MIP_HUMAN
ID MIP_HUMAN Reviewed; 263 AA.
AC P30301; Q17R41;
DT 01-APR-1993, integrated into UniProtKB/Swiss-Prot.
DT 01-APR-1993, sequence version 1.
DT 03-AUG-2022, entry version 195.
DE RecName: Full=Lens fiber major intrinsic protein;
DE AltName: Full=Aquaporin-0;
DE AltName: Full=MIP26;
DE Short=MP26;
GN Name=MIP; Synonyms=AQP0;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=1840563; DOI=10.1016/0888-7543(91)90023-8;
RA Pisano M.M., Chepelinsky A.B.;
RT "Genomic cloning, complete nucleotide sequence, and structure of the human
RT gene encoding the major intrinsic protein (MIP) of the lens.";
RL Genomics 11:981-990(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16541075; DOI=10.1038/nature04569;
RA Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y.,
RA Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C.,
RA Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C.,
RA Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R.,
RA Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E.,
RA Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y.,
RA Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G.,
RA Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H.,
RA Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S.,
RA Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M.,
RA Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H.,
RA Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q.,
RA Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V.,
RA Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E.,
RA Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K.,
RA Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D.,
RA Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R.,
RA David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E.,
RA D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N.,
RA Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N.,
RA Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R.,
RA Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S.,
RA LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H.,
RA Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P.,
RA Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G.,
RA Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E.,
RA Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S.,
RA Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O.,
RA Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J.,
RA Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A.,
RA Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M.,
RA Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I.,
RA Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A.,
RA Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y.,
RA Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A.,
RA Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F.,
RA Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L.,
RA Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G.,
RA Gibbs R.A.;
RT "The finished DNA sequence of human chromosome 12.";
RL Nature 440:346-351(2006).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Testis;
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 project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP PHOSPHORYLATION AT SER-235, DEAMIDATION AT ASN-246 AND ASN-259, AND
RP IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=10634618;
RA Schey K.L., Little M., Fowler J.G., Crouch R.K.;
RT "Characterization of human lens major intrinsic protein structure.";
RL Invest. Ophthalmol. Vis. Sci. 41:175-182(2000).
RN [5]
RP INVOLVEMENT IN CTRCT15, AND VARIANTS CTRCT15 GLY-134 AND ARG-138.
RX PubMed=10802646; DOI=10.1038/75538;
RA Berry V., Francis P., Kaushal S., Moore A., Bhattacharya S.;
RT "Missense mutations in MIP underlie autosomal dominant 'polymorphic' and
RT lamellar cataracts linked to 12q.";
RL Nat. Genet. 25:15-17(2000).
RN [6]
RP INVOLVEMENT IN CTRCT15.
RX PubMed=16564824; DOI=10.1016/j.ajo.2005.11.008;
RA Geyer D.D., Spence M.A., Johannes M., Flodman P., Clancy K.P., Berry R.,
RA Sparkes R.S., Jonsen M.D., Isenberg S.J., Bateman J.B.;
RT "Novel single-base deletional mutation in major intrinsic protein (MIP) in
RT autosomal dominant cataract.";
RL Am. J. Ophthalmol. 141:761-763(2006).
RN [7]
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 [8]
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=30790544; DOI=10.1016/j.exer.2019.02.001;
RA Tapodi A., Clemens D.M., Uwineza A., Goldberg M.W., Thinon E., Heal W.P.,
RA Tate E.W., Nemeth-Cahalan K., Vorontsova I., Jarrin M., Hall J.E.,
RA Quinlan R.A.;
RT "BFSP1 C-terminal domains released by post-translational processing events
RT can alter significantly the calcium regulation of AQP0 water
RT permeability.";
RL Exp. Eye Res. 185:107585-107585(2019).
RN [9]
RP VARIANTS CTRCT15 GLY-134 AND ARG-138.
RX PubMed=11001937; DOI=10.1093/oxfordjournals.hmg.a018925;
RA Francis P., Chung J.-J., Yasui M., Berry V., Moore A., Wyatt M.K.,
RA Wistow G., Bhattacharya S.S., Agre P.;
RT "Functional impairment of lens aquaporin in two families with dominantly
RT inherited cataracts.";
RL Hum. Mol. Genet. 9:2329-2334(2000).
RN [10]
RP VARIANT CTRCT15 CYS-33.
