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P30301

- MIP_HUMAN

UniProt

P30301 - MIP_HUMAN

Protein

Lens fiber major intrinsic protein

Gene

MIP

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 140 (01 Oct 2014)
      Sequence version 1 (01 Apr 1993)
      Previous versions | rss
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    Functioni

    Water channel. Channel activity is down-regulated by CALM when cytoplasmic Ca2+ levels are increased. May be responsible for regulating the osmolarity of the lens. Interactions between homotetramers from adjoining membranes may stabilize cell junctions in the eye lens core By similarity.By similarity

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sitei149 – 1491Important for water channel gatingBy similarity

    GO - Molecular functioni

    1. calmodulin binding Source: UniProtKB
    2. structural constituent of eye lens Source: UniProtKB-KW
    3. transporter activity Source: ProtInc
    4. water channel activity Source: UniProtKB

    GO - Biological processi

    1. canalicular bile acid transport Source: Ensembl
    2. lens development in camera-type eye Source: Ensembl
    3. response to stimulus Source: UniProtKB-KW
    4. transmembrane transport Source: Reactome
    5. visual perception Source: UniProtKB-KW
    6. water transport Source: UniProtKB

    Keywords - Molecular functioni

    Eye lens protein

    Keywords - Biological processi

    Sensory transduction, Transport, Vision

    Enzyme and pathway databases

    ReactomeiREACT_23826. Passive transport by Aquaporins.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Lens fiber major intrinsic protein
    Alternative name(s):
    Aquaporin-0
    MIP26
    Short name:
    MP26
    Gene namesi
    Name:MIP
    Synonyms:AQP0
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 12

    Organism-specific databases

    HGNCiHGNC:7103. MIP.

    Subcellular locationi

    GO - Cellular componenti

    1. gap junction Source: UniProtKB-SubCell
    2. integral component of plasma membrane Source: UniProtKB
    3. intracellular canaliculus Source: Ensembl
    4. intracellular membrane-bounded organelle Source: Ensembl
    5. plasma membrane Source: Reactome

    Keywords - Cellular componenti

    Cell junction, Cell membrane, Gap junction, Membrane

    Pathology & Biotechi

    Involvement in diseasei

    Cataract 15, multiple types (CTRCT15) [MIM:615274]: An opacification of the crystalline lens of the eye that frequently results in visual impairment or blindness. Opacities vary in morphology, are often confined to a portion of the lens, and may be static or progressive. CTRCT15 includes polymorphic, progressive punctate lamellar, cortical, anterior and posterior polar, nonprogressive lamellar with sutural opacities, embryonic nuclear, and pulverulent cortical, among others.3 Publications
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti134 – 1341E → G in CTRCT15; non-progressive lamellar cataract; loss of activity. 2 Publications
    VAR_011497
    Natural varianti138 – 1381T → R in CTRCT15; progressive polymorphic and lamellar cataract; loss of activity. 2 Publications
    VAR_011498

    Keywords - Diseasei

    Cataract, Disease mutation

    Organism-specific databases

    MIMi615274. phenotype.
    Orphaneti98985. Cataract with Y-shaped suture opacities.
    98989. Cerulean cataract.
    98991. Nuclear cataract.
    98994. Total congenital cataract.
    98995. Zonular cataract.
    PharmGKBiPA30821.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 263263Lens fiber major intrinsic proteinPRO_0000063912Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei235 – 2351Phosphoserine1 Publication
    Modified residuei245 – 2451PhosphoserineBy similarity
    Modified residuei246 – 2461Deamidated asparagine; by deterioration1 Publication
    Modified residuei259 – 2591Deamidated asparagine; by deterioration1 Publication

    Post-translational modificationi

    Subject to partial proteolytic cleavage in the eye lens core. Partial proteolysis promotes interactions between tetramers from adjoining membranes By similarity.By similarity

    Keywords - PTMi

    Phosphoprotein

    Proteomic databases

    PaxDbiP30301.
    PRIDEiP30301.

    2D gel databases

    OGPiP30301.

    PTM databases

    PhosphoSiteiP30301.

    Miscellaneous databases

    PMAP-CutDBP30301.

    Expressioni

    Tissue specificityi

    Major component of lens fiber gap junctions.

    Gene expression databases

    BgeeiP30301.
    CleanExiHS_MIP.
    GenevestigatoriP30301.

    Interactioni

    Subunit structurei

    Homotetramer. Homooctamer formed by head-to-head interaction between homotetramers from adjoining membranes. Interacts with CALM; one CALM molecule interacts with the cytoplasmic domains of two aquaporins, leading to channel closure By similarity.By similarity

    Protein-protein interaction databases

    BioGridi110430. 6 interactions.
    IntActiP30301. 1 interaction.
    MINTiMINT-8415310.
    STRINGi9606.ENSP00000257979.

    Structurei

    3D structure databases

    ProteinModelPortaliP30301.
    SMRiP30301. Positions 2-263.
    ModBaseiSearch...
    MobiDBiSearch...

