ID LAAT1_HUMAN Reviewed; 291 AA. AC Q6ZP29; B3KWQ5; Q6ZMJ3; Q6ZP27; Q9NXC7; DT 03-APR-2007, integrated into UniProtKB/Swiss-Prot. DT 05-JUL-2004, sequence version 1. DT 24-JAN-2024, entry version 139. DE RecName: Full=Lysosomal amino acid transporter 1 homolog {ECO:0000305}; DE AltName: Full=PQ-loop repeat-containing protein 2; DE AltName: Full=Solute carrier family 66 member 1 {ECO:0000312|HGNC:HGNC:26001}; GN Name=SLC66A1 {ECO:0000312|HGNC:HGNC:26001}; GN Synonyms=PQLC2 {ECO:0000312|HGNC:HGNC:26001}; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). RC TISSUE=Adipose tissue, Hepatoma, Macrophage, and Small intestine; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16710414; DOI=10.1038/nature04727; RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K., RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.; RT "The DNA sequence and biological annotation of human chromosome 1."; RL Nature 441:315-321(2006). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3). RC TISSUE=Kidney; 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). RN [4] RP FUNCTION. RX PubMed=23169667; DOI=10.1073/pnas.1211198109; RA Jezegou A., Llinares E., Anne C., Kieffer-Jaquinod S., O'Regan S., RA Aupetit J., Chabli A., Sagne C., Debacker C., Chadefaux-Vekemans B., RA Journet A., Andre B., Gasnier B.; RT "Heptahelical protein PQLC2 is a lysosomal cationic amino acid exporter RT underlying the action of cysteamine in cystinosis therapy."; RL Proc. Natl. Acad. Sci. U.S.A. 109:E3434-E3443(2012). RN [5] RP FUNCTION, SUBCELLULAR LOCATION, AND MUTAGENESIS OF PRO-55 AND RP 288-LEU-LEU-289. RX PubMed=22822152; DOI=10.1126/science.1220281; RA Liu B., Du H., Rutkowski R., Gartner A., Wang X.; RT "LAAT-1 is the lysosomal lysine/arginine transporter that maintains amino RT acid homeostasis."; RL Science 337:351-354(2012). CC -!- FUNCTION: Amino acid transporter that specifically mediates the pH- CC dependent export of the cationic amino acids arginine, histidine and CC lysine from lysosomes. {ECO:0000269|PubMed:22822152, CC ECO:0000269|PubMed:23169667}. CC -!- INTERACTION: CC Q6ZP29-3; Q13520: AQP6; NbExp=3; IntAct=EBI-12889586, EBI-13059134; CC Q6ZP29-3; P36382: GJA5; NbExp=3; IntAct=EBI-12889586, EBI-750433; CC Q6ZP29-3; P48165: GJA8; NbExp=3; IntAct=EBI-12889586, EBI-17458373; CC Q6ZP29-3; P36383: GJC1; NbExp=3; IntAct=EBI-12889586, EBI-11979659; CC Q6ZP29-3; Q8TDT2: GPR152; NbExp=3; IntAct=EBI-12889586, EBI-13345167; CC Q6ZP29-3; Q9NZD1: GPRC5D; NbExp=3; IntAct=EBI-12889586, EBI-13067820; CC Q6ZP29-3; Q9NZG7: NINJ2; NbExp=3; IntAct=EBI-12889586, EBI-10317425; CC Q6ZP29-3; Q9NQQ7-3: SLC35C2; NbExp=3; IntAct=EBI-12889586, EBI-17295964; CC Q6ZP29-3; Q9NP94: SLC39A2; NbExp=3; IntAct=EBI-12889586, EBI-12898013; CC Q6ZP29-3; Q9NUM3: SLC39A9; NbExp=3; IntAct=EBI-12889586, EBI-2823239; CC -!- SUBCELLULAR LOCATION: Lysosome membrane {ECO:0000269|PubMed:22822152}; CC Multi-pass membrane protein {ECO:0000269|PubMed:22822152}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; CC IsoId=Q6ZP29-1; Sequence=Displayed; CC Name=2; CC IsoId=Q6ZP29-2; Sequence=VSP_024151; CC Name=3; CC IsoId=Q6ZP29-3; Sequence=VSP_024152; CC -!- DOMAIN: The di-leucine motif mediates lysosomal localization. CC {ECO:0000269|PubMed:22822152}. CC -!