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Protein

Amyloid-beta A4 precursor protein-binding family B member 1

Gene

Apbb1

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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 transcription 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).1 Publication

GO - Molecular functioni

  • amyloid-beta binding Source: RGD
  • chromatin binding Source: Ensembl
  • histone binding Source: Ensembl
  • proline-rich region binding Source: Ensembl
  • protein complex binding Source: RGD
  • tau protein binding Source: RGD
  • transcription factor binding Source: UniProtKB

GO - Biological processi

  • apoptotic process Source: UniProtKB-KW
  • cell cycle arrest Source: UniProtKB
  • double-strand break repair Source: UniProtKB
  • histone H4 acetylation Source: UniProtKB
  • negative regulation of cell growth Source: UniProtKB
  • negative regulation of thymidylate synthase biosynthetic process Source: UniProtKB
  • negative regulation of transcription from RNA polymerase II promoter Source: Ensembl
  • positive regulation of apoptotic process Source: UniProtKB
  • positive regulation of DNA repair Source: UniProtKB
  • positive regulation of neuron projection development Source: RGD
  • positive regulation of protein secretion Source: RGD
  • positive regulation of transcription, DNA-templated Source: UniProtKB
  • positive regulation of transcription from RNA polymerase II promoter Source: RGD
  • regulation of transcription, DNA-templated Source: UniProtKB
  • response to iron ion Source: RGD
  • transcription, DNA-templated Source: UniProtKB-KW

Keywordsi

Molecular functionActivator, Chromatin regulator, Repressor
Biological processApoptosis, DNA damage, Transcription, Transcription regulation

Enzyme and pathway databases

ReactomeiR-RNO-5693565. Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks.

Names & Taxonomyi

Protein namesi
Recommended name:
Amyloid-beta A4 precursor protein-binding family B member 1
Alternative name(s):
Protein Fe65
Gene namesi
Name:Apbb1
Synonyms:Fe65
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 1

Organism-specific databases

RGDi2122. Apbb1.

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cell membrane, Cell projection, Cytoplasm, Membrane, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi655C → F: Abolishes interaction with APP and impairs the function in DNA repair. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000760511 – 711Amyloid-beta A4 precursor protein-binding family B member 1Add BLAST711

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei135PhosphoserineBy similarity1
Modified residuei518PhosphoserineBy similarity1
Modified residuei548Phosphotyrosine; by ABL1By similarity1
Modified residuei611Phosphoserine; by SGK11 Publication1

Post-translational modificationi

Phosphorylated following nuclear translocation. Phosphorylation at Tyr-547 enhances the transcription activation activity and reduces the affinity with RASD1/DEXRAS1. Phosphorylation at Ser-611 by SGK1 promotes its localization to the nucleus.1 Publication

Keywords - PTMi

Phosphoprotein

Proteomic databases

PaxDbiP46933.
PRIDEiP46933.

PTM databases

iPTMnetiP46933.
PhosphoSitePlusiP46933.

Expressioni

Tissue specificityi

Brain, not in liver, very low in other tissues. The long (neuron-specific) form is expressed only in brain.

Gene expression databases

BgeeiENSRNOG00000018020.
ExpressionAtlasiP46933. baseline and differential.

Interactioni

Subunit structurei

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 amyloid-beta precursor protein). Interacts (via the WW domain) with histone H2AX (when phosphorylated on 'Tyr-142'). Interacts with MAPK8. Interacts (via the WW domain) with proline-rich regions of APBB1IP and ENAH. Interacts with TSHZ1 and TSHZ2 (By similarity). Interacts (via PID domain 1) with KAT5/TIP60. Interacts (via PID domain 2) with RASD1/DEXRAS1; impairs the transcription activation activity. Interacts (via PID domain 1) with TSHZ3 (via homeobox domain). Interacts (via WWW domain) with NEK6. Interacts (via WWW domain) with ABL1 (By similarity).By similarity

Binary interactionsi

WithEntry#Exp.IntActNotes
H2AFXP161042EBI-15759525,EBI-494830From Homo sapiens.

GO - Molecular functioni

  • histone binding Source: Ensembl
  • proline-rich region binding Source: Ensembl
  • protein complex binding Source: RGD
  • tau protein binding Source: RGD
  • transcription factor binding Source: UniProtKB

Protein-protein interaction databases

BioGridi248339. 3 interactors.
DIPiDIP-682N.
ELMiP46933.
IntActiP46933. 4 interactors.
MINTiMINT-150919.
STRINGi10116.ENSRNOP00000024402.

Structurei

3D structure databases

ProteinModelPortaliP46933.
SMRiP46933.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini254 – 286WWPROSITE-ProRule annotationAdd BLAST33
Domaini365 – 533PID 1PROSITE-ProRule annotationAdd BLAST169
Domaini538 – 700PID 2PROSITE-ProRule annotationAdd BLAST163

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi148 – 188Glu-richAdd BLAST41

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiENOG410IEKA. Eukaryota.
ENOG410YEVS. LUCA.
GeneTreeiENSGT00390000000002.
HOGENOMiHOG000033983.
HOVERGENiHBG050524.
InParanoidiP46933.
KOiK04529.
OMAiSYHKHNL.
PhylomeDBiP46933.

