ID   UT2_MOUSE               Reviewed;         930 AA.
AC   Q8R4T9; B2RWS5; Q8K5D0; Q9ES04; Q9ES05;
DT   23-MAR-2010, integrated into UniProtKB/Swiss-Prot.
DT   23-MAR-2010, sequence version 2.
DT   24-JAN-2024, entry version 117.
DE   RecName: Full=Urea transporter 2;
DE   AltName: Full=Solute carrier family 14 member 2;
DE   AltName: Full=Urea transporter, kidney;
GN   Name=Slc14a2; Synonyms=Ut2;
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] (ISOFORMS A3 AND A5), TISSUE SPECIFICITY
RP   (ISOFORMS A3 AND A5), FUNCTION (ISOFORMS A3 AND A5), TRANSPORTER ACTIVITY
RP   (ISOFORMS A3 AND A5), AND ACTIVITY REGULATION (ISOFORMS A3 AND A5).
RC   STRAIN=MF1; TISSUE=Kidney inner medulla, and Testis;
RX   PubMed=11029290; DOI=10.1152/ajpcell.2000.279.5.c1425;
RA   Fenton R.A., Howorth A., Cooper G.J., Meccariello R., Morris I.D.,
RA   Smith C.P.;
RT   "Molecular characterization of a novel UT-A urea transporter isoform (UT-
RT   A5) in testis.";
RL   Am. J. Physiol. 279:C1425-C1431(2000).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS A1 AND A2).
RC   STRAIN=MF1; TISSUE=Kidney inner medulla;
RX   PubMed=11880324; DOI=10.1152/ajprenal.00264.2001;
RA   Fenton R.A., Cottingham C.A., Stewart G.S., Howorth A., Hewitt J.A.,
RA   Smith C.P.;
RT   "Structure and characterization of the mouse UT-A gene (Slc14a2).";
RL   Am. J. Physiol. 282:F630-F638(2002).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM A2), FUNCTION (ISOFORMS A1; A2 AND A3),
RP   TRANSPORTER ACTIVITY (ISOFORMS A1; A2 AND 3), ACTIVITY REGULATION (ISOFORMS
RP   A1; A2 AND A3), TISSUE SPECIFICITY (ISOFORMS A1; A2 AND A3), AND
RP   SUBCELLULAR LOCATION.
RC   STRAIN=MF1; TISSUE=Kidney inner medulla;
RX   PubMed=12217874; DOI=10.1152/ajprenal.00263.2001;
RA   Fenton R.A., Stewart G.S., Carpenter B., Howorth A., Potter E.A.,
RA   Cooper G.J., Smith C.P.;
RT   "Characterization of mouse urea transporters UT-A1 and UT-A2.";
RL   Am. J. Physiol. 283:F817-F825(2002).
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 A1).
RC   TISSUE=Brain;
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   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Kidney;
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: [Isoform A1]: Mediates the transport of urea driven by a
CC       concentration gradient across the cell membrane of the renal inner
CC       medullary collecting duct which is critical to the urinary
CC       concentrating mechanism. {ECO:0000269|PubMed:12217874}.
CC   -!- FUNCTION: [Isoform A2]: Mediates the transport of urea driven by a
CC       concentration gradient across the cell membrane of the renal inner
CC       medullary collecting duct which is critical to the urinary
CC       concentrating mechanism. {ECO:0000269|PubMed:12217874}.
CC   -!- FUNCTION: [Isoform A3]: Mediates the transport of urea driven by a
CC       concentration gradient across the cell membrane of the renal inner
CC       medullary collecting duct which is critical to the urinary
CC       concentrating mechanism. {ECO:0000269|PubMed:11029290,
CC       ECO:0000269|PubMed:12217874}.
CC   -!- FUNCTION: [Isoform A5]: Mediates the transport of urea driven by a
CC       concentration gradient across the cell membrane (PubMed:11029290).
CC       Implicated in the urea movement across the blood-testis barrier and
CC       does not translocate water (PubMed:11029290).
CC       {ECO:0000269|PubMed:11029290}.
