Reviewed, UniProtKB/Swiss-Prot Q8WW43 (APH1B_HUMAN)

Names and origin

Protein names

Recommended name:
    Gamma-secretase subunit APH-1B
      Short name=APH-1b
Alternative name(s):
    Aph-1beta
    Presenilin-stabilization factor-like

Gene names

Name:	APH1B
Synonyms:	PSFL
ORF Names:	UNQ688/PRO1328

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	257 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	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.
Subunit structure	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.
Subcellular location	Membrane; Multi-pass membrane proteinPotential.
Tissue specificity	Weakly or not expressed in leukocytes, lung, placenta, small intestine, liver, kidney, spleen thymus, colon, skeletal muscle, heart and brain.
Sequence similarities	Belongs to the APH-1 family.

Ontologies

Keywords
Biological process	Notch signaling pathway
Cellular component	Membrane
Domain	Transmembrane
Gene Ontology (GO)
Cellular component	transport vesicle Inferred from direct assay. Source: LIFEdb
Molecular function	protein binding Ref.5 Inferred from physical interaction. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view
Molecule processing
	Chain	1 – 257	257	Gamma-secretase subunit APH-1B
Regions
	Transmembrane	5 – 25	21	1 Potential
	Transmembrane	32 – 52	21	2 Potential
	Transmembrane	71 – 91	21	3 Potential
	Transmembrane	115 – 135	21	4 Potential
	Transmembrane	158 – 178	21	5 Potential
	Transmembrane	186 – 206	21	6 Potential
	Transmembrane	213 – 233	21	7 Potential
Experimental info
	Sequence conflict	27	1	T → I in AAQ89061. Ref.3
	Sequence conflict	83	1	Q → R Ref.1 Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Q8WW43-1 [UniParc]. Last modified March 15, 2005. Version 3. Checksum: A7A0C0076E20990A	FASTA	257	28,460
	10 20 30 40 50 60 MTAAVFFGCA FIAFGPALAL YVFTIATEPL RIIFLIAGAF FWLVSLLISS LVWFMARVII 70 80 90 100 110 120 DNKDGPTQKY LLIFGAFVSV YIQEMFRFAY YKLLKKASEG LKSINPGETA PSMRLLAYVS 130 140 150 160 170 180 GLGFGIMSGV FSFVNTLSDS LGPGTVGIHG DSPQFFLYSA FMTLVIILLH VFWGIVFFDG 190 200 210 220 230 240 CEKKKWGILL IVLLTHLLVS AQTFISSYYG INLASAFIIL VLMGTWAFLA AGGSCRSLKL 250 CLLCQDKNFL LYNQRSR

References

	« Hide 'large scale' referencesShow 'large scale' references »
[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].
[2]	"Towards a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs." Wiemann S., Weil B., Wellenreuther R., Gassenhuber J., Glassl S., Ansorge W., Boecher M., Bloecker H., Bauersachs S., Blum H., Lauber J., Duesterhoeft A., Beyer A., Koehrer K., Strack N., Mewes H.-W., Ottenwaelder B., Obermaier B. , Tampe J., Heubner D., Wambutt R., Korn B., Klein M., Poustka A. Genome Res. 11:422-435(2001) [PubMed: 11230166] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain.
[3]	"The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment." Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J., Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P., Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E. , Heldens S., Huang A., Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D., Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L., Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C., Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J., Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M. Genome Res. 13:2265-2270(2003) [PubMed: 12975309] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[4]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Placenta.
[5]	"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: 12297508] [Abstract] Cited for: FUNCTION, INTERACTION WITH PSEN1 AND PSEN2. Tissue: Glioblastoma.
[6]	"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: 12740439] [Abstract] Cited for: TISSUE SPECIFICITY.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	AF508794 mRNA. Translation: AAN63817.1. AL136671 mRNA. Translation: CAB66606.1. AY358698 mRNA. Translation: AAQ89061.1. BC020905 mRNA. Translation: AAH20905.1.
RefSeq	NP_112591.2.
UniGene	Hs.511703
3D structure databases
ModBase	Search...
Genome annotation databases
Ensembl	ENSG00000138613. Homo sapiens. [Contig view]
GeneID	83464.
KEGG	hsa:83464.
Organism-specific databases
H-InvDB	HIX0012322.
HGNC	HGNC:24080. APH1B.
MIM	607630. gene.
PharmGKB	PA142672600.
GenAtlas	Search...
GeneCards	Search...
Phylogenomic databases
HOGENOM	Q8WW43.
HOVERGEN	Q8WW43.
Enzyme and pathway databases
Reactome	REACT_299. Signaling by Notch.
Gene expression databases
ArrayExpress	Q8WW43.
CleanEx	HS_APH1B.
GermOnline	ENSG00000138613. Homo sapiens.
Family and domain databases
InterPro	IPR009294. Aph-1. [Graphical view]
PANTHER	PTHR12889. Aph-1. 1 hit.
Pfam	PF06105. Aph-1. 1 hit. [Graphical view]
ProDom	Q8WW43. [Graphical view] [Entries sharing at least one domain]
BLOCKS	Search...
Other Resources
SOURCE	Search...
ProtoNet	Search...

Entry information

Entry name

APH1B_HUMAN

Accession

Primary (citable) accession number: Q8WW43
Secondary accession number(s): Q6UWQ1, Q9H0S0

Entry history

Integrated into UniProtKB/Swiss-Prot:	September 26, 2003
Last sequence update:	March 15, 2005
Last modified:	September 2, 2008
This is version 48 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)