Family and domain databases

CDDicd00201. WW. 1 hit.
Gene3Di2.30.29.30. 2 hits.
InterProiView protein in InterPro
IPR011993. PH_dom-like.
IPR006020. PTB/PI_dom.
IPR001202. WW_dom.
IPR036020. WW_dom_sf.
PfamiView protein in Pfam
PF00640. PID. 2 hits.
PF00397. WW. 1 hit.
SMARTiView protein in SMART
SM00462. PTB. 2 hits.
SM00456. WW. 1 hit.
SUPFAMiSSF50729. SSF50729. 2 hits.
SSF51045. SSF51045. 1 hit.
PROSITEiView protein in PROSITE
PS01179. PID. 2 hits.
PS01159. WW_DOMAIN_1. 1 hit.
PS50020. WW_DOMAIN_2. 1 hit.

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P46933-1) [UniParc]FASTAAdd to basket
Also known as: Long

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.

« Hide

        10         20         30         40         50
MSVPSSLSQS AINANSHGGP ALSFPFPLHA AHNQLLNAKL QATAVVPKDL
60 70 80 90 100
RSAMGEGSVP EPGPANAKWL KEGQNQLRRA ATAHRDQNRN VTLTLAEEAS
110 120 130 140 150
QEAETAPLGP KGLMHLYSEL ELSAHNAANR GLHGSALIIN TQGLGPDEGE
160 170 180 190 200
EKAAGEVEEE DEDEEEEDEE EEDLSSPQGL PEPLENVEVP SGPQVLTDGP
210 220 230 240 250
REHSKSASLL FGMRNSAASD EDSSWATLSQ GSPSYGSPED TDSFWNPNAF
260 270 280 290 300
ETDSDLPAGW MRVQDTSGTY YWHIPTGTTQ WEPPGRASPS QGNSPQEESQ
310 320 330 340 350
LTWTGFAHQE GFEEGEFWKD EPSEEAPMEL GLKDPEEGTL PFSAQSLSPE
360 370 380 390 400
PVPQEEENLP QRNANPGIKC FAVRSLGWVE MTEEELAPGR SSVAVNNCIR
410 420 430 440 450
QLSYHKNNLH DPMSGGWGEG KDLLLQLEDE TLKLVEPQNQ TLLHAQPIVS
460 470 480 490 500
IRVWGVGRDS GRERDFAYVA RDKLTQMLKC HVFRCEAPAK NIATSLHEIC
510 520 530 540 550
SKIMSERRNA RCLVNGLSLD HSKLVDVPFQ VEFPAPKNEL VQKFQVYYLG
560 570 580 590 600
NVPVAKPVGV DVINGALESV LSSSSREQWT PSHVSVAPAT LTILHQQTEA
610 620 630 640 650
VLGECRVRFL SFLAVGRDVH TFAFIMAAGP ASFCCHMFWC EPNAASLSEA
660 670 680 690 700
VQAACMLRYQ KCLDARSQTS TSCLPAPPAE SVARRVGWTV RRGVQSLWGS
710
LKPKRLGSQT P
Length:711
Mass (Da):77,656
Last modified:September 27, 2004 - v3
Checksum:iA6C9820F5D2BD7BE
GO
Isoform 2 (identifier: P46933-2) [UniParc]FASTAAdd to basket
Also known as: Short

The sequence of this isoform differs from the canonical sequence as follows:
     463-464: Missing.

Show »
Length:709
Mass (Da):77,371
Checksum:i5658754E0D449B6E
GO

Sequence cautioni

P46933: The sequence CAA42999 differs from that shown. Reason: Frameshift at position 127.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti137L → K (PubMed:1923810).Curated1
Sequence conflicti150 – 154EEKAA → GRRQR in CAA42999 (PubMed:1923810).Curated5
Sequence conflicti172E → EEEDEEEE in CAA42999 (PubMed:1923810).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_006798463 – 464Missing in isoform 2. 1 Publication2

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF333983 mRNA. Translation: AAK20835.1.
X60469 mRNA. Translation: CAA42999.1. Frameshift.
X60468 mRNA. Translation: CAA42998.1.
PIRiS22571.
S50818.
RefSeqiNP_536726.1. NM_080478.1. [P46933-1]
XP_006229998.1. XM_006229936.3. [P46933-1]
UniGeneiRn.19953.

Genome annotation databases

EnsembliENSRNOT00000024402; ENSRNOP00000024402; ENSRNOG00000018020. [P46933-2]
GeneIDi29722.
KEGGirno:29722.
UCSCiRGD:2122. rat. [P46933-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiAPBB1_RAT
AccessioniPrimary (citable) accession number: P46933
Secondary accession number(s): Q99MK3
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 1, 1995
Last sequence update: September 27, 2004
Last modified: October 25, 2017
This is version 131 of the entry and version 3 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome