ID   AQP9_HUMAN              Reviewed;         295 AA.
AC   O43315; Q9NP32;
DT   15-DEC-1998, integrated into UniProtKB/Swiss-Prot.
DT   11-JAN-2011, sequence version 2.
DT   27-MAR-2024, entry version 190.
DE   RecName: Full=Aquaporin-9;
DE            Short=AQP-9;
DE   AltName: Full=Aquaglyceroporin-9;
DE   AltName: Full=Small solute channel 1;
GN   Name=AQP9; Synonyms=SSC1;
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], FUNCTION, SUBCELLULAR LOCATION, TISSUE
RP   SPECIFICITY, AND VARIANT ALA-279.
RC   TISSUE=Liver;
RX   PubMed=9514918; DOI=10.1006/bbrc.1998.8252;
RA   Ishibashi K., Kuwahara M., Gu Y., Tanaka Y., Marumo F., Sasaki S.;
RT   "Cloning and functional expression of a new aquaporin (AQP9) abundantly
RT   expressed in the peripheral leukocytes permeable to water and urea, but not
RT   to glycerol.";
RL   Biochem. Biophys. Res. Commun. 244:268-274(1998).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, SUBCELLULAR LOCATION, TISSUE
RP   SPECIFICITY, AND VARIANT ALA-279.
RX   PubMed=10564231; DOI=10.1152/ajprenal.1999.277.5.f685;
RA   Tsukaguchi H., Weremowicz S., Morton C.C., Hediger M.A.;
RT   "Functional and molecular characterization of the human neutral solute
RT   channel aquaporin-9.";
RL   Am. J. Physiol. 277:F685-F696(1999).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=16572171; DOI=10.1038/nature04601;
RA   Zody M.C., Garber M., Sharpe T., Young S.K., Rowen L., O'Neill K.,
RA   Whittaker C.A., Kamal M., Chang J.L., Cuomo C.A., Dewar K.,
RA   FitzGerald M.G., Kodira C.D., Madan A., Qin S., Yang X., Abbasi N.,
RA   Abouelleil A., Arachchi H.M., Baradarani L., Birditt B., Bloom S.,
RA   Bloom T., Borowsky M.L., Burke J., Butler J., Cook A., DeArellano K.,
RA   DeCaprio D., Dorris L. III, Dors M., Eichler E.E., Engels R., Fahey J.,
RA   Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G., Johnson E.,
RA   Jones C., Kamat A., Kaur A., Locke D.P., Madan A., Munson G., Jaffe D.B.,
RA   Lui A., Macdonald P., Mauceli E., Naylor J.W., Nesbitt R., Nicol R.,
RA   O'Leary S.B., Ratcliffe A., Rounsley S., She X., Sneddon K.M.B.,
RA   Stewart S., Sougnez C., Stone S.M., Topham K., Vincent D., Wang S.,
RA   Zimmer A.R., Birren B.W., Hood L., Lander E.S., Nusbaum C.;
RT   "Analysis of the DNA sequence and duplication history of human chromosome
RT   15.";
RL   Nature 440:671-675(2006).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT ALA-279.
RC   TISSUE=Liver;
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   [5]
RP   FUNCTION.
RX   PubMed=30420639; DOI=10.1038/s41467-018-07176-z;
RA   Gotfryd K., Mosca A.F., Missel J.W., Truelsen S.F., Wang K., Spulber M.,
RA   Krabbe S., Helix-Nielsen C., Laforenza U., Soveral G., Pedersen P.A.,
RA   Gourdon P.;
RT   "Human adipose glycerol flux is regulated by a pH gate in AQP10.";
RL   Nat. Commun. 9:4749-4749(2018).
CC   -!- FUNCTION: Forms a water channel with a broad specificity. Also
CC       permeable glycerol and urea. Mediates passage of a wide variety of
CC       small, non-charged solutes including carbamides, polyols, purines, and
CC       pyrimidines. {ECO:0000269|PubMed:10564231, ECO:0000269|PubMed:30420639,
CC       ECO:0000269|PubMed:9514918}.
