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[1]
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NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
Ugawa S.,
Shimada S.;
"Mus musculus mRNA for ASIC1b.";
Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases.
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[2]
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NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
STRAIN=C57BL/6;
TISSUE=Brain;
DOI=10.1101/gr.2596504; PubMed=15489334 [NCBI, ExPASy, EBI, Israel, Japan] The MGC Project Team;
"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).";
Genome Res. 14:2121-2127(2004).
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[3]
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SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND FUNCTION.
DOI=10.1016/S0896-6273(02)00661-X; PubMed=11988176 [NCBI, ExPASy, EBI, Israel, Japan]
Wemmie J.A.,
Chen J.,
Askwith C.C.,
Hruska-Hageman A.M.,
Price M.P.,
Nolan B.C.,
Yoder P.G.,
Lamani E.,
Hoshi T.,
Freeman J.H. Jr.,
Welsh M.J.;
"The acid-activated ion channel ASIC contributes to synaptic plasticity, learning, and memory.";
Neuron 34:463-477(2002).
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[4]
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TISSUE SPECIFICITY, AND FUNCTION.
PubMed=12843249 [NCBI, ExPASy, EBI, Israel, Japan]
Wemmie J.A.,
Askwith C.C.,
Lamani E.,
Cassell M.D.,
Freeman J.H. Jr.,
Welsh M.J.;
"Acid-sensing ion channel 1 is localized in brain regions with high synaptic density and contributes to fear conditioning.";
J. Neurosci. 23:5496-5502(2003).
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[5]
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FUNCTION.
DOI=10.1016/j.cell.2004.08.026; PubMed=15369669 [NCBI, ExPASy, EBI, Israel, Japan]
Xiong Z.-G.,
Zhu X.-M.,
Chu X.-P.,
Minami M.,
Hey J.,
Wei W.-L.,
MacDonald J.F.,
Wemmie J.A.,
Price M.P.,
Welsh M.J.,
Simon R.P.;
"Neuroprotection in ischemia: blocking calcium-permeable acid-sensing ion channels.";
Cell 118:687-698(2004).
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[6]
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FUNCTION, AND TISSUE SPECIFICITY.
DOI=10.1053/j.gastro.2004.08.061; PubMed=15578512 [NCBI, ExPASy, EBI, Israel, Japan]
Page A.J.,
Brierley S.M.,
Martin C.M.,
Martinez-Salgado C.,
Wemmie J.A.,
Brennan T.J.,
Symonds E.,
Omari T.,
Lewin G.R.,
Welsh M.J.,
Blackshaw L.A.;
"The ion channel ASIC1 contributes to visceral but not cutaneous mechanoreceptor function.";
Gastroenterology 127:1739-1747(2004).
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[7]
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INTERACTION WITH STOM.
DOI=10.1074/jbc.M407708200; PubMed=15471860 [NCBI, ExPASy, EBI, Israel, Japan]
Price M.P.,
Thompson R.J.,
Eshcol J.O.,
Wemmie J.A.,
Benson C.J.;
"Stomatin modulates gating of acid-sensing ion channels.";
J. Biol. Chem. 279:53886-53891(2004).
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[8]
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FUNCTION.
DOI=10.1073/pnas.0608018103; PubMed=17060608 [NCBI, ExPASy, EBI, Israel, Japan]
Zha X.-M.,
Wemmie J.A.,
Green S.H.,
Welsh M.J.;
"Acid-sensing ion channel 1a is a postsynaptic proton receptor that affects the density of dendritic spines.";
Proc. Natl. Acad. Sci. U.S.A. 103:16556-16561(2006).
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[9]
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FUNCTION IN CONTROL OF FEAR, AND DISRUPTION PHENOTYPE.
DOI=10.1016/j.biopsych.2007.05.008; PubMed=17662962 [NCBI, ExPASy, EBI, Israel, Japan]
Coryell M.W.,
Ziemann A.E.,
Westmoreland P.J.,
Haenfler J.M.,
Kurjakovic Z.,
Zha X.-M.,
Price M.,
Schnizler M.K.,
Wemmie J.A.;
"Targeting ASIC1a reduces innate fear and alters neuronal activity in the fear circuit.";
Biol. Psychiatry 62:1140-1148(2007).
