Reviewed, UniProtKB/Swiss-Prot Q9QXJ1 (APBB1_MOUSE)

Names and origin

Protein names

Recommended name:
    Amyloid beta A4 precursor protein-binding family B member 1
Alternative name(s):
    Protein Fe65

Gene names

Name:	Apbb1
Synonyms:	Fe65

Organism

Mus musculus (Mouse)

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus

Protein attributes

Sequence length	710 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Adapter protein that forms a transcriptionally active complex with the gamma-secretase-derived amyloid precursor protein (APP) intracellular domain. Plays a central role in the response to DNA damage by translocating to the nucleus and inducing apoptosis. May act by specifically recognizing and binding histone H2AX phosphorylated on 'Tyr-142' (H2AXY142ph) at double-strand breaks (DSBs), recruiting other pro-apoptosis factors such as MAPK8/JNK1. Required for histone H4 acetylation at double-strand breaks (DSBs). Its ability to specifically bind modified histones and chromatin modifying enzymes such as HTATIP/TIP60, probably explains its trancription activation activity.
Subunit structure	Component of a complex, at least composed of APBB1, RASD1/DEXRAS1 and APP. Interacts (via PID domain 2) with APP (with the intracellular domain of the beta-amyloid precursor protein). Interacts (via PID domain 2) with RASD1/DEXRAS1; impairs the trancription activation activity. Interacts (via PID domain 1) with HTATIP/TIP60. Interacts (via the WW domain) with histone H2AX (when phosphorylated on 'Tyr-142). Interacts with MAPK8 By similarity. Interacts (via the WW domain) with proline-rich regions of APBB1IP and ENAH.
Subcellular location	Cell membrane. Cytoplasm. Nucleus. Note: In normal conditions, it mainly localizes to the cytoplasm, while a small fraction is tethered to the cell membrane via its interaction with APP. Following exposure to DNA damaging agents, it is released from cell membrane and translocates to the nucleus. Nuclear translocation is under the regulation of APP.
Post-translational modification	Phosphorylated following nuclear translocation. Phosphorylation at Tyr-546 enhances the transcription activation activity and reduces the affinity with RASD1/DEXRAS1 By similarity.
Disruption phenotype	No phenotype in normal conditions. Displays an increased sensitivity to genotoxic stress and exposur to DNA damaging agents.
Sequence similarities	Contains 2 PID domains. Contains 1 WW domain.

Ontologies

Keywords
Biological process	Apoptosis DNA damage Transcription Transcription regulation
Cellular component	Cell membrane Cytoplasm Membrane Nucleus
Coding sequence diversity	Alternative splicing
Domain	Repeat
Molecular function	Chromatin regulator
PTM	Phosphoprotein
Gene Ontology (GO)
Biological process	actin filament-based movement Non-traceable author statement. Source: UniProtKB axon guidance Inferred from genetic interaction. Source: MGI cell cycle arrest Inferred from direct assay. Source: UniProtKB double-strand break repair Ref.5 Inferred from mutant phenotype. Source: UniProtKB extracellular matrix organization Inferred from genetic interaction. Source: MGI histone H4 acetylation Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of S phase of mitotic cell cycle Inferred from direct assay. Source: UniProtKB negative regulation of cell growth Inferred from direct assay. Source: UniProtKB negative regulation of thymidylate synthase biosynthetic process Inferred from direct assay. Source: UniProtKB neuron migration Inferred from genetic interaction. Source: MGI positive regulation of DNA repair Ref.5 Inferred from mutant phenotype. Source: UniProtKB positive regulation of apoptosis Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of transcription from RNA polymerase II promoter Inferred from genetic interaction. Source: MGI protein stabilization Non-traceable author statement. Source: UniProtKB visual learning Inferred from mutant phenotype. Source: MGI
Cellular component	cytoplasm Ref.5 Inferred from direct assay. Source: UniProtKB growth cone Inferred from sequence or structural similarity. Source: UniProtKB lamellipodium Inferred from sequence or structural similarity. Source: UniProtKB nucleus Ref.5 Inferred from direct assay. Source: UniProtKB synapse Inferred from sequence or structural similarity. Source: UniProtKB
Molecular function	beta-amyloid binding Ref.3 Ref.5 Inferred from physical interaction. Source: UniProtKB histone acetyltransferase binding Non-traceable author statement. Source: UniProtKB transcription factor binding Inferred from direct assay. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
App	P12023	1	EBI-81338,EBI-78814

Alternative products

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

Isoform 1 (identifier: Q9QXJ1-1)

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: Q9QXJ1-2)

