AQP4

Protein identityUniProt · HPA

UniProt accession

P55087

Gene

AQP4

Ensembl

ENSG00000171885

Chromosome

18

Canonical length

323 aa

Protein class

Human disease related genes, Metabolic proteins, Predicted membrane proteins, Transporters

Subcellular location

Plasma membrane,Cell Junctions

Quaternary structure

Homotetramer

OverviewNCBI Gene

This gene encodes a member of the aquaporin family of intrinsic membrane proteins that function as water-selective channels in the plasma membranes of many cells. This protein is the predominant aquaporin found in brain and has an important role in brain water homeostasis. Alternatively spliced transcript variants encoding different isoforms have been described for this gene. Additional isoforms, resulting from the use of alternative in-frame translation initiation codons, have also been described. Recent studies provided evidence for translational readthrough in this gene, and expression of C-terminally extended isoforms via the use of an alternative in-frame translation termination codon. [provided by RefSeq, Jun 2018]

Canonical amino-acid sequenceUniProt

323 residues, UniProt reviewed canonical sequence.

>P55087|AQP4
     1  MSDRPTARRW GKCGPLCTRE NIMVAFKGVW TQAFWKAVTA EFLAMLIFVL LSLGSTINWG
    61  GTEKPLPVDM VLISLCFGLS IATMVQCFGH ISGGHINPAV TVAMVCTRKI SIAKSVFYIA
   121  AQCLGAIIGA GILYLVTPPS VVGGLGVTMV HGNLTAGHGL LVELIITFQL VFTIFASCDS
   181  KRTDVTGSIA LAIGFSVAIG HLFAINYTGA SMNPARSFGP AVIMGNWENH WIYWVGPIIG
   241  AVLAGGLYEY VFCPDVEFKR RFKEAFSKAA QQTKGSYMEV EDNRSQVETD DLILKPGVVH
   301  VIDVDRGEEK KGKDQSGEVL SSV

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against AQP4 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Cell surface

Secreted

No

Transmembrane segments

6

Mean surface accessibility (rSASA)

0.37

Highest tissue expression

354 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about AQP4.

Disease | AllUniProt

Conditions AQP4 is implicated in, by any mechanism.

• Megalencephalic leukoencephalopathy with subcortical cysts 4, remitting (MLC4) MIM:620448

Disease | GeneticClinVar

2 pathogenic / likely-pathogenic of 54 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Intellectual disability
• Megalencephalic leukoencephalopathy with subcortical cysts 4, remitting

Disease | ImmuneIEDB

Conditions an epitope on AQP4 was assayed in.

• neuromyelitis optica B and T cell
• multiple sclerosis B and T cell
• autoimmune disease of central nervous system T cell
• Sjogren's syndrome B cell
• systemic lupus erythematosus B cell

Disease | AutoantibodyPubMed

Conditions in which antibodies against AQP4 are reported. Each links to that disease's full target list.

• Neuromyelitis Optica 1,174
• Multiple Sclerosis 220
• Sjogren's Syndrome 32
• Neoplasm Recurrence, Local 27
• Lupus Erythematosus, Systemic 26
• COVID-19 21
• Myasthenia Gravis 21
• Encephalitis 17
• Autoimmune Diseases of the Nervous System 14
• Encephalomyelitis, Autoimmune, Experimental 11
• Paraneoplastic Syndromes, Nervous System 7
• Seizures 7
• Lung Neoplasms 6
• Pain 6
• Adenocarcinoma 5
• Brain Diseases 5
• Breast Neoplasms 5
• Muscle Weakness 5
• Guillain-Barre Syndrome 4
• Hashimoto Disease 4

Showing 20 of 59 — disease pages carrying at least 10 antigens.

ReferencesPubMed · IEDB

Publications for AQP4 from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.

Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. IEDB — curated epitope assays from the Immune Epitope Database (Vita et al., Nucleic Acids Research 2019). Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.99

gnomAD pLI

0

gnomAD missense Z

-0.19

DepMap mean gene effect

0.06

DepMap dependency class

none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 2% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• cellular response to type II interferon
• cerebrospinal fluid circulation
• intracellular water homeostasis
• multicellular organismal-level water homeostasis
• protein homotetramerization
• renal water homeostasis
• water transport

Molecular functions

• identical protein binding
• water channel activity

Cellular components

• astrocyte end-foot
• basolateral plasma membrane
• cytoplasm
• endosome membrane
• external side of plasma membrane
• extracellular region
• plasma membrane
• sarcolemma

Protein domainsUniProt · Pfam · InterPro

• Major intrinsic protein
• Major intrinsic protein, conserved site
• Aquaporin-like
• Aquaporin transporter
• Major intrinsic protein

KeywordsUniProt

• Cell membrane
• Cell projection
• Endosome
• Glycoprotein
• Lipoprotein
• Membrane
• Palmitate
• Phosphoprotein
• Repeat
• Transmembrane
• Transmembrane helix
• Transport