ID AQP1_HUMAN STANDARD; PRT; 268 AA. AC P29972; Q8TBI5; Q8TDC1; DT 01-APR-1993 (Rel. 25, Created) DT 05-JUL-2004 (Rel. 44, Last sequence update) DT 25-JAN-2005 (Rel. 46, Last annotation update) DE Aquaporin-CHIP (Water channel protein for red blood cells and kidney DE proximal tubule) (Aquaporin 1) (AQP-1) (Urine water channel). GN Name=AQP1; Synonyms=CHIP28; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Primates; Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP SEQUENCE FROM N.A., AND PARTIAL SEQUENCE. RX MEDLINE=92107900; PubMed=1722319; RA Preston G.M., Agre P.; RT "Isolation of the cDNA for erythrocyte integral membrane protein of 28 RT kilodaltons: member of an ancient channel family."; RL Proc. Natl. Acad. Sci. U.S.A. 88:11110-11114(1991). RN [2] RP SEQUENCE FROM N.A. RX MEDLINE=93340184; PubMed=8340403; RA Moon C., Preston G.M., Griffin C.A., Jabs E.W., Agre P.; RT "The human aquaporin-CHIP gene. Structure, organization, and RT chromosomal localization."; RL J. Biol. Chem. 268:15772-15778(1993). RN [3] RP SEQUENCE FROM N.A. RC TISSUE=Retinal pigment epithelium; RX MEDLINE=96326579; PubMed=8703970; DOI=10.1016/0005-2736(96)00076-4; RA Ruiz A.C., Bok D.; RT "Characterization of the 3' UTR sequence encoded by the AQP-1 gene in RT human retinal pigment epithelium."; RL Biochim. Biophys. Acta 1282:174-178(1996). RN [4] RP SEQUENCE FROM N.A. RC TISSUE=Uterus; RX MEDLINE=94290349; PubMed=7517253; RA Li X., Yu H., Koide S.S.; RT "The water channel gene in human uterus."; RL Biochem. Mol. Biol. Int. 32:371-377(1994). RN [5] RP SEQUENCE FROM N.A. RX MEDLINE=22737999; PubMed=12853948; DOI=10.1038/nature01782; RA Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H., RA Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., RA Wylie K., Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H., RA Sun H., Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., RA Vanbrunt A., Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., RA Ozersky P., Bielicki L., Scott K., Holmes A., Harkins R., Harris A., RA Strong C.M., Hou S., Tomlinson C., Dauphin-Kohlberg S., RA Kozlowicz-Reilly A., Leonard S., Rohlfing T., Rock S.M., RA Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., Strowmatt C., RA Latreille P., Miller N., Johnson D., Murray J., Woessner J.P., RA Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., Spieth J., RA Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., Cook L.L., RA Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., Mardis E.R., RA Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E., RA Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., RA Simms E., Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., RA Baertsch R.A., Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., RA Bailey J.A., Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., RA Eddy S.R., McPherson J.D., Olson M.V., Eichler E.E., Green E.D., RA Waterston R.H., Wilson R.K.; RT "The DNA sequence of human chromosome 7."; RL