ID AQP4_HUMAN Reviewed; 323 AA. AC P55087; P78564; DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1997, sequence version 2. DT 12-SEP-2018, entry version 163. DE RecName: Full=Aquaporin-4; DE Short=AQP-4; DE AltName: Full=Mercurial-insensitive water channel; DE Short=MIWC; DE AltName: Full=WCH4; GN Name=AQP4; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RC TISSUE=Fetal brain; RX PubMed=7559426; DOI=10.1074/jbc.270.39.22907; RA Yang B., Ma T., Verkman A.S.; RT "cDNA cloning, gene organization, and chromosomal localization of a RT human mercurial insensitive water channel. Evidence for distinct RT transcriptional units."; RL J. Biol. Chem. 270:22907-22913(1995). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA]. RX PubMed=8601457; DOI=10.1016/0014-5793(96)00092-0; RA Misaka T., Abe K., Iwabuchi K., Kusakabe Y., Ichinose M., Miki K., RA Emori Y., Arai S.; RT "A water channel closely related to rat brain aquaporin 4 is expressed RT in acid- and pepsinogen-secretory cells of human stomach."; RL FEBS Lett. 381:208-212(1996). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA]. RX PubMed=8855281; DOI=10.1073/pnas.93.20.10908; RA Lu M., Lee M.D., Smith B.L., Jung J.S., Agre P., Verdijk M.A.J., RA Merkx G., Rijss J.P.L., Deen P.M.T.; RT "The human AQP4 gene: definition of the locus encoding two water RT channel polypeptides in brain."; RL Proc. Natl. Acad. Sci. U.S.A. 93:10908-10912(1996). 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., RA Taylor T.D., Whittaker C.A., Chang J.L., Cuomo C.A., Dewar K., RA FitzGerald M.G., Yang X., Abouelleil A., Allen N.R., Anderson S., RA Bloom T., Bugalter B., Butler J., Cook A., DeCaprio D., Engels R., RA Garber M., Gnirke A., Hafez N., Hall J.L., Norman C.H., Itoh T., RA Jaffe D.B., Kuroki Y., Lehoczky J., Lui A., Macdonald P., Mauceli E., RA Mikkelsen T.S., Naylor J.W., Nicol R., Nguyen C., Noguchi H., RA 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]. RC TISSUE=Lung; 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 RT project: the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [6] RP SUBUNIT. RX PubMed=22328087; DOI=10.1093/hmg/dds032; RA Lanciotti A., Brignone M.S., Molinari P., Visentin S., De Nuccio C., RA Macchia G., Aiello C., Bertini E., Aloisi F., Petrucci T.C., RA Ambrosini E.; RT "Megalencephalic leukoencephalopathy with subcortical cysts protein 1 RT functionally cooperates with the TRPV4 cation channel to activate the RT response of astrocytes to osmotic stress: dysregulation by RT pathological mutations."; RL Hum. Mol. Genet. 21:2166-2180(2012). RN [7] RP X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 32-254, AND SUBUNIT. RX PubMed=19383790; DOI=10.1073/pnas.0902725106; RA Ho J.D., Yeh R., Sandstrom A., Chorny I., Harries W.E., Robbins R.A., RA Miercke L.J., Stroud R.M.; RT "Crystal structure of human aquaporin 4 at 1.8 A and its mechanism of RT conductance."; RL Proc. Natl. Acad. Sci. U.S.A. 106:7437-7442(2009). CC -!- FUNCTION: Forms a water-specific channel. Osmoreceptor which CC regulates body water balance and mediates water flow within the CC central nervous system. CC -!- SUBUNIT: Homotetramer. Part of a complex containing MLC1, TRPV4, CC HEPACAM and ATP1B1. {ECO:0000269|PubMed:19383790, CC ECO:0000269|PubMed:22328087}. CC -!- INTERACTION: CC O43889-2:CREB3; NbExp=3; IntAct=EBI-10104898, EBI-625022; CC -!- SUBCELLULAR LOCATION: Membrane; Multi-pass membrane protein. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=2; CC IsoId=P55087-1; Sequence=Displayed; CC Name=1; CC IsoId=P55087-2; Sequence=VSP_003232; CC -!