LAAT1_HUMAN
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 03-AUG-2022, entry version 132.
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};
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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. [Q6ZP29-2]
DR RefSeq; XP_006710774.1; XM_006710711.2. [Q6ZP29-2]
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 GlyGen; Q6ZP29; 1 site.
DR iPTMnet; Q6ZP29; -.
DR PhosphoSitePlus; Q6ZP29; -.
DR BioMuta; PQLC2; -.
DR DMDM; 74749590; -.
DR PaxDb; Q6ZP29; -.
DR PeptideAtlas; Q6ZP29; -.
DR PRIDE; Q6ZP29; -.
DR Antibodypedia; 46685; 92 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 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; LAQCFYY; -.
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; 10 hits in 1078 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 107 other tissues.
DR ExpressionAtlas; Q6ZP29; baseline and differential.
DR Genevisible; Q6ZP29; HS.
DR GO; GO:0016021; C:integral component of membrane; IBA:GO_Central.
DR GO; GO:0031301; C:integral component of organelle membrane; IDA:UniProtKB.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA.
DR GO; GO:0005765; C:lysosomal 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: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 InterPro; IPR006603; PQ-loop_rpt.
DR Pfam; PF04193; PQ-loop; 2.
DR SMART; SM00679; CTNS; 2.
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
