PSENEN
entrez
55851
canonical
uniprot
Q9NZ42
canonical
ensembl
ENSG00000205155
resolver
ensp
ENSP00000222266
resolver
ensp
ENSP00000468411
resolver
ensp
ENSP00000526544
resolver
ensp
ENSP00000526545
resolver
ensp
ENSP00000601760
resolver
enst
ENST00000222266
resolver
enst
ENST00000587708
resolver
enst
ENST00000856485
resolver
enst
ENST00000856486
resolver
enst
ENST00000931701
resolver
genesymbol
PSENEN
resolver
genesymbol_syn
PEN2
resolver
hgnc
HGNC:30100
resolver
uniprot
B2R5L9
resolver
uniprot_entry
PEN2_HUMAN
resolver
uniprot_sec
B2R5L9
resolver
amino_acid_sequence
MNLERVSNEEKLNLCRKYYLGGFAFLPFLWLVNIFWFFREAFLVPAYTEQSQIKGYVWRSAVGFLFWVIVLTSWITIFQIYRPRWGALGDYLSFTIPLGTP
uniprot
proteins
disease_involvement
DISEASE: Acne inversa, familial, 2, with or without Dowling-Degos disease (ACNINV2) [MIM:613736]: An autosomal dominant form of acne inversa, a chronic relapsing inflammatory disease of the hair follicles characterized by recurrent draining sinuses, painful skin abscesses, and disfiguring scars. Manifestations typically appear after puberty. Some ACNINV2 patients also exhibit reticulate hyperpigmentation consistent with Dowling-Degos disease. {ECO:0000269|PubMed:20929727}. Note=The disease is caused by variants affecting the gene represented in this entry.
uniprot
proteins
function
FUNCTION: Essential subunit of the gamma-secretase complex, an endoprotease complex that catalyzes the intramembrane cleavage of integral membrane proteins such as Notch receptors and APP (amyloid-beta precursor protein) (PubMed:12522139, PubMed:12679784, PubMed:12740439, PubMed:12763021, PubMed:24941111, PubMed:30598546, PubMed:30630874). The gamma-secretase complex plays a role in Notch and Wnt signaling cascades and regulation of downstream processes via its role in processing key regulatory proteins, and by regulating cytosolic CTNNB1 levels (Probable). PSENEN modulates both endoproteolysis of presenilin and gamma-secretase activity (PubMed:12522139, PubMed:12679784, PubMed:12740439, PubMed:12763021, PubMed:24941111). Besides its role in gamma-secretase complex, acts as a regulator of AMP-activated protein kinase (AMPK) activity in response to calorie restriction: binds metformin, an antidiabetic drug, promoting association with ATP6AP1, a subunit of the V-ATPase complex, leading to V-ATPase complex inhibition on lysosomes and AMPK activation via the AXIN1-STK11/LKB1 axis (By similarity). {ECO:0000250|UniProtKB:Q9CQR7, ECO:0000269|PubMed:12522139, ECO:0000269|PubMed:12679784, ECO:0000269|PubMed:12740439, ECO:0000269|PubMed:12763021, ECO:0000269|PubMed:24941111, ECO:0000269|PubMed:30598546, ECO:0000269|PubMed:30630874, ECO:0000305}.
uniprot
proteins
mass_dalton
12029
uniprot
proteins
mutagenesis
MUTAGEN 10; /note="E->S: Induces a N-linked glycosylation on N-8."; /evidence="ECO:0000269|PubMed:12639958"; MUTAGEN 15; /note="C->A: Decreased APP processing by the gamma-secretase complex."; /evidence="ECO:0000269|PubMed:24941111"; MUTAGEN 15; /note="C->S: No effect on APP processing by the gamma-secretase complex."; /evidence="ECO:0000269|PubMed:24941111"; MUTAGEN 25; /note="F->A: Decreased APP processing by the gamma-secretase complex."; /evidence="ECO:0000269|PubMed:24941111"; MUTAGEN 26; /note="L->A: Decreased APP processing by the gamma-secretase complex."; /evidence="ECO:0000269|PubMed:24941111"; MUTAGEN 30; /note="W->A: Decreased expression levels, and decreased stimulation of presenilin endoproteolysis."; /evidence="ECO:0000269|PubMed:24941111"; MUTAGEN 33; /note="N->A: Increased expression at the cell membrane."; /evidence="ECO:0000269|PubMed:24941111"; MUTAGEN 36; /note="W->A: Decreased APP processing by the gamma-secretase complex."; /evidence="ECO:0000269|PubMed:24941111"; MUTAGEN 46; /note="A->N: No effect."; /evidence="ECO:0000269|PubMed:12639958"; MUTAGEN 54; /note="K->A: Decreased APP processing by the gamma-secretase complex."; /evidence="ECO:0000269|PubMed:24941111"; MUTAGEN 93; /note="S->N: Induces a N-linked glycosylation."; /evidence="ECO:0000269|PubMed:12639958"; MUTAGEN 94; /note="F->A: Decreased APP processing by the gamma-secretase complex."; /evidence="ECO:0000269|PubMed:24941111
uniprot
proteins
protein_family
PEN-2 family
uniprot
proteins
pubmed
12110170
uniprot
proteins
pubmed
12198112
uniprot
proteins
pubmed
12522139
uniprot
proteins
pubmed
12639958
uniprot
proteins
pubmed
12679784
uniprot
proteins
pubmed
12740439
uniprot
proteins
pubmed
12763021
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
20929727
uniprot
proteins
pubmed
24941111
uniprot
proteins
pubmed
25043039
uniprot
proteins
pubmed
26280335
uniprot
proteins
pubmed
26623517
uniprot
proteins
pubmed
30598546
uniprot
proteins
pubmed
30630874
uniprot
proteins
sequence_length
101
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Endoplasmic reticulum membrane {ECO:0000269|PubMed:12522139, ECO:0000269|PubMed:12639958}; Multi-pass membrane protein {ECO:0000269|PubMed:12639958, ECO:0000269|PubMed:25043039, ECO:0000269|PubMed:26280335, ECO:0000269|PubMed:26623517, ECO:0000269|PubMed:30598546, ECO:0000269|PubMed:30630874}. Golgi apparatus, Golgi stack membrane {ECO:0000269|PubMed:12522139, ECO:0000269|PubMed:12639958}; Multi-pass membrane protein {ECO:0000269|PubMed:12639958, ECO:0000269|PubMed:25043039, ECO:0000269|PubMed:26280335, ECO:0000269|PubMed:26623517, ECO:0000269|PubMed:30598546, ECO:0000269|PubMed:30630874}. Cell membrane {ECO:0000269|PubMed:24941111}; Multi-pass membrane protein {ECO:0000269|PubMed:12639958, ECO:0000269|PubMed:25043039, ECO:0000269|PubMed:26280335, ECO:0000269|PubMed:26623517}. Membrane {ECO:0000269|PubMed:12198112}; Multi-pass membrane protein {ECO:0000269|PubMed:12639958, ECO:0000269|PubMed:25043039, ECO:0000269|PubMed:26280335, ECO:0000269|PubMed:26623517, ECO:0000269|PubMed:30598546, ECO:0000269|PubMed:30630874}. Note=Predominantly located in the endoplasmic reticulum and in the cis-Golgi. {ECO:0000269|PubMed:12639958}.
uniprot
proteins
transmembrane_region
TRANSMEM 58..78; /note="Helical"; /evidence="ECO:0000269|PubMed:26280335
uniprot
proteins