- MISCELLANEOUS: May play a role in the export from lysosomes of CC cysteamine-cysteine mixed disulfide (MxD), the product formed upon CC treatment by cysteamine of patients with cystinosis, a disease CC characterized by the accumulation of cystine in the lysosomes. CC {ECO:0000305|PubMed:23169667}. CC -!- SIMILARITY: Belongs to the laat-1 family. {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=BAA91088.1; Type=Frameshift; Evidence={ECO:0000305}; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AK000327; BAA91088.1; ALT_FRAME; mRNA. DR EMBL; AK125580; BAG54217.1; -; mRNA. DR EMBL; AK130171; BAC85296.1; -; mRNA. DR EMBL; AK130175; BAC85298.1; -; mRNA. DR EMBL; AK172745; BAD18732.1; -; mRNA. DR EMBL; AL035413; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC015324; AAH15324.1; -; mRNA. DR CCDS; CCDS195.2; -. [Q6ZP29-1] DR CCDS; CCDS30618.1; -. [Q6ZP29-3] DR RefSeq; NP_001035214.1; NM_001040125.1. [Q6ZP29-1] DR RefSeq; NP_001035215.1; NM_001040126.1. [Q6ZP29-3] DR RefSeq; NP_001274460.1; NM_001287531.1. [Q6ZP29-2] DR RefSeq; NP_060235.2; NM_017765.2. [Q6ZP29-1] DR RefSeq; XP_005245973.1; XM_005245916.2. [Q6ZP29-1] DR RefSeq; XP_006710773.1; XM_006710710.2. DR RefSeq; XP_006710774.1; XM_006710711.2. DR AlphaFoldDB; Q6ZP29; -. DR SMR; Q6ZP29; -. DR BioGRID; 120242; 13. DR IntAct; Q6ZP29; 10. DR STRING; 9606.ENSP00000364295; -. DR TCDB; 2.A.43.2.1; the lysosomal cystine transporter (lct) family. DR GlyCosmos; Q6ZP29; 1 site, No reported glycans. DR GlyGen; Q6ZP29; 1 site. DR iPTMnet; Q6ZP29; -. DR PhosphoSitePlus; Q6ZP29; -. DR BioMuta; PQLC2; -. DR DMDM; 74749590; -. DR PaxDb; 9606-ENSP00000364295; -. DR PeptideAtlas; Q6ZP29; -. DR Pumba; Q6ZP29; -. DR Antibodypedia; 46685; 95 antibodies from 17 providers. DR DNASU; 54896; -. DR Ensembl; ENST00000375153.8; ENSP00000364295.3; ENSG00000040487.13. [Q6ZP29-1] DR Ensembl; ENST00000375155.7; ENSP00000364297.3; ENSG00000040487.13. [Q6ZP29-1] DR Ensembl; ENST00000400548.6; ENSP00000383395.2; ENSG00000040487.13. [Q6ZP29-3] DR GeneID; 54896; -. DR KEGG; hsa:54896; -. DR MANE-Select; ENST00000375153.8; ENSP00000364295.3; NM_001040125.2; NP_001035214.1. DR UCSC; uc001bby.4; human. [Q6ZP29-1] DR AGR; HGNC:26001; -. DR CTD; 54896; -. DR DisGeNET; 54896; -. DR GeneCards; SLC66A1; -. DR HGNC; HGNC:26001; SLC66A1. DR HPA; ENSG00000040487; Low tissue specificity. DR MIM; 614760; gene. DR neXtProt; NX_Q6ZP29; -. DR OpenTargets; ENSG00000040487; -. DR VEuPathDB; HostDB:ENSG00000040487; -. DR eggNOG; KOG2913; Eukaryota. DR GeneTree; ENSGT00390000003344; -. DR HOGENOM; CLU_019699_3_0_1; -. DR InParanoid; Q6ZP29; -. DR OMA; DMCIFIQ; -. DR OrthoDB; 179669at2759; -. DR PhylomeDB; Q6ZP29; -. DR TreeFam; TF313694; -. DR PathwayCommons; Q6ZP29; -. DR Reactome; R-HSA-5223345; Miscellaneous transport and binding events. DR SignaLink; Q6ZP29; -. DR BioGRID-ORCS; 54896; 14 hits in 1152 CRISPR screens. DR ChiTaRS; PQLC2; human. DR GenomeRNAi; 54896; -. DR Pharos; Q6ZP29; Tbio. DR PRO; PR:Q6ZP29; -. DR Proteomes; UP000005640; Chromosome 1. DR RNAct; Q6ZP29; Protein. DR Bgee; ENSG00000040487; Expressed in right hemisphere of cerebellum and 109 other cell types or tissues. DR ExpressionAtlas; Q6ZP29; baseline and differential. DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA. DR GO; GO:0005765; C:lysosomal membrane; IDA:UniProtKB. DR GO; GO:0031090; C:organelle membrane; IDA:UniProtKB. DR GO; GO:0015174; F:basic amino acid transmembrane transporter