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Protein

Lens fiber major intrinsic protein

Gene

MIP

Organism
Bos taurus (Bovine)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Water channel (PubMed:23893133). 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 similarity1 Publication

Sites

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

GO - Molecular functioni

  • calmodulin binding Source: UniProtKB
  • gap junction channel activity Source: UniProtKB
  • glycerol channel activity Source: GO_Central
  • structural constituent of eye lens Source: UniProtKB-KW
  • water channel activity Source: UniProtKB

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Eye lens protein

Keywords - Biological processi

Transport

Enzyme and pathway databases

ReactomeiR-BTA-432047. Passive transport by Aquaporins.

Protein family/group databases

TCDBi1.A.8.8.2. the major intrinsic protein (mip) family.

Names & Taxonomyi

Protein namesi
Recommended name:
Lens fiber major intrinsic protein
Alternative name(s):
Aquaporin-0
MIP26
Short name:
MP26
Gene namesi
Name:MIP
OrganismiBos taurus (Bovine)
Taxonomic identifieri9913 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCetartiodactylaRuminantiaPecoraBovidaeBovinaeBos
Proteomesi
  • UP000009136 Componenti: Chromosome 5

Subcellular locationi

  • Cell membrane By similarity; Multi-pass membrane protein By similarity
  • Cell junctiongap junction By similarity

Topology

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

GO - Cellular componenti

  • apical plasma membrane Source: GO_Central
  • endoplasmic reticulum Source: UniProtKB
  • gap junction Source: UniProtKB-SubCell
  • integral component of plasma membrane Source: UniProtKB
  • plasma membrane Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cell junction, Cell membrane, Gap junction, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi149 – 1491Y → G: Increases constitutive water permeability. Abolishes regulation by cytoplasmic calcium levels. 1 Publication
Mutagenesisi149 – 1491Y → L: Strongly decreases water permeability. Abolishes regulation by cytoplasmic calcium levels. 1 Publication
Mutagenesisi149 – 1491Y → S: Slightly decreases water permeability, but has a minor effect on the regulation by cytoplasmic calcium levels. 1 Publication
Mutagenesisi227 – 2271L → A: Strongly reduced CALM binding. 1 Publication
Mutagenesisi230 – 2301V → A: Strongly reduced CALM binding. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 263263Lens fiber major intrinsic proteinPRO_0000063910Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei235 – 2351Phosphoserine1 Publication
Modified residuei243 – 2431Phosphoserine; by PKA1 Publication
Modified residuei245 – 2451Phosphoserine1 Publication
Modified residuei246 – 2461Deamidated asparagine1 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

PaxDbiP06624.

PTM databases

iPTMnetiP06624.

Expressioni

Tissue specificityi

Major component of lens fiber gap junctions.

Developmental stagei

Higher expression in pre-natal (1-5 months gestation) than in postnatal (4-6 months) calf lens.

Interactioni

Subunit structurei

Homotetramer (PubMed:15377788, PubMed:16309700). Homooctamer formed by head-to-head interaction between homotetramers from adjoining membranes (PubMed:15377788, PubMed:16309700). Interacts with CALM; one CALM molecule interacts with the cytoplasmic domains of two aquaporins, leading to channel closure (PubMed:23893133).3 Publications

GO - Molecular functioni

  • calmodulin binding Source: UniProtKB

Protein-protein interaction databases

DIPiDIP-60546N.
STRINGi9913.ENSBTAP00000013360.

Structurei

Secondary structure

1
263
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi10 – 3122Combined sources
Helixi38 – 5922Combined sources
Turni60 – 634Combined sources
Helixi69 – 779Combined sources
Helixi83 – 10725Combined sources
Turni110 – 1123Combined sources
Turni114 – 1174Combined sources
Helixi127 – 14923Combined sources
Helixi160 – 17920Combined sources
Helixi185 – 19511Combined sources
Turni199 – 2024Combined sources
Helixi203 – 22018Combined sources
Turni221 – 2233Combined sources
Helixi230 – 2389Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1YMGX-ray2.24A1-263[»]
2C32X-ray7.01A1-263[»]
ProteinModelPortaliP06624.
SMRiP06624. Positions 2-263.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP06624.

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni227 – 23711Interaction with CALMAdd
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.

Sequence similaritiesi

Keywords - Domaini

Repeat, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG0223. Eukaryota.
COG0580. LUCA.
GeneTreeiENSGT00760000119223.
HOGENOMiHOG000288286.
HOVERGENiHBG000312.
InParanoidiP06624.
KOiK09863.
OMAiCELVFVI.
OrthoDBiEOG7N8ZWD.
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.

