GRIN2A

GRIN2A
ساختارهای موجود
PDB	جستجوی هم‌ساخت‌شناسی: PDBe RCSB
فهرست شناسه‌های PDB
	3NFL, 5H8Q, 5H8H, 5H8N, 5H8F, 5I2N, 5I2K, 5KDT, 5KCJ
معین‌کننده‌ها
نام‌های دیگر	GRIN2A, EPND, FESD, GluN2A, LKS, NMDAR2A, NR2A, glutamate ionotropic receptor NMDA type subunit 2A
شناسه‌های بیرونی	OMIM: 138253 MGI: 95820 HomoloGene: 645 GeneCards: GRIN2A
موقعیت ژن (موش)
کروموزوم	کروموزوم ۱۶ (موش)
پایان	9,813,424 bp
الگوی گسترش RNA
	More reference expression data
هستی‌شناسی ژن
عملکرد ملکولی	• calcium channel activity; • zinc ion binding; • NMDA glutamate receptor activity; • metal ion binding; • ion channel activity; • GO:0001948، GO:0016582 پیوند پروتئینی; • ionotropic glutamate receptor activity; • cation channel activity; • extracellularly glutamate-gated ion channel activity; • amyloid-beta binding; • glutamate-gated calcium ion channel activity; • signaling receptor activity;
ترکیبات سلولی	• integral component of membrane; • postsynaptic membrane; • membrane; • synaptic vesicle; • GO:0097483، GO:0097481 postsynaptic density; • پوسته یاخته; • سیناپس; • integral component of plasma membrane; • NMDA selective glutamate receptor complex; • cell surface; • پیوند میان‌یاخته‌ای; • شبکه آندوپلاسمی; • neuron projection; • presynaptic membrane; • postsynaptic density membrane; • integral component of postsynaptic density membrane; • synaptic membrane; • glutamatergic synapse; • cell projection; • dendritic spine;
فرایند زیستی	• یادگیری بصری; • GO:0034613 protein localization; • glutamate receptor signaling pathway; • عصب‌زایی; • واکنش یکه خوردن; • regulation of sensory perception of pain; • positive regulation of long-term synaptic potentiation; • GO:1903363 negative regulation of protein catabolic process; • response to amphetamine; • regulation of membrane potential; • directional locomotion; • modulation of chemical synaptic transmission; • حافظه; • serotonin metabolic process; • ion transport; • یادگیری; • cation transmembrane transport; • MAPK cascade; • regulation of synaptic plasticity; • خواب; • dopamine metabolic process; • ionotropic glutamate receptor signaling pathway; • response to wounding; • calcium ion transmembrane transport; • locomotion; • regulation of postsynaptic membrane potential; • excitatory postsynaptic potential; • learning or memory; • positive regulation of apoptotic process; • درد نوسیسپتیو; • response to ethanol; • calcium ion transport; • تقویت طولانی مدت; • chemical synaptic transmission; • GO:0032320، GO:0032321، GO:0032855، GO:0043089، GO:0032854 positive regulation of GTPase activity; • ion transmembrane transport; • regulation of ion transmembrane transport; • GO:0015915 transport; • brain development; • calcium-mediated signaling; • activation of cysteine-type endopeptidase activity; • GO:0060401 calcium ion transmembrane import into cytosol; • excitatory chemical synaptic transmission; • protein localization to postsynaptic membrane; • cellular response to amyloid-beta; • regulation of NMDA receptor activity;
	منابع: آمیگو / کوئیک‌گو
هم‌ساخت‌شناسی
	2903
	14811
	ENSG00000183454
	ENSMUSG00000059003
	Q12879
	P35436
	NM_001134407، NM_001134408، XM_017023172، XM_017023173، XM_047433993، XM_047433994 NM_000833، NM_001134407، NM_001134408، XM_017023172، XM_017023173، XM_047433993، XM_047433994
	XM_006521795 NM_008170، XM_006521795
	NP_001127879، NP_001127880، XP_011520760، XP_011520763، XP_016878661، XP_016878662 NP_000824، NP_001127879، NP_001127880، XP_011520760، XP_011520763، XP_016878661، XP_016878662
	XP_006521858 NP_032196، XP_006521858
	ویکی‌داده
مشاهده/ویرایش انسان	مشاهده/ویرایش موش

GRIN2A یکی از زیرواحدهای گیرنده NMDA است که در انسان توسط ژنی با همین نام کدگذاری می‌شود. این زیرواحد دارای ۱۴۶۴ اسید آمینه است.^[۴] ایزوفرم‌های کوتاه GluN2A موجود در پستانداران را می‌توان با اتصال آمینو اسیدهای جایگزین نیز تولید کرد و این پلی‌پپتید جدید حاوی ۱۲۸۱ اسید آمینه خواهد بود.^[۵]^[۶]