CC   -!- CATALYTIC ACTIVITY: [Isoform A1]:
CC       Reaction=urea(in) = urea(out); Xref=Rhea:RHEA:32799, ChEBI:CHEBI:16199;
CC         Evidence={ECO:0000269|PubMed:12217874};
CC   -!- CATALYTIC ACTIVITY: [Isoform A2]:
CC       Reaction=urea(in) = urea(out); Xref=Rhea:RHEA:32799, ChEBI:CHEBI:16199;
CC         Evidence={ECO:0000269|PubMed:12217874};
CC   -!- CATALYTIC ACTIVITY: [Isoform A3]:
CC       Reaction=urea(in) = urea(out); Xref=Rhea:RHEA:32799, ChEBI:CHEBI:16199;
CC         Evidence={ECO:0000269|PubMed:11029290, ECO:0000269|PubMed:12217874};
CC   -!- CATALYTIC ACTIVITY: [Isoform A5]:
CC       Reaction=urea(in) = urea(out); Xref=Rhea:RHEA:32799, ChEBI:CHEBI:16199;
CC         Evidence={ECO:0000269|PubMed:11029290};
CC   -!- ACTIVITY REGULATION: [Isoform A1]: Inhibited by phloretin
CC       (PubMed:12217874). Activated by forskolin, 3-isobutyl-1-methylxanthine
CC       (IBMX) and cAMP (PubMed:12217874). {ECO:0000269|PubMed:12217874}.
CC   -!- ACTIVITY REGULATION: [Isoform A2]: Inhibited by phloretin.
CC       {ECO:0000269|PubMed:12217874}.
CC   -!- ACTIVITY REGULATION: [Isoform A3]: Inhibited by phloretin
CC       (PubMed:11029290). Activated by forskolin, 3-isobutyl-1-methylxanthine
CC       (IBMX) and cAMP (PubMed:12217874). {ECO:0000269|PubMed:11029290,
CC       ECO:0000269|PubMed:12217874}.
CC   -!- ACTIVITY REGULATION: [Isoform A5]: Inhibited by phloretin.
CC       {ECO:0000269|PubMed:11029290}.
CC   -!- SUBCELLULAR LOCATION: Apical cell membrane
CC       {ECO:0000269|PubMed:12217874}; Multi-pass membrane protein
CC       {ECO:0000255}. Basolateral cell membrane {ECO:0000269|PubMed:12217874};
CC       Multi-pass membrane protein {ECO:0000255}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=4;
CC       Name=A1; Synonyms=UTA-1;
CC         IsoId=Q8R4T9-1; Sequence=Displayed;
CC       Name=A2; Synonyms=UTA-2;
CC         IsoId=Q8R4T9-2; Sequence=VSP_038810;
CC       Name=A3; Synonyms=UTA-3;
CC         IsoId=Q8R4T9-3; Sequence=VSP_038811, VSP_038812;
CC       Name=A5; Synonyms=UTA-5;
CC         IsoId=Q8R4T9-4; Sequence=VSP_038809, VSP_038811, VSP_038812;
CC   -!- TISSUE SPECIFICITY: [Isoform A1]: Highly expressed in kidney medulla
CC       (at protein level) (PubMed:12217874). Also detected in testes, heart,
CC       brain and liver (at protein level) (PubMed:12217874). In the kidney,
CC       present in thin descending limbs of the loop of Henle and in the middle
CC       and terminal inner medullary collecting ducts.
CC       {ECO:0000269|PubMed:12217874}.
CC   -!- TISSUE SPECIFICITY: [Isoform A2]: Expressed in the kidney medulla.
CC       {ECO:0000269|PubMed:12217874}.
CC   -!- TISSUE SPECIFICITY: [Isoform A3]: Expressed in the kidney medulla.
CC       {ECO:0000269|PubMed:11029290, ECO:0000269|PubMed:12217874}.
CC   -!- TISSUE SPECIFICITY: [Isoform A5]: Expressed in the peritubular myoid
CC       cells forming the outermost layer of the seminiferous tubules within
CC       the testes and is not detected in kidney (PubMed:11029290). Expression
CC       levels are coordinated with the stage of testes development and
CC       increase 15 days postpartum, commensurate with the start of
CC       seminiferous tubule fluid movement (PubMed:11029290).
CC       {ECO:0000269|PubMed:11029290}.
