NMDE1_XENLA
ID NMDE1_XENLA Reviewed; 1451 AA.
AC B7ZSK1; A9QW72; B7ZSK2;
DT 25-OCT-2017, integrated into UniProtKB/Swiss-Prot.
DT 03-MAR-2009, sequence version 1.
DT 03-AUG-2022, entry version 59.
DE RecName: Full=Glutamate receptor ionotropic, NMDA 2A;
DE Short=GluN2A;
DE AltName: Full=N-methyl D-aspartate receptor subtype 2A;
DE Short=NMDAR2A;
DE Short=NR2A {ECO:0000303|PubMed:18216193};
DE Flags: Precursor;
GN Name=grin2a;
OS Xenopus laevis (African clawed frog).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Amphibia;
OC Batrachia; Anura; Pipoidea; Pipidae; Xenopodinae; Xenopus; Xenopus.
OX NCBI_TaxID=8355 {ECO:0000312|EMBL:AAI70551.1};
RN [1] {ECO:0000312|EMBL:ABX60543.1}
RP NUCLEOTIDE SEQUENCE [MRNA], AND FUNCTION.
RX PubMed=18216193; DOI=10.1523/jneurosci.5078-07.2008;
RA Ewald R.C., Van Keuren-Jensen K.R., Aizenman C.D., Cline H.T.;
RT "Roles of NR2A and NR2B in the development of dendritic arbor morphology in
RT vivo.";
RL J. Neurosci. 28:850-861(2008).
RN [2] {ECO:0000312|EMBL:AAI70551.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Oocyte {ECO:0000312|EMBL:AAI70551.1};
RG NIH - Xenopus Gene Collection (XGC) project;
RL Submitted (NOV-2008) to the EMBL/GenBank/DDBJ databases.
RN [3] {ECO:0007744|PDB:5UOW, ECO:0007744|PDB:5UP2}
RP STRUCTURE BY ELECTRON MICROSCOPY (4.50 ANGSTROMS) OF 1-834 IN COMPLEX WITH
RP GLUTAMATE; GRIN1 AND GRIN2B, FUNCTION, SUBCELLULAR LOCATION, TOPOLOGY,
RP SUBUNIT, AND DISULFIDE BONDS.
RX PubMed=28232581; DOI=10.1126/science.aal3729;
RA Lu W., Du J., Goehring A., Gouaux E.;
RT "Cryo-EM structures of the triheteromeric NMDA receptor and its allosteric
RT modulation.";
RL Science 355:0-0(2017).
CC -!- FUNCTION: Component of NMDA receptor complexes that function as
CC heterotetrameric, ligand-gated ion channels with high calcium
CC permeability and voltage-dependent sensitivity to magnesium. Channel
CC activation requires binding of the neurotransmitter glutamate to the
CC epsilon subunit, glycine binding to the zeta subunit, plus membrane
CC depolarization to eliminate channel inhibition by Mg(2+)
CC (PubMed:28232581). Sensitivity to glutamate and channel kinetics depend
CC on the subunit composition (Probable). Plays a role in dendritic
CC branching in brain neurons and in synaptic plasticity
CC (PubMed:18216193). {ECO:0000269|PubMed:18216193,
CC ECO:0000269|PubMed:28232581, ECO:0000305}.
CC -!- SUBUNIT: Heterotetramer. Forms heterotetrameric channels composed of
CC two zeta subunits (grin1), and two epsilon subunits (grin2a, grin2b,
CC grin2c or grin2d) (in vitro) (PubMed:28232581). In vivo, the subunit
CC composition may depend on the expression levels of the different
CC subunits (Probable). {ECO:0000269|PubMed:28232581, ECO:0000305}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:28232581};
CC Multi-pass membrane protein {ECO:0000269|PubMed:28232581}. Postsynaptic
CC cell membrane {ECO:0000250|UniProtKB:Q00959}; Multi-pass membrane
CC protein {ECO:0000255}.
CC -!- DOMAIN: Contains an N-terminal domain, a ligand-binding domain and a
CC transmembrane domain. Agonist binding to the extracellular ligand-
CC binding domains triggers channel gating. {ECO:0000305|PubMed:28232581}.
CC -!- DOMAIN: A hydrophobic region that gives rise to the prediction of a
CC transmembrane span does not cross the membrane, but is part of a
CC discontinuously helical region that dips into the membrane and is
CC probably part of the pore and of the selectivity filter.
CC {ECO:0000305|PubMed:28232581}.
CC -!- SIMILARITY: Belongs to the glutamate-gated ion channel (TC 1.A.10.1)
CC family. {ECO:0000255}.
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DR EMBL; EU275164; ABX60543.1; -; mRNA.
DR EMBL; BC170551; AAI70551.1; -; mRNA.
DR EMBL; BC170552; AAI70552.1; -; mRNA.
DR RefSeq; NP_001106367.1; NM_001112896.1.
DR PDB; 5UOW; EM; 4.50 A; B=1-834.
