S28A3_HUMAN
ID S28A3_HUMAN Reviewed; 691 AA.
AC Q9HAS3; A8K9Y4; B1AML0; B2RA51; B4E2S8; F5GYE3;
DT 18-MAR-2008, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2001, sequence version 1.
DT 03-AUG-2022, entry version 159.
DE RecName: Full=Solute carrier family 28 member 3;
DE AltName: Full=Concentrative Na(+)-nucleoside cotransporter 3 {ECO:0000303|PubMed:11032837};
DE Short=CNT 3 {ECO:0000303|PubMed:11032837};
DE Short=hCNT3 {ECO:0000303|PubMed:11032837};
GN Name=SLC28A3; Synonyms=CNT3 {ECO:0000303|PubMed:11032837};
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 [MRNA] (ISOFORM 1), INDUCTION, TISSUE SPECIFICITY,
RP BIOPHYSICOCHEMICAL PROPERTIES, FUNCTION, AND TRANSPORTER ACTIVITY.
RX PubMed=11032837; DOI=10.1074/jbc.m007746200;
RA Ritzel M.W.L., Ng A.M.L., Yao S.Y.M., Graham K., Loewen S.K., Smith K.M.,
RA Ritzel R.G., Mowles D.A., Carpenter P., Chen X.-Z., Karpinski E.,
RA Hyde R.J., Baldwin S.A., Cass C.E., Young J.D.;
RT "Molecular identification and characterization of novel human and mouse
RT concentrative Na+-nucleoside cotransporter proteins (hCNT3 and mCNT3)
RT broadly selective for purine and pyrimidine nucleosides (system cib).";
RL J. Biol. Chem. 276:2914-2927(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), AND VARIANTS
RP CYS-113; THR-366 AND PHE-513.
RC TISSUE=Trachea;
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164053; DOI=10.1038/nature02465;
RA Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L.,
RA Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R.,
RA Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S.,
RA Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K.,
RA Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C.,
RA Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E.,
RA Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M.,
RA Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J.,
RA Frankish A., Frankland J.A., French L., Fricker D.G., Garner P.,
RA Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S.,
RA Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E.,
RA Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D.,
RA Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E.,
RA Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K.,
RA Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S.,
RA Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J.,
RA Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E.,
RA McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V.,
RA Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S.,
RA Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K.,
RA Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J.,
RA Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M.,
RA West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L.,
RA Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M.,
RA Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J.,
RA Dunham I.;
RT "DNA sequence and analysis of human chromosome 9.";
RL Nature 429:369-374(2004).
RN [4]
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 (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Colon;
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 [6]
RP FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, AND VARIANTS ASN-5; PHE-131 AND
RP PHE-513.
RX PubMed=15861042; DOI=10.1097/01213011-200503000-00006;
RA Damaraju S., Zhang J., Visser F., Tackaberry T., Dufour J., Smith K.M.,
RA Slugoski M., Ritzel M.W.L., Baldwin S.A., Young J.D., Cass C.E.;
RT "Identification and functional characterization of variants in human
RT concentrative nucleoside transporter 3, hCNT3 (SLC28A3), arising from
RT single nucleotide polymorphisms in coding regions of the hCNT3 gene.";
RL Pharmacogenet. Genomics 15:173-182(2005).
RN [7]
RP FUNCTION.
RX PubMed=16446384; DOI=10.1124/mol.105.018945;
RA Hu H., Endres C.J., Chang C., Umapathy N.S., Lee E.-W., Fei Y.-J.,
RA Itagaki S., Swaan P.W., Ganapathy V., Unadkat J.D.;
RT "Electrophysiological characterization and modeling of the structure
RT activity relationship of the human concentrative nucleoside transporter 3
RT (hCNT3).";
RL Mol. Pharmacol. 69:1542-1553(2006).
RN [8]
RP FUNCTION.
RX PubMed=17140564; DOI=10.1016/j.ejphar.2006.10.062;
RA Yamamoto T., Kuniki K., Takekuma Y., Hirano T., Iseki K., Sugawara M.;
RT "Ribavirin uptake by cultured human choriocarcinoma (BeWo) cells and
RT Xenopus laevis oocytes expressing recombinant plasma membrane human
RT nucleoside transporters.";
RL Eur. J. Pharmacol. 557:1-8(2007).