CC   -!- SIMILARITY: Belongs to the urea transporter family. {ECO:0000305}.
CC   -!- CAUTION: It is uncertain whether Met-1 or Met-10 is the initiator.
CC       {ECO:0000305}.
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DR   EMBL; AF258601; AAG32167.1; -; mRNA.
DR   EMBL; AF258602; AAG32168.1; -; mRNA.
DR   EMBL; AF366052; AAM00357.1; -; mRNA.
DR   EMBL; AF367359; AAM21206.1; -; mRNA.
DR   EMBL; CH466528; EDL09434.1; -; Genomic_DNA.
DR   EMBL; BC150680; AAI50681.1; -; mRNA.
DR   CCDS; CCDS29361.1; -. [Q8R4T9-1]
DR   CCDS; CCDS50331.1; -. [Q8R4T9-4]
DR   CCDS; CCDS89283.1; -. [Q8R4T9-2]
DR   CCDS; CCDS89284.1; -. [Q8R4T9-3]
DR   RefSeq; NP_001103744.1; NM_001110274.1.
DR   RefSeq; NP_109608.1; NM_030683.3.
DR   AlphaFoldDB; Q8R4T9; -.
DR   SMR; Q8R4T9; -.
DR   STRING; 10090.ENSMUSP00000157851; -.
DR   GlyCosmos; Q8R4T9; 1 site, No reported glycans.
DR   GlyGen; Q8R4T9; 1 site.
DR   iPTMnet; Q8R4T9; -.
DR   PhosphoSitePlus; Q8R4T9; -.
DR   EPD; Q8R4T9; -.
DR   PaxDb; 10090-ENSMUSP00000025434; -.
DR   ProteomicsDB; 297946; -. [Q8R4T9-1]
DR   ProteomicsDB; 297947; -. [Q8R4T9-2]
DR   ProteomicsDB; 297948; -. [Q8R4T9-3]
DR   ProteomicsDB; 297949; -. [Q8R4T9-4]
DR   DNASU; 27411; -.
DR   GeneID; 27411; -.
DR   KEGG; mmu:27411; -.
DR   UCSC; uc008fsh.2; mouse. [Q8R4T9-3]
DR   UCSC; uc012bfh.1; mouse. [Q8R4T9-4]
DR   AGR; MGI:1351653; -.
DR   CTD; 8170; -.
DR   MGI; MGI:1351653; Slc14a2.
DR   eggNOG; ENOG502QWSG; Eukaryota.
DR   InParanoid; Q8R4T9; -.
DR   OrthoDB; 3682310at2759; -.
DR   PhylomeDB; Q8R4T9; -.
DR   Reactome; R-MMU-425366; Transport of bile salts and organic acids, metal ions and amine compounds.
DR   BioGRID-ORCS; 27411; 6 hits in 70 CRISPR screens.
DR   ChiTaRS; Slc14a2; mouse.
DR   PRO; PR:Q8R4T9; -.
DR   Proteomes; UP000000589; Unplaced.
DR   RNAct; Q8R4T9; Protein.
DR   GO; GO:0016324; C:apical plasma membrane; IDA:UniProtKB.
DR   GO; GO:0016323; C:basolateral plasma membrane; IDA:UniProtKB.
DR   GO; GO:0016020; C:membrane; ISS:MGI.
DR   GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR   GO; GO:0050839; F:cell adhesion molecule binding; ISO:MGI.
DR   GO; GO:0015204; F:urea transmembrane transporter activity; IDA:UniProtKB.
DR   GO; GO:0071918; P:urea transmembrane transport; IBA:GO_Central.
DR   GO; GO:0015840; P:urea transport; ISO:MGI.
DR   Gene3D; 1.10.3430.10; Ammonium transporter AmtB like domains; 2.
DR   InterPro; IPR029020; Ammonium/urea_transptr.
DR   InterPro; IPR004937; Urea_transporter.
DR   PANTHER; PTHR10464; UREA TRANSPORTER; 1.
DR   PANTHER; PTHR10464:SF6; UREA TRANSPORTER 2; 1.
DR   Pfam; PF03253; UT; 2.
PE   1: Evidence at protein level;
KW   Alternative splicing; Cell membrane; Glycoprotein; Membrane;
KW   Phosphoprotein; Reference proteome; Transmembrane; Transmembrane helix.