عملکرد

گیرنده‌های NMDA که GRIN2A یکی از زیر واحدهای سازنده آن‌هاست، یک دسته از گیرنده‌های گلوتامات یونوتروپیک هستند. ثابت شده است که کانال‌های NMDA در ایجاد حافظه طولانی مدت نقش دارند، این عملکرد وابسته به فعالیت در کارایی ارتباط سیناپسی است که تصور می‌شود زمینه‌ساز انواع خاصی از حافظه و یادگیری باشد.^[۷]

اهمیّت بالینی

انواع مختلف این ژن با اثر محافظتی قهوه بر بیماری پارکینسون مرتبط هستند.^[۸]^[۹] جهش در توالی‌های GRIN2A با صرع مقاوم به درمان مرتبط است.^[۱۰] توالی یابی کل ژنوم منجر به کشف ارتباط بین جهش در GRIN2A و طیف گسترده‌ای از بیماری‌های عصبی، از جمله صرع، ناتوانی ذهنی، اختلالات اوتیسمی، تأخیر در رشد، و اسکیزوفرنی شده است.^[۱۱]

تعامل‌های پروتئینی

ثابت شده است که GRIN2A با پروتئین‌های زیر در تعامل است:

DLG1^[۱۲]
DLG3^[۱۳]^[۱۴]
DLG4^[۱۴]^[۱۳]^[۱۵]^[۱۶]^[۱۷]
FYN^[۱۸]
Interleukin 16
PTK2B
Src

