NMDE1_PANTR
ID NMDE1_PANTR Reviewed; 1464 AA.
AC Q5IS45;
DT 15-MAR-2005, integrated into UniProtKB/Swiss-Prot.
DT 15-FEB-2005, sequence version 1.
DT 03-AUG-2022, entry version 121.
DE RecName: Full=Glutamate receptor ionotropic, NMDA 2A;
DE Short=GluN2A;
DE AltName: Full=Glutamate [NMDA] receptor subunit epsilon-1;
DE AltName: Full=N-methyl D-aspartate receptor subtype 2A;
DE Short=NMDAR2A;
DE Short=NR2A;
DE Flags: Precursor;
GN Name=GRIN2A;
OS Pan troglodytes (Chimpanzee).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Pan.
OX NCBI_TaxID=9598;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=15620360; DOI=10.1016/j.cell.2004.11.040;
RA Dorus S., Vallender E.J., Evans P.D., Anderson J.R., Gilbert S.L.,
RA Mahowald M., Wyckoff G.J., Malcom C.M., Lahn B.T.;
RT "Accelerated evolution of nervous system genes in the origin of Homo
RT sapiens.";
RL Cell 119:1027-1040(2004).
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+). Sensitivity
CC to glutamate and channel kinetics depend on the subunit composition;
CC cchannels containing GRIN1 and GRIN2A have lower sensitivity to
CC glutamate and faster deactivation kinetics than channels formed by
CC GRIN1 and GRIN2B. Contributes to the slow phase of excitatory
CC postsynaptic current, long-term synaptic potentiation, and learning (By
CC similarity). {ECO:0000250|UniProtKB:P35436,
CC ECO:0000250|UniProtKB:Q00959}.
CC -!- SUBUNIT: Heterotetramer (By similarity). Forms heterotetrameric
CC channels composed of two zeta subunits (GRIN1), and two epsilon
CC subunits (GRIN2A, GRIN2B, GRIN2C or GRIN2D) (in vitro). Can also form
CC heterotetrameric channels that contain at least one zeta subunit
CC (GRIN1), at least one epsilon subunit, plus GRIN3A or GRIN3B (By
CC similarity). In vivo, the subunit composition may depend on the
CC expression levels of the different subunits. Found in a complex with
CC GRIN1, GRIN3A and PPP2CB (By similarity). Found in a complex with GRIN1
CC and GRIN3B (By similarity). Interacts with AIP1 (By similarity).
CC Interacts with HIP1 and NETO1. Interacts with SNX27 (via PDZ domain);
CC the interaction is required for recycling to the plasma membrane when
CC endocytosed and prevent degradation in lysosomes (By similarity).
CC Interacts with PDZ domains of PATJ and DLG4. Interacts with LRFN2 (By
CC similarity). Interacts with RPH3A and DLG4; this ternary complex
CC regulates NMDA receptor composition at postsynaptic membranes (By
CC similarity). Interacts with SORCS2 (By similarity). Interacts with ARC;
CC preventing ARC oligomerization (By similarity).
CC {ECO:0000250|UniProtKB:P35436, ECO:0000250|UniProtKB:Q00959}.
CC -!- SUBCELLULAR LOCATION: Cell projection, dendritic spine
CC {ECO:0000250|UniProtKB:P35436}. Cell membrane
CC {ECO:0000250|UniProtKB:P35436}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:P35436}. Synapse {ECO:0000250|UniProtKB:P35436}.
CC Postsynaptic cell membrane {ECO:0000250|UniProtKB:Q00959}; Multi-pass
CC membrane protein {ECO:0000250|UniProtKB:Q00959}. Cytoplasmic vesicle
CC membrane {ECO:0000250|UniProtKB:P35436}. Note=Expression at the
CC dendrite cell membrane and at synapses is regulated by SORCS2 and the
CC retromer complex. {ECO:0000250|UniProtKB:P35436}.
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.
CC {ECO:0000250|UniProtKB:Q00959}.
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:0000250|UniProtKB:B7ZSK1}.
CC -!- SIMILARITY: Belongs to the glutamate-gated ion channel (TC 1.A.10.1)
CC family. NR2A/GRIN2A subfamily. {ECO:0000305}.
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DR EMBL; AY665283; AAV74321.1; -; mRNA.
DR RefSeq; NP_001029361.1; NM_001034189.1.
DR AlphaFoldDB; Q5IS45; -.
DR SMR; Q5IS45; -.