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini1 – 88CytoplasmicBy similarity
    Topological domaini33 – 386ExtracellularBy similarity
    Topological domaini79 – 846CytoplasmicBy similarity
    Topological domaini108 – 12619ExtracellularBy similarityAdd
    BLAST
    Topological domaini148 – 15912CytoplasmicBy similarityAdd
    BLAST
    Topological domaini195 – 2006ExtracellularBy similarity
    Topological domaini220 – 26344CytoplasmicBy similarityAdd
    BLAST

    Intramembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Intramembranei62 – 676By similarity
    Intramembranei68 – 7811HelicalBy similarityAdd
    BLAST
    Intramembranei177 – 1837By similarity
    Intramembranei184 – 19411HelicalBy similarityAdd
    BLAST

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei9 – 3224HelicalBy similarityAdd
    BLAST
    Transmembranei39 – 6123HelicalBy similarityAdd
    BLAST
    Transmembranei85 – 10723HelicalBy similarityAdd
    BLAST
    Transmembranei127 – 14721HelicalBy similarityAdd
    BLAST
    Transmembranei160 – 17617HelicalBy similarityAdd
    BLAST
    Transmembranei201 – 21919HelicalBy similarityAdd
    BLAST

    Family & Domainsi

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni227 – 23711Interaction with CALMBy similarityAdd
    BLAST

    Motif

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Motifi68 – 703NPA 1
    Motifi184 – 1863NPA 2

    Domaini

    Aquaporins contain two tandem repeats each containing two membrane-spanning helices and a pore-forming loop with the signature motif Asn-Pro-Ala (NPA). Each tandem repeat contains a loop and a short helix that enter and leave the lipid bilayer on the same side By similarity.By similarity

    Sequence similaritiesi

    Keywords - Domaini

    Repeat, Transmembrane, Transmembrane helix

    Phylogenomic databases

    eggNOGiCOG0580.
    HOGENOMiHOG000288286.
    HOVERGENiHBG000312.
    InParanoidiP30301.
    KOiK09863.
    OMAiMWELRST.
    OrthoDBiEOG7N8ZWD.
    PhylomeDBiP30301.
    TreeFamiTF312940.

    Family and domain databases

    Gene3Di1.20.1080.10. 1 hit.
    InterProiIPR023271. Aquaporin-like.
    IPR000425. MIP.
    IPR022357. MIP_CS.
    [Graphical view]
    PANTHERiPTHR19139. PTHR19139. 1 hit.
    PfamiPF00230. MIP. 1 hit.
    [Graphical view]
    PRINTSiPR00783. MINTRINSICP.
    SUPFAMiSSF81338. SSF81338. 1 hit.
    TIGRFAMsiTIGR00861. MIP. 1 hit.
    PROSITEiPS00221. MIP. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    P30301-1 [UniParc]FASTAAdd to Basket

    « Hide

    MWELRSASFW RAIFAEFFAT LFYVFFGLGS SLRWAPGPLH VLQVAMAFGL    50
    ALATLVQSVG HISGAHVNPA VTFAFLVGSQ MSLLRAFCYM AAQLLGAVAG 100
    AAVLYSVTPP AVRGNLALNT LHPAVSVGQA TTVEIFLTLQ FVLCIFATYD 150
    ERRNGQLGSV ALAVGFSLAL GHLFGMYYTG AGMNPARSFA PAILTGNFTN 200
    HWVYWVGPII GGGLGSLLYD FLLFPRLKSI SERLSVLKGA KPDVSNGQPE 250
    VTGEPVELNT QAL 263
    Length:263
    Mass (Da):28,122
    Last modified:April 1, 1993 - v1
    Checksum:i6A864C8AA53CBC4B
    GO

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti134 – 1341E → G in CTRCT15; non-progressive lamellar cataract; loss of activity. 2 Publications
    VAR_011497
    Natural varianti138 – 1381T → R in CTRCT15; progressive polymorphic and lamellar cataract; loss of activity. 2 Publications
    VAR_011498

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    U36308 Genomic DNA. Translation: AAC02794.2.
    AC024884 Genomic DNA. No translation available.
    BC074913 mRNA. Translation: AAH74913.1.
    BC117474 mRNA. Translation: AAI17475.1.
    CCDSiCCDS8919.1.
    PIRiA55279.
    RefSeqiNP_036196.1. NM_012064.3.
    UniGeneiHs.574026.

    Genome annotation databases

    EnsembliENST00000257979; ENSP00000257979; ENSG00000135517.
    GeneIDi4284.
    KEGGihsa:4284.
    UCSCiuc001slh.3. human.

    Polymorphism databases

    DMDMi266537.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    U36308 Genomic DNA. Translation: AAC02794.2 .
    AC024884 Genomic DNA. No translation available.
    BC074913 mRNA. Translation: AAH74913.1 .
    BC117474 mRNA. Translation: AAI17475.1 .
    CCDSi CCDS8919.1.
    PIRi A55279.
    RefSeqi NP_036196.1. NM_012064.3.
    UniGenei Hs.574026.

