PSEN2

PSEN2
Identifikatori
Aliasi	PSEN2
Vanjski ID-jevi	OMIM: 600759 MGI: 109284 HomoloGene: 386 GeneCards: PSEN2
Lokacija gena (čovjek)
Hrom.	Hromosom 1 (čovjek)
Kraj	226,927,726 bp
Lokacija gena (miš)
Hrom.	Hromosom 1 (miš)
Kraj	180,091,003 bp
Obrazac RNK ekspresije
	; ; ; ;
	Više referentnih podataka o ekspresiji
Ontologija gena
Molekularna funkcija	• endopeptidase activity; • GO:0070122 peptidase activity; • GO:0001948, GO:0016582 vezivanje za proteine; • hydrolase activity; • aspartic endopeptidase activity, intramembrane cleaving; • aspartic-type endopeptidase activity;
Ćelijska komponenta	• integral component of membrane; • centrosom; • Golđijev aparat; • endoplasmic reticulum membrane; • membrana; • Golđijeva membrana; • ćelijska membrana; • integral component of plasma membrane; • soma; • nuclear inner membrane; • Z discdkac; • Endoplazmatski retikulum; • perinuklearno područje citoplazme; • kinetohor; • mitochondrial inner membrane; • lysosomal membrane; • cell cortex; • cell surface; • Akson; • growth cone; • Nervno-mišićna veza; • ciliary rootlet; • dendritic shaft; • Lipidni splav; • jedro; • early endosome; • Sinapsna vezikula; • apical plasma membrane; • GO:0009327 makromolekulani kompleks; • synaptic membrane; • integral component of presynaptic membrane; • intracellular anatomical structure;
Biološki proces	• Notch signaling pathway; • GO:0007243 intracellular signal transduction; • response to hypoxia; • ephrin receptor signaling pathway; • protein processing; • GO:0048554 positive regulation of catalytic activity; • negative regulation of apoptotic process; • amyloid-beta metabolic process; • Proteoliza; • membrane protein ectodomain proteolysis; • membrane protein intracellular domain proteolysis; • positive regulation of apoptotic process; • Notch receptor processing; • calcium ion transport; • amyloid precursor protein catabolic process; • Notch receptor processing, ligand-dependent; • regulation of calcium import into the mitochondrion; • mitochondrion-endoplasmic reticulum membrane tethering;
	Izvori:Amigo / QuickGO
Ortolozi
	5664
	19165
	ENSG00000143801
	ENSMUSG00000010609
	P49810
	Q61144
	NM_000447; NM_012486
	NM_001128605; NM_011183
	NP_000438; NP_036618
	NP_001122077; NP_035313
	Wikipodaci
Pogledaj/uredi – čovjek	Pogledaj/uredi – miš

Presenilin-2 jest protein koji je kod ljudi kodiran genom PSEN2 sa hromosoma 1.^[5]

Aminokiselinska sekvenca

Dužina polipeptidnog lanca je 448 aminokiselina, a molekulska težina 50.140 Da.^[6]

C: Cistein

D: Asparaginska kiselina

E: Glutaminska kiselina

F: Fenilalanin

G: Glicin

H: Histidin

I: Izoleucin

K: Lizin

L: Leucin

M: Metionin

N: Asparagin

P: Prolin

Q: Glutamin

R: Arginin

S: Serin

T: Treonin

V: Valin

W: Triptofan

Y: Tirozin

10	20	30	40	50
MLTFMASDSE	EEVCDERTSL	MSAESPTPRS	CQEGRQGPED	GENTAQWRSQ
ENEEDGEEDP	DRYVCSGVPG	RPPGLEEELT	LKYGAKHVIM	LFVPVTLCMI
VVVATIKSVR	FYTEKNGQLI	YTPFTEDTPS	VGQRLLNSVL	NTLIMISVIV
VMTIFLVVLY	KYRCYKFIHG	WLIMSSLMLL	FLFTYIYLGE	VLKTYNVAMD
YPTLLLTVWN	FGAVGMVCIH	WKGPLVLQQA	YLIMISALMA	LVFIKYLPEW
SAWVILGAIS	VYDLVAVLCP	KGPLRMLVET	AQERNEPIFP	ALIYSSAMVW
TVGMAKLDPS	SQGALQLPYD	PEMEEDSYDS	FGEPSYPEVF	EPPLTGYPGE
ELEEEEERGV	KLGLGDFIFY	SVLVGKAAAT	GSGDWNTTLA	CFVAILIGLC
LTLLLLAVFK	KALPALPISI	TFGLIFYFST	DNLVRPFMDT	LASHQLYI