RN [9]
RP SUBCELLULAR LOCATION, AND ALTERNATIVE SPLICING.
RX PubMed=18827020; DOI=10.1096/fj.08-113902;
RA Errasti-Murugarren E., Molina-Arcas M., Casado F.J., Pastor-Anglada M.;
RT "A splice variant of the SLC28A3 gene encodes a novel human concentrative
RT nucleoside transporter-3 (hCNT3) protein localized in the endoplasmic
RT reticulum.";
RL FASEB J. 23:172-182(2009).
RN [10]
RP FUNCTION, SUBCELLULAR LOCATION, AND MUTAGENESIS OF SER-568.
RX PubMed=21998139; DOI=10.1152/ajpcell.00198.2011;
RA Cano-Soldado P., Gorraitz E., Errasti-Murugarren E., Casado F.J.,
RA Lostao M.P., Pastor-Anglada M.;
RT "Functional analysis of the human concentrative nucleoside transporter-1
RT variant hCNT1S546P provides insight into the sodium-binding pocket.";
RL Am. J. Physiol. 302:C257-C266(2012).
RN [11] {ECO:0007744|PDB:6KSW}
RP STRUCTURE BY ELECTRON MICROSCOPY (3.60 ANGSTROMS) OF 70-691.
RX PubMed=32776918; DOI=10.1371/journal.pbio.3000790;
RA Zhou Y., Liao L., Wang C., Li J., Chi P., Xiao Q., Liu Q., Guo L., Sun L.,
RA Deng D.;
RT "Cryo-EM structure of the human concentrative nucleoside transporter
RT CNT3.";
RL PLoS Biol. 18:e3000790-e3000790(2020).
RN [12]
RP VARIANTS LYS-4; ASN-5; HIS-62; LYS-67; CYS-113; VAL-328; GLN-349; ARG-367;
RP ILE-418 AND HIS-585, AND CHARACTERIZATION OF VARIANT ARG-367.
RX PubMed=15738947; DOI=10.1038/sj.tpj.6500303;
RA Badagnani I., Chan W., Castro R.A., Brett C.M., Huang C.C., Stryke D.,
RA Kawamoto M., Johns S.J., Ferrin T.E., Carlson E.J., Burchard E.G.,
RA Giacomini K.M.;
RT "Functional analysis of genetic variants in the human concentrative
RT nucleoside transporter 3 (CNT3; SLC28A3).";
RL Pharmacogenomics J. 5:157-165(2005).
RN [13]
RP VARIANT ARG-602, AND CHARACTERIZATION OF VARIANT ARG-602.
RX PubMed=17993510; DOI=10.1124/mol.107.041848;
RA Errasti-Murugarren E., Cano-Soldado P., Pastor-Anglada M., Casado F.J.;
RT "Functional characterization of a nucleoside-derived drug transporter
RT variant (hCNT3C602R) showing altered sodium-binding capacity.";
RL Mol. Pharmacol. 73:379-386(2008).
