Reviewed, UniProtKB/Swiss-Prot P29972 (AQP1_HUMAN)

Names and origin

Protein names

Recommended name:
    Aquaporin-1
      Short name=AQP-1
Alternative name(s):
    Aquaporin-CHIP
    Water channel protein for red blood cells and kidney proximal tubule
    Urine water channel

Gene names

Name:	AQP1
Synonyms:	CHIP28

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	269 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Forms a water-specific channel that provides the plasma membranes of red cells and kidney proximal tubules with high permeability to water, thereby permitting water to move in the direction of an osmotic gradient. Ref.10
Subunit structure	Homotetramer.
Subcellular location	Membrane; Multi-pass membrane protein.
Tissue specificity	Expressed in a number of tissues including erythrocytes, renal tubules, retinal pigment epithelium, heart, lung, skeletal muscle, kidney and pancreas. Weakly expressed in brain, placenta and liver.
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	AQP1 is responsible for the Colton blood group system. Approximately 92% of Caucasians are Co(A+B-) (Ala-46), approximately 8% are Co(A+B+), and only 0.2% are Co(A-B+) (Val-46). Co(A-B-) which is very rare, is due to a complete absence of AQP1.
Miscellaneous	Pharmacologically inhibited by submillimolar concentrations of mercury.
Sequence similarities	Belongs to the MIP/aquaporin (TC 1.A.8) family. [View classification]

Ontologies

Keywords
Biological process	Transport
Cellular component	Membrane
Coding sequence diversity	Polymorphism
Domain	Repeat Transmembrane
Molecular function	Blood group antigen
PTM	Glycoprotein Phosphoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing
Gene Ontology (GO)
Biological process	ammonium transport Inferred from direct assay. Source: UniProtKB carbon dioxide transport Inferred from direct assay. Source: UniProtKB excretion Ref.1 Traceable author statement. Source: ProtInc water transport Ref.20 Traceable author statement. Source: ProtInc
Cellular component	apical plasma membrane Inferred from direct assay. Source: UniProtKB basolateral plasma membrane Inferred from direct assay. Source: UniProtKB integral to plasma membrane Ref.1 Traceable author statement. Source: ProtInc
Molecular function	ammonia transporter activity Inferred from direct assay. Source: UniProtKB protein binding Inferred from physical interaction. Source: IntAct
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
MDFI	Q99750	3	EBI-745213,EBI-724076

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed Ref.9

Chain

2 – 269

268

Aquaporin-1

PRO_0000063920

Regions

Topological domain

2 – 7

6

Cytoplasmic Ref.12

Transmembrane

8 – 36

29

Helix 1

Topological domain

37 – 48

12

Extracellular Ref.12

Transmembrane

49 – 66

18

Helix 2

Topological domain

67 – 70

4

Cytoplasmic Ref.12

Topological domain

71 – 76

6

In membrane Ref.12

Transmembrane

77 – 84

8

Helix B

Topological domain

85 – 94

10

Cytoplasmic Ref.12

Transmembrane

95 – 115

21

Helix 3

Topological domain

116 – 136

21

Extracellular Ref.12

Transmembrane

137 – 155

19

Helix 4

Topological domain

156 – 166

11

Cytoplasmic Ref.12

Transmembrane

167 – 183

17

Helix 5

Topological domain

184 – 186

3

Extracellular Ref.12

Topological domain

187 – 192

6

In membrane Ref.12

Transmembrane

193 – 200

8

Helix E

Topological domain

201 – 207

7

Extracellular Ref.12

Transmembrane

208 – 228

21

Helix 6

Topological domain

229 – 269

41

Cytoplasmic Ref.12

Motif

76 – 78

3

NPA 1

Motif

192 – 194

3

NPA 2

Compositional bias

159 – 162

4

Poly-Arg

Sites

Site

56

1

Substrate discrimination

Site

180

1

Substrate discrimination

Site

189

1

Hg(2+)-sensitive residue

Site

195

1

Substrate discrimination

Amino acid modifications

Modified residue

246

1

Phosphothreonine By similarity

Modified residue

247

1

Phosphoserine By similarity

Modified residue

262

1

Phosphoserine Ref.13

Glycosylation

42

1

N-linked (GlcNAc...)