Funkcija

Kod Alzheimerove bolesti (AD), pacijenti sa naslijeđenim oblikom nose mutacije u presenilinskim proteinima (PSEN1; PSEN2) ili amiloidnom prekursoru proteina (APP). Ove mutacije povezane sa bolešću rezultiraju povećanom proizvodnjom dužeg oblika varijante amiloid-beta (glavna komponenta amiloidnih naslaga pronađenih u mozgu AD). Pretpostavlja se da presenilini reguli procesiranje APP kroz svoje efekte na gama-sekretazu, enzim koji cijepa APP. Takođe, smatra se da su presenilini uključeni u cepanje Notch receptora, tako da oni ili direktno regulišu aktivnost gama-sekretaze ili su sami proteaza enzimi. Identifikovana su dva alternativna transkripta PSEN2.^[7]

U melanocitnim ćelijama, ekspresija gena PSEN2 može biti regulirana MITF-om.^[8]

Interakcije

Pokazalo se da PSEN2 u u interakciji sa:

Reference

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000143801 - Ensembl, maj 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000010609 - Ensembl, maj 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.
^ Levy-Lahad E, Wasco W, Poorkaj P, Romano DM, Oshima J, Pettingell WH, Yu CE, Jondro PD, Schmidt SD, Wang K (septembar 1995). "Candidate gene for the chromosome 1 familial Alzheimer's disease locus". Science. 269 (5226): 973–977. Bibcode:1995Sci...269..973L. doi:10.1126/science.7638622. PMID 7638622. S2CID 27296868.
^ "UniProt, P49810" (jezik: engleski). Pristupljeno 16. 12. 2021.
^ "Entrez Gene: PSEN2 presenilin 2 (Alzheimer disease 4)".
^ Hoek KS, Schlegel NC, Eichhoff OM, Widmer DS, Praetorius C, Einarsson SO, Valgeirsdottir S, Bergsteinsdottir K, Schepsky A, Dummer R, Steingrimsson E (2008). "Novel MITF targets identified using a two-step DNA microarray strategy". Pigment Cell Melanoma Res. 21 (6): 665–676. doi:10.1111/j.1755-148X.2008.00505.x. PMID 19067971.
^ Passer BJ, Pellegrini L, Vito P, Ganjei JK, D'Adamio L (august 1999). "Interaction of Alzheimer's presenilin-1 and presenilin-2 with Bcl-X(L). A potential role in modulating the threshold of cell death". J. Biol. Chem. 274 (34): 24007–13. doi:10.1074/jbc.274.34.24007. PMID 10446169.
^ Shinozaki K, Maruyama K, Kume H, Tomita T, Saido TC, Iwatsubo T, Obata K (maj 1998). "The presenilin 2 loop domain interacts with the mu-calpain C-terminal region". Int. J. Mol. Med. 1 (5): 797–9. doi:10.3892/ijmm.1.5.797. PMID 9852298.
^ Stabler SM, Ostrowski LL, Janicki SM, Monteiro MJ (juni 1999). "A myristoylated calcium-binding protein that preferentially interacts with the Alzheimer's disease presenilin 2 protein". J. Cell Biol. 145 (6): 1277–92. doi:10.1083/jcb.145.6.1277. PMC 2133148. PMID 10366599.
^ Buxbaum JD, Choi EK, Luo Y, Lilliehook C, Crowley AC, Merriam DE, Wasco W (oktobar 1998). "Calsenilin: a calcium-binding protein that interacts with the presenilins and regulates the levels of a presenilin fragment". Nat. Med. 4 (10): 1177–81. doi:10.1038/2673. PMID 9771752. S2CID 10799492.
^ Choi EK, Zaidi NF, Miller JS, Crowley AC, Merriam DE, Lilliehook C, Buxbaum JD, Wasco W (juni 2001). "Calsenilin is a substrate for caspase-3 that preferentially interacts with the familial Alzheimer's disease-associated C-terminal fragment of presenilin 2". J. Biol. Chem. 276 (22): 19197–204. doi:10.1074/jbc.M008597200. PMID 11278424.
