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1.A.7.1.5
The purinergic receptor, P2X4, is sensitive to the macrocyclic lactone, ivermectin, which allosterically modulates both ion conduction and channel gating (Samways et al., 2012). The gating mechanism has been discussed (Du et al., 2012) and considered to be determined by the conformation of the transmembrane domain (Minato et al. 2016; Pierdominici-Sottile et al. 2016). The crystal structure of the ATP-gated P2X(4) ion channel in the closed state has been reported (Kawate et al., 2009). Unobstructed lateral portals are preferentially used as access routes to the pores of P2X receptors (Samways et al., 2011).  Activation is ATP-dependent and rapid, but desensitization occurs within seconds and is ATP-independent (Stojilkovic et al. 2010). Ectodomain cysteines play roles in agonist binding and channel gating (Rokic et al. 2010).  Evermectin has distinct effects on opening and dilation of the channel pore, the first accounting for increased peak current amplitude, and the latter correlating with changes in the kinetics of receptor deactivation (Zemkova et al. 2014). Conserved amino acids within the regions linking the ectodomain with the pore-forming transmembrane domain may contribute to signal transduction and channel gating (Gao et al. 2015; Jelínkova et al. 2008). Binding of ATP produces distortions in the chains that eliminate restrictions on the interchain displacements, leading to the opening of the pore (Pierdominici-Sottile et al. 2016). The purinergic receptors, P2RX4 and P2RX7, affect susceptibility to multiple sclerosis (MS) (Sadovnick et al. 2017).

Accession Number:Q99571
Protein Name:P2X purinoceptor 4
Length:388
Molecular Weight:43369.00
Species:Homo sapiens (Human) [9606]
Number of TMSs:2
Location1 / Topology2 / Orientation3: Membrane1 / Multi-pass membrane protein2
Substrate ions

Cross database links:

Genevestigator: Q99571 Q99571
eggNOG: prNOG05100 prNOG05100
HEGENOM: HBG713324 HBG713324
Entrez Gene ID: 5025   
Pfam: PF00864   
KEGG: hsa:5025    hsa:5025   

Gene Ontology

GO:0030054 C:cell junction
GO:0005887 C:integral to plasma membrane
GO:0048471 C:perinuclear region of cytoplasm
GO:0005524 F:ATP binding
GO:0045296 F:cadherin binding
GO:0005507 F:copper ion binding
GO:0004931 F:extracellular ATP-gated cation channel activity
GO:0042803 F:protein homodimerization activity
GO:0001614 F:purinergic nucleotide receptor activity
GO:0005102 F:receptor binding
GO:0008270 F:zinc ion binding
GO:0042118 P:endothelial cell activation
GO:0051899 P:membrane depolarization
GO:0010614 P:negative regulation of cardiac muscle hypertrophy
GO:0010524 P:positive regulation of calcium ion transport into cytosol
GO:0050850 P:positive regulation of calcium-mediated signaling
GO:0045429 P:positive regulation of nitric oxide biosynthetic process
GO:0032308 P:positive regulation of prostaglandin secretion
GO:0042981 P:regulation of apoptotic process
GO:0008217 P:regulation of blood pressure
GO:0055117 P:regulation of cardiac muscle contraction
GO:0002028 P:regulation of sodium ion transport
GO:0055119 P:relaxation of cardiac muscle
GO:0033198 P:response to ATP
GO:0034405 P:response to fluid shear stress
GO:0019233 P:sensory perception of pain
GO:0001894 P:tissue homeostasis

References (6)

[1] “Characterization of recombinant human P2X4 receptor reveals pharmacological differences to the rat homologue.”  Garcia-Guzman M.et.al.   9016352
[2] “The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).”  The MGC Project Teamet.al.   15489334
[3] “Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry.”  Chen R.et.al.   19159218
[4] “Characterization of recombinant human P2X4 receptor reveals pharmacological differences to the rat homologue.”  Garcia-Guzman M.et.al.   9016352
[5] “The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).”  The MGC Project Teamet.al.   15489334
[6] “Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry.”  Chen R.et.al.   19159218

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FASTA formatted sequence
1:	MAGCCAALAA FLFEYDTPRI VLIRSRKVGL MNRAVQLLIL AYVIGWVFVW EKGYQETDSV 
61:	VSSVTTKVKG VAVTNTSKLG FRIWDVADYV IPAQEENSLF VMTNVILTMN QTQGLCPEIP 
121:	DATTVCKSDA SCTAGSAGTH SNGVSTGRCV AFNGSVKTCE VAAWCPVEDD THVPQPAFLK 
181:	AAENFTLLVK NNIWYPKFNF SKRNILPNIT TTYLKSCIYD AKTDPFCPIF RLGKIVENAG 
241:	HSFQDMAVEG GIMGIQVNWD CNLDRAASLC LPRYSFRRLD TRDVEHNVSP GYNFRFAKYY 
301:	RDLAGNEQRT LIKAYGIRFD IIVFGKAGKF DIIPTMINIG SGLALLGMAT VLCDIIVLYC 
361:	MKKRLYYREK KYKYVEDYEQ GLASELDQ