O35240 · ASIC3_RAT
- ProteinAcid-sensing ion channel 3
- GeneAsic3
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids533 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Cation channel with high affinity for sodium, which is gated by extracellular protons and inhibited by the diuretic amiloride. Generates a biphasic current with a fast inactivating and a slow sustained phase. In sensory neurons is proposed to mediate the pain induced by acidosis that occurs in ischemic, damaged or inflamed tissue. May be involved in hyperalgesia. May play a role in mechanoreception. Heteromeric channel assembly seems to modulate channel properties.
Miscellaneous
Potentiated by FMRFamide-related neuropeptides (By similarity).
Sensitized and potentiated by NPFF and NPSF. Regulated by lactate and Ca2+. Specifically inhibited by APETx2, a sea anemone toxin. Inhibited by anti-inflammatory drugs like salicylic acid.
Sensitized and potentiated by NPFF and NPSF. Regulated by lactate and Ca2+. Specifically inhibited by APETx2, a sea anemone toxin. Inhibited by anti-inflammatory drugs like salicylic acid.
Features
Showing features for site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Site | 26 | Potassium ion selectivity and permeability | ||||
Sequence: T |
GO annotations
all annotations | all molecular function | virus receptor activity | dna binding | rna binding | cytoskeletal motor activity | catalytic activity | gtpase activity | structural molecule activity | transporter activity | cytoskeletal protein binding | lipid binding | cyclase activity | antioxidant activity | oxidoreductase activity | transferase activity | hydrolase activity | lyase activity | isomerase activity | ligase activity | protein tag activity | cargo receptor activity | histone binding | protein folding chaperone | translation regulator activity | nutrient reservoir activity | receptor ligand activity | molecular transducer activity | molecular adaptor activity | toxin activity | cell adhesion mediator activity | molecular function regulator activity | virus coreceptor activity | catalytic activity, acting on a protein | catalytic activity, acting on dna | catalytic activity, acting on rna | molecular carrier activity | transcription regulator activity | general transcription initiation factor activity | molecular sensor activity | molecular sequestering activity | atp-dependent activity | other molecular function | all biological process | mitotic cell cycle | cytokinesis | cytoplasmic translation | immune system process | muscle system process | circulatory system process | renal system process | respiratory system process | carbohydrate metabolic process | generation of precursor metabolites and energy | dna replication | dna repair | dna recombination | chromatin organization | dna-templated transcription | regulation of dna-templated transcription | trna metabolic process | protein folding | protein glycosylation | amino acid metabolic process | modified amino acid metabolic process | lipid metabolic process | vitamin metabolic process | sulfur compound metabolic process | intracellular protein transport | nucleocytoplasmic transport | autophagy | inflammatory response | mitochondrion organization | cytoskeleton organization | microtubule-based movement | peroxisome organization | lysosome organization | chromosome segregation | cell adhesion | establishment or maintenance of cell polarity | programmed cell death | photosynthesis | mrna metabolic process | snrna metabolic process | vesicle-mediated transport | reproductive process | digestive system process | signaling | cell differentiation | protein catabolic process | extracellular matrix organization | regulatory ncrna-mediated gene silencing | telomere organization | cell junction organization | wound healing | ribosome biogenesis | cilium organization | anatomical structure development | cell motility | nervous system process | endocrine process | protein maturation | transmembrane transport | nucleobase-containing small molecule metabolic process | hepaticobiliary system process | membrane organization | protein-containing complex assembly | cell wall organization or biogenesis | nitrogen cycle metabolic process | protein localization to plasma membrane | defense response to other organism | detoxification | meiotic nuclear division | mitotic nuclear division | mitochondrial gene expression | carbohydrate derivative metabolic process | other biological process | all cellular component | nuclear chromosome | extracellular region | extracellular space | cell wall | nucleus | nuclear envelope | nucleoplasm | chromosome | nucleolus | mitochondrion | lysosome | endosome | vacuole | peroxisome | endoplasmic reticulum | golgi apparatus | lipid droplet | microtubule organizing center | cytosol | ribosome | cytoskeleton | plasma membrane | cilium | plastid | thylakoid | external encapsulating structure | extracellular matrix | cytoplasmic vesicle | organelle | other cellular component | |||
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Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Protein family/group databases
Names & Taxonomy
Protein names
- Recommended nameAcid-sensing ion channel 3
- Short namesASIC3
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Rattus
Accessions
- Primary accessionO35240
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Cell membrane ; Multi-pass membrane protein
Note: In part cytoplasmic in cochlea cells (By similarity).