^ Tanahashi H, Tabira T (septembar 2000). "Alzheimer's disease-associated presenilin 2 interacts with DRAL, an LIM-domain protein". Hum. Mol. Genet. 9 (15): 2281–9. doi:10.1093/oxfordjournals.hmg.a018919. PMID 11001931.
^ Zhang W, Han SW, McKeel DW, Goate A, Wu JY (februar 1998). "Interaction of presenilins with the filamin family of actin-binding proteins". J. Neurosci. 18 (3): 914–22. doi:10.1523/JNEUROSCI.18-03-00914.1998. PMC 2042137. PMID 9437013.
^ Morohashi Y, Hatano N, Ohya S, Takikawa R, Watabiki T, Takasugi N, Imaizumi Y, Tomita T, Iwatsubo T (april 2002). "Molecular cloning and characterization of CALP/KChIP4, a novel EF-hand protein interacting with presenilin 2 and voltage-gated potassium channel subunit Kv4". J. Biol. Chem. 277 (17): 14965–75. doi:10.1074/jbc.M200897200. PMID 11847232.
^ Lee SF, Shah S, Li H, Yu C, Han W, Yu G (novembar 2002). "Mammalian APH-1 interacts with presenilin and nicastrin and is required for intramembrane proteolysis of amyloid-beta precursor protein and Notch". J. Biol. Chem. 277 (47): 45013–9. doi:10.1074/jbc.M208164200. PMID 12297508.
^ Yu G, Nishimura M, Arawaka S, Levitan D, Zhang L, Tandon A, Song YQ, Rogaeva E, Chen F, Kawarai T, Supala A, Levesque L, Yu H, Yang DS, Holmes E, Milman P, Liang Y, Zhang DM, Xu DH, Sato C, Rogaev E, Smith M, Janus C, Zhang Y, Aebersold R, Farrer LS, Sorbi S, Bruni A, Fraser P, St George-Hyslop P (septembar 2000). "Nicastrin modulates presenilin-mediated notch/glp-1 signal transduction and betaAPP processing". Nature. 407 (6800): 48–54. Bibcode:2000Natur.407...48Y. doi:10.1038/35024009. PMID 10993067. S2CID 4339220.
^ Mah AL, Perry G, Smith MA, Monteiro MJ (novembar 2000). "Identification of ubiquilin, a novel presenilin interactor that increases presenilin protein accumulation". J. Cell Biol. 151 (4): 847–62. doi:10.1083/jcb.151.4.847. PMC 2169435. PMID 11076969.

Dopunska literatura

Cruts M, Van Broeckhoven C (1998). "Presenilin mutations in Alzheimer's disease". Hum. Mutat. 11 (3): 183–190. doi:10.1002/(SICI)1098-1004(1998)11:3<183::AID-HUMU1>3.0.CO;2-J. PMID 9521418.
McGeer PL, Kawamata T, McGeer EG (1998). "Localization and possible functions of presenilins in brain". Reviews in the Neurosciences. 9 (1): 1–15. doi:10.1515/REVNEURO.1998.9.1.1. PMID 9683324. S2CID 22791458.
Nishimura M, Yu G, St George-Hyslop PH (1999). "Biology of presenilins as causative molecules for Alzheimer disease". Clin. Genet. 55 (4): 219–225. doi:10.1034/j.1399-0004.1999.550401.x. PMID 10361981. S2CID 35128500.
da Costa CA (2006). "Recent insights on the pro-apoptotic phenotype elicited by presenilin 2 and its caspase and presenilinase-derived fragments". Current Alzheimer Research. 2 (5): 507–514. doi:10.2174/156720505774932278. PMID 16375654.
Wolfe MS (2007). "When loss is gain: reduced presenilin proteolytic function leads to increased Abeta42/Abeta40. Talking Point on the role of presenilin mutations in Alzheimer disease". EMBO Rep. 8 (2): 136–140. doi:10.1038/sj.embor.7400896. PMC 1796780. PMID 17268504.
De Strooper B (2007). "Loss-of-function presenilin mutations in Alzheimer disease. Talking Point on the role of presenilin mutations in Alzheimer disease". EMBO Rep. 8 (2): 141–146. doi:10.1038/sj.embor.7400897. PMC 1796779. PMID 17268505.

