UT2_RAT
ID UT2_RAT Reviewed; 929 AA.
AC Q62668; Q9R1Y7; Q9WTT8; Q9Z2R3;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 05-FEB-2008, sequence version 2.
DT 03-AUG-2022, entry version 142.
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 Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), FUNCTION (ISOFORM 2), TRANSPORTER
RP ACTIVITY (ISOFORM 2), TISSUE SPECIFICITY (ISOFORM 2), AND INDUCTION(ISOFORM
RP 2).
RC STRAIN=Sprague-Dawley; TISSUE=Kidney;
RX PubMed=7657826; DOI=10.1172/jci118194;
RA Smith C.P., Lee W.-S., Martial S., Knepper M.A., You G., Sands J.M.,
RA Hediger M.A.;
RT "Cloning and regulation of expression of the rat kidney urea transporter
RT (rUT2).";
RL J. Clin. Invest. 96:1556-1563(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION (ISOFORM 1), TRANSPORTER
RP ACTIVITY (ISOFORM 1), TISSUE SPECIFICITY (ISOFORM 1), AND ACTIVITY
RP REGULATION (ISOFORM 1).
RC STRAIN=Sprague-Dawley; TISSUE=Kidney inner medulla;
RX PubMed=8958221; DOI=10.1172/jci119077;
RA Shayakul C., Steel A., Hediger M.A.;
RT "Molecular cloning and characterization of the vasopressin-regulated urea
RT transporter of rat kidney collecting ducts.";
RL J. Clin. Invest. 98:2580-2587(1996).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 3 AND 4), FUNCTION (ISOFORMS 3 AND 4),
RP TRANSPORTER ACTIVITY (ISOFORMS 3 AND 4), ACTIVITY REGULATION (ISOFORMS 3
RP AND 4), AND TISSUE SPECIFICITY (ISOFORMS 3 AND 4).
RC STRAIN=Sprague-Dawley; TISSUE=Kidney inner medulla;
RX PubMed=10215321; DOI=10.1681/asn.v102230;
RA Karakashian A., Timmer R.T., Klein J.D., Gunn R.B., Sands J.M.,
RA Bagnasco S.M.;
RT "Cloning and characterization of two new isoforms of the rat kidney urea
RT transporter: UT-A3 and UT-A4.";
RL J. Am. Soc. Nephrol. 10:230-237(1999).
RN [4]
RP FUNCTION (ISOFORM 2), TRANSPORTER ACTIVITY (ISOFORM 2), AND ACTIVITY
RP REGULATION (ISOFORM 2).
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 [5]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), FUNCTION (ISOFORM 3), TRANSPORTER
RP ACTIVITY (ISOFORM 3), ACTIVITY REGULATION (ISOFORM 3), AND TISSUE
RP SPECIFICITY (ISOFORM 3).
RC STRAIN=Sprague-Dawley; TISSUE=Kidney;
RX PubMed=11181411; DOI=10.1152/ajprenal.2001.280.3.f487;
RA Shayakul C., Tsukaguchi H., Berger U.V., Hediger M.A.;
RT "Molecular characterization of a novel urea transporter from kidney inner
RT medullary collecting ducts.";
RL Am. J. Physiol. 280:F487-F494(2001).
RN [6]
RP FUNCTION (ISOFORM 1), TRANSPORTER ACTIVITY (ISOFORM 1), ACTIVITY REGULATION
RP (ISOFORM 1), SUBCELLULAR LOCATION (ISOFORM 1), AND TISSUE SPECIFICITY
RP (ISOFORM 1).
RX PubMed=16959825; DOI=10.1681/asn.2006030246;
RA Klein J.D., Froehlich O., Blount M.A., Martin C.F., Smith T.D., Sands J.M.;
RT "Vasopressin increases plasma membrane accumulation of urea transporter UT-
RT A1 in rat inner medullary collecting ducts.";
RL J. Am. Soc. Nephrol. 17:2680-2686(2006).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-486, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=16641100; DOI=10.1073/pnas.0600895103;
RA Hoffert J.D., Pisitkun T., Wang G., Shen R.-F., Knepper M.A.;
RT "Quantitative phosphoproteomics of vasopressin-sensitive renal cells:
RT regulation of aquaporin-2 phosphorylation at two sites.";
RL Proc. Natl. Acad. Sci. U.S.A. 103:7159-7164(2006).
