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Gamma-secretase subunit PEN-2 (Presenilin enhancer protein 2 homolog)

 PEN2_DANRE              Reviewed;         101 AA.
Q8JHF0; Q568W9;
26-SEP-2003, integrated into UniProtKB/Swiss-Prot.
01-OCT-2002, sequence version 1.
28-FEB-2018, entry version 93.
RecName: Full=Gamma-secretase subunit PEN-2;
AltName: Full=Presenilin enhancer protein 2 homolog;
Name=psenen; Synonyms=pen2; ORFNames=zgc:109727;
Danio rerio (Zebrafish) (Brachydanio rerio).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes;
Cyprinidae; Danio.
NCBI_TaxID=7955;
[1]
NUCLEOTIDE SEQUENCE [MRNA].
PubMed=12110170; DOI=10.1016/S1534-5807(02)00189-2;
Francis R., McGrath G., Zhang J., Ruddy D.A., Sym M., Apfeld J.,
Nicoll M., Maxwell M., Hai B., Ellis M.C., Parks A.L., Xu W., Li J.,
Gurney M., Myers R.L., Himes C.S., Hiebsch R., Ruble C., Nye J.S.,
Curtis D.;
"aph-1 and pen-2 are required for Notch pathway signaling, gamma-
secretase cleavage of betaAPP, and presenilin protein accumulation.";
Dev. Cell 3:85-97(2002).
[2]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
TISSUE=Olfactory epithelium;
NIH - Zebrafish Gene Collection (ZGC) project;
Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases.
-!- 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). 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. {ECO:0000250|UniProtKB:Q9NZ42}.
-!- SUBUNIT: The functional gamma-secretase complex is composed of at
least four polypeptides: a presenilin homodimer (psen1 or psen2),
nicastrin (ncstn), aph1 (aph1a or aph1b) and pen2.
{ECO:0000250|UniProtKB:Q9NZ42}.
-!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
{ECO:0000250|UniProtKB:Q9NZ42}; Multi-pass membrane protein
{ECO:0000250|UniProtKB:Q9NZ42}. Golgi apparatus, Golgi stack
membrane {ECO:0000250|UniProtKB:Q9NZ42}; Multi-pass membrane
protein {ECO:0000250|UniProtKB:Q9NZ42}. Cell membrane
{ECO:0000250|UniProtKB:Q9NZ42}; Multi-pass membrane protein
{ECO:0000250|UniProtKB:Q9NZ42}. Membrane
{ECO:0000250|UniProtKB:Q9NZ42}; Multi-pass membrane protein
{ECO:0000250|UniProtKB:Q9NZ42}. Note=Predominantly located in the
endoplasmic reticulum and in the cis-Golgi.
{ECO:0000250|UniProtKB:Q9NZ42}.
-!- SIMILARITY: Belongs to the PEN-2 family. {ECO:0000305}.
-!- CAUTION: 3D-structure analysis of the human homolog indicates that
the membrane topology differs from the predictions. Contrary to
predictions, the N-terminus contains two short helices that dip
into the membrane, but do not cross it. The C-terminus contains
the single transmembrane helix. This gives rise to a topology
where the N-terminus is cytoplasmic and the C-terminus is lumenal.
{ECO:0000305}.
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EMBL; AF512427; AAM88324.1; -; mRNA.
EMBL; BC092674; AAH92674.1; -; mRNA.
RefSeq; NP_991139.1; NM_205576.1.
UniGene; Dr.151555; -.
SMR; Q8JHF0; -.
STRING; 7955.ENSDARP00000090230; -.
PaxDb; Q8JHF0; -.
Ensembl; ENSDART00000099456; ENSDARP00000090230; ENSDARG00000068698.
GeneID; 402810; -.
KEGG; dre:402810; -.
CTD; 55851; -.
ZFIN; ZDB-GENE-040218-1; psenen.
eggNOG; KOG3402; Eukaryota.
eggNOG; ENOG4111W09; LUCA.
GeneTree; ENSGT00390000016319; -.
HOGENOM; HOG000006914; -.
HOVERGEN; HBG045628; -.
InParanoid; Q8JHF0; -.
KO; K06170; -.
OMA; WFFQEAF; -.
OrthoDB; EOG091G0X8A; -.
PhylomeDB; Q8JHF0; -.
TreeFam; TF313116; -.
Reactome; R-DRE-1251985; Nuclear signaling by ERBB4.
Reactome; R-DRE-193692; Regulated proteolysis of p75NTR.
Reactome; R-DRE-3928665; EPH-ephrin mediated repulsion of cells.
Reactome; R-DRE-9013507; NOTCH3 Activation and Transmission of Signal to the Nucleus.
Reactome; R-DRE-9017802; Noncanonical activation of NOTCH3.
PRO; PR:Q8JHF0; -.
Proteomes; UP000000437; Chromosome 15.
Bgee; ENSDARG00000068698; -.
GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
GO; GO:0070765; C:gamma-secretase complex; ISS:UniProtKB.
GO; GO:0032580; C:Golgi cisterna membrane; IEA:UniProtKB-SubCell.
GO; GO:0016021; C:integral component of membrane; ISS:UniProtKB.
GO; GO:0042982; P:amyloid precursor protein metabolic process; ISS:UniProtKB.
GO; GO:0034205; P:amyloid-beta formation; ISS:UniProtKB.
GO; GO:0048066; P:developmental pigmentation; IMP:ZFIN.
GO; GO:0097324; P:melanocyte migration; IMP:ZFIN.
GO; GO:0043066; P:negative regulation of apoptotic process; IMP:ZFIN.
GO; GO:0043524; P:negative regulation of neuron apoptotic process; IMP:ZFIN.
GO; GO:0007220; P:Notch receptor processing; IBA:GO_Central.
GO; GO:0007219; P:Notch signaling pathway; IEA:UniProtKB-KW.
InterPro; IPR019379; Gamma_Secretase_Asp_P_PEN2.
PANTHER; PTHR16318; PTHR16318; 1.
Pfam; PF10251; PEN-2; 1.
3: Inferred from homology;
Cell membrane; Complete proteome; Endoplasmic reticulum;
Golgi apparatus; Membrane; Notch signaling pathway;
Reference proteome; Transmembrane; Transmembrane helix.
CHAIN 1 101 Gamma-secretase subunit PEN-2.
/FTId=PRO_0000190902.
TOPO_DOM 1 17 Cytoplasmic.
{ECO:0000250|UniProtKB:Q9NZ42}.
INTRAMEM 18 36 Helical. {ECO:0000250|UniProtKB:Q9NZ42}.
TOPO_DOM 37 57 Cytoplasmic.
{ECO:0000250|UniProtKB:Q9NZ42}.
TRANSMEM 58 78 Helical. {ECO:0000250|UniProtKB:Q9NZ42}.
TOPO_DOM 79 101 Lumenal. {ECO:0000250|UniProtKB:Q9NZ42}.
CONFLICT 25 25 F -> L (in Ref. 2; AAH92674).
{ECO:0000305}.
SEQUENCE 101 AA; 11851 MW; 9D853E232F824DF5 CRC64;
MNLERIPNEE KLSLCRRYYL GGFAFLPFLW LVNILWFFKE AFLKPAYTEQ PQIKSYVKKS
ALGLLLWVAV LTTWITVFQH FRAQWGEVGD YLSFTIPLGT A


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