MIP_SHEEP
ID MIP_SHEEP Reviewed; 263 AA.
AC Q6J8I9;
DT 05-JUL-2005, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 03-AUG-2022, entry version 107.
DE RecName: Full=Lens fiber major intrinsic protein;
DE AltName: Full=Aquaporin-0;
GN Name=MIP; Synonyms=AQP0;
OS Ovis aries (Sheep).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Caprinae; Ovis.
OX NCBI_TaxID=9940;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], TISSUE SPECIFICITY, SUBCELLULAR
RP LOCATION, FUNCTION, PARTIAL PROTEOLYSIS, AND STRUCTURE BY ELECTRON
RP MICROSCOPY (3.0 ANGSTROMS) OF 5-239.
RX PubMed=15141214; DOI=10.1038/nature02503;
RA Gonen T., Sliz P., Kistler J., Cheng Y., Walz T.;
RT "Aquaporin-0 membrane junctions reveal the structure of a closed water
RT pore.";
RL Nature 429:193-197(2004).
RN [2]
RP PARTIAL PROTEIN SEQUENCE, FUNCTION, SUBCELLULAR LOCATION, SUBUNIT,
RP PROTEOLYTIC CLEAVAGE, TISSUE SPECIFICITY, AND IDENTIFICATION BY MASS
RP SPECTROMETRY.
RX PubMed=15351655; DOI=10.1016/j.jmb.2004.07.076;
RA Gonen T., Cheng Y., Kistler J., Walz T.;
RT "Aquaporin-0 membrane junctions form upon proteolytic cleavage.";
RL J. Mol. Biol. 342:1337-1345(2004).
RN [3]
RP X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS), SUBUNIT, FUNCTION, AND MEMBRANE
RP TOPOLOGY.
RX PubMed=16319884; DOI=10.1038/nature04321;
RA Gonen T., Cheng Y., Sliz P., Hiroaki Y., Fujiyoshi Y., Harrison S.C.,
RA Walz T.;
RT "Lipid-protein interactions in double-layered two-dimensional AQP0
RT crystals.";
RL Nature 438:633-638(2005).
RN [4]
RP STRUCTURE BY ELECTRON MICROSCOPY (2.50 ANGSTROMS) OF 7-226, MEMBRANE
RP TOPOLOGY, SUBUNIT, AND FUNCTION.
RX PubMed=20389283; DOI=10.1038/emboj.2010.68;
RA Hite R.K., Li Z., Walz T.;
RT "Principles of membrane protein interactions with annular lipids deduced
RT from aquaporin-0 2D crystals.";
RL EMBO J. 29:1652-1658(2010).
RN [5]
RP STRUCTURE BY ELECTRON MICROSCOPY (25 ANGSTROMS) IN COMPLEX WITH CALM,
RP MEMBRANE TOPOLOGY, SUBCELLULAR LOCATION, SUBUNIT, FUNCTION, AND TISSUE
RP SPECIFICITY.
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).
CC -!- FUNCTION: Water channel. Channel activity is down-regulated by CALM
CC when cytoplasmic Ca(2+) levels are increased. May be responsible for
CC regulating the osmolarity of the lens. Interactions between
CC homotetramers from adjoining membranes may stabilize cell junctions in
CC the eye lens core. Plays a role in cell-to-cell adhesion and
CC facilitates gap junction coupling (By similarity).
CC {ECO:0000250|UniProtKB:P30301, ECO:0000269|PubMed:15141214,
CC ECO:0000269|PubMed:15351655, ECO:0000269|PubMed:16319884,
CC ECO:0000269|PubMed:20389283, ECO:0000269|PubMed:23893133}.
CC -!- SUBUNIT: Homotetramer. Homooctamer formed by head-to-head interaction
CC between homotetramers from adjoining membranes. Interacts with CALM;
CC one CALM molecule interacts with the cytoplasmic domains of two
CC aquaporins, leading to channel closure. Interacts (via C-terminus) with
CC BFSP1 (via C-terminus) in aged lens fiber cells (By similarity).
CC {ECO:0000250|UniProtKB:P06624, ECO:0000269|PubMed:15351655,
CC ECO:0000269|PubMed:16319884, ECO:0000269|PubMed:20389283,
CC ECO:0000269|PubMed:23893133}.
CC -!- INTERACTION:
CC Q6J8I9; P62158: CALM3; Xeno; NbExp=2; IntAct=EBI-15728125, EBI-397435;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:15141214,
CC ECO:0000269|PubMed:15351655, ECO:0000269|PubMed:23893133}; Multi-pass
CC membrane protein {ECO:0000305}. Cell junction, gap junction
CC {ECO:0000269|PubMed:15141214, ECO:0000269|PubMed:15351655,
CC ECO:0000269|PubMed:23893133}.
CC -!- TISSUE SPECIFICITY: Detected in eye lens (at protein level).
CC {ECO:0000269|PubMed:15141214, ECO:0000269|PubMed:15351655,
CC ECO:0000269|PubMed:23893133}.
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. {ECO:0000269|PubMed:15351655}.
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:0000250|UniProtKB:P30301}.
CC -!- SIMILARITY: Belongs to the MIP/aquaporin (TC 1.A.8) family.
CC {ECO:0000305}.
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DR EMBL; AY573927; AAT09161.1; -; Genomic_DNA.
