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Protein

Gamma-secretase subunit APH-1B

Gene

APH1B

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Probable subunit of the gamma-secretase complex, an endoprotease complex that catalyzes the intramembrane cleavage of integral proteins such as Notch receptors and APP (beta-amyloid precursor protein). It probably represents a stabilizing cofactor for the presenilin homodimer that promotes the formation of a stable complex. Probably present in a minority of gamma-secretase complexes compared to APH1A.1 Publication

GO - Molecular functioni

  • peptidase activity Source: MGI

GO - Biological processi

Complete GO annotation...

Keywords - Biological processi

Notch signaling pathway

Enzyme and pathway databases

ReactomeiREACT_116022. Nuclear signaling by ERBB4.
REACT_118614. Activated NOTCH1 Transmits Signal to the Nucleus.
REACT_118636. Signaling by NOTCH4.
REACT_118862. Signaling by NOTCH3.
REACT_13443. Regulated proteolysis of p75NTR.
REACT_13643. NRIF signals cell death from the nucleus.
REACT_160205. NOTCH2 Activation and Transmission of Signal to the Nucleus.
REACT_160243. Constitutive Signaling by NOTCH1 PEST Domain Mutants.
REACT_160254. Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants.
REACT_264198. EPH-ephrin mediated repulsion of cells.
SignaLinkiQ8WW43.

Names & Taxonomyi

Protein namesi
Recommended name:
Gamma-secretase subunit APH-1B
Short name:
APH-1b
Alternative name(s):
Aph-1beta
Presenilin-stabilization factor-like
Gene namesi
Name:APH1B
Synonyms:PSFL
ORF Names:UNQ688/PRO1328
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640 Componenti: Chromosome 15

Organism-specific databases

HGNCiHGNC:24080. APH1B.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Transmembranei5 – 2521Helical; Name=1Sequence AnalysisAdd
BLAST
Transmembranei32 – 5221Helical; Name=2Sequence AnalysisAdd
BLAST
Transmembranei71 – 9121Helical; Name=3Sequence AnalysisAdd
BLAST
Transmembranei115 – 13521Helical; Name=4Sequence AnalysisAdd
BLAST
Transmembranei158 – 17821Helical; Name=5Sequence AnalysisAdd
BLAST
Transmembranei186 – 20621Helical; Name=6Sequence AnalysisAdd
BLAST
Transmembranei213 – 23321Helical; Name=7Sequence AnalysisAdd
BLAST

GO - Cellular componenti

  • integral component of membrane Source: MGI
  • plasma membrane Source: Reactome
  • transport vesicle Source: LIFEdb
Complete GO annotation...

Keywords - Cellular componenti

Membrane

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA142672600.

Polymorphism and mutation databases

BioMutaiAPH1B.
DMDMi61252592.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 257257Gamma-secretase subunit APH-1BPRO_0000221052Add
BLAST

Proteomic databases

PaxDbiQ8WW43.
PRIDEiQ8WW43.

PTM databases

PhosphoSiteiQ8WW43.

Expressioni

Tissue specificityi

Weakly or not expressed in leukocytes, lung, placenta, small intestine, liver, kidney, spleen thymus, colon, skeletal muscle, heart and brain.1 Publication

Gene expression databases

BgeeiQ8WW43.
CleanExiHS_APH1B.
ExpressionAtlasiQ8WW43. baseline and differential.
GenevestigatoriQ8WW43.

Interactioni

Subunit structurei

Probable component of the gamma-secretase complex, a complex composed of a presenilin homodimer (PSEN1 or PSEN2), nicastrin (NCSTN), APH1 (APH1A or APH1B) and PEN2. Such minimal complex is sufficient for secretase activity, although other components may exist (By similarity). Interacts with PSEN1 and PSEN2.By similarity1 Publication

Protein-protein interaction databases

BioGridi123659. 5 interactions.
IntActiQ8WW43. 1 interaction.
MINTiMINT-4721718.
STRINGi9606.ENSP00000261879.

Structurei

3D structure databases

ProteinModelPortaliQ8WW43.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the APH-1 family.Curated

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiNOG300477.
GeneTreeiENSGT00390000002049.
HOGENOMiHOG000007541.
HOVERGENiHBG050541.
InParanoidiQ8WW43.
KOiK06172.
OMAiFRFGYYK.
PhylomeDBiQ8WW43.
TreeFamiTF314362.

