ID   AQP1_HUMAN              Reviewed;         269 AA.
AC   P29972; B5BU39; Q8TBI5; Q8TDC1;
DT   01-APR-1993, integrated into UniProtKB/Swiss-Prot.
DT   23-JAN-2007, sequence version 3.
DT   09-FEB-2010, entry version 118.
DE   RecName: Full=Aquaporin-1;
DE            Short=AQP-1;
DE   AltName: Full=Aquaporin-CHIP;
DE   AltName: Full=Water channel protein for red blood cells and kidney proximal tubule;
DE   AltName: Full=Urine water channel;
GN   Name=AQP1; Synonyms=CHIP28;
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], AND PARTIAL PROTEIN SEQUENCE.
RX   MEDLINE=92107900; PubMed=1722319; DOI=10.1073/pnas.88.24.11110;
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   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
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   NUCLEOTIDE SEQUENCE [MRNA].
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   NUCLEOTIDE SEQUENCE [MRNA].
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   NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS VAL-45 AND ASP-165.
RG   SeattleSNPs variation discovery resource;
RL   Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases.
RN   [6]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX   PubMed=19054851; DOI=10.1038/nmeth.1273;
RA   Goshima N., Kawamura Y., Fukumoto A., Miura A., Honma R., Satoh R.,
RA   Wakamatsu A., Yamamoto J., Kimura K., Nishikawa T., Andoh T., Iida Y.,
RA   Ishikawa K., Ito E., Kagawa N., Kaminaga C., Kanehori K., Kawakami B.,
RA   Kenmochi K., Kimura R., Kobayashi M., Kuroita T., Kuwayama H.,
RA   Maruyama Y., Matsuo K., Minami K., Mitsubori M., Mori M.,
RA   Morishita R., Murase A., Nishikawa A., Nishikawa S., Okamoto T.,
RA   Sakagami N., Sakamoto Y., Sasaki Y., Seki T., Sono S., Sugiyama A.,
RA   Sumiya T., Takayama T., Takayama Y., Takeda H., Togashi T., Yahata K.,
RA   Yamada H., Yanagisawa Y., Endo Y., Imamoto F., Kisu Y., Tanaka S.,
RA   Isogai T., Imai J., Watanabe S., Nomura N.;
RT   "Human protein factory for converting the transcriptome into an in
RT   vitro-expressed proteome.";
RL   Nat. Methods 5:1011-1017(2008).
RN   [7]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
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   [8]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA   Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA   Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA   Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA   Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA   Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA   Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA   Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA   Venter J.C.;
RL   Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN   [9]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Brain;
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   [10]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 5-269.
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   [11]
RP   PROTEIN SEQUENCE OF 2-36.
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   [12]
RP   FUNCTION.
RX   MEDLINE=92229472; PubMed=1373524; DOI=10.1126/science.256.5055.385;
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   [13]
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   [14]
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   [15]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-262, AND MASS
RP   SPECTROMETRY.
RX   PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA   Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA   Greff Z., Keri G., Stemmann O., Mann M.;
RT   "Kinase-selective enrichment enables quantitative phosphoproteomics of
RT   the kinome across the cell cycle.";
RL   Mol. Cell 31:438-448(2008).
RN   [16]
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   [17]
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   [18]
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   [19]
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   [20]
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   [21]
RP   VARIANT BLOOD GROUP COLTON VAL-45.
RX   MEDLINE=94365170; PubMed=7521882; DOI=10.1172/JCI117418;
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   [22]
RP   VARIANT LEU-38.
RX   MEDLINE=94360246; PubMed=7521540; DOI=10.1126/science.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   -!- INTERACTION:
CC       Q99750:MDFI; NbExp=3; IntAct=EBI-745213, EBI-724076;
CC   -!- SUBCELLULAR LOCATION: Membrane; Multi-pass 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-46),
CC       approximately 8% are Co(A+B+), and only 0.2% are Co(A-B+) (Val-
CC       46). 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   -!- WEB RESOURCE: Name=dbRBC/BGMUT; Note=Blood group antigen gene
CC       mutation database;
CC       URL="http://www.ncbi.nlm.nih.gov/gv/mhc/xslcgi.cgi?cmd=bgmut/systems_info&system=colton";
CC   -!- WEB RESOURCE: Name=SeattleSNPs;
CC       URL="http://pga.gs.washington.edu/data/aqp1/";
CC   -!- WEB RESOURCE: Name=Protein Spotlight; Note=Liquid states - Issue
CC       36 of July 2003;
CC       URL="http://www.expasy.org/spotlight/back_issues/sptlt036.shtml";
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DR   EMBL; M77829; AAA58425.1; -; mRNA.