CC -!- FUNCTION: Sodium-dependent, pyrimidine- and purine-selective
CC (PubMed:11032837, PubMed:15861042, PubMed:16446384, PubMed:17140564,
CC PubMed:21998139). Involved in the homeostasis of endogenous nucleosides
CC (PubMed:11032837, PubMed:15861042). Exhibits the transport
CC characteristics of the nucleoside transport system cib or N3 subtype
CC (N3/cib) (with marked transport of both thymidine and inosine)
CC (PubMed:11032837). Employs a 2:1 sodium/nucleoside ratio
CC (PubMed:11032837). Also able to transport gemcitabine, 3'-azido-3'-
CC deoxythymidine (AZT), ribavirin and 3-deazauridine (PubMed:11032837,
CC PubMed:17140564). {ECO:0000269|PubMed:11032837,
CC ECO:0000269|PubMed:15861042, ECO:0000269|PubMed:16446384,
CC ECO:0000269|PubMed:17140564, ECO:0000269|PubMed:21998139}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2 Na(+)(out) + thymidine(out) = 2 Na(+)(in) + thymidine(in);
CC Xref=Rhea:RHEA:69899, ChEBI:CHEBI:17748, ChEBI:CHEBI:29101;
CC Evidence={ECO:0000269|PubMed:11032837};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=cytidine(out) + 2 Na(+)(out) = cytidine(in) + 2 Na(+)(in);
CC Xref=Rhea:RHEA:69903, ChEBI:CHEBI:17562, ChEBI:CHEBI:29101;
CC Evidence={ECO:0000269|PubMed:11032837};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2 Na(+)(out) + uridine(out) = 2 Na(+)(in) + uridine(in);
CC Xref=Rhea:RHEA:69907, ChEBI:CHEBI:16704, ChEBI:CHEBI:29101;
CC Evidence={ECO:0000269|PubMed:11032837};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=adenosine(out) + 2 Na(+)(out) = adenosine(in) + 2 Na(+)(in);
CC Xref=Rhea:RHEA:69911, ChEBI:CHEBI:16335, ChEBI:CHEBI:29101;
CC Evidence={ECO:0000269|PubMed:11032837};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=guanosine(out) + 2 Na(+)(out) = guanosine(in) + 2 Na(+)(in);
CC Xref=Rhea:RHEA:69915, ChEBI:CHEBI:16750, ChEBI:CHEBI:29101;
CC Evidence={ECO:0000269|PubMed:11032837};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=inosine(out) + 2 Na(+)(out) = inosine(in) + 2 Na(+)(in);
CC Xref=Rhea:RHEA:69919, ChEBI:CHEBI:17596, ChEBI:CHEBI:29101;
CC Evidence={ECO:0000269|PubMed:11032837};
CC -!- CATALYTIC ACTIVITY: [Isoform 1]:
CC Reaction=2 Na(+)(out) + uridine(out) = 2 Na(+)(in) + uridine(in);
CC Xref=Rhea:RHEA:69907, ChEBI:CHEBI:16704, ChEBI:CHEBI:29101;
CC Evidence={ECO:0000269|PubMed:32776918};
CC -!- CATALYTIC ACTIVITY: [Isoform 2]:
CC Reaction=2 Na(+)(out) + uridine(out) = 2 Na(+)(in) + uridine(in);
CC Xref=Rhea:RHEA:69907, ChEBI:CHEBI:16704, ChEBI:CHEBI:29101;
CC Evidence={ECO:0000269|PubMed:32776918};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=21.6 uM for uridine {ECO:0000269|PubMed:11032837,
CC ECO:0000269|PubMed:15861042};
CC KM=15.4 uM for cytidine {ECO:0000269|PubMed:11032837,
CC ECO:0000269|PubMed:15861042};
CC KM=21.2 uM for thymidine {ECO:0000269|PubMed:11032837,
CC ECO:0000269|PubMed:15861042};
CC KM=15.1 uM for adenosine {ECO:0000269|PubMed:11032837,
CC ECO:0000269|PubMed:15861042};
CC KM=43 uM for guanosine {ECO:0000269|PubMed:11032837,
CC ECO:0000269|PubMed:15861042};
CC KM=52.5 uM for inosine {ECO:0000269|PubMed:11032837,
CC ECO:0000269|PubMed:15861042};
CC Vmax=25.8 pmol/min/mg enzyme for uridine uptake
CC {ECO:0000269|PubMed:11032837, ECO:0000269|PubMed:15861042};
CC Vmax=32.8 pmol/min/mg enzyme for cytidine uptake
CC {ECO:0000269|PubMed:11032837, ECO:0000269|PubMed:15861042};
CC Vmax=24.2 pmol/min/mg enzyme for thymidine uptake
CC {ECO:0000269|PubMed:11032837, ECO:0000269|PubMed:15861042};
CC Vmax=30.4 pmol/min/mg enzyme for adenosine uptake
CC {ECO:0000269|PubMed:11032837, ECO:0000269|PubMed:15861042};
CC Vmax=51.4 pmol/min/mg enzyme for guanosine uptake
CC {ECO:0000269|PubMed:11032837, ECO:0000269|PubMed:15861042};
CC Vmax=44.8 pmol/min/mg enzyme for inosine uptake
CC {ECO:0000269|PubMed:11032837, ECO:0000269|PubMed:15861042};
CC -!- SUBUNIT: Homotrimer. {ECO:0000269|PubMed:32776918}.
CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Cell membrane
CC {ECO:0000269|PubMed:21998139}; Multi-pass membrane protein
CC {ECO:0000269|PubMed:32776918}.
CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:18827020}; Multi-pass membrane protein
CC {ECO:0000269|PubMed:32776918}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9HAS3-1; Sequence=Displayed;
CC Name=2; Synonyms=hCNT3ins {ECO:0000303|PubMed:18827020};
CC IsoId=Q9HAS3-2; Sequence=VSP_053848;
CC -!- TISSUE SPECIFICITY: Expressed in pancreas, bone marrow, trachea,
CC mammary gland, liver, prostate, and regions of intestine, brain, lung,
CC placenta, testis, kidney, and heart. {ECO:0000269|PubMed:11032837}.
CC -!- INDUCTION: Up-regulated by phorbol myristate acetate (PMA) in HL-60
CC cells. {ECO:0000269|PubMed:11032837}.
CC -!- MISCELLANEOUS: [Isoform 2]: Exhibits a shorter half-life than isoform
CC 1, degraded via a proteasome-dependent pathway. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the concentrative nucleoside transporter (CNT)
CC (TC 2.A.41) family. {ECO:0000305}.
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DR EMBL; AF305210; AAG22551.1; -; mRNA.
DR EMBL; AK292849; BAF85538.1; -; mRNA.
DR EMBL; AK304406; BAG65240.1; -; mRNA.
DR EMBL; AK314039; BAG36748.1; -; mRNA.
DR EMBL; AL353787; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL356134; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC093821; AAH93821.1; -; mRNA.
DR EMBL; BC093823; AAH93823.1; -; mRNA.
DR EMBL; CH471089; EAW62686.1; -; Genomic_DNA.
DR CCDS; CCDS6670.1; -. [Q9HAS3-1]
DR RefSeq; NP_001186562.1; NM_001199633.1. [Q9HAS3-1]
DR RefSeq; NP_071410.1; NM_022127.2. [Q9HAS3-1]
DR PDB; 6KSW; EM; 3.60 A; A/B/C=70-691.
DR PDBsum; 6KSW; -.
DR AlphaFoldDB; Q9HAS3; -.
DR SMR; Q9HAS3; -.
DR BioGRID; 122045; 1.
DR STRING; 9606.ENSP00000365413; -.
DR BindingDB; Q9HAS3; -.
DR ChEMBL; CHEMBL5707; -.
DR DrugBank; DB00640; Adenosine.
DR DrugBank; DB00993; Azathioprine.
DR DrugBank; DB00242; Cladribine.
DR DrugBank; DB01073; Fludarabine.
DR DrugBank; DB00441; Gemcitabine.
DR DrugBank; DB04335; Inosine.
DR DrugBank; DB01033; Mercaptopurine.
DR DrugBank; DB00811; Ribavirin.
DR DrugBank; DB09327; Tegafur-uracil.
DR DrugBank; DB04485; Thymidine.
DR GuidetoPHARMACOLOGY; 1116; -.
DR TCDB; 2.A.41.2.8; the concentrative nucleoside transporter (cnt) family.
DR iPTMnet; Q9HAS3; -.
DR PhosphoSitePlus; Q9HAS3; -.
DR BioMuta; SLC28A3; -.
DR DMDM; 74752767; -.
DR EPD; Q9HAS3; -.
DR MassIVE; Q9HAS3; -.
DR PaxDb; Q9HAS3; -.
DR PeptideAtlas; Q9HAS3; -.
DR PRIDE; Q9HAS3; -.
DR ProteomicsDB; 24712; -.
DR ProteomicsDB; 81424; -. [Q9HAS3-1]
DR Antibodypedia; 13126; 72 antibodies from 15 providers.
DR DNASU; 64078; -.
DR Ensembl; ENST00000376238.5; ENSP00000365413.4; ENSG00000197506.8. [Q9HAS3-1]
DR GeneID; 64078; -.
DR KEGG; hsa:64078; -.
DR MANE-Select; ENST00000376238.5; ENSP00000365413.4; NM_001199633.2; NP_001186562.1.
DR UCSC; uc010mpz.4; human. [Q9HAS3-1]
DR CTD; 64078; -.
