ID   DIRC2_HUMAN             Reviewed;         478 AA.
AC   Q96SL1; A8K561; Q8NBX9;
DT   09-JAN-2007, integrated into UniProtKB/Swiss-Prot.
DT   01-DEC-2001, sequence version 1.
DT   14-DEC-2022, entry version 147.
DE   RecName: Full=Solute carrier family 49 member 4 {ECO:0000305};
DE   AltName: Full=Disrupted in renal cancer protein 2;
DE   AltName: Full=Disrupted in renal carcinoma protein 2 {ECO:0000303|PubMed:21692750};
GN   Name=SLC49A4 {ECO:0000312|HGNC:HGNC:16628};
GN   Synonyms=DIRC2 {ECO:0000303|PubMed:11912179, ECO:0000303|PubMed:21692750};
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=Placenta;
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].
RA   Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA   Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA   Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA   Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA   Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA   Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA   Hunkapiller M.W., Myers E.W., Venter J.C.;
RL   Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC   TISSUE=Skin;
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   CHROMOSOMAL TRANSLOCATION, AND TISSUE SPECIFICITY.
RX   PubMed=11912179; DOI=10.1093/hmg/11.6.641;
RA   Bodmer D., Eleveld M., Kater-Baats E., Janssen I., Janssen B., Weterman M.,
RA   Schoenmakers E., Nickerson M., Linehan M., Zbar B., van Kessel A.G.;
RT   "Disruption of a novel MFS transporter gene, DIRC2, by a familial renal
RT   cell carcinoma-associated t(2;3)(q35;q21).";
RL   Hum. Mol. Genet. 11:641-649(2002).
RN   [5]
RP   FUNCTION, GLYCOSYLATION AT ASN-209, PROTEOLYTIC PROCESSING, MUTAGENESIS OF
RP   14-LEU-LEU-15, AND SUBCELLULAR LOCATION.
RX   PubMed=21692750; DOI=10.1042/bj20110166;
RA   Savalas L.R., Gasnier B., Damme M., Lubke T., Wrocklage C., Debacker C.,
RA   Jezegou A., Reinheckel T., Hasilik A., Saftig P., Schroder B.;
RT   "Disrupted in renal carcinoma 2 (DIRC2), a novel transporter of the
RT   lysosomal membrane, is proteolytically processed by cathepsin L.";
RL   Biochem. J. 439:113-128(2011).
CC   -!- FUNCTION: Electrogenic metabolite transporter.
CC       {ECO:0000269|PubMed:21692750}.
CC   -!- SUBCELLULAR LOCATION: Lysosome membrane {ECO:0000269|PubMed:21692750};
CC       Multi-pass membrane protein {ECO:0000269|PubMed:21692750}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1;
CC         IsoId=Q96SL1-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=Q96SL1-2; Sequence=VSP_022302, VSP_022303;
CC   -!- TISSUE SPECIFICITY: Ubiquitous. Expressed in proximal tubular cells of
CC       the kidney. {ECO:0000269|PubMed:11912179}.
CC   -!- PTM: Cleaved in lysosomes by cathepsin L between Leu-214 and Ala-261,
CC       generating a N-glycosylated N-terminal and a non-glycosylated C-
CC       terminal fragment. {ECO:0000269|PubMed:21692750}.
CC   -!- DISEASE: Note=A chromosomal aberration involving DIRC2 has been found
CC       in a family with renal carcinoma. Translocation t(2;3)(q35;q21)
CC       (PubMed:11912179). {ECO:0000269|PubMed:11912179}.
CC   -!- SIMILARITY: Belongs to the major facilitator superfamily.
CC       {ECO:0000305}.
CC   -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC       Haematology;
CC       URL="http://atlasgeneticsoncology.org/Genes/DIRC2ID497.html";
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DR   EMBL; AK027690; BAB55300.1; -; mRNA.
DR   EMBL; AK075158; BAC11440.1; -; mRNA.
DR   EMBL; AK291176; BAF83865.1; -; mRNA.
DR   EMBL; CH471052; EAW79462.1; -; Genomic_DNA.
DR   EMBL; BC039821; AAH39821.1; -; mRNA.
DR   CCDS; CCDS3018.1; -. [Q96SL1-1]
DR   RefSeq; NP_116228.1; NM_032839.2. [Q96SL1-1]
DR   AlphaFoldDB; Q96SL1; -.
DR   SMR; Q96SL1; -.
DR   BioGRID; 124360; 5.
DR   IntAct; Q96SL1; 3.
DR   MINT; Q96SL1; -.
DR   STRING; 9606.ENSP00000261038; -.
DR   TCDB; 2.A.1.28.6; the major facilitator superfamily (mfs).
DR   GlyGen; Q96SL1; 1 site.
DR   iPTMnet; Q96SL1; -.
DR   PhosphoSitePlus; Q96SL1; -.
DR   SwissPalm; Q96SL1; -.
DR   BioMuta; DIRC2; -.
DR   DMDM; 74732717; -.
DR   EPD; Q96SL1; -.
DR   jPOST; Q96SL1; -.
DR   MassIVE; Q96SL1; -.
DR   MaxQB; Q96SL1; -.
DR   PaxDb; Q96SL1; -.
DR   PeptideAtlas; Q96SL1; -.
DR   ProteomicsDB; 78124; -. [Q96SL1-1]
DR   ProteomicsDB; 78125; -. [Q96SL1-2]
DR   Antibodypedia; 32929; 121 antibodies from 21 providers.
DR   DNASU; 84925; -.
