UT2_HUMAN
ID UT2_HUMAN Reviewed; 920 AA.
AC Q15849; A8K8Q7; Q2TBD6; Q96PH5;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 23-MAR-2010, sequence version 3.
DT 03-AUG-2022, entry version 170.
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=HUT2, UT2;
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 2), FUNCTION (ISOFORM 2), TRANSPORTER
RP ACTIVITY (ISOFORM 2), ACTIVITY REGULATION (ISOFORM 2), AND TISSUE
RP SPECIFICITY (ISOFORM 2).
RC TISSUE=Kidney;
RX PubMed=8647271; DOI=10.1016/0014-5793(96)00425-5;
RA Olives B., Sonia M., Mattei M.-G., Matassi G., Rousselet G., Ripoche P.,
RA Cartron J.-P., Bailly P.;
RT "Molecular characterization of a new urea transporter in the human
RT kidney.";
RL FEBS Lett. 386:156-160(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION (ISOFORM 1), TRANSPORTER
RP ACTIVITY (ISOFORM 1), TISSUE SPECIFICITY (ISOFORM 1), AND VARIANTS VAL-132
RP AND GLN-510.
RC TISSUE=Kidney;
RX PubMed=11502588; DOI=10.1152/ajprenal.2001.281.3.f400;
RA Bagnasco S.M., Peng T., Janech M.G., Karakashian A., Sands J.M.;
RT "Cloning and characterization of the human urea transporter UT-A1 and
RT mapping of the human Slc14a2 gene.";
RL Am. J. Physiol. 281:F400-F406(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANTS VAL-132
RP AND GLN-510.
RC TISSUE=Testis;
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16177791; DOI=10.1038/nature03983;
RA Nusbaum C., Zody M.C., Borowsky M.L., Kamal M., Kodira C.D., Taylor T.D.,
RA Whittaker C.A., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Yang X.,
RA Abouelleil A., Allen N.R., Anderson S., Bloom T., Bugalter B., Butler J.,
RA Cook A., DeCaprio D., Engels R., Garber M., Gnirke A., Hafez N., Hall J.L.,
RA Norman C.H., Itoh T., Jaffe D.B., Kuroki Y., Lehoczky J., Lui A.,
RA Macdonald P., Mauceli E., Mikkelsen T.S., Naylor J.W., Nicol R., Nguyen C.,
RA Noguchi H., O'Leary S.B., Piqani B., Smith C.L., Talamas J.A., Topham K.,
RA Totoki Y., Toyoda A., Wain H.M., Young S.K., Zeng Q., Zimmer A.R.,
RA Fujiyama A., Hattori M., Birren B.W., Sakaki Y., Lander E.S.;
RT "DNA sequence and analysis of human chromosome 18.";
RL Nature 437:551-555(2005).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANTS VAL-132;
RP GLN-510 AND THR-880.
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 (ISOFORM 2), TRANSPORTER ACTIVITY (ISOFORM 2), AND ACTIVITY
RP REGULATION (ISOFORM 2).
RX PubMed=8997401; DOI=10.1152/ajprenal.1996.271.6.f1264;
RA Martial S., Olives B., Abrami L., Couriaud C., Bailly P., You G.,
RA Hediger M.A., Cartron J.P., Ripoche P., Rousselet G.;
RT "Functional differentiation of the human red blood cell and kidney urea
RT transporters.";
RL Am. J. Physiol. 271:F1264-F1268(1996).
RN [7]
RP FUNCTION (ISOFORM 1), TRANSPORTER ACTIVITY (ISOFORM 1), INTERACTION WITH
RP SNAPIN (ISOFORM 1), AND SUBCELLULAR LOCATION (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 renal inner
CC medullary collecting duct which is critical to the urinary
CC concentrating mechanism. {ECO:0000269|PubMed:11502588,
CC ECO:0000269|PubMed:17702749}.
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:8647271,
CC ECO:0000269|PubMed:8997401}.
