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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 (PubMed:24120416). 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). Plays a role in cell-to-cell adhesion and facilitates gap junction coupling (PubMed:24120416).By similarity1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei149Important for water channel gatingBy similarity1

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
  • transporter activity Source: ProtInc
  • water channel activity Source: UniProtKB

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Eye lens protein

Keywords - Biological processi

Sensory transduction, Transport, Vision

Enzyme and pathway databases

BioCyciZFISH:ENSG00000135517-MONOMER.
ReactomeiR-HSA-432047. Passive transport by Aquaporins.
SIGNORiP30301.

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
Proteomesi
  • UP000005640 Componenti: Chromosome 12

Organism-specific databases

HGNCiHGNC:7103. MIP.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 8CytoplasmicBy similarity8
Transmembranei9 – 32HelicalBy similarityAdd BLAST24
Topological domaini33 – 38ExtracellularBy similarity6
Transmembranei39 – 61HelicalBy similarityAdd BLAST23
Intramembranei62 – 67By similarity6
Intramembranei68 – 78HelicalBy similarityAdd BLAST11
Topological domaini79 – 84CytoplasmicBy similarity6
Transmembranei85 – 107HelicalBy similarityAdd BLAST23
Topological domaini108 – 126ExtracellularBy similarityAdd BLAST19
Transmembranei127 – 147HelicalBy similarityAdd BLAST21
Topological domaini148 – 159CytoplasmicBy similarityAdd BLAST12
Transmembranei160 – 176HelicalBy similarityAdd BLAST17
Intramembranei177 – 183By similarity7
Intramembranei184 – 194HelicalBy similarityAdd BLAST11
Topological domaini195 – 200ExtracellularBy similarity6
Transmembranei201 – 219HelicalBy similarityAdd BLAST19
Topological domaini220 – 263CytoplasmicBy similarityAdd BLAST44

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

Involvement in diseasei

Cataract 15, multiple types (CTRCT15)10 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)DescriptionActionsGraphical viewLength
Natural variantiVAR_07160133R → C in CTRCT15; reduces cell-to-cell adhesion, reduces cell-to-cell gap junction coupling, no loss of cell membrane localization, no loss of water channel activity. 2 Publications1
Natural variantiVAR_071602107V → I in CTRCT15. 1 PublicationCorresponds to variant rs74641138dbSNPEnsembl.1
Natural variantiVAR_011497134E → G in CTRCT15; non-progressive lamellar cataract; loss of activity. 2 PublicationsCorresponds to variant rs121917869dbSNPEnsembl.1
Natural variantiVAR_011498138T → R in CTRCT15; progressive polymorphic and lamellar cataract; loss of activity. 2 PublicationsCorresponds to variant rs121917867dbSNPEnsembl.1
Natural variantiVAR_075528150D → H in CTRCT15; loss of plasma membrane expression. 1 Publication1
Natural variantiVAR_075529165G → D in CTRCT15; loss of plasma membrane expression. 1 Publication1
Natural variantiVAR_071603187R → C in CTRCT15. 1 PublicationCorresponds to variant rs267603585dbSNPEnsembl.1
Natural variantiVAR_071604233R → K in CTRCT15. 1 Publication1

Keywords - Diseasei

Cataract, Disease mutation

Organism-specific databases

DisGeNETi4284.
MalaCardsiMIP.
MIMi615274. phenotype.
OpenTargetsiENSG00000135517.
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)DescriptionActionsGraphical viewLength
ChainiPRO_00000639121 – 263Lens fiber major intrinsic proteinAdd BLAST263

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei235Phosphoserine1 Publication1
Modified residuei245PhosphoserineBy similarity1
Modified residuei246Deamidated asparagine; by deterioration1 Publication1
Modified residuei259Deamidated asparagine; by deterioration1 Publication1

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

iPTMnetiP30301.
PhosphoSitePlusiP30301.

Miscellaneous databases

PMAP-CutDBP30301.

Expressioni

Tissue specificityi

Major component of lens fiber gap junctions.