DR RefSeq; NP_001153230.1; NM_001159758.1.
DR PDB; 1SOR; X-ray; 3.00 A; A=5-239.
DR PDB; 2B6O; X-ray; 1.90 A; A=1-263.
DR PDB; 2B6P; X-ray; 2.40 A; A=1-263.
DR PDB; 3J41; EM; 25.00 A; A/B/C/D=1-263.
DR PDB; 3M9I; EM; 2.50 A; A=7-226.
DR PDBsum; 1SOR; -.
DR PDBsum; 2B6O; -.
DR PDBsum; 2B6P; -.
DR PDBsum; 3J41; -.
DR PDBsum; 3M9I; -.
DR AlphaFoldDB; Q6J8I9; -.
DR SMR; Q6J8I9; -.
DR DIP; DIP-46234N; -.
DR IntAct; Q6J8I9; 1.
DR STRING; 9940.ENSOARP00000009442; -.
DR Ensembl; ENSOART00000009579; ENSOARP00000009442; ENSOARG00000008796.
DR Ensembl; ENSOART00020003963; ENSOARP00020003255; ENSOARG00020002585.
DR GeneID; 100294602; -.
DR KEGG; oas:100294602; -.
DR CTD; 4284; -.
DR eggNOG; KOG0223; Eukaryota.
DR HOGENOM; CLU_020019_3_3_1; -.
DR OMA; WTPGPLH; -.
DR OrthoDB; 1152704at2759; -.
DR EvolutionaryTrace; Q6J8I9; -.
DR Proteomes; UP000002356; Chromosome 3.
DR Bgee; ENSOARG00000008796; Expressed in abdominal lymph node and 47 other tissues.
DR GO; GO:0005783; C:endoplasmic reticulum; ISS:UniProtKB.
DR GO; GO:0005921; C:gap junction; IEA:UniProtKB-SubCell.
DR GO; GO:0005887; C:integral component of plasma membrane; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0005516; F:calmodulin binding; ISS:UniProtKB.
DR GO; GO:0005212; F:structural constituent of eye lens; IEA:UniProtKB-KW.
DR GO; GO:0015250; F:water channel activity; ISS: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:0050896; P:response to stimulus; IEA:UniProtKB-KW.
DR GO; GO:0007601; P:visual perception; IEA:Ensembl.
DR GO; GO:0006833; P:water transport; ISS: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; Sensory transduction; Transmembrane;
KW Transmembrane helix; Transport.
FT CHAIN 1..263
FT /note="Lens fiber major intrinsic protein"
FT /id="PRO_0000063915"
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:0000250"
FT REGION 240..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 /evidence="ECO:0000250"
FT SITE 246
FT /note="Interaction with BFSP1"
FT /evidence="ECO:0000250|UniProtKB:P06624"
FT SITE 250
FT /note="interaction with BFSP1"
FT /evidence="ECO:0000250|UniProtKB:P06624"
FT MOD_RES 235
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P06624"
FT MOD_RES 243
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P06624"
FT MOD_RES 245
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P06624"
FT HELIX 6..31
FT /evidence="ECO:0007829|PDB:2B6O"
FT STRAND 36..38
FT /evidence="ECO:0007829|PDB:2B6O"
FT HELIX 40..58
FT /evidence="ECO:0007829|PDB:2B6O"
FT HELIX 59..61
FT /evidence="ECO:0007829|PDB:2B6O"
FT HELIX 69..77
FT /evidence="ECO:0007829|PDB:2B6O"
FT HELIX 83..107
FT /evidence="ECO:0007829|PDB:2B6O"
FT TURN 110..112
FT /evidence="ECO:0007829|PDB:2B6O"
FT STRAND 114..117
FT /evidence="ECO:0007829|PDB:1SOR"
FT HELIX 127..148
FT /evidence="ECO:0007829|PDB:2B6O"
FT HELIX 160..175
FT /evidence="ECO:0007829|PDB:2B6O"
FT TURN 176..178
FT /evidence="ECO:0007829|PDB:2B6O"
FT HELIX 185..195
FT /evidence="ECO:0007829|PDB:2B6O"
FT TURN 199..202
FT /evidence="ECO:0007829|PDB:3M9I"
FT HELIX 203..220
FT /evidence="ECO:0007829|PDB:2B6O"
FT TURN 221..223
FT /evidence="ECO:0007829|PDB:2B6O"
FT HELIX 230..233
FT /evidence="ECO:0007829|PDB:2B6O"
FT HELIX 234..236
FT /evidence="ECO:0007829|PDB:2B6O"
SQ SEQUENCE 263 AA; 28263 MW; 1BF16D4E6662C5A6 CRC64;
MWELRSASFW RAIFAEFFAT LFYVFFGLGA SLRWAPGPLH VLQVALAFGL ALATLVQAVG
HISGAHVNPA VTFAFLVGSQ MSLLRAICYV VAQLLGAVAG AAVLYSVTPP AVRGNLALNT
LHPGVSVGQA TIVEIFLTLQ FVLCIFATYD ERRNGRLGSV ALAVGFSLTL GHLFGMYYTG
AGMNPARSFA PAILTRNFTN HWVYWVGPVI GAGLGSLLYD FLLFPRLKSV SERLSILKGT
RPSESNGQPE VTGEPVELKT QAL