RN [8]
RP INTERACTION WITH SNAPIN (ISOFORM 1).
RX PubMed=17702749; DOI=10.1074/jbc.m705866200;
RA Mistry A.C., Mallick R., Froehlich O., Klein J.D., Rehm A., Chen G.,
RA Sands J.M.;
RT "The UT-A1 urea transporter interacts with snapin, a SNARE-associated
RT protein.";
RL J. Biol. Chem. 282:30097-30106(2007).
CC -!- FUNCTION: [Isoform 1]: Mediates the transport of urea driven by a
CC concentration gradient across the cell membrane of the kidney inner
CC medullary collecting duct which is critical to the urinary
CC concentrating mechanism. {ECO:0000269|PubMed:16959825,
CC ECO:0000269|PubMed:8958221}.
CC -!- FUNCTION: [Isoform 2]: Mediates the transport of urea driven by a
CC concentration gradient across the cell membrane of the kidney inner
CC medullary collecting duct which is critical to the urinary
CC concentrating mechanism. {ECO:0000269|PubMed:11029290,
CC ECO:0000269|PubMed:7657826}.
CC -!- FUNCTION: [Isoform 3]: Mediates the transport of urea driven by a
CC concentration gradient across the cell membrane of the kidney inner
CC medullary collecting duct which is critical to the urinary
CC concentrating mechanism. {ECO:0000269|PubMed:10215321,
CC ECO:0000269|PubMed:11181411}.
CC -!- FUNCTION: [Isoform 4]: Mediates the transport of urea driven by a
CC concentration gradient across the cell membrane of the kidney inner
CC medullary collecting duct which is critical to the urinary
CC concentrating mechanism. {ECO:0000269|PubMed:10215321}.
CC -!- CATALYTIC ACTIVITY: [Isoform 1]:
CC Reaction=urea(in) = urea(out); Xref=Rhea:RHEA:32799, ChEBI:CHEBI:16199;
CC Evidence={ECO:0000269|PubMed:16959825, ECO:0000269|PubMed:8958221};
CC -!- CATALYTIC ACTIVITY: [Isoform 2]:
CC Reaction=urea(in) = urea(out); Xref=Rhea:RHEA:32799, ChEBI:CHEBI:16199;
CC Evidence={ECO:0000269|PubMed:11029290, ECO:0000269|PubMed:7657826};
CC -!- CATALYTIC ACTIVITY: [Isoform 3]:
CC Reaction=urea(in) = urea(out); Xref=Rhea:RHEA:32799, ChEBI:CHEBI:16199;
CC Evidence={ECO:0000269|PubMed:10215321, ECO:0000269|PubMed:11181411};
CC -!- CATALYTIC ACTIVITY: [Isoform 4]:
CC Reaction=urea(in) = urea(out); Xref=Rhea:RHEA:32799, ChEBI:CHEBI:16199;
CC Evidence={ECO:0000269|PubMed:10215321};
CC -!- ACTIVITY REGULATION: [Isoform 1]: Inhibited by phloretin
CC (PubMed:8958221). Activated by vasopressin, forskolin, 3-isobutyl-1-
CC methylxanthine (IBMX) and cAMP (PubMed:16959825).
CC {ECO:0000269|PubMed:16959825, ECO:0000269|PubMed:8958221}.
CC -!- ACTIVITY REGULATION: [Isoform 2]: Inhibited by phloretin.
CC {ECO:0000269|PubMed:11029290}.
CC -!- ACTIVITY REGULATION: [Isoform 3]: Inhibited by urea analogs and
CC phloretin and activated by forskolin. {ECO:0000269|PubMed:10215321,
CC ECO:0000269|PubMed:11181411}.
CC -!- ACTIVITY REGULATION: [Isoform 4]: Inhibited by phloretin and activated
CC by forskolin. {ECO:0000269|PubMed:10215321}.
CC -!- SUBUNIT: [Isoform 1]: Interacts with SNAPIN which enhances its urea
CC transport activity. {ECO:0000269|PubMed:17702749}.
