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P49810

- PSN2_HUMAN

UniProt

P49810 - PSN2_HUMAN

Protein

Presenilin-2

Gene

PSEN2

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 159 (01 Oct 2014)
      Sequence version 1 (01 Oct 1996)
      Previous versions | rss
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    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.2 Publications

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Active sitei263 – 26311 Publication
    Active sitei366 – 36612 Publications

    GO - Molecular functioni

    1. aspartic-type endopeptidase activity Source: InterPro
    2. endopeptidase activity Source: RefGenome
    3. protein binding Source: UniProtKB

    GO - Biological processi

    1. amyloid precursor protein catabolic process Source: HGNC
    2. anagen Source: Ensembl
    3. apoptotic signaling pathway Source: Reactome
    4. beta-amyloid metabolic process Source: RefGenome
    5. brain morphogenesis Source: Ensembl
    6. calcium ion transport Source: RefGenome
    7. cardiac muscle contraction Source: Ensembl
    8. cell fate specification Source: Ensembl
    9. dorsal/ventral neural tube patterning Source: Ensembl
    10. embryonic limb morphogenesis Source: Ensembl
    11. endoplasmic reticulum calcium ion homeostasis Source: Ensembl
    12. forebrain development Source: Ensembl
    13. hematopoietic progenitor cell differentiation Source: Ensembl
    14. intracellular signal transduction Source: InterPro
    15. locomotion Source: Ensembl
    16. lung alveolus development Source: Ensembl
    17. membrane protein ectodomain proteolysis Source: HGNC
    18. membrane protein intracellular domain proteolysis Source: Reactome
    19. memory Source: Ensembl
    20. myeloid leukocyte differentiation Source: Ensembl
    21. negative regulation of apoptotic process Source: RefGenome
    22. negative regulation of extrinsic apoptotic signaling pathway via death domain receptors Source: Ensembl
    23. negative regulation of protein binding Source: Ensembl
    24. negative regulation of protein complex assembly Source: Ensembl
    25. negative regulation of protein phosphorylation Source: Ensembl
    26. neurotrophin TRK receptor signaling pathway Source: Reactome
    27. Notch receptor processing Source: HGNC
    28. Notch signaling pathway Source: Reactome
    29. positive regulation of apoptotic process Source: Reactome
    30. positive regulation of catalytic activity Source: HGNC
    31. positive regulation of coagulation Source: Ensembl
    32. positive regulation of extrinsic apoptotic signaling pathway via death domain receptors Source: Ensembl
    33. protein processing Source: HGNC
    34. protein transport Source: Ensembl
    35. regulation of epidermal growth factor-activated receptor activity Source: Ensembl
    36. regulation of synaptic plasticity Source: Ensembl
    37. response to hypoxia Source: Ensembl
    38. somitogenesis Source: Ensembl
    39. T cell activation involved in immune response Source: Ensembl
    40. T cell receptor signaling pathway Source: Ensembl
    41. thymus development Source: Ensembl

    Keywords - Molecular functioni

    Hydrolase, Protease

    Keywords - Biological processi

    Notch signaling pathway

    Enzyme and pathway databases

    ReactomeiREACT_116022. Nuclear signaling by ERBB4.
    REACT_118614. Activated NOTCH1 Transmits Signal to the Nucleus.
    REACT_118636. Signaling by NOTCH4.
    REACT_118862. Signaling by NOTCH3.
    REACT_13443. Regulated proteolysis of p75NTR.
    REACT_13643. NRIF signals cell death from the nucleus.
    REACT_160205. NOTCH2 Activation and Transmission of Signal to the Nucleus.
    REACT_160243. Constitutive Signaling by NOTCH1 PEST Domain Mutants.
    REACT_160254. Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants.
    SignaLinkiP49810.

    Protein family/group databases

    MEROPSiA22.002.
    TCDBi1.A.54.1.2. the presenilin er ca(2+) leak channel (presenilin) family.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Presenilin-2 (EC:3.4.23.-)
    Short name:
    PS-2
    Alternative name(s):
    AD3LP
    AD5
    E5-1
    STM-2
    Cleaved into the following 2 chains:
    Gene namesi
    Name:PSEN2
    Synonyms:AD4, PS2, PSNL2, STM2
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 1

    Organism-specific databases

    HGNCiHGNC:9509. PSEN2.

