MIP_BOVIN
ID MIP_BOVIN Reviewed; 263 AA.
AC P06624;
DT 01-JAN-1988, integrated into UniProtKB/Swiss-Prot.
DT 01-JAN-1988, sequence version 1.
DT 03-AUG-2022, entry version 165.
DE RecName: Full=Lens fiber major intrinsic protein;
DE AltName: Full=Aquaporin-0;
DE AltName: Full=MIP26;
DE Short=MP26;
GN Name=MIP;
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND PROTEIN SEQUENCE OF 1-39.
RX PubMed=6207938; DOI=10.1016/0092-8674(84)90190-9;
RA Gorin M.B., Yancey S.B., Cline J., Revel J.-P., Horwitz J.;
RT "The major intrinsic protein (MIP) of the bovine lens fiber membrane:
RT characterization and structure based on cDNA cloning.";
RL Cell 39:49-59(1984).
RN [2]
RP PROTEIN SEQUENCE OF 1-33.
RC TISSUE=Lens;
RX PubMed=3882455; DOI=10.1016/0014-5793(85)81116-9;
RA Ngoc L.D., Paroutaud P., Dunia I., Benedetti E.L., Hoebeke J.;
RT "Sequence analysis of peptide fragments from the intrinsic membrane protein
RT of calf lens fibers MP26 and its natural maturation product MP22.";
RL FEBS Lett. 181:74-78(1985).
RN [3]
RP PROTEIN SEQUENCE OF 239-259, PHOSPHORYLATION AT SER-243 AND SER-245, AND
RP DEAMIDATION AT ASN-246.
RC TISSUE=Lens;
RX PubMed=2176601; DOI=10.1111/j.1432-1033.1990.tb15650.x;
RA Lampe P.D., Johnson R.G.;
RT "Amino acid sequence of in vivo phosphorylation sites in the main intrinsic
RT protein (MIP) of lens membranes.";
RL Eur. J. Biochem. 194:541-547(1990).
RN [4]
RP PHOSPHORYLATION AT SER-235.
RC TISSUE=Lens;
RX PubMed=9375569;
RA Schey K.L., Fowler J.G., Schwartz J.C., Busman M., Dillon J., Crouch R.K.;
RT "Complete map and identification of the phosphorylation site of bovine lens
RT major intrinsic protein.";
RL Invest. Ophthalmol. Vis. Sci. 38:2508-2515(1997).
RN [5]
RP FUNCTION, INTERACTION WITH CALM, AND MUTAGENESIS OF TYR-149; LEU-227 AND
RP VAL-230.
RX PubMed=23893133; DOI=10.1038/nsmb.2630;
RA Reichow S.L., Clemens D.M., Freites J.A., Nemeth-Cahalan K.L., Heyden M.,
RA Tobias D.J., Hall J.E., Gonen T.;
RT "Allosteric mechanism of water-channel gating by Ca(2+)-calmodulin.";
RL Nat. Struct. Mol. Biol. 20:1085-1092(2013).
RN [6]
RP FATTY ACYLATION.
RX PubMed=27378310; DOI=10.1016/j.bbamem.2016.06.026;
RA Ismail V.S., Mosely J.A., Tapodi A., Quinlan R.A., Sanderson J.M.;
RT "The lipidation profile of aquaporin-0 correlates with the acyl composition
RT of phosphoethanolamine lipids in lens membranes.";
RL Biochim. Biophys. Acta 1858:2763-2768(2016).
RN [7]
RP INTERACTION WITH BFSP1.
RX PubMed=28259670; DOI=10.1016/j.exer.2017.02.012;
RA Wang Z., Schey K.L.;
RT "Identification of a direct Aquaporin-0 binding site in the lens-specific
RT cytoskeletal protein filensin.";
RL Exp. Eye Res. 159:23-29(2017).
RN [8]
RP X-RAY CRYSTALLOGRAPHY (2.24 ANGSTROMS), MEMBRANE TOPOLOGY, AND SUBUNIT.
