P49810 (PSN2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	448 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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.20 Ref.21 Ref.22 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.23
Sequence similarities	Belongs to the peptidase A22A family.

Ontologies

Keywords
Biological process	Notch signaling pathway
Cellular component	Endoplasmic reticulum Golgi apparatus Membrane
Coding sequence diversity	Alternative splicing
Disease	Alzheimer disease Amyloidosis Cardiomyopathy Disease mutation Neurodegeneration
Domain	Transmembrane Transmembrane helix
Molecular function	Hydrolase Protease
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	Notch 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: Compara T cell receptor signaling pathway Inferred from electronic annotation. Source: Compara amyloid precursor protein catabolic process Traceable author statement PubMed 15274632. Source: HGNC anagen Inferred from electronic annotation. Source: Compara apoptotic process Traceable author statement. Source: Reactome beta-amyloid metabolic process Inferred from Biological aspect of Ancestor. Source: RefGenome brain morphogenesis Inferred from electronic annotation. Source: Compara calcium ion transport Inferred from Biological aspect of Ancestor. Source: RefGenome cardiac muscle contraction Inferred from electronic annotation. Source: Compara cell fate specification Inferred from electronic annotation. Source: Compara dorsal/ventral neural tube patterning Inferred from electronic annotation. Source: Compara embryonic limb morphogenesis Inferred from electronic annotation. Source: Compara endoplasmic reticulum calcium ion homeostasis Inferred from electronic annotation. Source: Compara forebrain development Inferred from electronic annotation. Source: Compara hematopoietic progenitor cell differentiation Inferred from electronic annotation. Source: Compara intracellular signal transduction Inferred from electronic annotation. Source: InterPro locomotion Inferred from electronic annotation. Source: Compara lung alveolus development Inferred from electronic annotation. Source: Compara 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: Compara myeloid leukocyte differentiation Inferred from electronic annotation. Source: Compara negative regulation of protein phosphorylation Inferred from electronic annotation. Source: Compara nerve growth factor receptor signaling pathway Traceable author statement. Source: Reactome positive regulation of apoptotic process Inferred from electronic annotation. Source: Compara positive regulation of catalytic activity Inferred from direct assay PubMed 15274632. Source: HGNC positive regulation of coagulation Inferred from electronic annotation. Source: Compara protein processing Inferred from direct assay PubMed 15274632. Source: HGNC protein transport Inferred from electronic annotation. Source: Compara regulation of epidermal growth factor-activated receptor activity Inferred from electronic annotation. Source: Compara regulation of protein binding Inferred from electronic annotation. Source: Compara regulation of synaptic plasticity Inferred from electronic annotation. Source: Compara response to hypoxia Inferred from electronic annotation. Source: Compara somitogenesis Inferred from electronic annotation. Source: Compara thymus development Inferred from electronic annotation. Source: Compara
Cellular_component	Golgi 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: Compara 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 to 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
Molecular_function	aspartic-type endopeptidase activity Inferred from electronic annotation. Source: InterPro endopeptidase activity Inferred from Biological aspect of Ancestor. Source: RefGenome
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
DYNC1H1	Q14204	3	EBI-2010251,EBI-356015
ECSIT	Q9BQ95	4	EBI-2010251,EBI-712452
PDCD4	Q53EL6	3	EBI-2010251,EBI-935824

