APBB1_RAT
ID APBB1_RAT Reviewed; 711 AA.
AC P46933; Q99MK3;
DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
DT 27-SEP-2004, sequence version 3.
DT 03-AUG-2022, entry version 160.
DE RecName: Full=Amyloid beta precursor protein binding family B member 1 {ECO:0000250|UniProtKB:O00213};
DE AltName: Full=Amyloid-beta A4 precursor protein-binding family B member 1 {ECO:0000312|RGD:2122};
DE AltName: Full=Protein Fe65 {ECO:0000250|UniProtKB:Q9QXJ1};
GN Name=Apbb1 {ECO:0000312|RGD:2122};
GN Synonyms=Fe65 {ECO:0000303|PubMed:18304449},
GN Rir {ECO:0000250|UniProtKB:Q9QXJ1};
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RA Cao X., Suedhof T.C.;
RT "Nuclear signaling of APP cytoplasmic tail.";
RL Submitted (JAN-2001) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 121-711 (ISOFORM 2).
RC TISSUE=Brain;
RX PubMed=1923810; DOI=10.1093/nar/19.19.5269;
RA Duilio A., Zambrano N., Mogavero A.R., Ammendola R., Cimino F., Russo T.;
RT "A rat brain mRNA encoding a transcriptional activator homologous to the
RT DNA binding domain of retroviral integrases.";
RL Nucleic Acids Res. 19:5269-5274(1991).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 243-530, AND TISSUE SPECIFICITY.
RC TISSUE=Brain;
RX PubMed=7800475; DOI=10.1093/nar/22.23.4876;
RA Faraonio R., Minopoli G., Porcellini A., Costanzo F., Cimino F., Russo T.;
RT "The DNA sequence encompassing the transcription start site of a TATA-less
RT promoter contains enough information to drive neuron-specific
RT transcription.";
RL Nucleic Acids Res. 22:4876-4883(1994).
RN [4]
RP PHOSPHORYLATION AT SER-611, AND SUBCELLULAR LOCATION.
RX PubMed=18304449; DOI=10.5483/bmbrep.2008.41.1.041;
RA Lee E.J., Chun J., Hyun S., Ahn H.R., Jeong J.M., Hong S.K., Hong J.T.,
RA Chang I.K., Jeon H.Y., Han Y.S., Auh C.K., Park J.I., Kang S.S.;
RT "Regulation Fe65 localization to the nucleus by SGK1 phosphorylation of its
RT Ser566 residue.";
RL BMB Rep. 41:41-47(2008).
RN [5]
RP INTERACTION WITH TSHZ3, AND SUBCELLULAR LOCATION.
RX PubMed=19343227; DOI=10.1371/journal.pone.0005071;
RA Kajiwara Y., Akram A., Katsel P., Haroutunian V., Schmeidler J.,
RA Beecham G., Haines J.L., Pericak-Vance M.A., Buxbaum J.D.;
RT "FE65 binds Teashirt, inhibiting expression of the primate-specific
RT caspase-4.";
RL PLoS ONE 4:E5071-E5071(2009).
RN [6]
RP FUNCTION, INTERACTION WITH KAT5, AND MUTAGENESIS OF CYS-655.
RX PubMed=19282473; DOI=10.1073/pnas.0810869106;
RA Stante M., Minopoli G., Passaro F., Raia M., Vecchio L.D., Russo T.;
RT "Fe65 is required for Tip60-directed histone H4 acetylation at DNA strand
RT breaks.";
RL Proc. Natl. Acad. Sci. U.S.A. 106:5093-5098(2009).
CC -!- FUNCTION: Transcription coregulator that can have both coactivator and
CC corepressor functions. Adapter protein that forms a transcriptionally
CC active complex with the gamma-secretase-derived amyloid precursor
CC protein (APP) intracellular domain. Plays a central role in the
CC response to DNA damage by translocating to the nucleus and inducing
CC apoptosis. May act by specifically recognizing and binding histone H2AX
CC phosphorylated on 'Tyr-142' (H2AXY142ph) at double-strand breaks
CC (DSBs), recruiting other pro-apoptosis factors such as MAPK8/JNK1.
CC Required for histone H4 acetylation at double-strand breaks (DSBs) (By
CC similarity). Its ability to specifically bind modified histones and
CC chromatin modifying enzymes such as KAT5/TIP60, probably explains its
CC transcription activation activity (PubMed:19282473). Functions in
CC association with TSHZ3, SET and HDAC factors as a transcriptional
CC repressor, that inhibits the expression of CASP4. Associates with
CC chromatin in a region surrounding the CASP4 transcriptional start
CC site(s) (By similarity). Involved in hippocampal neurite branching and
CC neuromuscular junction formation, as a result plays a role in spatial
CC memory functioning. Plays a role in the maintenance of lens
CC transparency. May play a role in muscle cell strength (By similarity).