Gene expression databases

BgeeiENSG00000135517.
CleanExiHS_MIP.
GenevisibleiP30301. HS.

Interactioni

Subunit structurei

Homotetramer (PubMed:24120416). 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 similarity1 Publication

GO - Molecular functioni

Protein-protein interaction databases

BioGridi110430. 5 interactors.
IntActiP30301. 4 interactors.
MINTiMINT-8415310.
STRINGi9606.ENSP00000257979.

Structurei

3D structure databases

ProteinModelPortaliP30301.
SMRiP30301.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni227 – 237Interaction with CALMBy similarityAdd BLAST11

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi68 – 70NPA 13
Motifi184 – 186NPA 23

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

eggNOGiKOG0223. Eukaryota.
COG0580. LUCA.
GeneTreeiENSGT00760000119223.
HOGENOMiHOG000288286.
HOVERGENiHBG000312.
InParanoidiP30301.
KOiK09863.
OMAiMWELRST.
OrthoDBiEOG091G166T.
PhylomeDBiP30301.
TreeFamiTF312940.

Family and domain databases

CDDicd00333. MIP. 1 hit.
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)DescriptionActionsGraphical viewLength
Natural variantiVAR_07160133R → C in CTRCT15; reduces cell-to-cell adhesion, reduces cell-to-cell gap junction coupling, no loss of cell membrane localization, no loss of water channel activity. 2 Publications1
Natural variantiVAR_071602107V → I in CTRCT15. 1 PublicationCorresponds to variant rs74641138dbSNPEnsembl.1
Natural variantiVAR_011497134E → G in CTRCT15; non-progressive lamellar cataract; loss of activity. 2 PublicationsCorresponds to variant rs121917869dbSNPEnsembl.1
Natural variantiVAR_011498138T → R in CTRCT15; progressive polymorphic and lamellar cataract; loss of activity. 2 PublicationsCorresponds to variant rs121917867dbSNPEnsembl.1
Natural variantiVAR_075528150D → H in CTRCT15; loss of plasma membrane expression. 1 Publication1
Natural variantiVAR_075529165G → D in CTRCT15; loss of plasma membrane expression. 1 Publication1
Natural variantiVAR_071603187R → C in CTRCT15. 1 PublicationCorresponds to variant rs267603585dbSNPEnsembl.1
Natural variantiVAR_071604233R → K in CTRCT15. 1 Publication1

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.4. 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.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi110430. 5 interactors.
IntActiP30301. 4 interactors.
MINTiMINT-8415310.
STRINGi9606.ENSP00000257979.

PTM databases

iPTMnetiP30301.
PhosphoSitePlusiP30301.

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.4. human.

Organism-specific databases

CTDi4284.
DisGeNETi4284.
GeneCardsiMIP.
HGNCiHGNC:7103. MIP.
MalaCardsiMIP.
MIMi154050. gene.
615274. phenotype.
neXtProtiNX_P30301.
OpenTargetsiENSG00000135517.
Orphaneti98985. Cataract with Y-shaped suture opacities.
98989. Cerulean cataract.
98991. Nuclear cataract.
98994. Total congenital cataract.
98995. Zonular cataract.
PharmGKBiPA30821.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0223. Eukaryota.
COG0580. LUCA.
GeneTreeiENSGT00760000119223.
HOGENOMiHOG000288286.
HOVERGENiHBG000312.
InParanoidiP30301.
KOiK09863.
OMAiMWELRST.
OrthoDBiEOG091G166T.
PhylomeDBiP30301.
TreeFamiTF312940.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000135517-MONOMER.
ReactomeiR-HSA-432047. Passive transport by Aquaporins.
SIGNORiP30301.

Miscellaneous databases

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

Gene expression databases

BgeeiENSG00000135517.
CleanExiHS_MIP.
GenevisibleiP30301. HS.

Family and domain databases

CDDicd00333. MIP. 1 hit.
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...

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: November 30, 2016
This is version 162 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

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.