Glycosylation

205

1

N-linked (GlcNAc...) Potential

Natural variations

Natural variant

38

1

P → L in Co(A-B-) antigen; non functional AQP1; red cells show low osmotic water permeability. Ref.20

VAR_013279

Natural variant

45

1

A → V in Co(A-B+) antigen. dbSNP rs28362692. Ref.5 Ref.19

VAR_004400

Natural variant

165

1

G → D: dbSNP rs28362731. Ref.5

VAR_022318

Experimental info

Sequence conflict

45

1

A → T in AAH22486. Ref.7

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

269

Helix Strand Turn

Details...

Helix

8 – 35

28

Beta strand

37 – 42

6

Helix

48 – 65

18

Beta strand

68 – 71

4

Helix

76 – 83

8

Helix

94 – 114

21

Turn

119 – 122

4

Beta strand

132 – 135

4

Helix

136 – 154

19

Helix

166 – 182

17

Turn

183 – 185

3

Helix

192 – 199

8

Helix

207 – 227

21

Sequences

	Sequence		Length	Mass (Da)
	P29972-1 [UniParc]. Last modified January 23, 2007. Version 3. Checksum: BA204D82FB26352E	FASTA	269	28,526
	10 20 30 40 50 60 MASEFKKKLF WRAVVAEFLA TTLFVFISIG SALGFKYPVG NNQTAVQDNV KVSLAFGLSI 70 80 90 100 110 120 ATLAQSVGHI SGAHLNPAVT LGLLLSCQIS IFRALMYIIA QCVGAIVATA ILSGITSSLT 130 140 150 160 170 180 GNSLGRNDLA DGVNSGQGLG IEIIGTLQLV LCVLATTDRR RRDLGGSAPL AIGLSVALGH 190 200 210 220 230 240 LLAIDYTGCG INPARSFGSA VITHNFSNHW IFWVGPFIGG ALAVLIYDFI LAPRSSDLTD 250 260 RVKVWTSGQV EEYDLDADDI NSRVEMKPK