The sequence of this isoform differs from the canonical sequence as follows:
     462-463: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 710	710	Amyloid beta A4 precursor protein-binding family B member 1		PRO_0000076050
Regions
	Domain	253 – 285	33	WW
	Domain	370 – 509	140	PID 1
	Domain	542 – 699	158	PID 2
	Compositional bias	158 – 171	14	Glu-rich
Amino acid modifications
	Modified residue	546	1	Phosphotyrosine By similarity
Natural variations
	Alternative sequence	462 – 463	2	Missing in isoform 2.		VSP_011659
Experimental info
	Mutagenesis	280	1	W → F: Abolishes ligand binding; when associated with A-283. Ref.4
	Mutagenesis	283	1	P → A: Abolishes ligand binding; when associated with F-280. Ref.4
	Sequence conflict	92	1	T → A in AAF20141. Ref.1
	Sequence conflict	313	1	E → D in AAF20141. Ref.1
	Sequence conflict	630	1	A → S in BAC39033. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified September 27, 2004. Version 2. Checksum: 9E1A121C5408F979	FASTA	710	77,468
	10 20 30 40 50 60 MSVPSSLSQS AINANSHGGP ALSFPLPLHA AHNQLLNAKL QATAVVPKDL RSAMGEGSVP 70 80 90 100 110 120 EPGPANAKWL KEGQNQLRRA ATAHRDQNRN VTLTLAEEAS QEAETAPLGP KGLMHLYSEL 130 140 150 160 170 180 ELSAHNAANR GLHGSALIIN TQEQGPDEGE EKAAGEAEED DEDEEEEEEE EDLSSPPGLP 190 200 210 220 230 240 EPLENVEVPS GPQALTDGPR EHSKSASLLF GMRNSAASDE DSSWATLSQG SPSYGSPEDT 250 260 270 280 290 300 DSFWNPNAFE TDSDLPAGWM RVQDTSGTYY WHIPTGTTQW EPPGRASPSQ GSSPQEESQL 310 320 330 340 350 360 TWTGFAHQEG FEEGEFWKDE PSEEAPMELG LKDPEEATLS FPAQSLSPEP VPQEEEKLSQ 370 380 390 400 410 420 RNANPGIKCF AVRSLGWVEM TEEELAPGRS SVAVNNCIRQ LSYHKNNLHD PMAGGWGEGK 430 440 450 460 470 480 DLLLQLEDET LKLVEPQNQT LLHAQPIVSI RVWGVGRDSG RERDFAYVAR DKLTQMLKCH 490 500 510 520 530 540 VFRCEAPAKN IATSLHEICS KIMSERRNAR CLVNGLSLDH SKLVDVPFQV EFPAPKNELV 550 560 570 580 590 600 QKFQVYYLGN VPVAKPVGVD VINGALESVL SSSSREQWTP SHVSVAPATL TILHQQTEAV 610 620 630 640 650 660 LGECRVRFLS FLAVGRDVHT FAFIMAAGPA SFCCHMFWCE PNAASLSEAV QAACMLRYQK 670 680 690 700 710 CLDARSQTST SCLPAPPAES VARRVGWTVR RGVQSLWGSL KPKRLGSQTP
	Isoform 2. Checksum: 664B7C6D2383B148	FASTA	708	77,183
	10 20 30 40 50 60 MSVPSSLSQS AINANSHGGP ALSFPLPLHA AHNQLLNAKL QATAVVPKDL RSAMGEGSVP 70 80 90 100 110 120 EPGPANAKWL KEGQNQLRRA ATAHRDQNRN VTLTLAEEAS QEAETAPLGP KGLMHLYSEL 130 140 150 160 170 180 ELSAHNAANR GLHGSALIIN TQEQGPDEGE EKAAGEAEED DEDEEEEEEE EDLSSPPGLP 190 200 210 220 230 240 EPLENVEVPS GPQALTDGPR EHSKSASLLF GMRNSAASDE DSSWATLSQG SPSYGSPEDT 250 260 270 280 290 300 DSFWNPNAFE TDSDLPAGWM RVQDTSGTYY WHIPTGTTQW EPPGRASPSQ GSSPQEESQL 310 320 330 340 350 360 TWTGFAHQEG FEEGEFWKDE PSEEAPMELG LKDPEEATLS FPAQSLSPEP VPQEEEKLSQ 370 380 390 400 410 420 RNANPGIKCF AVRSLGWVEM TEEELAPGRS SVAVNNCIRQ LSYHKNNLHD PMAGGWGEGK 430 440 450 460 470 480 DLLLQLEDET LKLVEPQNQT LLHAQPIVSI RVWGVGRDSG RDFAYVARDK LTQMLKCHVF 490 500 510 520 530 540 RCEAPAKNIA TSLHEICSKI MSERRNARCL VNGLSLDHSK LVDVPFQVEF PAPKNELVQK 550 560 570 580 590 600 FQVYYLGNVP VAKPVGVDVI NGALESVLSS SSREQWTPSH VSVAPATLTI LHQQTEAVLG 610 620 630 640 650 660 ECRVRFLSFL AVGRDVHTFA FIMAAGPASF CCHMFWCEPN AASLSEAVQA ACMLRYQKCL 670 680 690 700 DARSQTSTSC LPAPPAESVA RRVGWTVRRG VQSLWGSLKP KRLGSQTP