Cell surface expression may be stabilized by interaction with LIN7B and cytoplasmic retention by interaction with DLG4
Cell surface expression may be stabilized by interaction with LIN7B and cytoplasmic retention by interaction with DLG4
Features
Showing features for topological domain, transmembrane.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Topological domain | 1-19 | Cytoplasmic | ||||
Sequence: MKPRSGLEEAQRRQASDIR | ||||||
Transmembrane | 20-40 | Helical | ||||
Sequence: VFASSCTMHGLGHIFGPGGLT | ||||||
Topological domain | 41-435 | Extracellular | ||||
Sequence: LRRGLWATAVLLSLAAFLYQVAERVRYYGEFHHKTTLDERESHQLTFPAVTLCNINPLRRSRLTPNDLHWAGTALLGLDPAEHAAYLRALGQPPAPPGFMPSPTFDMAQLYARAGHSLEDMLLDCRYRGQPCGPENFTVIFTRMGQCYTFNSGAHGAELLTTPKGGAGNGLEIMLDVQQEEYLPIWKDMEETPFEVGIRVQIHSQDEPPAIDQLGFGAAPGHQTFVSCQQQQLSFLPPPWGDCNTASLDPDDFDPEPSDPLGSPRPRPSPPYSLIGCRLACESRYVARKCGCRMMHMPGNSPVCSPQQYKDCASPALDAMLRKDTCVCPNPCATTRYAKELSMVRIPSRASARYLARKYNRSESYITENVLVLDIFFEALNYEAVEQKAAYEVSE | ||||||
Transmembrane | 436-456 | Helical | ||||
Sequence: LLGDIGGQMGLFIGASLLTIL | ||||||
Topological domain | 457-533 | Cytoplasmic | ||||
Sequence: EILDYLCEVFQDRVLGYFWNRRSAQKRSGNTLLQEELNGHRTHVPHLSLGPRPPTTPCAVTKTLSASHRTCYLVTRL |
Keywords
- Cellular component
Phenotypes & Variants
Features
Showing features for mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 20 | No effect on selectivity or channel function. | ||||
Sequence: V → P | ||||||
Mutagenesis | 21 | Loss of channel function. | ||||
Sequence: F → S | ||||||
Mutagenesis | 26 | Alters selectivity of the channel for sodium. No effect on channel function. | ||||
Sequence: T → K | ||||||
Mutagenesis | 40 | Loss of regulation by PKC through PRKCABP; when associated with G-523. | ||||
Sequence: T → G | ||||||
Mutagenesis | 523 | Loss of regulation by PKC through PRKCABP; when associated with G-40. | ||||
Sequence: S → G |
Chemistry
PTM/Processing
Features
Showing features for chain, modified residue, disulfide bond, glycosylation.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000181303 | 1-533 | Acid-sensing ion channel 3 | |||
Sequence: MKPRSGLEEAQRRQASDIRVFASSCTMHGLGHIFGPGGLTLRRGLWATAVLLSLAAFLYQVAERVRYYGEFHHKTTLDERESHQLTFPAVTLCNINPLRRSRLTPNDLHWAGTALLGLDPAEHAAYLRALGQPPAPPGFMPSPTFDMAQLYARAGHSLEDMLLDCRYRGQPCGPENFTVIFTRMGQCYTFNSGAHGAELLTTPKGGAGNGLEIMLDVQQEEYLPIWKDMEETPFEVGIRVQIHSQDEPPAIDQLGFGAAPGHQTFVSCQQQQLSFLPPPWGDCNTASLDPDDFDPEPSDPLGSPRPRPSPPYSLIGCRLACESRYVARKCGCRMMHMPGNSPVCSPQQYKDCASPALDAMLRKDTCVCPNPCATTRYAKELSMVRIPSRASARYLARKYNRSESYITENVLVLDIFFEALNYEAVEQKAAYEVSELLGDIGGQMGLFIGASLLTILEILDYLCEVFQDRVLGYFWNRRSAQKRSGNTLLQEELNGHRTHVPHLSLGPRPPTTPCAVTKTLSASHRTCYLVTRL | ||||||
Modified residue | 40 | Phosphothreonine; by PKC | ||||
Sequence: T | ||||||
Disulfide bond | 93↔187 | |||||
Sequence: CNINPLRRSRLTPNDLHWAGTALLGLDPAEHAAYLRALGQPPAPPGFMPSPTFDMAQLYARAGHSLEDMLLDCRYRGQPCGPENFTVIFTRMGQC | ||||||
Disulfide bond | 165↔172 | |||||
Sequence: CRYRGQPC | ||||||
Glycosylation | 176 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Disulfide bond | 283↔372 | |||||
Sequence: CNTASLDPDDFDPEPSDPLGSPRPRPSPPYSLIGCRLACESRYVARKCGCRMMHMPGNSPVCSPQQYKDCASPALDAMLRKDTCVCPNPC | ||||||
Disulfide bond | 317↔368 | |||||
Sequence: CRLACESRYVARKCGCRMMHMPGNSPVCSPQQYKDCASPALDAMLRKDTCVC | ||||||
Disulfide bond | 321↔366 | |||||
Sequence: CESRYVARKCGCRMMHMPGNSPVCSPQQYKDCASPALDAMLRKDTC | ||||||
Disulfide bond | 330↔352 | |||||
Sequence: CGCRMMHMPGNSPVCSPQQYKDC | ||||||
Disulfide bond | 332↔344 | |||||
Sequence: CRMMHMPGNSPVC | ||||||
Glycosylation | 400 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Modified residue | 523 | Phosphoserine; by PKC | ||||
Sequence: S |
Post-translational modification
Phosphorylated by PKA (By similarity).
