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P30301 (MIP_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 138. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Lens fiber major intrinsic protein
Alternative name(s):
Aquaporin-0
MIP26
Short name=MP26
Gene names
Name:MIP
Synonyms:AQP0
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length263 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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.

Subunit structure

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.

Subcellular location

Cell membrane; Multi-pass membrane protein. Cell junctiongap junction.

Tissue specificity

Major component of lens fiber gap junctions.

Domain

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.

Post-translational modification

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

Involvement in disease

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.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.5 Ref.6 Ref.7

Sequence similarities

Belongs to the MIP/aquaporin (TC 1.A.8) family. [View classification]

Ontologies

Keywords
   Biological processSensory transduction
Transport
Vision
   Cellular componentCell junction
Cell membrane
Gap junction
Membrane
   DiseaseCataract
Disease mutation
   DomainRepeat
Transmembrane
Transmembrane helix
   Molecular functionEye lens protein
   PTMPhosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processcanalicular bile acid transport

Inferred from electronic annotation. Source: Ensembl

lens development in camera-type eye

Inferred from electronic annotation. Source: Ensembl

response to stimulus

Inferred from electronic annotation. Source: UniProtKB-KW

transmembrane transport

Traceable author statement. Source: Reactome

visual perception

Inferred from electronic annotation. Source: UniProtKB-KW

water transport

Inferred from sequence or structural similarity. Source: UniProtKB

   Cellular_componentgap junction

Inferred from electronic annotation. Source: UniProtKB-SubCell

integral component of plasma membrane

Inferred from sequence or structural similarity. Source: UniProtKB

intracellular canaliculus

Inferred from electronic annotation. Source: Ensembl

intracellular membrane-bounded organelle

Inferred from electronic annotation. Source: Ensembl

plasma membrane

Traceable author statement. Source: Reactome

   Molecular_functioncalmodulin binding

Inferred from sequence or structural similarity. Source: UniProtKB

structural constituent of eye lens

Inferred from electronic annotation. Source: UniProtKB-KW

transporter activity

Traceable author statement Ref.1. Source: ProtInc

water channel activity

Inferred from sequence or structural similarity. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 263263Lens fiber major intrinsic protein
PRO_0000063912

Regions

Topological domain1 – 88Cytoplasmic By similarity
Transmembrane9 – 3224Helical; By similarity
Topological domain33 – 386Extracellular By similarity
Transmembrane39 – 6123Helical; By similarity
Intramembrane62 – 676 By similarity
Intramembrane68 – 7811Helical; By similarity
Topological domain79 – 846Cytoplasmic By similarity
Transmembrane85 – 10723Helical; By similarity
Topological domain108 – 12619Extracellular By similarity
Transmembrane127 – 14721Helical; By similarity
Topological domain148 – 15912Cytoplasmic By similarity
Transmembrane160 – 17617Helical; By similarity
Intramembrane177 – 1837 By similarity
Intramembrane184 – 19411Helical; By similarity
Topological domain195 – 2006Extracellular By similarity
Transmembrane201 – 21919Helical; By similarity
Topological domain220 – 26344Cytoplasmic By similarity
Region227 – 23711Interaction with CALM By similarity
Motif68 – 703NPA 1
Motif184 – 1863NPA 2

Sites

Site1491Important for water channel gating By similarity

Amino acid modifications

Modified residue2351Phosphoserine Ref.4
Modified residue2451Phosphoserine By similarity
Modified residue2461Deamidated asparagine; by deterioration Ref.4
Modified residue2591Deamidated asparagine; by deterioration Ref.4

Natural variations

Natural variant1341E → G in CTRCT15; non-progressive lamellar cataract; loss of activity. Ref.6 Ref.7
VAR_011497
Natural variant1381T → R in CTRCT15; progressive polymorphic and lamellar cataract; loss of activity. Ref.6 Ref.7
VAR_011498

Sequences

Sequence LengthMass (Da)Tools
P30301 [UniParc].

