P97887 (PSN1_RAT) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Presenilin-1
Short name=PS-1
EC=3.4.23.-

Alternative name(s):
Protein S182

Cleaved into the following 3 chains:

1. Presenilin-1 NTF subunit
2. Presenilin-1 CTF subunit
3. Presenilin-1 CTF12
   Short name=PS1-CTF12

Gene names

Name:	Psen1
Synonyms:	Psnl1

Organism

Rattus norvegicus (Rat)

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

Protein attributes

Sequence length	468 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at transcript 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. Stimulates cell-cell adhesion though its association with the E-cadherin/catenin complex. Under conditions of apoptosis or calcium influx, cleaves E-cadherin promoting the disassembly of the E-cadherin/catenin complex and increasing the pool of cytoplasmic beta-catenin, thus negatively regulating Wnt signaling. May also play a role in hematopoiesis By similarity.
Subunit structure	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. Other components which are associated with the complex include SLC25A64, SLC5A7, PHB and PSEN1 isoform 3. Predominantly heterodimer of a N-terminal (NTF) and a C-terminal (CTF) endoproteolytical fragment. Associates with proteolytic processed C-terminal fragments C83 and C99 of the amyloid precursor protein (APP). Associates with NOTCH1. Associates with cadherin/catenin adhesion complexes through direct binding to CDH1 or CDH2. Interaction with CDH1 stabilizes the complex and stimulates cell-cell aggregation. Interaction with CDH2 is essential for trafficking of CDH2 from the endoplasmic reticulum to the plasma membrane. Interacts with CTNND2, CTNNB1, HERPUD1, FLNA, FLNB, MTCH1, PKP4 and PARL. Interacts through its N-terminus with isoform 3 of GFAP. Interacts with DOCK3 By similarity.
Subcellular location	Endoplasmic reticulum membrane; Multi-pass membrane protein. Golgi apparatus membrane; Multi-pass membrane protein. Cell surface By similarity.
Domain	The PAL motif is required for normal active site conformation By similarity.
Post-translational modification	Heterogeneous proteolytic processing generates N-terminal (NTF) and C-terminal (CTF) fragments of approximately 35 and 20 kDa, respectively. During apoptosis, the C-terminal fragment (CTF) is further cleaved by caspase-3 to produce the fragment, PS1-CTF12 By similarity. After endoproteolysis, the C-terminal fragment (CTF) is phosphorylated on serine residues by PKA and/or PKC. Phosphorylation on Ser-347 inhibits endoproteolysis By similarity.
Sequence similarities	Belongs to the peptidase A22A family.

Ontologies

Keywords
Biological process	Apoptosis Cell adhesion Notch signaling pathway
Cellular component	Endoplasmic reticulum Golgi apparatus Membrane
Domain	Transmembrane Transmembrane helix
Molecular function	Hydrolase Protease
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	Notch receptor processing Inferred from Biological aspect of Ancestor. Source: RefGenome Notch signaling pathway Inferred from electronic annotation. Source: UniProtKB-KW amyloid precursor protein catabolic process Inferred from Biological aspect of Ancestor. Source: RefGenome anti-apoptosis Inferred from direct assay. Source: RGD beta-amyloid metabolic process Inferred from Biological aspect of Ancestor. Source: RefGenome eye photoreceptor cell development Non-traceable author statement. Source: RGD membrane protein ectodomain proteolysis Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of neuron apoptosis Inferred from mutant phenotype. Source: RGD protein processing Inferred from sequence or structural similarity. Source: UniProtKB smooth endoplasmic reticulum calcium ion homeostasis Inferred from Biological aspect of Ancestor. Source: RefGenome
Cellular component	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 direct assay. Source: RGD ciliary rootlet Inferred from Biological aspect of Ancestor. Source: RefGenome dendritic shaft Inferred from Biological aspect of Ancestor. Source: RefGenome 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 sequence or structural similarity. Source: UniProtKB lysosomal membrane Inferred from direct assay. Source: RGD membrane raft Inferred from direct assay. Source: RGD mitochondrial inner membrane Inferred from direct assay. Source: RGD neuromuscular junction Inferred from direct assay. Source: RGD neuronal cell body Inferred from Biological aspect of Ancestor. Source: RefGenome perinuclear region of cytoplasm Inferred from Biological aspect of Ancestor. Source: RefGenome synaptosome Inferred from direct assay. Source: RGD
Molecular function	aspartic-type endopeptidase activity Inferred from electronic annotation. Source: InterPro cadherin binding Inferred from Biological aspect of Ancestor. Source: RefGenome
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 298	298	Presenilin-1 NTF subunit By similarity		PRO_0000025599
	Chain	299 – 468	170	Presenilin-1 CTF subunit By similarity		PRO_0000025600
	Chain	347 – 468	122	Presenilin-1 CTF12 By similarity		PRO_0000236062
Regions
	Topological domain	1 – 82	82	Cytoplasmic Potential
	Transmembrane	83 – 103	21	Helical; Potential
	Topological domain	104 – 132	29	Lumenal Potential
	Transmembrane	133 – 153	21	Helical; Potential
	Topological domain	154 – 160	7	Cytoplasmic Potential
	Transmembrane	161 – 181	21	Helical; Potential
	Topological domain	182 – 194	13	Lumenal Potential
	Transmembrane	195 – 215	21	Helical; Potential
	Topological domain	216 – 220	5	Cytoplasmic Potential
	Transmembrane	221 – 241	21	Helical; Potential
	Topological domain	242 – 243	2	Lumenal Potential
	Transmembrane	244 – 264	21	Helical; Potential
	Topological domain	265 – 407	143	Cytoplasmic Potential
	Transmembrane	408 – 428	21	Helical; Potential
	Transmembrane	433 – 453	21	Helical; Potential
	Region	323 – 451	129	Required for interaction with CTNNB1 By similarity
	Region	373 – 400	28	Required for interaction with CTNND2 By similarity
	Region	465 – 468	4	Interaction with MTCH1 By similarity
	Motif	434 – 436	3	PAL
Sites
	Active site	257	1	By similarity
	Active site	386	1	By similarity
	Site	291 – 292	2	Cleavage; alternate By similarity
	Site	292 – 293	2	Cleavage; alternate By similarity
	Site	298 – 299	2	Cleavage By similarity
Amino acid modifications
	Modified residue	347	1	Phosphoserine; by PKC By similarity
	Modified residue	366	1	Phosphoserine By similarity
	Modified residue	368	1	Phosphoserine By similarity
	Modified residue	371	1	Phosphothreonine By similarity
	Modified residue	372	1	Phosphoserine By similarity
Experimental info
	Sequence conflict	234	1	A → S in BAA11564. Ref.2
	Sequence conflict	381	1	K → R in BAA11564. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	P97887 [UniParc]. Last modified May 1, 1997. Version 1. Checksum: 17CB791E88A16FC0	FASTA	468	52,790
	10 20 30 40 50 60 MTEIPAPLSY FQNAQMSEDS HSSSVRSQND NQERQQHHDR QRLDNPESIS NGRPQSNFTR 70 80 90 100 110 120 QVIEQDEEED EELTLKYGAK HVIMLFVPVT LCMVVVVATI KSVSFYTRKD GQLIYTPFTE 130 140 150 160 170 180 DTETVGQRAL HSILNAAIMI SVIVVMTILL VVLYKYRCYK VIHAWLIVSS LLLLFFFSFI 190 200 210 220 230 240 YLGEVFKTYN VAVDYITVAL LIWNFGVVGM IAIHWKGPLR LQQAYLIMIS ALMALVFIKY 250 260 270 280 290 300 LPEWTAWLIL AVISVYDLVA VLCPKGPLRM LVETAQERNE TLFPALIYSS TMVWLVNMAE 310 320 330 340 350 360 GDPEAQRRVP KNPKYSTQGT EREETQDTGT GSDDGGFSEE WEAQRDSHLG PHRSTPESRA 370 380 390 400 410 420 AVQELSGSIL TSEDPEERGV KLGLGDFIFY SVLVGKASAT ASGDWNTTIA CFVAILIGLC 430 440 450 460 LTLLLLAIFK KALPALPISI TFGLIFYFAT DYLVQPFMDQ LAFHQFYI