    Subcellular locationi

    Endoplasmic reticulum membrane 1 Publication; Multi-pass membrane protein 1 Publication. Golgi apparatus membrane 1 Publication; Multi-pass membrane protein 1 Publication

    GO - Cellular componenti

    1. apical plasma membrane Source: RefGenome
    2. axon Source: RefGenome
    3. cell cortex Source: RefGenome
    4. cell surface Source: RefGenome
    5. centrosome Source: UniProtKB
    6. ciliary rootlet Source: RefGenome
    7. cytosol Source: Ensembl
    8. dendritic shaft Source: RefGenome
    9. endoplasmic reticulum Source: HGNC
    10. endoplasmic reticulum membrane Source: UniProtKB-SubCell
    11. Golgi apparatus Source: HGNC
    12. Golgi membrane Source: UniProtKB-SubCell
    13. growth cone Source: RefGenome
    14. integral component of plasma membrane Source: HGNC
    15. kinetochore Source: UniProtKB
    16. lysosomal membrane Source: RefGenome
    17. membrane Source: UniProtKB
    18. membrane raft Source: RefGenome
    19. mitochondrial inner membrane Source: RefGenome
    20. neuromuscular junction Source: RefGenome
    21. neuronal cell body Source: RefGenome
    22. nuclear inner membrane Source: UniProtKB
    23. perinuclear region of cytoplasm Source: RefGenome
    24. plasma membrane Source: Reactome
    25. protein complex Source: UniProtKB
    26. Z disc Source: RefGenome

    Keywords - Cellular componenti

    Endoplasmic reticulum, Golgi apparatus, Membrane

    Pathology & Biotechi

    Involvement in diseasei

    Alzheimer disease 4 (AD4) [MIM:606889]: A familial early-onset form of Alzheimer disease. Alzheimer disease is a neurodegenerative disorder characterized by progressive dementia, loss of cognitive abilities, and deposition of fibrillar amyloid proteins as intraneuronal neurofibrillary tangles, extracellular amyloid plaques and vascular amyloid deposits. The major constituent of these plaques is the neurotoxic amyloid-beta-APP 40-42 peptide (s), derived proteolytically from the transmembrane precursor protein APP by sequential secretase processing. The cytotoxic C-terminal fragments (CTFs) and the caspase-cleaved products such as C31 derived from APP, are also implicated in neuronal death.6 Publications
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti62 – 621R → H in AD4; uncertain pathological significance. 2 Publications
    Corresponds to variant rs58973334 [ dbSNP | Ensembl ].
    VAR_006461
    Natural varianti71 – 711R → W in AD4; unknown pathological significance. 1 Publication
    VAR_070027
    Natural varianti122 – 1221T → P in AD4. 1 Publication
    VAR_009214
    Natural varianti130 – 1301S → L in CMD1V and AD4; unknown pathological significance. 2 Publications
    Corresponds to variant rs63750197 [ dbSNP | Ensembl ].
    VAR_064903
    Natural varianti141 – 1411N → I in AD4. 2 Publications
    VAR_006462
    Natural varianti148 – 1481V → I in AD4; late-onset Alzheimer disease. 1 Publication
    VAR_007958
    Natural varianti239 – 2391M → I in AD4. 1 Publication
    VAR_009215
    Natural varianti239 – 2391M → V in AD4; Italian patients. 1 Publication
    Corresponds to variant rs28936379 [ dbSNP | Ensembl ].
    VAR_006463
    Cardiomyopathy, dilated 1V (CMD1V) [MIM:613697]: A disorder characterized by ventricular dilation and impaired systolic function, resulting in congestive heart failure and arrhythmia. Patients are at risk of premature death.1 Publication
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti130 – 1301S → L in CMD1V and AD4; unknown pathological significance. 2 Publications
    Corresponds to variant rs63750197 [ dbSNP | Ensembl ].
    VAR_064903

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi263 – 2631D → A: Reduces production of amyloid beta in APP processing. 1 Publication
    Mutagenesisi366 – 3661D → A: Reduces production of amyloid beta in APP processing and of NICD in NOTCH1 processing. 2 Publications

