PSEN2: Difference between revisions

Jump to navigation Jump to search
VisualWikitext
m (Robot: Automated text replacement (-{{reflist}} +{{reflist|2}}, -<references /> +{{reflist|2}}, -{{WikiDoc Cardiology Network Infobox}} +))
 
m (Bot: HTTP→HTTPS)
Line 1: Line 1:
<!-- The PBB_Controls template provides controls for Protein Box Bot, please see Template:PBB_Controls for details. -->
{{redirect|AD4|the Dobbin Class destroyer tender|USS Whitney (AD-4)|the year|AD 4}}
{{PBB_Controls
{{Infobox_gene}}
| update_page = yes
'''Presenilin-2''' is a [[protein]] that in humans is encoded by the ''PSEN2'' [[gene]].<ref name="pmid7638622">{{cite journal | vauthors = Levy-Lahad E, Wasco W, Poorkaj P, Romano DM, Oshima J, Pettingell WH, Yu CE, Jondro PD, Schmidt SD, Wang K | title = Candidate gene for the chromosome 1 familial Alzheimer's disease locus | journal = Science | volume = 269 | issue = 5226 | pages = 973–977 | date = September 1995 | pmid = 7638622 | pmc = | doi = 10.1126/science.7638622 }}</ref>
| require_manual_inspection = no
| update_protein_box = yes
| update_summary = no
| update_citations = yes
}}


<!-- The GNF_Protein_box is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
== Function ==
{{GNF_Protein_box
| image =
| image_source =
| PDB =
| Name = Presenilin 2 (Alzheimer disease 4)
| HGNCid = 9509
| Symbol = PSEN2
| AltSymbols =; AD3L; AD4; PS2; STM2
| OMIM = 600759
| ECnumber = 
| Homologene = 386
| MGIid = 109284
| GeneAtlas_image1 = PBB_GE_PSEN2_204261_s_at_tn.png
| GeneAtlas_image2 = PBB_GE_PSEN2_204262_s_at_tn.png
| GeneAtlas_image3 = PBB_GE_PSEN2_211373_s_at_tn.png
| Function = {{GNF_GO|id=GO:0005515 |text = protein binding}} {{GNF_GO|id=GO:0008233 |text = peptidase activity}}
| Component = {{GNF_GO|id=GO:0000776 |text = kinetochore}} {{GNF_GO|id=GO:0005639 |text = integral to nuclear inner membrane}} {{GNF_GO|id=GO:0005783 |text = endoplasmic reticulum}} {{GNF_GO|id=GO:0005794 |text = Golgi apparatus}} {{GNF_GO|id=GO:0005887 |text = integral to plasma membrane}} {{GNF_GO|id=GO:0016020 |text = membrane}} {{GNF_GO|id=GO:0016021 |text = integral to membrane}}
| Process = {{GNF_GO|id=GO:0001708 |text = cell fate specification}} {{GNF_GO|id=GO:0006509 |text = membrane protein ectodomain proteolysis}} {{GNF_GO|id=GO:0007001 |text = chromosome organization and biogenesis (sensu Eukaryota)}} {{GNF_GO|id=GO:0007059 |text = chromosome segregation}} {{GNF_GO|id=GO:0007220 |text = Notch receptor processing}} {{GNF_GO|id=GO:0007242 |text = intracellular signaling cascade}} {{GNF_GO|id=GO:0008632 |text = apoptotic program}} {{GNF_GO|id=GO:0016485 |text = protein processing}} {{GNF_GO|id=GO:0030326 |text = embryonic limb morphogenesis}} {{GNF_GO|id=GO:0042640 |text = anagen}} {{GNF_GO|id=GO:0042987 |text = amyloid precursor protein catabolic process}} {{GNF_GO|id=GO:0043065 |text = positive regulation of apoptosis}} {{GNF_GO|id=GO:0043085 |text = positive regulation of enzyme activity}}
| Orthologs = {{GNF_Ortholog_box
    | Hs_EntrezGene = 5664
    | Hs_Ensembl = ENSG00000143801
    | Hs_RefseqProtein = NP_000438
    | Hs_RefseqmRNA = NM_000447
    | Hs_GenLoc_db = 
    | Hs_GenLoc_chr = 1
    | Hs_GenLoc_start = 225124887
    | Hs_GenLoc_end = 225150422
    | Hs_Uniprot = P49810
    | Mm_EntrezGene = 19165
    | Mm_Ensembl = ENSMUSG00000010609
    | Mm_RefseqmRNA = NM_011183
    | Mm_RefseqProtein = NP_035313
    | Mm_GenLoc_db = 
    | Mm_GenLoc_chr = 1
    | Mm_GenLoc_start = 182063681
    | Mm_GenLoc_end = 182082576
    | Mm_Uniprot = Q3U4P5
  }}
}}
'''Presenilin 2 (Alzheimer disease 4)''', also known as '''PSEN2''', is a human [[gene]].


