AQP5_HUMAN
ID AQP5_HUMAN Reviewed; 265 AA.
AC P55064; Q6FGW8;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1996, sequence version 1.
DT 03-AUG-2022, entry version 173.
DE RecName: Full=Aquaporin-5;
DE Short=AQP-5;
GN Name=AQP5;
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 [GENOMIC DNA], FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=8621489; DOI=10.1074/jbc.271.15.8599;
RA Lee M.D., Bhakta K.Y., Raina S., Yonescu R., Griffin C.A., Copeland N.G.,
RA Gilbert D.J., Jenkins N.A., Preston G.M., Agre P.;
RT "The human aquaporin-5 gene. Molecular characterization and chromosomal
RT localization.";
RL J. Biol. Chem. 271:8599-8604(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Testis;
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 [4]
RP FUNCTION, AND INTERACTION WITH TRPV4.
RX PubMed=16571723; DOI=10.1074/jbc.m600549200;
RA Liu X., Bandyopadhyay B.C., Bandyopadhyay B., Nakamoto T., Singh B.,
RA Liedtke W., Melvin J.E., Ambudkar I.;
RT "A role for AQP5 in activation of TRPV4 by hypotonicity: concerted
RT involvement of AQP5 and TRPV4 in regulation of cell volume recovery.";
RL J. Biol. Chem. 281:15485-15495(2006).
RN [5]
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=23473857; DOI=10.1016/j.jdermsci.2013.01.013;
RA Inoue R., Sohara E., Rai T., Satoh T., Yokozeki H., Sasaki S., Uchida S.;
RT "Immunolocalization and translocation of aquaporin-5 water channel in sweat
RT glands.";
RL J. Dermatol. Sci. 70:26-33(2013).
RN [6] {ECO:0007744|PDB:3D9S}
RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 2-265, FUNCTION, SUBUNIT, DOMAIN,
RP AND TOPOLOGY.
RX PubMed=18768791; DOI=10.1073/pnas.0801466105;
RA Horsefield R., Norden K., Fellert M., Backmark A., Tornroth-Horsefield S.,
RA Terwisscha van Scheltinga A.C., Kvassman J., Kjellbom P., Johanson U.,
RA Neutze R.;
RT "High-resolution X-ray structure of human aquaporin 5.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:13327-13332(2008).
RN [7] {ECO:0007744|PDB:5C5X, ECO:0007744|PDB:5DYE}
RP X-RAY CRYSTALLOGRAPHY (2.60 ANGSTROMS) OF 1-245 OF MUTANT GLU-156, SUBUNIT,
RP SUBCELLULAR LOCATION, MUTAGENESIS OF SER-156, DOMAIN, AND TOPOLOGY.
RX PubMed=26569106; DOI=10.1371/journal.pone.0143027;
RA Kitchen P., Oberg F., Sjohamn J., Hedfalk K., Bill R.M., Conner A.C.,
RA Conner M.T., Tornroth-Horsefield S.;
RT "Plasma Membrane Abundance of Human Aquaporin 5 Is Dynamically Regulated by
RT Multiple Pathways.";
RL PLoS ONE 10:e0143027-e0143027(2015).
RN [8]
RP VARIANTS PPKB GLU-38; SER-45; ASP-123; PHE-177 AND CYS-188,
RP CHARACTERIZATION OF VARIANTS GLU-38; SER-45; ASP-123; PHE-177 AND CYS-188,
RP AND SUBCELLULAR LOCATION.
RX PubMed=23830519; DOI=10.1016/j.ajhg.2013.06.008;
RA Blaydon D.C., Lind L.K., Plagnol V., Linton K.J., Smith F.J., Wilson N.J.,
RA McLean W.H., Munro C.S., South A.P., Leigh I.M., O'Toole E.A.,
RA Lundstroem A., Kelsell D.P.;
RT "Mutations in AQP5, encoding a water-channel protein, cause autosomal-
RT dominant diffuse nonepidermolytic palmoplantar keratoderma.";
RL Am. J. Hum. Genet. 93:330-335(2013).
