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P49810 (PSN2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 154. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Presenilin-2

Short name=PS-2
EC=3.4.23.-
Alternative name(s):
AD3LP
AD5
E5-1
STM-2

Cleaved into the following 2 chains:

  1. Presenilin-2 NTF subunit
  2. Presenilin-2 CTF subunit
Gene names
Name:PSEN2
Synonyms:AD4, PS2, PSNL2, STM2
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length448 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.13 Ref.14

Subunit structure

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. Ref.12 Ref.15

Subcellular location

Endoplasmic reticulum membrane; Multi-pass membrane protein. Golgi apparatus membrane; Multi-pass membrane protein Ref.11.

Tissue specificity

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. Ref.11

Domain

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

Post-translational modification

Heterogeneous proteolytic processing generates N-terminal and C-terminal fragments.

Phosphorylated on serine residues.

Involvement in disease

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. Ref.1 Ref.2 Ref.21 Ref.22 Ref.23 Ref.25

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. Ref.24

Sequence similarities

Belongs to the peptidase A22A family.

Ontologies

Keywords
   Biological processNotch signaling pathway
   Cellular componentEndoplasmic reticulum
Golgi apparatus
Membrane
   Coding sequence diversityAlternative splicing
   DiseaseAlzheimer disease
Amyloidosis
Cardiomyopathy
Disease mutation
Neurodegeneration
   DomainTransmembrane
Transmembrane helix
   Molecular functionHydrolase
Protease
   PTMPhosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processNotch receptor processing

Traceable author statement PubMed 15274632. Source: HGNC

Notch signaling pathway

Traceable author statement. Source: Reactome

T cell activation involved in immune response

Inferred from electronic annotation. Source: Ensembl

T cell receptor signaling pathway

Inferred from electronic annotation. Source: Ensembl

amyloid precursor protein catabolic process

Traceable author statement PubMed 15274632. Source: HGNC

anagen

Inferred from electronic annotation. Source: Ensembl

apoptotic signaling pathway

Traceable author statement. Source: Reactome

beta-amyloid metabolic process

Inferred from Biological aspect of Ancestor. Source: RefGenome

brain morphogenesis

Inferred from electronic annotation. Source: Ensembl

calcium ion transport

Inferred from Biological aspect of Ancestor. Source: RefGenome

cardiac muscle contraction

Inferred from electronic annotation. Source: Ensembl

cell fate specification

Inferred from electronic annotation. Source: Ensembl

dorsal/ventral neural tube patterning

Inferred from electronic annotation. Source: Ensembl

embryonic limb morphogenesis

Inferred from electronic annotation. Source: Ensembl

endoplasmic reticulum calcium ion homeostasis

Inferred from electronic annotation. Source: Ensembl

forebrain development

Inferred from electronic annotation. Source: Ensembl

hematopoietic progenitor cell differentiation

Inferred from electronic annotation. Source: Ensembl

intracellular signal transduction

Inferred from electronic annotation. Source: InterPro

locomotion

Inferred from electronic annotation. Source: Ensembl

lung alveolus development

Inferred from electronic annotation. Source: Ensembl

membrane protein ectodomain proteolysis

Inferred from direct assay PubMed 15274632. Source: HGNC

membrane protein intracellular domain proteolysis

Traceable author statement. Source: Reactome

memory

Inferred from electronic annotation. Source: Ensembl

myeloid leukocyte differentiation

Inferred from electronic annotation. Source: Ensembl

negative regulation of extrinsic apoptotic signaling pathway via death domain receptors

Inferred from electronic annotation. Source: Ensembl

negative regulation of protein binding

Inferred from electronic annotation. Source: Ensembl

negative regulation of protein complex assembly

Inferred from electronic annotation. Source: Ensembl

negative regulation of protein phosphorylation

Inferred from electronic annotation. Source: Ensembl

neurotrophin TRK receptor signaling pathway

Traceable author statement. Source: Reactome

positive regulation of apoptotic process

Traceable author statement. Source: Reactome

positive regulation of catalytic activity

Inferred from direct assay PubMed 15274632. Source: HGNC

positive regulation of coagulation

Inferred from electronic annotation. Source: Ensembl

positive regulation of extrinsic apoptotic signaling pathway via death domain receptors