Phosphorylated by PKC. In vitro, PRKCABP/PICK-1 is necessary for PKC phosphorylation and activation of a ASIC3/ACCN3-ASIC2/ASIC2b channel, but does not activate a homomeric ASIC3/ACCN3 channel
Phosphorylated by PKC. In vitro, PRKCABP/PICK-1 is necessary for PKC phosphorylation and activation of a ASIC3/ACCN3-ASIC2/ASIC2b channel, but does not activate a homomeric ASIC3/ACCN3 channel
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
Expressed in sciatic nerve and dorsal root ganglion (at protein level). Expressed in sensory neurons of dorsal root ganglion. Expressed in Golgi interneurons in the granular layer. Also found in superior cervical ganglia, spinal cord and brain stem.
Induction
Transcriptionally regulated by the proinflammatory mediators nerve growth factor, serotonin, interleukin-1 and bradykinin. Up-regulation upon tissue inflammation is abolished by anti-inflammatory drugs.
Developmental stage
Expression is first detected at 15.5 dpc. Strongly expressed perinatally.
Gene expression databases
Interaction
Subunit
Homotrimer or heterotrimer with other ASIC proteins (By similarity).
Interacts with LIN7B, MAGI1 and GOPC (By similarity).
Interacts with DLG4 and ASIC2. Interacts with STOM; this regulates channel activity. Homotrimeric ASIC3 and ASIC3-containing heterotrimers interact with the cono-RFamide CNF-Tx1.1, and probably CNF-Tx1.2 and CNF-Tx1.3 (AC P0DL71) (PubMed:28396446).
Interacts with LIN7B, MAGI1 and GOPC (By similarity).
Interacts with DLG4 and ASIC2. Interacts with STOM; this regulates channel activity. Homotrimeric ASIC3 and ASIC3-containing heterotrimers interact with the cono-RFamide CNF-Tx1.1, and probably CNF-Tx1.2 and CNF-Tx1.3 (AC P0DL71) (PubMed:28396446).
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | O35240 | Nherf1 Q9JJ19 | 5 | EBI-982374, EBI-982391 | |
BINARY | O35240 | Nherf2 Q920G2 | 2 | EBI-982374, EBI-982439 | |
XENO | O35240 | Patj Q63ZW7-3 | 2 | EBI-982374, EBI-8158524 | |
XENO | O35240 | Stom P54116 | 3 | EBI-982374, EBI-8004826 | |
BINARY | O35240 | Stoml3 D4A100 | 2 | EBI-982374, EBI-15615743 |
Protein-protein interaction databases
Chemistry
Structure
Family & Domains
Features
Showing features for region, motif.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 286-310 | Disordered | ||||
Sequence: ASLDPDDFDPEPSDPLGSPRPRPSP | ||||||
Motif | 530-533 | PDZ-binding | ||||
Sequence: VTRL |
Domain
The PDZ domain-binding motif is involved in interaction with LIN7A, GOPC and MAGI1/BAIAP1.
Sequence similarities
Belongs to the amiloride-sensitive sodium channel (TC 1.A.6) family. ASIC3 subfamily.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length533
- Mass (Da)59,227
- Last updated1998-01-01 v1
- Checksum294B57322C74B3DC
Computationally mapped potential isoform sequences
There is 1 potential isoform mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
A0A8I5ZRU8 | A0A8I5ZRU8_RAT | Asic3 | 443 |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AF013598 EMBL· GenBank· DDBJ | AAB69328.1 EMBL· GenBank· DDBJ | mRNA |