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P49810

- PSN2_HUMAN

UniProt

P49810 - PSN2_HUMAN

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Protein

Presenilin-2

Gene

PSEN2

Organism
Homo sapiens (Human)
Status
Reviewed - 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.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

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
Complete GO annotation...

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.
REACT_228189. EPH-ephrin mediated repulsion of cells.
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

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 – 36191CytoplasmicSequence AnalysisAdd
BLAST
Transmembranei362 – 38221HelicalSequence AnalysisAdd
BLAST
Topological domaini383 – 3886LumenalSequence Analysis
Transmembranei389 – 40921HelicalSequence AnalysisAdd
BLAST
Topological domaini410 – 4134CytoplasmicSequence Analysis
Intramembranei414 – 43421HelicalSequence AnalysisAdd
BLAST
Topological domaini435 – 44814CytoplasmicSequence AnalysisAdd
BLAST

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 basal body Source: Ensembl
  7. ciliary rootlet Source: RefGenome
  8. cytosol Source: Ensembl
  9. dendritic shaft Source: RefGenome
  10. endoplasmic reticulum Source: HGNC
  11. Golgi apparatus Source: HGNC
  12. growth cone Source: RefGenome
  13. integral component of plasma membrane Source: HGNC
  14. kinetochore Source: UniProtKB
  15. lysosomal membrane Source: RefGenome
  16. membrane Source: UniProtKB
  17. membrane raft Source: RefGenome
  18. mitochondrial inner membrane Source: RefGenome
  19. neuromuscular junction Source: RefGenome
  20. neuronal cell body Source: RefGenome
  21. nuclear inner membrane Source: UniProtKB
  22. perinuclear region of cytoplasm Source: RefGenome
  23. plasma membrane Source: Reactome
  24. protein complex Source: UniProtKB
  25. Z disc Source: RefGenome
Complete GO annotation...

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

BgeeiP49810.
CleanExiHS_PSEN2.
ExpressionAtlasiP49810. baseline and differential.
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. 53 interactions.
IntActiP49810. 22 interactions.
MINTiMINT-95242.
STRINGi9606.ENSP00000355747.

Structurei

3D structure databases

ProteinModelPortaliP49810.
SMRiP49810. 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.
GeneTreeiENSGT00390000016593.
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

        10         20         30         40         50
MLTFMASDSE EEVCDERTSL MSAESPTPRS CQEGRQGPED GENTAQWRSQ
60 70 80 90 100
ENEEDGEEDP DRYVCSGVPG RPPGLEEELT LKYGAKHVIM 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
YPTLLLTVWN FGAVGMVCIH WKGPLVLQQA YLIMISALMA LVFIKYLPEW
260 270 280 290 300
SAWVILGAIS VYDLVAVLCP KGPLRMLVET AQERNEPIFP ALIYSSAMVW
310 320 330 340 350
TVGMAKLDPS SQGALQLPYD PEMEEDSYDS FGEPSYPEVF EPPLTGYPGE
360 370 380 390 400
ELEEEEERGV KLGLGDFIFY SVLVGKAAAT GSGDWNTTLA CFVAILIGLC
410 420 430 440
LTLLLLAVFK KALPALPISI TFGLIFYFST DNLVRPFMDT LASHQLYI
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:
EMBLi
GenBanki
DDBJi
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:
EMBLi
GenBanki
DDBJi
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. 53 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.
GeneTreei ENSGT00390000016593.
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.
REACT_228189. EPH-ephrin mediated repulsion of cells.
SignaLinki P49810.

Miscellaneous databases

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

Gene expression databases

Bgeei P49810.
CleanExi HS_PSEN2.
ExpressionAtlasi P49810. baseline and differential.
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

« Hide 'large scale' publications
  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: November 26, 2014
This is version 161 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