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Overview

Uniprot IDD4A6L0
Protein NameMetabotropic glycine receptor
Gene NameGpr158
OrganismRattus norvegicus

Kla Sites from experimental identification

Position Flanking peptide
910 LSVIASAKEKTLGLA
919 KTLGLAGKTQTLVME

Function

Metabotropic receptor for glycine that controls synapse formation and function in the brain. Acts as an atypical G protein coupled receptor that recruits and regulates the RGS7-GNB5 complex instead of activating G proteins. In absence of glycine ligand, promotes the GTPase activator activity of RGS7, increasing the GTPase activity of G protein alpha subunits, thereby driving them into their inactive GDP-bound form. Glycine-binding changes the conformation of the intracellular surface, inhibiting the GTPase activator activity of the RGS7-GNB5 complex, promoting G protein alpha subunits into their active GTP-bound form and regulating cAMP levels. Also able to bind taurine, a compound closely related to glycine, but with a two-fold lower affinity. Glycine receptor-dependent regulation of cAMP controls key ion channels, kinases and neurotrophic factors involved in neuronal excitability and synaptic transmission (By similarity). Plays a pivotal role in regulating mood and cognition via its ability to regulate neuronal excitability in L2/L3 pyramidal neurons of the prefrontal cortex. Also involved in spatial learning by regulating hippocampal CA1 neuronal excitability. Acts as a synaptic organizer in the hippocampus, required for proper mossy fiber-CA3 neurocircuitry establishment, structure and function: induces presynaptic differentiation in contacting axons via its interaction with GPC4. In addition to glycine, may also act as a receptor for osteocalcin (BGLAP) hormone: osteocalcin-binding initiates a signaling response that prevents neuronal apoptosis in the hippocampus and regulates the synthesis of neurotransmitters (By similarity)

Protein Sequence

10 MGAMAYSLLL 20 CLLLAHLGLG 30 EVGASLDPSE 40 RPDSSRERTS 50 RGKQHGQQLP 60 RASAPDPSIP 70 WSRSTDGTIL 80 AQKLAEEVPM 90 DVASYLYTGD 100 FHQLKRANCS 110 GRYELAGLPG 120 KSPSLASSHP 130 SLHGALDTLT 140 HATNFLNMML 150 QSNKSREQTV 160 QDDLQWYQAL 170 VRSLLEGEPS 180 ISRAAITFST 190 ESLSTPAPQV 200 FLQATREESR 210 ILLQDLSSSA 220 HHLANATLET 230 EWFHGLRRKW 240 RPHLHRRGSN 250 QGPRGLGHSW 260 RRRDGLGGDR 270 SHVKWSPPFL 280 ECENGSYKPG 290 WLVTLSAAFY 300 GLQPNLVPEF 310 RGVMKVDINL 320 QKVDIDQCSS 330 DGWFSGTHKC 340 HLNNSECMPI 350 KGLGFVLGAY 360 QCVCKAGFYH 370 PRVFSVNNFQ 380 RRGPDHHFSG 390 STKDVSEEAH 400 VCLPCREGCP 410 FCADDRPCFV 420 QEDKYLRLAI 430 ISFQALCMLL 440 DFVSMLVVYH 450 FRKAKSIRAS 460 GLILLETILF 470 GSLLLYFPVV 480 ILYFEPSTFR 490 CILLRWVRLL 500 GFATVYGTVT 510 LKLHRVLKVF 520 LSRTAQRIPY 530 MTGGRVMRML 540 AVIVLVVFWF 550 LVGWTSSMCQ 560 NLERDILLVG 570 QGQTSDNLTF 580 NMCLIDRWDY 590 MTAVAEFLFL 600 LWGIYLCYAV 610 RTVPSAFHEP 620 RYMAVAVHNE 630 LIITAIFHTI 640 RFVLASRLQP 650 DWMLMLYFAH 660 THLTVTVTIG 670 LLLIPKFSHS 680 SNNPRDDIAT 690 EAYEDELDMG 700 RSGSYLNSSI 710 NSAWSEHSLD 720 PEDIRDELKK 730 LYAQLEIYKR 740 KKMITNNPHL 750 QKKRCSKKGL 760 GRSIMRRITE 770 IPETVSRQCS 780 KEDKEGTDHS 790 AAKGTGLVRK 800 NPTESSGNTG 810 RPKEESLKNR 820 VFSLKKSHST 830 YDHVRDQTDE 840 SSSLPTESQE 850 EEVTENSTLE 860 SLSSKKLTQK 870 VKEDSEAEST 880 ESVPLVCKSA 890 SAHNLSSEKK 900 PGHPRTSMLQ 910 KSLSVIASAK 920 EKTLGLAGKT 930 QTLVMEDRAK 940 SQKPQPKDRE 950 TNRKYSNSDN 960 TETNPNSNHT 970 EELRKPQKSG 980 IMKQQRVNLP 990 TANPDASSST 1000 TQIKDNFDIG 1010 EVCPWEVYDL 1020 TPGPVPSEPK 1030 AQKHVSIAAS 1040 EVEQNPASFS 1050 KEKSHHKPKA 1060 AEGLYQANHK 1070 SIDKTEVCPW 1080 ESHGQSPLED 1090 ENRLISKTPV 1100 LPGRAREENG 1110 SQLYTTNMCA 1120 GQYEELPPKA 1130 VASKVENENL 1140 NQMGDQEKQT 1150 SSSVDIIPGS 1160 CISSNNSPQP 1170 LTSRAEVCPW 1180 EFEPLEQPNA 1190 ERIVALPASS 1200 ALSASKIPGP RK

Gene Ontology

Classification GO ID Description
Cellular Component GO:0016020 membrane
Cellular Component GO:0005634 nucleus
Cellular Component GO:0005886 plasma membrane
Cellular Component GO:0098839 postsynaptic density membrane
Cellular Component GO:0045211 postsynaptic membrane
Cellular Component GO:0042734 presynaptic membrane
Molecular Function GO:0008047 enzyme activator activity
Molecular Function GO:0160079 G protein-coupled glycine receptor activity
Molecular Function GO:0004888 transmembrane signaling receptor activity
Biological Process GO:0007420 brain development
Biological Process GO:0050890 cognition
Biological Process GO:0007186 G protein-coupled receptor signaling pathway
Biological Process GO:0001956 positive regulation of neurotransmitter secretion
Biological Process GO:0072659 protein localization to plasma membrane
Biological Process GO:0008277 regulation of G protein-coupled receptor signaling pathway
Biological Process GO:0050807 regulation of synapse organization

Reference

[1] Chen Y, Sun W, Sun Z, Zhao H, Wu T et al.. Effect of electroacupuncture on hippocampal protein lactylation in a rat model of vascular dementia.. Front Neurol 16:1629474. 2025. PMID: 40963935.