Family and domain databases

InterProiIPR009294. Aph-1.
[Graphical view]
PANTHERiPTHR12889. PTHR12889. 1 hit.
PfamiPF06105. Aph-1. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q8WW43-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MTAAVFFGCA FIAFGPALAL YVFTIATEPL RIIFLIAGAF FWLVSLLISS
60 70 80 90 100
LVWFMARVII DNKDGPTQKY LLIFGAFVSV YIQEMFRFAY YKLLKKASEG
110 120 130 140 150
LKSINPGETA PSMRLLAYVS GLGFGIMSGV FSFVNTLSDS LGPGTVGIHG
160 170 180 190 200
DSPQFFLYSA FMTLVIILLH VFWGIVFFDG CEKKKWGILL IVLLTHLLVS
210 220 230 240 250
AQTFISSYYG INLASAFIIL VLMGTWAFLA AGGSCRSLKL CLLCQDKNFL

LYNQRSR
Length:257
Mass (Da):28,460
Last modified:March 15, 2005 - v3
Checksum:iA7A0C0076E20990A
GO
Isoform 2 (identifier: Q8WW43-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     119-159: Missing.

Note: Expressed at low levels in most tissues.

Show »
Length:216
Mass (Da):24,282
Checksum:i73F52F010DD3ECBA
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti27 – 271T → I in AAQ89061 (PubMed:12975309).Curated
Sequence conflicti83 – 831Q → R in AAN63817 (Ref. 1) Curated
Sequence conflicti83 – 831Q → R in CAB66606 (PubMed:11230166).Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti217 – 2171F → L.
Corresponds to variant rs1047552 [ dbSNP | Ensembl ].
VAR_048315

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei119 – 15941Missing in isoform 2. 1 PublicationVSP_042945Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF508794 mRNA. Translation: AAN63817.1.
AB189172 mRNA. Translation: BAD95573.1.
AL136671 mRNA. Translation: CAB66606.1.
AY358698 mRNA. Translation: AAQ89061.1.
AK291204 mRNA. Translation: BAF83893.1.
AC016207 Genomic DNA. No translation available.
CH471082 Genomic DNA. Translation: EAW77645.1.
BC020905 mRNA. Translation: AAH20905.1.
CCDSiCCDS10184.1. [Q8WW43-1]
CCDS45276.1. [Q8WW43-2]
RefSeqiNP_001139118.1. NM_001145646.1. [Q8WW43-2]
NP_112591.2. NM_031301.3. [Q8WW43-1]
UniGeneiHs.511703.

Genome annotation databases

EnsembliENST00000261879; ENSP00000261879; ENSG00000138613. [Q8WW43-1]
ENST00000380343; ENSP00000369700; ENSG00000138613. [Q8WW43-2]
GeneIDi83464.
KEGGihsa:83464.
UCSCiuc002ama.3. human. [Q8WW43-1]
uc002amb.3. human. [Q8WW43-2]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF508794 mRNA. Translation: AAN63817.1.
AB189172 mRNA. Translation: BAD95573.1.
AL136671 mRNA. Translation: CAB66606.1.
AY358698 mRNA. Translation: AAQ89061.1.
AK291204 mRNA. Translation: BAF83893.1.
AC016207 Genomic DNA. No translation available.
CH471082 Genomic DNA. Translation: EAW77645.1.
BC020905 mRNA. Translation: AAH20905.1.
CCDSiCCDS10184.1. [Q8WW43-1]
CCDS45276.1. [Q8WW43-2]
RefSeqiNP_001139118.1. NM_001145646.1. [Q8WW43-2]
NP_112591.2. NM_031301.3. [Q8WW43-1]
UniGeneiHs.511703.

3D structure databases

ProteinModelPortaliQ8WW43.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi123659. 5 interactions.
IntActiQ8WW43. 1 interaction.
MINTiMINT-4721718.
STRINGi9606.ENSP00000261879.

Chemistry

BindingDBiQ8WW43.
ChEMBLiCHEMBL2094135.

PTM databases

PhosphoSiteiQ8WW43.

Polymorphism and mutation databases

BioMutaiAPH1B.
DMDMi61252592.

Proteomic databases

PaxDbiQ8WW43.
PRIDEiQ8WW43.

Protocols and materials databases

DNASUi83464.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000261879; ENSP00000261879; ENSG00000138613. [Q8WW43-1]
ENST00000380343; ENSP00000369700; ENSG00000138613. [Q8WW43-2]
GeneIDi83464.
KEGGihsa:83464.
UCSCiuc002ama.3. human. [Q8WW43-1]
uc002amb.3. human. [Q8WW43-2]

Organism-specific databases

CTDi83464.
GeneCardsiGC15P065755.
HGNCiHGNC:24080. APH1B.
MIMi607630. gene.
neXtProtiNX_Q8WW43.
PharmGKBiPA142672600.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG300477.
GeneTreeiENSGT00390000002049.
HOGENOMiHOG000007541.
HOVERGENiHBG050541.
InParanoidiQ8WW43.
KOiK06172.
OMAiFRFGYYK.
PhylomeDBiQ8WW43.
TreeFamiTF314362.