DR   EMBL; U41517; AAC50648.1; -; mRNA.
DR   EMBL; U41518; AAC50649.1; -; mRNA.
DR   EMBL; S73482; AAB31193.1; -; mRNA.
DR   EMBL; AC004691; AAC16481.1; -; Genomic_DNA.
DR   EMBL; AC005155; AAC23788.1; -; Genomic_DNA.
DR   EMBL; AY953319; AAX24129.1; -; Genomic_DNA.
DR   EMBL; AB451275; BAG70089.1; -; mRNA.
DR   EMBL; AB451402; BAG70216.1; -; mRNA.
DR   EMBL; CH471073; EAW93971.1; -; Genomic_DNA.
DR   EMBL; BC022486; AAH22486.1; -; mRNA.
DR   EMBL; AF480415; AAL87136.1; -; Genomic_DNA.
DR   IPI; IPI00024689; -.
DR   PIR; A41616; A41616.
DR   PIR; I52366; I52366.
DR   RefSeq; NP_932766.1; -.
DR   UniGene; Hs.76152; -.
DR   PDB; 1FQY; X-ray; 3.80 A; A=1-269.
DR   PDB; 1H6I; X-ray; 3.54 A; A=1-269.
DR   PDB; 1IH5; X-ray; 3.70 A; A=1-269.
DR   PDBsum; 1FQY; -.
DR   PDBsum; 1H6I; -.
DR   PDBsum; 1IH5; -.
DR   SMR; P29972; 8-233.
DR   DIP; DIP-29607N; -.
DR   IntAct; P29972; 7.
DR   STRING; P29972; -.
DR   TCDB; 1.A.8.8.1; major intrinsic protein (MIP) family.
DR   PhosphoSite; P29972; -.
DR   PRIDE; P29972; -.
DR   Ensembl; ENST00000311813; ENSP00000311165; ENSG00000240583; Homo sapiens.
DR   GeneID; 358; -.
DR   KEGG; hsa:358; -.
DR   UCSC; uc003tbv.1; human.
DR   CTD; 358; -.
DR   GeneCards; GC07P030917; -.
DR   H-InvDB; HIX0006573; -.
DR   HGNC; HGNC:633; AQP1.
DR   HPA; CAB001707; -.
DR   HPA; HPA019206; -.
DR   MIM; 107776; gene.
DR   MIM; 110450; phenotype.
DR   PharmGKB; PA24918; -.
DR   eggNOG; prNOG13886; -.
DR   HOVERGEN; P29972; -.
DR   InParanoid; P29972; -.
DR   OMA; TGCSINP; -.
DR   PhylomeDB; P29972; -.
DR   DrugBank; DB00819; Acetazolamide.
DR   NextBio; 1497; -.
DR   ArrayExpress; P29972; -.
DR   Bgee; P29972; -.
DR   CleanEx; HS_AQP1; -.
DR   Genevestigator; P29972; -.
DR   GermOnline; ENSG00000106125; Homo sapiens.
DR   GO; GO:0016324; C:apical plasma membrane; IDA:UniProtKB.
DR   GO; GO:0016323; C:basolateral plasma membrane; IDA:UniProtKB.
DR   GO; GO:0005887; C:integral to plasma membrane; TAS:ProtInc.
DR   GO; GO:0051739; F:ammonia transporter activity; IDA:UniProtKB.
DR   GO; GO:0005515; F:protein binding; IPI:IntAct.
DR   GO; GO:0015696; P:ammonium transport; IDA:UniProtKB.
DR   GO; GO:0015670; P:carbon dioxide transport; IDA:UniProtKB.
DR   GO; GO:0007588; P:excretion; TAS:ProtInc.
DR   GO; GO:0055085; P:transmembrane transport; IEA:InterPro.
DR   GO; GO:0006833; P:water transport; TAS:ProtInc.