- TISSUE SPECIFICITY: Brain - muscle >> heart, kidney, lung, and CC trachea. CC -!- DOMAIN: Aquaporins contain two tandem repeats each containing CC three membrane-spanning domains and a pore-forming loop with the CC signature motif Asn-Pro-Ala (NPA). CC -!- PTM: Phosphorylation by PKC at Ser-180 reduces conductance by 50%. CC Phosphorylation by PKG at Ser-111 in response to glutamats CC increases conductance by 40% (By similarity). {ECO:0000250}. CC -!- SIMILARITY: Belongs to the MIP/aquaporin (TC 1.A.8) family. CC {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=AAC50284.1; Type=Erroneous initiation; Evidence={ECO:0000305}; CC Sequence=AAC52112.1; Type=Erroneous initiation; Evidence={ECO:0000305}; CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology CC and Haematology; CC URL="http://atlasgeneticsoncology.org/Genes/AQP4ID684ch18q11.html"; 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; U34846; AAC52112.1; ALT_INIT; mRNA. DR EMBL; U34845; AAC50284.1; ALT_INIT; mRNA. DR EMBL; D63412; BAA09715.1; -; mRNA. DR EMBL; U63622; AAB26957.1; -; mRNA. DR EMBL; U63623; AAB26958.1; -; mRNA. DR EMBL; AC018371; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC022286; AAH22286.1; -; mRNA. DR CCDS; CCDS11889.1; -. [P55087-1] DR CCDS; CCDS58617.1; -. [P55087-2] DR PIR; I39178; I39178. DR RefSeq; NP_001641.1; NM_001650.5. [P55087-1] DR RefSeq; NP_004019.1; NM_004028.4. [P55087-2] DR UniGene; Hs.315369; -. DR PDB; 3GD8; X-ray; 1.80 A; A=32-254. DR PDBsum; 3GD8; -. DR ProteinModelPortal; P55087; -. DR SMR; P55087; -. DR BioGrid; 106857; 2. DR DIP; DIP-48842N; -. DR IntAct; P55087; 3. DR STRING; 9606.ENSP00000372654; -. DR ChEMBL; CHEMBL5964; -. DR TCDB; 1.A.8.8.5; the major intrinsic protein (mip) family. DR iPTMnet; P55087; -. DR PhosphoSitePlus; P55087; -. DR SwissPalm; P55087; -. DR BioMuta; AQP4; -. DR DMDM; 2506859; -. DR PaxDb; P55087; -. DR PeptideAtlas; P55087; -. DR PRIDE; P55087; -. DR ProteomicsDB; 56788; -. DR ProteomicsDB; 56789; -. [P55087-2] DR DNASU; 361; -. DR Ensembl; ENST00000383168; ENSP00000372654; ENSG00000171885. [P55087-1] DR Ensembl; ENST00000440832; ENSP00000393121; ENSG00000171885. [P55087-2] DR Ensembl; ENST00000581374; ENSP00000462597; ENSG00000171885. [P55087-2] DR GeneID; 361; -. DR KEGG; hsa:361; -. DR UCSC; uc002kvz.4; human. [P55087-1] DR CTD; 361; -. DR DisGeNET; 361; -. DR EuPathDB; HostDB:ENSG00000171885.13; -. DR GeneCards; AQP4; -. DR HGNC; HGNC:637; AQP4. DR HPA; CAB005079; -. DR HPA; CAB058689; -. DR HPA; HPA014784; -. DR MIM; 600308; gene. DR neXtProt; NX_P55087; -. DR OpenTargets; ENSG00000171885; -. DR PharmGKB; PA24922; -. DR eggNOG; KOG0223; Eukaryota. DR eggNOG; COG0580; LUCA. DR GeneTree; ENSGT00760000119223; -. DR HOGENOM; HOG000288286; -. DR HOVERGEN; HBG000312; -. DR InParanoid; P55087; -. DR KO; K09866; -. DR OMA; TQPFWKA; -. DR OrthoDB; EOG091G166T; -. DR PhylomeDB; P55087; -. DR TreeFam; TF312940; -. DR Reactome; R-HSA-432040; Vasopressin regulates renal water homeostasis via Aquaporins. DR Reactome; R-HSA-432047; Passive transport by Aquaporins. DR SIGNOR; P55087; -. DR ChiTaRS; AQP4; human. DR EvolutionaryTrace; P55087; -. DR GeneWiki; Aquaporin_4; -. DR GenomeRNAi; 361; -. DR PRO; PR:P55087; -. DR Proteomes; UP000005640; Chromosome 18. DR Bgee; ENSG00000171885; Expressed in 154 organ(s), highest expression level in lateral globus pallidus. DR CleanEx; HS_AQP4; -. DR ExpressionAtlas; P55087; baseline and differential. DR Genevisible; P55087; HS. DR GO; GO:0016323; C:basolateral plasma membrane; IBA:GO_Central. