ID   UT1_MOUSE               Reviewed;         384 AA.
AC   Q8VHL0; Q3U542; Q497G1; Q5RJG2; Q6PDP4; Q9CZX3;
DT   30-AUG-2002, integrated into UniProtKB/Swiss-Prot.
DT   28-JUN-2011, sequence version 2.
DT   24-JAN-2024, entry version 143.
DE   RecName: Full=Urea transporter 1;
DE   AltName: Full=Solute carrier family 14 member 1;
DE   AltName: Full=Urea transporter B;
DE            Short=UT-B;
DE   AltName: Full=Urea transporter, erythrocyte;
GN   Name=Slc14a1;
OS   Mus musculus (Mouse).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Mus; Mus.
OX   NCBI_TaxID=10090;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, TRANSPORTER ACTIVITY,
RP   TISSUE SPECIFICITY, AND DISRUPTION PHENOTYPE.
RC   STRAIN=C57BL/6J; TISSUE=Kidney;
RX   PubMed=11792714; DOI=10.1074/jbc.m200207200;
RA   Yang B., Bankir L., Gillespie A., Epstein C.J., Verkman A.S.;
RT   "Urea-selective concentrating defect in transgenic mice lacking urea
RT   transporter UT-B.";
RL   J. Biol. Chem. 277:10633-10637(2002).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), SUBCELLULAR LOCATION, TISSUE
RP   SPECIFICITY, GLYCOSYLATION, AND INDUCTION.
RC   STRAIN=BALB/cJ; TISSUE=Kidney;
RX   PubMed=15563580; DOI=10.1152/ajpregu.00286.2004;
RA   Lucien N., Bruneval P., Lasbennes F., Belair M.F., Mandet C., Cartron J.P.,
RA   Bailly P., Trinh-Trang-Tan M.M.;
RT   "UT-B1 urea transporter is expressed along the urinary and gastrointestinal
RT   tracts of the mouse.";
RL   Am. J. Physiol. 288:R1046-R1056(2005).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC   STRAIN=C57BL/6J, and NOD; TISSUE=Embryo, and Thymus;
RX   PubMed=16141072; DOI=10.1126/science.1112014;
RA   Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA   Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA   Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA   Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA   Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA   Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA   Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA   Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA   Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA   Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA   Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA   Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA   Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA   Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA   Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA   Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA   Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA   Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA   Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA   Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA   Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA   Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA   Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA   Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA   Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA   van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA   Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA   Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA   Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA   Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA   Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA   Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA   Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA   Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT   "The transcriptional landscape of the mammalian genome.";
RL   Science 309:1559-1563(2005).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA   Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL   Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC   STRAIN=C57BL/6J, and C57BL/6NCr;
RC   TISSUE=Eye, Head, and Hematopoietic stem cell;
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, DISRUPTION PHENOTYPE, SUBCELLULAR LOCATION, AND TISSUE
RP   SPECIFICITY.
RX   PubMed=12133842; DOI=10.1074/jbc.m206948200;
RA   Yang B., Verkman A.S.;
RT   "Analysis of double knockout mice lacking aquaporin-1 and urea transporter
RT   UT-B. Evidence for UT-B-facilitated water transport in erythrocytes.";
RL   J. Biol. Chem. 277:36782-36786(2002).
RN   [7]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-39 (ISOFORM 2), AND
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Spleen;
RX   PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA   Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA   Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT   "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL   Cell 143:1174-1189(2010).
CC   -!- FUNCTION: Mediates the transport of urea driven by a concentration
CC       gradient across the cell membranes of erythrocytes and the renal inner
CC       medullary collecting duct which is critical to the urinary
CC       concentrating mechanism (PubMed:11792714). Facilitates water transport
CC       in erythrocytes (PubMed:12133842). {ECO:0000269|PubMed:11792714,
CC       ECO:0000269|PubMed:12133842}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=urea(in) = urea(out); Xref=Rhea:RHEA:32799, ChEBI:CHEBI:16199;
CC         Evidence={ECO:0000269|PubMed:11792714};
CC   -!- SUBUNIT: Homotrimer; each subunit contains a pore through which urea
CC       permeates (By similarity). Identified in a complex with STOM (By
CC       similarity). {ECO:0000250|UniProtKB:Q13336,
CC       ECO:0000250|UniProtKB:Q5QF96}.
CC   -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:12133842,
CC       ECO:0000269|PubMed:15563580}; Multi-pass membrane protein
CC       {ECO:0000255}. Basolateral cell membrane {ECO:0000269|PubMed:15563580};
CC       Multi-pass membrane protein {ECO:0000255}. Note=Restricted to the
CC       basolateral membrane in various portions of the urothelium.
CC       {ECO:0000269|PubMed:15563580}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1;
CC         IsoId=Q8VHL0-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=Q8VHL0-2; Sequence=VSP_041574;
CC   -!- TISSUE SPECIFICITY: Expressed in brain, kidney, heart, liver, lung,
CC       skeletal muscle, spleen, testis, ureter and urinary bladder (at protein
CC       level). Along the gastrointestinal tract, detected in colon, jejunum
CC       and stomach (at protein level). In the kidney, expressed in some
CC       microvessels of the inner and outer medulla, but not all (at protein
CC       level). Not detected in the cortex (at protein level). Detected in the
CC       urothelium all along the urinary tract, including the papilla surface,
CC       the ureter, the bladder and the urethra (at protein level). In the
CC       brain, expressed at the border of the corpus callosum and striatum in
CC       astrocytic cellular processes surrounding blood microvessels (at
CC       protein level). Detected in erythrocytes (at protein level).
CC       {ECO:0000269|PubMed:11792714, ECO:0000269|PubMed:12133842,
CC       ECO:0000269|PubMed:15563580}.
CC   -!- INDUCTION: Down-regulated by water deprivation in urinary bladder and
CC       ureter, but not in kidney medulla, colon, testis nor brain.
CC       {ECO:0000269|PubMed:15563580}.
CC   -!- PTM: N-glycosylated in red blood cells, as well as in most non-
CC       erythroid tissues, except in the gastrocnemius muscle and in the
CC       gastrointestinal tract, including liver, colon and stomach.
CC       {ECO:0000269|PubMed:15563580}.
CC   -!- DISRUPTION PHENOTYPE: Mutant mice exhibit grossly normal appearance,
CC       activity and behavior. Plasma sodium, potassium, chloride, bicarbonate
CC       and creatinine concentrations, as well as hematocrit, are similar to
CC       wild type animals. Urea permeability in erythrocytes is 45-fold lower
CC       than that from wild-type mice. Daily urine output is 1.5-fold greater
CC       and urine osmolarity is lower than in wild-type mice. After 24 hours of
CC       water deprivation, plasma urea concentration is 30% higher and urine
CC       urea concentration 35% lower in mutant mice than in wild-type animals.
CC       Mice lacking both Aqp1 and Slc14a1 are born at the expected Mendelian
CC       ratio, but do not thrive; half of them die within ten days after birth
CC       and none are alive after two weeks. Urine osmolality is somewhat lower
CC       than that observed with mice lacking Aqp1. Besides, erythrocyte water
CC       permeability is significantly lower than in mice lacking only Aqp1.
CC       {ECO:0000269|PubMed:11792714, ECO:0000269|PubMed:12133842}.
CC   -!- SIMILARITY: Belongs to the urea transporter family. {ECO:0000305}.
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DR   EMBL; AF448798; AAL47138.1; -; mRNA.
DR   EMBL; AJ420967; CAD12807.1; -; mRNA.
DR   EMBL; AK012066; BAB28004.1; -; mRNA.
DR   EMBL; AK041979; BAC31119.1; -; mRNA.
DR   EMBL; AK153891; BAE32238.1; -; mRNA.
DR   EMBL; CH466528; EDL09437.1; -; Genomic_DNA.
DR   EMBL; CH466528; EDL09438.1; -; Genomic_DNA.
DR   EMBL; BC058594; AAH58594.2; -; mRNA.
DR   EMBL; BC086673; AAH86673.1; -; mRNA.
DR   EMBL; BC100570; AAI00571.2; -; mRNA.
DR   CCDS; CCDS29360.1; -. [Q8VHL0-1]
DR   CCDS; CCDS50330.1; -. [Q8VHL0-2]
DR   RefSeq; NP_001164481.1; NM_001171010.1. [Q8VHL0-2]
DR   RefSeq; NP_001164482.1; NM_001171011.1. [Q8VHL0-1]
DR   RefSeq; NP_082398.1; NM_028122.4. [Q8VHL0-1]
DR   AlphaFoldDB; Q8VHL0; -.
DR   SMR; Q8VHL0; -.
DR   STRING; 10090.ENSMUSP00000125114; -.
DR   BindingDB; Q8VHL0; -.
DR   ChEMBL; CHEMBL2163171; -.
DR   GuidetoPHARMACOLOGY; 982; -.
DR   GlyCosmos; Q8VHL0; 1 site, No reported glycans.
DR   GlyGen; Q8VHL0; 1 site.
DR   iPTMnet; Q8VHL0; -.
DR   PhosphoSitePlus; Q8VHL0; -.
DR   SwissPalm; Q8VHL0; -.
DR   EPD; Q8VHL0; -.
DR   MaxQB; Q8VHL0; -.
DR   PaxDb; 10090-ENSMUSP00000125114; -.
DR   PeptideAtlas; Q8VHL0; -.
DR   ProteomicsDB; 299662; -. [Q8VHL0-1]
DR   ProteomicsDB; 299663; -. [Q8VHL0-2]
DR   Antibodypedia; 22414; 192 antibodies from 26 providers.
DR   DNASU; 108052; -.
DR   Ensembl; ENSMUST00000091813.12; ENSMUSP00000089421.6; ENSMUSG00000059336.15. [Q8VHL0-1]
DR   Ensembl; ENSMUST00000160292.8; ENSMUSP00000125114.2; ENSMUSG00000059336.15. [Q8VHL0-2]
DR   Ensembl; ENSMUST00000160639.2; ENSMUSP00000125367.2; ENSMUSG00000059336.15. [Q8VHL0-1]
DR   GeneID; 108052; -.
