 AA.
AC   Q91XQ6;
DT   19-SEP-2006, integrated into UniProtKB/Swiss-Prot.
DT   01-DEC-2001, sequence version 1.
DT   24-JAN-2024, entry version 136.
DE   RecName: Full=Lysosomal-associated transmembrane protein 4B {ECO:0000250|UniProtKB:Q86VI4};
GN   Name=Laptm4b {ECO:0000312|MGI:MGI:1890494};
OS   Mus musculus (Mouse).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Mus; Mus.
OX   NCBI_TaxID=10090;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   STRAIN=C57BL/6J; TISSUE=Brain;
RA   Hogue D.L.;
RL   Submitted (OCT-2000) to the EMBL/GenBank/DDBJ databases.
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=C57BL/6J; TISSUE=Hypothalamus, and Testis;
RX   PubMed=16141072; DOI=10.1126/science.1112014;
RA   Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA   Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA   Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA   Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA   Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA   Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA   Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA   Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA   Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA   Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA   Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA   Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA   Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA   Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA   Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA   Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA   Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA   Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA   Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA   Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA   Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA   Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA   Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA   Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA   Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA   van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA   Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA   Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA   Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA   Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA   Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA   Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA   Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA   Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT   "The transcriptional landscape of the mammalian genome.";
RL   Science 309:1559-1563(2005).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Eye;
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA project:
RT   the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
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; AF317418; AAK69596.1; -; mRNA.
DR   EMBL; AK077269; BAC36721.1; -; mRNA.
DR   EMBL; AK077933; BAC37072.1; -; mRNA.
DR   EMBL; AK079581; BAC37691.1; -; mRNA.
DR   EMBL; AK082807; BAC38630.1; -; mRNA.
DR   EMBL; BC019120; AAH19120.1; -; mRNA.
DR   CCDS; CCDS27416.1; -.
DR   RefSeq; NP_277056.1; NM_033521.3.
DR   AlphaFoldDB; Q91XQ6; -.
DR   STRING; 10090.ENSMUSP00000022867; -.
DR   iPTMnet; Q91XQ6; -.
DR   PhosphoSitePlus; Q91XQ6; -.
DR   SwissPalm; Q91XQ6; -.
DR   MaxQB; Q91XQ6; -.
DR   PaxDb; 10090-ENSMUSP00000022867; -.
DR   ProteomicsDB; 264832; -.
DR   Antibodypedia; 26024; 172 antibodies from 27 providers.
DR   DNASU; 114128; -.
DR   Ensembl; ENSMUST00000022867.5; ENSMUSP00000022867.4; ENSMUSG00000022257.5.
DR   GeneID; 114128; -.
DR   KEGG; mmu:114128; -.
DR   UCSC; uc007vlj.1; mouse.
DR   AGR; MGI:1890494; -.
DR   CTD; 55353; -.
DR   MGI; MGI:1890494; Laptm4b.
DR   VEuPathDB; HostDB:ENSMUSG00000022257; -.
DR   eggNOG; ENOG502QSAX; Eukaryota.
DR   GeneTree; ENSGT00940000153446; -.
DR   HOGENOM; CLU_059239_1_0_1; -.
DR   InParanoid; Q91XQ6; -.
DR   OMA; YDDPANG; -.
DR   OrthoDB; 2902684at2759; -.
DR   PhylomeDB; Q91XQ6; -.
DR   TreeFam; TF330843; -.
DR   BioGRID-ORCS; 114128; 0 hits in 79 CRISPR screens.
DR   ChiTaRS; Laptm4b; mouse.
DR   PRO; PR:Q91XQ6; -.
DR   Proteomes; UP000000589; Chromosome 15.
DR   RNAct; Q91XQ6; Protein.
DR   Bgee; ENSMUSG00000022257; Expressed in motor neuron and 255 other cell types or tissues.
DR   ExpressionAtlas; Q91XQ6; baseline and differential.
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: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:0019900; F:kinase binding; ISO:MGI.
DR   GO; GO:1902936; F:phosphatidylinositol bisphosphate binding; ISS:UniProtKB.
DR   GO; GO:0031625; F:ubiquitin protein ligase binding; ISO:MGI.
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   PANTHER; PTHR12479; LYSOSOMAL-ASSOCIATED TRANSMEMBRANE PROTEIN; 1.
DR   PANTHER; PTHR12479:SF6; LYSOSOMAL-ASSOCIATED TRANSMEMBRANE PROTEIN 4B; 1.
DR   Pfam; PF03821; Mtp; 1.
DR   Genevisible; Q91XQ6; MM.
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..227
FT                   /note="Lysosomal-associated transmembrane protein 4B"
FT                   /id="PRO_0000249723"
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..222
FT                   /note="Required for NEDD4 interaction"
FT                   /evidence="ECO:0000250|UniProtKB:Q86VI4"
SQ   SEQUENCE   227 AA;  25395 MW;  FD3DC53C2682818D CRC64;
     MKMVAPWTRF YSHSCCLCCH VRTGTILLGV WYLIINAVVL LILLSALADP NQYHFSGSEL
     GGEFEFMDDA NMCIAIAISL LMILICAMAT YGAYKQHAAW IIPFFCYQIF DFALNTLVAI
     TVLVYPNSIQ EYIRQLPPSF PYRDDIMSVN PTCLVLIILL FIGILLTLKG YLISCVWSCY
     RYINGRNSSD VLVYVTSNDT TVLLPPYDDA TAVPSTAKEP PPPYVSA
//