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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 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).1 Publication

GO - Molecular functioni

  • beta-amyloid binding Source: UniProtKB
  • chromatin 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
  • 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
Complete GO annotation...

Keywords - Molecular functioni

Activator, Chromatin regulator, Repressor

Keywords - Biological processi

Apoptosis, 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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 1

Organism-specific databases

RGDi2122. Apbb1.

Subcellular locationi

  • Cell membrane
  • Cytoplasm
  • Nucleus
  • Cell projectiongrowth cone
  • Nucleus speckle By similarity

  • 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. Colocalizes with TSHZ3 in axonal growth cone. Colocalizes with NEK6 at the nuclear speckles (By similarity). Phosphorylation at Ser-611 by SGK1 promotes its localization to the nucleus.By similarity

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
  • dendritic spine Source: RGD
  • growth cone Source: UniProtKB
  • growth cone filopodium Source: RGD
  • growth cone lamellipodium Source: RGD
  • lamellipodium Source: UniProtKB
  • main axon Source: RGD
  • neuronal cell body Source: RGD
  • nuclear speck Source: UniProtKB-SubCell
  • nucleus Source: UniProtKB
  • perinuclear region of cytoplasm Source: RGD
  • postsynaptic membrane Source: RGD
  • presynaptic membrane Source: RGD
  • protein complex Source: RGD
  • synapse Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cell projection, Cytoplasm, Membrane, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi655 – 6551C → F: Abolishes interaction with APP and impairs the function in DNA repair. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 711711Amyloid beta A4 precursor protein-binding family B member 1PRO_0000076051Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei135 – 1351PhosphoserineBy similarity
Modified residuei518 – 5181PhosphoserineBy similarity
Modified residuei548 – 5481Phosphotyrosine; by ABL1By similarity
Modified residuei611 – 6111Phosphoserine; by SGK11 Publication

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.
PhosphoSiteiP46933.

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

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 beta-amyloid 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 trancription 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

GO - Molecular functioni

  • protein complex binding Source: RGD
  • tau protein binding Source: RGD
  • transcription factor binding Source: UniProtKB

Protein-protein interaction databases

BioGridi248339. 2 interactions.
DIPiDIP-682N.
IntActiP46933. 3 interactions.
MINTiMINT-150919.
STRINGi10116.ENSRNOP00000024402.

Structurei

3D structure databases

ProteinModelPortaliP46933.
SMRiP46933. Positions 242-291, 367-506, 534-655.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini254 – 28633WWPROSITE-ProRule annotationAdd
BLAST
Domaini365 – 533169PID 1PROSITE-ProRule annotationAdd
BLAST
Domaini538 – 700163PID 2PROSITE-ProRule annotationAdd
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi148 – 18841Glu-richAdd
BLAST

Sequence similaritiesi

Contains 2 PID domains.PROSITE-ProRule annotation
Contains 1 WW domain.PROSITE-ProRule annotation

Keywords - Domaini

Repeat

Phylogenomic databases

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

Family and domain databases

Gene3Di2.30.29.30. 2 hits.
InterProiIPR011993. PH_dom-like.
IPR006020. PTB/PI_dom.
IPR001202. WW_dom.
[Graphical view]
PfamiPF00640. PID. 2 hits.
[Graphical view]
SMARTiSM00462. PTB. 2 hits.
SM00456. WW. 1 hit.
[Graphical view]
SUPFAMiSSF50729. SSF50729. 2 hits.
SSF51045. SSF51045. 1 hit.
PROSITEiPS01179. PID. 2 hits.
PS01159. WW_DOMAIN_1. 1 hit.
PS50020. WW_DOMAIN_2. 1 hit.
[Graphical view]

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

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

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti137 – 1371L → K (PubMed:1923810).Curated
Sequence conflicti150 – 1545EEKAA → GRRQR in CAA42999 (PubMed:1923810).Curated
Sequence conflicti172 – 1721E → EEEDEEEE in CAA42999 (PubMed:1923810).Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei463 – 4642Missing in isoform 2. 1 PublicationVSP_006798

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_006229936.2. [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

Cross-referencesi

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_006229936.2. [P46933-1]
UniGeneiRn.19953.

3D structure databases

ProteinModelPortaliP46933.
SMRiP46933. Positions 242-291, 367-506, 534-655.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi248339. 2 interactions.
DIPiDIP-682N.
IntActiP46933. 3 interactions.
MINTiMINT-150919.
STRINGi10116.ENSRNOP00000024402.

PTM databases

iPTMnetiP46933.
PhosphoSiteiP46933.

Proteomic databases

PaxDbiP46933.
PRIDEiP46933.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi322.
RGDi2122. Apbb1.

Phylogenomic databases

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

Enzyme and pathway databases

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

Miscellaneous databases

PROiP46933.

Gene expression databases

ExpressionAtlasiP46933. baseline and differential.

Family and domain databases

Gene3Di2.30.29.30. 2 hits.
InterProiIPR011993. PH_dom-like.
IPR006020. PTB/PI_dom.
IPR001202. WW_dom.
[Graphical view]
PfamiPF00640. PID. 2 hits.
[Graphical view]
SMARTiSM00462. PTB. 2 hits.
SM00456. WW. 1 hit.
[Graphical view]
SUPFAMiSSF50729. SSF50729. 2 hits.
SSF51045. SSF51045. 1 hit.
PROSITEiPS01179. PID. 2 hits.
PS01159. WW_DOMAIN_1. 1 hit.
PS50020. WW_DOMAIN_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiAPBB1_RAT
AccessioniPrimary (citable) accession number: P46933
Secondary accession number(s): Q99MK3
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1995
Last sequence update: September 27, 2004
Last modified: September 7, 2016
This is version 120 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.