Q9QXJ1 (APBB1_MOUSE) Reviewed, UniProtKB/Swiss-Prot

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 › Mus

Protein attributes

Sequence length	710 AA.
Sequence status	Complete.
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 KAT5/TIP60, probably explains its trancription activation activity. Function in association with TSHZ3, SET and HDAC factors as a transcriptional repressor, that inhibits the expression of CASP4. Associates with chromatin in a region surrounding the CASP4 transcriptional start site(s). Ref.6
Subunit structure	Interacts with SET. Found in a trimeric complex with HDAC1 and TSHZ3; the interaction between HDAC1 and APBB1 is mediated by TSHZ3 By similarity. 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 KAT5/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. Interacts (via PID domain 1) with TSHZ3 (via homeobox domain). Interacts with TSHZ1 and TSHZ2. Interacts (via WWW domain) with NEK6. Interacts (via WWW domain) with ABL1 By similarity. Ref.5 Ref.7
Subcellular location	Cell membrane. Cytoplasm. Nucleus. Cell projection › growth cone By similarity. Nucleus speckle By similarity. Note: Colocalizes with TSHZ3 in the nucleus and in axonal growth cone. Co-localizes with NEK6 at the nuclear speckles By similarity. 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. Phosphorylation at Ser-610 by SGK1 promotes its localization to the nucleus By similarity. Ref.6
Post-translational modification	Phosphorylated following nuclear translocation. Phosphorylation at Tyr-546 enhances the transcription activation activity and reduces the affinity with RASD1/DEXRAS1. Phosphorylation at Ser-610 by SGK1 promotes its localization to the nucleus By similarity. Ref.6
Disruption phenotype	No phenotype in normal conditions. Displays an increased sensitivity to genotoxic stress and exposur to DNA damaging agents. Ref.6
Sequence similarities	Contains 2 PID domains. Contains 1 WW domain.

Ontologies

Keywords
Biological process	Apoptosis DNA damage Transcription Transcription regulation
Cellular component	Cell membrane Cell projection Cytoplasm Membrane Nucleus
Coding sequence diversity	Alternative splicing
Domain	Repeat
Molecular function	Activator Chromatin regulator Repressor
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	actin filament-based movement Non-traceable author statement. Source: UniProtKB apoptotic process Inferred from electronic annotation. Source: UniProtKB-KW axon guidance Inferred from genetic interaction. Source: MGI cell cycle arrest Inferred from direct assay. Source: UniProtKB double-strand break repair Inferred from mutant phenotype Ref.6. 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 neuron differentiation Inferred from mutant phenotype. Source: MGI 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 Inferred from mutant phenotype Ref.6. Source: UniProtKB positive regulation of apoptotic process Inferred from sequence or structural similarity. Source: UniProtKB protein stabilization Non-traceable author statement. Source: UniProtKB transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW visual learning Inferred from mutant phenotype. Source: MGI
Cellular component	growth cone Inferred from sequence or structural similarity. Source: UniProtKB lamellipodium Inferred from sequence or structural similarity. Source: UniProtKB nuclear speck Inferred from electronic annotation. Source: UniProtKB-SubCell plasma membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	beta-amyloid binding Inferred from physical interaction Ref.6. 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	2	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	547	1	Phosphotyrosine; by ABL1 By similarity
	Modified residue	610	1	Phosphoserine; by SGK1 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.5
	Mutagenesis	283	1	P → A: Abolishes ligand binding; when associated with F-280. Ref.5
	Sequence conflict	92	1	T → A in AAF20141. Ref.1
	Sequence conflict	313	1	E → D in AAF20141. Ref.1
	Sequence conflict	461 – 462	2	SN → RE in BAC39033. Ref.2
	Sequence conflict	461 – 462	2	SN → RE in BAE37645. Ref.2
	Sequence conflict	630	1	A → S in BAC39033. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified July 27, 2011. Version 3. Checksum: 9CFD571C50584979	FASTA	710	77,384
	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 SNRDFAYVAR 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 [UniParc]. Checksum: 234B7C6D9383B148	FASTA	708	77,114
	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 SDFAYVARDK 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]	"Lineage-specific biology revealed by a finished genome assembly of the mouse." Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S. , Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R., Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K., Eichler E.E., Ponting C.P. PLoS Biol. 7:E1000112-E1000112(2009) [PubMed: 19468303] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: C57BL/6.
[4]	"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.
[5]	"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.
[6]	"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.
[7]	"FE65 binds Teashirt, inhibiting expression of the primate-specific caspase-4." Kajiwara Y., Akram A., Katsel P., Haroutunian V., Schmeidler J., Beecham G., Haines J.L., Pericak-Vance M.A., Buxbaum J.D. PLoS ONE 4:E5071-E5071(2009) [PubMed: 19343227] [Abstract] Cited for: INTERACTION WITH TSHZ1; TSHZ2 AND TSHZ3.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF206720 mRNA. Translation: AAF20141.1. AK030748 mRNA. Translation: BAC27116.1. AK083830 mRNA. Translation: BAC39033.1. AK164140 mRNA. Translation: BAE37645.1. AC125227 Genomic DNA. No translation available. L77865 mRNA. Translation: AAB51603.1.
IPI	IPI00387261. IPI00626699.
RefSeq	NP_033815.1. NM_009685.2.
UniGene	Mm.38469.
3D structure databases
ProteinModelPortal	Q9QXJ1.
SMR	Q9QXJ1. Positions 241-290, 366-666.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9QXJ1. 1 interaction.
MINT	MINT-142893.
STRING	Q9QXJ1.
PTM databases
PhosphoSite	Q9QXJ1.
Proteomic databases
PRIDE	Q9QXJ1.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000081165; ENSMUSP00000079932; ENSMUSG00000037032.
GeneID	11785.
KEGG	mmu:11785.
UCSC	uc009iyi.1. mouse.
Organism-specific databases
CTD	322.
MGI	MGI:107765. Apbb1.
Phylogenomic databases
eggNOG	roNOG12845.
GeneTree	ENSGT00390000000002.
HOGENOM	HBG443527.
HOVERGEN	HBG050524.
InParanoid	Q9QXJ1.
OrthoDB	EOG4X3H12.
Gene expression databases
ArrayExpress	Q9QXJ1.
Bgee	Q9QXJ1.
Genevestigator	Q9QXJ1.
GermOnline	ENSMUSG00000037032. Mus musculus.
Family and domain databases
InterPro	IPR011993. PH_type. IPR006020. PTyr_interaction_dom. IPR001202. WW_Rsp5_WWP. [Graphical view]
Gene3D	G3DSA:2.20.70.10. G3DSA:2.20.70.10. 1 hit. G3DSA:2.30.29.30. PH_type. 2 hits.
KO	K04529.
Pfam	PF00640. PID. 2 hits. PF00397. WW. 1 hit. [Graphical view]
SMART	SM00462. PTB. 2 hits. SM00456. WW. 1 hit. [Graphical view]
SUPFAM	SSF51045. WW_Rsp5_WWP. 1 hit.
PROSITE	PS01179. PID. 2 hits. PS01159. WW_DOMAIN_1. 1 hit. PS50020. WW_DOMAIN_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	279601.
SOURCE	Search...

Entry information

Entry name

APBB1_MOUSE

Accession

Primary (citable) accession number: Q9QXJ1
Secondary accession number(s): E9QNW5 , O08642, Q3TPU0, Q8BNF4, Q8BSR9

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 11, 2001
Last sequence update:	July 27, 2011
Last modified:	January 25, 2012
This is version 89 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program