APH1B_MOUSE
ID APH1B_MOUSE Reviewed; 257 AA.
AC Q8C7N7; Q3U3B5; Q8CEC9;
DT 26-SEP-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2003, sequence version 1.
DT 03-AUG-2022, entry version 134.
DE RecName: Full=Gamma-secretase subunit APH-1B;
DE Short=APH-1b;
DE AltName: Full=Aph-1beta;
GN Name=Aph1b;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC STRAIN=C57BL/6J, and NOD; TISSUE=Hippocampus, and Skin;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=C57BL/6J; TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
CC -!- FUNCTION: Probable subunit of the gamma-secretase complex, an
CC endoprotease complex that catalyzes the intramembrane cleavage of
CC integral proteins such as Notch receptors and APP (amyloid-beta
CC precursor protein). It probably represents a stabilizing cofactor for
CC the presenilin homodimer that promotes the formation of a stable
CC complex. Probably present in a minority of gamma-secretase complexes
CC compared to APH1A (By similarity). {ECO:0000250}.
CC -!- SUBUNIT: Probable component of the gamma-secretase complex, a complex
CC composed of a presenilin homodimer (PSEN1 or PSEN2), nicastrin (NCSTN),
CC APH1 (APH1A or APH1B) and PEN2. Such minimal complex is sufficient for
CC secretase activity, although other components may exist (By
CC similarity). Interacts with PSEN1 and PSEN2 (By similarity).
CC {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000305}; Multi-pass membrane
CC protein {ECO:0000305}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q8C7N7-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8C7N7-2; Sequence=VSP_008359, VSP_008360;
CC -!- SIMILARITY: Belongs to the APH-1 family. {ECO:0000305}.
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DR EMBL; AK028521; BAC25988.1; -; mRNA.
DR EMBL; AK049828; BAC33940.1; -; mRNA.
DR EMBL; AK154847; BAE32873.1; -; mRNA.
DR EMBL; BC079659; AAH79659.1; -; mRNA.
DR CCDS; CCDS23307.1; -. [Q8C7N7-1]
DR RefSeq; NP_808251.1; NM_177583.4. [Q8C7N7-1]
DR AlphaFoldDB; Q8C7N7; -.
DR SMR; Q8C7N7; -.
DR BioGRID; 228950; 14.
DR ComplexPortal; CPX-4235; Gamma-secretase complex, Aph1b-Psen1 variant.
DR ComplexPortal; CPX-4237; Gamma-secretase complex, Aph1b-Psen2 variant.
DR STRING; 10090.ENSMUSP00000034934; -.
DR PhosphoSitePlus; Q8C7N7; -.
DR MaxQB; Q8C7N7; -.
DR PaxDb; Q8C7N7; -.
DR PRIDE; Q8C7N7; -.
DR ProteomicsDB; 296371; -. [Q8C7N7-1]
DR ProteomicsDB; 296372; -. [Q8C7N7-2]
DR DNASU; 208117; -.
DR Ensembl; ENSMUST00000034934; ENSMUSP00000034934; ENSMUSG00000032375. [Q8C7N7-1]
DR Ensembl; ENSMUST00000168309; ENSMUSP00000125816; ENSMUSG00000032375. [Q8C7N7-2]
DR GeneID; 208117; -.
DR KEGG; mmu:208117; -.
DR UCSC; uc009qfe.1; mouse. [Q8C7N7-1]
DR CTD; 83464; -.
DR MGI; MGI:3522097; Aph1b.
DR VEuPathDB; HostDB:ENSMUSG00000032375; -.
DR eggNOG; KOG3972; Eukaryota.
DR GeneTree; ENSGT00390000002049; -.
DR HOGENOM; CLU_086389_0_0_1; -.
DR InParanoid; Q8C7N7; -.
DR OMA; EKKKWYV; -.
DR OrthoDB; 1085102at2759; -.
DR PhylomeDB; Q8C7N7; -.
DR TreeFam; TF314362; -.
DR Reactome; R-MMU-1251985; Nuclear signaling by ERBB4.
DR Reactome; R-MMU-193692; Regulated proteolysis of p75NTR.
DR Reactome; R-MMU-205043; NRIF signals cell death from the nucleus.
DR Reactome; R-MMU-3928665; EPH-ephrin mediated repulsion of cells.
DR Reactome; R-MMU-9013507; NOTCH3 Activation and Transmission of Signal to the Nucleus.
DR Reactome; R-MMU-9017802; Noncanonical activation of NOTCH3.