CC -!- CATALYTIC ACTIVITY: [Isoform 1]:
CC Reaction=urea(in) = urea(out); Xref=Rhea:RHEA:32799, ChEBI:CHEBI:16199;
CC Evidence={ECO:0000269|PubMed:11502588, ECO:0000269|PubMed:17702749};
CC -!- CATALYTIC ACTIVITY: [Isoform 2]:
CC Reaction=urea(in) = urea(out); Xref=Rhea:RHEA:32799, ChEBI:CHEBI:16199;
CC Evidence={ECO:0000269|PubMed:8647271, ECO:0000269|PubMed:8997401};
CC -!- ACTIVITY REGULATION: [Isoform 2]: Inhibited by phloretin.
CC {ECO:0000269|PubMed:8647271, ECO:0000269|PubMed:8997401}.
CC -!- SUBUNIT: [Isoform 1]: Interacts with SNAPIN which enhances its urea
CC transport activity. {ECO:0000269|PubMed:17702749}.
CC -!- INTERACTION:
CC Q15849; Q8WVX3-2: C4orf3; NbExp=3; IntAct=EBI-1573290, EBI-12003442;
CC Q15849; Q96FZ5: CMTM7; NbExp=3; IntAct=EBI-1573290, EBI-2807956;
CC Q15849; Q08426: EHHADH; NbExp=3; IntAct=EBI-1573290, EBI-2339219;
CC Q15849; O43561-2: LAT; NbExp=3; IntAct=EBI-1573290, EBI-8070286;
CC Q15849; Q7Z4F1: LRP10; NbExp=3; IntAct=EBI-1573290, EBI-2830349;
CC Q15849; P26678: PLN; NbExp=3; IntAct=EBI-1573290, EBI-692836;
CC Q15849; Q04941: PLP2; NbExp=3; IntAct=EBI-1573290, EBI-608347;
CC Q15849; Q96IW7: SEC22A; NbExp=3; IntAct=EBI-1573290, EBI-8652744;
CC Q15849; Q5BJF2: TMEM97; NbExp=4; IntAct=EBI-1573290, EBI-12111910;
CC Q15849; P01375: TNF; NbExp=3; IntAct=EBI-1573290, EBI-359977;
CC Q15849; A5PKU2: TUSC5; NbExp=3; IntAct=EBI-1573290, EBI-11988865;
CC Q15849; O95183: VAMP5; NbExp=3; IntAct=EBI-1573290, EBI-10191195;
CC Q15849-1; O95295: SNAPIN; NbExp=5; IntAct=EBI-1633392, EBI-296723;
CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Apical cell membrane
CC {ECO:0000269|PubMed:17702749}; Multi-pass membrane protein
CC {ECO:0000255}. Cell membrane {ECO:0000269|PubMed:17702749}; Multi-pass
CC membrane protein {ECO:0000255}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=UT-A1;
CC IsoId=Q15849-1; Sequence=Displayed;
CC Name=2; Synonyms=UT-A2;
CC IsoId=Q15849-2; Sequence=VSP_031171;
CC -!- TISSUE SPECIFICITY: [Isoform 1]: Epressed in the inner medulla of the
CC kidney (at protein level). {ECO:0000269|PubMed:11502588}.
CC -!- TISSUE SPECIFICITY: [Isoform 2]: Expressed in the kidney.
CC {ECO:0000269|PubMed:8647271}.
CC -!- SIMILARITY: Belongs to the urea transporter family. {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; X96969; CAA65657.1; -; mRNA.
DR EMBL; AF349446; AAL08485.1; -; mRNA.
DR EMBL; AK292422; BAF85111.1; -; mRNA.
DR EMBL; AC023421; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC110446; AAI10447.1; -; mRNA.
DR CCDS; CCDS11924.1; -. [Q15849-1]
DR PIR; S71339; S71339.
DR RefSeq; NP_001229621.1; NM_001242692.1. [Q15849-1]
DR RefSeq; NP_009094.3; NM_007163.3. [Q15849-1]
DR RefSeq; XP_016881504.1; XM_017026015.1.
DR AlphaFoldDB; Q15849; -.
DR SMR; Q15849; -.
