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P49810

- PSN2_HUMAN

UniProt

P49810 - PSN2_HUMAN

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Protein
Presenilin-2
Gene
PSEN2, AD4, PS2, PSNL2, STM2
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 – 2631 Inferred
Active sitei366 – 3661 Inferred

GO - Molecular functioni

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

GO - Biological processi

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

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 8787Cytoplasmic Reviewed prediction
Add
BLAST
Transmembranei88 – 10821Helical; Reviewed prediction
Add
BLAST
Topological domaini109 – 13830Lumenal Reviewed prediction
Add
BLAST
Transmembranei139 – 15921Helical; Reviewed prediction
Add
BLAST
Topological domaini160 – 1667Cytoplasmic Reviewed prediction
Transmembranei167 – 18721Helical; Reviewed prediction
Add
BLAST
Topological domaini188 – 20013Lumenal Reviewed prediction
Add
BLAST
Transmembranei201 – 22121Helical; Reviewed prediction
Add
BLAST
Topological domaini222 – 2232Cytoplasmic Reviewed prediction
Transmembranei224 – 24421Helical; Reviewed prediction
Add
BLAST
Topological domaini245 – 2495Lumenal Reviewed prediction
Transmembranei250 – 27021Helical; Reviewed prediction
Add
BLAST
Topological domaini271 – 36191Cytoplasmic Reviewed prediction
Add
BLAST
Transmembranei362 – 38221Helical; Reviewed prediction
Add
BLAST
Topological domaini383 – 3886Lumenal Reviewed prediction
Transmembranei389 – 40921Helical; Reviewed prediction
Add
BLAST
Topological domaini410 – 4134Cytoplasmic Reviewed prediction
Intramembranei414 – 43421Helical; Reviewed prediction
Add
BLAST
Topological domaini435 – 44814Cytoplasmic Reviewed prediction
Add
BLAST

GO - Cellular componenti

  1. Golgi apparatus Source: HGNC
  2. Golgi membrane Source: UniProtKB-SubCell
  3. Z disc Source: RefGenome
  4. apical plasma membrane Source: RefGenome
  5. axon Source: RefGenome
  6. cell cortex Source: RefGenome
  7. cell surface Source: RefGenome
  8. centrosome Source: UniProtKB
  9. ciliary rootlet Source: RefGenome
  10. cytosol Source: Ensembl
  11. dendritic shaft Source: RefGenome
  12. endoplasmic reticulum Source: HGNC
  13. endoplasmic reticulum membrane Source: UniProtKB-SubCell
  14. growth cone Source: RefGenome
  15. integral component of plasma membrane Source: HGNC
  16. kinetochore Source: UniProtKB
  17. lysosomal membrane Source: RefGenome
  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
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.
Note: The disease is caused by mutations affecting the gene represented in this entry.6 Publications
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.
Note: The disease is caused by mutations affecting the gene represented in this entry.1 Publication
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 subunit By similarity
PRO_0000025603Add
BLAST
Chaini298 – 448151Presenilin-2 CTF subunit By similarity
PRO_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.

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.2 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.

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.

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

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.
VSP_005194Add
BLAST
Alternative sequencei324 – 3241Missing in isoform 3.
VSP_043648

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti123 – 1231P → T1 Publication
Sequence conflicti123 – 1231P → T1 Publication
Sequence conflicti295 – 2951S → L in AAL16812. 1 Publication
Sequence conflicti325 – 3251Missing in AAC50290. 1 Publication
Sequence conflicti358 – 3581R → SQG in AAC50290. 1 Publication
Sequence conflicti432 – 44817NLVRP…HQLYI → RKHSRFIQMN1 Publication
Add
BLAST

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...

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

« 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: September 3, 2014
This is version 158 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

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