RX PubMed=17893667;
RA Gu F., Zhai H., Li D., Zhao L., Li C., Huang S., Ma X.;
RT "A novel mutation in major intrinsic protein of the lens gene (MIP)
RT underlies autosomal dominant cataract in a Chinese family.";
RL Mol. Vis. 13:1651-1656(2007).
RN [11]
RP VARIANT CTRCT15 LYS-233.
RX PubMed=17960133;
RA Lin H., Hejtmancik J.F., Qi Y.;
RT "A substitution of arginine to lysine at the COOH-terminus of MIP caused a
RT different binocular phenotype in a congenital cataract family.";
RL Mol. Vis. 13:1822-1827(2007).
RN [12]
RP VARIANT CTRCT15 ILE-107.
RX PubMed=20361015;
RA Wang W., Jiang J., Zhu Y., Li J., Jin C., Shentu X., Yao K.;
RT "A novel mutation in the major intrinsic protein (MIP) associated with
RT autosomal dominant congenital cataracts in a Chinese family.";
RL Mol. Vis. 16:534-539(2010).
RN [13]
RP VARIANT CTRCT15 CYS-187.
RX PubMed=21245956;
RA Wang K.J., Li S.S., Yun B., Ma W.X., Jiang T.G., Zhu S.Q.;
RT "A novel mutation in MIP associated with congenital nuclear cataract in a
RT Chinese family.";
RL Mol. Vis. 17:70-77(2011).
RN [14]
RP VARIANT CTRCT15 ASP-165, CHARACTERIZATION OF VARIANT CTRCT15 ASP-165, AND
RP SUBCELLULAR LOCATION.
RX PubMed=23116563; DOI=10.1016/j.exer.2012.10.010;
RA Senthil Kumar G., Kyle J.W., Minogue P.J., Dinesh Kumar K., Vasantha K.,
RA Berthoud V.M., Beyer E.C., Santhiya S.T.;
RT "An MIP/AQP0 mutation with impaired trafficking and function underlies an
RT autosomal dominant congenital lamellar cataract.";
RL Exp. Eye Res. 110:136-141(2013).
RN [15]
RP VARIANT CTRCT15 CYS-33, CHARACTERIZATION OF VARIANT CTRCT15 CYS-33,
RP FUNCTION, SUBUNIT, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=24120416; DOI=10.1016/j.exer.2013.09.019;
RA Kumari S.S., Gandhi J., Mustehsan M.H., Eren S., Varadaraj K.;
RT "Functional characterization of an AQP0 missense mutation, R33C, that
RT causes dominant congenital lens cataract, reveals impaired cell-to-cell
RT adhesion.";
RL Exp. Eye Res. 116:371-385(2013).
RN [16]
RP VARIANT CTRCT15 HIS-150, CHARACTERIZATION OF VARIANT CTRCT15 HIS-150, AND
RP SUBCELLULAR LOCATION.
RX PubMed=25946197; DOI=10.1371/journal.pone.0126679;
RA Shentu X., Miao Q., Tang X., Yin H., Zhao Y.;
RT "Identification and functional analysis of a novel MIP gene mutation
RT associated with congenital cataract in a Chinese family.";
RL PLoS ONE 10:E0126679-E0126679(2015).
RN [17]
RP VARIANT CTRCT15 211-GLY--LEU-263 DEL.
RX PubMed=28839118; DOI=10.1534/g3.117.300109;
RA Javadiyan S., Craig J.E., Souzeau E., Sharma S., Lower K.M., Mackey D.A.,
RA Staffieri S.E., Elder J.E., Taranath D., Straga T., Black J., Pater J.,
RA Casey T., Hewitt A.W., Burdon K.P.;
RT "High-Throughput Genetic Screening of 51 Pediatric Cataract Genes
RT Identifies Causative Mutations in Inherited Pediatric Cataract in South
RT Eastern Australia.";
RL G3 (Bethesda) 7:3257-3268(2017).
RN [18]
RP VARIANTS CTRCT15 ASP-165; CYS-177 AND 204-TYR--LEU-263 DEL.
RX PubMed=29914532; DOI=10.1186/s13023-018-0828-0;
RA Li J., Leng Y., Han S., Yan L., Lu C., Luo Y., Zhang X., Cao L.;
RT "Clinical and genetic characteristics of Chinese patients with familial or
RT sporadic pediatric cataract.";
RL Orphanet J. Rare Dis. 13:94-94(2018).