DR BioGRID; 113822; 18.
DR IntAct; Q15849; 15.
DR STRING; 9606.ENSP00000255226; -.
DR DrugBank; DB03904; Urea.
DR TCDB; 1.A.28.1.6; the urea transporter (ut) family.
DR GlyGen; Q15849; 1 site.
DR iPTMnet; Q15849; -.
DR PhosphoSitePlus; Q15849; -.
DR BioMuta; SLC14A2; -.
DR DMDM; 292495053; -.
DR MassIVE; Q15849; -.
DR PaxDb; Q15849; -.
DR PeptideAtlas; Q15849; -.
DR PRIDE; Q15849; -.
DR ProteomicsDB; 60792; -. [Q15849-1]
DR Antibodypedia; 22411; 70 antibodies from 17 providers.
DR DNASU; 8170; -.
DR Ensembl; ENST00000255226.11; ENSP00000255226.5; ENSG00000132874.15. [Q15849-1]
DR Ensembl; ENST00000586448.5; ENSP00000465953.1; ENSG00000132874.15. [Q15849-1]
DR GeneID; 8170; -.
DR KEGG; hsa:8170; -.
DR MANE-Select; ENST00000255226.11; ENSP00000255226.5; NM_007163.4; NP_009094.3.
DR UCSC; uc002lbe.4; human. [Q15849-1]
DR CTD; 8170; -.
DR DisGeNET; 8170; -.
DR GeneCards; SLC14A2; -.
DR HGNC; HGNC:10919; SLC14A2.
DR HPA; ENSG00000132874; Tissue enhanced (adipose tissue, kidney).
DR MIM; 601611; gene.
DR neXtProt; NX_Q15849; -.
DR OpenTargets; ENSG00000132874; -.
DR PharmGKB; PA35811; -.
DR VEuPathDB; HostDB:ENSG00000132874; -.
DR eggNOG; ENOG502QWSG; Eukaryota.
DR GeneTree; ENSGT00390000018729; -.
DR HOGENOM; CLU_340555_0_0_1; -.
DR InParanoid; Q15849; -.
DR OMA; ECRSWLK; -.
DR OrthoDB; 1478665at2759; -.
DR PhylomeDB; Q15849; -.
DR PathwayCommons; Q15849; -.
DR Reactome; R-HSA-425366; Transport of bile salts and organic acids, metal ions and amine compounds.
DR SignaLink; Q15849; -.
DR BioGRID-ORCS; 8170; 11 hits in 1062 CRISPR screens.
DR ChiTaRS; SLC14A2; human.
DR GeneWiki; SLC14A2; -.
DR GenomeRNAi; 8170; -.
DR Pharos; Q15849; Tbio.
DR PRO; PR:Q15849; -.
DR Proteomes; UP000005640; Chromosome 18.
DR RNAct; Q15849; protein.
DR Bgee; ENSG00000132874; Expressed in right adrenal gland and 65 other tissues.
DR ExpressionAtlas; Q15849; baseline and differential.
DR Genevisible; Q15849; HS.
DR GO; GO:0016324; C:apical plasma membrane; IDA:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; TAS:ProtInc.
DR GO; GO:0016020; C:membrane; TAS:ProtInc.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0050839; F:cell adhesion molecule binding; IDA:MGI.
DR GO; GO:0015204; F:urea transmembrane transporter activity; IDA:UniProtKB.
DR GO; GO:0055085; P:transmembrane transport; TAS:Reactome.
DR GO; GO:0071918; P:urea transmembrane transport; IBA:GO_Central.
DR GO; GO:0015840; P:urea transport; TAS:ProtInc.
