Q92482 (AQP3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Aquaporin-3
Short name=AQP-3

Alternative name(s):
Aquaglyceroporin-3

Gene names

Name:

AQP3

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	292 AA.
Sequence status	Complete.
Protein existence	Evidence at transcript level

General annotation (Comments)

Function	Water channel required to promote glycerol permeability and water transport across cell membranes. Acts as a glycerol transporter in skin and plays an important role in regulating SC (stratum corneum) and epidermal glycerol content. Involved in skin hydration, wound healing, and tumorigenesis. Provides kidney medullary collecting duct with high permeability to water, thereby permitting water to move in the direction of an osmotic gradient. Slightly permeable to urea and may function as a water and urea exit mechanism in antidiuresis in collecting duct cells. It may play an important role in gastrointestinal tract water transport and in glycerol metabolism By similarity.
Subcellular location	Basolateral cell membrane; Multi-pass membrane protein. Note: In collecting ducts of kidney.
Tissue specificity	Widely expressed in epithelial cells of kidney (collecting ducts) and airways, in keratinocytes, immature dendritic cells and erythrocytes. Isoform 2 is not detectable in erythrocytes at the protein level.
Induction	Up-regulated by magnesium. Ref.11
Domain	Aquaporins contain two tandem repeats each containing three membrane-spanning domains and a pore-forming loop with the signature motif Asn-Pro-Ala (NPA).
Polymorphism	AQP3 is responsible for the GIL blood group system. Isoform 2 is detected in GIL-negative individuals that lack functional AQP3.
Sequence similarities	Belongs to the MIP/aquaporin (TC 1.A.8) family. [View classification]

Ontologies

Keywords
Biological process	Transport
Cellular component	Cell membrane Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Repeat Transmembrane Transmembrane helix
Molecular function	Blood group antigen
PTM	Glycoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	excretion Traceable author statement PubMed 7543093. Source: ProtInc odontogenesis Inferred from expression pattern PubMed 12522663. Source: UniProtKB positive regulation of immune system process Inferred from direct assay PubMed 17943189. Source: BHF-UCL regulation of keratinocyte differentiation Traceable author statement PubMed 17943189. Source: BHF-UCL renal water absorption Inferred from electronic annotation. Source: Compara response to calcium ion Traceable author statement PubMed 17943189. Source: BHF-UCL response to retinoic acid Inferred from direct assay PubMed 17943189. Source: BHF-UCL response to vitamin D Traceable author statement PubMed 17943189. Source: BHF-UCL urea transport Inferred from electronic annotation. Source: Compara
Cellular_component	basolateral plasma membrane Inferred from electronic annotation. Source: UniProtKB-SubCell cell-cell junction Inferred from direct assay PubMed 18718702. Source: UniProtKB cytoplasm Inferred from direct assay PubMed 18718702PubMed 19545896. Source: UniProtKB integral to membrane Inferred by curator PubMed 17943189. Source: BHF-UCL plasma membrane Inferred from direct assay PubMed 14521551PubMed 18718702PubMed 19545896. Source: UniProtKB
Molecular_function	glycerol channel activity Inferred from direct assay PubMed 17943189. Source: BHF-UCL water channel activity Traceable author statement PubMed 17943189. Source: BHF-UCL
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q92482-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: Q92482-2)

Also known as: delta5;

The sequence of this isoform differs from the canonical sequence as follows:
     165-281: FIGTASLIVC...PPPSNEEENV → DRPALVVGAH...FPLDLAQIAP
     282-292: Missing.