    Keywords - Diseasei

    Alzheimer disease, Amyloidosis, Cardiomyopathy, Disease mutation, Neurodegeneration

    Organism-specific databases

    MIMi606889. phenotype.
    613697. phenotype.
    Orphaneti1020. Early-onset autosomal dominant Alzheimer disease.
    154. Familial isolated dilated cardiomyopathy.
    PharmGKBiPA33856.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 297297Presenilin-2 NTF subunitBy similarityPRO_0000025603Add
    BLAST
    Chaini298 – 448151Presenilin-2 CTF subunitBy similarityPRO_0000025604Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei22 – 221Phosphoserine1 Publication
    Modified residuei25 – 251Phosphoserine1 Publication

    Post-translational modificationi

    Heterogeneous proteolytic processing generates N-terminal and C-terminal fragments.
    Phosphorylated on serine residues.1 Publication

    Keywords - PTMi

    Phosphoprotein

    Proteomic databases

    MaxQBiP49810.
    PaxDbiP49810.
    PRIDEiP49810.

    PTM databases

    PhosphoSiteiP49810.

    Expressioni

    Tissue specificityi

    Isoform 1 is seen in the placenta, skeletal muscle and heart while isoform 2 is seen in the heart, brain, placenta, liver, skeletal muscle and kidney.1 Publication

    Gene expression databases

    ArrayExpressiP49810.
    BgeeiP49810.
    CleanExiHS_PSEN2.
    GenevestigatoriP49810.

    Organism-specific databases

    HPAiCAB013634.
    HPA038005.

    Interactioni

    Subunit structurei

    Interacts with DOCK3 By similarity. 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 HERPUD1, FLNA, FLNB and PARL.By similarity2 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    DYNC1H1Q142043EBI-2010251,EBI-356015
    ECSITQ9BQ954EBI-2010251,EBI-712452
    PDCD4Q53EL63EBI-2010251,EBI-935824

    Protein-protein interaction databases

    BioGridi111643. 48 interactions.
    IntActiP49810. 22 interactions.
    MINTiMINT-95242.
    STRINGi9606.ENSP00000355747.

    Structurei

    3D structure databases

    ProteinModelPortaliP49810.
    SMRiP49810. Positions 298-448.
    ModBaseiSearch...
    MobiDBiSearch...

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini1 – 8787CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini109 – 13830LumenalSequence AnalysisAdd
    BLAST
    Topological domaini160 – 1667CytoplasmicSequence Analysis
    Topological domaini188 – 20013LumenalSequence AnalysisAdd
    BLAST
    Topological domaini222 – 2232CytoplasmicSequence Analysis
    Topological domaini245 – 2495LumenalSequence Analysis
    Topological domaini271 – 36191CytoplasmicSequence AnalysisAdd
    BLAST
    Topological domaini383 – 3886LumenalSequence Analysis
    Topological domaini410 – 4134CytoplasmicSequence Analysis
    Topological domaini435 – 44814CytoplasmicSequence AnalysisAdd
    BLAST

    Intramembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Intramembranei414 – 43421HelicalSequence AnalysisAdd
    BLAST

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei88 – 10821HelicalSequence AnalysisAdd
    BLAST
    Transmembranei139 – 15921HelicalSequence AnalysisAdd
    BLAST
    Transmembranei167 – 18721HelicalSequence AnalysisAdd
    BLAST
    Transmembranei201 – 22121HelicalSequence AnalysisAdd
    BLAST
    Transmembranei224 – 24421HelicalSequence AnalysisAdd
    BLAST
    Transmembranei250 – 27021HelicalSequence AnalysisAdd
    BLAST
    Transmembranei362 – 38221HelicalSequence AnalysisAdd
    BLAST
    Transmembranei389 – 40921HelicalSequence AnalysisAdd
    BLAST

    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.
    InParanoidiP49810.
    KOiK04522.
    PhylomeDBiP49810.
    TreeFamiTF315040.

    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. 2 hits.
    [Graphical view]
    PRINTSiPR01072. PRESENILIN.
    PR01074. PRESENILIN2.
    SMARTiSM00730. PSN. 1 hit.
    [Graphical view]

    Sequences (3)i

    Sequence statusi: Complete.