CC   -!- INTERACTION:
CC       O43315; Q08AM2: ADAM33; NbExp=3; IntAct=EBI-17444777, EBI-10225815;
CC       O43315; Q9NVV5-2: AIG1; NbExp=3; IntAct=EBI-17444777, EBI-11957045;
CC       O43315; P05090: APOD; NbExp=3; IntAct=EBI-17444777, EBI-715495;
CC       O43315; Q9P0B6: CCDC167; NbExp=3; IntAct=EBI-17444777, EBI-9083477;
CC       O43315; Q8N6F1-2: CLDN19; NbExp=3; IntAct=EBI-17444777, EBI-12256978;
CC       O43315; Q7Z7G2: CPLX4; NbExp=3; IntAct=EBI-17444777, EBI-18013275;
CC       O43315; Q4LDR2: CTXN3; NbExp=3; IntAct=EBI-17444777, EBI-12019274;
CC       O43315; Q9BV81: EMC6; NbExp=3; IntAct=EBI-17444777, EBI-2820492;
CC       O43315; Q14802-3: FXYD3; NbExp=3; IntAct=EBI-17444777, EBI-12175685;
CC       O43315; O75084: FZD7; NbExp=3; IntAct=EBI-17444777, EBI-746917;
CC       O43315; P01350: GAST; NbExp=3; IntAct=EBI-17444777, EBI-3436637;
CC       O43315; Q9UM44: HHLA2; NbExp=3; IntAct=EBI-17444777, EBI-2867874;
CC       O43315; P24593: IGFBP5; NbExp=3; IntAct=EBI-17444777, EBI-720480;
CC       O43315; Q8TAF8: LHFPL5; NbExp=3; IntAct=EBI-17444777, EBI-2820517;
CC       O43315; P30301: MIP; NbExp=3; IntAct=EBI-17444777, EBI-8449636;
CC       O43315; P09466: PAEP; NbExp=3; IntAct=EBI-17444777, EBI-465167;
CC       O43315; Q9NRX5: SERINC1; NbExp=3; IntAct=EBI-17444777, EBI-2683145;
CC       O43315; O95470: SGPL1; NbExp=3; IntAct=EBI-17444777, EBI-1046170;
CC       O43315; Q9NVC3: SLC38A7; NbExp=3; IntAct=EBI-17444777, EBI-10314552;
CC       O43315; P02787: TF; NbExp=3; IntAct=EBI-17444777, EBI-714319;
CC       O43315; Q9BVK6: TMED9; NbExp=3; IntAct=EBI-17444777, EBI-1056827;
CC       O43315; Q9BVC6: TMEM109; NbExp=3; IntAct=EBI-17444777, EBI-1057733;
CC   -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:10564231,
CC       ECO:0000269|PubMed:9514918}; Multi-pass membrane protein {ECO:0000305}.
CC   -!- TISSUE SPECIFICITY: Highly expressed in peripheral leukocytes. Also
CC       expressed in liver, lung, and spleen. {ECO:0000269|PubMed:10564231,
CC       ECO:0000269|PubMed:9514918}.
CC   -!- DOMAIN: Aquaporins contain two tandem repeats each containing three
CC       membrane-spanning domains and a pore-forming loop with the signature
CC       motif Asn-Pro-Ala (NPA). {ECO:0000250|UniProtKB:Q96PS8}.
CC   -!- SIMILARITY: Belongs to the MIP/aquaporin (TC 1.A.8) family.
CC       {ECO:0000305}.
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DR   EMBL; AB008775; BAA24864.1; -; mRNA.
DR   EMBL; AF016495; AAF16677.1; -; mRNA.
DR   EMBL; AF102870; AAF27983.1; -; Genomic_DNA.
DR   EMBL; AC025431; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AC066616; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BC026258; AAH26258.1; -; mRNA.
DR   CCDS; CCDS10165.1; -.
DR   PIR; JC5973; JC5973.
DR   RefSeq; NP_066190.2; NM_020980.4.
DR   AlphaFoldDB; O43315; -.
DR   SMR; O43315; -.
DR   BioGRID; 106861; 42.
DR   IntAct; O43315; 22.
DR   STRING; 9606.ENSP00000219919; -.
DR   BindingDB; O43315; -.
DR   DrugBank; DB09462; Glycerin.
DR   TCDB; 1.A.8.9.14; the major intrinsic protein (mip) family.
DR   iPTMnet; O43315; -.
