NMDE2_CANLF
ID NMDE2_CANLF Reviewed; 1485 AA.
AC Q5R1P3;
DT 29-MAY-2007, integrated into UniProtKB/Swiss-Prot.
DT 04-JAN-2005, sequence version 1.
DT 03-AUG-2022, entry version 123.
DE RecName: Full=Glutamate receptor ionotropic, NMDA 2B;
DE Short=GluN2B;
DE AltName: Full=Glutamate [NMDA] receptor subunit epsilon-2;
DE AltName: Full=N-methyl D-aspartate receptor subtype 2B;
DE Short=NMDAR2B;
DE Short=NR2B;
DE Flags: Precursor;
GN Name=GRIN2B;
OS Canis lupus familiaris (Dog) (Canis familiaris).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Carnivora; Caniformia; Canidae; Canis.
OX NCBI_TaxID=9615;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Brain cortex;
RA Taki K., Shinjo K.;
RT "Canis familiaris glutamate receptor, ionotropic, NMDA2B (Grin2b), mRNA,
RT complete cds.";
RL Submitted (DEC-2004) to the EMBL/GenBank/DDBJ databases.
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 (By
CC similarity). In concert with DAPK1 at extrasynaptic sites, acts as a
CC central mediator for stroke damage. Its phosphorylation at Ser-1303 by
CC DAPK1 enhances synaptic NMDA receptor channel activity inducing
CC injurious Ca2+ influx through them, resulting in an irreversible
CC neuronal death. Contributes to neural pattern formation in the
CC developing brain. Plays a role in long-term depression (LTD) of
CC hippocampus membrane currents and in synaptic plasticity (By
CC similarity). {ECO:0000250|UniProtKB:Q00960,
CC ECO:0000250|UniProtKB:Q01097}.
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). Can also form heterotetrameric channels
CC that contain at least one zeta subunit (GRIN1), at least one epsilon
CC subunit, plus GRIN3A or GRIN3B. In vivo, the subunit composition may
CC depend on the expression levels of the different subunits. Found in a
CC complex with GRIN1, GRIN3A and PPP2CB. Found in a complex with GRIN1
CC and GRIN3B. Interacts with MAGI3. Interacts with HIP1 and Neto1.
CC Interacts with PDZ domains of PATJ, DLG3 and DLG4. Interacts with DAPK1
CC (By similarity). Found in a complex with GRIN1 and PRR7. Interacts with
CC PRR7 (By similarity). Interacts with CAMK2A (By similarity). Interacts
CC with ARC; preventing ARC oligomerization (By similarity). Interacts
CC with TMEM25 (By similarity). {ECO:0000250|UniProtKB:Q00960,
CC ECO:0000250|UniProtKB:Q01097, ECO:0000250|UniProtKB:Q13224}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:Q00960};
CC Multi-pass membrane protein {ECO:0000250|UniProtKB:Q00960}.
CC Postsynaptic cell membrane {ECO:0000250|UniProtKB:Q00960}; Multi-pass
CC membrane protein {ECO:0000250|UniProtKB:Q00960}. Late endosome
CC {ECO:0000250|UniProtKB:Q01097}. Lysosome
CC {ECO:0000250|UniProtKB:Q01097}. Cytoplasm, cytoskeleton
CC {ECO:0000250|UniProtKB:Q01097}. Note=Co-localizes with the motor
CC protein KIF17 along microtubules. {ECO:0000250|UniProtKB:Q01097}.
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:Q00960}.
CC -!- PTM: Phosphorylated on tyrosine residues (By similarity).
CC Phosphorylation at Ser-1303 by DAPK1 enhances synaptic NMDA receptor
CC channel activity (By similarity). {ECO:0000250|UniProtKB:Q00960,
CC ECO:0000250|UniProtKB:Q01097}.
CC -!- SIMILARITY: Belongs to the glutamate-gated ion channel (TC 1.A.10.1)
CC family. NR2B/GRIN2B subfamily. {ECO:0000305}.
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DR EMBL; AB195992; BAD74215.1; -; mRNA.
DR RefSeq; NP_001008719.1; NM_001008719.1.
DR RefSeq; XP_005636773.1; XM_005636716.2.
DR RefSeq; XP_013963742.1; XM_014108267.1.
DR RefSeq; XP_013963743.1; XM_014108268.1.
DR AlphaFoldDB; Q5R1P3; -.
DR SMR; Q5R1P3; -.
DR STRING; 9615.ENSCAFP00000039796; -.
DR PaxDb; Q5R1P3; -.
DR Ensembl; ENSCAFT00030047919; ENSCAFP00030041923; ENSCAFG00030025940.
DR Ensembl; ENSCAFT00040043337; ENSCAFP00040037805; ENSCAFG00040023322.
DR Ensembl; ENSCAFT00845040679; ENSCAFP00845031842; ENSCAFG00845022981.