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

    This entry describes 3 isoformsi produced by alternative splicing. Align

    Isoform 1 (identifier: P49810-1) [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

    MLTFMASDSE EEVCDERTSL MSAESPTPRS CQEGRQGPED GENTAQWRSQ    50
    ENEEDGEEDP DRYVCSGVPG RPPGLEEELT LKYGAKHVIM LFVPVTLCMI 100
    VVVATIKSVR FYTEKNGQLI YTPFTEDTPS VGQRLLNSVL NTLIMISVIV 150
    VMTIFLVVLY KYRCYKFIHG WLIMSSLMLL FLFTYIYLGE VLKTYNVAMD 200
    YPTLLLTVWN FGAVGMVCIH WKGPLVLQQA YLIMISALMA LVFIKYLPEW 250
    SAWVILGAIS VYDLVAVLCP KGPLRMLVET AQERNEPIFP ALIYSSAMVW 300
    TVGMAKLDPS SQGALQLPYD PEMEEDSYDS FGEPSYPEVF EPPLTGYPGE 350
    ELEEEEERGV KLGLGDFIFY SVLVGKAAAT GSGDWNTTLA CFVAILIGLC 400
    LTLLLLAVFK KALPALPISI TFGLIFYFST DNLVRPFMDT LASHQLYI 448
    Length:448
    Mass (Da):50,140
    Last modified:October 1, 1996 - v1
    Checksum:iA927EEC623468116
    GO
    Isoform 2 (identifier: P49810-2) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         263-296: Missing.

    Show »
    Length:414
    Mass (Da):46,387
    Checksum:i75A03F21290BAFF8
    GO
    Isoform 3 (identifier: P49810-3) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         324-324: Missing.

    Note: No experimental confirmation available.

    Show »
    Length:447
    Mass (Da):50,011
    Checksum:iAA9D4FD8CB46E669
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti123 – 1231P → T(PubMed:7638622)Curated
    Sequence conflicti123 – 1231P → T1 PublicationCurated
    Sequence conflicti295 – 2951S → L in AAL16812. 1 PublicationCurated
    Sequence conflicti325 – 3251Missing in AAC50290. (PubMed:8618867)Curated
    Sequence conflicti358 – 3581R → SQG in AAC50290. (PubMed:8618867)Curated
    Sequence conflicti432 – 44817NLVRP…HQLYI → RKHSRFIQMN(PubMed:8618867)CuratedAdd
    BLAST

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti62 – 621R → H in AD4; uncertain pathological significance. 2 Publications
    Corresponds to variant rs58973334 [ dbSNP | Ensembl ].
    VAR_006461
    Natural varianti71 – 711R → W in AD4; unknown pathological significance. 1 Publication
    VAR_070027
    Natural varianti122 – 1221T → P in AD4. 1 Publication
    VAR_009214
    Natural varianti130 – 1301S → L in CMD1V and AD4; unknown pathological significance. 2 Publications
    Corresponds to variant rs63750197 [ dbSNP | Ensembl ].
    VAR_064903
    Natural varianti141 – 1411N → I in AD4. 2 Publications
    VAR_006462
    Natural varianti148 – 1481V → I in AD4; late-onset Alzheimer disease. 1 Publication
    VAR_007958
    Natural varianti239 – 2391M → I in AD4. 1 Publication
    VAR_009215
    Natural varianti239 – 2391M → V in AD4; Italian patients. 1 Publication
    Corresponds to variant rs28936379 [ dbSNP | Ensembl ].
    VAR_006463

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei263 – 29634Missing in isoform 2. CuratedVSP_005194Add
    BLAST
    Alternative sequencei324 – 3241Missing in isoform 3. 1 PublicationVSP_043648

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    L43964 mRNA. Translation: AAB59557.1.
    L44577 mRNA. Translation: AAC42012.1.
    U34349 mRNA. Translation: AAC50290.1.
    U50871 Genomic DNA. Translation: AAB50054.1.
    BT006984 mRNA. Translation: AAP35630.1.
    AK292299 mRNA. Translation: BAF84988.1.
    AL391628 Genomic DNA. Translation: CAH73110.1.
    CH471098 Genomic DNA. Translation: EAW69798.1.
    CH471098 Genomic DNA. Translation: EAW69800.1.
    BC006365 mRNA. Translation: AAH06365.1.
    AF416718 mRNA. Translation: AAL16812.1.
    CCDSiCCDS1556.1. [P49810-1]
    CCDS44324.1. [P49810-3]
    PIRiA56993.
    I39174.
    RefSeqiNP_000438.2. NM_000447.2. [P49810-1]
    NP_036618.2. NM_012486.2. [P49810-3]
    XP_005273256.1. XM_005273199.1. [P49810-1]
    UniGeneiHs.25363.