    3D structure databases

    ProteinModelPortali P30301.
    SMRi P30301. Positions 2-263.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 110430. 6 interactions.
    IntActi P30301. 1 interaction.
    MINTi MINT-8415310.
    STRINGi 9606.ENSP00000257979.

    Chemistry

    GuidetoPHARMACOLOGYi 687.

    PTM databases

    PhosphoSitei P30301.

    Polymorphism databases

    DMDMi 266537.

    2D gel databases

    OGPi P30301.

    Proteomic databases

    PaxDbi P30301.
    PRIDEi P30301.

    Protocols and materials databases

    DNASUi 4284.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000257979 ; ENSP00000257979 ; ENSG00000135517 .
    GeneIDi 4284.
    KEGGi hsa:4284.
    UCSCi uc001slh.3. human.

    Organism-specific databases

    CTDi 4284.
    GeneCardsi GC12M056843.
    HGNCi HGNC:7103. MIP.
    MIMi 154050. gene.
    615274. phenotype.
    neXtProti NX_P30301.
    Orphaneti 98985. Cataract with Y-shaped suture opacities.
    98989. Cerulean cataract.
    98991. Nuclear cataract.
    98994. Total congenital cataract.
    98995. Zonular cataract.
    PharmGKBi PA30821.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi COG0580.
    HOGENOMi HOG000288286.
    HOVERGENi HBG000312.
    InParanoidi P30301.
    KOi K09863.
    OMAi MWELRST.
    OrthoDBi EOG7N8ZWD.
    PhylomeDBi P30301.
    TreeFami TF312940.

    Enzyme and pathway databases

    Reactomei REACT_23826. Passive transport by Aquaporins.

    Miscellaneous databases

    GeneWikii MIP_(gene).
    GenomeRNAii 4284.
    NextBioi 16853.
    PMAP-CutDB P30301.
    PROi P30301.
    SOURCEi Search...

    Gene expression databases

    Bgeei P30301.
    CleanExi HS_MIP.
    Genevestigatori P30301.

    Family and domain databases

    Gene3Di 1.20.1080.10. 1 hit.
    InterProi IPR023271. Aquaporin-like.
    IPR000425. MIP.
    IPR022357. MIP_CS.
    [Graphical view ]
    PANTHERi PTHR19139. PTHR19139. 1 hit.
    Pfami PF00230. MIP. 1 hit.
    [Graphical view ]
    PRINTSi PR00783. MINTRINSICP.
    SUPFAMi SSF81338. SSF81338. 1 hit.
    TIGRFAMsi TIGR00861. MIP. 1 hit.
    PROSITEi PS00221. MIP. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Genomic cloning, complete nucleotide sequence, and structure of the human gene encoding the major intrinsic protein (MIP) of the lens."
      Pisano M.M., Chepelinsky A.B.
      Genomics 11:981-990(1991) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    2. "The finished DNA sequence of human chromosome 12."
      Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R.
      , Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H., Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S., Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H., Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q., Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V., Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E., Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K., Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D., Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R., David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E., D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N., Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N., Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R., Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S., LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H., Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P., Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G., Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E., Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S., Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O., Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J., Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A., Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M., Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I., Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A., Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y., Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A., Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F., Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L., Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G., Gibbs R.A.
      Nature 440:346-351(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    3. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
      Tissue: Testis.
    4. "Characterization of human lens major intrinsic protein structure."
      Schey K.L., Little M., Fowler J.G., Crouch R.K.
      Invest. Ophthalmol. Vis. Sci. 41:175-182(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION AT SER-235, DEAMIDATION AT ASN-246 AND ASN-259, IDENTIFICATION BY MASS SPECTROMETRY.
    5. "Novel single-base deletional mutation in major intrinsic protein (MIP) in autosomal dominant cataract."
      Geyer D.D., Spence M.A., Johannes M., Flodman P., Clancy K.P., Berry R., Sparkes R.S., Jonsen M.D., Isenberg S.J., Bateman J.B.
      Am. J. Ophthalmol. 141:761-763(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: INVOLVEMENT IN CTRCT15.
    6. "Missense mutations in MIP underlie autosomal dominant 'polymorphic' and lamellar cataracts linked to 12q."
      Berry V., Francis P., Kaushal S., Moore A., Bhattacharya S.
      Nat. Genet. 25:15-17(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANTS CTRCT15 GLY-134 AND ARG-138.
    7. "Functional impairment of lens aquaporin in two families with dominantly inherited cataracts."
      Francis P., Chung J.-J., Yasui M., Berry V., Moore A., Wyatt M.K., Wistow G., Bhattacharya S.S., Agre P.
      Hum. Mol. Genet. 9:2329-2334(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANTS CTRCT15 GLY-134 AND ARG-138.

    Entry informationi

    Entry nameiMIP_HUMAN
    AccessioniPrimary (citable) accession number: P30301
    Secondary accession number(s): Q17R41
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: April 1, 1993
    Last sequence update: April 1, 1993
    Last modified: October 1, 2014
    This is version 140 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. Human chromosome 12
      Human chromosome 12: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3