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Protein

Presenilin-2

Gene

Psen2

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Probable catalytic subunit of the gamma-secretase complex, an endoprotease complex that catalyzes the intramembrane cleavage of integral membrane proteins such as Notch receptors and APP (beta-amyloid precursor protein). Requires the other members of the gamma-secretase complex to have a protease activity. May play a role in intracellular signaling and gene expression or in linking chromatin to the nuclear membrane. May function in the cytoplasmic partitioning of proteins (By similarity).By similarity

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Active sitei263 – 2631By similarity
Active sitei366 – 3661By similarity

GO - Molecular functioni

  • aspartic-type endopeptidase activity Source: InterPro
  • endopeptidase activity Source: MGI

GO - Biological processi

  • amyloid precursor protein catabolic process Source: GO_Central
  • beta-amyloid metabolic process Source: MGI
  • brain morphogenesis Source: MGI
  • cardiac muscle contraction Source: MGI
  • cell fate specification Source: MGI
  • cellular protein metabolic process Source: MGI
  • dorsal/ventral neural tube patterning Source: MGI
  • embryonic limb morphogenesis Source: MGI
  • endoplasmic reticulum calcium ion homeostasis Source: MGI
  • forebrain development Source: MGI
  • hair follicle development Source: MGI
  • hematopoietic progenitor cell differentiation Source: MGI
  • intracellular signal transduction Source: InterPro
  • learning or memory Source: MGI
  • locomotion Source: MGI
  • lung alveolus development Source: MGI
  • membrane protein ectodomain proteolysis Source: HGNC
  • memory Source: MGI
  • myeloid leukocyte differentiation Source: MGI
  • negative regulation of apoptotic signaling pathway Source: MGI
  • negative regulation of epidermal growth factor-activated receptor activity Source: BHF-UCL
  • negative regulation of extrinsic apoptotic signaling pathway via death domain receptors Source: MGI
  • negative regulation of protein binding Source: MGI
  • negative regulation of protein complex assembly Source: MGI
  • negative regulation of protein phosphorylation Source: MGI
  • negative regulation of protein ubiquitination involved in ubiquitin-dependent protein catabolic process Source: BHF-UCL
  • negative regulation of transcription from RNA polymerase II promoter Source: BHF-UCL
  • negative regulation of ubiquitin-protein transferase activity Source: BHF-UCL
  • Notch receptor processing Source: GO_Central
  • Notch signaling pathway Source: MGI
  • positive regulation of apoptotic process Source: MGI
  • positive regulation of catalytic activity Source: HGNC
  • positive regulation of coagulation Source: MGI
  • positive regulation of extrinsic apoptotic signaling pathway via death domain receptors Source: MGI
  • positive regulation of proteasomal ubiquitin-dependent protein catabolic process Source: BHF-UCL
  • positive regulation of receptor recycling Source: BHF-UCL
  • protein maturation Source: MGI
  • protein processing Source: HGNC
  • protein transport Source: MGI
  • regulation of epidermal growth factor-activated receptor activity Source: MGI
  • regulation of protein binding Source: MGI
  • regulation of synaptic plasticity Source: MGI
  • skin morphogenesis Source: BHF-UCL
  • somitogenesis Source: MGI
  • T cell activation involved in immune response Source: MGI
  • T cell receptor signaling pathway Source: MGI
  • thymus development Source: MGI
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Protease

Keywords - Biological processi

Notch signaling pathway

Enzyme and pathway databases

ReactomeiREACT_279153. Signaling by NOTCH3.
REACT_286692. Activated NOTCH1 Transmits Signal to the Nucleus.
REACT_312443. NOTCH2 Activation and Transmission of Signal to the Nucleus.
REACT_314615. EPH-ephrin mediated repulsion of cells.
REACT_315710. Regulated proteolysis of p75NTR.
REACT_342872. NRIF signals cell death from the nucleus.
REACT_345101. Signaling by NOTCH4.
REACT_345486. Nuclear signaling by ERBB4.

Protein family/group databases

MEROPSiA22.002.