RX PubMed=15377788; DOI=10.1073/pnas.0405274101;
RA Harries W.E., Akhavan D., Miercke L.J., Khademi S., Stroud R.M.;
RT "The channel architecture of aquaporin 0 at a 2.2-A resolution.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:14045-14050(2004).
RN [9]
RP X-RAY CRYSTALLOGRAPHY (7.01 ANGSTROMS), MEMBRANE TOPOLOGY, AND SUBUNIT.
RX PubMed=16309700; DOI=10.1016/j.jmb.2005.10.032;
RA Palanivelu D.V., Kozono D.E., Engel A., Suda K., Lustig A., Agre P.,
RA Schirmer T.;
RT "Co-axial association of recombinant eye lens aquaporin-0 observed in
RT loosely packed 3D crystals.";
RL J. Mol. Biol. 355:605-611(2006).
CC -!- FUNCTION: Water channel (PubMed:23893133). Channel activity is down-
CC regulated by CALM when cytoplasmic Ca(2+) levels are increased. May be
CC responsible for regulating the osmolarity of the lens. Interactions
CC between homotetramers from adjoining membranes may stabilize cell
CC junctions in the eye lens core (By similarity). Plays a role in cell-
CC to-cell adhesion and facilitates gap junction coupling.
CC {ECO:0000250|UniProtKB:P30301, ECO:0000250|UniProtKB:Q6J8I9,
CC ECO:0000269|PubMed:23893133}.
CC -!- SUBUNIT: Homotetramer (PubMed:15377788, PubMed:16309700). Homooctamer
CC formed by head-to-head interaction between homotetramers from adjoining
CC membranes (PubMed:15377788, PubMed:16309700). Interacts with CALM; one
CC CALM molecule interacts with the cytoplasmic domains of two aquaporins,
CC leading to channel closure (PubMed:23893133). Interacts (via C-
CC terminus) with BFSP1 (via C-terminus) in aged lens fiber cells
CC (PubMed:28259670). {ECO:0000269|PubMed:15377788,
CC ECO:0000269|PubMed:16309700, ECO:0000269|PubMed:23893133,
CC ECO:0000269|PubMed:28259670}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:P30301};
CC Multi-pass membrane protein {ECO:0000250|UniProtKB:Q6J8I9}. Cell
CC junction, gap junction {ECO:0000250|UniProtKB:P30301}.
CC -!- TISSUE SPECIFICITY: Major component of lens fiber gap junctions.
CC -!- DEVELOPMENTAL STAGE: Higher expression in pre-natal (1-5 months
CC gestation) than in postnatal (4-6 months) calf lens.
CC -!- DOMAIN: Aquaporins contain two tandem repeats each containing two
CC membrane-spanning helices and a pore-forming loop with the signature
CC motif Asn-Pro-Ala (NPA). Each tandem repeat contains a loop and a short
CC helix that enter and leave the lipid bilayer on the same side.
CC -!- PTM: Subject to partial proteolytic cleavage in the eye lens core.
CC Partial proteolysis promotes interactions between tetramers from
CC adjoining membranes (By similarity). {ECO:0000250}.
CC -!- PTM: Fatty acylated at Met-1 and Lys-238. The acyl modifications, in
CC decreasing order of ion abundance, are: oleoyl (C18:1) > palmitoyl
CC (C16:0) > stearoyl (C18:0) > eicosenoyl (C20:1) > dihomo-gamma-
CC linolenoyl (C20:3) > palmitoleoyl (C16:1) > eicosadienoyl (C20:2).
CC {ECO:0000269|PubMed:27378310}.
CC -!- SIMILARITY: Belongs to the MIP/aquaporin (TC 1.A.8) family.
CC {ECO:0000305}.
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; K02818; AAA30622.1; -; mRNA.
DR PIR; A23251; MMBOLM.
DR RefSeq; NP_776362.1; NM_173937.2.
DR PDB; 1YMG; X-ray; 2.24 A; A=1-263.
DR PDB; 2C32; X-ray; 7.01 A; A=1-263.