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Isolation of the cDNA for erythrocyte integral membrane protein of 28 kilodaltons: member of an ancient channel family." Preston G.M., Agre P. Proc. Natl. Acad. Sci. U.S.A. 88:11110-11114(1991) [PubMed: 1722319] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE.
[2]	"The human aquaporin-CHIP gene. Structure, organization, and chromosomal localization." Moon C., Preston G.M., Griffin C.A., Jabs E.W., Agre P. J. Biol. Chem. 268:15772-15778(1993) [PubMed: 8340403] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]	"Characterization of the 3' UTR sequence encoded by the AQP-1 gene in human retinal pigment epithelium." Ruiz A.C., Bok D. Biochim. Biophys. Acta 1282:174-178(1996) [PubMed: 8703970] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Retinal pigment epithelium.
[4]	"The water channel gene in human uterus." Li X., Yu H., Koide S.S. Biochem. Mol. Biol. Int. 32:371-377(1994) [PubMed: 7517253] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Uterus.
[5]	SeattleSNPs variation discovery resource Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS VAL-45 AND ASP-165.
[6]	"The DNA sequence of human chromosome 7." Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H., Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K., Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A., Delehaunty K.D., Miner T.L. , Nash W.E., Cordes M., Du H., Sun H., Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A., Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P., Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M., Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S., Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., Strowmatt C., Latreille P., Miller N., Johnson D., Murray J., Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E., Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E., Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A., Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A., Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R., McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H., Wilson R.K. Nature 424:157-164(2003) [PubMed: 12853948] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	"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: Brain.
[8]	"Human chondrocytes in situ express aquaporin water channels: changes in AQP1 abundance in pathologies of articular cartilage." Trujillo E., Gonzalez T., Martin-Vasallo P., Marples D., Mobasheri A. Submitted (FEB-2002) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE OF 5-269. Tissue: Articular cartilage.
[9]	"Erythrocyte Mr 28,000 transmembrane protein exists as a multisubunit oligomer similar to channel proteins." Smith B.L., Agre P. J. Biol. Chem. 266:6407-6415(1991) [PubMed: 2007592] [Abstract] Cited for: PROTEIN SEQUENCE OF 2-36.
[10]	"Appearance of water channels in Xenopus oocytes expressing red cell CHIP28 protein." Preston G.M., Carroll T.P., Guggino W.B., Agre P. Science 256:385-387(1992) [PubMed: 1373524] [Abstract] Cited for: FUNCTION.
[11]	"The mercury-sensitive residue at cysteine 189 in the CHIP28 water channel." Preston G.M., Jung J.S., Guggino W.B., Agre P. J. Biol. Chem. 268:17-20(1993) [PubMed: 7677994] [Abstract] Cited for: TARGET OF MERCURY INHIBITION.
[12]	"Membrane topology of aquaporin CHIP. Analysis of functional epitope-scanning mutants by vectorial proteolysis." Preston G.M., Jung J.S., Guggino W.B., Agre P. J. Biol. Chem. 269:1668-1673(1994) [PubMed: 7507481] [Abstract] Cited for: TOPOLOGY.
[13]	"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle." Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M. Mol. Cell 31:438-448(2008) [PubMed: 18691976] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-262, MASS SPECTROMETRY.
[14]	"The three-dimensional structure of human erythrocyte aquaporin CHIP." Walz T., Smith B.L., Agre P., Engel A. EMBO J. 13:2985-2993(1994) [PubMed: 7518771] [Abstract] Cited for: STRUCTURE BY ELECTRON MICROSCOPY (1.6 ANGSTROMS).
[15]	"The three-dimensional structure of aquaporin-1." Walz T., Hirai T., Murata K., Heymann J.B., Mitsuoka K., Fujiyoshi Y., Smith B.L., Agre P., Engel A. Nature 387:624-627(1997) [PubMed: 9177353] [Abstract] Cited for: STRUCTURE BY ELECTRON MICROSCOPY (6 ANGSTROMS).
[16]	"Structural determinants of water permeation through aquaporin-1." Murata K., Mitsuoka K., Hirai T., Walz T., Agre P., Heymann J.B., Engel A., Fujiyoshi Y. Nature 407:599-605(2000) [PubMed: 11034202] [Abstract] Cited for: STRUCTURE BY ELECTRON MICROSCOPY (3.8 ANGSTROMS).
[17]	"A refined structure of human aquaporin-1." de Groot B.L., Engel A., Grubmueller H. FEBS Lett. 504:206-211(2001) [PubMed: 11532455] [Abstract] Cited for: STRUCTURE BY ELECTRON MICROSCOPY (3.54 ANGSTROMS).
[18]	"Visualization of a water-selective pore by electron crystallography in vitreous ice." Ren G., Reddy V.S., Cheng A., Melnyk P., Mitra A.K. Proc. Natl. Acad. Sci. U.S.A. 98:1398-1403(2001) [PubMed: 11171962] [Abstract] Cited for: STRUCTURE BY ELECTRON MICROSCOPY (3.7 ANGSTROMS).
[19]	"Human red cell aquaporin CHIP. I. Molecular characterization of ABH and Colton blood group antigens." Smith B.L., Preston G.M., Spring F., Anstee D.J., Agre P. J. Clin. Invest. 94:1043-1049(1994) [PubMed: 7521882] [Abstract] Cited for: VARIANT BLOOD GROUP COLTON VAL-45.
[20]	"Mutations in aquaporin-1 in phenotypically normal humans without functional CHIP water channels." Preston G.M., Smith B.L., Zeidel M.L., Moulds J.J., Agre P. Science 265:1585-1587(1994) [PubMed: 7521540] [Abstract] Cited for: VARIANT LEU-38.
+	Additional computationally mapped references.

Web resources

dbRBC/BGMUT

Blood group antigen gene mutation database

SeattleSNPs

Protein Spotlight

Liquid states - Issue 36 of July 2003

Cross-references

Sequence databases

EMBLGenBankDDBJ

M77829 mRNA. Translation: AAA58425.1.
U41517 mRNA. Translation: AAC50648.1.
U41518 mRNA. Translation: AAC50649.1.
S73482 mRNA. Translation: AAB31193.1.
AC004691 Genomic DNA. Translation: AAC16481.1.
AC005155 Genomic DNA. Translation: AAC23788.1.
AY953319 Genomic DNA. Translation: AAX24129.1.
BC022486 mRNA. Translation: AAH22486.1.
AF480415 Genomic DNA. Translation: AAL87136.1.

