ASIC1_HUMAN - PTM Information in dbPTM

Basic Information of Protein

• UniProt ID: ASIC1_HUMAN
• UniProt AC: P78348
• Protein Name: Acid-sensing ion channel 1 {ECO:0000303|PubMed:10798398}
• Gene Name: ASIC1
• Organism: Homo sapiens (Human).
• Sequence Length: 528
• Subcellular Localization: Cell membrane ; Multi-pass membrane protein . Localizes in synaptosomes at dendritic synapses of neurons. Colocalizes with DLG4 (By similarity)..
• Protein Description: Isoform 2 and isoform 3 function as proton-gated sodium channels; they are activated by a drop of the extracellular pH and then become rapidly desensitized. The channel generates a biphasic current with a fast inactivating and a slow sustained phase. Has high selectivity for sodium ions and can also transport lithium ions with high efficiency. Isoform 2 can also transport potassium, but with lower efficiency. It is nearly impermeable to the larger rubidium and cesium ions. Isoform 3 can also transport calcium ions. 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.; Isoform 1 does not display proton-gated cation channel activity..
• Protein Sequence: MELKAEEEEVGGVQPVSIQAFASSSTLHGLAHIFSYERLSLKRALWALCFLGSLAVLLCVCTERVQYYFHYHHVTKLDEVAASQLTFPAVTLCNLNEFRFSQVSKNDLYHAGELLALLNNRYEIPDTQMADEKQLEILQDKANFRSFKPKPFNMREFYDRAGHDIRDMLLSCHFRGEVCSAEDFKVVFTRYGKCYTFNSGRDGRPRLKTMKGGTGNGLEIMLDIQQDEYLPVWGETDETSFEAGIKVQIHSQDEPPFIDQLGFGVAPGFQTFVACQEQRLIYLPPPWGTCKAVTMDSDLDFFDSYSITACRIDCETRYLVENCNCRMVHMPGDAPYCTPEQYKECADPALDFLVEKDQEYCVCEMPCNLTRYGKELSMVKIPSKASAKYLAKKFNKSEQYIGENILVLDIFFEVLNYETIEQKKAYEIAGLLGDIGGQMGLFIGASILTVLELFDYAYEVIKHKLCRRGKCQKEAKRSSADKGVALSLDDVKRHNPCESLRGHPAGMTYAANILPHHPARGTFEDFTC

Overview of Protein Modification Sites with Functional and Structural Information

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
25	Phosphorylation	IQAFASSSTLHGLAH EEEEECCCHHHHHHH	32.28	-
40	Phosphorylation	IFSYERLSLKRALWA HHCHHHHHHHHHHHH	37.76	-
133	Ubiquitination	DTQMADEKQLEILQD CCCCCCHHHHHHHHH	61.81	-
189	Phosphorylation	EDFKVVFTRYGKCYT HHCEEEEEECCEEEE	16.04	26657352
191	Phosphorylation	FKVVFTRYGKCYTFN CEEEEEECCEEEEEC	20.20	30576142
193 (in isoform 1)	Ubiquitination	-	18.35	-
195	Phosphorylation	FTRYGKCYTFNSGRD EEECCEEEEECCCCC	20.18	26657352
199	Phosphorylation	GKCYTFNSGRDGRPR CEEEEECCCCCCCCC	30.89	30576142
316	Phosphorylation	ACRIDCETRYLVENC EEECCCCHHHEEECC	30.83	-
368	N-linked_Glycosylation	CVCEMPCNLTRYGKE EEEECCCCCCCCCCC	38.28	UniProtKB CARBOHYD
374 (in isoform 1)	Ubiquitination	-	46.69	-
383	Phosphorylation	LSMVKIPSKASAKYL CEEEECCCHHHHHHH	44.31	24719451
395	N-linked_Glycosylation	KYLAKKFNKSEQYIG HHHHHHCCCCHHHHC	56.68	UniProtKB CARBOHYD
478	Phosphorylation	CQKEAKRSSADKGVA CHHHHHHCCCCCCCE	29.22	24719451
479	Phosphorylation	QKEAKRSSADKGVAL HHHHHHCCCCCCCEE	44.51	12578970
487	Phosphorylation	ADKGVALSLDDVKRH CCCCCEECHHHHHHH	21.73	23312004
492	Ubiquitination	ALSLDDVKRHNPCES EECHHHHHHHCCCHH	55.74	-
499	Phosphorylation	KRHNPCESLRGHPAG HHHCCCHHHCCCCCC	30.04	29449344
509	Phosphorylation	GHPAGMTYAANILPH CCCCCCCHHHHCCCC	8.53	29978859
525	Phosphorylation	PARGTFEDFTC---- CCCCCCCCCCC----	39.71	12578970

Upstream regulatory proteins (kinases for phosphorylation sites, E3 ubiquitin ligases of ubiquitination sites, ...)

Modified Location	Modified Residue	Modification	Type of Upstream Proteins	Gene Name of Upstream Proteins	UniProt AC of Upstream Proteins	Sources
479	S	Phosphorylation	Kinase	PKA-FAMILY	-	GPS
479	S	Phosphorylation	Kinase	PKA	-	Uniprot
479	S	Phosphorylation	Kinase	PKA_GROUP	-	PhosphoELM
525	S	Phosphorylation	Kinase	PRKACA	P17612	GPS

Functions of PTM Sites

Oops, there are no descriptions of PTM sites of ASIC1_HUMAN !!

Disease-associated PTM Sites based on SAP

* Distance = the distance between SAP position and PTM sites.

Oops, there are no SNP-PTM records of ASIC1_HUMAN !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
PICK1_HUMAN	PICK1	physical	12578970
ASIC2_HUMAN	ASIC2	physical	28514442
TR10B_HUMAN	TNFRSF10B	physical	28514442
S27A3_HUMAN	SLC27A3	physical	28514442
UFSP2_HUMAN	UFSP2	physical	28514442
E2AK3_HUMAN	EIF2AK3	physical	28514442
HMOX2_HUMAN	HMOX2	physical	28514442

Drug and Disease Associations

• Kegg Disease
• There are no disease associations of PTM sites.
• OMIM Disease
• There are no disease associations of PTM sites.
• Kegg Drug
• There are no disease associations of PTM sites.
• DrugBank
• There are no disease associations of PTM sites.

Related Literatures of Post-Translational Modification

Phosphorylation

"cAMP-dependent protein kinase phosphorylation of the acid-sensing ionchannel-1 regulates its binding to the protein interacting with C-kinase-1.";
Leonard A.S., Yermolaieva O., Hruska-Hageman A., Askwith C.C.,Price M.P., Wemmie J.A., Welsh M.J.;
Proc. Natl. Acad. Sci. U.S.A. 100:2029-2034(2003).
Cited for: PHOSPHORYLATION BY PKA, MUTAGENESIS OF SER-478 AND SER-479,PHOSPHORYLATION AT SER-479, INTERACTION WITH PRKCABP, AND SUBCELLULARLOCATION.
PubMed: 12578970