CC -!- FUNCTION: Forms a water-specific channel (PubMed:8621489,
CC PubMed:18768791). Plays an important role in fluid secretion in
CC salivary glands (By similarity). Required for TRPV4 activation by
CC hypotonicity. Together with TRPV4, controls regulatory volume decrease
CC in salivary epithelial cells (PubMed:16571723). Seems to play a
CC redundant role in water transport in the eye, lung and in sweat glands
CC (By similarity). {ECO:0000250|UniProtKB:Q9WTY4,
CC ECO:0000269|PubMed:16571723, ECO:0000269|PubMed:18768791,
CC ECO:0000269|PubMed:8621489}.
CC -!- SUBUNIT: Homotetramer (PubMed:18768791, PubMed:26569106). Interacts
CC with TRPV4; the interaction is probably indirect and regulates TRPV4
CC activation by hypotonicity. {ECO:0000269|PubMed:16571723,
CC ECO:0000269|PubMed:18768791, ECO:0000269|PubMed:26569106}.
CC -!- INTERACTION:
CC P55064; P55064: AQP5; NbExp=2; IntAct=EBI-746103, EBI-746103;
CC P55064; P61978: HNRNPK; NbExp=3; IntAct=EBI-746103, EBI-304185;
CC P55064; Q15323: KRT31; NbExp=3; IntAct=EBI-746103, EBI-948001;
CC P55064; Q6A162: KRT40; NbExp=3; IntAct=EBI-746103, EBI-10171697;
CC P55064; Q99750: MDFI; NbExp=3; IntAct=EBI-746103, EBI-724076;
CC P55064; Q7Z3S9: NOTCH2NLA; NbExp=3; IntAct=EBI-746103, EBI-945833;
CC -!- SUBCELLULAR LOCATION: Apical cell membrane
CC {ECO:0000269|PubMed:23473857}; Multi-pass membrane protein
CC {ECO:0000269|PubMed:18768791, ECO:0000269|PubMed:26569106}. Cell
CC membrane {ECO:0000269|PubMed:23830519, ECO:0000269|PubMed:26569106,
CC ECO:0000269|PubMed:8621489}; Multi-pass membrane protein
CC {ECO:0000269|PubMed:18768791, ECO:0000269|PubMed:26569106}. Cytoplasmic
CC vesicle membrane {ECO:0000269|PubMed:26569106}; Multi-pass membrane
CC protein {ECO:0000269|PubMed:18768791, ECO:0000269|PubMed:26569106}.
CC Note=Hypotonicity increases location at the cell membrane.
CC Phosphorylation decreases location at the cell membrane.
CC {ECO:0000269|PubMed:26569106}.
CC -!- TISSUE SPECIFICITY: Detected in skin eccrine sweat glands, at the
CC apical cell membrane and at intercellular canaliculi (at protein
CC level). {ECO:0000269|PubMed:23473857}.
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:0000269|PubMed:18768791,
CC ECO:0000269|PubMed:26569106}.
CC -!- DISEASE: Keratoderma, palmoplantar, Bothnian type (PPKB) [MIM:600231]:
CC A dermatological disorder characterized by diffuse non-epidermolytic
CC hyperkeratosis of the skin of palms and soles. PPKB is frequently
CC complicated by fungal infections. {ECO:0000269|PubMed:23830519}.
CC Note=The disease is caused by variants affecting the gene represented
CC in this entry.
CC -!- SIMILARITY: Belongs to the MIP/aquaporin (TC 1.A.8) family.
CC {ECO:0000305}.
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DR EMBL; U46569; AAC50474.1; -; Genomic_DNA.
DR EMBL; U46566; AAC50474.1; JOINED; Genomic_DNA.
DR EMBL; U46567; AAC50474.1; JOINED; Genomic_DNA.
DR EMBL; U46568; AAC50474.1; JOINED; Genomic_DNA.
DR EMBL; CR541989; CAG46786.1; -; mRNA.
DR EMBL; CR542022; CAG46819.1; -; mRNA.
DR EMBL; BC032946; AAH32946.1; -; mRNA.
DR CCDS; CCDS8793.1; -.
DR RefSeq; NP_001642.1; NM_001651.3.