Inferred from electronic annotation. Source: Ensembl

protein processing

Inferred from direct assay PubMed 15274632. Source: HGNC

protein transport

Inferred from electronic annotation. Source: Ensembl

regulation of epidermal growth factor-activated receptor activity

Inferred from electronic annotation. Source: Ensembl

regulation of synaptic plasticity

Inferred from electronic annotation. Source: Ensembl

response to hypoxia

Inferred from electronic annotation. Source: Ensembl

somitogenesis

Inferred from electronic annotation. Source: Ensembl

thymus development

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentGolgi apparatus

Inferred from direct assay PubMed 15274632. Source: HGNC

Golgi membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

Z disc

Inferred from Biological aspect of Ancestor. Source: RefGenome

apical plasma membrane

Inferred from Biological aspect of Ancestor. Source: RefGenome

axon

Inferred from Biological aspect of Ancestor. Source: RefGenome

cell cortex

Inferred from Biological aspect of Ancestor. Source: RefGenome

cell surface

Inferred from Biological aspect of Ancestor. Source: RefGenome

centrosome

Inferred from direct assay PubMed 9298903. Source: UniProtKB

ciliary rootlet

Inferred from Biological aspect of Ancestor. Source: RefGenome

cytosol

Inferred from electronic annotation. Source: Ensembl

dendritic shaft

Inferred from Biological aspect of Ancestor. Source: RefGenome

endoplasmic reticulum

Inferred from direct assay PubMed 15274632. Source: HGNC

endoplasmic reticulum membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

growth cone

Inferred from Biological aspect of Ancestor. Source: RefGenome

integral component of plasma membrane

Inferred from direct assay PubMed 15274632. Source: HGNC

kinetochore

Inferred from direct assay PubMed 9298903. Source: UniProtKB

lysosomal membrane

Inferred from Biological aspect of Ancestor. Source: RefGenome

membrane raft

Inferred from Biological aspect of Ancestor. Source: RefGenome

mitochondrial inner membrane

Inferred from Biological aspect of Ancestor. Source: RefGenome

neuromuscular junction

Inferred from Biological aspect of Ancestor. Source: RefGenome

neuronal cell body

Inferred from Biological aspect of Ancestor. Source: RefGenome

nuclear inner membrane

Inferred from direct assay PubMed 9298903. Source: UniProtKB

perinuclear region of cytoplasm

Inferred from Biological aspect of Ancestor. Source: RefGenome

plasma membrane

Traceable author statement. Source: Reactome

protein complex

Inferred from direct assay PubMed 9632714. Source: UniProtKB

   Molecular_functionaspartic-type endopeptidase activity

Inferred from electronic annotation. Source: InterPro

endopeptidase activity

Inferred from Biological aspect of Ancestor. Source: RefGenome

Complete GO annotation...

Binary interactions

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P49810-1)

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.
Isoform 2 (identifier: P49810-2)

The sequence of this isoform differs from the canonical sequence as follows:
     263-296: Missing.
Isoform 3 (identifier: P49810-3)

The sequence of this isoform differs from the canonical sequence as follows:
     324-324: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 297297Presenilin-2 NTF subunit By similarity
PRO_0000025603
Chain298 – 448151Presenilin-2 CTF subunit By similarity
PRO_0000025604

Regions

Topological domain1 – 8787Cytoplasmic Potential
Transmembrane88 – 10821Helical; Potential
Topological domain109 – 13830Lumenal Potential
Transmembrane139 – 15921Helical; Potential
Topological domain160 – 1667Cytoplasmic Potential
Transmembrane167 – 18721Helical; Potential
Topological domain188 – 20013Lumenal Potential
Transmembrane201 – 22121Helical; Potential
Topological domain222 – 2232Cytoplasmic Potential
Transmembrane224 – 24421Helical; Potential
Topological domain245 – 2495Lumenal Potential
Transmembrane250 – 27021Helical; Potential
Topological domain271 – 36191Cytoplasmic Potential
Transmembrane362 – 38221Helical; Potential
Topological domain383 – 3886Lumenal Potential
Transmembrane389 – 40921Helical; Potential
Topological domain410 – 4134Cytoplasmic Potential
Intramembrane414 – 43421Helical; Potential
Topological domain435 – 44814Cytoplasmic Potential
Motif414 – 4163PAL