CC {ECO:0000250|UniProtKB:O00213, ECO:0000250|UniProtKB:Q9QXJ1,
CC ECO:0000269|PubMed:19282473}.
CC -!- SUBUNIT: Component of a complex, at least composed of APBB1,
CC RASD1/DEXRAS1 and APP (By similarity). Interacts (via PID domain 2)
CC with APP (with the intracellular domain of the amyloid-beta precursor
CC protein) (By similarity). Interacts (via PID domain 2) with
CC RASD1/DEXRAS1; impairs the transcription activation activity (By
CC similarity). Interacts (via PID domain 1) with KAT5/TIP60
CC (PubMed:19282473). Interacts (via the WW domain) with the proline-rich
CC region of APBB1IP (By similarity). Interacts with TSHZ1 and TSHZ2 (By
CC similarity). Interacts (via the WW domain) with histone H2AX (when
CC phosphorylated on 'Tyr-142') and the proline-rich region of ENAH (By
CC similarity). Interacts with MAPK8 (By similarity). Interacts (via PID
CC domain 1) with TSHZ3 (via homeobox domain) (PubMed:19343227). Interacts
CC with SET (By similarity). Found in a trimeric complex with HDAC1 and
CC TSHZ3; the interaction between HDAC1 and APBB1 is mediated by TSHZ3 (By
CC similarity). Interacts (via WWW domain) with NEK6 (By similarity).
CC Interacts (via WWW domain) with ABL1. Interacts with RNF157 (By
CC similarity). {ECO:0000250|UniProtKB:O00213,
CC ECO:0000250|UniProtKB:Q9QXJ1, ECO:0000269|PubMed:19282473,
CC ECO:0000269|PubMed:19343227}.
CC -!- INTERACTION:
CC P46933-1; P16104: H2AX; Xeno; NbExp=2; IntAct=EBI-15759525, EBI-494830;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:O00213}.
CC Cytoplasm {ECO:0000250|UniProtKB:O00213}. Nucleus
CC {ECO:0000269|PubMed:18304449}. Cell projection, growth cone
CC {ECO:0000269|PubMed:19343227}. Nucleus speckle
CC {ECO:0000250|UniProtKB:O00213}. Note=Colocalizes with TSHZ3 in axonal
CC growth cone (PubMed:19343227). Colocalizes with TSHZ3 in the nucleus.
CC In normal conditions, it mainly localizes to the cytoplasm, while a
CC small fraction is tethered to the cell membrane via its interaction
CC with APP. Following exposure to DNA damaging agents, it is released
CC from cell membrane and translocates to the nucleus. Nuclear
CC translocation is under the regulation of APP. Colocalizes with NEK6 at
CC the nuclear speckles (By similarity). Phosphorylation at Ser-610 by
CC SGK1 promotes its localization to the nucleus (PubMed:18304449).
CC {ECO:0000250|UniProtKB:O00213, ECO:0000269|PubMed:18304449,
CC ECO:0000269|PubMed:19343227}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=Long {ECO:0000303|PubMed:7800475};
CC IsoId=P46933-1; Sequence=Displayed;
CC Name=2; Synonyms=Short {ECO:0000303|PubMed:7800475};
CC IsoId=P46933-2; Sequence=VSP_006798;
CC -!- TISSUE SPECIFICITY: Brain, not in liver, very low in other tissues. The
CC long (neuron-specific) form is expressed only in brain.
CC {ECO:0000269|PubMed:7800475}.
CC -!- PTM: Polyubiquitination by RNF157 leads to degradation by the
CC proteasome. {ECO:0000250|UniProtKB:O00213}.
CC -!- PTM: Phosphorylation at Ser-611 by SGK1 promotes its localization to
CC the nucleus (PubMed:18304449). Phosphorylated following nuclear
CC translocation. Phosphorylation at Tyr-547 by ABL1 enhances
CC transcriptional activation activity and reduces the affinity for
CC RASD1/DEXRAS1 (By similarity). {ECO:0000250|UniProtKB:O00213,
CC ECO:0000269|PubMed:18304449}.
CC -!- PTM: Acetylation at Lys-205 and Lys-702 by KAT5 promotes its
CC transcription activator activity. {ECO:0000250|UniProtKB:O00213}.
CC -!- SEQUENCE CAUTION:
CC Sequence=CAA42999.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; AF333983; AAK20835.1; -; mRNA.
DR EMBL; X60469; CAA42999.1; ALT_FRAME; mRNA.
DR EMBL; X60468; CAA42998.1; -; mRNA.
DR PIR; S22571; S22571.
DR PIR; S50818; S50818.