DR GeneID; 494009; -.
DR KEGG; cfa:494009; -.
DR CTD; 2904; -.
DR VEuPathDB; HostDB:ENSCAFG00845022981; -.
DR eggNOG; KOG1053; Eukaryota.
DR GeneTree; ENSGT00940000155964; -.
DR InParanoid; Q5R1P3; -.
DR TreeFam; TF314731; -.
DR Reactome; R-CFA-3928662; EPHB-mediated forward signaling.
DR Reactome; R-CFA-438066; Unblocking of NMDA receptors, glutamate binding and activation.
DR Reactome; R-CFA-5673001; RAF/MAP kinase cascade.
DR Reactome; R-CFA-8849932; Synaptic adhesion-like molecules.
DR Reactome; R-CFA-9609736; Assembly and cell surface presentation of NMDA receptors.
DR Proteomes; UP000002254; Chromosome 27.
DR Bgee; ENSCAFG00000013148; Expressed in prefrontal cortex and 9 other tissues.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0005856; C:cytoskeleton; IEA:UniProtKB-SubCell.
DR GO; GO:0005887; C:integral component of plasma membrane; ISS:UniProtKB.
DR GO; GO:0005770; C:late endosome; ISS:UniProtKB.
DR GO; GO:0005764; C:lysosome; 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:0016595; F:glutamate binding; ISS:UniProtKB.
DR GO; GO:0022849; F:glutamate-gated calcium ion channel activity; ISS:UniProtKB.
DR GO; GO:0016594; F:glycine binding; IEA:Ensembl.
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 GO; GO:0051290; P:protein heterotetramerization; ISS:UniProtKB.
DR GO; GO:0045471; P:response to ethanol; IEA:Ensembl.
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; Cytoplasm; Cytoskeleton; Disulfide bond; Endosome;
KW Glycoprotein; Ion channel; Ion transport; Ligand-gated ion channel;
KW Lysosome; Magnesium; Membrane; Metal-binding; Phosphoprotein;
KW Postsynaptic cell membrane; Receptor; Reference proteome; Signal; Synapse;
KW Transmembrane; Transmembrane helix; Transport; Zinc.
FT SIGNAL 1..26
FT /evidence="ECO:0000255"
FT CHAIN 27..1485
FT /note="Glutamate receptor ionotropic, NMDA 2B"
FT /id="PRO_0000289579"
FT TOPO_DOM 27..557
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:Q00960"
FT TRANSMEM 558..576
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:Q00960"
FT TOPO_DOM 577..603
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q00960"
FT INTRAMEM 604..623
FT /note="Discontinuously helical"
FT /evidence="ECO:0000250|UniProtKB:Q00960"
FT TOPO_DOM 624..630
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q00960"
FT TRANSMEM 631..646
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:Q00960"
FT TOPO_DOM 647..817
FT /note="Extracellular"
FT /evidence="ECO:0000250|UniProtKB:Q00960"
FT TRANSMEM 818..837
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:Q00960"
FT TOPO_DOM 838..1485
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q00960"
FT REGION 604..623
FT /note="Pore-forming"
FT /evidence="ECO:0000250|UniProtKB:A7XY94"
FT REGION 1074..1097
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1162..1194
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1269..1302
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1292..1304
FT /note="Interaction with DAPK1"
FT /evidence="ECO:0000250|UniProtKB:Q01097"
FT MOTIF 1483..1485
FT /note="PDZ-binding"
FT /evidence="ECO:0000250"
FT COMPBIAS 1079..1097
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1276..1291
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 127
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:Q00960"
FT BINDING 284
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:Q00960"
FT BINDING 514
FT /ligand="L-glutamate"
FT /ligand_id="ChEBI:CHEBI:29985"
FT /evidence="ECO:0000250|UniProtKB:Q00960"
FT BINDING 519
FT /ligand="L-glutamate"
FT /ligand_id="ChEBI:CHEBI:29985"
FT /evidence="ECO:0000250|UniProtKB:Q00960"
FT BINDING 690..691
FT /ligand="L-glutamate"
FT /ligand_id="ChEBI:CHEBI:29985"
FT /evidence="ECO:0000250|UniProtKB:Q00960"
FT BINDING 732
FT /ligand="L-glutamate"