<!-- The PBB_Summary template is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
[[Alzheimer's disease]] (AD) patients with an inherited form of the disease carry mutations in the [[presenilin]] proteins ([[PSEN1]]; PSEN2) or the [[amyloid precursor protein]] (APP).  These disease-linked mutations result in increased production of the longer form of [[amyloid-beta]] (main component of [[amyloid]] deposits found in AD brains).  Presenilins are postulated to regulate APP processing through their effects on [[gamma-secretase]], an enzyme that cleaves APP.  Also, it is thought that the presenilins are involved in the cleavage of the [[Notch receptor]], such that they either directly regulate gamma-secretase activity or themselves are [[protease]] enzymes.  Two alternative transcripts of PSEN2 have been identified.<ref>{{cite web | title = Entrez Gene: PSEN2 presenilin 2 (Alzheimer disease 4)| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=5664| accessdate = }}</ref>
{{PBB_Summary
| section_title =
| summary_text = [[Alzheimer's disease]] (AD) patients with an inherited form of the disease carry mutations in the [[presenilin]] proteins ([[PSEN1]]; PSEN2) or the [[amyloid precursor protein]] (APP).  These disease-linked mutations result in increased production of the longer form of [[amyloid-beta]] (main component of [[amyloid]] deposits found in AD brains).  Presenilins are postulated to regulate APP processing through their effects on [[gamma-secretase]], an enzyme that cleaves APP.  Also, it is thought that the presenilins are involved in the cleavage of the [[Notch receptor]], such that that they either directly regulate gamma-secretase activity or themselves are [[protease]] enzymes.  Two alternative transcripts of PSEN2 have been identified.<ref>{{cite web | title = Entrez Gene: PSEN2 presenilin 2 (Alzheimer disease 4)| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=5664| accessdate = }}</ref>
}}


==References==
In melanocytic cells PSEN2 gene expression may be regulated by [[Microphthalmia-associated transcription factor|MITF]].<ref name="pmid19067971">{{cite journal | vauthors = Hoek KS, Schlegel NC, Eichhoff OM, Widmer DS, Praetorius C, Einarsson SO, Valgeirsdottir S, Bergsteinsdottir K, Schepsky A, Dummer R, Steingrimsson E | title = Novel MITF targets identified using a two-step DNA microarray strategy | journal = Pigment Cell Melanoma Res. | volume = 21 | issue = 6 | pages = 665–676 | year = 2008 | pmid = 19067971 | doi = 10.1111/j.1755-148X.2008.00505.x }}</ref>
{{reflist|2}}
 