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..920
FT /note="Urea transporter 2"
FT /id="PRO_0000065739"
FT TRANSMEM 151..170
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 176..196
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 204..224
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 233..253
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 272..291
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 302..322
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 346..366
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 370..390
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 392..412
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 600..620
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 638..658
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 666..686
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 695..715
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 764..784
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 803..823
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 832..852
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 854..874
FT /note="Helical"
FT /evidence="ECO:0000255"
FT REGION 25..57
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 446..467
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 43..57
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 477
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q62668"
FT CARBOHYD 733
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VAR_SEQ 1..523
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:8647271"
FT /id="VSP_031171"
FT VARIANT 37
FT /note="T -> I (in dbSNP:rs34461862)"
FT /id="VAR_057016"
FT VARIANT 132
FT /note="I -> V (in dbSNP:rs1484873)"
FT /evidence="ECO:0000269|PubMed:11502588,
FT ECO:0000269|PubMed:14702039, ECO:0000269|PubMed:15489334"
FT /id="VAR_060255"
FT VARIANT 443
FT /note="G -> S (in dbSNP:rs35245152)"
FT /id="VAR_057017"
FT VARIANT 510
FT /note="R -> Q (in dbSNP:rs9960464)"
FT /evidence="ECO:0000269|PubMed:11502588,
FT ECO:0000269|PubMed:14702039, ECO:0000269|PubMed:15489334"
FT /id="VAR_060256"
FT VARIANT 750
FT /note="V -> I (in dbSNP:rs1123617)"
FT /id="VAR_057018"
FT VARIANT 880
FT /note="A -> T (in dbSNP:rs3745009)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_038690"
FT CONFLICT 195
FT /note="V -> A (in Ref. 2; AAL08485)"
FT /evidence="ECO:0000305"
FT CONFLICT 515
FT /note="T -> I (in Ref. 3; BAF85111)"
FT /evidence="ECO:0000305"
FT CONFLICT 723
FT /note="T -> A (in Ref. 2; AAL08485)"
FT /evidence="ECO:0000305"
FT CONFLICT 905
FT /note="N -> D (in Ref. 3; BAF85111)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 920 AA; 101209 MW; 23BF379DC0767619 CRC64;
MSDPHSSPLL PEPLSSRYKL YEAEFTSPSW PSTSPDTHPA LPLLEMPEEK DLRSSNEDSH
IVKIEKLNER SKRKDDGVAH RDSAGQRCIC LSKAVGYLTG DMKEYRIWLK DKHLALQFID
WVLRGTAQVM FINNPLSGLI IFIGLLIQNP WWTITGGLGT VVSTLTALAL GQDRSAIASG
LHGYNGMLVG LLMAVFSEKL DYYWWLLFPV TFTAMSCPVL SSALNSIFSK WDLPVFTLPF
NIAVTLYLAA TGHYNLFFPT TLVEPVSSVP NITWTEMEMP LLLQAIPVGV GQVYGCDNPW
TGGVFLVALF ISSPLICLHA AIGSIVGLLA ALSVATPFET IYTGLWSYNC VLSCIAIGGM
FYALTWQTHL LALICALFCA YMEAAISNIM SVVGVPPGTW AFCLATIIFL LLTTNNPAIF
RLPLSKVTYP EANRIYYLTV KSGEEEKAPS GGGGEHPPTA GPKVEEGSEA VLSKHRSVFH
IEWSSIRRRS KVFGKGEHQE RQNKDPFPYR YRKPTVELLD LDTMEESSEI KVETNISKTS
WIRSSMAASG KRVSKALSYI TGEMKECGEG LKDKSPVFQF FDWVLRGTSQ VMFVNNPLSG
ILIILGLFIQ NPWWAISGCL GTIMSTLTAL ILSQDKSAIA AGFHGYNGVL VGLLMAVFSD
KGDYYWWLLL PVIIMSMSCP ILSSALGTIF SKWDLPVFTL PFNITVTLYL AATGHYNLFF
PTTLLQPASA MPNITWSEVQ VPLLLRAIPV GIGQVYGCDN PWTGGIFLIA LFISSPLICL
HAAIGSTMGM LAALTIATPF DSIYFGLCGF NSTLACIAIG GMFYVITWQT HLLAIACALF
AAYLGAALAN MLSVFGLPPC TWPFCLSALT FLLLTTNNPA IYKLPLSKVT YPEANRIYYL
SQERNRRASI ITKYQAYDVS