    Genome annotation databases

    EnsembliENST00000366783; ENSP00000355747; ENSG00000143801. [P49810-1]
    ENST00000422240; ENSP00000403737; ENSG00000143801. [P49810-3]
    GeneIDi5664.
    KEGGihsa:5664.
    UCSCiuc009xeo.1. human. [P49810-1]
    uc009xep.1. human. [P49810-3]

    Polymorphism databases

    DMDMi1709858.

    Keywords - Coding sequence diversityi

    Alternative splicing

    Cross-referencesi

    Web resourcesi

    Alzheimer Research Forum

    Presenilins mutations

    Atlas of Genetics and Cytogenetics in Oncology and Haematology

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    L43964 mRNA. Translation: AAB59557.1 .
    L44577 mRNA. Translation: AAC42012.1 .
    U34349 mRNA. Translation: AAC50290.1 .
    U50871 Genomic DNA. Translation: AAB50054.1 .
    BT006984 mRNA. Translation: AAP35630.1 .
    AK292299 mRNA. Translation: BAF84988.1 .
    AL391628 Genomic DNA. Translation: CAH73110.1 .
    CH471098 Genomic DNA. Translation: EAW69798.1 .
    CH471098 Genomic DNA. Translation: EAW69800.1 .
    BC006365 mRNA. Translation: AAH06365.1 .
    AF416718 mRNA. Translation: AAL16812.1 .
    CCDSi CCDS1556.1. [P49810-1 ]
    CCDS44324.1. [P49810-3 ]
    PIRi A56993.
    I39174.
    RefSeqi NP_000438.2. NM_000447.2. [P49810-1 ]
    NP_036618.2. NM_012486.2. [P49810-3 ]
    XP_005273256.1. XM_005273199.1. [P49810-1 ]
    UniGenei Hs.25363.

    3D structure databases

    ProteinModelPortali P49810.
    SMRi P49810. Positions 298-448.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 111643. 48 interactions.
    IntActi P49810. 22 interactions.
    MINTi MINT-95242.
    STRINGi 9606.ENSP00000355747.

    Chemistry

    BindingDBi P49810.
    ChEMBLi CHEMBL3708.

    Protein family/group databases

    MEROPSi A22.002.
    TCDBi 1.A.54.1.2. the presenilin er ca(2+) leak channel (presenilin) family.

    PTM databases

    PhosphoSitei P49810.

    Polymorphism databases

    DMDMi 1709858.

    Proteomic databases

    MaxQBi P49810.
    PaxDbi P49810.
    PRIDEi P49810.

    Protocols and materials databases

    DNASUi 5664.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000366783 ; ENSP00000355747 ; ENSG00000143801 . [P49810-1 ]
    ENST00000422240 ; ENSP00000403737 ; ENSG00000143801 . [P49810-3 ]
    GeneIDi 5664.
    KEGGi hsa:5664.
    UCSCi uc009xeo.1. human. [P49810-1 ]
    uc009xep.1. human. [P49810-3 ]

    Organism-specific databases

    CTDi 5664.
    GeneCardsi GC01P227058.
    GeneReviewsi PSEN2.
    HGNCi HGNC:9509. PSEN2.
    HPAi CAB013634.
    HPA038005.
    MIMi 600759. gene.
    606889. phenotype.
    613697. phenotype.
    neXtProti NX_P49810.
    Orphaneti 1020. Early-onset autosomal dominant Alzheimer disease.
    154. Familial isolated dilated cardiomyopathy.
    PharmGKBi PA33856.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG237920.
    HOGENOMi HOG000240228.
    HOVERGENi HBG011375.
    InParanoidi P49810.
    KOi K04522.
    PhylomeDBi P49810.
    TreeFami TF315040.