DR PDB; 3D9S; X-ray; 2.00 A; A/B/C/D=2-265.
DR PDB; 5C5X; X-ray; 2.60 A; A/B/C/D/E/F/G/H=1-245.
DR PDB; 5DYE; X-ray; 3.50 A; A/B/C/D=1-265.
DR PDBsum; 3D9S; -.
DR PDBsum; 5C5X; -.
DR PDBsum; 5DYE; -.
DR AlphaFoldDB; P55064; -.
DR SMR; P55064; -.
DR BioGRID; 106858; 12.
DR DIP; DIP-46292N; -.
DR IntAct; P55064; 8.
DR MINT; P55064; -.
DR STRING; 9606.ENSP00000293599; -.
DR ChEMBL; CHEMBL4523244; -.
DR TCDB; 1.A.8.8.9; the major intrinsic protein (mip) family.
DR GlyGen; P55064; 2 sites.
DR iPTMnet; P55064; -.
DR PhosphoSitePlus; P55064; -.
DR SwissPalm; P55064; -.
DR BioMuta; AQP5; -.
DR DMDM; 1703358; -.
DR jPOST; P55064; -.
DR MassIVE; P55064; -.
DR PaxDb; P55064; -.
DR PeptideAtlas; P55064; -.
DR PRIDE; P55064; -.
DR ProteomicsDB; 56775; -.
DR ABCD; P55064; 1 sequenced antibody.
DR Antibodypedia; 26098; 326 antibodies from 33 providers.
DR DNASU; 362; -.
DR Ensembl; ENST00000293599.7; ENSP00000293599.5; ENSG00000161798.7.
DR GeneID; 362; -.
DR KEGG; hsa:362; -.
DR MANE-Select; ENST00000293599.7; ENSP00000293599.5; NM_001651.4; NP_001642.1.
DR UCSC; uc001rvo.4; human.
DR CTD; 362; -.
DR DisGeNET; 362; -.
DR GeneCards; AQP5; -.
DR HGNC; HGNC:638; AQP5.
DR HPA; ENSG00000161798; Group enriched (salivary gland, testis).
DR MalaCards; AQP5; -.
DR MIM; 600231; phenotype.
DR MIM; 600442; gene.
DR neXtProt; NX_P55064; -.
DR OpenTargets; ENSG00000161798; -.
DR Orphanet; 2337; Non-epidermolytic palmoplantar keratoderma.
DR PharmGKB; PA24923; -.
DR VEuPathDB; HostDB:ENSG00000161798; -.
DR eggNOG; KOG0223; Eukaryota.
DR GeneTree; ENSGT00940000161557; -.
DR HOGENOM; CLU_020019_3_3_1; -.
DR InParanoid; P55064; -.
DR OMA; KKEVCSA; -.
DR OrthoDB; 1152704at2759; -.
DR PhylomeDB; P55064; -.
DR TreeFam; TF312940; -.
DR PathwayCommons; P55064; -.
DR Reactome; R-HSA-432047; Passive transport by Aquaporins.
DR SignaLink; P55064; -.
DR BioGRID-ORCS; 362; 18 hits in 1064 CRISPR screens.
DR ChiTaRS; AQP5; human.
DR EvolutionaryTrace; P55064; -.
DR GeneWiki; AQP5; -.
DR GenomeRNAi; 362; -.
DR Pharos; P55064; Tbio.
DR PRO; PR:P55064; -.
DR Proteomes; UP000005640; Chromosome 12.
DR RNAct; P55064; protein.
DR Bgee; ENSG00000161798; Expressed in olfactory segment of nasal mucosa and 112 other tissues.
DR Genevisible; P55064; HS.
DR GO; GO:0016324; C:apical plasma membrane; IDA:UniProtKB.
DR GO; GO:0009925; C:basal plasma membrane; IEA:Ensembl.
DR GO; GO:0030659; C:cytoplasmic vesicle membrane; IDA:UniProtKB.
DR GO; GO:0005783; C:endoplasmic reticulum; IEA:Ensembl.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IBA:GO_Central.
DR GO; GO:0005887; C:integral component of plasma membrane; IDA:UniProtKB.