DR PDBsum; 1YMG; -.
DR PDBsum; 2C32; -.
DR AlphaFoldDB; P06624; -.
DR SMR; P06624; -.
DR DIP; DIP-60546N; -.
DR IntAct; P06624; 1.
DR STRING; 9913.ENSBTAP00000013360; -.
DR TCDB; 1.A.8.8.2; the major intrinsic protein (mip) family.
DR iPTMnet; P06624; -.
DR PaxDb; P06624; -.
DR Ensembl; ENSBTAT00000013360; ENSBTAP00000013360; ENSBTAG00000010127.
DR GeneID; 280859; -.
DR KEGG; bta:280859; -.
DR CTD; 4284; -.
DR VEuPathDB; HostDB:ENSBTAG00000010127; -.
DR VGNC; VGNC:31482; MIP.
DR eggNOG; KOG0223; Eukaryota.
DR GeneTree; ENSGT00940000156260; -.
DR HOGENOM; CLU_020019_3_3_1; -.
DR InParanoid; P06624; -.
DR OMA; WTPGPLH; -.
DR OrthoDB; 1152704at2759; -.
DR TreeFam; TF312940; -.
DR Reactome; R-BTA-432047; Passive transport by Aquaporins.
DR EvolutionaryTrace; P06624; -.
DR Proteomes; UP000009136; Chromosome 5.
DR Bgee; ENSBTAG00000010127; Expressed in pigment epithelium of eye and 32 other tissues.
DR GO; GO:0016324; C:apical plasma membrane; IBA:GO_Central.
DR GO; GO:0005783; C:endoplasmic reticulum; ISS:UniProtKB.
DR GO; GO:0005921; C:gap junction; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IBA:GO_Central.
DR GO; GO:0005887; C:integral component of plasma membrane; IMP:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0005516; F:calmodulin binding; IMP:UniProtKB.
DR GO; GO:0005212; F:structural constituent of eye lens; IEA:UniProtKB-KW.
DR GO; GO:0015250; F:water channel activity; IMP:UniProtKB.
DR GO; GO:1990349; P:gap junction-mediated intercellular transport; ISS:UniProtKB.
DR GO; GO:0002088; P:lens development in camera-type eye; IEA:Ensembl.
DR GO; GO:0045785; P:positive regulation of cell adhesion; ISS:UniProtKB.
DR GO; GO:0051289; P:protein homotetramerization; ISS:UniProtKB.
DR GO; GO:0007601; P:visual perception; IEA:Ensembl.
DR GO; GO:0006833; P:water transport; IMP:UniProtKB.
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; Cell junction; Cell membrane; Direct protein sequencing;
KW Eye lens protein; Gap junction; Lipoprotein; Membrane; Phosphoprotein;
KW Reference proteome; Repeat; Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..263
FT /note="Lens fiber major intrinsic protein"
FT /id="PRO_0000063910"
FT TOPO_DOM 1..8
FT /note="Cytoplasmic"
FT TRANSMEM 9..32
FT /note="Helical"
FT TOPO_DOM 33..38
FT /note="Extracellular"
FT TRANSMEM 39..61
FT /note="Helical"
FT INTRAMEM 62..67
FT INTRAMEM 68..78
FT /note="Helical"
FT TOPO_DOM 79..84
FT /note="Cytoplasmic"
FT TRANSMEM 85..107
FT /note="Helical"
FT TOPO_DOM 108..126
FT /note="Extracellular"
FT TRANSMEM 127..147
FT /note="Helical"
FT TOPO_DOM 148..159
FT /note="Cytoplasmic"
FT TRANSMEM 160..176
FT /note="Helical"
FT INTRAMEM 177..183
FT INTRAMEM 184..194
FT /note="Helical"
FT TOPO_DOM 195..200
FT /note="Extracellular"
FT TRANSMEM 201..219
FT /note="Helical"
FT TOPO_DOM 220..263
FT /note="Cytoplasmic"
FT REGION 227..237
FT /note="Interaction with CALM"
FT /evidence="ECO:0000269|PubMed:23893133"
FT REGION 239..263
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 68..70
FT /note="NPA 1"
FT MOTIF 184..186
FT /note="NPA 2"
FT SITE 149
FT /note="Important for water channel gating"
FT SITE 246
FT /note="Interaction with BFSP1"
FT /evidence="ECO:0000269|PubMed:28259670"
FT SITE 250
FT /note="interaction with BFSP1"
FT /evidence="ECO:0000269|PubMed:28259670"
FT MOD_RES 235
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:9375569"
FT MOD_RES 243
FT /note="Phosphoserine; by PKA"
FT /evidence="ECO:0000269|PubMed:2176601"
FT MOD_RES 245
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:2176601"
FT MOD_RES 246
FT /note="Deamidated asparagine"
FT /evidence="ECO:0000269|PubMed:2176601"
FT MUTAGEN 149
FT /note="Y->G: Increases constitutive water permeability.
