P55087 (AQP4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Aquaporin-4
Short name=AQP-4

Alternative name(s):
Mercurial-insensitive water channel
Short name=MIWC
WCH4

Gene names

Name:

AQP4

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	323 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Forms a water-specific channel. Osmoreceptor which regulates body water balance and mediates water flow within the central nervous system.
Subunit structure	Homotetramer. Ref.6
Subcellular location	Membrane; Multi-pass membrane protein.
Tissue specificity	Brain - muscle >> heart, kidney, lung, and trachea.
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).
Post-translational modification	Phosphorylation by PKC at Ser-180 reduces conductance by 50%. Phosphorylation by PKG at Ser-111 in response to glutamats increases conductance by 40% By similarity.
Sequence similarities	Belongs to the MIP/aquaporin (TC 1.A.8) family. [View classification]
Sequence caution	The sequence AAC50284.1 differs from that shown. Reason: Erroneous initiation. The sequence AAC52112.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Biological process	Transport
Cellular component	Membrane
Coding sequence diversity	Alternative splicing
Domain	Repeat Transmembrane Transmembrane helix
PTM	Glycoprotein Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	cellular response to interferon-gamma Inferred from direct assay. Source: UniProtKB excretion Traceable author statement. Source: ProtInc nervous system development Traceable author statement. Source: ProtInc
Cellular component	cytoplasm Inferred from direct assay. Source: UniProtKB external side of plasma membrane Inferred from direct assay. Source: UniProtKB integral to plasma membrane Traceable author statement. Source: ProtInc
Molecular function	water channel activity Inferred from experiment. Source: Reactome
Complete GO annotation...

Alternative products

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

Isoform 2 (identifier: P55087-1)

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 1 (identifier: P55087-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-22: Missing.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 323

323

Aquaporin-4

PRO_0000063948

Regions

Topological domain

1 – 36

36

Cytoplasmic Potential

Transmembrane

37 – 57

21

Helical; Potential

Topological domain

58 – 64

7

Extracellular Potential

Transmembrane

65 – 85

21

Helical; Potential

Topological domain

86 – 115

30

Cytoplasmic Potential

Transmembrane

116 – 136

21

Helical; Potential

Topological domain

137 – 155

19

Extracellular Potential

Transmembrane

156 – 176

21

Helical; Potential

Topological domain

177 – 184

8

Cytoplasmic Potential

Transmembrane

185 – 205

21

Helical; Potential

Topological domain

206 – 231

26

Extracellular Potential

Transmembrane

232 – 252

21

Helical; Potential

Topological domain

253 – 323

71

Cytoplasmic Potential

Motif

97 – 99

3

NPA 1

Motif

213 – 215

3

NPA 2

Amino acid modifications

Modified residue

111

1

Phosphoserine; by PKG By similarity

Modified residue

180

1

Phosphoserine; by PKC By similarity

Modified residue

285

1

Phosphoserine By similarity

Modified residue

321

1

Phosphoserine By similarity

Glycosylation

153

1

N-linked (GlcNAc...) Potential

Glycosylation

206

1

N-linked (GlcNAc...) Potential

Natural variations

Alternative sequence

1 – 22

22

Missing in isoform 1.

VSP_003232

Experimental info

Sequence conflict

246

1

G → A in AAC52112. Ref.1

Sequence conflict

287 – 288

2

VE → AK in AAC52112. Ref.1

Sequence conflict

296

1

P → L in AAC52112. Ref.1

Secondary structure

1

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323

Helix Strand Turn

Details...

Helix

33 – 52

20

Helix

70 – 76

7

Helix

80 – 87

8

Helix

98 – 106

9

Helix

112 – 123

12

Helix

133 – 136

4

Turn

139 – 141

3

Helix

161 – 177

17

Helix

189 – 192

4

Turn

196 – 198

3

Turn

202 – 207

6

Helix

214 – 217

4

Turn

221 – 223

3

Helix

230 – 233

4

Helix

248 – 252

5

Sequences

	Sequence		Length	Mass (Da)
	Isoform 2 [UniParc]. Last modified November 1, 1997. Version 2. Checksum: 1A1600CF0DC11052	FASTA	323	34,830
	10 20 30 40 50 60 MSDRPTARRW GKCGPLCTRE NIMVAFKGVW TQAFWKAVTA EFLAMLIFVL LSLGSTINWG 70 80 90 100 110 120 GTEKPLPVDM VLISLCFGLS IATMVQCFGH ISGGHINPAV TVAMVCTRKI SIAKSVFYIA 130 140 150 160 170 180 AQCLGAIIGA GILYLVTPPS VVGGLGVTMV HGNLTAGHGL LVELIITFQL VFTIFASCDS 190 200 210 220 230 240 KRTDVTGSIA LAIGFSVAIG HLFAINYTGA SMNPARSFGP AVIMGNWENH WIYWVGPIIG 250 260 270 280 290 300 AVLAGGLYEY VFCPDVEFKR RFKEAFSKAA QQTKGSYMEV EDNRSQVETD DLILKPGVVH 310 320 VIDVDRGEEK KGKDQSGEVL SSV
	Isoform 1 [UniParc]. Checksum: C91C3D006C1B75A0	FASTA	301	32,300
	10 20 30 40 50 60 MVAFKGVWTQ AFWKAVTAEF LAMLIFVLLS LGSTINWGGT EKPLPVDMVL ISLCFGLSIA 70 80 90 100 110 120 TMVQCFGHIS GGHINPAVTV AMVCTRKISI AKSVFYIAAQ CLGAIIGAGI LYLVTPPSVV 130 140 150 160 170 180 GGLGVTMVHG NLTAGHGLLV ELIITFQLVF TIFASCDSKR TDVTGSIALA IGFSVAIGHL 190 200 210 220 230 240 FAINYTGASM NPARSFGPAV IMGNWENHWI YWVGPIIGAV LAGGLYEYVF CPDVEFKRRF 250 260 270 280 290 300 KEAFSKAAQQ TKGSYMEVED NRSQVETDDL ILKPGVVHVI DVDRGEEKKG KDQSGEVLSS V

