PEN2_DANRE
ID PEN2_DANRE Reviewed; 101 AA.
AC Q8JHF0; Q568W9;
DT 26-SEP-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2002, sequence version 1.
DT 03-AUG-2022, entry version 109.
DE RecName: Full=Gamma-secretase subunit PEN-2;
DE AltName: Full=Presenilin enhancer protein 2 homolog;
GN Name=psenen; Synonyms=pen2; ORFNames=zgc:109727;
OS Danio rerio (Zebrafish) (Brachydanio rerio).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes;
OC Danionidae; Danioninae; Danio.
OX NCBI_TaxID=7955;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=12110170; DOI=10.1016/s1534-5807(02)00189-2;
RA Francis R., McGrath G., Zhang J., Ruddy D.A., Sym M., Apfeld J., Nicoll M.,
RA Maxwell M., Hai B., Ellis M.C., Parks A.L., Xu W., Li J., Gurney M.,
RA Myers R.L., Himes C.S., Hiebsch R., Ruble C., Nye J.S., Curtis D.;
RT "aph-1 and pen-2 are required for Notch pathway signaling, gamma-secretase
RT cleavage of betaAPP, and presenilin protein accumulation.";
RL Dev. Cell 3:85-97(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Olfactory epithelium;
RG NIH - Zebrafish Gene Collection (ZGC) project;
RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Essential subunit of the gamma-secretase complex, an
CC endoprotease complex that catalyzes the intramembrane cleavage of
CC integral membrane proteins such as Notch receptors and APP (amyloid-
CC beta precursor protein). The gamma-secretase complex plays a role in
CC Notch and Wnt signaling cascades and regulation of downstream processes
CC via its role in processing key regulatory proteins.
CC {ECO:0000250|UniProtKB:Q9NZ42}.
CC -!- SUBUNIT: The functional gamma-secretase complex is composed of at least
CC four polypeptides: a presenilin homodimer (psen1 or psen2), nicastrin
CC (ncstn), aph1 (aph1a or aph1b) and psenen.
CC {ECO:0000250|UniProtKB:Q9NZ42}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:Q9NZ42}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:Q9NZ42}. Golgi apparatus, Golgi stack membrane
CC {ECO:0000250|UniProtKB:Q9NZ42}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:Q9NZ42}. Cell membrane
CC {ECO:0000250|UniProtKB:Q9NZ42}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:Q9NZ42}. Membrane
CC {ECO:0000250|UniProtKB:Q9NZ42}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:Q9NZ42}. Note=Predominantly located in the
CC endoplasmic reticulum and in the cis-Golgi.
CC {ECO:0000250|UniProtKB:Q9NZ42}.
CC -!- SIMILARITY: Belongs to the PEN-2 family. {ECO:0000305}.
CC -!- CAUTION: 3D-structure analysis of the human homolog indicates that the
CC membrane topology differs from the predictions. Contrary to
CC predictions, the N-terminus contains two short helices that dip into
CC the membrane, but do not cross it. The C-terminus contains the single
CC transmembrane helix. This gives rise to a topology where the N-terminus
CC is cytoplasmic and the C-terminus is lumenal. {ECO:0000305}.
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DR EMBL; AF512427; AAM88324.1; -; mRNA.
DR EMBL; BC092674; AAH92674.1; -; mRNA.
DR RefSeq; NP_991139.1; NM_205576.1.
DR AlphaFoldDB; Q8JHF0; -.
DR SMR; Q8JHF0; -.
DR STRING; 7955.ENSDARP00000090230; -.
DR PaxDb; Q8JHF0; -.
DR Ensembl; ENSDART00000099456; ENSDARP00000090230; ENSDARG00000068698.
DR Ensembl; ENSDART00000186625; ENSDARP00000153835; ENSDARG00000068698.
DR GeneID; 402810; -.
DR KEGG; dre:402810; -.
DR CTD; 55851; -.
DR ZFIN; ZDB-GENE-040218-1; psenen.
DR eggNOG; KOG3402; Eukaryota.
DR GeneTree; ENSGT00390000016319; -.
DR HOGENOM; CLU_124142_2_0_1; -.
DR InParanoid; Q8JHF0; -.
DR OMA; WYFRAGF; -.
DR OrthoDB; 1517974at2759; -.
DR PhylomeDB; Q8JHF0; -.
DR TreeFam; TF313116; -.
DR Reactome; R-DRE-1251985; Nuclear signaling by ERBB4.
DR Reactome; R-DRE-193692; Regulated proteolysis of p75NTR.
DR Reactome; R-DRE-205043; NRIF signals cell death from the nucleus.
DR Reactome; R-DRE-3928665; EPH-ephrin mediated repulsion of cells.
DR PRO; PR:Q8JHF0; -.
DR Proteomes; UP000000437; Genome assembly.
DR Proteomes; UP000814640; Chromosome 15.
DR Bgee; ENSDARG00000068698; Expressed in gastrula and 34 other tissues.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0070765; C:gamma-secretase complex; ISS:UniProtKB.
DR GO; GO:0032580; C:Golgi cisterna membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; ISS:UniProtKB.
DR GO; GO:0042982; P:amyloid precursor protein metabolic process; ISS:UniProtKB.
DR GO; GO:0034205; P:amyloid-beta formation; ISS:UniProtKB.
DR GO; GO:0048066; P:developmental pigmentation; IMP:ZFIN.
DR GO; GO:0097324; P:melanocyte migration; IMP:ZFIN.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IMP:ZFIN.
DR GO; GO:0043524; P:negative regulation of neuron apoptotic process; IMP:ZFIN.
DR GO; GO:0007220; P:Notch receptor processing; IBA:GO_Central.
DR GO; GO:0007219; P:Notch signaling pathway; IEA:UniProtKB-KW.
DR InterPro; IPR019379; Gamma_Secretase_Asp_P_PEN2.
DR PANTHER; PTHR16318; PTHR16318; 1.
DR Pfam; PF10251; PEN-2; 1.
PE 3: Inferred from homology;
KW Cell membrane; Endoplasmic reticulum; Golgi apparatus; Membrane;
KW Notch signaling pathway; Reference proteome; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..101
FT /note="Gamma-secretase subunit PEN-2"
FT /id="PRO_0000190902"
FT TOPO_DOM 1..17
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q9NZ42"
FT INTRAMEM 18..36
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:Q9NZ42"
FT TOPO_DOM 37..57
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q9NZ42"
FT TRANSMEM 58..78
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:Q9NZ42"
FT TOPO_DOM 79..101
FT /note="Lumenal"
FT /evidence="ECO:0000250|UniProtKB:Q9NZ42"
FT CONFLICT 25
FT /note="F -> L (in Ref. 2; AAH92674)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 101 AA; 11851 MW; 9D853E232F824DF5 CRC64;
MNLERIPNEE KLSLCRRYYL GGFAFLPFLW LVNILWFFKE AFLKPAYTEQ PQIKSYVKKS
ALGLLLWVAV LTTWITVFQH FRAQWGEVGD YLSFTIPLGT A
