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)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › 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	Defects in MIP are a cause of cataract autosomal dominant (ADC) [MIM:604219]. Cataract is 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. Cataract is the most common treatable cause of visual disability in childhood. 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	response to stimulus Inferred from electronic annotation. Source: UniProtKB-KW visual perception Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	gap junction Inferred from electronic annotation. Source: UniProtKB-SubCell integral to plasma membrane Traceable author statement. Source: ProtInc
Molecular function	structural constituent of eye lens Inferred from electronic annotation. Source: UniProtKB-KW
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: 1840563] [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: 16541075] [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: 15489334] [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: 10634618] [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: 10802646] [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: 11001937] [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.
SMR	P30301. Positions 2-263.
ModBase	Search...
Protein-protein interaction databases
STRING	P30301.
PTM databases
PhosphoSite	P30301.
Polymorphism databases
DMDM	266537.
2D gel databases
OGP	P30301.
Proteomic databases
PRIDE	P30301.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000257979; ENSP00000257979; ENSG00000135517.
GeneID	4284.
KEGG	hsa:4284.
UCSC	uc001slh.1. human.
Organism-specific databases
CTD	4284.
GeneCards	GC12M056843.
H-InvDB	HIX0036831.
HGNC	HGNC:7103. MIP.
MIM	154050. gene+phenotype. 604219. phenotype.
neXtProt	NX_P30301.
Orphanet	98995. Zonular cataract.
PharmGKB	PA30821.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG08264.
GeneTree	ENSGT00550000074347.
HOGENOM	HBG705794.
HOVERGEN	HBG000312.
InParanoid	P30301.
OMA	DSNGQPE.
OrthoDB	EOG4CJVHW.
PhylomeDB	P30301.
Enzyme and pathway databases
Reactome	REACT_15518. Transmembrane transport of small molecules.
Gene expression databases
ArrayExpress	P30301.
Bgee	P30301.
CleanEx	HS_MIP.
Genevestigator	P30301.
GermOnline	ENSG00000135517. Homo sapiens.
Family and domain databases
InterPro	IPR012269. Aquaporin. IPR023271. Aquaporin-like. IPR000425. MIP. IPR022357. MIP_CS. [Graphical view]
Gene3D	G3DSA:1.20.1080.10. MIP. 1 hit.
KO	K09863.
PANTHER	PTHR19139. MIP. 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
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:	January 25, 2012
This is version 114 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.