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1.A.9.3.1
Adult strychnine-sensitive glycine-inhibited chloride (anion selective) heteropentameric channel (GlyR; GLRA1) consisting of α1- and β-subunits (Cascio, 2004; Sivilotti, 2010). Ivermectin potentiates glycine-induced channel activation (Wang and Lynch, 2012). Molecular sites for the positive allosteric modulation of glycine receptors by endocannabinoids have been identified (Yévenes and Zeilhofer, 2011). Different subunits contribute asymmetrically to channel conductances via residues in the extracellular domain (Moroni et al., 2011; Xiong et al., 2012). Dominant and recessive mutations in GLRA1 are the major causes of hyperekplexia or startle disease (Gimenez et al., 2012).  Open channel 3-d structures are known (Mowrey et al. 2013).  Desensitization is regulated by interactions between the second and third transmembrane segments which affect the ion channel lumen near its intracellular end. The GABAAR and GlyR pore blocker, picrotoxin (TC# 8.C.1), prevents desensitization (Gielen et al. 2015).  The x-ray structure of the α1 GlyR transmembrane domain has been reported (Moraga-Cid et al. 2015), and residue S296 in hGlyR-alpha1 is involved in potentiation by Delta(9)-tetrahydrocannabinol (THC) (Wells et al. 2015).  The structure has also been elucidated by cryo EM (Du et al. 2015) and by x-ray crystalography (Huang et al. 2015). The latter presented a 3.0 A X-ray structure of the human glycine receptor-alpha3 homopentamer in complex with the high affinity, high-specificity antagonist, strychnine. The structure allowed exploration of the molecular recognition of antagonists. Comparisons with previous structures revealed a mechanism for antagonist-induced inactivation of Cys-loop receptors, involving an expansion of the orthosteric binding site in the extracellular domain that is coupled to closure of the ion pore in the transmembrane domain. The GlyR beta8-beta9 loop is an essential regulator of conformational rearrangements during ion channel opening and closing (Schaefer et al. 2017). Association of GlyR with the anchoring protein, gephyrin (Q9NQX3), is due to  a hydrophobic interaction formed by Phe 330 of gephyrin and Phe 398 and Ile 400 of the GlyR beta-loop (Kim et al. 2006). Alcohols and volatile anesthetics enhance the function of inhibitory glycine receptors (GlyRs) by binding to a single anaesthetic binding site (Roberts et al. 2006). Aromatic residues in the GlyR M1, M3 and M4 α-helices are essential for receptor function (Tang and Lummis 2018). The neurological disorder, startle disease, is caused by glycinergic dysfunction, mainly due to missense mutations in genes encoding GlyR subunits (GLRA1 and GLRB). Another neurological disease with a phenotype similar to startle disease is a special form of stiff-person syndrome (SPS), which is most probably due to the development of GlyR autoantibodies (Schaefer et al. 2018).

Accession Number:P48167
Protein Name:Glycine receptor subunit beta aka GLRB
Length:497
Molecular Weight:56122.00
Species:Homo sapiens (Human) [9606]
Number of TMSs:4
Location1 / Topology2 / Orientation3: Cell junction1 / Multi-pass membrane protein2
Substrate Cl-

Cross database links:

Genevestigator: P48167
eggNOG: prNOG13895
HEGENOM: HBG506497
RefSeq: NP_000815.1    NP_001159532.1    NP_001159533.1   
Entrez Gene ID: 2743   
Pfam: PF02931    PF02932   
Drugbank: Drugbank Link   
OMIM: 138492  gene
149400  phenotype
KEGG: hsa:2743   

Gene Ontology

GO:0030054 C:cell junction
GO:0034707 C:chloride channel complex
GO:0005887 C:integral to plasma membrane
GO:0045211 C:postsynaptic membrane
GO:0005515 F:protein binding
GO:0004872 F:receptor activity
GO:0006821 P:chloride transport
GO:0007399 P:nervous system development
GO:0007218 P:neuropeptide signaling pathway
GO:0001964 P:startle response

References (5)

[1] “The human glycine receptor beta subunit: primary structure, functional characterisation and chromosomal localisation of the human and murine genes.”  Handford C.A.et.al.   8717357
[2] “The human glycine receptor beta subunit gene (GLRB): structure, refined chromosomal localization, and population polymorphism.”  Milani N.et.al.   9676428
[3] “Complete sequencing and characterization of 21,243 full-length human cDNAs.”  Ota T.et.al.   14702039
[4] “The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).”  The MGC Project Teamet.al.   15489334
[5] “Hyperekplexia associated with compound heterozygote mutations in the beta-subunit of the human inhibitory glycine receptor (GLRB).”  Rees M.I.et.al.   11929858

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FASTA formatted sequence
1:	MKFLLTTAFL ILISLWVEEA YSKEKSSKKG KGKKKQYLCP SQQSAEDLAR VPANSTSNIL 
61:	NRLLVSYDPR IRPNFKGIPV DVVVNIFINS FGSIQETTMD YRVNIFLRQK WNDPRLKLPS 
121:	DFRGSDALTV DPTMYKCLWK PDLFFANEKS ANFHDVTQEN ILLFIFRDGD VLVSMRLSIT 
181:	LSCPLDLTLF PMDTQRCKMQ LESFGYTTDD LRFIWQSGDP VQLEKIALPQ FDIKKEDIEY 
241:	GNCTKYYKGT GYYTCVEVIF TLRRQVGFYM MGVYAPTLLI VVLSWLSFWI NPDASAARVP 
301:	LGIFSVLSLA SECTTLAAEL PKVSYVKALD VWLIACLLFG FASLVEYAVV QVMLNNPKRV 
361:	EAEKARIAKA EQADGKGGNV AKKNTVNGTG TPVHISTLQV GETRCKKVCT SKSDLRSNDF 
421:	SIVGSLPRDF ELSNYDCYGK PIEVNNGLGK SQAKNNKKPP PAKPVIPTAA KRIDLYARAL 
481:	FPFCFLFFNV IYWSIYL