CC -!- FUNCTION: Water channel (PubMed:24120416). 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 (PubMed:24120416). {ECO:0000250|UniProtKB:Q6J8I9,
CC ECO:0000269|PubMed:24120416}.
CC -!- SUBUNIT: Homotetramer (PubMed:24120416). Homooctamer formed by head-to-
CC head interaction between homotetramers from adjoining membranes.
CC Interacts with CALM; one CALM molecule interacts with the cytoplasmic
CC domains of two aquaporins, leading to channel closure (By similarity).
CC Interacts (via C-terminus) with BFSP1 (via C-terminus) in aged lens
CC fiber cells (By similarity). {ECO:0000250|UniProtKB:P06624,
CC ECO:0000269|PubMed:24120416}.
CC -!- INTERACTION:
CC P30301; Q86WK6: AMIGO1; NbExp=3; IntAct=EBI-8449636, EBI-19125216;
CC P30301; O43315: AQP9; NbExp=3; IntAct=EBI-8449636, EBI-17444777;
CC P30301; Q99437: ATP6V0B; NbExp=3; IntAct=EBI-8449636, EBI-3904417;
CC P30301; P25942: CD40; NbExp=3; IntAct=EBI-8449636, EBI-525714;
CC P30301; Q8N5K1: CISD2; NbExp=3; IntAct=EBI-8449636, EBI-1045797;
CC P30301; O00501: CLDN5; NbExp=3; IntAct=EBI-8449636, EBI-18400628;
CC P30301; Q9Y282: ERGIC3; NbExp=3; IntAct=EBI-8449636, EBI-781551;
CC P30301; P60508: ERVFRD-1; NbExp=3; IntAct=EBI-8449636, EBI-17973325;
CC P30301; Q5JX71: FAM209A; NbExp=3; IntAct=EBI-8449636, EBI-18304435;
CC P30301; P12318-2: FCGR2A; NbExp=3; IntAct=EBI-8449636, EBI-17187481;
CC P30301; Q0VDC6: FKBP1A; NbExp=3; IntAct=EBI-8449636, EBI-10226858;
CC P30301; O95377: GJB5; NbExp=3; IntAct=EBI-8449636, EBI-3909454;
CC P30301; Q8NBJ4: GOLM1; NbExp=3; IntAct=EBI-8449636, EBI-712073;
CC P30301; Q8TED1: GPX8; NbExp=3; IntAct=EBI-8449636, EBI-11721746;
CC P30301; P54652: HSPA2; NbExp=3; IntAct=EBI-8449636, EBI-356991;
CC P30301; P48051: KCNJ6; NbExp=3; IntAct=EBI-8449636, EBI-12017638;
CC P30301; Q8TAF8: LHFPL5; NbExp=3; IntAct=EBI-8449636, EBI-2820517;
CC P30301; Q7Z4F1: LRP10; NbExp=3; IntAct=EBI-8449636, EBI-2830349;
CC P30301; Q9HCJ2: LRRC4C; NbExp=3; IntAct=EBI-8449636, EBI-3925442;
CC P30301; Q9GZY8-5: MFF; NbExp=3; IntAct=EBI-8449636, EBI-11956541;
CC P30301; O14880: MGST3; NbExp=3; IntAct=EBI-8449636, EBI-724754;
CC P30301; Q9HC36: MRM3; NbExp=3; IntAct=EBI-8449636, EBI-1045440;
CC P30301; Q9Y676: MRPS18B; NbExp=3; IntAct=EBI-8449636, EBI-750085;
CC P30301; P15941-11: MUC1; NbExp=3; IntAct=EBI-8449636, EBI-17263240;
CC P30301; Q13113: PDZK1IP1; NbExp=3; IntAct=EBI-8449636, EBI-716063;
CC P30301; Q8NC24: RELL2; NbExp=3; IntAct=EBI-8449636, EBI-10269209;
CC P30301; Q9NR31: SAR1A; NbExp=3; IntAct=EBI-8449636, EBI-3920694;
CC P30301; O95470: SGPL1; NbExp=3; IntAct=EBI-8449636, EBI-1046170;
CC P30301; Q13336-2: SLC14A1; NbExp=3; IntAct=EBI-8449636, EBI-19141793;
CC P30301; P54219-3: SLC18A1; NbExp=3; IntAct=EBI-8449636, EBI-17595455;
CC P30301; Q8WWF3: SSMEM1; NbExp=3; IntAct=EBI-8449636, EBI-17280858;
CC P30301; Q16623: STX1A; NbExp=3; IntAct=EBI-8449636, EBI-712466;
CC P30301; P32856-2: STX2; NbExp=3; IntAct=EBI-8449636, EBI-11956649;
CC P30301; Q96A49: SYAP1; NbExp=3; IntAct=EBI-8449636, EBI-10770179;
