Q8WW43 (APH1B_HUMAN) Reviewed, UniProtKB/Swiss-Prot

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) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	257 AA.
Sequence status	Complete.
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.9
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. Ref.9
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.10
Sequence similarities	Belongs to the APH-1 family.

Ontologies

Keywords
Biological process	Notch signaling pathway
Cellular component	Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Transmembrane Transmembrane helix
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	Notch receptor processing Traceable author statement. Source: Reactome Notch signaling pathway Traceable author statement. Source: Reactome apoptotic process Traceable author statement. Source: Reactome membrane protein intracellular domain proteolysis Traceable author statement. Source: Reactome nerve growth factor receptor signaling pathway Traceable author statement. Source: Reactome positive regulation of catalytic activity Inferred from electronic annotation. Source: InterPro protein processing Inferred from direct assay Ref.9. Source: MGI
Cellular_component	integral to membrane Inferred from direct assay Ref.9. Source: MGI plasma membrane Traceable author statement. Source: Reactome transport vesicle Inferred from direct assay. Source: LIFEdb
Molecular_function	peptidase activity Inferred from direct assay Ref.9. Source: MGI
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
PSEN2	P49810	1	EBI-2606497,EBI-2010251

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q8WW43-1)

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.

Isoform 2 (identifier: Q8WW43-2)

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

Note: Expressed at low levels in most tissues.

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	Helical; Name=1; Potential
	Transmembrane	32 – 52	21	Helical; Name=2; Potential
	Transmembrane	71 – 91	21	Helical; Name=3; Potential
	Transmembrane	115 – 135	21	Helical; Name=4; Potential
	Transmembrane	158 – 178	21	Helical; Name=5; Potential
	Transmembrane	186 – 206	21	Helical; Name=6; Potential
	Transmembrane	213 – 233	21	Helical; Name=7; Potential
Natural variations
	Alternative sequence	119 – 159	41	Missing in isoform 2.		VSP_042945
	Natural variant	217	1	F → L. Corresponds to variant rs1047552 [ dbSNP | Ensembl ].		VAR_048315
Experimental info
	Sequence conflict	27	1	T → I in AAQ89061. Ref.4
	Sequence conflict	83	1	Q → R in AAN63817. Ref.1
	Sequence conflict	83	1	Q → R in CAB66606. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 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
	Isoform 2 [UniParc]. Checksum: 73F52F010DD3ECBA	FASTA	216	24,282
	10 20 30 40 50 60 MTAAVFFGCA FIAFGPALAL YVFTIATEPL RIIFLIAGAF FWLVSLLISS LVWFMARVII 70 80 90 100 110 120 DNKDGPTQKY LLIFGAFVSV YIQEMFRFAY YKLLKKASEG LKSINPGETA PSMRLLAYAF 130 140 150 160 170 180 MTLVIILLHV FWGIVFFDGC EKKKWGILLI VLLTHLLVSA QTFISSYYGI NLASAFIILV 190 200 210 LMGTWAFLAA GGSCRSLKLC LLCQDKNFLL YNQRSR

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] (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]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Brain.
[4]	"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] [Europe PMC] [Abstract] 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]	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].
[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.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	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.
IPI	IPI00291632. IPI00556559.
RefSeq	NP_001139118.1. NM_001145646.1. NP_112591.2. NM_031301.3.
UniGene	Hs.511703.
3D structure databases
ProteinModelPortal	Q8WW43.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q8WW43. 1 interaction.
STRING	9606.ENSP00000261879.
PTM databases
PhosphoSite	Q8WW43.
Polymorphism databases
DMDM	61252592.
Proteomic databases
PaxDb	Q8WW43.
PRIDE	Q8WW43.
Protocols and materials databases
DNASU	83464.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000261879; ENSP00000261879; ENSG00000138613. ENST00000380343; ENSP00000369700; ENSG00000138613.
GeneID	83464.
KEGG	hsa:83464.
UCSC	uc002ama.3. human.
Organism-specific databases
CTD	83464.
GeneCards	GC15P063647.
HGNC	HGNC:24080. APH1B.
MIM	607630. gene.
neXtProt	NX_Q8WW43.
PharmGKB	PA142672600.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG300477.
HOGENOM	HOG000007541.
HOVERGEN	HBG050541.
InParanoid	Q8WW43.
KO	K06172.
OMA	TFLSPHY.
OrthoDB	EOG4K6G55.
PhylomeDB	Q8WW43.
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_111102. Signal Transduction. REACT_691. A third proteolytic cleavage releases NICD.
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. PTHR12889. 1 hit.
Pfam	PF06105. Aph-1. 1 hit. [Graphical view]
ProtoNet	Search...
Other
BindingDB	Q8WW43.
ChEMBL	CHEMBL2385.
GenomeRNAi	83464.
NextBio	72393.
SOURCE	Search...

Entry information

Entry name

APH1B_HUMAN

Accession

Primary (citable) accession number: Q8WW43
Secondary accession number(s): A8K589 , Q564N3, Q6UWQ1, Q9H0S0

Entry history

Integrated into UniProtKB/Swiss-Prot:	September 26, 2003
Last sequence update:	March 15, 2005
Last modified:	May 1, 2013
This is version 95 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

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.