DR RefSeq; NP_536726.1; NM_080478.1. [P46933-1]
DR RefSeq; XP_006229998.1; XM_006229936.3. [P46933-1]
DR AlphaFoldDB; P46933; -.
DR BMRB; P46933; -.
DR SMR; P46933; -.
DR BioGRID; 248339; 4.
DR DIP; DIP-682N; -.
DR ELM; P46933; -.
DR IntAct; P46933; 5.
DR MINT; P46933; -.
DR STRING; 10116.ENSRNOP00000024402; -.
DR iPTMnet; P46933; -.
DR PhosphoSitePlus; P46933; -.
DR PaxDb; P46933; -.
DR PRIDE; P46933; -.
DR GeneID; 29722; -.
DR KEGG; rno:29722; -.
DR UCSC; RGD:2122; rat. [P46933-1]
DR CTD; 322; -.
DR RGD; 2122; Apbb1.
DR VEuPathDB; HostDB:ENSRNOG00000018020; -.
DR eggNOG; ENOG502QT08; Eukaryota.
DR InParanoid; P46933; -.
DR OMA; NDNSRVG; -.
DR OrthoDB; 437627at2759; -.
DR PhylomeDB; P46933; -.
DR Reactome; R-RNO-5693565; Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks.
DR PRO; PR:P46933; -.
DR Proteomes; UP000002494; Chromosome 1.
DR Bgee; ENSRNOG00000018020; Expressed in frontal cortex and 19 other tissues.
DR ExpressionAtlas; P46933; baseline and differential.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0043197; C:dendritic spine; IDA:RGD.
DR GO; GO:0098978; C:glutamatergic synapse; ISO:RGD.
DR GO; GO:0030426; C:growth cone; IDA:UniProtKB.
DR GO; GO:1990812; C:growth cone filopodium; IDA:RGD.
DR GO; GO:1990761; C:growth cone lamellipodium; IDA:RGD.
DR GO; GO:0030027; C:lamellipodium; ISS:UniProtKB.
DR GO; GO:0044304; C:main axon; IDA:RGD.
DR GO; GO:0031594; C:neuromuscular junction; ISO:RGD.
DR GO; GO:0043025; C:neuronal cell body; IDA:RGD.
DR GO; GO:0016607; C:nuclear speck; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:RGD.
DR GO; GO:0045211; C:postsynaptic membrane; IDA:RGD.
DR GO; GO:0098793; C:presynapse; IDA:SynGO.
DR GO; GO:0042734; C:presynaptic membrane; IDA:RGD.
DR GO; GO:0032991; C:protein-containing complex; IDA:RGD.
DR GO; GO:0098685; C:Schaffer collateral - CA1 synapse; ISO:RGD.
DR GO; GO:0045202; C:synapse; ISS:UniProtKB.
DR GO; GO:0001540; F:amyloid-beta binding; IPI:RGD.
DR GO; GO:0003682; F:chromatin binding; ISO:RGD.
DR GO; GO:0140297; F:DNA-binding transcription factor binding; IPI:UniProtKB.
DR GO; GO:0042393; F:histone binding; ISO:RGD.
DR GO; GO:0070064; F:proline-rich region binding; ISO:RGD.
DR GO; GO:0044877; F:protein-containing complex binding; IPI:RGD.
DR GO; GO:0048156; F:tau protein binding; IPI:RGD.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; ISO:RGD.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0007411; P:axon guidance; ISO:RGD.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; ISO:RGD.
DR GO; GO:0006325; P:chromatin organization; IEA:UniProtKB-KW.
DR GO; GO:0006302; P:double-strand break repair; IMP:UniProtKB.
DR GO; GO:0030198; P:extracellular matrix organization; ISO:RGD.
DR GO; GO:0043967; P:histone H4 acetylation; IMP:UniProtKB.
DR GO; GO:1902807; P:negative regulation of cell cycle G1/S phase transition; IDA:UniProtKB.
DR GO; GO:0045665; P:negative regulation of neuron differentiation; ISO:RGD.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:UniProtKB.
DR GO; GO:0001764; P:neuron migration; ISO:RGD.
DR GO; GO:0043065; P:positive regulation of apoptotic process; IMP:UniProtKB.
DR GO; GO:0045739; P:positive regulation of DNA repair; IMP:UniProtKB.
DR GO; GO:0010976; P:positive regulation of neuron projection development; IMP:RGD.
DR GO; GO:0050714; P:positive regulation of protein secretion; IMP:RGD.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:RGD.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IDA:UniProtKB.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; IBA:GO_Central.
DR GO; GO:0010039; P:response to iron ion; IEP:RGD.
DR GO; GO:0006939; P:smooth muscle contraction; ISS:UniProtKB.
