Selected-GenAtlas references	SOURCE	GeneCards	NCBI Gene	Swiss-Prot	Orphanet	Ensembl
	HGNC	UniGene	Nucleotide	OMIM		UCSC

Home Page

FLASH GENE

Symbol

PSENEN

contributors: mct - updated : 14-03-2018

HGNC name	presenilin enhancer gamma-secretase subunit
HGNC id	30100

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

EXPRESSION

Type

widely

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Digestive stomach       highly Nervous brain         Urinary bladder       highly

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Blood / hematopoietic bone marrow       Connective bone

cells

System Cell Pubmed Species Stage Rna symbol Blood/Hematopoietic leukocyte

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	N-terminus of PSENEN is exposed to the cytoplasm, thus indicating that hydrophobic domains (HP1) does not traverse the lipid bilayer as a transmembrane domain, and first fourteen AAs of the HP1 are required for gamma-secretase activity
	two transmembrane domains
	C-terminal domain determining its function in the stabilization of presenilin fragments, that is lumenal
	C-terminus , but the

HOMOLOGY

interspecies

homolog to murine Pen2

Homologene

FAMILY

gamma-secretase protein complex

CATEGORY

enzyme , signaling

SUBCELLULAR LOCALIZATION	plasma membrane
	intracellular
	intracellular,cytoplasm,organelle,membrane
	intracellular,cytoplasm,organelle,endoplasmic reticulum
	intracellular,cytoplasm,organelle,Golgi
	intracellular,nucleus

basic FUNCTION	member of the gamma-secretase complex, playing a role, with PSEN1, NCSTN, APH1A, necessary and sufficient to reconstitute gamma-secretase activity
	required for triggering PSEN1 endoproteolysis
	required for endoproteolytic processing of presenilin and conferring gamma-secretase activity to the complex
	concerted transcription of PSENEN and U2AF1L4 can be necessary for regulation of T-cell activity
	rather than solely being a catalyst for gamma-secretase endoproteolysis, PSENEN may also stabilize the complex prior to PSEN1 endoproteolysis, allowing time for full assembly and proper trafficking
	might likely be closely related to APP burden in aging nervous system (PMUID: 25736404)
	plays a crucial role in substrate binding, a mechanism by which PSENEN contributes directly to the catalytic mechanism of gamma-secretase activity

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

a component	part of gamma-secretase complex, composed of four non-covalently bound transmembrane proteins Presenilin, Nicastrin APH1A, APH1B, PSENEN, that is responsible for the intramembranous cleavage of amyloid precursor protein (APP) and NOTCH
	PSEN1 or PSEN2, nicastrin (NCSTN), anterior pharynx-defective 1 (APH1A), and PSENEN have been considered the minimal essential subunits required to form an active gamma-secretase complex

INTERACTION

DNA

RNA

small molecule

protein	downregulation of RER1 leads to increased surface localization of PSENEN, whereas overexpression of RER1 stabilizes unassembled PSENEN
	can interact with ferritin light chain (FTL), an important component of the iron storage protein ferritin
	iron can increase gamma-secretase activity through promoting the level of FTL that interacts with and stabilizes PSENEN, providing a new molecular link between iron, PSENEN/gamma-secretase and A&
	946;PP generation in Alzheimer disease
	extracellular domain of NCSTN directly binds PSENEN at the thin end

cell & other

REGULATION

Other

TP53-dependent regulation of PSENEN expression by other members of the gamma-secretase complex, namely presenilins

ASSOCIATED DISORDERS

corresponding disease(s)

ACNINV2

Susceptibility

to Alzheimer disease

Variant & Polymorphism

Candidate gene

Marker

Therapy target

ANIMAL & CELL MODELS