activity; ISS:UniProtKB. DR GO; GO:0061459; F:L-arginine transmembrane transporter activity; IDA:UniProtKB. DR GO; GO:0015189; F:L-lysine transmembrane transporter activity; IDA:UniProtKB. DR GO; GO:0080144; P:intracellular amino acid homeostasis; IDA:UniProtKB. DR GO; GO:1903826; P:L-arginine transmembrane transport; IDA:UniProtKB. DR GO; GO:0015819; P:lysine transport; IDA:UniProtKB. DR GO; GO:0055085; P:transmembrane transport; TAS:Reactome. DR Gene3D; 1.20.1280.290; -; 2. DR InterPro; IPR006603; PQ-loop_rpt. DR PANTHER; PTHR16201:SF36; LYSOSOMAL AMINO ACID TRANSPORTER 1 HOMOLOG; 1. DR PANTHER; PTHR16201; SEVEN TRANSMEMBRANE PROTEIN 1-RELATED; 1. DR Pfam; PF04193; PQ-loop; 2. DR SMART; SM00679; CTNS; 2. DR Genevisible; Q6ZP29; HS. PE 1: Evidence at protein level; KW Alternative splicing; Amino-acid transport; Glycoprotein; Lysosome; KW Membrane; Reference proteome; Repeat; Transmembrane; Transmembrane helix; KW Transport. FT CHAIN 1..291 FT /note="Lysosomal amino acid transporter 1 homolog" FT /id="PRO_0000282434" FT TOPO_DOM 1..37 FT /note="Lumenal" FT /evidence="ECO:0000255" FT TRANSMEM 38..58 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 59..71 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 72..92 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 93..98 FT /note="Lumenal" FT /evidence="ECO:0000255" FT TRANSMEM 99..119 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 120..134 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 135..155 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 156..182 FT /note="Lumenal" FT /evidence="ECO:0000255" FT TRANSMEM 183..203 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 204..214 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 215..235 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 236..254 FT /note="Lumenal" FT /evidence="ECO:0000255" FT TRANSMEM 255..275 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 276..291 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT DOMAIN 34..100 FT /note="PQ-loop 1" FT DOMAIN 184..243 FT /note="PQ-loop 2" FT MOTIF 288..289 FT /note="Di-leucine motif" FT CARBOHYD 10 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT VAR_SEQ 1..111 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_024151" FT VAR_SEQ 1..65 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_024152" FT VARIANT 16 FT /note="S -> N (in dbSNP:rs12140547)" FT /id="VAR_031409" FT MUTAGEN 55 FT /note="P->L: Abolishes uptake of arginine and lysine." FT /evidence="ECO:0000269|PubMed:22822152" FT MUTAGEN 288..289 FT /note="Missing: Abolishes lysosomal localization." FT /evidence="ECO:0000269|PubMed:22822152" FT CONFLICT 29 FT /note="C -> R (in Ref. 1; BAC85298)" FT /evidence="ECO:0000305" FT CONFLICT 173 FT /note="G -> D (in Ref. 1; BAG54217)" FT /evidence="ECO:0000305" FT CONFLICT 191 FT /note="S -> F (in Ref. 1; BAD18732)" FT /evidence="ECO:0000305" FT CONFLICT 286 FT /note="E -> K (in Ref. 1; BAG54217)" FT /evidence="ECO:0000305" SQ SEQUENCE 291 AA; 31947 MW; B544D3BFA5458920 CRC64; MVWKKLGSRN FSSCPSGSIQ WIWDVLGECA QDGWDEASVG LGLISILCFA ASTFPQFIKA YKTGNMDQAL SLWFLLGWIG GDSCNLIGSF LADQLPLQTY TAVYYVLADL VMLTLYFYYK FRTRPSLLSA PINSVLLFLM GMACATPLLS AAGPVAAPRE AFRGRALLSV ESGSKPFTRQ EVIGFVIGSI SSVLYLLSRL PQIRTNFLRK STQGISYSLF ALVMLGNTLY GLSVLLKNPE EGQSEGSYLL HHLPWLVGSL GVLLLDTIIS IQFLVYRRST AASELEPLLP S //