CC -!- INTERACTION:
CC Q62668-1; O95295: SNAPIN; Xeno; NbExp=6; IntAct=EBI-1635608, EBI-296723;
CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Apical cell membrane
CC {ECO:0000269|PubMed:16959825}; Multi-pass membrane protein
CC {ECO:0000255}. Cell membrane {ECO:0000269|PubMed:16959825}; Multi-pass
CC membrane protein {ECO:0000255}. Note=Vasopressin increases expression
CC in the cell membrane. {ECO:0000269|PubMed:16959825}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1; Synonyms=UT-A1;
CC IsoId=Q62668-1; Sequence=Displayed;
CC Name=2; Synonyms=UT-A2;
CC IsoId=Q62668-2; Sequence=VSP_031172;
CC Name=3; Synonyms=UT-A3;
CC IsoId=Q62668-3; Sequence=VSP_031174;
CC Name=4; Synonyms=UT-A4;
CC IsoId=Q62668-4; Sequence=VSP_031173;
CC -!- TISSUE SPECIFICITY: [Isoform 1]: Expressed in the inner medulla of the
CC kidney. {ECO:0000269|PubMed:16959825, ECO:0000269|PubMed:8958221}.
CC -!- TISSUE SPECIFICITY: [Isoform 2]: Expressed in the inner medulla of the
CC kidney. {ECO:0000269|PubMed:7657826}.
CC -!- TISSUE SPECIFICITY: [Isoform 3]: Expressed in both the inner and outer
CC renal medulla of the kidney. {ECO:0000269|PubMed:10215321,
CC ECO:0000269|PubMed:11181411}.
CC -!- TISSUE SPECIFICITY: [Isoform 4]: Expressed in both the inner and outer
CC renal medulla of the kidney. {ECO:0000269|PubMed:10215321}.
CC -!- INDUCTION: [Isoform 2]: Induced by dehydration.
CC {ECO:0000269|PubMed:7657826}.
CC -!- SIMILARITY: Belongs to the urea transporter family. {ECO:0000305}.
CC -!- CAUTION: It is uncertain whether Met-1 or Met-9 is the initiator.
CC {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; U09957; AAA84392.1; -; mRNA.
DR EMBL; U77971; AAB50197.1; -; mRNA.
DR EMBL; AF041788; AAD23098.1; -; mRNA.
DR EMBL; AF042167; AAD23099.1; -; mRNA.
DR EMBL; AF031642; AAD01938.1; -; mRNA.
DR RefSeq; NP_001103740.1; NM_001110270.1. [Q62668-2]
DR RefSeq; NP_062220.2; NM_019347.2.
DR RefSeq; NP_808877.2; NM_177962.3.
DR AlphaFoldDB; Q62668; -.
DR SMR; Q62668; -.
DR BioGRID; 248522; 2.
DR IntAct; Q62668; 5.
DR STRING; 10116.ENSRNOP00000022417; -.
DR BindingDB; Q62668; -.
DR ChEMBL; CHEMBL3739246; -.
DR GuidetoPHARMACOLOGY; 983; -.
DR TCDB; 1.A.28.1.1; the urea transporter (ut) family.
DR GlyGen; Q62668; 1 site.
DR iPTMnet; Q62668; -.
DR PaxDb; Q62668; -.
DR GeneID; 54302; -.
DR KEGG; rno:54302; -.
DR CTD; 8170; -.
DR RGD; 3689; Slc14a2.
DR VEuPathDB; HostDB:ENSRNOG00000061714; -.
DR eggNOG; ENOG502QWSG; Eukaryota.
DR InParanoid; Q62668; -.
DR OMA; CPDWATA; -.
DR OrthoDB; 1478665at2759; -.
DR PhylomeDB; Q62668; -.
DR Reactome; R-RNO-425366; Transport of bile salts and organic acids, metal ions and amine compounds.
DR PRO; PR:Q62668; -.
DR Proteomes; UP000002494; Chromosome 18.
DR Bgee; ENSRNOG00000056021; Expressed in adult mammalian kidney and 5 other tissues.
DR GO; GO:0016324; C:apical plasma membrane; IDA:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0050839; F:cell adhesion molecule binding; ISO:RGD.
DR GO; GO:0015204; F:urea transmembrane transporter activity; IDA:UniProtKB.
DR GO; GO:0009414; P:response to water deprivation; IEP:RGD.