DR GO; GO:0005902; C:microvillus; IEA:Ensembl.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0015250; F:water channel activity; IDA:UniProtKB.
DR GO; GO:0048593; P:camera-type eye morphogenesis; IEA:Ensembl.
DR GO; GO:0015670; P:carbon dioxide transport; IDA:UniProtKB.
DR GO; GO:0071476; P:cellular hypotonic response; IDA:UniProtKB.
DR GO; GO:0042476; P:odontogenesis; IEP:UniProtKB.
DR GO; GO:0030157; P:pancreatic juice secretion; IEP:UniProtKB.
DR GO; GO:0051289; P:protein homotetramerization; IDA:UniProtKB.
DR GO; GO:0046541; P:saliva secretion; IEA:Ensembl.
DR GO; GO:0006833; P:water transport; IDA:UniProtKB.
DR CDD; cd00333; MIP; 1.
DR Gene3D; 1.20.1080.10; -; 1.
DR InterPro; IPR023271; Aquaporin-like.
DR InterPro; IPR023276; Aquaporin_5.
DR InterPro; IPR034294; Aquaporin_transptr.
DR InterPro; IPR000425; MIP.
DR InterPro; IPR022357; MIP_CS.
DR PANTHER; PTHR19139; PTHR19139; 1.
DR PANTHER; PTHR19139:SF38; PTHR19139:SF38; 1.
DR Pfam; PF00230; MIP; 1.
DR PRINTS; PR02017; AQUAPORIN5.
DR PRINTS; PR00783; MINTRINSICP.
DR SUPFAM; SSF81338; SSF81338; 1.
DR TIGRFAMs; TIGR00861; MIP; 1.
DR PROSITE; PS00221; MIP; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cell membrane; Cytoplasmic vesicle; Disease variant;
KW Glycoprotein; Membrane; Palmoplantar keratoderma; Reference proteome;
KW Repeat; Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..265
FT /note="Aquaporin-5"
FT /id="PRO_0000063951"
FT TOPO_DOM 1..12
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:18768791,
FT ECO:0000269|PubMed:26569106"
FT TRANSMEM 13..33
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:18768791,
FT ECO:0000269|PubMed:26569106"
FT TOPO_DOM 34..39
FT /note="Extracellular"
FT /evidence="ECO:0000269|PubMed:18768791,
FT ECO:0000269|PubMed:26569106"
FT TRANSMEM 40..60
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:18768791,
FT ECO:0000269|PubMed:26569106"
FT TOPO_DOM 61..65
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:18768791,
FT ECO:0000269|PubMed:26569106"
FT INTRAMEM 66..74
FT /note="Discontinuously helical"
FT /evidence="ECO:0000269|PubMed:18768791,
FT ECO:0000269|PubMed:26569106"
FT TOPO_DOM 75..87
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:18768791,
FT ECO:0000269|PubMed:26569106"
FT TRANSMEM 88..108
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:18768791,
FT ECO:0000269|PubMed:26569106"
FT TOPO_DOM 109..126
FT /note="Extracellular"
FT /evidence="ECO:0000269|PubMed:18768791,
FT ECO:0000269|PubMed:26569106"
FT TRANSMEM 127..147
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:18768791,
FT ECO:0000269|PubMed:26569106"
FT TOPO_DOM 148..158
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:18768791,
FT ECO:0000269|PubMed:26569106"
FT TRANSMEM 159..179
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:18768791,
FT ECO:0000269|PubMed:26569106"
FT TOPO_DOM 180
FT /note="Extracellular"
FT /evidence="ECO:0000269|PubMed:18768791,
FT ECO:0000269|PubMed:26569106"
FT INTRAMEM 181..191
FT /note="Discontinuously helical"
FT /evidence="ECO:0000269|PubMed:18768791,