CC P30301; P21579: SYT1; NbExp=3; IntAct=EBI-8449636, EBI-524909;
CC P30301; Q8N9I0: SYT2; NbExp=3; IntAct=EBI-8449636, EBI-8032987;
CC P30301; Q96CE8: TM4SF18; NbExp=3; IntAct=EBI-8449636, EBI-13351685;
CC P30301; Q8IV31: TMEM139; NbExp=3; IntAct=EBI-8449636, EBI-7238458;
CC P30301; Q6P9G4: TMEM154; NbExp=3; IntAct=EBI-8449636, EBI-13329239;
CC P30301; Q4KMG9: TMEM52B; NbExp=3; IntAct=EBI-8449636, EBI-18178701;
CC P30301; Q9Y320: TMX2; NbExp=3; IntAct=EBI-8449636, EBI-6447886;
CC P30301; O95159: ZFPL1; NbExp=3; IntAct=EBI-8449636, EBI-718439;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:23116563,
CC ECO:0000269|PubMed:24120416, ECO:0000269|PubMed:25946197,
CC ECO:0000269|PubMed:30790544}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:Q6J8I9}. Cell junction, gap junction
CC {ECO:0000269|PubMed:24120416}.
CC -!- TISSUE SPECIFICITY: Expressed in the cortex and nucleus of the retina
CC lens (at protein level) (PubMed:30790544). Major component of lens
CC fiber gap junctions (PubMed:24120416). {ECO:0000269|PubMed:24120416,
CC ECO:0000269|PubMed:30790544}.
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 (By
CC similarity). {ECO:0000250}.
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 -!- DISEASE: Cataract 15, multiple types (CTRCT15) [MIM:615274]: An
CC opacification of the crystalline lens of the eye that frequently
CC results in visual impairment or blindness. Opacities vary in
CC morphology, are often confined to a portion of the lens, and may be
CC static or progressive. CTRCT15 includes polymorphic, progressive
CC punctate lamellar, cortical, anterior and posterior polar,
CC nonprogressive lamellar with sutural opacities, embryonic nuclear, and
CC pulverulent cortical, among others. {ECO:0000269|PubMed:10802646,
CC ECO:0000269|PubMed:11001937, ECO:0000269|PubMed:16564824,
CC ECO:0000269|PubMed:17893667, ECO:0000269|PubMed:17960133,
CC ECO:0000269|PubMed:20361015, ECO:0000269|PubMed:21245956,
CC ECO:0000269|PubMed:23116563, ECO:0000269|PubMed:24120416,
CC ECO:0000269|PubMed:25946197, ECO:0000269|PubMed:28839118,
CC ECO:0000269|PubMed:29914532}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the MIP/aquaporin (TC 1.A.8) family.
CC {ECO:0000305}.
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DR EMBL; U36308; AAC02794.2; -; Genomic_DNA.
DR EMBL; AC024884; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC074913; AAH74913.1; -; mRNA.
DR EMBL; BC117474; AAI17475.1; -; mRNA.
DR CCDS; CCDS8919.1; -.
DR PIR; A55279; A55279.
DR RefSeq; NP_036196.1; NM_012064.3.
DR AlphaFoldDB; P30301; -.
DR SMR; P30301; -.
DR BioGRID; 110430; 50.
DR IntAct; P30301; 43.
DR MINT; P30301; -.
DR STRING; 9606.ENSP00000257979; -.
DR DrugBank; DB02451; B-nonylglucoside.
DR iPTMnet; P30301; -.
DR PhosphoSitePlus; P30301; -.
DR BioMuta; MIP; -.
DR DMDM; 266537; -.
DR OGP; P30301; -.
DR PaxDb; P30301; -.
DR PeptideAtlas; P30301; -.
DR PRIDE; P30301; -.
DR Antibodypedia; 28228; 246 antibodies from 27 providers.
DR DNASU; 4284; -.
DR Ensembl; ENST00000652304.1; ENSP00000498622.1; ENSG00000135517.9.