منابع

↑ ^۱٫۰ ^۱٫۱ ^۱٫۲ GRCm38: Ensembl release 89: ENSMUSG00000059003 - Ensembl, May 2017
↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
↑ Kalsi G, Whiting P, Bourdelles BL, Callen D, Barnard EA, Gurling H (February 1998). "Localization of the human NMDAR2D receptor subunit gene (GRIN2D) to 19q13.1-qter, the NMDAR2A subunit gene to 16p13.2 (GRIN2A), and the NMDAR2C subunit gene (GRIN2C) to 17q24-q25 using somatic cell hybrid and radiation hybrid mapping panels". Genomics. 47 (3): 423–425. doi:10.1006/geno.1997.5132. PMID 9480759.
↑ Warming H, Pegasiou CM, Pitera AP, Kariis H, Houghton SD, Kurbatskaya K, et al. (July 2019). "A primate-specific short GluN2A-NMDA receptor isoform is expressed in the human brain". Molecular Brain. 12 (1): 64. doi:10.1186/s13041-019-0485-9. PMC 6610962. PMID 31272478.
↑ Herbrechter R, Hube N, Buchholz R, Reiner A (July 2021). "Splicing and editing of ionotropic glutamate receptors: a comprehensive analysis based on human RNA-Seq data". Cellular and Molecular Life Sciences. 78 (14): 5605–5630. doi:10.1007/s00018-021-03865-z. PMC 8257547. PMID 34100982.
↑ "Entrez Gene: GRIN2A glutamate receptor, ionotropic, N-methyl D-aspartate 2A".
↑ Hamza TH, Chen H, Hill-Burns EM, Rhodes SL, Montimurro J, Kay DM, et al. (August 2011). "Genome-wide gene-environment study identifies glutamate receptor gene GRIN2A as a Parkinson's disease modifier gene via interaction with coffee". PLOS Genetics. 7 (8): e1002237. doi:10.1371/journal.pgen.1002237. PMC 3158052. PMID 21876681.
↑ Yamada-Fowler N, Fredrikson M, Söderkvist P (June 2014). "Caffeine interaction with glutamate receptor gene GRIN2A: Parkinson's disease in Swedish population". PLOS ONE. 9 (6): e99294. Bibcode:2014PLoSO...999294Y. doi:10.1371/journal.pone.0099294. PMC 4051678. PMID 24915238.
↑ Venkateswaran S, Myers KA, Smith AC, Beaulieu CL, Schwartzentruber JA, Majewski J, et al. (July 2014). "Whole-exome sequencing in an individual with severe global developmental delay and intractable epilepsy identifies a novel, de novo GRIN2A mutation". Epilepsia. 55 (7): e75–e79. doi:10.1111/epi.12663. PMID 24903190. S2CID 205116246.
↑ Yuan H, Low CM, Moody OA, Jenkins A, Traynelis SF (July 2015). "Ionotropic GABA and Glutamate Receptor Mutations and Human Neurologic Diseases". Molecular Pharmacology. 88 (1): 203–217. doi:10.1124/mol.115.097998. PMC 4468639. PMID 25904555.
↑ Gardoni, Fabrizio; Mauceri, Daniela; Fiorentini, Chiara; Bellone, Camilla; Missale, Cristina; Cattabeni, Flaminio; Luca, Monica Di (2003). "CaMKII-dependent Phosphorylation Regulates SAP97/NR2A Interaction". Journal of Biological Chemistry. 278 (45): 44745–44752. doi:10.1074/jbc.m303576200. ISSN 0021-9258.
↑ ^۱۳٫۰ ^۱۳٫۱ Irie, M.; Hata, Y.; Takeuchi, M.; Ichtchenko, K.; Toyoda, A.; Hirao, K.; Takai, Y.; Rosahl, T. W.; Südhof, T. C. (1997-09-05). "Binding of Neuroligins to PSD-95". Science (به انگلیسی). 277 (5331): 1511–1515. doi:10.1126/science.277.5331.1511. ISSN 0036-8075.
↑ ^۱۴٫۰ ^۱۴٫۱ Lim, Indra Adi; Hall, Duane D.; Hell, Johannes W. (2006). "Selectivity and Promiscuity of the First and Second PDZ Domains of PSD-95 and Synapse-associated Protein 102". Journal of Biological Chemistry. 277 (24): 21697–21711. doi:10.1074/jbc.m112339200. ISSN 0021-9258.
↑ Hou, Xiao-Yu; Zhang, Guang-Yi; Yan, Jing-Zhi; Chen, Min; Liu, Yong (2002). "Activation of NMDA receptors and L-type voltage-gated calcium channels mediates enhanced formation of Fyn–PSD95–NR2A complex after transient brain ischemia". Brain Research. 955 (1–2): 123–132. doi:10.1016/s0006-8993(02)03376-0. ISSN 0006-8993.
↑ Satoh, Kiyotoshi; Yanai, Hiroyuki; Senda, Takao; Kohu, Kazuyoshi; Nakamura, Tsutomu; Okumura, Nobuaki; Matsumine, Akihiko; Kobayashi, Shigeru; Toyoshima, Kumao (1997). "DAP‐1, a novel protein that interacts with the guanylate kinase‐like domains of hDLG and PSD‐95". Genes to Cells (به انگلیسی). 2 (6): 415–424. doi:10.1046/j.1365-2443.1997.1310329.x. ISSN 1356-9597.
↑ ""A developmental change in NMDA receptor-associated proteins at hippocampal synapses"" (به انگلیسی).
↑ Hou, Xiao-Yu; Zhang, Guang-Yi; Yan, Jing-Zhi; Chen, Min; Liu, Yong (2002). "Activation of NMDA receptors and L-type voltage-gated calcium channels mediates enhanced formation of Fyn–PSD95–NR2A complex after transient brain ischemia". Brain Research (به انگلیسی). 955 (1–2): 123–132. doi:10.1016/S0006-8993(02)03376-0.

[refGRCm38Ensembl-1] ۱٫۰ ^۱٫۱ ^۱٫۲ GRCm38: Ensembl release 89: ENSMUSG00000059003 - Ensembl, May 2017

[2] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[3] "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[pmid_9480759-4] Kalsi G, Whiting P, Bourdelles BL, Callen D, Barnard EA, Gurling H (February 1998). "Localization of the human NMDAR2D receptor subunit gene (GRIN2D) to 19q13.1-qter, the NMDAR2A subunit gene to 16p13.2 (GRIN2A), and the NMDAR2C subunit gene (GRIN2C) to 17q24-q25 using somatic cell hybrid and radiation hybrid mapping panels". Genomics. 47 (3): 423–425. doi:10.1006/geno.1997.5132. PMID 9480759.

[5] Warming H, Pegasiou CM, Pitera AP, Kariis H, Houghton SD, Kurbatskaya K, et al. (July 2019). "A primate-specific short GluN2A-NMDA receptor isoform is expressed in the human brain". Molecular Brain. 12 (1): 64. doi:10.1186/s13041-019-0485-9. PMC 6610962. PMID 31272478.

[6] Herbrechter R, Hube N, Buchholz R, Reiner A (July 2021). "Splicing and editing of ionotropic glutamate receptors: a comprehensive analysis based on human RNA-Seq data". Cellular and Molecular Life Sciences. 78 (14): 5605–5630. doi:10.1007/s00018-021-03865-z. PMC 8257547. PMID 34100982.