FT /ligand_id="ChEBI:CHEBI:29985"
FT /evidence="ECO:0000250|UniProtKB:Q00960"
FT SITE 615
FT /note="Functional determinant of NMDA receptors"
FT /evidence="ECO:0000250"
FT MOD_RES 882
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q01097"
FT MOD_RES 886
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q00960"
FT MOD_RES 917
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q01097"
FT MOD_RES 920
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q01097"
FT MOD_RES 962
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q01097"
FT MOD_RES 1039
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q01097"
FT MOD_RES 1058
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q01097"
FT MOD_RES 1061
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q01097"
FT MOD_RES 1064
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q01097"
FT MOD_RES 1109
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q01097"
FT MOD_RES 1133
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q01097"
FT MOD_RES 1143
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q01097"
FT MOD_RES 1155
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q01097"
FT MOD_RES 1255
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q01097"
FT MOD_RES 1259
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q01097"
FT MOD_RES 1303
FT /note="Phosphoserine; by DAPK1"
FT /evidence="ECO:0000250|UniProtKB:Q01097"
FT MOD_RES 1475
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q01097"
FT CARBOHYD 74
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 341
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 348
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 491
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 542
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 688
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 86..321
FT /evidence="ECO:0000250|UniProtKB:Q00960"
FT DISULFID 429..456
FT /evidence="ECO:0000250|UniProtKB:Q00960"
FT DISULFID 436..457
FT /evidence="ECO:0000250|UniProtKB:Q00960"
FT DISULFID 746..801
FT /evidence="ECO:0000250|UniProtKB:Q00960"
SQ SEQUENCE 1485 AA; 166244 MW; 526E5868F98BDE1D CRC64;
MKPRAECCSP KFWLVLAVLA VSGSRARSQK SPPSIGIAVI LVGTSDEVAI KDAHEKDDFH
HLSVVPRVEL VAMNETDPKS IITRICDLMS DRKIQGVVFA DDTDQEAIAQ ILDFISAQTL
TPILGIHGGS SMIMADKDES SMFFQFGPSI EQQASVMLNI MEEYDWYIFS IVTTYFPGYQ
DFVNKIRSTI ENSFVGWELE EVLLLDMSLD DGDSKIQNQL KKLQSPIILL YCTKEEATYI
FEVANSVGLT GYGYTWIVPS LVAGDTDTVP SEFPTGLISV SYDEWDYGLP ARVRDGIAII
TTAASDMLSE HSFIPEPKSS CYNTHEKRIY QSNMLNRYLI NVTFEGRNLS FSEDGYQMHP
KLVIILLNKE RKWERVGKWK DKSLQMKYYV WPRMCPETEE QEDDHLSIVT LEEAPFVIVE
SVDPLSGTCM RNTVPCQKRI VSENKTDEEP GYIKKCCKGF CIDILKKISK SVKFTYDLYL
VTNGKHGKKI NGTWNGMIGE VVMKRAYMAV GSLTINEERS EVVDFSVPFI ETGISVMVSR
SNGTVSPSAF LEPFSADVWV MMFVMLLIVS AVAVFVFEYF SPVGYNRCLA DGREPGGPSF
TIGKAIWLLW GLVFNNSVPV QNPKGTTSKI MVSVWAFFAV IFLASYTANL AAFMIQEEYV
DQVSGLSDKK FQRPNDFSPP FRFGTVPNGS TERNIRNNYA EMHAYMGKFN QRGVDDALLS
LKTGKLDAFI YDAAVLNYMA GRDEGCKLVT IGSGKVFAST GYGIAIQKDS GWKRQVDLAI
LQLFGDGEME ELEALWLTGI CHNEKNEVMS SQLDIDNMAG VFYMLGAAMA LSLITFICEH
LFYWQFRHCF MGVCSGKPGM VFSISRGIYS CIHGVAIEER QSVMNSPTAT MNNTHSNILR
LLRTAKNMAN LSGVNGSPQS ALDFIRRESS VYDISEHRRS FTHSDCKSYN NPPCEENLFS
DYISEVERTF GNLQLKDSNV YQDHYHHHHR PHSIGSASSI DGLYDCDNPP FTTQPRSISK
KPLDLGLPSS KHSQLSDLYG KFSFKSDRYS GHDDLIRSDV SDISTHTVTY GNIEGNAAKR
RKQQYKDSLK KRPASAKSRR EFDEIELAYR RRPPRSPDHK RYFRDKEGLR DFYLDQFRTK
ENSPHWEHVD LTDIYKEQSD DFKRDSVSGG GPCTNRSHLK HGAGDKHGVV SGVPAPWEKN
LSNVDWEDRS GGNFCRSCPS KLHNYSTAVT GQNSGRQACI RCEACKKAGN LYDISEDNSL
QELDQPAAPV AVPSNAPSTK YPQSPTNSKA QKKTRNKLRR QHSYDTFVDL QKEEAALAPR
SVSLKDKGRF LDGSPYAHMF ETPAGESTFA NHESSVAAAG HRHHNNPGGG GYMLSKSLYP
DRVTQNPFIP TFGDDQCLLH GSKSYFFRQP TVAGAPKARP DFRALVTNKP VVSALHGAVP
GRFQKDICIG NQSNPCVPNN KNPRAFNGSS NGHVYEKLSS IESDV
