SubmitCancel

Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.

Q8WW43

- APH1B_HUMAN

UniProt

Q8WW43 - APH1B_HUMAN

(max 400 entries)x

Your basket is currently empty.

Select item(s) and click on "Add to basket" to create your own collection here
(400 entries max)

Protein
Gamma-secretase subunit APH-1B
Gene
APH1B, PSFL, UNQ688/PRO1328
Organism
Homo sapiens (Human)
Status
Reviewed - 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

  1. peptidase activity Source: MGI
  2. protein binding Source: UniProtKB

GO - Biological processi

  1. Notch receptor processing Source: Reactome
  2. Notch signaling pathway Source: Reactome
  3. apoptotic signaling pathway Source: Reactome
  4. membrane protein intracellular domain proteolysis Source: Reactome
  5. neurotrophin TRK receptor signaling pathway Source: Reactome
  6. positive regulation of apoptotic process Source: Reactome
  7. positive regulation of catalytic activity Source: InterPro
  8. protein processing Source: MGI
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.
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: Chromosome 15

Organism-specific databases

HGNCiHGNC:24080. APH1B.

Subcellular locationi

Topology

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

GO - Cellular componenti

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

Keywords - Cellular componenti

Membrane

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA142672600.

PTM / Processingi

Molecule processing

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

ArrayExpressiQ8WW43.
BgeeiQ8WW43.
CleanExiHS_APH1B.
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 PSEN2.1 Publication

Protein-protein interaction databases

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

Structurei

3D structure databases

ProteinModelPortaliQ8WW43.

Family & Domainsi

Sequence similaritiesi

Belongs to the APH-1 family.

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiNOG300477.
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. Align

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

MTAAVFFGCA FIAFGPALAL YVFTIATEPL RIIFLIAGAF FWLVSLLISS    50
LVWFMARVII DNKDGPTQKY LLIFGAFVSV YIQEMFRFAY YKLLKKASEG 100
LKSINPGETA PSMRLLAYVS GLGFGIMSGV FSFVNTLSDS LGPGTVGIHG 150
DSPQFFLYSA FMTLVIILLH VFWGIVFFDG CEKKKWGILL IVLLTHLLVS 200
AQTFISSYYG INLASAFIIL VLMGTWAFLA AGGSCRSLKL CLLCQDKNFL 250
LYNQRSR 257
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

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.
VSP_042945Add
BLAST

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti27 – 271T → I in AAQ89061. 1 Publication
Sequence conflicti83 – 831Q → R in AAN63817. 1 Publication
Sequence conflicti83 – 831Q → R in CAB66606. 1 Publication

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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]

Polymorphism databases

DMDMi61252592.

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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 .
CCDSi CCDS10184.1. [Q8WW43-1 ]
CCDS45276.1. [Q8WW43-2 ]
RefSeqi NP_001139118.1. NM_001145646.1. [Q8WW43-2 ]
NP_112591.2. NM_031301.3. [Q8WW43-1 ]
UniGenei Hs.511703.

3D structure databases

ProteinModelPortali Q8WW43.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 123659. 5 interactions.
IntActi Q8WW43. 1 interaction.
MINTi MINT-4721718.
STRINGi 9606.ENSP00000261879.

Chemistry

BindingDBi Q8WW43.
ChEMBLi CHEMBL2094135.

PTM databases

PhosphoSitei Q8WW43.

Polymorphism databases

DMDMi 61252592.

Proteomic databases

PaxDbi Q8WW43.
PRIDEi Q8WW43.

Protocols and materials databases

DNASUi 83464.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000261879 ; ENSP00000261879 ; ENSG00000138613 . [Q8WW43-1 ]
ENST00000380343 ; ENSP00000369700 ; ENSG00000138613 . [Q8WW43-2 ]
GeneIDi 83464.
KEGGi hsa:83464.
UCSCi uc002ama.3. human. [Q8WW43-1 ]
uc002amb.3. human. [Q8WW43-2 ]

Organism-specific databases

CTDi 83464.
GeneCardsi GC15P064873.
HGNCi HGNC:24080. APH1B.
MIMi 607630. gene.
neXtProti NX_Q8WW43.
PharmGKBi PA142672600.
GenAtlasi Search...

Phylogenomic databases

eggNOGi NOG300477.
HOGENOMi HOG000007541.
HOVERGENi HBG050541.
InParanoidi Q8WW43.
KOi K06172.
OMAi FRFGYYK.
PhylomeDBi Q8WW43.
TreeFami TF314362.

Enzyme and pathway databases

Reactomei REACT_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.
SignaLinki Q8WW43.

Miscellaneous databases

GenomeRNAii 83464.
NextBioi 72393.
PROi Q8WW43.
SOURCEi Search...

Gene expression databases

ArrayExpressi Q8WW43.
Bgeei Q8WW43.
CleanExi HS_APH1B.
Genevestigatori Q8WW43.

Family and domain databases

InterProi IPR009294. Aph-1.
[Graphical view ]
PANTHERi PTHR12889. PTHR12889. 1 hit.
Pfami PF06105. Aph-1. 1 hit.
[Graphical view ]
ProtoNeti Search...

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: September 3, 2014
This is version 108 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