APH1_CAEEL
ID APH1_CAEEL Reviewed; 308 AA.
AC O45876;
DT 26-SEP-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-1998, sequence version 1.
DT 03-AUG-2022, entry version 130.
DE RecName: Full=Gamma-secretase subunit aph-1;
DE AltName: Full=Anterior-pharynx-defective protein 1;
DE AltName: Full=Presenilin enhancer protein 1;
GN Name=aph-1; Synonyms=pen-1; ORFNames=VF36H2L.1;
OS Caenorhabditis elegans.
OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC Caenorhabditis.
OX NCBI_TaxID=6239;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, AND MUTAGENESIS OF GLY-123.
RC STRAIN=Bristol N2; TISSUE=Embryo;
RX PubMed=11792846; DOI=10.1073/pnas.022523499;
RA Goutte C., Tsunozaki M., Hale V.A., Priess J.R.;
RT "APH-1 is a multipass membrane protein essential for the Notch signaling
RT pathway in Caenorhabditis elegans embryos.";
RL Proc. Natl. Acad. Sci. U.S.A. 99:775-779(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND FUNCTION.
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Bristol N2;
RX PubMed=9851916; DOI=10.1126/science.282.5396.2012;
RG The C. elegans sequencing consortium;
RT "Genome sequence of the nematode C. elegans: a platform for investigating
RT biology.";
RL Science 282:2012-2018(1998).
CC -!- FUNCTION: Essential subunit of the gamma-secretase complex, an
CC endoprotease complex that catalyzes the intramembrane cleavage of
CC integral proteins such as Notch receptors (lin-12 or glp-1). It may
CC represent a stabilizing cofactor for the presenilin homodimer that
CC promotes the formation of a stable complex. Required for the
CC localization of aph-2. {ECO:0000269|PubMed:11792846,
CC ECO:0000269|PubMed:12110170}.
CC -!- SUBUNIT: Component of the gamma-secretase complex, a complex probably
CC composed of the presenilin homodimer (sel-12, hop-1 or spe-4),
CC nicastrin (aph-2), aph-1 and pen-2. {ECO:0000305}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000305}; Multi-pass membrane
CC protein {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the APH-1 family. {ECO:0000305}.
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DR EMBL; AL021466; CAA16282.1; -; Genomic_DNA.
DR PIR; T26007; T26007.
DR RefSeq; NP_492469.1; NM_060068.5.
DR AlphaFoldDB; O45876; -.
DR SMR; O45876; -.
DR BioGRID; 38178; 4.
DR STRING; 6239.VF36H2L.1; -.
DR EPD; O45876; -.
DR PaxDb; O45876; -.
DR PeptideAtlas; O45876; -.
DR EnsemblMetazoa; VF36H2L.1.1; VF36H2L.1.1; WBGene00000147.
DR GeneID; 172747; -.
DR KEGG; cel:CELE_VF36H2L.1; -.
DR UCSC; VF36H2L.1; c. elegans.
DR CTD; 33467; -.
DR WormBase; VF36H2L.1; CE16526; WBGene00000147; aph-1.
DR eggNOG; KOG3972; Eukaryota.
DR GeneTree; ENSGT00390000002049; -.
DR HOGENOM; CLU_842600_0_0_1; -.
DR InParanoid; O45876; -.
DR OMA; FFNAFDT; -.
DR OrthoDB; 1085102at2759; -.
DR PhylomeDB; O45876; -.
DR Reactome; R-CEL-1251985; Nuclear signaling by ERBB4.
DR SignaLink; O45876; -.
DR PRO; PR:O45876; -.
DR Proteomes; UP000001940; Chromosome I.
DR Bgee; WBGene00000147; Expressed in pharyngeal muscle cell (C elegans) and 4 other tissues.
DR GO; GO:0005783; C:endoplasmic reticulum; IBA:GO_Central.
DR GO; GO:0070765; C:gamma-secretase complex; ISS:WormBase.
DR GO; GO:0016021; C:integral component of membrane; IBA:GO_Central.
DR GO; GO:0030674; F:protein-macromolecule adaptor activity; IBA:GO_Central.
DR GO; GO:0045165; P:cell fate commitment; IGI:WormBase.
DR GO; GO:0060581; P:cell fate commitment involved in pattern specification; IMP:WormBase.
DR GO; GO:0009792; P:embryo development ending in birth or egg hatching; IMP:WormBase.
DR GO; GO:0048598; P:embryonic morphogenesis; IMP:WormBase.
DR GO; GO:0007220; P:Notch receptor processing; IBA:GO_Central.
DR GO; GO:0007219; P:Notch signaling pathway; IMP:WormBase.
DR GO; GO:0048599; P:oocyte development; IMP:WormBase.
DR GO; GO:0060465; P:pharynx development; IMP:WormBase.
DR GO; GO:0043085; P:positive regulation of catalytic activity; IEA:InterPro.
DR GO; GO:0034394; P:protein localization to cell surface; IMP:WormBase.
DR GO; GO:0016485; P:protein processing; IBA:GO_Central.
DR InterPro; IPR009294; Aph-1.
DR PANTHER; PTHR12889; PTHR12889; 1.
DR Pfam; PF06105; Aph-1; 1.
PE 1: Evidence at protein level;
KW Membrane; Notch signaling pathway; Reference proteome; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..308
FT /note="Gamma-secretase subunit aph-1"
FT /id="PRO_0000221057"
FT TRANSMEM 5..25
FT /note="Helical; Name=1"
FT /evidence="ECO:0000255"
FT TRANSMEM 32..52
FT /note="Helical; Name=2"
FT /evidence="ECO:0000255"
FT TRANSMEM 53..73
FT /note="Helical; Name=3"
FT /evidence="ECO:0000255"
FT TRANSMEM 122..142
FT /note="Helical; Name=4"
FT /evidence="ECO:0000255"
FT TRANSMEM 170..190
FT /note="Helical; Name=5"
FT /evidence="ECO:0000255"
FT TRANSMEM 200..220
FT /note="Helical; Name=6"
FT /evidence="ECO:0000255"
FT TRANSMEM 230..250
FT /note="Helical; Name=7"
FT /evidence="ECO:0000255"
FT REGION 286..308
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 290..308
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MUTAGEN 123
FT /note="G->D: In OR28; defects in localization of aph-2."
FT /evidence="ECO:0000269|PubMed:11792846"
SQ SEQUENCE 308 AA; 33548 MW; 6A2ACA6247022B34 CRC64;
MGYLLTIACY IASFSPSIAL FCSFIAHDPV RIILFFLGSF FWLVSLLFSS LAWLGLSTVL
PDTFLLSLTV CIIAQELSRV AYFMLLKKAQ RGLNKITRQG QISVAPGVSD LHNARHMLAL
VCGLGMGVIS ALFYTMNAFA IFSGPGTIGL PNALKTGEID TNRAGKYLPL CYTLSAILLT
LFHVTWTIMV WDSCHKIGRI PSAFVPGAAA VVSHLLVTFL SSLNSRGFHV LVFAVQFLIL
LICIAYCNVI MGGTISSFVN GIGQSITDAV TLKQVRTLIE ERKLRTQRQS VPDEPMTERA
GTSNTVNA