DR GO; GO:0050808; P:synapse organization; ISO:RGD.
DR CDD; cd00201; WW; 1.
DR Gene3D; 2.30.29.30; -; 2.
DR InterPro; IPR039576; APBB1/2/3.
DR InterPro; IPR011993; PH-like_dom_sf.
DR InterPro; IPR006020; PTB/PI_dom.
DR InterPro; IPR001202; WW_dom.
DR InterPro; IPR036020; WW_dom_sf.
DR PANTHER; PTHR14058; PTHR14058; 1.
DR Pfam; PF00640; PID; 2.
DR Pfam; PF00397; WW; 1.
DR SMART; SM00462; PTB; 2.
DR SMART; SM00456; WW; 1.
DR SUPFAM; SSF51045; SSF51045; 1.
DR PROSITE; PS01179; PID; 2.
DR PROSITE; PS01159; WW_DOMAIN_1; 1.
DR PROSITE; PS50020; WW_DOMAIN_2; 1.
PE 1: Evidence at protein level;
KW Acetylation; Activator; Alternative splicing; Apoptosis; Cell membrane;
KW Cell projection; Chromatin regulator; Cytoplasm; DNA damage; Membrane;
KW Nucleus; Phosphoprotein; Reference proteome; Repeat; Repressor;
KW Transcription; Transcription regulation; Ubl conjugation.
FT CHAIN 1..711
FT /note="Amyloid beta precursor protein binding family B
FT member 1"
FT /id="PRO_0000076051"
FT DOMAIN 254..286
FT /note="WW"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00224"
FT DOMAIN 365..533
FT /note="PID 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00148"
FT DOMAIN 538..700
FT /note="PID 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00148"
FT REGION 140..257
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 277..300
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 320..364
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 152..176
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 209..250
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 135
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9QXJ1"
FT MOD_RES 205
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:O00213"
FT MOD_RES 518
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9QXJ1"
FT MOD_RES 548
FT /note="Phosphotyrosine; by ABL1"
FT /evidence="ECO:0000250|UniProtKB:O00213"
FT MOD_RES 611
FT /note="Phosphoserine; by SGK1"
FT /evidence="ECO:0000269|PubMed:18304449"
FT MOD_RES 702
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:O00213"
FT VAR_SEQ 463..464
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:1923810"
FT /id="VSP_006798"
FT MUTAGEN 655
FT /note="C->F: Abolishes interaction with APP and impairs the
FT function in DNA repair."
FT /evidence="ECO:0000269|PubMed:19282473"
FT CONFLICT 137
FT /note="L -> K (in Ref. 2)"
FT /evidence="ECO:0000305"
FT CONFLICT 150..154
FT /note="EEKAA -> GRRQR (in Ref. 2; CAA42999)"
FT /evidence="ECO:0000305"
FT CONFLICT 172
FT /note="E -> EEEDEEEE (in Ref. 2; CAA42999)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 711 AA; 77656 MW; A6C9820F5D2BD7BE CRC64;
MSVPSSLSQS AINANSHGGP ALSFPFPLHA AHNQLLNAKL QATAVVPKDL RSAMGEGSVP
EPGPANAKWL KEGQNQLRRA ATAHRDQNRN VTLTLAEEAS QEAETAPLGP KGLMHLYSEL
ELSAHNAANR GLHGSALIIN TQGLGPDEGE EKAAGEVEEE DEDEEEEDEE EEDLSSPQGL
PEPLENVEVP SGPQVLTDGP REHSKSASLL FGMRNSAASD EDSSWATLSQ GSPSYGSPED
TDSFWNPNAF ETDSDLPAGW MRVQDTSGTY YWHIPTGTTQ WEPPGRASPS QGNSPQEESQ
LTWTGFAHQE GFEEGEFWKD EPSEEAPMEL GLKDPEEGTL PFSAQSLSPE PVPQEEENLP
QRNANPGIKC FAVRSLGWVE MTEEELAPGR SSVAVNNCIR QLSYHKNNLH DPMSGGWGEG
KDLLLQLEDE TLKLVEPQNQ TLLHAQPIVS IRVWGVGRDS GRERDFAYVA RDKLTQMLKC
HVFRCEAPAK NIATSLHEIC SKIMSERRNA RCLVNGLSLD HSKLVDVPFQ VEFPAPKNEL
VQKFQVYYLG NVPVAKPVGV DVINGALESV LSSSSREQWT PSHVSVAPAT LTILHQQTEA
VLGECRVRFL SFLAVGRDVH TFAFIMAAGP ASFCCHMFWC EPNAASLSEA VQAACMLRYQ
KCLDARSQTS TSCLPAPPAE SVARRVGWTV RRGVQSLWGS LKPKRLGSQT P