DR   PhosphoSitePlus; O43315; -.
DR   BioMuta; AQP9; -.
DR   MassIVE; O43315; -.
DR   PaxDb; 9606-ENSP00000219919; -.
DR   PeptideAtlas; O43315; -.
DR   ProteomicsDB; 48894; -.
DR   Antibodypedia; 53183; 187 antibodies from 26 providers.
DR   DNASU; 366; -.
DR   Ensembl; ENST00000219919.9; ENSP00000219919.4; ENSG00000103569.11.
DR   GeneID; 366; -.
DR   KEGG; hsa:366; -.
DR   MANE-Select; ENST00000219919.9; ENSP00000219919.4; NM_020980.5; NP_066190.2.
DR   UCSC; uc002aez.3; human.
DR   AGR; HGNC:643; -.
DR   CTD; 366; -.
DR   DisGeNET; 366; -.
DR   GeneCards; AQP9; -.
DR   HGNC; HGNC:643; AQP9.
DR   HPA; ENSG00000103569; Tissue enriched (liver).
DR   MIM; 602914; gene+phenotype.
DR   neXtProt; NX_O43315; -.
DR   OpenTargets; ENSG00000103569; -.
DR   PharmGKB; PA24927; -.
DR   VEuPathDB; HostDB:ENSG00000103569; -.
DR   eggNOG; KOG0224; Eukaryota.
DR   GeneTree; ENSGT00940000160582; -.
DR   InParanoid; O43315; -.
DR   OMA; WGFAVLT; -.
DR   OrthoDB; 5490746at2759; -.
DR   PhylomeDB; O43315; -.
DR   TreeFam; TF313173; -.
DR   BioCyc; MetaCyc:ENSG00000103569-MONOMER; -.
DR   PathwayCommons; O43315; -.
DR   Reactome; R-HSA-432030; Transport of glycerol from adipocytes to the liver by Aquaporins.
DR   Reactome; R-HSA-432047; Passive transport by Aquaporins.
DR   SignaLink; O43315; -.
DR   SIGNOR; O43315; -.
DR   BioGRID-ORCS; 366; 11 hits in 1141 CRISPR screens.
DR   GeneWiki; AQP9; -.
DR   GenomeRNAi; 366; -.
DR   Pharos; O43315; Tbio.
DR   PRO; PR:O43315; -.
DR   Proteomes; UP000005640; Chromosome 15.
DR   RNAct; O43315; Protein.
DR   Bgee; ENSG00000103569; Expressed in blood and 115 other cell types or tissues.
DR   ExpressionAtlas; O43315; baseline and differential.
DR   GO; GO:0016323; C:basolateral plasma membrane; IBA:GO_Central.
DR   GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:UniProtKB.
DR   GO; GO:0005886; C:plasma membrane; IMP:UniProtKB.
DR   GO; GO:0015254; F:glycerol channel activity; IDA:UniProtKB.
DR   GO; GO:0005345; F:purine nucleobase transmembrane transporter activity; ISS:UniProtKB.
DR   GO; GO:0005350; F:pyrimidine nucleobase transmembrane transporter activity; ISS:UniProtKB.
DR   GO; GO:0015265; F:urea channel activity; IMP:UniProtKB.
DR   GO; GO:0015204; F:urea transmembrane transporter activity; ISS:UniProtKB.
DR   GO; GO:0015250; F:water channel activity; IDA:UniProtKB.
DR   GO; GO:0015837; P:amine transport; ISS:UniProtKB.
DR   GO; GO:0015722; P:canalicular bile acid transport; IEA:Ensembl.
DR   GO; GO:0071320; P:cellular response to cAMP; IEP:UniProtKB.
DR   GO; GO:0015793; P:glycerol transmembrane transport; IDA:UniProtKB.
DR   GO; GO:0006863; P:purine nucleobase transport; ISS:UniProtKB.
DR   GO; GO:0015855; P:pyrimidine nucleobase transport; ISS:UniProtKB.
DR   GO; GO:0048265; P:response to pain; IEA:Ensembl.
DR   GO; GO:0071918; P:urea transmembrane transport; IMP:UniProtKB.
DR   GO; GO:0006833; P:water transport; IDA:UniProtKB.
DR   CDD; cd00333; MIP; 1.
