ID   E5RG63_HUMAN            Unreviewed;       304 AA.
AC   E5RG63;
DT   08-FEB-2011, integrated into UniProtKB/TrEMBL.
DT   08-FEB-2011, sequence version 1.
DT   27-MAR-2024, entry version 89.
DE   RecName: Full=Presenilin {ECO:0000256|RuleBase:RU361148};
DE            EC=3.4.23.- {ECO:0000256|RuleBase:RU361148};
GN   Name=PSEN2 {ECO:0000313|Ensembl:ENSP00000427806.1};
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC   Homo.
OX   NCBI_TaxID=9606 {ECO:0000313|Ensembl:ENSP00000427806.1, ECO:0000313|Proteomes:UP000005640};
RN   [1] {ECO:0000313|Ensembl:ENSP00000427806.1, ECO:0000313|Proteomes:UP000005640}
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=16710414; DOI=10.1038/nature04727;
RA   Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA   Scott C.E., Howe K.L., Woodfine K., Spencer C.C., Jones M.C., Gillson C.,
RA   Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA   Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA   Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA   Ashwell R.I., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H.,
RA   Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D.,
RA   Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C.,
RA   Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R.,
RA   Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A.,
RA   Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.,
RA   Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V.,
RA   Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.,
RA   Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R.,
RA   Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D.,
RA   Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A.,
RA   Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M.,
RA   Loveland J., Lovell J., Lush M.J., Lyne R., Martin S.,
RA   Mashreghi-Mohammadi M., Matthews L., Matthews N.S., McLaren S., Milne S.,
RA   Mistry S., Moore M.J., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A.,
RA   Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S.,
RA   Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G.,
RA   Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S.,
RA   Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A.,
RA   Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L.,
RA   Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z.,
RA   Coulson A., Vaudin M., Sulston J.E., Durbin R., Hubbard T., Wooster R.,
RA   Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V.,
RA   Beck S., Rogers J., Bentley D.R., Banerjee R., Bryant S.P., Burford D.C.,
RA   Burrill W.D., Clegg S.M., Dhami P., Dovey O., Faulkner L.M., Gribble S.M.,
RA   Langford C.F., Pandian R.D., Porter K.M., Prigmore E.;
RT   "The DNA sequence and biological annotation of human chromosome 1.";
RL   Nature 441:315-321(2006).
RN   [2] {ECO:0000313|Ensembl:ENSP00000427806.1}
RP   IDENTIFICATION.
RG   Ensembl;
RL   Submitted (NOV-2023) to UniProtKB.
CC   -!- FUNCTION: Probable subunit of the gamma-secretase complex, an
CC       endoprotease complex that catalyzes the intramembrane cleavage of
CC       integral membrane proteins such as Notch receptors.
CC       {ECO:0000256|RuleBase:RU361148}.
CC   -!- SUBUNIT: Homodimer. {ECO:0000256|RuleBase:RU361148}.
CC   -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC       {ECO:0000256|RuleBase:RU361148}; Multi-pass membrane protein
CC       {ECO:0000256|RuleBase:RU361148}. Golgi apparatus membrane
CC       {ECO:0000256|RuleBase:RU361148}; Multi-pass membrane protein
CC       {ECO:0000256|RuleBase:RU361148}. Membrane
CC       {ECO:0000256|ARBA:ARBA00004141}; Multi-pass membrane protein
CC       {ECO:0000256|ARBA:ARBA00004141}.
CC   -!- DOMAIN: The PAL motif is required for normal active site conformation.
CC       {ECO:0000256|RuleBase:RU361148}.
CC   -!- SIMILARITY: Belongs to the peptidase A22A family.
CC       {ECO:0000256|ARBA:ARBA00008604, ECO:0000256|RuleBase:RU361148}.
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DR   EMBL; AL359732; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AL391628; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   AlphaFoldDB; E5RG63; -.
DR   SMR; E5RG63; -.
DR   EPD; E5RG63; -.
DR   MassIVE; E5RG63; -.
DR   MaxQB; E5RG63; -.
DR   PeptideAtlas; E5RG63; -.
DR   ProteomicsDB; 15567; -.
DR   Antibodypedia; 4424; 495 antibodies from 40 providers.
DR   Ensembl; ENST00000472139.2; ENSP00000427806.1; ENSG00000143801.18.
DR   UCSC; uc057pzf.1; human.
DR   HGNC; HGNC:9509; PSEN2.
DR   NIAGADS; ENSG00000143801; -.
DR   VEuPathDB; HostDB:ENSG00000143801; -.
DR   GeneTree; ENSGT00940000157923; -.