DR DisGeNET; 64078; -.
DR GeneCards; SLC28A3; -.
DR HGNC; HGNC:16484; SLC28A3.
DR HPA; ENSG00000197506; Tissue enhanced (choroid plexus, salivary gland).
DR MIM; 608269; gene.
DR neXtProt; NX_Q9HAS3; -.
DR OpenTargets; ENSG00000197506; -.
DR PharmGKB; PA426; -.
DR VEuPathDB; HostDB:ENSG00000197506; -.
DR eggNOG; KOG3747; Eukaryota.
DR GeneTree; ENSGT00390000016025; -.
DR HOGENOM; CLU_016813_3_0_1; -.
DR InParanoid; Q9HAS3; -.
DR OMA; IMLYAMC; -.
DR PhylomeDB; Q9HAS3; -.
DR TreeFam; TF314131; -.
DR PathwayCommons; Q9HAS3; -.
DR Reactome; R-HSA-83936; Transport of nucleosides and free purine and pyrimidine bases across the plasma membrane.
DR Reactome; R-HSA-9748787; Azathioprine ADME.
DR SABIO-RK; Q9HAS3; -.
DR BioGRID-ORCS; 64078; 11 hits in 1070 CRISPR screens.
DR ChiTaRS; SLC28A3; human.
DR GenomeRNAi; 64078; -.
DR Pharos; Q9HAS3; Tchem.
DR PRO; PR:Q9HAS3; -.
DR Proteomes; UP000005640; Chromosome 9.
DR RNAct; Q9HAS3; protein.
DR Bgee; ENSG00000197506; Expressed in cartilage tissue and 121 other tissues.
DR Genevisible; Q9HAS3; HS.
DR GO; GO:0031526; C:brush border membrane; ISS:ARUK-UCL.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0005337; F:nucleoside transmembrane transporter activity; IBA:GO_Central.
DR GO; GO:0005415; F:nucleoside:sodium symporter activity; IBA:GO_Central.
DR GO; GO:0005345; F:purine nucleobase transmembrane transporter activity; NAS:ARUK-UCL.
DR GO; GO:0015390; F:purine-specific nucleoside:sodium symporter activity; IBA:GO_Central.
DR GO; GO:0015389; F:pyrimidine- and adenine-specific:sodium symporter activity; IBA:GO_Central.
DR GO; GO:0015293; F:symporter activity; IBA:GO_Central.
DR GO; GO:0015213; F:uridine transmembrane transporter activity; IDA:ARUK-UCL.
DR GO; GO:1901642; P:nucleoside transmembrane transport; IDA:ARUK-UCL.
DR GO; GO:1904823; P:purine nucleobase transmembrane transport; NAS:ARUK-UCL.
DR GO; GO:0015860; P:purine nucleoside transmembrane transport; IBA:GO_Central.
DR GO; GO:0015864; P:pyrimidine nucleoside transport; IBA:GO_Central.
DR GO; GO:0072531; P:pyrimidine-containing compound transmembrane transport; IDA:ARUK-UCL.
DR GO; GO:0015862; P:uridine transport; IDA:ARUK-UCL.
DR GO; GO:0006855; P:xenobiotic transmembrane transport; TAS:Reactome.
DR InterPro; IPR008276; C_nuclsd_transpt.
DR InterPro; IPR018270; C_nuclsd_transpt_met_bac.
DR InterPro; IPR030211; CNT3.
DR InterPro; IPR011657; CNT_C_dom.
DR InterPro; IPR002668; CNT_N_dom.
DR InterPro; IPR011642; Gate_dom.
DR PANTHER; PTHR10590; PTHR10590; 1.
DR PANTHER; PTHR10590:SF18; PTHR10590:SF18; 1.
DR Pfam; PF07670; Gate; 1.
DR Pfam; PF07662; Nucleos_tra2_C; 1.
DR Pfam; PF01773; Nucleos_tra2_N; 1.
DR TIGRFAMs; TIGR00804; nupC; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cell membrane; Endoplasmic reticulum;
KW Membrane; Reference proteome; Symport; Transmembrane; Transmembrane helix;
KW Transport.