FT ECO:0000269|PubMed:26569106"
FT TOPO_DOM 192..203
FT /note="Extracellular"
FT /evidence="ECO:0000269|PubMed:18768791,
FT ECO:0000269|PubMed:26569106"
FT TRANSMEM 204..224
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:18768791,
FT ECO:0000269|PubMed:26569106"
FT TOPO_DOM 225..265
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:18768791,
FT ECO:0000269|PubMed:26569106"
FT MOTIF 69..71
FT /note="NPA 1"
FT /evidence="ECO:0000305|PubMed:18768791,
FT ECO:0000305|PubMed:26569106"
FT MOTIF 185..187
FT /note="NPA 2"
FT /evidence="ECO:0000305|PubMed:18768791,
FT ECO:0000305|PubMed:26569106"
FT CARBOHYD 124
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 125
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VARIANT 38
FT /note="A -> E (in PPKB; retains the ability to traffic to
FT the cell membrane; dbSNP:rs398123054)"
FT /evidence="ECO:0000269|PubMed:23830519"
FT /id="VAR_070442"
FT VARIANT 45
FT /note="I -> S (in PPKB; retains the ability to traffic to
FT the cell membrane; dbSNP:rs398123055)"
FT /evidence="ECO:0000269|PubMed:23830519"
FT /id="VAR_070443"
FT VARIANT 123
FT /note="N -> D (in PPKB; retains the ability to traffic to
FT the cell membrane; dbSNP:rs398123057)"
FT /evidence="ECO:0000269|PubMed:23830519"
FT /id="VAR_070444"
FT VARIANT 177
FT /note="I -> F (in PPKB; retains the ability to traffic to
FT the cell membrane; dbSNP:rs398123056)"
FT /evidence="ECO:0000269|PubMed:23830519"
FT /id="VAR_070445"
FT VARIANT 188
FT /note="R -> C (in PPKB; retains the ability to traffic to
FT the cell membrane; dbSNP:rs368292687)"
FT /evidence="ECO:0000269|PubMed:23830519"
FT /id="VAR_070446"
FT MUTAGEN 156
FT /note="S->A: No effect on location at the cell membrane."
FT /evidence="ECO:0000269|PubMed:26569106"
FT MUTAGEN 156
FT /note="S->E: Increased location at the cell membrane."
FT /evidence="ECO:0000269|PubMed:26569106"
FT HELIX 2..5
FT /evidence="ECO:0007829|PDB:3D9S"
FT HELIX 8..32
FT /evidence="ECO:0007829|PDB:3D9S"
FT STRAND 36..38
FT /evidence="ECO:0007829|PDB:3D9S"
FT HELIX 42..64
FT /evidence="ECO:0007829|PDB:3D9S"
FT HELIX 70..78
FT /evidence="ECO:0007829|PDB:3D9S"
FT STRAND 80..82
FT /evidence="ECO:0007829|PDB:3D9S"
FT HELIX 84..108
FT /evidence="ECO:0007829|PDB:3D9S"
FT HELIX 111..114
FT /evidence="ECO:0007829|PDB:3D9S"
FT TURN 115..118
FT /evidence="ECO:0007829|PDB:3D9S"
FT STRAND 124..126
FT /evidence="ECO:0007829|PDB:5DYE"
FT HELIX 128..150
FT /evidence="ECO:0007829|PDB:3D9S"
FT HELIX 161..180
FT /evidence="ECO:0007829|PDB:3D9S"
FT HELIX 186..196
FT /evidence="ECO:0007829|PDB:3D9S"
FT HELIX 203..223
FT /evidence="ECO:0007829|PDB:3D9S"
FT TURN 233..235
FT /evidence="ECO:0007829|PDB:3D9S"
FT HELIX 236..239
FT /evidence="ECO:0007829|PDB:3D9S"
SQ SEQUENCE 265 AA; 28292 MW; 053C10E6A17EAFDA CRC64;
MKKEVCSVAF LKAVFAEFLA TLIFVFFGLG SALKWPSALP TILQIALAFG LAIGTLAQAL
GPVSGGHINP AITLALLVGN QISLLRAFFY VAAQLVGAIA GAGILYGVAP LNARGNLAVN
ALNNNTTQGQ AMVVELILTF QLALCIFAST DSRRTSPVGS PALSIGLSVT LGHLVGIYFT
GCSMNPARSF GPAVVMNRFS PAHWVFWVGP IVGAVLAAIL YFYLLFPNSL SLSERVAIIK
GTYEPDEDWE EQREERKKTM ELTTR