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	Liakicheva A.V., Ivanova N.B., Belyavsky A.V. Submitted (NOV-1999) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
[2]	"The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y. Science 309:1559-1563(2005) [PubMed: 16141072] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). Strain: C57BL/6J. Tissue: Hippocampus and Spinal ganglion.
[3]	"cDNA cloning and chromosome mapping of the human Fe65 gene: interaction of the conserved cytoplasmic domains of the human beta-amyloid precursor protein and its homologues with the mouse Fe65 protein." Bressler S.L., Gray M.D., Sopher B.L., Hu Q., Hearn M.G., Pham D.G., Dinulos M.B., Fukuchi K., Sisodia S.S., Miller M.A., Disteche C.M., Martin G.M. Hum. Mol. Genet. 5:1589-1598(1996) [PubMed: 8894693] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 498-674. Tissue: Embryo.
[4]	"The WW domain of neural protein FE65 interacts with proline-rich motifs in Mena, the mammalian homolog of Drosophila enabled." Ermekova K.S., Zambrano N., Linn H., Minopoli G., Gertler F., Russo T., Sudol M. J. Biol. Chem. 272:32869-32877(1997) [PubMed: 9407065] [Abstract] Cited for: INTERACTION WITH APBB1IP AND ENAH, MUTAGENESIS OF TRP-280 AND PRO-283.
[5]	"Essential roles for Fe65, Alzheimer amyloid precursor-binding protein, in the cellular response to DNA damage." Minopoli G., Stante M., Napolitano F., Telese F., Aloia L., De Felice M., Di Lauro R., Pacelli R., Brunetti A., Zambrano N., Russo T. J. Biol. Chem. 282:831-835(2007) [PubMed: 17121854] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, PHOSPHORYLATION, DISRUPTION PHENOTYPE.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	AF206720 mRNA. Translation: AAF20141.1. AK030748 mRNA. Translation: BAC27116.1. AK083830 mRNA. Translation: BAC39033.1. AK164140 mRNA. Translation: BAE37645.1. L77865 mRNA. Translation: AAB51603.1.
IPI	IPI00387261. IPI00626699.
RefSeq	NP_033815.1.
UniGene	Mm.38469
3D structure databases
SMR	Q9QXJ1. Positions 241-290.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9QXJ1. 1 interaction.
PTM databases
PhosphoSite	Q9QXJ1.
Genome annotation databases
Ensembl	ENSMUSG00000037032. Mus musculus. [Contig view]
GeneID	11785.
KEGG	mmu:11785.
Organism-specific databases
MGI	MGI:107765. Apbb1.
Phylogenomic databases
HOGENOM	Q9QXJ1.
HOVERGEN	Q9QXJ1.
Gene expression databases
ArrayExpress	Q9QXJ1.
Bgee	Q9QXJ1.
GermOnline	ENSMUSG00000037032. Mus musculus.
Family and domain databases
InterPro	IPR011993. PH_type. IPR006020. PTB_PID. IPR001202. WW_Rsp5_WWP. [Graphical view]
Gene3D	G3DSA:2.30.29.30. PH_type. 2 hits.
Pfam	PF00640. PID. 2 hits. PF00397. WW. 1 hit. [Graphical view]
SMART	SM00462. PTB. 2 hits. SM00456. WW. 1 hit. [Graphical view]
PROSITE	PS01179. PID. 2 hits. PS01159. WW_DOMAIN_1. 1 hit. PS50020. WW_DOMAIN_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	279601.
SOURCE	Search...

Entry information

Entry name

APBB1_MOUSE

Accession

Primary (citable) accession number: Q9QXJ1
Secondary accession number(s): O08642 , Q3TPU0, Q8BNF4, Q8BSR9

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 11, 2001
Last sequence update:	September 27, 2004
Last modified:	June 16, 2009
This is version 62 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)