==Further reading==
== Interactions ==
 
PSEN2 has been shown to [[Protein-protein interaction|interact]] with:
{{div col|colwidth=20em}}
* [[BCL2-like 1 (gene)|BCL2-like 1]],<ref name = pmid10446169>{{cite journal | vauthors = Passer BJ, Pellegrini L, Vito P, Ganjei JK, D'Adamio L | title = Interaction of Alzheimer's presenilin-1 and presenilin-2 with Bcl-X(L). A potential role in modulating the threshold of cell death | journal = J. Biol. Chem. | volume = 274 | issue = 34 | pages = 24007–13 | date = August 1999 | pmid = 10446169 | doi =  10.1074/jbc.274.34.24007}}</ref>
* [[CAPN1]],<ref name = pmid9852298>{{cite journal | vauthors = Shinozaki K, Maruyama K, Kume H, Tomita T, Saido TC, Iwatsubo T, Obata K | title = The presenilin 2 loop domain interacts with the mu-calpain C-terminal region | journal = Int. J. Mol. Med. | volume = 1 | issue = 5 | pages = 797–9 | date = May 1998 | pmid = 9852298 | doi =  10.3892/ijmm.1.5.797}}</ref>
* [[CIB1]],<ref name = pmid10366599>{{cite journal | vauthors = Stabler SM, Ostrowski LL, Janicki SM, Monteiro MJ | title = A myristoylated calcium-binding protein that preferentially interacts with the Alzheimer's disease presenilin 2 protein | journal = J. Cell Biol. | volume = 145 | issue = 6 | pages = 1277–92 | date = June 1999 | pmid = 10366599 | pmc = 2133148 | doi =  10.1083/jcb.145.6.1277}}</ref>
* [[Calsenilin]],<ref name = pmid9771752>{{cite journal | vauthors = Buxbaum JD, Choi EK, Luo Y, Lilliehook C, Crowley AC, Merriam DE, Wasco W | title = Calsenilin: a calcium-binding protein that interacts with the presenilins and regulates the levels of a presenilin fragment | journal = Nat. Med. | volume = 4 | issue = 10 | pages = 1177–81 | date = October 1998 | pmid = 9771752 | doi = 10.1038/2673 }}</ref><ref name = pmid11278424>{{cite journal | vauthors = Choi EK, Zaidi NF, Miller JS, Crowley AC, Merriam DE, Lilliehook C, Buxbaum JD, Wasco W | title = Calsenilin is a substrate for caspase-3 that preferentially interacts with the familial Alzheimer's disease-associated C-terminal fragment of presenilin 2 | journal = J. Biol. Chem. | volume = 276 | issue = 22 | pages = 19197–204 | date = June 2001 | pmid = 11278424 | doi = 10.1074/jbc.M008597200 }}</ref>
* [[FHL2]],<ref name = pmid11001931>{{cite journal | vauthors = Tanahashi H, Tabira T | title = Alzheimer's disease-associated presenilin 2 interacts with DRAL, an LIM-domain protein | journal = Hum. Mol. Genet. | volume = 9 | issue = 15 | pages = 2281–9 | date = September 2000 | pmid = 11001931 | doi =  10.1093/oxfordjournals.hmg.a018919}}</ref>
* [[FLNB]],<ref name = pmid9437013>{{cite journal | vauthors = Zhang W, Han SW, McKeel DW, Goate A, Wu JY | title = Interaction of presenilins with the filamin family of actin-binding proteins | journal = J. Neurosci. | volume = 18 | issue = 3 | pages = 914–22 | date = February 1998 | pmid = 9437013 | pmc = 2042137 | doi =  }}</ref>
* [[KCNIP4]],<ref name = pmid11847232>{{cite journal | vauthors = Morohashi Y, Hatano N, Ohya S, Takikawa R, Watabiki T, Takasugi N, Imaizumi Y, Tomita T, Iwatsubo T | title = Molecular cloning and characterization of CALP/KChIP4, a novel EF-hand protein interacting with presenilin 2 and voltage-gated potassium channel subunit Kv4 | journal = J. Biol. Chem. | volume = 277 | issue = 17 | pages = 14965–75 | date = April 2002 | pmid = 11847232 | doi = 10.1074/jbc.M200897200 }}</ref>
* [[Nicastrin]],<ref name = pmid12297508>{{cite journal | vauthors = Lee SF, Shah S, Li H, Yu C, Han W, Yu G | title = Mammalian APH-1 interacts with presenilin and nicastrin and is required for intramembrane proteolysis of amyloid-beta precursor protein and Notch | journal = J. Biol. Chem. | volume = 277 | issue = 47 | pages = 45013–9 | date = November 2002 | pmid = 12297508 | doi = 10.1074/jbc.M208164200 }}</ref><ref name = pmid10993067>{{cite journal | vauthors = 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 | title = Nicastrin modulates presenilin-mediated notch/glp-1 signal transduction and betaAPP processing | journal = Nature | volume = 407 | issue = 6800 | pages = 48–54 | date = September 2000 | pmid = 10993067 | doi = 10.1038/35024009 }}</ref>  and
* [[UBQLN1]].<ref name = pmid11076969>{{cite journal | vauthors = Mah AL, Perry G, Smith MA, Monteiro MJ | title = Identification of ubiquilin, a novel presenilin interactor that increases presenilin protein accumulation | journal = J. Cell Biol. | volume = 151 | issue = 4 | pages = 847–62 | date = November 2000 | pmid = 11076969 | pmc = 2169435 | doi =  10.1083/jcb.151.4.847}}</ref>
{{Div col end}}
 