Nature 424:157-164(2003). RN [6] RP SEQUENCE FROM N.A. RC TISSUE=Brain; RX MEDLINE=22388257; PubMed=12477932; DOI=10.1073/pnas.242603899; RA Strausberg R.L., Feingold E.A., Grouse L.H., Derge J.G., RA Klausner R.D., Collins F.S., Wagner L., Shenmen C.M., Schuler G.D., RA Altschul S.F., Zeeberg B., Buetow K.H., Schaefer C.F., Bhat N.K., RA Hopkins R.F., Jordan H., Moore T., Max S.I., Wang J., Hsieh F., RA Diatchenko L., Marusina K., Farmer A.A., Rubin G.M., Hong L., RA Stapleton M., Soares M.B., Bonaldo M.F., Casavant T.L., Scheetz T.E., RA Brownstein M.J., Usdin T.B., Toshiyuki S., Carninci P., Prange C., RA Raha S.S., Loquellano N.A., Peters G.J., Abramson R.D., Mullahy S.J., RA Bosak S.A., McEwan P.J., McKernan K.J., Malek J.A., Gunaratne P.H., RA Richards S., Worley K.C., Hale S., Garcia A.M., Gay L.J., Hulyk S.W., RA Villalon D.K., Muzny D.M., Sodergren E.J., Lu X., Gibbs R.A., RA Fahey J., Helton E., Ketteman M., Madan A., Rodrigues S., Sanchez A., RA Whiting M., Madan A., Young A.C., Shevchenko Y., Bouffard G.G., RA Blakesley R.W., Touchman J.W., Green E.D., Dickson M.C., RA Rodriguez A.C., Grimwood J., Schmutz J., Myers R.M., RA Butterfield Y.S.N., Krzywinski M.I., Skalska U., Smailus D.E., RA Schnerch A., Schein J.E., Jones S.J.M., Marra M.A.; RT "Generation and initial analysis of more than 15,000 full-length human RT and mouse cDNA sequences."; RL Proc. Natl. Acad. Sci. U.S.A. 99:16899-16903(2002). RN [7] RP SEQUENCE OF 4-268 FROM N.A. RC TISSUE=Articular cartilage; RA Trujillo E., Gonzalez T., Martin-Vasallo P., Marples D., Mobasheri A.; RT "Human chondrocytes in situ express aquaporin water channels: changes RT in AQP1 abundance in pathologies of articular cartilage."; RL Submitted (FEB-2002) to the EMBL/GenBank/DDBJ databases. RN [8] RP SEQUENCE OF 1-35. RX PubMed=2007592; RA Smith B.L., Agre P.; RT "Erythrocyte Mr 28,000 transmembrane protein exists as a multisubunit RT oligomer similar to channel proteins."; RL J. Biol. Chem. 266:6407-6415(1991). RN [9] RP FUNCTION. RX MEDLINE=92229472; PubMed=1373524; RA Preston G.M., Carroll T.P., Guggino W.B., Agre P.; RT "Appearance of water channels in Xenopus oocytes expressing red cell RT CHIP28 protein."; RL Science 256:385-387(1992). RN [10] RP TARGET OF MERCURY INHIBITION. RX MEDLINE=93106996; PubMed=7677994; RA Preston G.M., Jung J.S., Guggino W.B., Agre P.; RT "The mercury-sensitive residue at cysteine 189 in the CHIP28 water RT channel."; RL J. Biol. Chem. 268:17-20(1993). RN [11] RP TOPOLOGY. RX MEDLINE=94124503; PubMed=7507481; RA Preston G.M., Jung J.S., Guggino W.B., Agre P.; RT "Membrane topology of aquaporin CHIP. Analysis of functional epitope- RT scanning mutants by vectorial proteolysis."; RL J. Biol. Chem. 269:1668-1673(1994). RN [12] RP STRUCTURE BY ELECTRON MICROSCOPY (1.6 ANGSTROMS). RX MEDLINE=94313979; PubMed=7518771; RA Walz T., Smith B.L., Agre P., Engel A.; RT "The three-dimensional structure of human erythrocyte aquaporin RT CHIP."; RL EMBO J. 