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0009897; C:external side of plasma membrane; IDA:UniProtKB. DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central. DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB. DR GO; GO:0042802; F:identical protein binding; IPI:IntAct. DR GO; GO:0015250; F:water channel activity; EXP:Reactome. DR GO; GO:0005372; F:water transmembrane transporter activity; TAS:ProtInc. DR GO; GO:0071346; P:cellular response to interferon-gamma; IDA:UniProtKB. DR GO; GO:0034220; P:ion transmembrane transport; IBA:GO_Central. DR GO; GO:0050891; P:multicellular organismal water homeostasis; IEP:UniProtKB. DR GO; GO:0003091; P:renal water homeostasis; TAS:Reactome. DR GO; GO:0006833; P:water transport; TAS:Reactome. DR CDD; cd00333; MIP; 1. DR Gene3D; 1.20.1080.10; -; 1. DR InterPro; IPR023271; Aquaporin-like. DR InterPro; IPR034294; Aquaporin_transptr. DR InterPro; IPR000425; MIP. DR InterPro; IPR022357; MIP_CS. DR PANTHER; PTHR19139; PTHR19139; 1. DR Pfam; PF00230; MIP; 1. 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; Alternative splicing; Complete proteome; Glycoprotein; KW Membrane; Phosphoprotein; Reference proteome; Repeat; Transmembrane; KW Transmembrane helix; Transport. FT CHAIN 1 323 Aquaporin-4. FT /FTId=PRO_0000063948. FT TOPO_DOM 1 36 Cytoplasmic. {ECO:0000255}. FT TRANSMEM 37 57 Helical. {ECO:0000255}. FT TOPO_DOM 58 64 Extracellular. {ECO:0000255}. FT TRANSMEM 65 85 Helical. {ECO:0000255}. FT TOPO_DOM 86 115 Cytoplasmic. {ECO:0000255}. FT TRANSMEM 116 136 Helical. {ECO:0000255}. FT TOPO_DOM 137 155 Extracellular. {ECO:0000255}. FT TRANSMEM 156 176 Helical. {ECO:0000255}. FT TOPO_DOM 177 184 Cytoplasmic. {ECO:0000255}. FT TRANSMEM 185 205 Helical. {ECO:0000255}. FT TOPO_DOM 206 231 Extracellular. {ECO:0000255}. FT TRANSMEM 232 252 Helical. {ECO:0000255}. FT TOPO_DOM 253 323 Cytoplasmic. {ECO:0000255}. FT MOTIF 97 99 NPA 1. FT MOTIF 213 215 NPA 2. FT MOD_RES 111 111 Phosphoserine; by PKG. FT {ECO:0000250|UniProtKB:P47863}. FT MOD_RES 180 180 Phosphoserine; by PKC. FT {ECO:0000250|UniProtKB:P47863}. FT MOD_RES 276 276 Phosphoserine. FT {ECO:0000250|UniProtKB:P47863}. FT MOD_RES 285 285 Phosphoserine. FT {ECO:0000250|UniProtKB:P55088}. FT MOD_RES 289 289 Phosphothreonine. FT {ECO:0000250|UniProtKB:P55088}. FT MOD_RES 321 321 Phosphoserine. FT {ECO:0000250|UniProtKB:P47863}. FT CARBOHYD 153 153 N-linked (GlcNAc...) asparagine. FT {ECO:0000255}. FT CARBOHYD 206 206 N-linked (GlcNAc...) asparagine. FT {ECO:0000255}. FT VAR_SEQ 1 22 Missing (in isoform 1). {ECO:0000305}. FT /FTId=VSP_003232. FT CONFLICT 246 246 G -> A (in Ref. 1; AAC52112). FT {ECO:0000305}. FT CONFLICT 287 288 VE -> AK (in Ref. 1; AAC52112). FT {ECO:0000305}. FT CONFLICT 296 296 P -> L (in Ref. 1; AAC52112). FT {ECO:0000305}. FT HELIX 33 55 {ECO:0000244|PDB:3GD8}. FT TURN 59 63 {ECO:0000244|PDB:3GD8}. FT HELIX 70 92 {ECO:0000244|PDB:3GD8}. FT HELIX 98 106 {ECO:0000244|PDB:3GD8}. FT HELIX 112 136 {ECO:0000244|PDB:3GD8}. FT HELIX 139 142 {ECO:0000244|PDB:3GD8}. FT TURN 143 146 {ECO:0000244|PDB:3GD8}. FT HELIX 156 177 {ECO:0000244|PDB:3GD8}. FT HELIX 189 208 {ECO:0000244|PDB:3GD8}. FT HELIX 214 224 {ECO:0000244|PDB:3GD8}. FT TURN 228 231 {ECO:0000244|PDB:3GD8}. FT HELIX 232 250 {ECO:0000244|PDB:3GD8}. SQ SEQUENCE 323 AA; 34830 MW; 1A1600CF0DC11052 CRC64; MSDRPTARRW GKCGPLCTRE NIMVAFKGVW TQAFWKAVTA EFLAMLIFVL LSLGSTINWG GTEKPLPVDM VLISLCFGLS IATMVQCFGH ISGGHINPAV TVAMVCTRKI SIAKSVFYIA AQCLGAIIGA GILYLVTPPS VVGGLGVTMV HGNLTAGHGL LVELIITFQL VFTIFASCDS KRTDVTGSIA LAIGFSVAIG HLFAINYTGA SMNPARSFGP AVIMGNWENH WIYWVGPIIG AVLAGGLYEY VFCPDVEFKR RFKEAFSKAA QQTKGSYMEV EDNRSQVETD DLILKPGVVH VIDVDRGEEK KGKDQSGEVL SSV //