FT   CHAIN           1..930
FT                   /note="Urea transporter 2"
FT                   /id="PRO_0000392531"
FT   TRANSMEM        145..165
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        185..205
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        213..233
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        242..262
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        280..300
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        311..331
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        350..372
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        401..421
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        610..630
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        648..668
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        676..696
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        705..725
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        774..794
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        813..833
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        842..862
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        864..884
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   REGION          1..90
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          452..479
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        29..48
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        52..90
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        461..476
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOD_RES         487
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q62668"
FT   CARBOHYD        743
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   VAR_SEQ         1..533
FT                   /note="Missing (in isoform A2)"
FT                   /evidence="ECO:0000303|PubMed:11880324,
FT                   ECO:0000303|PubMed:12217874"
FT                   /id="VSP_038810"
FT   VAR_SEQ         1..138
FT                   /note="Missing (in isoform A5)"
FT                   /evidence="ECO:0000303|PubMed:11029290"
FT                   /id="VSP_038809"
FT   VAR_SEQ         461
FT                   /note="G -> D (in isoform A3 and isoform A5)"
FT                   /evidence="ECO:0000303|PubMed:11029290"
FT                   /id="VSP_038811"
FT   VAR_SEQ         462..930
FT                   /note="Missing (in isoform A3 and isoform A5)"
FT                   /evidence="ECO:0000303|PubMed:11029290"
FT                   /id="VSP_038812"
FT   CONFLICT        313
FT                   /note="V -> M (in Ref. 1; AAG32167/AAG32168, 2; AAM00357
FT                   and 4; EDL09434)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        538
FT                   /note="T -> A (in Ref. 5; AAI50681)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        898
FT                   /note="K -> R (in Ref. 2; AAM00357 and 3; AAM21206)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   930 AA;  102047 MW;  298727BAFBE66D46 CRC64;
     MSDHHPLKEM SDSNSSPLLP EPLSSRYKLY ESELSSPTWP SSSQDTHPAL PLLEMPEEKD
     LRSSDEDSHI VKIEKPNERN KRRESEVSRR ASAGRGGFSL FQAVSYLTGD MKECKNWLKD
     KPLVLQFLDW VLRGAAQVMF VNNPISGLII FIGLLIQNPW WTIAGTLGTV ASTLAALALS
     QDRSAIASGL HGYNGMLVGL LMAVFSEKLD YYWWLLFPVT FTSMACPIIS SALSTIFAKW
     DLPVFTLPFN IALTLYLAAT GHYNLFFPTT LIKPASAAPN ITWTEIEMPL LLQTIPVGVG
     QVYGCDNPWT GGVILVALFI SSPLICLHAA IGSIVGLLAA LTVATPFETI YLGLWSYNCV
     LSCIAIGGMF YALTWQTHLL ALVCALFCAY MGAALSNTMA VVGVPSGTWA FCLSTLTFLL
     LTSNNTGIYK LPLSKVTYPE ANRIYFLTVR RSEEEKSPNG GSGEQSHGSG QWKAEESSET
     VLPRRRSVFH IEWSSIRRRS KVFGKGEHQE RQTKEPLPCP YRKPTVELFD LDTMEESTEI
     KVEANTARTS WIQSSMVAGG KRVSKALSYI TGEMKECGEG LKDKSPVFQF LDWVLRGMSQ
     VMFVNNPLSG ILIVLGLFVQ NPWWAISGCL GTVMSTLTAL ILSQDKSAIA AGLHGYNGVL
     VGLLMAVFSD KGNYYWWLLL PVIVMSMTCP ILSSALSTVF SKWDLPVFTL PFNIAVTLYL
     AATGHHNLFF PTTLLQPATT TPNITWSDIQ VSLLLRAIPV GIGQVYGCDN PWTGGIFLVA
     LFISSPLICL HAAIGSTIGM LAALSIATPF DSIYFGLCGF NSTLACIAIG GMFYVITWQT
     HLLAIACALF AAYLGAALAN MLSVFGLPPC TWPFCLSALT FLLLTSNNPA IYKLPLSKVT
     YPEANRIYFL SQEKNRRAST ITKYQAYDVS
//