13:2985-2993(1994). RN [13] RP STRUCTURE BY ELECTRON MICROSCOPY (6 ANGSTROMS). RX MEDLINE=97320502; PubMed=9177353; DOI=10.1038/42512; RA Walz T., Hirai T., Murata K., Heymann J.B., Mitsuoka K., Fujiyoshi Y., RA Smith B.L., Agre P., Engel A.; RT "The three-dimensional structure of aquaporin-1."; RL Nature 387:624-627(1997). RN [14] RP STRUCTURE BY ELECTRON MICROSCOPY (3.8 ANGSTROMS). RX MEDLINE=20487015; PubMed=11034202; DOI=10.1038/35036519; RA Murata K., Mitsuoka K., Hirai T., Walz T., Agre P., Heymann J.B., RA Engel A., Fujiyoshi Y.; RT "Structural determinants of water permeation through aquaporin-1."; RL Nature 407:599-605(2000). RN [15] RP STRUCTURE BY ELECTRON MICROSCOPY (3.54 ANGSTROMS). RX MEDLINE=21423577; PubMed=11532455; DOI=10.1016/S0014-5793(01)02743-0; RA de Groot B.L., Engel A., Grubmueller H.; RT "A refined structure of human aquaporin-1."; RL FEBS Lett. 504:206-211(2001). RN [16] RP STRUCTURE BY ELECTRON MICROSCOPY (3.7 ANGSTROMS). RX PubMed=11171962; DOI=10.1073/pnas.041489198; RA Ren G., Reddy V.S., Cheng A., Melnyk P., Mitra A.K.; RT "Visualization of a water-selective pore by electron crystallography RT in vitreous ice."; RL Proc. Natl. Acad. Sci. U.S.A. 98:1398-1403(2001). RN [17] RP VARIANT BLOOD GROUP COLTON VAL-44. RX MEDLINE=94365170; PubMed=7521882; RA Smith B.L., Preston G.M., Spring F., Anstee D.J., Agre P.; RT "Human red cell aquaporin CHIP. I. Molecular characterization of ABH RT and Colton blood group antigens."; RL J. Clin. Invest. 94:1043-1049(1994). RN [18] RP VARIANT LEU-37. RX MEDLINE=94360246; PubMed=7521540; RA Preston G.M., Smith B.L., Zeidel M.L., Moulds J.J., Agre P.; RT "Mutations in aquaporin-1 in phenotypically normal humans without RT functional CHIP water channels."; RL Science 265:1585-1587(1994). CC -!- FUNCTION: Forms a water-specific channel that provides the plasma CC membranes of red cells and kidney proximal tubules with high CC permeability to water, thereby permitting water to move in the CC direction of an osmotic gradient. CC -!- SUBUNIT: Homotetramer. CC -!- SUBCELLULAR LOCATION: Integral membrane protein. CC -!- TISSUE SPECIFICITY: Expressed in a number of tissues including CC erythrocytes, renal tubules, retinal pigment epithelium, heart, CC lung, skeletal muscle, kidney and pancreas. Weakly expressed in CC brain, placenta and liver. 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 -!- POLYMORPHISM: AQP1 is responsible for the Colton blood group CC system. Approximately 92% of caucasians are Co(A+B-) (Ala-45), CC approximately 8% are Co(A+B+), and only 0.2% are Co(A-B+) (Val- CC 45). Co(A-B-) which is very rare, is due to a complete absence of CC AQP1. CC -!- MISCELLANEOUS: Pharmacologically inhibited by submillimolar CC concentrations of mercury. CC -!- SIMILARITY: Belongs to the MIP/aquaporin (TC 1.A.8) family. CC -!- DATABASE: NAME=Blood group antigen mutation database; CC NOTE=Colton (Co) blood group system; CC WWW="http://www.bioc.aecom.yu.edu/bgmut/colton.htm". CC -!