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Q8WW43 (APH1B_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified March 19, 2014. Version 104. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length257 AA.
Sequence statusComplete.
Protein existenceEvidence 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.

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 keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 257257Gamma-secretase subunit APH-1B
PRO_0000221052

Regions

Transmembrane5 – 2521Helical; Name=1; Potential
Transmembrane32 – 5221Helical; Name=2; Potential
Transmembrane71 – 9121Helical; Name=3; Potential
Transmembrane115 – 13521Helical; Name=4; Potential
Transmembrane158 – 17821Helical; Name=5; Potential
Transmembrane186 – 20621Helical; Name=6; Potential
Transmembrane213 – 23321Helical; Name=7; Potential

Natural variations

Alternative sequence119 – 15941Missing in isoform 2.
VSP_042945
Natural variant2171F → L.
Corresponds to variant rs1047552 [ dbSNP | Ensembl ].
VAR_048315

Experimental info

Sequence conflict271T → I in AAQ89061. Ref.4
Sequence conflict831Q → R in AAN63817. Ref.1
Sequence conflict831Q → R in CAB66606. Ref.3

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified March 15, 2005. Version 3.
Checksum: A7A0C0076E20990A

FASTA25728,460
        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 

« Hide

Isoform 2 [UniParc].

Checksum: 73F52F010DD3ECBA
Show »

FASTA21624,282

References

« Hide '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. expand/collapse author list , 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. expand/collapse author list , 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. expand/collapse author list , 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. expand/collapse author list , 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. expand/collapse author list , 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.
RefSeqNP_001139118.1. NM_001145646.1.
NP_112591.2. NM_031301.3.
UniGeneHs.511703.

3D structure databases

ProteinModelPortalQ8WW43.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid123659. 5 interactions.
IntActQ8WW43. 1 interaction.
MINTMINT-4721718.
STRING9606.ENSP00000261879.

Chemistry

BindingDBQ8WW43.
ChEMBLCHEMBL2094135.

PTM databases

PhosphoSiteQ8WW43.

Polymorphism databases

DMDM61252592.

Proteomic databases

PaxDbQ8WW43.
PRIDEQ8WW43.

Protocols and materials databases

DNASU83464.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000261879; ENSP00000261879; ENSG00000138613. [Q8WW43-1]
ENST00000380343; ENSP00000369700; ENSG00000138613. [Q8WW43-2]
GeneID83464.
KEGGhsa:83464.
UCSCuc002ama.3. human. [Q8WW43-1]
uc002amb.3. human. [Q8WW43-2]

Organism-specific databases

CTD83464.
GeneCardsGC15P064873.
HGNCHGNC:24080. APH1B.
MIM607630. gene.
neXtProtNX_Q8WW43.
PharmGKBPA142672600.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG300477.
HOGENOMHOG000007541.
HOVERGENHBG050541.
InParanoidQ8WW43.
KOK06172.
OMAFRFGYYK.
PhylomeDBQ8WW43.
TreeFamTF314362.

Enzyme and pathway databases

ReactomeREACT_111102. Signal Transduction.
REACT_116125. Disease.
REACT_691. A third proteolytic cleavage releases NICD.
SignaLinkQ8WW43.

Gene expression databases

ArrayExpressQ8WW43.
BgeeQ8WW43.
CleanExHS_APH1B.
GenevestigatorQ8WW43.

Family and domain databases

InterProIPR009294. Aph-1.
[Graphical view]
PANTHERPTHR12889. PTHR12889. 1 hit.
PfamPF06105. Aph-1. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GenomeRNAi83464.
NextBio72393.
PROQ8WW43.
SOURCESearch...

Entry information

Entry nameAPH1B_HUMAN
AccessionPrimary (citable) accession number: Q8WW43
Secondary accession number(s): A8K589 expand/collapse secondary AC list , Q564N3, Q6UWQ1, Q9H0S0
Entry history
Integrated into UniProtKB/Swiss-Prot: September 26, 2003
Last sequence update: March 15, 2005
Last modified: March 19, 2014
This is version 104 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 15

Human chromosome 15: entries, gene names and cross-references to MIM