DR PDB; 5UP2; EM; 6.00 A; B=1-834.
DR PDBsum; 5UOW; -.
DR PDBsum; 5UP2; -.
DR AlphaFoldDB; B7ZSK1; -.
DR SMR; B7ZSK1; -.
DR GeneID; 100127346; -.
DR KEGG; xla:100127346; -.
DR CTD; 100127346; -.
DR Xenbase; XB-GENE-1021446; grin2a.L.
DR OrthoDB; 188544at2759; -.
DR Proteomes; UP000186698; Chromosome 9_10L.
DR Bgee; 100127346; Expressed in brain and 1 other tissue.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0005887; C:integral component of plasma membrane; IDA:UniProtKB.
DR GO; GO:0017146; C:NMDA selective glutamate receptor complex; IDA:UniProtKB.
DR GO; GO:0045211; C:postsynaptic membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0022849; F:glutamate-gated calcium ion channel activity; ISS:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004972; F:NMDA glutamate receptor activity; IDA:UniProtKB.
DR GO; GO:0097553; P:calcium ion transmembrane import into cytosol; ISS:UniProtKB.
DR GO; GO:0051290; P:protein heterotetramerization; IDA:UniProtKB.
DR GO; GO:0010043; P:response to zinc ion; IDA:UniProtKB.
DR InterPro; IPR001828; ANF_lig-bd_rcpt.
DR InterPro; IPR019594; Glu/Gly-bd.
DR InterPro; IPR001508; Iono_rcpt_met.
DR InterPro; IPR001320; Iontro_rcpt.
DR InterPro; IPR018884; NMDAR2_C.
DR InterPro; IPR028082; Peripla_BP_I.
DR Pfam; PF01094; ANF_receptor; 1.
DR Pfam; PF00060; Lig_chan; 1.
DR Pfam; PF10613; Lig_chan-Glu_bd; 1.
DR Pfam; PF10565; NMDAR2_C; 1.
DR PRINTS; PR00177; NMDARECEPTOR.
DR SMART; SM00918; Lig_chan-Glu_bd; 1.
DR SMART; SM00079; PBPe; 1.
DR SUPFAM; SSF53822; SSF53822; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Calcium; Cell membrane; Disulfide bond; Glycoprotein;
KW Ion channel; Ion transport; Ligand-gated ion channel; Magnesium; Membrane;
KW Metal-binding; Postsynaptic cell membrane; Receptor; Reference proteome;
KW Signal; Synapse; Transmembrane; Transmembrane helix; Transport; Zinc.
FT SIGNAL 1..20
FT /evidence="ECO:0000255"
FT CHAIN 21..1451
FT /note="Glutamate receptor ionotropic, NMDA 2A"
FT /id="PRO_5002864231"
FT TOPO_DOM 21..547
FT /note="Extracellular"
FT /evidence="ECO:0000269|PubMed:28232581"
FT TRANSMEM 548..568
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:28232581"
FT TOPO_DOM 569..592
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:28232581"
FT INTRAMEM 593..612
FT /note="Discontinuously helical"
FT /evidence="ECO:0000269|PubMed:28232581"
FT TOPO_DOM 613..617
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:28232581"
FT TRANSMEM 618..637
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:28232581"
FT TOPO_DOM 638..808
FT /note="Extracellular"
FT /evidence="ECO:0000269|PubMed:28232581"
FT TRANSMEM 809..829
FT /note="Helical"
FT /evidence="ECO:0000269|PubMed:28232581"
FT TOPO_DOM 830..1451
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:28232581"
FT REGION 591..612
FT /note="Pore-forming"
FT /evidence="ECO:0000305"
FT REGION 1011..1080
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1100..1165
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1011..1031
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1032..1046
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1100..1117
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1138..1156
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 120
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:Q00959"
FT BINDING 274
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:Q00959"
FT BINDING 503..505
FT /ligand="L-glutamate"