FT CHAIN 1..691
FT /note="Solute carrier family 28 member 3"
FT /id="PRO_0000324146"
FT TOPO_DOM 1..102
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 103..123
FT /note="Helical; Name=TM1"
FT /evidence="ECO:0000269|PubMed:32776918,
FT ECO:0007744|PDB:6KSW"
FT TOPO_DOM 124..128
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 129..149
FT /note="Helical; Name=TM2"
FT /evidence="ECO:0000269|PubMed:32776918,
FT ECO:0007744|PDB:6KSW"
FT TOPO_DOM 150..173
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 174..194
FT /note="Helical; Name=TM3"
FT /evidence="ECO:0000269|PubMed:32776918,
FT ECO:0007744|PDB:6KSW"
FT TOPO_DOM 195..197
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 198..219
FT /note="Helical; Name=TM4"
FT /evidence="ECO:0000269|PubMed:32776918,
FT ECO:0007744|PDB:6KSW"
FT TOPO_DOM 220..227
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 228..247
FT /note="Helical; Name=TM5"
FT /evidence="ECO:0000269|PubMed:32776918,
FT ECO:0007744|PDB:6KSW"
FT TOPO_DOM 248..284
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 285..305
FT /note="Helical; Name=TM6"
FT /evidence="ECO:0000269|PubMed:32776918,
FT ECO:0007744|PDB:6KSW"
FT TOPO_DOM 306..329
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT INTRAMEM 330..348
FT /note="Helical; Name=HP1"
FT /evidence="ECO:0000269|PubMed:32776918,
FT ECO:0007744|PDB:6KSW"
FT TOPO_DOM 349..361
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 362..384
FT /note="Helical; Name=TM7"
FT /evidence="ECO:0000269|PubMed:32776918,
FT ECO:0007744|PDB:6KSW"
FT TOPO_DOM 385..386
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 387..408
FT /note="Helical; Name=TM8"
FT /evidence="ECO:0000269|PubMed:32776918,
FT ECO:0007744|PDB:6KSW"
FT TOPO_DOM 409..443
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 444..469
FT /note="Helical; Name=TM9"
FT /evidence="ECO:0000269|PubMed:32776918,
FT ECO:0007744|PDB:6KSW"
FT TOPO_DOM 470..507
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT INTRAMEM 508..527
FT /note="Helical; Name=HP2"
FT /evidence="ECO:0000269|PubMed:32776918,
FT ECO:0007744|PDB:6KSW"
FT TOPO_DOM 528..566
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 567..577
FT /note="Helical; Name=TM10"
FT /evidence="ECO:0000269|PubMed:32776918,
FT ECO:0007744|PDB:6KSW"
FT TOPO_DOM 578..590
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 591..613
FT /note="Helical; Name=TM11"
FT /evidence="ECO:0000269|PubMed:32776918,
FT ECO:0007744|PDB:6KSW"
FT TOPO_DOM 614..691
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT REGION 1..78
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 17..43
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 44..78
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 1..69
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_053848"
FT VARIANT 4
FT /note="R -> K (in dbSNP:rs11568401)"
FT /evidence="ECO:0000269|PubMed:15738947"
FT /id="VAR_039665"
FT VARIANT 5
FT /note="S -> N (in dbSNP:rs11568403)"
FT /evidence="ECO:0000269|PubMed:15738947,
FT ECO:0000269|PubMed:15861042"
