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Protein

Lens fiber major intrinsic protein

Gene

MIP

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

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

GO - Biological processi

Complete GO annotation...

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 Componenti: Chromosome 12

Organism-specific databases

HGNCiHGNC:7103. MIP.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 88CytoplasmicBy similarity
Transmembranei9 – 3224HelicalBy similarityAdd
BLAST
Topological domaini33 – 386ExtracellularBy similarity
Transmembranei39 – 6123HelicalBy similarityAdd
BLAST
Intramembranei62 – 676By similarity
Intramembranei68 – 7811HelicalBy similarityAdd
BLAST
Topological domaini79 – 846CytoplasmicBy similarity
Transmembranei85 – 10723HelicalBy similarityAdd
BLAST
Topological domaini108 – 12619ExtracellularBy similarityAdd
BLAST
Transmembranei127 – 14721HelicalBy similarityAdd
BLAST
Topological domaini148 – 15912CytoplasmicBy similarityAdd
BLAST
Transmembranei160 – 17617HelicalBy similarityAdd
BLAST
Intramembranei177 – 1837By similarity
Intramembranei184 – 19411HelicalBy similarityAdd
BLAST
Topological domaini195 – 2006ExtracellularBy similarity
Transmembranei201 – 21919HelicalBy similarityAdd
BLAST
Topological domaini220 – 26344CytoplasmicBy similarityAdd
BLAST

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell junction, Cell membrane, Gap junction, Membrane

Pathology & Biotechi

Involvement in diseasei

Cataract 15, multiple types (CTRCT15)7 Publications

The disease is caused by mutations affecting the gene represented in this entry.

Disease descriptionAn 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.

See also OMIM:615274
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti33 – 331R → C in CTRCT15. 1 Publication
VAR_071601
Natural varianti107 – 1071V → I in CTRCT15. 1 Publication
VAR_071602
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
Natural varianti187 – 1871R → C in CTRCT15. 1 Publication
VAR_071603
Natural varianti233 – 2331R → K in CTRCT15. 1 Publication
VAR_071604

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.

Polymorphism and mutation databases

BioMutaiMIP.
DMDMi266537.

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.
GenevisibleiP30301. HS.

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. 5 interactions.
IntActiP30301. 1 interaction.
MINTiMINT-8415310.
STRINGi9606.ENSP00000257979.

Structurei

3D structure databases

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

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.
GeneTreeiENSGT00760000119223.
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

        10         20         30         40         50
MWELRSASFW RAIFAEFFAT LFYVFFGLGS SLRWAPGPLH VLQVAMAFGL
60 70 80 90 100
ALATLVQSVG HISGAHVNPA VTFAFLVGSQ MSLLRAFCYM AAQLLGAVAG
110 120 130 140 150
AAVLYSVTPP AVRGNLALNT LHPAVSVGQA TTVEIFLTLQ FVLCIFATYD
160 170 180 190 200
ERRNGQLGSV ALAVGFSLAL GHLFGMYYTG AGMNPARSFA PAILTGNFTN
210 220 230 240 250
HWVYWVGPII GGGLGSLLYD FLLFPRLKSI SERLSVLKGA KPDVSNGQPE
260
VTGEPVELNT QAL
Length:263
Mass (Da):28,122
Last modified:April 1, 1993 - v1
Checksum:i6A864C8AA53CBC4B
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti33 – 331R → C in CTRCT15. 1 Publication
VAR_071601
Natural varianti107 – 1071V → I in CTRCT15. 1 Publication
VAR_071602
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
Natural varianti187 – 1871R → C in CTRCT15. 1 Publication
VAR_071603
Natural varianti233 – 2331R → K in CTRCT15. 1 Publication
VAR_071604

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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.

3D structure databases

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

Protein-protein interaction databases

BioGridi110430. 5 interactions.
IntActiP30301. 1 interaction.
MINTiMINT-8415310.
STRINGi9606.ENSP00000257979.

Chemistry

GuidetoPHARMACOLOGYi687.

PTM databases

PhosphoSiteiP30301.

Polymorphism and mutation databases

BioMutaiMIP.
DMDMi266537.

2D gel databases

OGPiP30301.

Proteomic databases

PaxDbiP30301.
PRIDEiP30301.

Protocols and materials databases

DNASUi4284.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi4284.
GeneCardsiGC12M056843.
HGNCiHGNC:7103. MIP.
MIMi154050. gene.
615274. phenotype.
neXtProtiNX_P30301.
Orphaneti98985. Cataract with Y-shaped suture opacities.
98989. Cerulean cataract.
98991. Nuclear cataract.
98994. Total congenital cataract.
98995. Zonular cataract.
PharmGKBiPA30821.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiCOG0580.
GeneTreeiENSGT00760000119223.
HOGENOMiHOG000288286.
HOVERGENiHBG000312.
InParanoidiP30301.
KOiK09863.
OMAiMWELRST.
OrthoDBiEOG7N8ZWD.
PhylomeDBiP30301.
TreeFamiTF312940.

Enzyme and pathway databases

ReactomeiREACT_23826. Passive transport by Aquaporins.

Miscellaneous databases

GeneWikiiMIP_(gene).
GenomeRNAii4284.
NextBioi16853.
PMAP-CutDBP30301.
PROiP30301.
SOURCEiSearch...

Gene expression databases

BgeeiP30301.
CleanExiHS_MIP.
GenevisibleiP30301. HS.

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]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  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. "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: INVOLVEMENT IN CTRCT15, VARIANTS CTRCT15 GLY-134 AND ARG-138.
  6. "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.
  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.
  8. "A novel mutation in major intrinsic protein of the lens gene (MIP) underlies autosomal dominant cataract in a Chinese family."
    Gu F., Zhai H., Li D., Zhao L., Li C., Huang S., Ma X.
    Mol. Vis. 13:1651-1656(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANT CTRCT15 CYS-33.
  9. "A substitution of arginine to lysine at the COOH-terminus of MIP caused a different binocular phenotype in a congenital cataract family."
    Lin H., Hejtmancik J.F., Qi Y.
    Mol. Vis. 13:1822-1827(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANT CTRCT15 LYS-233.
  10. "A novel mutation in the major intrinsic protein (MIP) associated with autosomal dominant congenital cataracts in a Chinese family."
    Wang W., Jiang J., Zhu Y., Li J., Jin C., Shentu X., Yao K.
    Mol. Vis. 16:534-539(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANT CTRCT15 ILE-107.
  11. "A novel mutation in MIP associated with congenital nuclear cataract in a Chinese family."
    Wang K.J., Li S.S., Yun B., Ma W.X., Jiang T.G., Zhu S.Q.
    Mol. Vis. 17:70-77(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANT CTRCT15 CYS-187.

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: June 24, 2015
This is version 148 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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.