P30301 (MIP_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Lens fiber major intrinsic protein

Alternative name(s):
Aquaporin-0
MIP26
Short name=MP26

Gene names

Name:	MIP
Synonyms:	AQP0

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	263 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Water channel. 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 By similarity.
Subcellular location	Cell membrane; Multi-pass membrane protein. Cell junction › gap 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 autosomal dominant (ADC) [MIM:604219]: 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. In general, the more posteriorly located and dense an opacity, the greater the impact on visual function. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.5 Ref.6
Sequence similarities	Belongs to the MIP/aquaporin (TC 1.A.8) family. [View classification]

Ontologies

Keywords
Biological process	Sensory transduction Transport Vision
Cellular component	Cell junction Cell membrane Gap junction Membrane
Disease	Cataract Disease mutation
Domain	Repeat Transmembrane Transmembrane helix
Molecular function	Eye lens protein
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	canalicular bile acid transport Inferred from electronic annotation. Source: Compara lens development in camera-type eye Inferred from electronic annotation. Source: Compara 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 Traceable author statement. Source: Reactome
Cellular_component	gap junction Inferred from electronic annotation. Source: UniProtKB-SubCell integral to plasma membrane Traceable author statement Ref.1. Source: ProtInc intracellular canaliculus Inferred from electronic annotation. Source: Compara intracellular membrane-bounded organelle Inferred from electronic annotation. Source: Compara
Molecular_function	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 electronic annotation. Source: Compara
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 263	263	Lens fiber major intrinsic protein		PRO_0000063912
Regions
	Topological domain	1 – 8	8	Cytoplasmic By similarity
	Transmembrane	9 – 32	24	Helical; By similarity
	Topological domain	33 – 38	6	Extracellular By similarity
	Transmembrane	39 – 61	23	Helical; By similarity
	Intramembrane	62 – 67	6	By similarity
	Intramembrane	68 – 78	11	Helical; By similarity
	Topological domain	79 – 84	6	Cytoplasmic By similarity
	Transmembrane	85 – 107	23	Helical; By similarity
	Topological domain	108 – 126	19	Extracellular By similarity
	Transmembrane	127 – 147	21	Helical; By similarity
	Topological domain	148 – 159	12	Cytoplasmic By similarity
	Transmembrane	160 – 176	17	Helical; By similarity
	Intramembrane	177 – 183	7	By similarity
	Intramembrane	184 – 194	11	Helical; By similarity
	Topological domain	195 – 200	6	Extracellular By similarity
	Transmembrane	201 – 219	19	Helical; By similarity
	Topological domain	220 – 263	44	Cytoplasmic By similarity
	Motif	68 – 70	3	NPA 1
	Motif	184 – 186	3	NPA 2
Amino acid modifications
	Modified residue	235	1	Phosphoserine Ref.4
	Modified residue	245	1	Phosphoserine By similarity
	Modified residue	246	1	Deamidated asparagine; by deterioration Ref.4
	Modified residue	259	1	Deamidated asparagine; by deterioration Ref.4
Natural variations
	Natural variant	134	1	E → G in ADC; non-progressive lamellar cataract; loss of activity. Ref.5 Ref.6		VAR_011497
	Natural variant	138	1	T → R in ADC; progressive polymorphic and lamellar cataract; loss of activity. Ref.5 Ref.6		VAR_011498

Sequences

	Sequence		Length	Mass (Da)
	P30301 [UniParc]. Last modified April 1, 1993. Version 1. Checksum: 6A864C8AA53CBC4B	FASTA	263	28,122
	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

References

	« Hide 'large scale' referencesShow '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. , 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, 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: VARIANTS ADC GLY-134 AND ARG-138.
[6]	"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 ADC 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.
IPI	IPI00026069.
PIR	A55279.
RefSeq	NP_036196.1. NM_012064.3.
UniGene	Hs.574026.
3D structure databases
ProteinModelPortal	P30301.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000257979.
PTM databases
PhosphoSite	P30301.
Polymorphism databases
DMDM	266537.
2D gel databases
OGP	P30301.
Proteomic databases
PaxDb	P30301.
PRIDE	P30301.
Protocols and materials databases
DNASU	4284.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000257979; ENSP00000257979; ENSG00000135517.
GeneID	4284.
KEGG	hsa:4284.
UCSC	uc001slh.3. human.
Organism-specific databases
CTD	4284.
GeneCards	GC12M056843.
HGNC	HGNC:7103. MIP.
MIM	154050. gene+phenotype. 604219. phenotype.
neXtProt	NX_P30301.
Orphanet	98995. Zonular cataract.
PharmGKB	PA30821.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG0580.
HOGENOM	HOG000288286.
HOVERGEN	HBG000312.
InParanoid	P30301.
KO	K09863.
OMA	WEFRSMN.
OrthoDB	EOG4CJVHW.
PhylomeDB	P30301.
Enzyme and pathway databases
Reactome	REACT_15518. Transmembrane transport of small molecules.
Gene expression databases
Bgee	P30301.
CleanEx	HS_MIP.
Genevestigator	P30301.
GermOnline	ENSG00000135517. Homo sapiens.
Family and domain databases
Gene3D	1.20.1080.10. 1 hit.
InterPro	IPR023271. Aquaporin-like. IPR000425. MIP. IPR022357. MIP_CS. [Graphical view]
PANTHER	PTHR19139. PTHR19139. 1 hit.
Pfam	PF00230. MIP. 1 hit. [Graphical view]
PRINTS	PR00783. MINTRINSICP.
SUPFAM	SSF81338. MIP. 1 hit.
TIGRFAMs	TIGR00861. MIP. 1 hit.
PROSITE	PS00221. MIP. 1 hit. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	4284.
NextBio	16853.
PMAP-CutDB	P30301.
SOURCE	Search...

Entry information

Entry name

MIP_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 127 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.