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 key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 297	297	Presenilin-2 NTF subunit By similarity		PRO_0000025603
	Chain	298 – 448	151	Presenilin-2 CTF subunit By similarity		PRO_0000025604
Regions
	Topological domain	1 – 87	87	Cytoplasmic Potential
	Transmembrane	88 – 108	21	Helical; Potential
	Topological domain	109 – 138	30	Lumenal Potential
	Transmembrane	139 – 159	21	Helical; Potential
	Topological domain	160 – 166	7	Cytoplasmic Potential
	Transmembrane	167 – 187	21	Helical; Potential
	Topological domain	188 – 200	13	Lumenal Potential
	Transmembrane	201 – 221	21	Helical; Potential
	Topological domain	222 – 223	2	Cytoplasmic Potential
	Transmembrane	224 – 244	21	Helical; Potential
	Topological domain	245 – 249	5	Lumenal Potential
	Transmembrane	250 – 270	21	Helical; Potential
	Topological domain	271 – 361	91	Cytoplasmic Potential
	Transmembrane	362 – 382	21	Helical; Potential
	Topological domain	383 – 388	6	Lumenal Potential
	Transmembrane	389 – 409	21	Helical; Potential
	Topological domain	410 – 413	4	Cytoplasmic Potential
	Intramembrane	414 – 434	21	Helical; Potential
	Topological domain	435 – 448	14	Cytoplasmic Potential
	Motif	414 – 416	3	PAL
Sites
	Active site	263	1	Probable
	Active site	366	1	Probable
Amino acid modifications
	Modified residue	22	1	Phosphoserine Ref.19
	Modified residue	25	1	Phosphoserine Ref.19
	Modified residue	30	1	Phosphoserine By similarity
Natural variations
	Alternative sequence	263 – 296	34	Missing in isoform 2.		VSP_005194
	Alternative sequence	324	1	Missing in isoform 3.		VSP_043648
	Natural variant	62	1	R → H in AD4. Ref.20 Corresponds to variant rs58973334 [ dbSNP | Ensembl ].		VAR_006461
	Natural variant	122	1	T → P in AD4. Ref.22		VAR_009214
	Natural variant	130	1	S → L in CMD1V. Ref.23		VAR_064903
	Natural variant	141	1	N → I in AD4; Volga German patients. Ref.1 Ref.2		VAR_006462
	Natural variant	148	1	V → I in AD4; LOAD; Spanish patients. Ref.21		VAR_007958
	Natural variant	239	1	M → I in AD4. Ref.22		VAR_009215
	Natural variant	239	1	M → V in AD4; Italian patients. Ref.2 Corresponds to variant rs28936379 [ dbSNP | Ensembl ].		VAR_006463
Experimental info
	Mutagenesis	263	1	D → A: Reduces production of amyloid beta in APP processing. Ref.14
	Mutagenesis	366	1	D → A: Reduces production of amyloid beta in APP processing and of NICD in NOTCH1 processing. Ref.13 Ref.14
	Sequence conflict	123	1	P → T Ref.1
	Sequence conflict	123	1	P → T Ref.10
	Sequence conflict	295	1	S → L in AAL16812. Ref.10
	Sequence conflict	325	1	Missing in AAC50290. Ref.3
	Sequence conflict	358	1	R → SQG in AAC50290. Ref.3
	Sequence conflict	432 – 448	17	NLVRP…HQLYI → RKHSRFIQMN Ref.3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified October 1, 1996. Version 1. Checksum: A927EEC623468116	FASTA	448	50,140
	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
	Isoform 2 [UniParc]. Checksum: 75A03F21290BAFF8	FASTA	414	46,387
	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 VYAMVWTVGM AKLDPSSQGA LQLPYDPEME EDSYDSFGEP 310 320 330 340 350 360 SYPEVFEPPL TGYPGEELEE EEERGVKLGL GDFIFYSVLV GKAAATGSGD WNTTLACFVA 370 380 390 400 410 ILIGLCLTLL LLAVFKKALP ALPISITFGL IFYFSTDNLV RPFMDTLASH QLYI
	Isoform 3 [UniParc]. Checksum: AA9D4FD8CB46E669	FASTA	447	50,011
	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 PEMEDSYDSF GEPSYPEVFE PPLTGYPGEE LEEEEERGVK 370 380 390 400 410 420 LGLGDFIFYS VLVGKAAATG SGDWNTTLAC FVAILIGLCL TLLLLAVFKK ALPALPISIT 430 440 FGLIFYFSTD NLVRPFMDTL ASHQLYI

References

	« Hide 'large scale' referencesShow '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. , 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]	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. , 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]	"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, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[20]	"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.
[21]	"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.
[22]	"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.
[23]	"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.
+	Additional computationally mapped references.

Web resources

Alzheimer Research Forum

Presenilins mutations

GeneReviews

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.
IPI	IPI00184584. IPI00218471. IPI00377103.
PIR	A56993. I39174.
RefSeq	NP_000438.2. NM_000447.2. NP_036618.2. NM_012486.2.
UniGene	Hs.25363.
3D structure databases
ProteinModelPortal	P49810.
ModBase	Search...
Protein-protein interaction databases
IntAct	P49810. 17 interactions.
MINT	MINT-95242.
STRING	9606.ENSP00000355747.
Protein family/group databases
MEROPS	A22.002.
TCDB	1.A.54.1.2. presenilin ER Ca2+ leak channel (Presenilin) family.
PTM databases
PhosphoSite	P49810.
Polymorphism databases
DMDM	1709858.
Proteomic databases
PaxDb	P49810.
PRIDE	P49810.
Protocols and materials databases
DNASU	5664.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000366783; ENSP00000355747; ENSG00000143801. ENST00000422240; ENSP00000403737; ENSG00000143801.
GeneID	5664.
KEGG	hsa:5664.
UCSC	uc009xeo.1. human.
Organism-specific databases
CTD	5664.
GeneCards	GC01P227058.
HGNC	HGNC:9509. PSEN2.
HPA	CAB013634.
MIM	600759. gene. 606889. phenotype. 613697. phenotype.
neXtProt	NX_P49810.
Orphanet	1020. Early-onset autosomal dominant Alzheimer disease. 154. Familial isolated dilated cardiomyopathy.
PharmGKB	PA33856.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG237920.
HOGENOM	HOG000240228.
HOVERGEN	HBG011375.
InParanoid	P49810.
KO	K04522.
OrthoDB	EOG4RJG1V.
PhylomeDB	P49810.
Enzyme and pathway databases
Reactome	REACT_111102. Signal Transduction. REACT_691. A third proteolytic cleavage releases NICD.
Gene expression databases
ArrayExpress	P49810.
Bgee	P49810.
CleanEx	HS_PSEN2.
Genevestigator	P49810.
GermOnline	ENSG00000143801. Homo sapiens.
Family and domain databases
InterPro	IPR001493. Pept_A22A_PS2. IPR006639. Peptidase_A22. IPR001108. Peptidase_A22A. [Graphical view]
PANTHER	PTHR10202. PTHR10202. 1 hit.
Pfam	PF01080. Presenilin. 2 hits. [Graphical view]
PRINTS	PR01072. PRESENILIN. PR01074. PRESENILIN2.
SMART	SM00730. PSN. 1 hit. [Graphical view]
ProtoNet	Search...
Other
BindingDB	P49810.
ChEMBL	CHEMBL3708.
ChiTaRS	PSEN2. human.
GenomeRNAi	5664.
NextBio	22010.
SOURCE	Search...

Entry information

Entry name

PSN2_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 143 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.