DR   KEGG; mmu:108052; -.
DR   UCSC; uc008fsc.2; mouse. [Q8VHL0-1]
DR   UCSC; uc008fsd.2; mouse. [Q8VHL0-2]
DR   AGR; MGI:1351654; -.
DR   CTD; 6563; -.
DR   MGI; MGI:1351654; Slc14a1.
DR   VEuPathDB; HostDB:ENSMUSG00000059336; -.
DR   eggNOG; ENOG502S2GD; Eukaryota.
DR   GeneTree; ENSGT00390000018729; -.
DR   HOGENOM; CLU_047509_1_0_1; -.
DR   InParanoid; Q8VHL0; -.
DR   OrthoDB; 3682310at2759; -.
DR   TreeFam; TF332858; -.
DR   Reactome; R-MMU-425366; Transport of bile salts and organic acids, metal ions and amine compounds.
DR   BioGRID-ORCS; 108052; 1 hit in 77 CRISPR screens.
DR   ChiTaRS; Slc14a1; mouse.
DR   PRO; PR:Q8VHL0; -.
DR   Proteomes; UP000000589; Chromosome 18.
DR   RNAct; Q8VHL0; Protein.
DR   Bgee; ENSMUSG00000059336; Expressed in bone marrow and 90 other cell types or tissues.
DR   GO; GO:0016323; C:basolateral plasma membrane; IDA:UniProtKB.
DR   GO; GO:0016020; C:membrane; TAS:MGI.
DR   GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR   GO; GO:0015265; F:urea channel activity; ISS:UniProtKB.
DR   GO; GO:0015204; F:urea transmembrane transporter activity; IMP:MGI.
DR   GO; GO:0005372; F:water transmembrane transporter activity; IDA:MGI.
DR   GO; GO:0051649; P:establishment of localization in cell; IGI:MGI.
DR   GO; GO:0071918; P:urea transmembrane transport; ISS:UniProtKB.
DR   GO; GO:0015840; P:urea transport; IMP:MGI.
DR   GO; GO:0006833; P:water transport; IDA:MGI.
DR   Gene3D; 1.10.3430.10; Ammonium transporter AmtB like domains; 1.
DR   InterPro; IPR029020; Ammonium/urea_transptr.
DR   InterPro; IPR004937; Urea_transporter.
DR   PANTHER; PTHR10464; UREA TRANSPORTER; 1.
DR   PANTHER; PTHR10464:SF5; UREA TRANSPORTER 1; 1.
DR   Pfam; PF03253; UT; 1.
DR   PIRSF; PIRSF016502; Urea_transporter; 1.
DR   Genevisible; Q8VHL0; MM.
PE   1: Evidence at protein level;
KW   Alternative splicing; Cell membrane; Glycoprotein; Membrane;
KW   Phosphoprotein; Reference proteome; Transmembrane; Transmembrane helix;
KW   Transport.
FT   CHAIN           1..384
FT                   /note="Urea transporter 1"
FT                   /id="PRO_0000065738"
FT   TRANSMEM        61..81
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        85..105
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        111..131
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        138..158
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        168..188
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        250..270
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        276..296
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        305..325
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        327..347
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   SITE            334
FT                   /note="Important for channel permeability"
FT                   /evidence="ECO:0000250|UniProtKB:Q5QF96"
FT   CARBOHYD        206
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   VAR_SEQ         1
FT                   /note="M -> MNGQSLTGGTDDAHHGPLWIDPFGNRGDKAAPEGFRRLSLALAQRWR
FT                   EQEPEEEIAM (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:16141072"
FT                   /id="VSP_041574"
FT   CONFLICT        8
FT                   /note="V -> A (in Ref. 1; AAL47138)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        50
FT                   /note="V -> A (in Ref. 5; AAI00571)"
FT                   /evidence="ECO:0000305"
FT   MOD_RES         Q8VHL0-2:39
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:21183079"
SQ   SEQUENCE   384 AA;  42126 MW;  E66ED087341C07B7 CRC64;
     MEDSPTMVKV DRGENQILSC RGRRCGFKVL GYVTGDMKEF ANWLKDKPVV LQFMDWILRG
     ISQVVFVSNP ISGILILVGL LVQNPWWALC GCVGTVVSTL TALLLSQDRS AIAAGLQGYN
     ATLVGILMAV FSNKGDYFWW LIFPVSAMSM TCPVFSSALS SVLSKWDLPV FTLPFNMALS
     MYLSATGHYN TFFPSKLFTP VSSVPNITWS ELSALELLKS LPVGVGQIYG CDNPWTGGIF
     LCAILLSSPL MCLHAAIGSL LGVIAGLSLA APFEDIYFGL WGFNSSLACI AIGGMFMALT
     WQTHLLALAC ALFTAYFGAC MAHLMAVVHL PACTWSFCLA TLLFLLLTTK NPNIYRMPLS
     KVTYSEENRI FYLQNKKRMV ESPL
//