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular cloning and expression of the rat homologue of presenilin-1." Takahashi H., Murayama M., Takashima A., Mercken M., Nakazato Y., Noguchi K., Imahori K. Neurosci. Lett. 206:113-116(1996) [PubMed: 8710164] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Strain: Wistar. Tissue: Brain.
[2]	"Cloning of the cDNA encoding rat presenilin-1." Taniguchi T., Hashimoto T., Taniguchi R., Shimada K., Kawamata T., Yasuda M., Nakai M., Terashima A., Koizumi T., Maeda K., Tanaka C. Gene 186:73-75(1997) [PubMed: 9047347] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Strain: Wistar. Tissue: Brain.
[3]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Lung.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	D82363 mRNA. Translation: BAA11564.1. D82578 mRNA. Translation: BAA11575.1. BC070887 mRNA. Translation: AAH70887.1.
IPI	IPI00326970.
RefSeq	NP_062036.2. NM_019163.3.
UniGene	Rn.44440.
3D structure databases
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-48909N.
IntAct	P97887. 4 interactions.
STRING	P97887.
Protein family/group databases
MEROPS	A22.001.
PTM databases
PhosphoSite	P97887.
Proteomic databases
PRIDE	P97887.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSRNOT00000012495; ENSRNOP00000012495; ENSRNOG00000009110.
GeneID	29192.
KEGG	rno:29192.
UCSC	NM_019163. rat.
Organism-specific databases
CTD	5663.
RGD	3425. Psen1.
Phylogenomic databases
eggNOG	roNOG12441.
GeneTree	ENSGT00390000016593.
HOVERGEN	HBG011375.
InParanoid	P97887.
OMA	CYLAIIS.
OrthoDB	EOG4TF0KN.
PhylomeDB	P97887.
Gene expression databases
ArrayExpress	P97887.
Genevestigator	P97887.
GermOnline	ENSRNOG00000009110. Rattus norvegicus.
Family and domain databases
InterPro	IPR002031. Pept_A22A_PS1. IPR006639. Peptidase_A22. IPR001108. Peptidase_A22A. [Graphical view]
KO	K04505.
PANTHER	PTHR10202:SF7. Pept_A22A_PS1. 1 hit. PTHR10202. Peptidase_A22A. 1 hit.
Pfam	PF01080. Presenilin. 1 hit. [Graphical view]
PRINTS	PR01072. PRESENILIN. PR01073. PRESENILIN1.
SMART	SM00730. PSN. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	608323.

Entry information

Entry name

PSN1_RAT

Accession

Primary (citable) accession number: P97887
Secondary accession number(s): P97529

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 15, 1999
Last sequence update:	May 1, 1997
Last modified:	November 16, 2011
This is version 99 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program