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- FUNCTION: Cation channel with high affinity for sodium, which is gated by extracellular protons and inhibited by the diuretic amiloride. Also permeable for Ca(2+), Li(+) and K(+). Generates a biphasic current with a fast inactivating and a slow sustained phase. Mediates glutamate-independent Ca(2+) entry into neurons upon acidosis. This Ca(2+) overloading is toxic for cortical neurons and may be in part responsible for ischemic brain injury. Heteromeric channel assembly seems to modulate channel properties. Functions as a postsynaptic proton receptor that influences intracellular Ca(2+) concentration and calmodulin-dependent protein kinase II phosphorylation and thereby the density of dendritic spines. Modulates activity in the circuits underlying innate fear.
- SUBUNIT: Homotetramer or heterotetramer with other ASIC proteins (Probable). Interacts with PRKCABP and ACCN1 (By similarity). Interacts with STOM.
- SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein (By similarity). Note=Localizes in synaptosomes at dendritic synapses of neurons. Colocalizes with DLG4.
- ALTERNATIVE PRODUCTS:
2 named isoforms [FASTA] produced by alternative splicing.
- TISSUE SPECIFICITY: Expressed in brain areas receiving strong excitatory corticofugal input. In hippocampus, expressed in the hilus of the dentate gyrus. In the cerebral cortex expressed in anterior and posterior cingulate cortex, sensory and motor cortices. In the sensory cortex strongest expression is detected in the whisker barrel field. In sensorimotor and cingulate cortex expression is elevated in layer III. Also expressed in basal ganglia, striatum, ventral pallidum, olfactory tubercle, and nucleus accumbens. Weakly expressed in thalamus with the exception of the habenula and the medial septal nuclei. In olfactory bulb, preferentially expressed in the glomerular layer, within glomeruli. Expressed in cerebellum in the molecular and granule cell layers. Strongly expressed in amygdala complex, particularly in the lateral and basolateral nuclei. Isoform 1 is more abundant in brain compared to isoform 2 (at protein level). Expressed in the nodose ganglion and dorsal root ganglion. Expressed in dendritic spine cells.
- PTM: Phosphorylation by PKA regulates interaction with PRKCABP and subcellular location. Phosphorylation by PKC may regulate the channel (By similarity).
- DISRUPTION PHENOTYPE: Mice display reduced spatial learning and memory capability, associated with absence of proton-gated currents in hippocampal neurons and impairment of hippocampal long term potentiation (LTP). They also show an increased mechanosensitivity of colonic and gastroesophageal mechanoreceptors and prolonged gastric emptying and an altered fear conditioning.
- MISCELLANEOUS: Potentiated by Ca(2+), Mg(2+), Ba(2+), multivalent cations and potentiated by FMRFamide-related neuropeptides. PH dependence may be regulated by serine proteases. Inhibited by anti-inflammatory drugs like salicylic acid (By similarity).
- SIMILARITY: Belongs to the amiloride-sensitive sodium channel family.
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Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms.
Distributed under the Creative Commons Attribution-NoDerivs License.
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| Length: 526 AA [This is the length of the unprocessed precursor] |
Molecular weight: 59668 Da [This is the MW of the unprocessed precursor] |
CRC64: 5462B3FEB5532726 [This is a checksum on the sequence] |
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10 20 30 40 50 60
MELKTEEEEV GGVQPVSIQA FASSSTLHGL AHIFSYERLS LKRALWALCF LGSLAVLLCV
70 80 90 100 110 120
CTERVQYYFC YHHVTKLDEV AASQLTFPAV TLCNLNEFRF SQVSKNDLYH AGELLALLNN
130 140 150 160 170 180
RYEIPDTQMA DEKQLEILQD KANFRSFKPK PFNMREFYDR AGHDIRDMLL SCHFRGEACS
190 200 210 220 230 240
AEDFKVVFTR YGKCYTFNSG QDGRPRLKTM KGGTGNGLEI MLDIQQDEYL PVWGETDETS
250 260 270 280 290 300
FEAGIKVQIH SQDEPPFIDQ LGFGVAPGFQ TFVSCQEQRL IYLPSPWGTC NAVTMDSDFF
310 320 330 340 350 360
DSYSITACRI DCETRYLVEN CNCRMVHMPG DAPYCTPEQY KECADPALDF LVEKDQEYCV
370 380 390 400 410 420
CEMPCNLTRY GKELSMVKIP SKASAKYLAK KFNKSEQYIG ENILVLDIFF EVLNYETIEQ
430 440 450 460 470 480
KKAYEIAGLL GDIGGQMGLF IGASILTVLE LFDYAYEVIK HRLCRRGKCQ KEAKRNSADK
490 500 510 520
GVALSLDDVK RHNPCESLRG HPAGMTYAAN ILPHHPARGT FEDFTC
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Q6NXK8 in FASTA format |
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