Note: Due to a polymorphism at the 5'-splice donor site of intron 5, leading to exon 5 skipping and premature termination of translation. This is the molecular basis of the GIL blood group.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 292	292	Aquaporin-3		PRO_0000063943
Regions
	Topological domain	1 – 28	28	Cytoplasmic Potential
	Transmembrane	29 – 49	21	Helical; Potential
	Topological domain	50 – 53	4	Extracellular Potential
	Transmembrane	54 – 74	21	Helical; Potential
	Topological domain	75 – 109	35	Cytoplasmic Potential
	Transmembrane	110 – 130	21	Helical; Potential
	Topological domain	131 – 157	27	Extracellular Potential
	Transmembrane	158 – 178	21	Helical; Potential
	Topological domain	179 – 188	10	Cytoplasmic Potential
	Transmembrane	189 – 209	21	Helical; Potential
	Topological domain	210 – 244	35	Extracellular Potential
	Transmembrane	245 – 265	21	Helical; Potential
	Topological domain	266 – 292	27	Cytoplasmic Potential
	Motif	83 – 85	3	NPA 1
	Motif	215 – 217	3	NPA 2
Amino acid modifications
	Glycosylation	141	1	N-linked (GlcNAc...) Potential
Natural variations
	Alternative sequence	165 – 281	117	FIGTA…EEENV → DRPALVVGAHRVPTPGLHCG CLRVPADDRLPPGAAPTLQR GRECEAGPCEAQGADLSGKG HLPLRCPGLEHPLTVQGHSQ EAPLHDPPFQAKELPIYPHP TKTAPSGFPLDLAQIAP in isoform 2.		VSP_003229
	Alternative sequence	282 – 292	11	Missing in isoform 2.		VSP_003230
	Natural variant	43	1	V → M. Ref.7 Corresponds to variant rs34942735 [ dbSNP | Ensembl ].		VAR_025089
Experimental info
	Sequence conflict	23	1	R → G in BAF84897. Ref.6
	Sequence conflict	137	1	V → A in CAG46822. Ref.4

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified November 1, 1997. Version 2. Checksum: A9555E9576EABA9C	FASTA	292	31,544
	10 20 30 40 50 60 MGRQKELVSR CGEMLHIRYR LLRQALAECL GTLILVMFGC GSVAQVVLSR GTHGGFLTIN 70 80 90 100 110 120 LAFGFAVTLG ILIAGQVSGA HLNPAVTFAM CFLAREPWIK LPIYTLAQTL GAFLGAGIVF 130 140 150 160 170 180 GLYYDAIWHF ADNQLFVSGP NGTAGIFATY PSGHLDMING FFDQFIGTAS LIVCVLAIVD 190 200 210 220 230 240 PYNNPVPRGL EAFTVGLVVL VIGTSMGFNS GYAVNPARDF GPRLFTALAG WGSAVFTTGQ 250 260 270 280 290 HWWWVPIVSP LLGSIAGVFV YQLMIGCHLE QPPPSNEEEN VKLAHVKHKE QI
	Isoform 2 (delta5) [UniParc]. Checksum: C46894A001707CC5	FASTA	281	29,987
	10 20 30 40 50 60 MGRQKELVSR CGEMLHIRYR LLRQALAECL GTLILVMFGC GSVAQVVLSR GTHGGFLTIN 70 80 90 100 110 120 LAFGFAVTLG ILIAGQVSGA HLNPAVTFAM CFLAREPWIK LPIYTLAQTL GAFLGAGIVF 130 140 150 160 170 180 GLYYDAIWHF ADNQLFVSGP NGTAGIFATY PSGHLDMING FFDQDRPALV VGAHRVPTPG 190 200 210 220 230 240 LHCGCLRVPA DDRLPPGAAP TLQRGRECEA GPCEAQGADL SGKGHLPLRC PGLEHPLTVQ 250 260 270 280 GHSQEAPLHD PPFQAKELPI YPHPTKTAPS GFPLDLAQIA P

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Structure and chromosomal localization of a human water channel (AQP3) gene." Ishibashi K., Sasaki S., Saito F., Ikeuchi T., Marumo F. Genomics 27:352-354(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Kidney.
[2]	Ishibashi K. Submitted (OCT-1996) to the EMBL/GenBank/DDBJ databases Cited for: SEQUENCE REVISION TO 91; 96 AND 186.
[3]	"AQP3 deficiency in humans and the molecular basis of a novel blood group system, GIL." Roudier N., Ripoche P., Gane P., Le Pennec P.Y., Daniels G., Cartron J.-P., Bailly P. J. Biol. Chem. 277:45854-45859(2002) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), GIL BLOOD GROUP SYSTEM. Tissue: Blood.
[4]	"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)." Halleck A., Ebert L., Mkoundinya M., Schick M., Eisenstein S., Neubert P., Kstrang K., Schatten R., Shen B., Henze S., Mar W., Korn B., Zuo D., Hu Y., LaBaer J. Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[5]	"Cloning of human full-length CDSs in BD Creator(TM) system donor vector." Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A. Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[6]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Esophagus and Trachea.
[7]	SeattleSNPs variation discovery resource Submitted (JUN-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT MET-43.
[8]	"DNA sequence and analysis of human chromosome 9." Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L., Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R., Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S., Bagguley C.L. , Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E., Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M., Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J., Frankish A., Frankland J.A., French L., Fricker D.G., Garner P., Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S., Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E., Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D., Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E., Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K., Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J., Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E., McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V., Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S., Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K., Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J., Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L., Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M., Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J., Dunham I. Nature 429:369-374(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[9]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[10]	"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] (ISOFORM 1). Tissue: Lung.
[11]	"Regulation of aquaporin 3 expression by magnesium ion." Okahira M., Kubota M., Iguchi K., Usui S., Hirano K. Eur. J. Pharmacol. 588:26-32(2008) [PubMed] [Europe PMC] [Abstract] Cited for: INDUCTION.
+	Additional computationally mapped references.