FT /ligand_id="ChEBI:CHEBI:29985"
FT /evidence="ECO:0000250|UniProtKB:Q00959"
FT BINDING 510
FT /ligand="L-glutamate"
FT /ligand_id="ChEBI:CHEBI:29985"
FT /evidence="ECO:0000250|UniProtKB:Q00959"
FT BINDING 681..682
FT /ligand="L-glutamate"
FT /ligand_id="ChEBI:CHEBI:29985"
FT /evidence="ECO:0000250|UniProtKB:Q00959"
FT BINDING 722..723
FT /ligand="L-glutamate"
FT /ligand_id="ChEBI:CHEBI:29985"
FT /evidence="ECO:0000250|UniProtKB:Q00959"
FT CARBOHYD 67
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 332
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 372
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 435
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 436
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 533
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 679
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT DISULFID 79..312
FT /evidence="ECO:0000269|PubMed:28232581,
FT ECO:0007744|PDB:5UOW, ECO:0007744|PDB:5UP2"
FT DISULFID 421..447
FT /evidence="ECO:0000269|PubMed:28232581,
FT ECO:0007744|PDB:5UOW, ECO:0007744|PDB:5UP2"
FT DISULFID 428..448
FT /evidence="ECO:0000269|PubMed:28232581,
FT ECO:0007744|PDB:5UOW, ECO:0007744|PDB:5UP2"
FT DISULFID 737..792
FT /evidence="ECO:0000269|PubMed:28232581,
FT ECO:0007744|PDB:5UOW, ECO:0007744|PDB:5UP2"
FT CONFLICT 259
FT /note="I -> M (in Ref. 1; ABX60543)"
FT /evidence="ECO:0000305"
FT CONFLICT 760
FT /note="G -> V (in Ref. 1; ABX60543)"
FT /evidence="ECO:0000305"
FT CONFLICT 965
FT /note="N -> S (in Ref. 1; ABX60543)"
FT /evidence="ECO:0000305"
FT CONFLICT 1031
FT /note="I -> T (in Ref. 2; AAI70552)"
FT /evidence="ECO:0000305"
FT CONFLICT 1431
FT /note="V -> G (in Ref. 1; ABX60543)"
FT /evidence="ECO:0000305"
FT CONFLICT 1432
FT /note="V -> G (in Ref. 2; AAI70552)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1451 AA; 164602 MW; D15245B98B954F4C CRC64;
MGMFVLLLYT FLYAGDLGHG AEKSFPVLNI AVILGRTRYI TERDIRSLWT RDMSLDFDVN
VVTLLVNQTD PKSIITHVCD LMSGTKIHGV VFGDDTDQEA IAQILDFVSS QTFIPILGIH
GGSSMIMADK DEMSTFFQFG ASIKQQATVM LNIMEEYDWH VFSVITSNFP GYRDFISFIK
TTVDNSFVGW EVQNYITLDT SYTDAQTLTQ LKKIHSSVIL LYCSKDEATY IFEEARSLGL
MGYGFVWIVP SLVTGNTDII PYEFPSGLVS VSYDDWDYGI EARVRDGLGI ITTAASAMLE
KHSVIPEAKT SCYGQNERND PPLHTLHNFM INVTWDGKDL SFTEDGYQAN PKLVVLLLNM
EREWEKVGKW ENKSLNMKYP VWPRITASLD SDHDDNHLSI VTLEEAPFVI VENIDYLTGT
CVRNTVPCRK YFRLNNSTTE GTSVKKCCKG FCIDILKKLS KTVKFTYDLY LVTNGKHGKK
IKNVWNGMIG EVVYKRAVMA VGSLTINEER SVAVDFSVPF VETGISVMVS RSNGTVSPSA
FLEPFSASVW VMMFVMLLLV SAMAVFIFEY FSPVGYNRNL AQGKDPHGPS FTIGKAVWLL
WGLVFNNSVP VQNPKGTTSK IIVSIWAFFA VIFLASYTAN LAAFMIQEEF VDQVTGLSDN
KFQRPHDYSP PFRFGTVPNG STERNIRNNY PDMHQYMVKF HQKGVQDALV SLKTGKLDAF
IYDAAVLNYM AGRDEGCKLV TIGSGYIFAT TGYGIALQKG SRWKRPIDLA LLQFVGDGEM
EELEKLWLTG ICHTEKNEVM SSQLDIDNMA GVFYMLAAAM ALSLITFVWE HLFYWKLRFC
FTGVCTGTPG LLFSISRGIY SCIHGVHIEE KKKSPDFSFT ASQTNMLKLL RASKNIANLS
NLNQSQCNSP KRTSDYIQRN SLLTDMVLDK GNLTYSDNRP FQQKDIYSEN TYDLAMLSAN
CPKDNLNNYV FQGQHPLTLN ESNPNTVEVA VSAEAKVNTR PRQLWKKSVE TLRQTQGSVN
ENGTEESKSS IKNQRFLPED GHFSDVSEAS SRATCHIDSE NNNKHRKSKD NLKKRPVSAK
YARECSEVEL SYLKIKHGPN RDKVYTIDGD KEPSFIMDQP KYSENSPDQD DEDYPDVYQD
HNDNYRKTEP LQSDRTPLHS EGRLPNNDIQ YKLFSKHYNL KEKNTSMSDA NDRHRQNSTH
CRSCLSNMPN YTGHYTARSP YKCDDCLHTG KLYDIDEDQM LHEAANSMHS EDFYEHNWLE
NNALHFQKKN KLRINRQHSC DNINKPREHD LGRPPRSLSL KEKERYIQEN PFAKFVIVPP
EKLLGNNASL FTDSLKDSKR SKSLYPDNSS DNPFLHSYQE TQKLSHGRSS SDIYKQSSLP
KARNDNYLRS SIKSTTSYSS RDGRVPDDMC VSEYALPYVT SNNSVYSAPR VVNSCSNRRV
FKKMPSLESD V