DR STRING; 9598.ENSPTRP00000013242; -.
DR PaxDb; Q5IS45; -.
DR GeneID; 454396; -.
DR KEGG; ptr:454396; -.
DR CTD; 2903; -.
DR eggNOG; KOG1053; Eukaryota.
DR InParanoid; Q5IS45; -.
DR Proteomes; UP000002277; Unplaced.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0030659; C:cytoplasmic vesicle membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0043197; C:dendritic spine; IEA:UniProtKB-SubCell.
DR GO; GO:0005887; C:integral component of plasma membrane; ISS:UniProtKB.
DR GO; GO:0017146; C:NMDA selective glutamate receptor complex; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0014069; C:postsynaptic density; ISS:UniProtKB.
DR GO; GO:0098839; C:postsynaptic density membrane; IBA:GO_Central.
DR GO; GO:0022849; F:glutamate-gated calcium ion channel activity; ISS:UniProtKB.
DR GO; GO:0015276; F:ligand-gated ion channel activity; IBA:GO_Central.
DR GO; GO:0004972; F:NMDA glutamate receptor activity; ISS:UniProtKB.
DR GO; GO:0038023; F:signaling receptor activity; IBA:GO_Central.
DR GO; GO:0008270; F:zinc ion binding; ISS:UniProtKB.
DR GO; GO:0097553; P:calcium ion transmembrane import into cytosol; ISS:UniProtKB.
DR GO; GO:0060079; P:excitatory postsynaptic potential; IBA:GO_Central.
DR GO; GO:0060291; P:long-term synaptic potentiation; IBA:GO_Central.
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 2: Evidence at transcript level;
KW Calcium; Cell membrane; Cell projection; Cytoplasmic vesicle;
KW Disulfide bond; Glycoprotein; Ion channel; Ion transport;
KW Ligand-gated ion channel; Magnesium; Membrane; Metal-binding;
KW Phosphoprotein; Postsynaptic cell membrane; Receptor; Reference proteome;
KW Signal; Synapse; Transmembrane; Transmembrane helix; Transport; Zinc.
FT SIGNAL 1..22
FT /evidence="ECO:0000255"
FT CHAIN 23..1464
FT /note="Glutamate receptor ionotropic, NMDA 2A"
FT /id="PRO_0000011575"
FT TOPO_DOM 23..555
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 556..576
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:B7ZSK1"
FT TOPO_DOM 577..600
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT INTRAMEM 601..620
FT /note="Discontinuously helical"
FT /evidence="ECO:0000250|UniProtKB:B7ZSK1"
FT TOPO_DOM 621..625
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 626..645
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:B7ZSK1"
FT TOPO_DOM 646..816
FT /note="Extracellular"
FT /evidence="ECO:0000305"
FT TRANSMEM 817..837
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:B7ZSK1"
FT TOPO_DOM 838..1464
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT REGION 599..620
FT /note="Pore-forming"
FT /evidence="ECO:0000250|UniProtKB:B7ZSK1"
FT REGION 1001..1088
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1148..1180
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1335..1372
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 1462..1464
FT /note="PDZ-binding"
FT /evidence="ECO:0000305"
FT COMPBIAS 1019..1036
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1037..1088
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1157..1180
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1353..1372
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 44
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:Q00959"
FT BINDING 128
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:Q00959"
FT BINDING 266
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:Q00959"
FT BINDING 282
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:Q00959"
FT BINDING 511..513