DR   Ensembl; ENST00000261038.6; ENSP00000261038.5; ENSG00000138463.9. [Q96SL1-1]
DR   GeneID; 84925; -.
DR   KEGG; hsa:84925; -.
DR   MANE-Select; ENST00000261038.6; ENSP00000261038.5; NM_032839.3; NP_116228.1.
DR   UCSC; uc003efw.5; human. [Q96SL1-1]
DR   AGR; HGNC:16628; -.
DR   CTD; 84925; -.
DR   DisGeNET; 84925; -.
DR   GeneCards; SLC49A4; -.
DR   HGNC; HGNC:16628; SLC49A4.
DR   HPA; ENSG00000138463; Low tissue specificity.
DR   MalaCards; SLC49A4; -.
DR   MIM; 602773; gene.
DR   neXtProt; NX_Q96SL1; -.
DR   OpenTargets; ENSG00000138463; -.
DR   Orphanet; 422526; Hereditary clear cell renal cell carcinoma.
DR   PharmGKB; PA27341; -.
DR   VEuPathDB; HostDB:ENSG00000138463; -.
DR   eggNOG; KOG2563; Eukaryota.
DR   GeneTree; ENSGT01030000234625; -.
DR   HOGENOM; CLU_023132_4_1_1; -.
DR   InParanoid; Q96SL1; -.
DR   OMA; CLNSVTH; -.
DR   OrthoDB; 702737at2759; -.
DR   PhylomeDB; Q96SL1; -.
DR   TreeFam; TF314292; -.
DR   PathwayCommons; Q96SL1; -.
DR   SignaLink; Q96SL1; -.
DR   BioGRID-ORCS; 84925; 9 hits in 1070 CRISPR screens.
DR   ChiTaRS; DIRC2; human.
DR   GenomeRNAi; 84925; -.
DR   Pharos; Q96SL1; Tbio.
DR   PRO; PR:Q96SL1; -.
DR   Proteomes; UP000005640; Chromosome 3.
DR   RNAct; Q96SL1; protein.
DR   Bgee; ENSG00000138463; Expressed in secondary oocyte and 185 other tissues.
DR   ExpressionAtlas; Q96SL1; baseline and differential.
DR   Genevisible; Q96SL1; HS.
DR   GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA.
DR   GO; GO:0005765; C:lysosomal membrane; IEA:UniProtKB-SubCell.
DR   Gene3D; 1.20.1250.20; -; 1.
DR   InterPro; IPR036259; MFS_trans_sf.
DR   SUPFAM; SSF103473; MFS general substrate transporter; 1.
PE   1: Evidence at protein level;
KW   Alternative splicing; Chromosomal rearrangement; Glycoprotein; Lysosome;
KW   Membrane; Reference proteome; Transmembrane; Transmembrane helix;
KW   Transport.
FT   CHAIN           1..478
FT                   /note="Solute carrier family 49 member 4"
FT                   /id="PRO_0000271338"
FT   TOPO_DOM        1..51
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        52..72
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        73..89
FT                   /note="Lumenal"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        90..110
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        111..117
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        118..138
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        139..155
FT                   /note="Lumenal"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        156..176
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        177..184
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        185..205
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        206..229
FT                   /note="Lumenal"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        230..250
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        251..281
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        282..302
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        303..314
FT                   /note="Lumenal"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        315..335
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        336..347
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        348..368
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        369..384
FT                   /note="Lumenal"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        385..405
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        406..414
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        415..435
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        436..442
FT                   /note="Lumenal"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        443..463
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        464..478
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   MOTIF           14..15
FT                   /note="Mediates lysosomal localization"
FT   CARBOHYD        209
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000269|PubMed:21692750"
FT   VAR_SEQ         380..411
FT                   /note="VTLYASCILLGVFLNSSVPIFFELFVETVYPV -> EMGFRHVVQAGLELLS
FT                   LSDSPTLASQNVGIAD (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:14702039"
FT                   /id="VSP_022302"
FT   VAR_SEQ         412..478
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:14702039"
FT                   /id="VSP_022303"
FT   MUTAGEN         14..15
FT                   /note="LL->AA: Abolishes lysosomal localization."
FT                   /evidence="ECO:0000269|PubMed:21692750"
SQ   SEQUENCE   478 AA;  52088 MW;  B752B98647711B89 CRC64;
     MGSRWSSEEE RQPLLGPGLG PGLGASWRSR EAAAAALPAA VPGPGRVYGR RWLVLLLFSL
     LAFVQGLVWN TWGPIQNSAR QAYGFSSWDI ALLVLWGPIG FLPCFAFMWL LDKRGLRITV
     LLTSFLMVLG TGLRCIPISD LILKRRLIHG GQMLNGLAGP TVMNAAPFLS TTWFSADERA
     TATAIASMLS YLGGACAFLV GPLVVPAPNG TSPLLAAESS RAHIKDRIEA VLYAEFGVVC
     LIFSATLAYF PPRPPLPPSV AAASQRLSYR RSVCRLLSNF RFLMIALAYA IPLGVFAGWS
     GVLDLILTPA HVSQVDAGWI GFWSIVGGCV VGIAMARFAD FIRGMLKLIL LLLFSGATLS
     STWFTLTCLN SITHLPLTTV TLYASCILLG VFLNSSVPIF FELFVETVYP VPEGITCGVV
     TFLSNMFMGV LLFFLTFYHT ELSWFNWCLP GSCLLSLLLI LCFRESYDRL YLDVVVSV
//