[7] "Entrez Gene: GRIN2A glutamate receptor, ionotropic, N-methyl D-aspartate 2A".

[8] Hamza TH, Chen H, Hill-Burns EM, Rhodes SL, Montimurro J, Kay DM, et al. (August 2011). "Genome-wide gene-environment study identifies glutamate receptor gene GRIN2A as a Parkinson's disease modifier gene via interaction with coffee". PLOS Genetics. 7 (8): e1002237. doi:10.1371/journal.pgen.1002237. PMC 3158052. PMID 21876681.

[9] Yamada-Fowler N, Fredrikson M, Söderkvist P (June 2014). "Caffeine interaction with glutamate receptor gene GRIN2A: Parkinson's disease in Swedish population". PLOS ONE. 9 (6): e99294. Bibcode:2014PLoSO...999294Y. doi:10.1371/journal.pone.0099294. PMC 4051678. PMID 24915238.

[10] Venkateswaran S, Myers KA, Smith AC, Beaulieu CL, Schwartzentruber JA, Majewski J, et al. (July 2014). "Whole-exome sequencing in an individual with severe global developmental delay and intractable epilepsy identifies a novel, de novo GRIN2A mutation". Epilepsia. 55 (7): e75–e79. doi:10.1111/epi.12663. PMID 24903190. S2CID 205116246.

[YuanLow2015-11] Yuan H, Low CM, Moody OA, Jenkins A, Traynelis SF (July 2015). "Ionotropic GABA and Glutamate Receptor Mutations and Human Neurologic Diseases". Molecular Pharmacology. 88 (1): 203–217. doi:10.1124/mol.115.097998. PMC 4468639. PMID 25904555.

[12] Gardoni, Fabrizio; Mauceri, Daniela; Fiorentini, Chiara; Bellone, Camilla; Missale, Cristina; Cattabeni, Flaminio; Luca, Monica Di (2003). "CaMKII-dependent Phosphorylation Regulates SAP97/NR2A Interaction". Journal of Biological Chemistry. 278 (45): 44745–44752. doi:10.1074/jbc.m303576200. ISSN 0021-9258.

[:0-13] ۱۳٫۰ ^۱۳٫۱ Irie, M.; Hata, Y.; Takeuchi, M.; Ichtchenko, K.; Toyoda, A.; Hirao, K.; Takai, Y.; Rosahl, T. W.; Südhof, T. C. (1997-09-05). "Binding of Neuroligins to PSD-95". Science (به انگلیسی). 277 (5331): 1511–1515. doi:10.1126/science.277.5331.1511. ISSN 0036-8075.

[:1-14] ۱۴٫۰ ^۱۴٫۱ Lim, Indra Adi; Hall, Duane D.; Hell, Johannes W. (2006). "Selectivity and Promiscuity of the First and Second PDZ Domains of PSD-95 and Synapse-associated Protein 102". Journal of Biological Chemistry. 277 (24): 21697–21711. doi:10.1074/jbc.m112339200. ISSN 0021-9258.

[15] Hou, Xiao-Yu; Zhang, Guang-Yi; Yan, Jing-Zhi; Chen, Min; Liu, Yong (2002). "Activation of NMDA receptors and L-type voltage-gated calcium channels mediates enhanced formation of Fyn–PSD95–NR2A complex after transient brain ischemia". Brain Research. 955 (1–2): 123–132. doi:10.1016/s0006-8993(02)03376-0. ISSN 0006-8993.

[16] Satoh, Kiyotoshi; Yanai, Hiroyuki; Senda, Takao; Kohu, Kazuyoshi; Nakamura, Tsutomu; Okumura, Nobuaki; Matsumine, Akihiko; Kobayashi, Shigeru; Toyoshima, Kumao (1997). "DAP‐1, a novel protein that interacts with the guanylate kinase‐like domains of hDLG and PSD‐95". Genes to Cells (به انگلیسی). 2 (6): 415–424. doi:10.1046/j.1365-2443.1997.1310329.x. ISSN 1356-9597.

[17] ""A developmental change in NMDA receptor-associated proteins at hippocampal synapses"" (به انگلیسی).

[18] Hou, Xiao-Yu; Zhang, Guang-Yi; Yan, Jing-Zhi; Chen, Min; Liu, Yong (2002). "Activation of NMDA receptors and L-type voltage-gated calcium channels mediates enhanced formation of Fyn–PSD95–NR2A complex after transient brain ischemia". Brain Research (به انگلیسی). 955 (1–2): 123–132. doi:10.1016/S0006-8993(02)03376-0.

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