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Protein

Lens fiber major intrinsic protein

Gene

MIP

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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
  • structural constituent of eye lens Source: UniProtKB-KW
  • water channel activity Source: UniProtKB

GO - Biological processi

Keywordsi

Molecular functionEye lens protein
Biological processSensory transduction, Transport, Vision

Enzyme and pathway databases

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

EuPathDBiHostDB:ENSG00000135517.6
HGNCiHGNC:7103 MIP
MIMi154050 gene
neXtProtiNX_P30301

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

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

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 PublicationsCorresponds to variant dbSNP:rs864309693EnsemblClinVar.1
Natural variantiVAR_071602107V → I in CTRCT15. 1 PublicationCorresponds to variant dbSNP:rs74641138EnsemblClinVar.1
Natural variantiVAR_011497134E → G in CTRCT15; non-progressive lamellar cataract; loss of activity. 2 PublicationsCorresponds to variant dbSNP:rs121917869EnsemblClinVar.1
Natural variantiVAR_011498138T → R in CTRCT15; progressive polymorphic and lamellar cataract; loss of activity. 2 PublicationsCorresponds to variant dbSNP:rs121917867EnsemblClinVar.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 dbSNP:rs267603585Ensembl.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
Fatty acylated at Met-1 and Lys-238. The acyl modifications, in decreasing order of ion abundance, are: oleoyl (C18:1) > palmitoyl (C16:0) > stearoyl (C18:0) > eicosenoyl (C20:1) > dihomo-gamma-linolenoyl (C20:3) > palmitoleoyl (C16:1) > eicosadienoyl (C20:2).1 Publication

Keywords - PTMi

Lipoprotein, Palmitate, Phosphoprotein

Proteomic databases

PaxDbiP30301
PeptideAtlasiP30301
PRIDEiP30301
ProteomicsDBi54651

2D gel databases

OGPiP30301

PTM databases

iPTMnetiP30301
PhosphoSitePlusiP30301

Miscellaneous databases

PMAP-CutDBiP30301

Expressioni

Tissue specificityi

Major component of lens fiber gap junctions.

Gene expression databases

BgeeiENSG00000135517 Expressed in 39 organ(s), highest expression level in lens of camera-type eye
CleanExiHS_MIP
GenevisibleiP30301 HS

Organism-specific databases

HPAiHPA014940

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, 6 interactors
IntActiP30301, 36 interactors
MINTiP30301
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
OMAiHLMGMYY
OrthoDBiEOG091G166T
PhylomeDBiP30301
TreeFamiTF312940

Family and domain databases

CDDicd00333 MIP, 1 hit
Gene3Di1.20.1080.10, 1 hit
InterProiView protein in InterPro
IPR023271 Aquaporin-like
IPR034294 Aquaporin_transptr
IPR000425 MIP
IPR022357 MIP_CS
PANTHERiPTHR19139 PTHR19139, 1 hit
PfamiView protein in Pfam
PF00230 MIP, 1 hit
PRINTSiPR00783 MINTRINSICP
SUPFAMiSSF81338 SSF81338, 1 hit
TIGRFAMsiTIGR00861 MIP, 1 hit
PROSITEiView protein in PROSITE
PS00221 MIP, 1 hit

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 PublicationsCorresponds to variant dbSNP:rs864309693EnsemblClinVar.1
Natural variantiVAR_071602107V → I in CTRCT15. 1 PublicationCorresponds to variant dbSNP:rs74641138EnsemblClinVar.1
Natural variantiVAR_011497134E → G in CTRCT15; non-progressive lamellar cataract; loss of activity. 2 PublicationsCorresponds to variant dbSNP:rs121917869EnsemblClinVar.1
Natural variantiVAR_011498138T → R in CTRCT15; progressive polymorphic and lamellar cataract; loss of activity. 2 PublicationsCorresponds to variant dbSNP:rs121917867EnsemblClinVar.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 dbSNP:rs267603585Ensembl.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

Similar proteinsi

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, 6 interactors
IntActiP30301, 36 interactors
MINTiP30301
STRINGi9606.ENSP00000257979

PTM databases

iPTMnetiP30301
PhosphoSitePlusiP30301

Polymorphism and mutation databases

BioMutaiMIP
DMDMi266537

2D gel databases

OGPiP30301

Proteomic databases

PaxDbiP30301
PeptideAtlasiP30301
PRIDEiP30301
ProteomicsDBi54651

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
EuPathDBiHostDB:ENSG00000135517.6
GeneCardsiMIP
HGNCiHGNC:7103 MIP
HPAiHPA014940
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
OMAiHLMGMYY
OrthoDBiEOG091G166T
PhylomeDBiP30301
TreeFamiTF312940

Enzyme and pathway databases

ReactomeiR-HSA-432047 Passive transport by Aquaporins
SIGNORiP30301

Miscellaneous databases

ChiTaRSiMIP human
GeneWikiiMIP_(gene)
GenomeRNAii4284
PMAP-CutDBiP30301
PROiPR:P30301
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000135517 Expressed in 39 organ(s), highest expression level in lens of camera-type eye
CleanExiHS_MIP
GenevisibleiP30301 HS

Family and domain databases

CDDicd00333 MIP, 1 hit
Gene3Di1.20.1080.10, 1 hit
InterProiView protein in InterPro
IPR023271 Aquaporin-like
IPR034294 Aquaporin_transptr
IPR000425 MIP
IPR022357 MIP_CS
PANTHERiPTHR19139 PTHR19139, 1 hit
PfamiView protein in Pfam
PF00230 MIP, 1 hit
PRINTSiPR00783 MINTRINSICP
SUPFAMiSSF81338 SSF81338, 1 hit
TIGRFAMsiTIGR00861 MIP, 1 hit
PROSITEiView protein in PROSITE
PS00221 MIP, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiMIP_HUMAN
AccessioniPrimary (citable) accession number: P30301
Secondary accession number(s): Q17R41
Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 1, 1993
Last sequence update: April 1, 1993
Last modified: September 12, 2018
This is version 172 of the entry and version 1 of the sequence. See 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 entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  2. SIMILARITY comments
    Index of protein domains and families
  3. Human chromosome 12
    Human chromosome 12: entries, gene names and cross-references to MIM
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
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