FT Abolishes regulation by cytoplasmic calcium levels."
FT /evidence="ECO:0000269|PubMed:23893133"
FT MUTAGEN 149
FT /note="Y->L: Strongly decreases water permeability.
FT Abolishes regulation by cytoplasmic calcium levels."
FT /evidence="ECO:0000269|PubMed:23893133"
FT MUTAGEN 149
FT /note="Y->S: Slightly decreases water permeability, but has
FT a minor effect on the regulation by cytoplasmic calcium
FT levels."
FT /evidence="ECO:0000269|PubMed:23893133"
FT MUTAGEN 227
FT /note="L->A: Strongly reduced CALM binding."
FT /evidence="ECO:0000269|PubMed:23893133"
FT MUTAGEN 230
FT /note="V->A: Strongly reduced CALM binding."
FT /evidence="ECO:0000269|PubMed:23893133"
FT CONFLICT 14
FT /note="C -> L (in Ref. 2; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 29..33
FT /note="GASLR -> RAFLL (in Ref. 2; AA sequence)"
FT /evidence="ECO:0000305"
FT HELIX 10..31
FT /evidence="ECO:0007829|PDB:1YMG"
FT HELIX 38..59
FT /evidence="ECO:0007829|PDB:1YMG"
FT TURN 60..63
FT /evidence="ECO:0007829|PDB:1YMG"
FT HELIX 69..77
FT /evidence="ECO:0007829|PDB:1YMG"
FT HELIX 83..107
FT /evidence="ECO:0007829|PDB:1YMG"
FT TURN 110..112
FT /evidence="ECO:0007829|PDB:1YMG"
FT TURN 114..117
FT /evidence="ECO:0007829|PDB:1YMG"
FT HELIX 127..149
FT /evidence="ECO:0007829|PDB:1YMG"
FT HELIX 160..179
FT /evidence="ECO:0007829|PDB:1YMG"
FT HELIX 185..195
FT /evidence="ECO:0007829|PDB:1YMG"
FT TURN 199..202
FT /evidence="ECO:0007829|PDB:1YMG"
FT HELIX 203..220
FT /evidence="ECO:0007829|PDB:1YMG"
FT TURN 221..223
FT /evidence="ECO:0007829|PDB:1YMG"
FT HELIX 230..238
FT /evidence="ECO:0007829|PDB:1YMG"
SQ SEQUENCE 263 AA; 28223 MW; E08C2C4F33398D4E CRC64;
MWELRSASFW RAICAEFFAS LFYVFFGLGA SLRWAPGPLH VLQVALAFGL ALATLVQAVG
HISGAHVNPA VTFAFLVGSQ MSLLRAICYM VAQLLGAVAG AAVLYSVTPP AVRGNLALNT
LHPGVSVGQA TIVEIFLTLQ FVLCIFATYD ERRNGRLGSV ALAVGFSLTL GHLFGMYYTG
AGMNPARSFA PAILTRNFTN HWVYWVGPVI GAGLGSLLYD FLLFPRLKSV SERLSILKGS
RPSESNGQPE VTGEPVELKT QAL