DR GO; GO:0071918; P:urea transmembrane transport; IBA:GO_Central.
DR GO; GO:0015840; P:urea transport; IDA:RGD.
DR Gene3D; 1.10.3430.10; -; 2.
DR InterPro; IPR029020; Ammonium/urea_transptr.
DR InterPro; IPR004937; Urea_transporter.
DR PANTHER; PTHR10464; PTHR10464; 3.
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;
KW Transport.
FT CHAIN 1..929
FT /note="Urea transporter 2"
FT /id="PRO_0000065741"
FT TRANSMEM 133..155
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 162..179
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 184..204
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 212..232
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 241..261
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 310..330
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 349..371
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 378..399
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 400..420
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 609..629
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 647..667
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 675..695
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 704..724
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 773..793
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 812..832
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 841..861
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 863..883
FT /note="Helical"
FT /evidence="ECO:0000255"
FT REGION 1..89
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 451..480
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 28..47
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 51..89
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 486
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:16641100"
FT CARBOHYD 742
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VAR_SEQ 1..532
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:7657826"
FT /id="VSP_031172"
FT VAR_SEQ 252..714
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:10215321"
FT /id="VSP_031173"
FT VAR_SEQ 461..929
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:10215321,
FT ECO:0000303|PubMed:11181411"
FT /id="VSP_031174"
FT CONFLICT 17
FT /note="P -> L (in Ref. 3; AAD23098/AAD23099)"
FT /evidence="ECO:0000305"
FT CONFLICT 96
FT /note="A -> G (in Ref. 3; AAD23098/AAD23099)"
FT /evidence="ECO:0000305"
FT CONFLICT 460
FT /note="G -> D (in Ref. 3; AAD23098 and 5; AAD01938)"
FT /evidence="ECO:0000305"
FT CONFLICT 780
FT /note="L -> P (in Ref. 3; AAD23099)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 929 AA; 101896 MW; 1D12D9D27764AC26 CRC64;
MSDHPLKEMS DNNRSPPLPE PLSSRYKLYE SELSSPTWPS SSQDTHPALP LLEMPEEKDL
RSSDEDSHIV KIEKPNERSK RRESELPRRA SAGRGAFSLF QAVSYLTGDM KECKNWLKDK
PLVLQFLDWV LRGAAQVMFV NNPLSGLIIF IGLLIQNPWW TIAGALGTVV STLAALALSQ
DRSAIASGLH GYNGMLVGLL VAVFSEKLDY YWWLLFPVTF ASMACPVISS ALSTVFAKWD
LPVFTLPFNI ALTLYLAATG HYNLFFPTTL VKPASSAPNI TWSEIEMPLL LQTIPVGVGQ
VYGCDNPWTG GVILVALFIS SPLICLHAAI GSIVGLLAAL TVATPFETIY TGLWSYNCVL
SCVAIGGMFY VLTWQTHLLA LVCALFCAYT GAALSNMMAV VGVPPGTWAF CLSTLTFLLL
TSNNPGIHKL PLSKVTYPEA NRIYFLTAKR SDEQKPPNGG GGEQSHGGGQ RKAEEGSETV
FPRRKSVFHI EWSSIRRRSK VFGKSEHQER QTKEPLPYLY RKPTVELLDL NTMEESSEIK
VETNTTRTTW IQSSMIAGGK RVSKALSYIT GEMKECGEGL KDKSPVFQFL DWVLRGTSQV
MFVNNPLSGI LIVLGLFVQN PWWAISGCLG TIMSTLTALI LSQDKSAIAA GLHGYNGVLV
GLLMAVFSDK GNYYWWLLLP VIVMSMTCPI LSSALSTVFS KWDLPVFTLP FNIAVTLYLA
ATGHYNLFFP TKLLQPAVTT PNITWSDVQV PLLLRAIPVG IGQVYGCDNP WTGGIFLVAL
FVSSPLICLH AAIGSTIGML AALSIATPFD SIYFGLCGFN STLACIAIGG MFYVITWQTH
LLAIACALFA AYLGAALANM LSVFGLPPCT WPFCLSALTF LLLTTNNPGI YKLPLSKVTY
PEANRIYFLS QEKNRRASMI TKYQAYDVS