DR   InterPro; IPR012269; Aquaporin.
DR   InterPro; IPR000425; MIP.
DR   Gene3D; G3DSA:1.20.1080.10; MIP; 1.
DR   PANTHER; PTHR19139; MIP; 1.
DR   Pfam; PF00230; MIP; 1.
DR   PRINTS; PR00783; MINTRINSICP.
DR   TIGRFAMs; TIGR00861; MIP; 1.
DR   PROSITE; PS00221; MIP; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Blood group antigen; Complete proteome;
KW   Direct protein sequencing; Glycoprotein; Membrane; Phosphoprotein;
KW   Polymorphism; Repeat; Transmembrane; Transport.
FT   INIT_MET      1      1       Removed.
FT   CHAIN         2    269       Aquaporin-1.
FT                                /FTId=PRO_0000063920.
FT   TOPO_DOM      2      7       Cytoplasmic.
FT   TRANSMEM      8     36       Helix 1.
FT   TOPO_DOM     37     48       Extracellular.
FT   TRANSMEM     49     66       Helix 2.
FT   TOPO_DOM     67     70       Cytoplasmic.
FT   TOPO_DOM     71     76       In membrane.
FT   TRANSMEM     77     84       Helix B.
FT   TOPO_DOM     85     94       Cytoplasmic.
FT   TRANSMEM     95    115       Helix 3.
FT   TOPO_DOM    116    136       Extracellular.
FT   TRANSMEM    137    155       Helix 4.
FT   TOPO_DOM    156    166       Cytoplasmic.
FT   TRANSMEM    167    183       Helix 5.
FT   TOPO_DOM    184    186       Extracellular.
FT   TOPO_DOM    187    192       In membrane.
FT   TRANSMEM    193    200       Helix E.
FT   TOPO_DOM    201    207       Extracellular.
FT   TRANSMEM    208    228       Helix 6.
FT   TOPO_DOM    229    269       Cytoplasmic.
FT   MOTIF        76     78       NPA 1.
FT   MOTIF       192    194       NPA 2.
FT   COMPBIAS    159    162       Poly-Arg.
FT   SITE         56     56       Substrate discrimination.
FT   SITE        180    180       Substrate discrimination.
FT   SITE        189    189       Hg(2+)-sensitive residue.
FT   SITE        195    195       Substrate discrimination.
FT   MOD_RES     246    246       Phosphothreonine (By similarity).
FT   MOD_RES     247    247       Phosphoserine (By similarity).
FT   MOD_RES     262    262       Phosphoserine.
FT   CARBOHYD     42     42       N-linked (GlcNAc...).
FT   CARBOHYD    205    205       N-linked (GlcNAc...) (Potential).
FT   VARIANT      38     38       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      45     45       A -> V (in Co(A-B+) antigen;
FT                                dbSNP:rs28362692).
FT                                /FTId=VAR_004400.
FT   VARIANT     165    165       G -> D (in dbSNP:rs28362731).
FT                                /FTId=VAR_022318.
FT   CONFLICT     45     45       A -> T (in Ref. 9; AAH22486).
FT   HELIX         8     35
FT   STRAND       37     42
FT   HELIX        48     65
FT   STRAND       68     71
FT   HELIX        76     83
FT   HELIX        94    114
FT   TURN        119    122
FT   STRAND      132    135
FT   HELIX       136    154
FT   HELIX       166    182
FT   TURN        183    185
FT   HELIX       192    199
FT   HELIX       207    227
SQ   SEQUENCE   269 AA;  28526 MW;  BA204D82FB26352E CRC64;
     MASEFKKKLF WRAVVAEFLA TTLFVFISIG SALGFKYPVG NNQTAVQDNV KVSLAFGLSI
     ATLAQSVGHI SGAHLNPAVT LGLLLSCQIS IFRALMYIIA QCVGAIVATA ILSGITSSLT
     GNSLGRNDLA DGVNSGQGLG IEIIGTLQLV LCVLATTDRR RRDLGGSAPL AIGLSVALGH
     LLAIDYTGCG INPARSFGSA VITHNFSNHW IFWVGPFIGG ALAVLIYDFI LAPRSSDLTD
     RVKVWTSGQV EEYDLDADDI NSRVEMKPK
//