Last modified April 1, 1993. Version 1.
Checksum: 6A864C8AA53CBC4B

FASTA26328,122
        10         20         30         40         50         60 
MWELRSASFW RAIFAEFFAT LFYVFFGLGS SLRWAPGPLH VLQVAMAFGL ALATLVQSVG 

        70         80         90        100        110        120 
HISGAHVNPA VTFAFLVGSQ MSLLRAFCYM AAQLLGAVAG AAVLYSVTPP AVRGNLALNT 

       130        140        150        160        170        180 
LHPAVSVGQA TTVEIFLTLQ FVLCIFATYD ERRNGQLGSV ALAVGFSLAL GHLFGMYYTG 

       190        200        210        220        230        240 
AGMNPARSFA PAILTGNFTN HWVYWVGPII GGGLGSLLYD FLLFPRLKSI SERLSVLKGA 

       250        260 
KPDVSNGQPE VTGEPVELNT QAL 

« Hide

References

« Hide 'large scale' references
[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. expand/collapse author list , 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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U36308 Genomic DNA. Translation: AAC02794.2.
AC024884 Genomic DNA. No translation available.
BC074913 mRNA. Translation: AAH74913.1.
BC117474 mRNA. Translation: AAI17475.1.
CCDSCCDS8919.1.
PIRA55279.
RefSeqNP_036196.1. NM_012064.3.
UniGeneHs.574026.

3D structure databases

ProteinModelPortalP30301.
SMRP30301. Positions 2-263.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid110430. 6 interactions.
IntActP30301. 1 interaction.
MINTMINT-8415310.
STRING9606.ENSP00000257979.

Chemistry

GuidetoPHARMACOLOGY687.

PTM databases

PhosphoSiteP30301.

Polymorphism databases

DMDM266537.

2D gel databases

OGPP30301.

Proteomic databases

PaxDbP30301.
PRIDEP30301.

Protocols and materials databases

DNASU4284.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000257979; ENSP00000257979; ENSG00000135517.
GeneID4284.
KEGGhsa:4284.
UCSCuc001slh.3. human.

Organism-specific databases

CTD4284.
GeneCardsGC12M056843.
HGNCHGNC:7103. MIP.
MIM154050. gene.
615274. phenotype.
neXtProtNX_P30301.
Orphanet98985. Cataract with Y-shaped suture opacities.
98989. Cerulean cataract.
98991. Nuclear cataract.
98994. Total congenital cataract.
98995. Zonular cataract.
PharmGKBPA30821.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0580.
HOGENOMHOG000288286.
HOVERGENHBG000312.
InParanoidP30301.
KOK09863.
OMAMWELRST.
OrthoDBEOG7N8ZWD.
PhylomeDBP30301.
TreeFamTF312940.

Enzyme and pathway databases

ReactomeREACT_15518. Transmembrane transport of small molecules.

Gene expression databases

BgeeP30301.
CleanExHS_MIP.
GenevestigatorP30301.

Family and domain databases

Gene3D1.20.1080.10. 1 hit.
InterProIPR023271. Aquaporin-like.
IPR000425. MIP.
IPR022357. MIP_CS.
[Graphical view]
PANTHERPTHR19139. PTHR19139. 1 hit.
PfamPF00230. MIP. 1 hit.
[Graphical view]
PRINTSPR00783. MINTRINSICP.
SUPFAMSSF81338. SSF81338. 1 hit.
TIGRFAMsTIGR00861. MIP. 1 hit.
PROSITEPS00221. MIP. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiMIP_(gene).
GenomeRNAi4284.
NextBio16853.
PMAP-CutDBP30301.
PROP30301.
SOURCESearch...

Entry information

Entry nameMIP_HUMAN
AccessionPrimary (citable) accession number: P30301
Secondary accession number(s): Q17R41
Entry history
Integrated into UniProtKB/Swiss-Prot: April 1, 1993
Last sequence update: April 1, 1993
Last modified: July 9, 2014
This is version 138 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 12

Human chromosome 12: entries, gene names and cross-references to MIM