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) [Complete proteome]

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. Ref.7
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 protein Potential.
Tissue specificity	Weakly or not expressed in leukocytes, lung, placenta, small intestine, liver, kidney, spleen thymus, colon, skeletal muscle, heart and brain. Ref.8
Sequence similarities	Belongs to the APH-1 family.

Ontologies

Keywords
Biological process	Notch signaling pathway
Cellular component	Membrane
Coding sequence diversity	Polymorphism
Domain	Transmembrane
Technical term	Complete proteome
Gene Ontology (GO)
Biological process	Notch signaling pathway Inferred from electronic annotation. Source: UniProtKB-KW apoptosis Inferred from Experiment. Source: Reactome induction of apoptosis by extracellular signals Inferred from Experiment. Source: Reactome membrane protein intracellular domain proteolysis Inferred from Experiment. Source: Reactome positive regulation of catalytic activity Inferred from electronic annotation. Source: InterPro protein processing Ref.7 Inferred from direct assay. Source: MGI
Cellular component	integral to membrane Ref.7 Inferred from direct assay. Source: MGI plasma membrane Inferred from Experiment. Source: Reactome transport vesicle Inferred from direct assay. Source: LIFEdb
Molecular function	peptidase activity Ref.7 Inferred from direct assay. Source: MGI protein binding Ref.7 Inferred from physical interaction. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 257	257	Gamma-secretase subunit APH-1B		PRO_0000221052
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
Natural variations
	Natural variant	217	1	F → L: dbSNP rs1047552.		VAR_048315
Experimental info
	Sequence conflict	27	1	T → I in AAQ89061. Ref.3
	Sequence conflict	83	1	Q → R Ref.1
	Sequence conflict	83	1	Q → R 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]	"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: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[5]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"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.
[7]	"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.
[8]	"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. AK291204 mRNA. Translation: BAF83893.1. CH471082 Genomic DNA. Translation: EAW77645.1. BC020905 mRNA. Translation: AAH20905.1.
IPI	IPI00291632.
RefSeq	NP_112591.2.
UniGene	Hs.511703
3D structure databases
ModBase	Search...
Protein-protein interaction databases
STRING	Q8WW43.
Proteomic databases
PRIDE	Q8WW43.
Genome annotation databases
Ensembl	ENST00000261879; ENSP00000261879; ENSG00000138613; Homo sapiens. [Genome view]
GeneID	83464.
UCSC	uc002ama.1. human.
Organism-specific databases
CTD	83464.
GeneCards	GC15P061357.
H-InvDB	HIX0012322.
HGNC	HGNC:24080. APH1B.
MIM	607630. gene.
PharmGKB	PA142672600.
GenAtlas	Search...
Phylogenomic databases
HOGENOM	Q8WW43.
HOVERGEN	Q8WW43.
OMA	DFLLFNQ
OrthoDB	EOG9W6RFQ
Enzyme and pathway databases
Pathway_Interaction_DB	p75ntrpathway. p75(NTR)-mediated signaling. ps1pathway. Presenilin action in Notch and Wnt signaling. syndecan_3_pathway. Syndecan-3-mediated signaling events.
Reactome	REACT_11061. Signalling by NGF. REACT_299. Signaling by Notch.
Gene expression databases
ArrayExpress	Q8WW43.
Bgee	Q8WW43.
CleanEx	HS_APH1B.
Genevestigator	Q8WW43.
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]
ProtoNet	Search...
Other Resources
NextBio	72393.
SOURCE	Search...

Entry information

Entry name

APH1B_HUMAN

Accession

Primary (citable) accession number: Q8WW43
Secondary accession number(s): A8K589, Q6UWQ1, Q9H0S0

Entry history

Integrated into UniProtKB/Swiss-Prot:	September 26, 2003
Last sequence update:	March 15, 2005
Last modified:	November 24, 2009
This is version 62 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

Disclaimer

Any 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.