DR GeneID; 4284; -.
DR KEGG; hsa:4284; -.
DR MANE-Select; ENST00000652304.1; ENSP00000498622.1; NM_012064.4; NP_036196.1.
DR UCSC; uc001slh.4; human.
DR CTD; 4284; -.
DR DisGeNET; 4284; -.
DR GeneCards; MIP; -.
DR HGNC; HGNC:7103; MIP.
DR HPA; ENSG00000135517; Not detected.
DR MalaCards; MIP; -.
DR MIM; 154050; gene.
DR MIM; 615274; phenotype.
DR neXtProt; NX_P30301; -.
DR OpenTargets; ENSG00000135517; -.
DR Orphanet; 98989; Cerulean cataract.
DR Orphanet; 441452; Early-onset lamellar cataract.
DR Orphanet; 98991; Early-onset nuclear cataract.
DR Orphanet; 98993; Early-onset posterior polar cataract.
DR Orphanet; 98985; Early-onset sutural cataract.
DR Orphanet; 98994; Total early-onset cataract.
DR PharmGKB; PA30821; -.
DR VEuPathDB; HostDB:ENSG00000135517; -.
DR eggNOG; KOG0223; Eukaryota.
DR GeneTree; ENSGT00940000156260; -.
DR HOGENOM; CLU_020019_3_3_1; -.
DR InParanoid; P30301; -.
DR OMA; WTPGPLH; -.
DR OrthoDB; 1152704at2759; -.
DR PhylomeDB; P30301; -.
DR TreeFam; TF312940; -.
DR PathwayCommons; P30301; -.
DR Reactome; R-HSA-432047; Passive transport by Aquaporins.
DR SignaLink; P30301; -.
DR SIGNOR; P30301; -.
DR BioGRID-ORCS; 4284; 11 hits in 1072 CRISPR screens.
DR ChiTaRS; MIP; human.
DR GeneWiki; MIP_(gene); -.
DR GenomeRNAi; 4284; -.
DR Pharos; P30301; Tbio.
DR PRO; PR:P30301; -.
DR Proteomes; UP000005640; Chromosome 12.
DR RNAct; P30301; protein.
DR Bgee; ENSG00000135517; Expressed in right lobe of liver and 71 other tissues.
DR Genevisible; P30301; HS.
DR GO; GO:0016324; C:apical plasma membrane; IBA:GO_Central.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA: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; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA: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; IDA:UniProtKB.
DR GO; GO:1990349; P:gap junction-mediated intercellular transport; IDA:UniProtKB.
DR GO; GO:0002088; P:lens development in camera-type eye; IEA:Ensembl.
DR GO; GO:0045785; P:positive regulation of cell adhesion; IDA:UniProtKB.
DR GO; GO:0051289; P:protein homotetramerization; IDA:UniProtKB.
DR GO; GO:0050896; P:response to stimulus; IEA:UniProtKB-KW.
DR GO; GO:0007601; P:visual perception; IEA:UniProtKB-KW.
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 Cataract; Cell junction; Cell membrane; Disease variant; Eye lens protein;
KW Gap junction; Lipoprotein; Membrane; Palmitate; Phosphoprotein;
KW Reference proteome; Repeat; Sensory transduction; Transmembrane;
KW Transmembrane helix; Transport; Vision.