Names & Taxonomyi

Protein namesi
Recommended name:
Presenilin-2 (EC:3.4.23.-)
Short name:
PS-2
Cleaved into the following 2 chains:
Gene namesi
Name:Psen2
Synonyms:Ad4h, Alg3, Ps-2, Psnl2
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589 Componenti: Unplaced

Organism-specific databases

MGIiMGI:109284. Psen2.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 8787CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei88 – 10821HelicalSequence AnalysisAdd
BLAST
Topological domaini109 – 13830LumenalSequence AnalysisAdd
BLAST
Transmembranei139 – 15921HelicalSequence AnalysisAdd
BLAST
Topological domaini160 – 1667CytoplasmicSequence Analysis
Transmembranei167 – 18721HelicalSequence AnalysisAdd
BLAST
Topological domaini188 – 20013LumenalSequence AnalysisAdd
BLAST
Transmembranei201 – 22121HelicalSequence AnalysisAdd
BLAST
Topological domaini222 – 2232CytoplasmicSequence Analysis
Transmembranei224 – 24421HelicalSequence AnalysisAdd
BLAST
Topological domaini245 – 2495LumenalSequence Analysis
Transmembranei250 – 27021HelicalSequence AnalysisAdd
BLAST
Topological domaini271 – 35888CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei359 – 37921HelicalSequence AnalysisAdd
BLAST
Topological domaini380 – 3889LumenalSequence Analysis
Transmembranei389 – 40921HelicalSequence AnalysisAdd
BLAST
Topological domaini410 – 4134CytoplasmicSequence Analysis
Intramembranei414 – 43421HelicalSequence AnalysisAdd
BLAST
Topological domaini435 – 44814CytoplasmicSequence AnalysisAdd
BLAST

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Endoplasmic reticulum, Golgi apparatus, Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 297297Presenilin-2 NTF subunitBy similarityPRO_0000025607Add
BLAST
Chaini298 – 448151Presenilin-2 CTF subunitPRO_0000025608Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei22 – 221PhosphoserineBy similarity
Modified residuei25 – 251PhosphoserineBy similarity
Modified residuei52 – 521Phosphoserine2 Publications

Keywords - PTMi

Phosphoprotein

Proteomic databases

MaxQBiQ61144.
PaxDbiQ61144.
PRIDEiQ61144.

PTM databases

PhosphoSiteiQ61144.

Expressioni

Tissue specificityi

Ubiquitously expressed. Highly expressed in the liver.

Gene expression databases

BgeeiQ61144.
CleanExiMM_PSEN2.
ExpressionAtlasiQ61144. baseline and differential.
GenevisibleiQ61144. MM.

Interactioni

Subunit structurei

Homodimer. Component of the gamma-secretase complex, a complex composed of a presenilin homodimer (PSEN1 or PSEN2), nicastrin (NCSTN), APH1 (APH1A or APH1B) and PEN2. Such minimal complex is sufficient for secretase activity, although other components may exist. Interacts with DOCK3. Interacts with HERPUD1, FLNA, FLNB and PARL (By similarity).By similarity

Protein-protein interaction databases

BioGridi202415. 11 interactions.
IntActiQ61144. 1 interaction.
STRINGi10090.ENSMUSP00000010753.

Structurei

3D structure databases

ProteinModelPortaliQ61144.
SMRiQ61144. Positions 298-448.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi414 – 4163PAL

Domaini

The PAL motif is required for normal active site conformation.By similarity

Sequence similaritiesi

Belongs to the peptidase A22A family.Curated

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiNOG237920.
HOGENOMiHOG000240228.
HOVERGENiHBG011375.
InParanoidiQ61144.
KOiK04522.
OrthoDBiEOG7NGQBG.
PhylomeDBiQ61144.