Enzyme and pathway databases

ReactomeiREACT_116022. Nuclear signaling by ERBB4.
REACT_118614. Activated NOTCH1 Transmits Signal to the Nucleus.
REACT_118636. Signaling by NOTCH4.
REACT_118862. Signaling by NOTCH3.
REACT_13443. Regulated proteolysis of p75NTR.
REACT_13643. NRIF signals cell death from the nucleus.
REACT_160205. NOTCH2 Activation and Transmission of Signal to the Nucleus.
REACT_160243. Constitutive Signaling by NOTCH1 PEST Domain Mutants.
REACT_160254. Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants.
REACT_264198. EPH-ephrin mediated repulsion of cells.
SignaLinkiQ8WW43.

Miscellaneous databases

ChiTaRSiAPH1B. human.
GenomeRNAii83464.
NextBioi72393.
PROiQ8WW43.
SOURCEiSearch...

Gene expression databases

BgeeiQ8WW43.
CleanExiHS_APH1B.
ExpressionAtlasiQ8WW43. baseline and differential.
GenevestigatoriQ8WW43.

Family and domain databases

InterProiIPR009294. Aph-1.
[Graphical view]
PANTHERiPTHR12889. PTHR12889. 1 hit.
PfamiPF06105. Aph-1. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "PSF is essential for gamma-secretase activity and stabilization of presenilin and nicastrin."
    Lee H.-J., Kim T.-W.
    Submitted (MAY-2002) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
  2. "Identification and characterization of a novel human APH-1b splice variant lacking exon 4."
    Saito S., Takahashi-Sasaki N., Araki W.
    Biochem. Biophys. Res. Commun. 330:1068-1072(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), ALTERNATIVE SPLICING.
  3. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
    Tissue: Brain.
  4. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
  5. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
    Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
    , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
    Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
  6. "Analysis of the DNA sequence and duplication history of human chromosome 15."
    Zody M.C., Garber M., Sharpe T., Young S.K., Rowen L., O'Neill K., Whittaker C.A., Kamal M., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Kodira C.D., Madan A., Qin S., Yang X., Abbasi N., Abouelleil A.
    , Arachchi H.M., Baradarani L., Birditt B., Bloom S., Bloom T., Borowsky M.L., Burke J., Butler J., Cook A., DeArellano K., DeCaprio D., Dorris L. III, Dors M., Eichler E.E., Engels R., Fahey J., Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G., Johnson E., Jones C., Kamat A., Kaur A., Locke D.P., Madan A., Munson G., Jaffe D.B., Lui A., Macdonald P., Mauceli E., Naylor J.W., Nesbitt R., Nicol R., O'Leary S.B., Ratcliffe A., Rounsley S., She X., Sneddon K.M.B., Stewart S., Sougnez C., Stone S.M., Topham K., Vincent D., Wang S., Zimmer A.R., Birren B.W., Hood L., Lander E.S., Nusbaum C.
    Nature 440:671-675(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  7. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  8. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
    Tissue: Placenta.
  9. "Mammalian APH-1 interacts with presenilin and nicastrin and is required for intramembrane proteolysis of amyloid-beta precursor protein and Notch."
    Lee S.-F., Shah S., Li H., Yu C., Han W., Yu G.
    J. Biol. Chem. 277:45013-45019(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH PSEN1 AND PSEN2.
    Tissue: Glioblastoma.
  10. "Gamma-secretase is a membrane protein complex comprised of presenilin, nicastrin, Aph-1, and Pen-2."
    Kimberly W.T., LaVoie M.J., Ostaszewski B.L., Ye W., Wolfe M.S., Selkoe D.J.
    Proc. Natl. Acad. Sci. U.S.A. 100:6382-6387(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: TISSUE SPECIFICITY.

Entry informationi

Entry nameiAPH1B_HUMAN
AccessioniPrimary (citable) accession number: Q8WW43
Secondary accession number(s): A8K589
, Q564N3, Q6UWQ1, Q9H0S0
Entry historyi
Integrated into UniProtKB/Swiss-Prot: September 26, 2003
Last sequence update: March 15, 2005
Last modified: April 29, 2015
This is version 115 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 15
    Human chromosome 15: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.