Sites

Active site2631 Probable
Active site3661 Probable

Amino acid modifications

Modified residue221Phosphoserine Ref.20
Modified residue251Phosphoserine Ref.20

Natural variations

Alternative sequence263 – 29634Missing in isoform 2.
VSP_005194
Alternative sequence3241Missing in isoform 3.
VSP_043648
Natural variant621R → H in AD4; uncertain pathological significance. Ref.21 Ref.25
Corresponds to variant rs58973334 [ dbSNP | Ensembl ].
VAR_006461
Natural variant711R → W in AD4; unknown pathological significance. Ref.25
VAR_070027
Natural variant1221T → P in AD4. Ref.23
VAR_009214
Natural variant1301S → L in CMD1V and AD4; unknown pathological significance. Ref.24 Ref.25
Corresponds to variant rs63750197 [ dbSNP | Ensembl ].
VAR_064903
Natural variant1411N → I in AD4. Ref.1 Ref.2
VAR_006462
Natural variant1481V → I in AD4; late-onset Alzheimer disease. Ref.22
VAR_007958
Natural variant2391M → I in AD4. Ref.23
VAR_009215
Natural variant2391M → V in AD4; Italian patients. Ref.2
Corresponds to variant rs28936379 [ dbSNP | Ensembl ].
VAR_006463

Experimental info

Mutagenesis2631D → A: Reduces production of amyloid beta in APP processing. Ref.14
Mutagenesis3661D → A: Reduces production of amyloid beta in APP processing and of NICD in NOTCH1 processing. Ref.13 Ref.14
Sequence conflict1231P → T Ref.1
Sequence conflict1231P → T Ref.10
Sequence conflict2951S → L in AAL16812. Ref.10
Sequence conflict3251Missing in AAC50290. Ref.3
Sequence conflict3581R → SQG in AAC50290. Ref.3
Sequence conflict432 – 44817NLVRP…HQLYI → RKHSRFIQMN Ref.3

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified October 1, 1996. Version 1.
Checksum: A927EEC623468116

FASTA44850,140
        10         20         30         40         50         60 
MLTFMASDSE EEVCDERTSL MSAESPTPRS CQEGRQGPED GENTAQWRSQ ENEEDGEEDP 

        70         80         90        100        110        120 
DRYVCSGVPG RPPGLEEELT LKYGAKHVIM LFVPVTLCMI VVVATIKSVR FYTEKNGQLI 

       130        140        150        160        170        180 
YTPFTEDTPS VGQRLLNSVL NTLIMISVIV VMTIFLVVLY KYRCYKFIHG WLIMSSLMLL 

       190        200        210        220        230        240 
FLFTYIYLGE VLKTYNVAMD YPTLLLTVWN FGAVGMVCIH WKGPLVLQQA YLIMISALMA 

       250        260        270        280        290        300 
LVFIKYLPEW SAWVILGAIS VYDLVAVLCP KGPLRMLVET AQERNEPIFP ALIYSSAMVW 

       310        320        330        340        350        360 
TVGMAKLDPS SQGALQLPYD PEMEEDSYDS FGEPSYPEVF EPPLTGYPGE ELEEEEERGV 

       370        380        390        400        410        420 
KLGLGDFIFY SVLVGKAAAT GSGDWNTTLA CFVAILIGLC LTLLLLAVFK KALPALPISI 

       430        440 
TFGLIFYFST DNLVRPFMDT LASHQLYI 

« Hide

Isoform 2 [UniParc].

Checksum: 75A03F21290BAFF8
Show »

FASTA41446,387
Isoform 3 [UniParc].