Family and domain databases

InterProiIPR001493. Pept_A22A_PS2.
IPR001108. Peptidase_A22A.
IPR006639. Preselin/SPP.
[Graphical view]
PANTHERiPTHR10202. PTHR10202. 1 hit.
PTHR10202:SF11. PTHR10202:SF11. 1 hit.
PfamiPF01080. Presenilin. 1 hit.
[Graphical view]
PRINTSiPR01072. PRESENILIN.
PR01074. PRESENILIN2.
SMARTiSM00730. PSN. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q61144-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MLAFMASDSE EEVCDERTSL MSAESPTSRS CQEGRPGPED GESTAQWRTQ
60 70 80 90 100
ESEEDCEEDP DRYACSGAPG RPSGLEEELT LKYGAKRVIM LFVPVTLCMI
110 120 130 140 150
VVVATIKSVR FYTEKNGQLI YTPFTEDTPS VGQRLLNSVL NTLIMISVIV
160 170 180 190 200
VMTIFLVVLY KYRCYKFIHG WLIMSSLMLL FLFTYIYLGE VLKTYNVAMD
210 220 230 240 250
YPTLFLAVWN FGAVGMVCIH WKGPLVLQQA YLIVISALMA LVFIKYLPEW
260 270 280 290 300
SAWVILGAIS VYDLVAVLCP KGPLRMLVET AQERNEPIFP ALIYSSAMVW
310 320 330 340 350
TVGMAKLDPS SQGALQLPYD PEMEEDSYDS FGEPSYPEAF EAPLPGYPGE
360 370 380 390 400
ELEEEEERGV KLGLGDFIFY SVLVGKAAAT GNGDWNTTLA CFIAILIGLC
410 420 430 440
LTLLLLAVFK KALPALPISI TFGLIFYFST DNLVRPFMDT LASHQLYI
Length:448
Mass (Da):49,983
Last modified:September 26, 2003 - v3
Checksum:i54787212DCBB2C78
GO
Isoform 2 (identifier: Q61144-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     296-332: SAMVWTVGMAKLDPSSQGALQLPYDPEMEEDSYDSFG → CEWSHASARHWGVSRWPFVEAWKWAVVLISDRLYILS
     333-448: Missing.

Note: No experimental confirmation available.
Show »
Length:332
Mass (Da):37,701
Checksum:iE598A662F7EA7D0C
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti40 – 401D → G in BAB29514 (PubMed:16141072).Curated
Sequence conflicti86 – 872KR → ND in BAB29514 (PubMed:16141072).Curated
Sequence conflicti87 – 871R → H (Ref. 2) Curated
Sequence conflicti87 – 871R → H (PubMed:15489334).Curated
Sequence conflicti226 – 2261V → A in AAC52937 (PubMed:8940094).Curated
Sequence conflicti324 – 3241Missing in AAB92660 (Ref. 2) Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei296 – 33237SAMVW…YDSFG → CEWSHASARHWGVSRWPFVE AWKWAVVLISDRLYILS in isoform 2. 1 PublicationVSP_008383Add
BLAST
Alternative sequencei333 – 448116Missing in isoform 2. 1 PublicationVSP_008384Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U57324 mRNA. Translation: AAC52937.1.
U57325 mRNA. Translation: AAC53311.1.
AF038935 mRNA. Translation: AAB92660.1.
AK014706 mRNA. Translation: BAB29514.1.
BC010403 mRNA. Translation: AAH10403.1.
U49111 mRNA. Translation: AAC52935.1.
CCDSiCCDS15567.1. [Q61144-1]
RefSeqiNP_001122077.1. NM_001128605.1.
NP_035313.2. NM_011183.3.
XP_006496775.1. XM_006496712.2.
UniGeneiMm.330850.

Genome annotation databases

GeneIDi19165.
KEGGimmu:19165.
UCSCiuc007dwe.1. mouse. [Q61144-2]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U57324 mRNA. Translation: AAC52937.1.
U57325 mRNA. Translation: AAC53311.1.
AF038935 mRNA. Translation: AAB92660.1.
AK014706 mRNA. Translation: BAB29514.1.
BC010403 mRNA. Translation: AAH10403.1.
U49111 mRNA. Translation: AAC52935.1.
CCDSiCCDS15567.1. [Q61144-1]
RefSeqiNP_001122077.1. NM_001128605.1.
NP_035313.2. NM_011183.3.
XP_006496775.1. XM_006496712.2.
UniGeneiMm.330850.