P06624-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MWELRSASFW RAICAEFFAS LFYVFFGLGA SLRWAPGPLH VLQVALAFGL
60 70 80 90 100
ALATLVQAVG HISGAHVNPA VTFAFLVGSQ MSLLRAICYM VAQLLGAVAG
110 120 130 140 150
AAVLYSVTPP AVRGNLALNT LHPGVSVGQA TIVEIFLTLQ FVLCIFATYD
160 170 180 190 200
ERRNGRLGSV ALAVGFSLTL GHLFGMYYTG AGMNPARSFA PAILTRNFTN
210 220 230 240 250
HWVYWVGPVI GAGLGSLLYD FLLFPRLKSV SERLSILKGS RPSESNGQPE
260
VTGEPVELKT QAL
Length:263
Mass (Da):28,223
Last modified:January 1, 1988 - v1
Checksum:iE08C2C4F33398D4E
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti14 – 141C → L AA sequence (PubMed:3882455).Curated
Sequence conflicti29 – 335GASLR → RAFLL AA sequence (PubMed:3882455).Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
K02818 mRNA. Translation: AAA30622.1.
PIRiA23251. MMBOLM.
RefSeqiNP_776362.1. NM_173937.2.
UniGeneiBt.4516.

Genome annotation databases

EnsembliENSBTAT00000013360; ENSBTAP00000013360; ENSBTAG00000010127.
GeneIDi280859.
KEGGibta:280859.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
K02818 mRNA. Translation: AAA30622.1.
PIRiA23251. MMBOLM.
RefSeqiNP_776362.1. NM_173937.2.
UniGeneiBt.4516.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1YMGX-ray2.24A1-263[»]
2C32X-ray7.01A1-263[»]
ProteinModelPortaliP06624.
SMRiP06624. Positions 2-263.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

DIPiDIP-60546N.
STRINGi9913.ENSBTAP00000013360.

Protein family/group databases

TCDBi1.A.8.8.2. the major intrinsic protein (mip) family.

PTM databases

iPTMnetiP06624.

Proteomic databases

PaxDbiP06624.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSBTAT00000013360; ENSBTAP00000013360; ENSBTAG00000010127.
GeneIDi280859.
KEGGibta:280859.

Organism-specific databases

CTDi4284.

Phylogenomic databases

eggNOGiKOG0223. Eukaryota.
COG0580. LUCA.
GeneTreeiENSGT00760000119223.
HOGENOMiHOG000288286.
HOVERGENiHBG000312.
InParanoidiP06624.
KOiK09863.
OMAiCELVFVI.
OrthoDBiEOG7N8ZWD.
TreeFamiTF312940.

Enzyme and pathway databases

ReactomeiR-BTA-432047. Passive transport by Aquaporins.

Miscellaneous databases

EvolutionaryTraceiP06624.

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

  1. "The major intrinsic protein (MIP) of the bovine lens fiber membrane: characterization and structure based on cDNA cloning."
    Gorin M.B., Yancey S.B., Cline J., Revel J.-P., Horwitz J.
    Cell 39:49-59(1984) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 1-39.
  2. "Sequence analysis of peptide fragments from the intrinsic membrane protein of calf lens fibers MP26 and its natural maturation product MP22."
    Ngoc L.D., Paroutaud P., Dunia I., Benedetti E.L., Hoebeke J.
    FEBS Lett. 181:74-78(1985) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEIN SEQUENCE OF 1-33.
    Tissue: Lens.
  3. "Amino acid sequence of in vivo phosphorylation sites in the main intrinsic protein (MIP) of lens membranes."
    Lampe P.D., Johnson R.G.
    Eur. J. Biochem. 194:541-547(1990) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEIN SEQUENCE OF 239-259, PHOSPHORYLATION AT SER-243 AND SER-245, DEAMIDATION AT ASN-246.
    Tissue: Lens.
  4. "Complete map and identification of the phosphorylation site of bovine lens major intrinsic protein."
    Schey K.L., Fowler J.G., Schwartz J.C., Busman M., Dillon J., Crouch R.K.
    Invest. Ophthalmol. Vis. Sci. 38:2508-2515(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION AT SER-235.
    Tissue: Lens.
  5. Cited for: FUNCTION, INTERACTION WITH CALM, MUTAGENESIS OF TYR-149; LEU-227 AND VAL-230.
  6. Cited for: X-RAY CRYSTALLOGRAPHY (2.24 ANGSTROMS), MEMBRANE TOPOLOGY, SUBUNIT.
  7. "Co-axial association of recombinant eye lens aquaporin-0 observed in loosely packed 3D crystals."
    Palanivelu D.V., Kozono D.E., Engel A., Suda K., Lustig A., Agre P., Schirmer T.
    J. Mol. Biol. 355:605-611(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (7.01 ANGSTROMS), MEMBRANE TOPOLOGY, SUBUNIT.

Entry informationi

Entry nameiMIP_BOVIN
AccessioniPrimary (citable) accession number: P06624
Entry historyi
Integrated into UniProtKB/Swiss-Prot: January 1, 1988
Last sequence update: January 1, 1988
Last modified: July 6, 2016
This is version 141 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. SIMILARITY comments
    Index of protein domains and families

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 one 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.