Web resources

dbRBC/BGMUT

Blood group antigen gene mutation database

SeattleSNPs

Cross-references

Sequence databases
EMBL GenBank DDBJ	AB001325 mRNA. Translation: BAA19237.1. AJ493597 mRNA. Translation: CAD38526.1. CR541991 mRNA. Translation: CAG46788.1. CR542025 mRNA. Translation: CAG46822.1. BT007199 mRNA. Translation: AAP35863.1. AK292208 mRNA. Translation: BAF84897.1. AK315760 mRNA. Translation: BAG38113.1. DQ083949 Genomic DNA. Translation: AAY68214.1. AL356218 Genomic DNA. Translation: CAI13311.1. CH471071 Genomic DNA. Translation: EAW58500.1. CH471071 Genomic DNA. Translation: EAW58504.1. BC013566 mRNA. Translation: AAH13566.1.
IPI	IPI00021558. IPI00216545.
PIR	A57119.
RefSeq	NP_004916.1. NM_004925.4.
UniGene	Hs.234642.
3D structure databases
ProteinModelPortal	Q92482.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q92482. 1 interaction.
STRING	9606.ENSP00000297991.
Polymorphism databases
DMDM	2497938.
Proteomic databases
PaxDb	Q92482.
PRIDE	Q92482.
Protocols and materials databases
DNASU	360.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000297991; ENSP00000297991; ENSG00000165272.
GeneID	360.
KEGG	hsa:360.
UCSC	uc003zsx.3. human.
Organism-specific databases
CTD	360.
GeneCards	GC09M033431.
HGNC	HGNC:636. AQP3.
MIM	600170. gene. 607457. phenotype.
neXtProt	NX_Q92482.
PharmGKB	PA24921.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG0580.
HOGENOM	HOG000288287.
HOVERGEN	HBG106057.
InParanoid	Q92482.
KO	K09876.
OMA	WAFANNQ.
OrthoDB	EOG4XD3RR.
PhylomeDB	Q92482.
Enzyme and pathway databases
Reactome	REACT_15518. Transmembrane transport of small molecules.
Gene expression databases
Bgee	Q92482.
CleanEx	HS_AQP3.
Genevestigator	Q92482.
GermOnline	ENSG00000165272. Homo sapiens.
Family and domain databases
Gene3D	1.20.1080.10. 1 hit.
InterPro	IPR023271. Aquaporin-like. IPR023275. Aquaporin_3. IPR000425. MIP. IPR022357. MIP_CS. [Graphical view]
PANTHER	PTHR19139. PTHR19139. 1 hit.
Pfam	PF00230. MIP. 1 hit. [Graphical view]
PRINTS	PR02015. AQUAPORIN3. PR00783. MINTRINSICP.
SUPFAM	SSF81338. MIP. 1 hit.
TIGRFAMs	TIGR00861. MIP. 1 hit.
PROSITE	PS00221. MIP. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	AQP3. human.
GenomeRNAi	360.
NextBio	1505.
SOURCE	Search...

Entry information

Entry name

AQP3_HUMAN

Accession

Primary (citable) accession number: Q92482
Secondary accession number(s): A8K843 , B2RE16, D3DRL3, O00108, Q6FGT2, Q6FGW6

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	November 1, 1997
Last modified:	May 1, 2013
This is version 120 of the entry and version 2 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.