    Enzyme and pathway databases

    Reactomei REACT_116022. Nuclear signaling by ERBB4.
    REACT_118614. Activated NOTCH1 Transmits Signal to the Nucleus.
    REACT_118636. Signaling by NOTCH4.
    REACT_118862. Signaling by NOTCH3.
    REACT_13443. Regulated proteolysis of p75NTR.
    REACT_13643. NRIF signals cell death from the nucleus.
    REACT_160205. NOTCH2 Activation and Transmission of Signal to the Nucleus.
    REACT_160243. Constitutive Signaling by NOTCH1 PEST Domain Mutants.
    REACT_160254. Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants.
    SignaLinki P49810.

    Miscellaneous databases

    ChiTaRSi PSEN2. human.
    GeneWikii PSEN2.
    GenomeRNAii 5664.
    NextBioi 22010.
    PROi P49810.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi P49810.
    Bgeei P49810.
    CleanExi HS_PSEN2.
    Genevestigatori P49810.

    Family and domain databases

    InterProi IPR001493. Pept_A22A_PS2.
    IPR001108. Peptidase_A22A.
    IPR006639. Preselin/SPP.
    [Graphical view ]
    PANTHERi PTHR10202. PTHR10202. 1 hit.
    PTHR10202:SF11. PTHR10202:SF11. 1 hit.
    Pfami PF01080. Presenilin. 2 hits.
    [Graphical view ]
    PRINTSi PR01072. PRESENILIN.
    PR01074. PRESENILIN2.
    SMARTi SM00730. PSN. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT AD4 ILE-141.
    2. "Familial Alzheimer's disease in kindreds with missense mutations in a gene on chromosome 1 related to the Alzheimer's disease type 3 gene."
      Rogaev E.I., Sherrington R., Rogaeva E.A., Levesque G., Ikeda M., Liang Y., Chi H., Lin C., Holman K., Tsuda T., Mar L., Sorbi S., Nacmias B., Piacentini S., Amaducci L., Chumakov I., Cohen D., Lannfelt L.
      , Fraser P.E., Rommens J.M., St George-Hyslop P.H.
      Nature 376:775-778(1995) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANTS AD4 ILE-141 AND VAL-239.
      Tissue: Brain and Colon.
    3. "Identification and expression analysis of a potential familial Alzheimer disease gene on chromosome 1 related to AD3."
      Li J., Ma J., Potter H.
      Proc. Natl. Acad. Sci. U.S.A. 92:12180-12184(1995) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    4. "Genomic structure and expression of STM2, the chromosome 1 familial Alzheimer disease gene."
      Levy-Lahad E., Poorkaj P., Wang K., Fu Y.H., Oshima J., Mulligan J., Schellenberg G.D.
      Genomics 34:198-204(1996) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    5. "Cloning of human full-length CDSs in BD Creator(TM) system donor vector."
      Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A.
      Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    6. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
      Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
      , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
      Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
      Tissue: Testis.
    7. "The DNA sequence and biological annotation of human chromosome 1."
      Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.
      , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.
      Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    8. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    9. "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].
      Tissue: Muscle.
    10. Xu Y., Hu X., Zhou Y., Peng X., Yuan J., Qiang B.
      Submitted (SEP-2001) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE OF 1-390.
    11. "Alzheimer-associated presenilins 1 and 2: neuronal expression in brain and localization to intracellular membranes in mammalian cells."
      Kovacs D.M., Fausett H.J., Page K.J., Kim T.-W., Moir R.D., Merriam D.E., Hollister R.D., Hallmark O.G., Mancini R., Felsenstein K.M., Hyman B.T., Tanzi R.E., Wasco W.
      Nat. Med. 2:224-229(1996) [PubMed] [Europe PMC] [Abstract]
      Cited for: SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
    12. "Interaction of presenilins with the filamin family of actin-binding proteins."
      Zhang W., Han S.W., McKeel D.W., Goate A., Wu J.Y.
      J. Neurosci. 18:914-922(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH FLNA AND FLNB.
    13. "A loss of function mutation of presenilin-2 interferes with amyloid beta-peptide production and notch signaling."
