Protein Details: Glutamate receptor ionotropic;NMDA 2B

Protein ID

ICDB_Pro_0820

Protein Name

Glutamate receptor ionotropic;NMDA 2B

Gene Name

GRIN2B; NMDAR2B

Organism

Homo sapiens (Human)

Length

1484 amino acids

AlphaFoldDB

AF-Q13224-F1-model_v4.pdb

Function

Component of NMDA receptor complexes that function as heterotetrameric;ligand-gated ion channels with high calcium permeability and voltage-dependent sensitivity to magnesium. Channel activation requires binding of the neurotransmitter glutamate to the epsilon subunit;glycine binding to the zeta subunit;plus membrane depolarization to eliminate channel inhibition by Mg(2+). Sensitivity to glutamate and channel kinetics depend on the subunit composition. In concert with DAPK1 at extrasynaptic sites;acts as a central mediator for stroke damage. Its phosphorylation at Ser-1303 by DAPK1 enhances synaptic NMDA receptor channel activity inducing injurious Ca2+ influx through them;resulting in an irreversible neuronal death. Contributes to neural pattern formation in the developing brain. Plays a role in long-term depression (LTD) of hippocampus membrane currents and in synaptic plasticity (By similarity).

Sequence

MKPRAECCSPKFWLVLAVLAVSGSRARSQKSPPSIGIAVILVGTSDEVAIKDAHEKDDFHHLSVVPRVELVAMNETDPKSIITRICDLMSDRKIQGVVFADDTDQEAIAQILDFISAQTLTPILGIHGGSSMIMADKDESSMFFQFGPSIEQQASVMLNIMEEYDWYIFSIVTTYFPGYQDFVNKIRSTIENSFVGWELEEVLLLDMSLDDGDSKIQNQLKKLQSPIILLYCTKEEATYIFEVANSVGLTGYGYTWIVPSLVAGDTDTVPAEFPTGLISVSYDEWDYGLPARVRDGIAIITTAASDMLSEHSFIPEPKSSCYNTHEKRIYQSNMLNRYLINVTFEGRNLSFSEDGYQMHPKLVIILLNKERKWERVGKWKDKSLQMKYYVWPRMCPETEEQEDDHLSIVTLEEAPFVIVESVDPLSGTCMRNTVPCQKRIVTENKTDEEPGYIKKCCKGFCIDILKKISKSVKFTYDLYLVTNGKHGKKINGTWNGMIGEVVMKRAYMAVGSLTINEERSEVVDFSVPFIETGISVMVSRSNGTVSPSAFLEPFSADVWVMMFVMLLIVSAVAVFVFEYFSPVGYNRCLADGREPGGPSFTIGKAIWLLWGLVFNNSVPVQNPKGTTSKIMVSVWAFFAVIFLASYTANLAAFMIQEEYVDQVSGLSDKKFQRPNDFSPPFRFGTVPNGSTERNIRNNYAEMHAYMGKFNQRGVDDALLSLKTGKLDAFIYDAAVLNYMAGRDEGCKLVTIGSGKVFASTGYGIAIQKDSGWKRQVDLAILQLFGDGEMEELEALWLTGICHNEKNEVMSSQLDIDNMAGVFYMLGAAMALSLITFICEHLFYWQFRHCFMGVCSGKPGMVFSISRGIYSCIHGVAIEERQSVMNSPTATMNNTHSNILRLLRTAKNMANLSGVNGSPQSALDFIRRESSVYDISEHRRSFTHSDCKSYNNPPCEENLFSDYISEVERTFGNLQLKDSNVYQDHYHHHHRPHSIGSASSIDGLYDCDNPPFTTQSRSISKKPLDIGLPSSKHSQLSDLYGKFSFKSDRYSGHDDLIRSDVSDISTHTVTYGNIEGNAAKRRKQQYKDSLKKRPASAKSRREFDEIELAYRRRPPRSPDHKRYFRDKEGLRDFYLDQFRTKENSPHWEHVDLTDIYKERSDDFKRDSVSGGGPCTNRSHIKHGTGDKHGVVSGVPAPWEKNLTNVEWEDRSGGNFCRSCPSKLHNYSTTVTGQNSGRQACIRCEACKKAGNLYDISEDNSLQELDQPAAPVAVTSNASTTKYPQSPTNSKAQKKNRNKLRRQHSYDTFVDLQKEEAALAPRSVSLKDKGRFMDGSPYAHMFEMSAGESTFANNKSSVPTAGHHHHNNPGGGYMLSKSLYPDRVTQNPFIPTFGDDQCLLHGSKSYFFRQPTVAGASKARPDFRALVTNKPVVSALHGAVPARFQKDICIGNQSNPCVPNNKNPRAFNGSSNGHVYEKLSSIESDV

PDB Structures

5EWJ 5EWL 5EWM 7EU8 7KL0 7KL1 7KL2 7UIS 7UJP 7UJQ 7UJR 7UJS 7UJT

Ligand Binding

1. DICL_CP

2. DICL_Pep

Binding Site

BINDING 127; /ligand="Zn(2+)"; BINDING 284; /ligand="Zn(2+)"; BINDING 514; BINDING 519; /ligand="L-glutamate"; BINDING 690..691; /ligand="L-glutamate"; BINDING 732; /ligand="L-glutamate"

Disease

Developmental And Epileptic Encephalopathy and Intellectual Developmental Disorder;Autosomal Dominant 6;With Or Without Seizures

Location

Primarily found in the fronto-parieto-temporal cortex and hippocampus pyramidal cells;lower expression in the basal ganglia

DOI ID

10.1016/0167-4781(94)00189-a; 10.1101/gr.2596504; 10.1006/geno.1994.1366; 10.1016/s0304-3940(97)00853-7; 10.1074/jbc.m909741199; 10.15252/embj.201593070; 10.1038/ng.677; 10.1021/acs.jmedchem.5b02010; 10.1016/j.neuron.2016.01.016; 10.1523/jneurosci.2068-16.2017; 10.1124/mol.116.106781; 10.1124/mol.115.103036; 10.1038/tp.2011.52; 10.1056/nejmoa1206524; 10.1126/science.1227764; 10.1002/ana.24073; 10.1016/j.ymgme.2014.04.001; 10.1371/journal.pgen.1004772; 10.1016/j.ajhg.2016.10.002; 10.1002/humu.23149; 10.1371/journal.pgen.1006536

RefSeq

NP_000825.2; XP_011518930.1; XP_011518931.1; XP_016874708.1