3D structure databases

ProteinModelPortaliQ61144.
SMRiQ61144. Positions 298-448.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi202415. 11 interactions.
IntActiQ61144. 1 interaction.
STRINGi10090.ENSMUSP00000010753.

Protein family/group databases

MEROPSiA22.002.

PTM databases

PhosphoSiteiQ61144.

Proteomic databases

MaxQBiQ61144.
PaxDbiQ61144.
PRIDEiQ61144.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi19165.
KEGGimmu:19165.
UCSCiuc007dwe.1. mouse. [Q61144-2]

Organism-specific databases

CTDi5664.
MGIiMGI:109284. Psen2.

Phylogenomic databases

eggNOGiNOG237920.
HOGENOMiHOG000240228.
HOVERGENiHBG011375.
InParanoidiQ61144.
KOiK04522.
OrthoDBiEOG7NGQBG.
PhylomeDBiQ61144.

Enzyme and pathway databases

ReactomeiREACT_279153. Signaling by NOTCH3.
REACT_286692. Activated NOTCH1 Transmits Signal to the Nucleus.
REACT_312443. NOTCH2 Activation and Transmission of Signal to the Nucleus.
REACT_314615. EPH-ephrin mediated repulsion of cells.
REACT_315710. Regulated proteolysis of p75NTR.
REACT_342872. NRIF signals cell death from the nucleus.
REACT_345101. Signaling by NOTCH4.
REACT_345486. Nuclear signaling by ERBB4.

Miscellaneous databases

ChiTaRSiPsen2. mouse.
NextBioi295826.
PROiQ61144.
SOURCEiSearch...

Gene expression databases

BgeeiQ61144.
CleanExiMM_PSEN2.
ExpressionAtlasiQ61144. baseline and differential.
GenevisibleiQ61144. MM.

Family and domain databases

InterProiIPR001493. Pept_A22A_PS2.
IPR001108. Peptidase_A22A.
IPR006639. Preselin/SPP.
[Graphical view]
PANTHERiPTHR10202. PTHR10202. 1 hit.
PTHR10202:SF11. PTHR10202:SF11. 1 hit.
PfamiPF01080. Presenilin. 1 hit.
[Graphical view]
PRINTSiPR01072. PRESENILIN.
PR01074. PRESENILIN2.
SMARTiSM00730. PSN. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Requirement of the familial Alzheimer's disease gene PS2 for apoptosis. Opposing effect of ALG-3."
    Vito P., Wolozin B., Ganjei J.K., Iwasaki K., Lacana E., D'Adamio L.
    J. Biol. Chem. 271:31025-31028(1996) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
    Tissue: Liver.
  2. "Molecular cloning of mouse presenilin 2 gene."
    Sahara N., Mori H., Shirasawa T.
    Submitted (DEC-1997) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
    Strain: NIH Swiss.
  3. "The transcriptional landscape of the mammalian genome."
    Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.
    , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
    Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
    Strain: C57BL/6J.
    Tissue: Head.
  4. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
    Tissue: Mammary tumor.
  5. "Interfering with apoptosis: Ca(2+)-binding protein ALG-2 and Alzheimer's disease gene ALG-3."
    Vito P., Lacana E., D'Adamio L.
    Science 271:521-525(1996) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 340-448 (ISOFORM 1).
    Tissue: Liver.
  6. "A novel mechanism for the regulation of amyloid precursor protein metabolism."
    Chen Q., Kimura H., Schubert D.
    J. Cell Biol. 158:79-89(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH DOCK3.
  7. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-52, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Liver.
  8. "The phagosomal proteome in interferon-gamma-activated macrophages."
    Trost M., English L., Lemieux S., Courcelles M., Desjardins M., Thibault P.
    Immunity 30:143-154(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-52, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].

Entry informationi

Entry nameiPSN2_MOUSE
AccessioniPrimary (citable) accession number: Q61144
Secondary accession number(s): O54977
, P97934, P97935, Q91VS3, Q9D616
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: September 26, 2003
Last modified: June 24, 2015
This is version 140 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. Peptidase families
    Classification of peptidase families and list of entries
  3. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.