      Steiner H., Duff K., Capell A., Romig H., Grim M.G., Lincoln S., Hardy J., Yu X., Picciano M., Fechteler K., Citron M., Kopan R., Pesold B., Keck S., Baader M., Tomita T., Iwatsubo T., Baumeister R., Haass C.
      J. Biol. Chem. 274:28669-28673(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, ACTIVE SITE ASP-366, MUTAGENESIS OF ASP-366.
    14. "The transmembrane aspartates in presenilin 1 and 2 are obligatory for gamma-secretase activity and amyloid beta-protein generation."
      Kimberly W.T., Xia W., Rahmati T., Wolfe M.S., Selkoe D.J.
      J. Biol. Chem. 275:3173-3178(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, ACTIVE SITES ASP-263 AND ASP-366, MUTAGENESIS OF ASP-263 AND ASP-366.
    15. "Endoplasmic reticulum stress-inducible protein, Herp, enhances presenilin-mediated generation of amyloid beta-protein."
      Sai X., Kawamura Y., Kokame K., Yamaguchi H., Shiraishi H., Suzuki R., Suzuki T., Kawaichi M., Miyata T., Kitamura T., De Strooper B., Yanagisawa K., Komano H.
      J. Biol. Chem. 277:12915-12920(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH HERPUD1.
    16. "Presenilin mutations in Alzheimer's disease."
      Cruts M., van Broeckhoven C.
      Hum. Mutat. 11:183-190(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: REVIEW ON VARIANTS.
    17. "Consensus analysis of signal peptide peptidase and homologous human aspartic proteases reveals opposite topology of catalytic domains compared with presenilins."
      Friedmann E., Lemberg M.K., Weihofen A., Dev K.K., Dengler U., Rovelli G., Martoglio B.
      J. Biol. Chem. 279:50790-50798(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: TOPOLOGY.
    18. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Cervix carcinoma.
    19. "Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach."
      Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.
      Anal. Chem. 81:4493-4501(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    20. "Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis."
      Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.
      Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-22 AND SER-25, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Cervix carcinoma.
    21. "Estimation of the genetic contribution of presenilin-1 and -2 mutations in a population-based study of presenile Alzheimer disease."
      Cruts M., van Duijn C.M., Backhovens H., van den Broeck M., Wehnert A., Serneels S., Sherrington R., Hutton M., Hardy J., St George-Hyslop P.H., Hofman A., van Broeckhoven C.
      Hum. Mol. Genet. 7:43-51(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT AD4 HIS-62.
    22. "A novel mutation in the predicted TM2 domain of the presenilin 2 gene in Spanish patient with late-onset Alzheimer's disease."
      Lao J.I., Beyer K., Fernandez-Novoa L., Cacabelos R.
      Neurogenetics 1:293-296(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT AD4 ILE-148.
    23. "High prevalence of pathogenic mutations in patients with early-onset dementia detected by sequence analyses of four different genes."
      Finckh U., Mueller-Thomsen T., Mann U., Eggers C., Marksteiner J., Meins W., Binetti G., Alberici A., Hock C., Nitsch R.M., Gal A.
      Am. J. Hum. Genet. 66:110-117(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANTS AD4 PRO-122 AND ILE-239.
    24. Cited for: VARIANT CMD1V LEU-130.
    25. "Identification of PSEN1 and PSEN2 gene mutations and variants in Turkish dementia patients."
      Lohmann E., Guerreiro R.J., Erginel-Unaltuna N., Gurunlian N., Bilgic B., Gurvit H., Hanagasi H.A., Luu N., Emre M., Singleton A.
      Neurobiol. Aging 33:1850.E17-1850.E27(2012) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANTS AD4 HIS-62; TRP-71 AND LEU-130.

    Entry informationi

    Entry nameiPSN2_HUMAN
    AccessioniPrimary (citable) accession number: P49810
    Secondary accession number(s): A8K8D4, B1AP21, Q96P32
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: October 1, 1996
    Last sequence update: October 1, 1996
    Last modified: October 1, 2014
    This is version 159 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. Human chromosome 1
      Human chromosome 1: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. Peptidase families
      Classification of peptidase families and list of entries
    6. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3