Checksum: AA9D4FD8CB46E669
Show »

FASTA44750,011

References

« Hide 'large scale' references
[1]"Candidate gene for the chromosome 1 familial Alzheimer's disease locus."
Levy-Lahad E., Wasco W., Poorkaj P., Romano D.M., Oshima J., Pettingell W.H. Jr., Yu C.-E., Jondro P.D., Schmidt S.D., Wang K., Crowley A.C., Fu Y.-H., Guenette S.Y., Galas D., Nemens E., Wijsman E.M., Bird T.D., Schellenberg G.D., Tanzi R.E.
Science 269:973-977(1995) [PubMed] [Europe PMC] [Abstract]
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. expand/collapse author list , 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. expand/collapse author list , 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. expand/collapse author list , 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]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
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]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
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]"Mutations of presenilin genes in dilated cardiomyopathy and heart failure."
Li D., Parks S.B., Kushner J.D., Nauman D., Burgess D., Ludwigsen S., Partain J., Nixon R.R., Allen C.N., Irwin R.P., Jakobs P.M., Litt M., Hershberger R.E.
Am. J. Hum. Genet. 79:1030-1039(2006) [PubMed] [Europe PMC] [Abstract]
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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
PIRA56993.
I39174.
RefSeqNP_000438.2. NM_000447.2.
NP_036618.2. NM_012486.2.
XP_005273256.1. XM_005273199.1.
UniGeneHs.25363.

3D structure databases

ProteinModelPortalP49810.
SMRP49810. Positions 298-448.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid111643. 48 interactions.
IntActP49810. 22 interactions.
MINTMINT-95242.
STRING9606.ENSP00000355747.

Chemistry

BindingDBP49810.
ChEMBLCHEMBL2094135.

Protein family/group databases

MEROPSA22.002.
TCDB1.A.54.1.2. the presenilin er ca(2+) leak channel (presenilin) family.

PTM databases

PhosphoSiteP49810.

Polymorphism databases

DMDM1709858.

Proteomic databases

PaxDbP49810.
PRIDEP49810.

Protocols and materials databases

DNASU5664.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000366783; ENSP00000355747; ENSG00000143801. [P49810-1]
ENST00000422240; ENSP00000403737; ENSG00000143801. [P49810-3]
GeneID5664.
KEGGhsa:5664.
UCSCuc009xeo.1. human. [P49810-1]
uc009xep.1. human. [P49810-3]

Organism-specific databases

CTD5664.
GeneCardsGC01P227058.
HGNCHGNC:9509. PSEN2.
HPACAB013634.
HPA038005.
MIM600759. gene.
606889. phenotype.
613697. phenotype.
neXtProtNX_P49810.
Orphanet1020. Early-onset autosomal dominant Alzheimer disease.
154. Familial isolated dilated cardiomyopathy.
PharmGKBPA33856.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG237920.
HOGENOMHOG000240228.
HOVERGENHBG011375.
InParanoidP49810.
KOK04522.
PhylomeDBP49810.
TreeFamTF315040.

Enzyme and pathway databases

ReactomeREACT_111102. Signal Transduction.
REACT_116125. Disease.
REACT_691. A third proteolytic cleavage releases NICD.
SignaLinkP49810.

Gene expression databases

ArrayExpressP49810.
BgeeP49810.
CleanExHS_PSEN2.
GenevestigatorP49810.

Family and domain databases

InterProIPR001493. Pept_A22A_PS2.
IPR001108. Peptidase_A22A.
IPR006639. Preselin/SPP.
[Graphical view]
PANTHERPTHR10202. PTHR10202. 1 hit.
PfamPF01080. Presenilin. 2 hits.
[Graphical view]
PRINTSPR01072. PRESENILIN.
PR01074. PRESENILIN2.
SMARTSM00730. PSN. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSPSEN2. human.
GeneWikiPSEN2.
GenomeRNAi5664.
NextBio22010.
PROP49810.
SOURCESearch...

Entry information

Entry namePSN2_HUMAN
AccessionPrimary (citable) accession number: P49810
Secondary accession number(s): A8K8D4, B1AP21, Q96P32
Entry history
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: October 1, 1996
Last modified: April 16, 2014
This is version 154 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Peptidase families

Classification of peptidase families and list of entries

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 1

Human chromosome 1: entries, gene names and cross-references to MIM