DR BioGRID-ORCS; 208117; 3 hits in 73 CRISPR screens.
DR ChiTaRS; Aph1b; mouse.
DR PRO; PR:Q8C7N7; -.
DR Proteomes; UP000000589; Chromosome 9.
DR RNAct; Q8C7N7; protein.
DR Bgee; ENSMUSG00000032375; Expressed in otolith organ and 216 other tissues.
DR ExpressionAtlas; Q8C7N7; baseline and differential.
DR Genevisible; Q8C7N7; MM.
DR GO; GO:0005783; C:endoplasmic reticulum; IBA:GO_Central.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IC:ComplexPortal.
DR GO; GO:0070765; C:gamma-secretase complex; IDA:MGI.
DR GO; GO:0000139; C:Golgi membrane; IC:ComplexPortal.
DR GO; GO:0016021; C:integral component of membrane; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0045202; C:synapse; IEA:GOC.
DR GO; GO:0030133; C:transport vesicle; ISO:MGI.
DR GO; GO:0061133; F:endopeptidase activator activity; ISO:MGI.
DR GO; GO:0030674; F:protein-macromolecule adaptor activity; ISO:MGI.
DR GO; GO:0042987; P:amyloid precursor protein catabolic process; ISO:MGI.
DR GO; GO:0034205; P:amyloid-beta formation; IGI:MGI.
DR GO; GO:0007626; P:locomotory behavior; ISO:MGI.
DR GO; GO:0006509; P:membrane protein ectodomain proteolysis; IGI:MGI.
DR GO; GO:0031293; P:membrane protein intracellular domain proteolysis; IC:ComplexPortal.
DR GO; GO:0007220; P:Notch receptor processing; ISO:MGI.
DR GO; GO:0007219; P:Notch signaling pathway; IBA:GO_Central.
DR GO; GO:0010950; P:positive regulation of endopeptidase activity; ISO:MGI.
DR GO; GO:0060134; P:prepulse inhibition; IGI:MGI.
DR GO; GO:0016485; P:protein processing; ISO:MGI.
DR GO; GO:0007614; P:short-term memory; IGI:MGI.
DR GO; GO:0001963; P:synaptic transmission, dopaminergic; IGI:MGI.
DR GO; GO:0035249; P:synaptic transmission, glutamatergic; IGI:MGI.
DR InterPro; IPR009294; Aph-1.
DR PANTHER; PTHR12889; PTHR12889; 1.
DR Pfam; PF06105; Aph-1; 1.
PE 2: Evidence at transcript level;
KW Alternative splicing; Membrane; Notch signaling pathway;
KW Reference proteome; Transmembrane; Transmembrane helix.
FT CHAIN 1..257
FT /note="Gamma-secretase subunit APH-1B"
FT /id="PRO_0000221053"
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 66..86
FT /note="Helical; Name=3"
FT /evidence="ECO:0000255"
FT TRANSMEM 115..135
FT /note="Helical; Name=4"
FT /evidence="ECO:0000255"
FT TRANSMEM 160..180
FT /note="Helical; Name=5"
FT /evidence="ECO:0000255"
FT TRANSMEM 186..206
FT /note="Helical; Name=6"
FT /evidence="ECO:0000255"
FT TRANSMEM 213..233
FT /note="Helical; Name=7"
FT /evidence="ECO:0000255"
FT VAR_SEQ 160..212
FT /note="AFMTLVVIMLHVFWGVVFFDGCEKNKWYTLLTVLLTHLVVSTQTFLSPYYEV
FT N -> VRISASPMDINSVSHSREPVLCAASKLVFPVGKVFDFLRPAAYSSDYLTPALS
FT (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_008359"
FT VAR_SEQ 213..257
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_008360"
SQ SEQUENCE 257 AA; 28703 MW; 52D39310695ED96A CRC64;
MTAAVFFGCA FIAFGPALAL YVFTIATDPL RVIFLIAGAF FWLVSLLLSS VFWFLVRVIT
DNRDGPVQNY LLIFGVLLSV CIQELFRLAY YKLLKKASEG LKSINPEETA PSMRLLAYVS
GLGFGIMSGV FSFVNTLSNS LGPGTVGIHG DSPQFFLNSA FMTLVVIMLH VFWGVVFFDG
CEKNKWYTLL TVLLTHLVVS TQTFLSPYYE VNLVTAYIIM VLMGIWAFYV AGGSCRSLKL
CLLCQDKDFL LYNQRSR