FT /id="VAR_039666"
FT VARIANT 62
FT /note="D -> H (in dbSNP:rs45621433)"
FT /evidence="ECO:0000269|PubMed:15738947"
FT /id="VAR_039667"
FT VARIANT 67
FT /note="R -> K (in dbSNP:rs11568411)"
FT /evidence="ECO:0000269|PubMed:15738947"
FT /id="VAR_039668"
FT VARIANT 113
FT /note="Y -> C (in dbSNP:rs10868138)"
FT /evidence="ECO:0000269|PubMed:14702039,
FT ECO:0000269|PubMed:15738947"
FT /id="VAR_039669"
FT VARIANT 131
FT /note="L -> F"
FT /evidence="ECO:0000269|PubMed:15861042"
FT /id="VAR_039670"
FT VARIANT 221
FT /note="P -> Q (in dbSNP:rs11140503)"
FT /id="VAR_039671"
FT VARIANT 328
FT /note="I -> V (in dbSNP:rs11568418)"
FT /evidence="ECO:0000269|PubMed:15738947"
FT /id="VAR_039672"
FT VARIANT 349
FT /note="R -> Q (in dbSNP:rs45525131)"
FT /evidence="ECO:0000269|PubMed:15738947"
FT /id="VAR_039673"
FT VARIANT 366
FT /note="A -> T (in dbSNP:rs140138960)"
FT /evidence="ECO:0000269|PubMed:14702039"
FT /id="VAR_070606"
FT VARIANT 367
FT /note="G -> R (reduced transport of inosine and thymidine;
FT dbSNP:rs11568388)"
FT /evidence="ECO:0000269|PubMed:15738947"
FT /id="VAR_039674"
FT VARIANT 418
FT /note="L -> I (in dbSNP:rs11568405)"
FT /evidence="ECO:0000269|PubMed:15738947"
FT /id="VAR_039675"
FT VARIANT 513
FT /note="Y -> F (in dbSNP:rs56350726)"
FT /evidence="ECO:0000269|PubMed:14702039,
FT ECO:0000269|PubMed:15861042"
FT /id="VAR_039676"
FT VARIANT 585
FT /note="R -> H (in dbSNP:rs11568398)"
FT /evidence="ECO:0000269|PubMed:15738947"
FT /id="VAR_039677"
FT VARIANT 602
FT /note="C -> R (lower concentrative capacity and altered
FT sodium binding capacity)"
FT /evidence="ECO:0000269|PubMed:17993510"
FT /id="VAR_039678"
FT MUTAGEN 568
FT /note="S->P: Decreased uridine transport. Normal
FT localization to the cell membrane."
FT /evidence="ECO:0000269|PubMed:21998139"
FT CONFLICT 251
FT /note="I -> V (in Ref. 2; BAG36748)"
FT /evidence="ECO:0000305"
FT CONFLICT 293
FT /note="V -> I (in Ref. 2; BAG36748)"
FT /evidence="ECO:0000305"
FT CONFLICT 505
FT /note="F -> L (in Ref. 2; BAG65240)"
FT /evidence="ECO:0000305"
FT CONFLICT 628
FT /note="A -> S (in Ref. 2; BAF85538)"
FT /evidence="ECO:0000305"
FT CONFLICT 639
FT /note="K -> E (in Ref. 2; BAG36748)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 691 AA; 76930 MW; 80FD14518A8BFA61 CRC64;
MELRSTAAPR AEGYSNVGFQ NEENFLENEN TSGNNSIRSR AVQSREHTNT KQDEEQVTVE
QDSPRNREHM EDDDEEMQQK GCLERRYDTV CGFCRKHKTT LRHIIWGILL AGYLVMVISA
CVLNFHRALP LFVITVAAIF FVVWDHLMAK YEHRIDEMLS PGRRLLNSHW FWLKWVIWSS
LVLAVIFWLA FDTAKLGQQQ LVSFGGLIMY IVLLFLFSKY PTRVYWRPVL WGIGLQFLLG
LLILRTDPGF IAFDWLGRQV QTFLEYTDAG ASFVFGEKYK DHFFAFKVLP IVVFFSTVMS
MLYYLGLMQW IIRKVGWIML VTTGSSPIES VVASGNIFVG QTESPLLVRP YLPYITKSEL
HAIMTAGFST IAGSVLGAYI SFGVPSSHLL TASVMSAPAS LAAAKLFWPE TEKPKITLKN
AMKMESGDSG NLLEAATQGA SSSISLVANI AVNLIAFLAL LSFMNSALSW FGNMFDYPQL
SFELICSYIF MPFSFMMGVE WQDSFMVARL IGYKTFFNEF VAYEHLSKWI HLRKEGGPKF
VNGVQQYISI RSEIIATYAL CGFANIGSLG IVIGGLTSMA PSRKRDIASG AVRALIAGTV
ACFMTACIAG ILSSTPVDIN CHHVLENAFN STFPGNTTKV IACCQSLLSS TVAKGPGEVI
PGGNHSLYSL KGCCTLLNPS TFNCNGISNT F