- DATABASE: NAME=Protein Spotlight; NOTE=Issue 36 of July 2003; CC WWW="http://www.expasy.org/spotlight/back_issues/sptlt036.shtml". 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; M77829; AAA58425.1; -. DR EMBL; U41517; AAC50648.1; -. DR EMBL; U41518; AAC50649.1; -. DR EMBL; S73482; AAB31193.1; -. DR EMBL; AC004691; AAC16481.1; -. DR EMBL; AC005155; AAC23788.1; -. DR EMBL; BC022486; AAH22486.1; -. DR EMBL; AF480415; AAL87136.1; -. DR PIR; A41616; A41616. DR PDB; 1FQY; EM; A=1-268. DR PDB; 1H6I; EM; A=1-268. DR PDB; 1IH5; EM; A=1-268. DR Genew; HGNC:633; AQP1. DR H-InvDB; HIX0006573; -. DR MIM; 107776; -. DR MIM; 110450; -. DR GO; GO:0005887; C:integral to plasma membrane; TAS. DR GO; GO:0005372; F:water transporter activity; TAS. DR GO; GO:0007588; P:excretion; TAS. DR GO; GO:0006833; P:water transport; TAS. DR InterPro; IPR000425; MIP. DR Pfam; PF00230; MIP; 1. DR PRINTS; PR00783; MINTRINSICP. DR ProDom; PD000295; MIP; 1. DR TIGRFAMs; TIGR00861; MIP; 1. DR PROSITE; PS00221; MIP; 1. KW 3D-structure; Blood group antigen; Direct protein sequencing; KW Glycoprotein; Polymorphism; Repeat; Transmembrane; Transport. FT INIT_MET 0 0 FT DOMAIN 1 6 Cytoplasmic. FT TRANSMEM 7 35 Helix 1. FT DOMAIN 36 47 Extracellular. FT TRANSMEM 48 65 Helix 2. FT DOMAIN 66 69 Cytoplasmic. FT DOMAIN 70 75 In membrane. FT TRANSMEM 76 83 Helix B. FT DOMAIN 84 93 Cytoplasmic. FT TRANSMEM 94 114 Helix 3. FT DOMAIN 115 135 Extracellular. FT TRANSMEM 136 154 Helix 4. FT DOMAIN 155 165 Cytoplasmic. FT TRANSMEM 166 182 Helix 5. FT DOMAIN 183 185 Extracellular. FT DOMAIN 186 191 In membrane. FT TRANSMEM 192 199 Helix E. FT DOMAIN 200 206 Extracellular. FT TRANSMEM 207 227 Helix 6. FT DOMAIN 228 268 Cytoplasmic. FT SITE 75 77 NPA 1. FT SITE 191 193 NPA 2. FT DOMAIN 158 161 Poly-Arg. FT SITE 55 55 Substrate discrimination. FT SITE 179 179 Substrate discrimination. FT SITE 188 188 Hg(2+)-sensitive residue. FT SITE 194 194 Substrate discrimination. FT CARBOHYD 41 41 N-linked (GlcNAc...). FT CARBOHYD 204 204 N-linked (GlcNAc...) (Potential). FT VARIANT 37 37 P -> L (in Co(A-B-) antigen; non FT functional AQP1; red cells show low FT osmotic water permeability). FT /FTId=VAR_013279. FT VARIANT 44 44 A -> V (in Co(A-B+) antigen). FT /FTId=VAR_004400. FT CONFLICT 44 44 A -> T (in Ref. 6). FT HELIX 9 35 FT TURN 40 41 FT TURN 43 44 FT TURN 48 48 FT HELIX 49 65 FT HELIX 66 68 FT TURN 69 70 FT HELIX 76 84 FT TURN 85 86 FT TURN 89 89 FT HELIX 90 112 FT HELIX 134 155 FT TURN 156 156 FT TURN 164 165 FT HELIX 167 182 FT TURN 183 185 FT HELIX 192 202 FT TURN 203 203 FT HELIX 206 209 FT HELIX 210 229 FT TURN 230 230 SQ SEQUENCE 268 AA; 28394 MW; 8D45E082EDCBA82E CRC64; ASEFKKKLFW RAVVAEFLAT TLFVFISIGS ALGFKYPVGN NQTAVQDNVK VSLAFGLSIA TLAQSVGHIS GAHLNPAVTL GLLLSCQISI FRALMYIIAQ CVGAIVATAI LSGITSSLTG NSLGRNDLAD GVNSGQGLGI EIIGTLQLVL CVLATTDRRR RDLGGSAPLA IGLSVALGHL LAIDYTGCGI NPARSFGSAV ITHNFSNHWI FWVGPFIGGA LAVLIYDFIL APRSSDLTDR VKVWTSGQVE EYDLDADDIN SRVEMKPK //