DR   Gene3D; 1.20.1080.10; Glycerol uptake facilitator protein; 1.
DR   InterPro; IPR023271; Aquaporin-like.
DR   InterPro; IPR015685; Aquaporin_9.
DR   InterPro; IPR000425; MIP.
DR   InterPro; IPR022357; MIP_CS.
DR   NCBIfam; TIGR00861; MIP; 1.
DR   PANTHER; PTHR43829; AQUAPORIN OR AQUAGLYCEROPORIN RELATED; 1.
DR   PANTHER; PTHR43829:SF6; AQUAPORIN-9; 1.
DR   Pfam; PF00230; MIP; 1.
DR   PRINTS; PR02021; AQUAPORIN9.
DR   PRINTS; PR00783; MINTRINSICP.
DR   SUPFAM; SSF81338; Aquaporin-like; 1.
DR   PROSITE; PS00221; MIP; 1.
DR   Genevisible; O43315; HS.
PE   1: Evidence at protein level;
KW   Cell membrane; Membrane; Reference proteome; Repeat; Transmembrane;
KW   Transmembrane helix; Transport.
FT   CHAIN           1..295
FT                   /note="Aquaporin-9"
FT                   /id="PRO_0000063964"
FT   TOPO_DOM        1..27
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000305"
FT   TRANSMEM        28..48
FT                   /note="Helical"
FT                   /evidence="ECO:0000250|UniProtKB:Q96PS8"
FT   TOPO_DOM        49..54
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000305"
FT   TRANSMEM        55..75
FT                   /note="Helical"
FT                   /evidence="ECO:0000250|UniProtKB:Q96PS8"
FT   TOPO_DOM        76..79
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000305"
FT   INTRAMEM        80..93
FT                   /note="Discontinuously helical"
FT                   /evidence="ECO:0000250|UniProtKB:Q96PS8"
FT   TOPO_DOM        94..99
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000305"
FT   TRANSMEM        100..124
FT                   /note="Helical"
FT                   /evidence="ECO:0000250|UniProtKB:Q96PS8"
FT   TOPO_DOM        125..158
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000305"
FT   TRANSMEM        159..179
FT                   /note="Helical"
FT                   /evidence="ECO:0000250|UniProtKB:Q96PS8"
FT   TOPO_DOM        180..189
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000305"
FT   TRANSMEM        190..209
FT                   /note="Helical"
FT                   /evidence="ECO:0000250|UniProtKB:Q96PS8"
FT   INTRAMEM        210..228
FT                   /note="Discontinuously helical"
FT                   /evidence="ECO:0000250|UniProtKB:Q96PS8"
FT   TOPO_DOM        229..245
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000305"
FT   TRANSMEM        246..266
FT                   /note="Helical"
FT                   /evidence="ECO:0000250|UniProtKB:Q96PS8"
FT   TOPO_DOM        267..295
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000305"
FT   MOTIF           84..86
FT                   /note="NPA 1"
FT                   /evidence="ECO:0000250|UniProtKB:Q96PS8"
FT   MOTIF           216..218
FT                   /note="NPA 2"
FT                   /evidence="ECO:0000250|UniProtKB:Q96PS8"
FT   VARIANT         279
FT                   /note="T -> A (in dbSNP:rs1867380)"
FT                   /evidence="ECO:0000269|PubMed:10564231,
FT                   ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:9514918"
FT                   /id="VAR_024538"
SQ   SEQUENCE   295 AA;  31431 MW;  B3B416CD9F1F9CAF CRC64;
     MQPEGAEKGK SFKQRLVLKS SLAKETLSEF LGTFILIVLG CGCVAQAILS RGRFGGVITI
     NVGFSMAVAM AIYVAGGVSG GHINPAVSLA MCLFGRMKWF KLPFYVGAQF LGAFVGAATV
     FGIYYDGLMS FAGGKLLIVG ENATAHIFAT YPAPYLSLAN AFADQVVATM ILLIIVFAIF
     DSRNLGAPRG LEPIAIGLLI IVIASSLGLN SGCAMNPARD LSPRLFTALA GWGFEVFRAG
     NNFWWIPVVG PLVGAVIGGL IYVLVIEIHH PEPDSVFKTE QSEDKPEKYE LSVIM
//