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"cDNA cloning, gene organization, and chromosomal localization of a human mercurial insensitive water channel. Evidence for distinct transcriptional units." Yang B., Ma T., Verkman A.S. J. Biol. Chem. 270:22907-22913(1995) [PubMed: 7559426] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Fetal brain.
[2]	"A water channel closely related to rat brain aquaporin 4 is expressed in acid- and pepsinogen-secretory cells of human stomach." Misaka T., Abe K., Iwabuchi K., Kusakabe Y., Ichinose M., Miki K., Emori Y., Arai S. FEBS Lett. 381:208-212(1996) [PubMed: 8601457] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	"The human AQP4 gene: definition of the locus encoding two water channel polypeptides in brain." Lu M., Lee M.D., Smith B.L., Jung J.S., Agre P., Verdijk M.A.J., Merkx G., Rijss J.P.L., Deen P.M.T. Proc. Natl. Acad. Sci. U.S.A. 93:10908-10912(1996) [PubMed: 8855281] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[4]	"DNA sequence and analysis of human chromosome 18." Nusbaum C., Zody M.C., Borowsky M.L., Kamal M., Kodira C.D., Taylor T.D., Whittaker C.A., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Yang X., Abouelleil A., Allen N.R., Anderson S., Bloom T., Bugalter B., Butler J. , Cook A., DeCaprio D., Engels R., Garber M., Gnirke A., Hafez N., Hall J.L., Norman C.H., Itoh T., Jaffe D.B., Kuroki Y., Lehoczky J., Lui A., Macdonald P., Mauceli E., Mikkelsen T.S., Naylor J.W., Nicol R., Nguyen C., Noguchi H., O'Leary S.B., Piqani B., Smith C.L., Talamas J.A., Topham K., Totoki Y., Toyoda A., Wain H.M., Young S.K., Zeng Q., Zimmer A.R., Fujiyama A., Hattori M., Birren B.W., Sakaki Y., Lander E.S. Nature 437:551-555(2005) [PubMed: 16177791] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"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: Lung.
[6]	"Crystal structure of human aquaporin 4 at 1.8 A and its mechanism of conductance." Ho J.D., Yeh R., Sandstrom A., Chorny I., Harries W.E., Robbins R.A., Miercke L.J., Stroud R.M. Proc. Natl. Acad. Sci. U.S.A. 106:7437-7442(2009) [PubMed: 19383790] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 32-254, SUBUNIT.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

U34846 mRNA. Translation: AAC52112.1. Different initiation.
U34845 mRNA. Translation: AAC50284.1. Different initiation.
D63412 mRNA. Translation: BAA09715.1.
U63622 mRNA. Translation: AAB26957.1.
U63623 mRNA. Translation: AAB26958.1.
AC018371 Genomic DNA. No translation available.
BC022286 mRNA. Translation: AAH22286.1.

IPI

IPI00022799.
IPI00221189.

PIR

I39178.

RefSeq

NP_001641.1. NM_001650.4.
NP_004019.1. NM_004028.3.

UniGene

Hs.315369.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3GD8	X-ray	1.80	A	32-254	[»]

ProteinModelPortal

P55087.

SMR

P55087. Positions 32-254.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-48842N.

STRING

P55087.

Protein family/group databases

TCDB

1.A.8.8.5. major intrinsic protein (MIP) family.

PTM databases

PhosphoSite

P55087.

Polymorphism databases

DMDM

2506859.

Proteomic databases

PRIDE

P55087.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000383168; ENSP00000372654; ENSG00000171885.

GeneID

361.

KEGG

hsa:361.

UCSC

uc002kvz.1. human.
uc002kwa.1. human.

Organism-specific databases

CTD

361.

GeneCards

GC18M024432.

H-InvDB

HIX0014377.

HGNC

HGNC:637. AQP4.

HPA

CAB005079.
HPA014784.

MIM

600308. gene.

neXtProt

NX_P55087.

PharmGKB

PA24922.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG04823.

HOGENOM

HBG705794.

HOVERGEN

HBG000312.

InParanoid

P55087.

OMA

AFWKAVT.

OrthoDB

EOG46Q6T5.

PhylomeDB

P55087.

Enzyme and pathway databases

Reactome

REACT_15518. Transmembrane transport of small molecules.

Gene expression databases

ArrayExpress

P55087.

Bgee

P55087.

CleanEx

HS_AQP4.

Genevestigator

P55087.

GermOnline

ENSG00000171885. 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

K09866.

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

1509.

SOURCE

Search...

Entry information

Entry name

AQP4_HUMAN

Accession

Primary (citable) accession number: P55087
Secondary accession number(s): P78564

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1996
Last sequence update:	November 1, 1997
Last modified:	January 25, 2012
This is version 107 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.