Vanjski linkovi

GeneReviews/NCBI/NIH/UW entry on Early-Onset Familial Alzheimer Disease

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000143801 - Ensembl, maj 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000010609 - Ensembl, maj 2017

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

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

[pmid7638622-5] Levy-Lahad E, Wasco W, Poorkaj P, Romano DM, Oshima J, Pettingell WH, Yu CE, Jondro PD, Schmidt SD, Wang K (septembar 1995). "Candidate gene for the chromosome 1 familial Alzheimer's disease locus". Science. 269 (5226): 973–977. Bibcode:1995Sci...269..973L. doi:10.1126/science.7638622. PMID 7638622. S2CID 27296868.

[UniProt-6] "UniProt, P49810" (jezik: engleski). Pristupljeno 16. 12. 2021.

[7] "Entrez Gene: PSEN2 presenilin 2 (Alzheimer disease 4)".

[pmid19067971-8] Hoek KS, Schlegel NC, Eichhoff OM, Widmer DS, Praetorius C, Einarsson SO, Valgeirsdottir S, Bergsteinsdottir K, Schepsky A, Dummer R, Steingrimsson E (2008). "Novel MITF targets identified using a two-step DNA microarray strategy". Pigment Cell Melanoma Res. 21 (6): 665–676. doi:10.1111/j.1755-148X.2008.00505.x. PMID 19067971.

[pmid10446169-9] Passer BJ, Pellegrini L, Vito P, Ganjei JK, D'Adamio L (august 1999). "Interaction of Alzheimer's presenilin-1 and presenilin-2 with Bcl-X(L). A potential role in modulating the threshold of cell death". J. Biol. Chem. 274 (34): 24007–13. doi:10.1074/jbc.274.34.24007. PMID 10446169.

[pmid9852298-10] Shinozaki K, Maruyama K, Kume H, Tomita T, Saido TC, Iwatsubo T, Obata K (maj 1998). "The presenilin 2 loop domain interacts with the mu-calpain C-terminal region". Int. J. Mol. Med. 1 (5): 797–9. doi:10.3892/ijmm.1.5.797. PMID 9852298.

[pmid10366599-11] Stabler SM, Ostrowski LL, Janicki SM, Monteiro MJ (juni 1999). "A myristoylated calcium-binding protein that preferentially interacts with the Alzheimer's disease presenilin 2 protein". J. Cell Biol. 145 (6): 1277–92. doi:10.1083/jcb.145.6.1277. PMC 2133148. PMID 10366599.

[pmid9771752-12] Buxbaum JD, Choi EK, Luo Y, Lilliehook C, Crowley AC, Merriam DE, Wasco W (oktobar 1998). "Calsenilin: a calcium-binding protein that interacts with the presenilins and regulates the levels of a presenilin fragment". Nat. Med. 4 (10): 1177–81. doi:10.1038/2673. PMID 9771752. S2CID 10799492.

[pmid11278424-13] Choi EK, Zaidi NF, Miller JS, Crowley AC, Merriam DE, Lilliehook C, Buxbaum JD, Wasco W (juni 2001). "Calsenilin is a substrate for caspase-3 that preferentially interacts with the familial Alzheimer's disease-associated C-terminal fragment of presenilin 2". J. Biol. Chem. 276 (22): 19197–204. doi:10.1074/jbc.M008597200. PMID 11278424.

[pmid11001931-14] Tanahashi H, Tabira T (septembar 2000). "Alzheimer's disease-associated presenilin 2 interacts with DRAL, an LIM-domain protein". Hum. Mol. Genet. 9 (15): 2281–9. doi:10.1093/oxfordjournals.hmg.a018919. PMID 11001931.

