CTNS_BOVIN
ID CTNS_BOVIN Reviewed; 367 AA.
AC A7MB63;
DT 08-APR-2008, integrated into UniProtKB/Swiss-Prot.
DT 02-OCT-2007, sequence version 1.
DT 03-AUG-2022, entry version 80.
DE RecName: Full=Cystinosin {ECO:0000305};
DE Flags: Precursor;
GN Name=CTNS {ECO:0000250|UniProtKB:O60931};
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Hereford; TISSUE=Fetal skin;
RG NIH - Mammalian Gene Collection (MGC) project;
RL Submitted (JUL-2007) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Cystine/H(+) symporter that mediates export of cystine, the
CC oxidized dimer of cysteine, from lysosomes. Plays an important role in
CC melanin synthesis by catalyzing cystine export from melanosomes,
CC possibly by inhibiting pheomelanin synthesis. In addition to cystine
CC export, also acts as a positive regulator of mTORC1 signaling in kidney
CC proximal tubular cells, via interactions with components of the v-
CC ATPase and Ragulator complexes. Also involved in small GTPase-regulated
CC vesicle trafficking and lysosomal localization of LAMP2A, independently
CC of cystine transporter activity. {ECO:0000250|UniProtKB:P57757}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H(+)(out) + L-cystine(out) = H(+)(in) + L-cystine(in);
CC Xref=Rhea:RHEA:66172, ChEBI:CHEBI:15378, ChEBI:CHEBI:35491;
CC Evidence={ECO:0000250|UniProtKB:O60931};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:66173;
CC Evidence={ECO:0000250|UniProtKB:O60931};
CC -!- SUBUNIT: Interacts with components of the V-ATPase complex. Interacts
CC with components of the Ragulator complex. Interacts with RRAGA/RagA and
CC RRAGC/RagC (By similarity). Interacts with AP-3 complex subunit mu
CC (AP3M1 or AP3M2) (By similarity). {ECO:0000250|UniProtKB:O60931,
CC ECO:0000250|UniProtKB:P57757}.
CC -!- SUBCELLULAR LOCATION: Lysosome membrane {ECO:0000250|UniProtKB:P57757};
CC Multi-pass membrane protein {ECO:0000255}. Melanosome membrane
CC {ECO:0000250|UniProtKB:O60931}; Multi-pass membrane protein
CC {ECO:0000255}. Note=AP-3 complex is required for localization to the
CC lysosome. {ECO:0000250|UniProtKB:O60931}.
CC -!- DOMAIN: The lysosomal targeting motif, together with te second PQ-loop
CC mediate targeting to the lysosome. {ECO:0000250|UniProtKB:O60931}.
CC -!- SIMILARITY: Belongs to the cystinosin family. {ECO:0000305}.
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DR EMBL; BC151357; AAI51358.1; -; mRNA.
DR RefSeq; NP_001095734.1; NM_001102264.1.
DR AlphaFoldDB; A7MB63; -.
DR STRING; 9913.ENSBTAP00000049590; -.
DR PaxDb; A7MB63; -.
DR Ensembl; ENSBTAT00000056260; ENSBTAP00000049590; ENSBTAG00000000831.
DR GeneID; 613527; -.
DR KEGG; bta:613527; -.
DR CTD; 1497; -.
DR VEuPathDB; HostDB:ENSBTAG00000000831; -.
DR VGNC; VGNC:27807; CTNS.
DR eggNOG; KOG3145; Eukaryota.
DR GeneTree; ENSGT00390000005338; -.
DR HOGENOM; CLU_046327_1_0_1; -.
DR InParanoid; A7MB63; -.
DR OMA; WIDVIYT; -.
DR OrthoDB; 1138417at2759; -.
DR TreeFam; TF313589; -.
DR Proteomes; UP000009136; Chromosome 19.
DR Bgee; ENSBTAG00000000831; Expressed in mammary gland and 105 other tissues.
DR ExpressionAtlas; A7MB63; baseline.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005765; C:lysosomal membrane; ISS:UniProtKB.
DR GO; GO:0042470; C:melanosome; ISS:UniProtKB.
DR GO; GO:0033162; C:melanosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005774; C:vacuolar membrane; IBA:GO_Central.
DR GO; GO:0015184; F:L-cystine transmembrane transporter activity; ISS:UniProtKB.
DR GO; GO:0015295; F:solute:proton symporter activity; ISS:UniProtKB.
DR GO; GO:0015811; P:L-cystine transport; ISS:UniProtKB.
DR GO; GO:0042438; P:melanin biosynthetic process; IEA:UniProtKB-KW.
DR GO; GO:0015031; P:protein transport; IEA:UniProtKB-KW.
DR GO; GO:0048021; P:regulation of melanin biosynthetic process; ISS:UniProtKB.
DR InterPro; IPR005282; LC_transporter.
DR InterPro; IPR006603; PQ-loop_rpt.
DR PANTHER; PTHR13131; PTHR13131; 1.
DR Pfam; PF04193; PQ-loop; 2.
DR SMART; SM00679; CTNS; 2.
DR TIGRFAMs; TIGR00951; 2A43; 1.
PE 2: Evidence at transcript level;
KW Glycoprotein; Lysosome; Melanin biosynthesis; Membrane; Protein transport;
KW Reference proteome; Repeat; Signal; Symport; Transmembrane;
KW Transmembrane helix; Transport.
FT SIGNAL 1..22
FT /evidence="ECO:0000250|UniProtKB:O60931"
FT CHAIN 23..367
FT /note="Cystinosin"
FT /id="PRO_0000328324"
FT TOPO_DOM 23..121
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 122..142
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 143..161
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 162..182
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 183..205
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 206..226
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 227..237
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 238..258
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 259..261
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 262..282
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 283..297
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 298..318
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 319..335
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 336..356
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 357..367
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 123..189
FT /note="PQ-loop 1"
FT DOMAIN 263..328
FT /note="PQ-loop 2"
FT MOTIF 362..366
FT /note="Lysosomal targeting motif"
FT /evidence="ECO:0000255"
FT BINDING 305
FT /ligand="H(+)"
FT /ligand_id="ChEBI:CHEBI:15378"
FT /note="protonated residue following cystine-binding"
FT /evidence="ECO:0000250|UniProtKB:O60931"
FT CARBOHYD 51
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 66
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 84
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 104
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 107
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
SQ SEQUENCE 367 AA; 41828 MW; 164337BB7521A5FC CRC64;
MIRRWLVIFI LFPLQLIEKC ESTVDFSVPP IVKLEKGSST SVSISLPRPL NATLVITFEI
TFRSKNVTIL QLPDEVVVPP GTTNSSFRVT SQSVGQVTTY LHGNHSNQTS PRIRFLVIHS
NIVSIINQVI GWIYFVAWSV SFYPQVITNW RRKSVVGLSF DFVVLNLMGF VAYSVFNIGL
FWVPSIKEQF LLKYPNGVNP VDSNDVFFSL HAVALTLVVI VQCLLYERGS QRVSWLAISF
LVLSWLFTLI ALIMAAVGAT TWLQFLFCFS YIKLAVTLVK YFPQAYMNFH YKSTEGWSIG
NVLLDFTGGS FSLLQMFLQS YNNDQWTLIF GDPTKFGLGI FSIIFDVVFF IQHFCLYRKK
PGYDQLN