== References ==
{{reflist}}
 
== Further reading ==
{{refbegin | 2}}
{{refbegin | 2}}
{{PBB_Further_reading
* {{cite journal | vauthors = Cruts M, Van Broeckhoven C | title = Presenilin mutations in Alzheimer's disease | journal = Hum. Mutat. | volume = 11 | issue = 3 | pages = 183–190 | year = 1998 | pmid = 9521418 | doi = 10.1002/(SICI)1098-1004(1998)11:3<183::AID-HUMU1>3.0.CO;2-J }}
| citations =
* {{cite journal | vauthors = McGeer PL, Kawamata T, McGeer EG | title = Localization and possible functions of presenilins in brain | journal = Reviews in the neurosciences | volume = 9 | issue = 1 | pages = 1–15 | year = 1998 | pmid = 9683324 | doi = 10.1515/REVNEURO.1998.9.1.1 }}
*{{cite journal | author=Cruts M, Van Broeckhoven C |title=Presenilin mutations in Alzheimer's disease. |journal=Hum. Mutat. |volume=11 |issue= 3 |pages= 183-90 |year= 1998 |pmid= 9521418 |doi= 10.1002/(SICI)1098-1004(1998)11:3<183::AID-HUMU1>3.0.CO;2-J }}
* {{cite journal | vauthors = Nishimura M, Yu G, St George-Hyslop PH | title = Biology of presenilins as causative molecules for Alzheimer disease | journal = Clin. Genet. | volume = 55 | issue = 4 | pages = 219–225 | year = 1999 | pmid = 10361981 | doi = 10.1034/j.1399-0004.1999.550401.x }}
*{{cite journal | author=McGeer PL, Kawamata T, McGeer EG |title=Localization and possible functions of presenilins in brain. |journal=Reviews in the neurosciences |volume=9 |issue= 1 |pages= 1-15 |year= 1998 |pmid= 9683324 |doi= }}
* {{cite journal | vauthors = da Costa CA | title = Recent insights on the pro-apoptotic phenotype elicited by presenilin 2 and its caspase and presenilinase-derived fragments | journal = Current Alzheimer research | volume = 2 | issue = 5 | pages = 507–514 | year = 2006 | pmid = 16375654 | doi = 10.2174/156720505774932278 }}
*{{cite journal | author=Nishimura M, Yu G, St George-Hyslop PH |title=Biology of presenilins as causative molecules for Alzheimer disease. |journal=Clin. Genet. |volume=55 |issue= 4 |pages= 219-25 |year= 1999 |pmid= 10361981 |doi= }}
* {{cite journal | vauthors = Wolfe MS | title = When loss is gain: reduced presenilin proteolytic function leads to increased Abeta42/Abeta40. Talking Point on the role of presenilin mutations in Alzheimer disease | journal = EMBO Rep. | volume = 8 | issue = 2 | pages = 136–140 | year = 2007 | pmid = 17268504 | pmc = 1796780 | doi = 10.1038/sj.embor.7400896 }}
*{{cite journal | author=da Costa CA |title=Recent insights on the pro-apoptotic phenotype elicited by presenilin 2 and its caspase and presenilinase-derived fragments. |journal=Current Alzheimer research |volume=2 |issue= 5 |pages= 507-14 |year= 2006 |pmid= 16375654 |doi= }}
* {{cite journal | vauthors = De Strooper B | title = Loss-of-function presenilin mutations in Alzheimer disease. Talking Point on the role of presenilin mutations in Alzheimer disease | journal = EMBO Rep. | volume = 8 | issue = 2 | pages = 141–146 | year = 2007 | pmid = 17268505 | pmc = 1796779 | doi = 10.1038/sj.embor.7400897 }}
*{{cite journal | author=Wolfe MS |title=When loss is gain: reduced presenilin proteolytic function leads to increased Abeta42/Abeta40. Talking Point on the role of presenilin mutations in Alzheimer disease. |journal=EMBO Rep. |volume=8 |issue= 2 |pages= 136-40 |year= 2007 |pmid= 17268504 |doi= 10.1038/sj.embor.7400896 }}
*{{cite journal | author=De Strooper B |title=Loss-of-function presenilin mutations in Alzheimer disease. Talking Point on the role of presenilin mutations in Alzheimer disease. |journal=EMBO Rep. |volume=8 |issue= 2 |pages= 141-6 |year= 2007 |pmid= 17268505 |doi= 10.1038/sj.embor.7400897 }}
}}
{{refend}}
{{refend}}