FT /ligand="L-glutamate"
FT /ligand_id="ChEBI:CHEBI:29985"
FT /evidence="ECO:0000250|UniProtKB:Q00959"
FT BINDING 518
FT /ligand="L-glutamate"
FT /ligand_id="ChEBI:CHEBI:29985"
FT /evidence="ECO:0000250|UniProtKB:Q00959"
FT BINDING 689..690
FT /ligand="L-glutamate"
FT /ligand_id="ChEBI:CHEBI:29985"
FT /evidence="ECO:0000250|UniProtKB:Q00959"
FT BINDING 730..731
FT /ligand="L-glutamate"
FT /ligand_id="ChEBI:CHEBI:29985"
FT /evidence="ECO:0000250|UniProtKB:Q00959"
FT SITE 614
FT /note="Functional determinant of NMDA receptors"
FT /evidence="ECO:0000250"
FT MOD_RES 882
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P35436"
FT MOD_RES 890
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P35436"
FT MOD_RES 929
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P35436"
FT MOD_RES 1025
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q00959"
FT MOD_RES 1059
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P35436"
FT MOD_RES 1062
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q00959"
FT MOD_RES 1198
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q00959"
FT MOD_RES 1291
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q00959"
FT CARBOHYD 75
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 340
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 380
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 443
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 444
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 541
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 687
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 87..320
FT /evidence="ECO:0000250|UniProtKB:Q00959"
FT DISULFID 429..455
FT /evidence="ECO:0000250|UniProtKB:Q00959"
FT DISULFID 436..456
FT /evidence="ECO:0000250|UniProtKB:Q00959"
FT DISULFID 745..800
FT /evidence="ECO:0000250|UniProtKB:Q00959"
SQ SEQUENCE 1464 AA; 165280 MW; 336AA93491F2F368 CRC64;
MGRVGYWTLL VLPALLVWRG PAPSAAAEKG PPALNIAVML GHSHDVTERE LRTLWGPEQA
AGLPLDVNVV ALLMNRTDPK SLITHVCDLM SGARIHGLVF GDDTDQEAVA QMLDFISSHT
FVPILGIHGG ASMIMNDKDP TSTFFQFGAS IQQQATVMLK IMQDYDWHVF SLVTTIFPGY
REFISFVKTT VDNSFVGWDM QNVITLDTSF EDAKTQVQLK KIHSSVILLY CSKDEAVLIL
SEARSLGLTG YDFFWIVPSL VSGNTELIPK EFPSGLISVS YDDWDYSLEA RVRDGIGILT
TAASSMLEKF SYIPEAKASC YGQMERPEVP MHTLHPFMVN VTWDGKDLSF TEEGYQVHPR
LVVIVLNKDR EWEKVGKWEN HTLSLRHAVW PRYKSFSDCE PDDNHLSIVT LEEAPFVIVE
DIDPLTETCV RNTVPCRKFV KINNSTNEGM NVKKCCKGFC IDILKKLSRT VKFTYDLYLV
TNGKHGKKVN NVWNGMIGEV VYQRAVMAVG SLTINEERSE VVDFSVPFVE TGISVMVSRS
NGTVSPSAFL EPFSASVWVM MFVMLLIVSA IAVFVFEYFS PVGYNRNLAK GKAPHGPSFT
IGKAIWLLWG LVFNNSVPVQ NPKGTTSKIM VSVWAFFAVI FLASYTANLA AFMIQEEFVD
QVTGLSDKKF QRPHDYSPPF RFGTVPNGST ERNIRNNYPY MHQYMTKFNQ KGVEDALVSL
KTGKLDAFIY DAAVLNYKAG RDEGCKLVTI GSGYIFATTG YGIALQKGSP WKRQIDLALL
QFVGDGEMEE LETLWLTGIC HNEKNEVMSS QLDIDNMAGV FYMLAAAMAL SLITFIWEHL
FYWKLRFCFT GVCSDRPGLL FSISRGIYSC IHGVHIEEKK KSPDFNLTGS QSNMLKLLRS
AKNISNMSNM NSSRMDSPKR AADFIQRGSL IMDMVSDKGN LMYSDNRSFQ GKESIFGDNM
NELQTFVANR QKDNLNNYVF QGQHPLTLNE SNPNTVEVAV STESKVNSRP RQLWKKSVDS
IRQDSLSQNP VSQRDEATAE NRTHSLKSPR YLPEEMAHSD ISETSNRATC HREPDNSKNP
KTKDNFKRSV ASKYPKDCSE VERTYLKTKS SSPRDKIYTI DGEKEPGFHL DPPQFVENVT
LPENVDFPDP YQDPSENLRK GDSTLPMNRN PLQNEEGLSN NDQYKLYSKH FTLKDKGSPH
SETSERYRQN STHCRSCLSN LPTYSGHFTM RSPFKCDACL RMGNLYDIDE DQMLQETGNP
ATGEQVYQQD WAQNNALQLQ KNKLRISRQH SYDNIVDKPR ELDLSRPSRS ISLKDRERLL
EGNFYGSLFS VPSSKLSGKK SSLFPQGLED SKRSKSLLPD HTSDNPFLHS HRDDQRLVIG
RCPSDPYKHS LPSQAVNDSY LRSSLRSTAS YCSRDSRGHN DVYISEHVMP YAANKNNMYS
TPRVLNSCSN RRVYKKMPSI ESDV