[pmid9437013-15] Zhang W, Han SW, McKeel DW, Goate A, Wu JY (februar 1998). "Interaction of presenilins with the filamin family of actin-binding proteins". J. Neurosci. 18 (3): 914–22. doi:10.1523/JNEUROSCI.18-03-00914.1998. PMC 2042137. PMID 9437013.

[pmid11847232-16] Morohashi Y, Hatano N, Ohya S, Takikawa R, Watabiki T, Takasugi N, Imaizumi Y, Tomita T, Iwatsubo T (april 2002). "Molecular cloning and characterization of CALP/KChIP4, a novel EF-hand protein interacting with presenilin 2 and voltage-gated potassium channel subunit Kv4". J. Biol. Chem. 277 (17): 14965–75. doi:10.1074/jbc.M200897200. PMID 11847232.

[pmid12297508-17] Lee SF, Shah S, Li H, Yu C, Han W, Yu G (novembar 2002). "Mammalian APH-1 interacts with presenilin and nicastrin and is required for intramembrane proteolysis of amyloid-beta precursor protein and Notch". J. Biol. Chem. 277 (47): 45013–9. doi:10.1074/jbc.M208164200. PMID 12297508.

[pmid10993067-18] Yu G, Nishimura M, Arawaka S, Levitan D, Zhang L, Tandon A, Song YQ, Rogaeva E, Chen F, Kawarai T, Supala A, Levesque L, Yu H, Yang DS, Holmes E, Milman P, Liang Y, Zhang DM, Xu DH, Sato C, Rogaev E, Smith M, Janus C, Zhang Y, Aebersold R, Farrer LS, Sorbi S, Bruni A, Fraser P, St George-Hyslop P (septembar 2000). "Nicastrin modulates presenilin-mediated notch/glp-1 signal transduction and betaAPP processing". Nature. 407 (6800): 48–54. Bibcode:2000Natur.407...48Y. doi:10.1038/35024009. PMID 10993067. S2CID 4339220.

[pmid11076969-19] Mah AL, Perry G, Smith MA, Monteiro MJ (novembar 2000). "Identification of ubiquilin, a novel presenilin interactor that increases presenilin protein accumulation". J. Cell Biol. 151 (4): 847–62. doi:10.1083/jcb.151.4.847. PMC 2169435. PMID 11076969.

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p r u Protein: ćelija membrane proteins (other than Cell surface receptor, enzimi, i citoskeleton)
Arrestin	SAG ARRB1 ARRB2 ARR3
Membrane-spanning 4A	MS4A1 MS4A2 MS4A3 MS4A4A MS4A4E MS4A5 MS4A6A MS4A6E MS4A7 MS4A8B MS4A9 MS4A10 MS4A12 MS4A13 MS4A14 MS4A15 MS4A18
Myelin	Myelin basic protein PMP2 Myelin proteolipid protein PLP1 Myelin oligodendrocyte glycoprotein Myelin-associated glycoprotein Myelin protein zero
Pulmonary surfactant	Pulmonary surfactant-associated protein B Pulmonary surfactant-associated protein C
Tetraspanin	TSPAN1 TSPAN2 TSPAN3 TSPAN4 TSPAN5 TSPAN6 TSPAN7 TSPAN8 TSPAN9 TSPAN10 TSPAN11 TSPAN12 TSPAN13 TSPAN14 TSPAN15 TSPAN16 TSPAN17 TSPAN18 TSPAN19 TSPAN20 TSPAN21 TSPAN22 TSPAN23 TSPAN24 TSPAN25 TSPAN26 TSPAN27 TSPAN28 TSPAN29 TSPAN30 TSPAN31 TSPAN32 TSPAN33 TSPAN34
Ostali/negrupisani	Calnexin LDL-receptor-related protein-associated protein Neurofibromin 2 Presenilin PSEN1 PSEN2 HFE Phospholipid transfer proteins Dysferlin STRC OTOF
također pogledati other cell membrane protein disorders