DR   HOGENOM; CLU_022975_3_0_1; -.
DR   OMA; WTTITFC; -.
DR   ChiTaRS; PSEN2; human.
DR   Proteomes; UP000005640; Chromosome 1.
DR   Bgee; ENSG00000143801; Expressed in body of pancreas and 98 other cell types or tissues.
DR   ExpressionAtlas; E5RG63; baseline and differential.
DR   GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0000139; C:Golgi membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0042500; F:aspartic endopeptidase activity, intramembrane cleaving; IEA:InterPro.
DR   GO; GO:0042987; P:amyloid precursor protein catabolic process; IEA:InterPro.
DR   GO; GO:0035556; P:intracellular signal transduction; IEA:InterPro.
DR   GO; GO:0007219; P:Notch signaling pathway; IEA:UniProtKB-KW.
DR   GO; GO:0016485; P:protein processing; IEA:InterPro.
DR   Gene3D; 1.10.472.100; Presenilin; 1.
DR   InterPro; IPR001493; Pept_A22A_PS2.
DR   InterPro; IPR001108; Peptidase_A22A.
DR   InterPro; IPR006639; Preselin/SPP.
DR   InterPro; IPR042524; Presenilin_C.
DR   PANTHER; PTHR10202; PRESENILIN; 1.
DR   PANTHER; PTHR10202:SF13; PRESENILIN-2; 1.
DR   Pfam; PF01080; Presenilin; 2.
DR   PRINTS; PR01072; PRESENILIN.
DR   PRINTS; PR01074; PRESENILIN2.
DR   SMART; SM00730; PSN; 1.
PE   1: Evidence at protein level;
KW   Endoplasmic reticulum {ECO:0000256|ARBA:ARBA00022824,
KW   ECO:0000256|RuleBase:RU361148};
KW   Golgi apparatus {ECO:0000256|ARBA:ARBA00023034,
KW   ECO:0000256|RuleBase:RU361148}; Hydrolase {ECO:0000256|RuleBase:RU361148};
KW   Membrane {ECO:0000256|ARBA:ARBA00023136, ECO:0000256|RuleBase:RU361148};
KW   Notch signaling pathway {ECO:0000256|ARBA:ARBA00022976,
KW   ECO:0000256|RuleBase:RU361148}; Protease {ECO:0000256|RuleBase:RU361148};
KW   Proteomics identification {ECO:0007829|PeptideAtlas:E5RG63};
KW   Reference proteome {ECO:0000313|Proteomes:UP000005640};
KW   Transmembrane {ECO:0000256|ARBA:ARBA00022692,
KW   ECO:0000256|RuleBase:RU361148};
KW   Transmembrane helix {ECO:0000256|ARBA:ARBA00022989,
KW   ECO:0000256|RuleBase:RU361148}.
FT   TRANSMEM        27..45
FT                   /note="Helical"
FT                   /evidence="ECO:0000256|RuleBase:RU361148"
FT   TRANSMEM        57..75
FT                   /note="Helical"
FT                   /evidence="ECO:0000256|RuleBase:RU361148"
FT   TRANSMEM        82..100
FT                   /note="Helical"
FT                   /evidence="ECO:0000256|RuleBase:RU361148"
FT   TRANSMEM        106..125
FT                   /note="Helical"
FT                   /evidence="ECO:0000256|RuleBase:RU361148"
FT   TRANSMEM        245..265
FT                   /note="Helical"
FT                   /evidence="ECO:0000256|RuleBase:RU361148"
FT   TRANSMEM        271..290
FT                   /note="Helical"
FT                   /evidence="ECO:0000256|RuleBase:RU361148"
SQ   SEQUENCE   304 AA;  34094 MW;  ACA44C3A83C8C38E CRC64;
     MISVIVVMTI FLVVLYKYRC YKFIHGWLIM SSLMLLFLFT YIYLGEVLKT YNVAMDYPTL
     LLTVWNFGAV GMVCIHWKGP LVLQQAYLIM ISALMALVFI KYLPEWSAWV ILGAISVYDL
     VAVLCPKGPL RMLVETAQER NEPIFPALIY SSAMVWTVGM AKLDPSSQGA LQLPYDPEME
     EDSYDSFGEP SYPEVFEPPL TGYPGEELEE EEERGVKLGL GDFIFYSVLV GKAAATGSGD
     WNTTLACFVA ILIGLCLTLL LLAVFKKALP ALPISITFGL IFYFSTDNLV RPFMDTLASH
     QLYI
//