FT CHAIN 1..263
FT /note="Lens fiber major intrinsic protein"
FT /id="PRO_0000063912"
FT TOPO_DOM 1..8
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT TRANSMEM 9..32
FT /note="Helical"
FT /evidence="ECO:0000250"
FT TOPO_DOM 33..38
FT /note="Extracellular"
FT /evidence="ECO:0000250"
FT TRANSMEM 39..61
FT /note="Helical"
FT /evidence="ECO:0000250"
FT INTRAMEM 62..67
FT /evidence="ECO:0000250"
FT INTRAMEM 68..78
FT /note="Helical"
FT /evidence="ECO:0000250"
FT TOPO_DOM 79..84
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT TRANSMEM 85..107
FT /note="Helical"
FT /evidence="ECO:0000250"
FT TOPO_DOM 108..126
FT /note="Extracellular"
FT /evidence="ECO:0000250"
FT TRANSMEM 127..147
FT /note="Helical"
FT /evidence="ECO:0000250"
FT TOPO_DOM 148..159
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT TRANSMEM 160..176
FT /note="Helical"
FT /evidence="ECO:0000250"
FT INTRAMEM 177..183
FT /evidence="ECO:0000250"
FT INTRAMEM 184..194
FT /note="Helical"
FT /evidence="ECO:0000250"
FT TOPO_DOM 195..200
FT /note="Extracellular"
FT /evidence="ECO:0000250"
FT TRANSMEM 201..219
FT /note="Helical"
FT /evidence="ECO:0000250"
FT TOPO_DOM 220..263
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250"
FT REGION 227..237
FT /note="Interaction with CALM"
FT /evidence="ECO:0000250"
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:0000269|PubMed:10634618"
FT MOD_RES 245
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P06624"
FT MOD_RES 246
FT /note="Deamidated asparagine; by deterioration"
FT /evidence="ECO:0000269|PubMed:10634618"
FT MOD_RES 259
FT /note="Deamidated asparagine; by deterioration"
FT /evidence="ECO:0000269|PubMed:10634618"
FT VARIANT 33
FT /note="R -> C (in CTRCT15; reduces cell-to-cell adhesion,
FT reduces cell-to-cell gap junction coupling, no loss of cell
FT membrane localization, no loss of water channel activity;
FT dbSNP:rs864309693)"
FT /evidence="ECO:0000269|PubMed:17893667,
FT ECO:0000269|PubMed:24120416"
FT /id="VAR_071601"
FT VARIANT 107
FT /note="V -> I (in CTRCT15; likely benign variant;
FT dbSNP:rs74641138)"
FT /evidence="ECO:0000269|PubMed:20361015"
FT /id="VAR_071602"
FT VARIANT 134
FT /note="E -> G (in CTRCT15; non-progressive lamellar
FT cataract; loss of activity; dbSNP:rs121917869)"
FT /evidence="ECO:0000269|PubMed:10802646,
FT ECO:0000269|PubMed:11001937"
FT /id="VAR_011497"
FT VARIANT 138
FT /note="T -> R (in CTRCT15; progressive polymorphic and
FT lamellar cataract; loss of activity; dbSNP:rs121917867)"
FT /evidence="ECO:0000269|PubMed:10802646,
FT ECO:0000269|PubMed:11001937"
FT /id="VAR_011498"
FT VARIANT 150
FT /note="D -> H (in CTRCT15; loss of plasma membrane
FT expression; dbSNP:rs778327521)"
FT /evidence="ECO:0000269|PubMed:25946197"
FT /id="VAR_075528"
FT VARIANT 165
FT /note="G -> D (in CTRCT15; unknown pathological
FT significance; loss of plasma membrane expression)"
FT /evidence="ECO:0000269|PubMed:23116563,
FT ECO:0000269|PubMed:29914532"
FT /id="VAR_075529"
FT VARIANT 177
FT /note="Y -> C (in CTRCT15; unknown pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:29914532"
FT /id="VAR_084819"
FT VARIANT 187
FT /note="R -> C (in CTRCT15; dbSNP:rs267603585)"
FT /evidence="ECO:0000269|PubMed:21245956"
FT /id="VAR_071603"
FT VARIANT 204..263
FT /note="Missing (in CTRCT15; unknown pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:29914532"
FT /id="VAR_084820"
FT VARIANT 211..263
FT /note="Missing (in CTRCT15; unknown pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:28839118"
FT /id="VAR_084821"
FT VARIANT 233
FT /note="R -> K (in CTRCT15; dbSNP:rs1555179699)"
FT /evidence="ECO:0000269|PubMed:17960133"
FT /id="VAR_071604"
SQ SEQUENCE 263 AA; 28122 MW; 6A864C8AA53CBC4B CRC64;
MWELRSASFW RAIFAEFFAT LFYVFFGLGS SLRWAPGPLH VLQVAMAFGL ALATLVQSVG
HISGAHVNPA VTFAFLVGSQ MSLLRAFCYM AAQLLGAVAG AAVLYSVTPP AVRGNLALNT
LHPAVSVGQA TTVEIFLTLQ FVLCIFATYD ERRNGQLGSV ALAVGFSLAL GHLFGMYYTG
AGMNPARSFA PAILTGNFTN HWVYWVGPII GGGLGSLLYD FLLFPRLKSI SERLSVLKGA
KPDVSNGQPE VTGEPVELNT QAL