IPI

IPI00024689.

PIR

A41616.
I52366.

RefSeq

NP_932766.1.

UniGene

Hs.660192
Hs.76152

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1FQY	X-ray	3.80	A	1-269	[»]
1H6I	X-ray	3.54	A	1-269	[»]
1IH5	X-ray	3.70	A	1-269	[»]

SMR

P29972. Positions 1-247.

ModBase

Search...

Protein-protein interaction databases

IntAct

P29972. 7 interactions.

STRING

P29972.

Protein family/group databases

TCDB

1.A.8.8.1. major intrinsic protein (MIP) family.

PTM databases

PhosphoSite

P29972.

Proteomic databases

PRIDE

P29972.

Genome annotation databases

Ensembl

ENST00000013222; ENSP00000013222; ENSG00000106125; Homo sapiens. [Genome view]
ENST00000265298; ENSP00000265298; ENSG00000106125; Homo sapiens. [Genome view]
ENST00000265299; ENSP00000265299; ENSG00000106125; Homo sapiens. [Genome view]
ENST00000311813; ENSP00000311165; ENSG00000106125; Homo sapiens. [Genome view]
ENST00000381693; ENSP00000371112; ENSG00000106125; Homo sapiens. [Genome view]
ENST00000409539; ENSP00000386961; ENSG00000106125; Homo sapiens. [Genome view]
ENST00000409611; ENSP00000387178; ENSG00000106125; Homo sapiens. [Genome view]
ENST00000409881; ENSP00000386332; ENSG00000106125; Homo sapiens. [Genome view]
ENST00000409899; ENSP00000386712; ENSG00000106125; Homo sapiens. [Genome view]
ENST00000413400; ENSP00000397179; ENSG00000106125; Homo sapiens. [Genome view]
ENST00000425612; ENSP00000389878; ENSG00000106125; Homo sapiens. [Genome view]
ENST00000434909; ENSP00000395059; ENSG00000106125; Homo sapiens. [Genome view]
ENST00000441328; ENSP00000405698; ENSG00000106125; Homo sapiens. [Genome view]
ENST00000451002; ENSP00000415137; ENSG00000106125; Homo sapiens. [Genome view]
ENST00000458257; ENSP00000390918; ENSG00000106125; Homo sapiens. [Genome view]

GeneID

358.

KEGG

hsa:358.

UCSC

uc003tbv.1. human.

Organism-specific databases

CTD

358.

GeneCards

GC07P030917.

H-InvDB

HIX0006573.

HGNC

HGNC:633. AQP1.

HPA

CAB001707.
HPA019206.

MIM

107776. gene.
110450. phenotype.

PharmGKB

PA24918.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

P29972.

HOVERGEN

P29972.

OMA

IFRALMY.

Gene expression databases

ArrayExpress

P29972.

Bgee

P29972.

CleanEx

HS_AQP1.

Genevestigator

P29972.

GermOnline

ENSG00000106125. Homo sapiens.

Family and domain databases

InterPro

IPR012269. Aquaporin.
IPR000425. MIP.
[Graphical view]

Gene3D

G3DSA:1.20.1080.10. MIP. 1 hit.

PANTHER

PTHR19139. MIP. 1 hit.

Pfam

PF00230. MIP. 1 hit.
[Graphical view]

PRINTS

PR00783. MINTRINSICP.

ProDom

PD000295. MIP. 1 hit.
[Graphical view] [Entries sharing at least one domain]

TIGRFAMs

TIGR00861. MIP. 1 hit.

PROSITE

PS00221. MIP. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

DrugBank

DB00819. Acetazolamide.

NextBio

1497.

SOURCE

Search...

Entry information

Entry name

AQP1_HUMAN

Accession

Primary (citable) accession number: P29972
Secondary accession number(s): Q8TBI5, Q8TDC1

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 1, 1993
Last sequence update:	January 23, 2007
Last modified:	November 3, 2009
This is version 114 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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.