DIRC2_HUMAN
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 03-AUG-2022, entry version 145.
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 BioMuta; DIRC2; -.
DR DMDM; 74732717; -.
DR EPD; Q96SL1; -.
DR jPOST; Q96SL1; -.
DR MassIVE; Q96SL1; -.
DR MaxQB; Q96SL1; -.
DR PaxDb; Q96SL1; -.
DR PeptideAtlas; Q96SL1; -.
DR PRIDE; Q96SL1; -.
DR ProteomicsDB; 78124; -. [Q96SL1-1]
DR ProteomicsDB; 78125; -. [Q96SL1-2]
DR Antibodypedia; 32929; 122 antibodies from 22 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 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:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
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; SSF103473; 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