{{protein-stub}}
== External links ==
{{WikiDoc Sources}}
* [https://www.ncbi.nlm.nih.gov/books/NBK1236/  GeneReviews/NCBI/NIH/UW entry on Early-Onset Familial Alzheimer Disease]
 
{{Membrane proteins}}
 
 
{{gene-1-stub}}

Revision as of 18:48, 7 September 2017

Lua error in Module:Redirect at line 65: could not parse redirect on page "AD4".

VALUE_ERROR (nil)
Identifiers
Aliases
External IDsGeneCards: [1]
Orthologs
SpeciesHumanMouse
Entrez

n/a

n/a

Ensembl

n/a

n/a

UniProt

n/a

n/a

RefSeq (mRNA)

n/a

n/a

RefSeq (protein)

n/a

n/a

Location (UCSC)n/an/a
PubMed searchn/an/a
Wikidata
View/Edit Human

Presenilin-2 is a protein that in humans is encoded by the PSEN2 gene.[1]

Function

Alzheimer's disease (AD) patients with an inherited form of the disease carry mutations in the presenilin proteins (PSEN1; PSEN2) or the amyloid precursor protein (APP). These disease-linked mutations result in increased production of the longer form of amyloid-beta (main component of amyloid deposits found in AD brains). Presenilins are postulated to regulate APP processing through their effects on gamma-secretase, an enzyme that cleaves APP. Also, it is thought that the presenilins are involved in the cleavage of the Notch receptor, such that they either directly regulate gamma-secretase activity or themselves are protease enzymes. Two alternative transcripts of PSEN2 have been identified.[2]

In melanocytic cells PSEN2 gene expression may be regulated by MITF.[3]

Interactions

PSEN2 has been shown to interact with:

References

  1. ↑ Levy-Lahad E, Wasco W, Poorkaj P, Romano DM, Oshima J, Pettingell WH, Yu CE, Jondro PD, Schmidt SD, Wang K (September 1995). "Candidate gene for the chromosome 1 familial Alzheimer's disease locus". Science. 269 (5226): 973–977. doi:10.1126/science.7638622. PMID 7638622.
  2. ↑ "Entrez Gene: PSEN2 presenilin 2 (Alzheimer disease 4)".
  3. ↑ 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.
  4. ↑ 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.
  5. ↑ Shinozaki K, Maruyama K, Kume H, Tomita T, Saido TC, Iwatsubo T, Obata K (May 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.
  6. ↑ Stabler SM, Ostrowski LL, Janicki SM, Monteiro MJ (June 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.
  7. ↑ Buxbaum JD, Choi EK, Luo Y, Lilliehook C, Crowley AC, Merriam DE, Wasco W (October 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.
  8. ↑ Choi EK, Zaidi NF, Miller JS, Crowley AC, Merriam DE, Lilliehook C, Buxbaum JD, Wasco W (June 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.
  9. ↑ Tanahashi H, Tabira T (September 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.
  10. ↑ Zhang W, Han SW, McKeel DW, Goate A, Wu JY (February 1998). "Interaction of presenilins with the filamin family of actin-binding proteins". J. Neurosci. 18 (3): 914–22. PMC 2042137. PMID 9437013.
  11. ↑ 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.
  12. ↑ Lee SF, Shah S, Li H, Yu C, Han W, Yu G (November 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.
  13. ↑ 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 (September 2000). "Nicastrin modulates presenilin-mediated notch/glp-1 signal transduction and betaAPP processing". Nature. 407 (6800): 48–54. doi:10.1038/35024009. PMID 10993067.
  14. ↑ Mah AL, Perry G, Smith MA, Monteiro MJ (November 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.

Further reading

External links


Retrieved from "https://www.wikidoc.org/index.php?title=PSEN2&oldid=1410836"