APBB1_HUMAN
ID APBB1_HUMAN Reviewed; 710 AA.
AC O00213; A1E379; A6NH82; A6NL69; B7Z1J5; B7Z1J6; B7Z2Y0; D3DQT2; Q7Z324;
AC Q96A93; V9GYK0; V9GYT4;
DT 11-JAN-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-1998, sequence version 2.
DT 03-AUG-2022, entry version 199.
DE RecName: Full=Amyloid beta precursor protein binding family B member 1 {ECO:0000312|HGNC:HGNC:581};
DE AltName: Full=Amyloid-beta A4 precursor protein-binding family B member 1 {ECO:0000250|UniProtKB:Q9QXJ1};
DE AltName: Full=Protein Fe65 {ECO:0000250|UniProtKB:Q9QXJ1};
GN Name=APBB1 {ECO:0000312|HGNC:HGNC:581};
GN Synonyms=FE65 {ECO:0000303|PubMed:8894693},
GN RIR {ECO:0000312|HGNC:HGNC:581};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=8894693; DOI=10.1093/hmg/5.10.1589;
RA Bressler S.L., Gray M.D., Sopher B.L., Hu Q., Hearn M.G., Pham D.G.,
RA Dinulos M.B., Fukuchi K., Sisodia S.S., Miller M.A., Disteche C.M.,
RA Martin G.M.;
RT "cDNA cloning and chromosome mapping of the human Fe65 gene: interaction of
RT the conserved cytoplasmic domains of the human beta-amyloid precursor
RT protein and its homologues with the mouse Fe65 protein.";
RL Hum. Mol. Genet. 5:1589-1598(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=9799084; DOI=10.1007/s004390050820;
RA Hu Q., Kukull W.A., Bressler S.L., Gray M.D., Cam J.A., Larson E.B.,
RA Martin G.M., Deeb S.S.;
RT "The human FE65 gene: genomic structure and an intronic biallelic
RT polymorphism associated with sporadic dementia of the Alzheimer type.";
RL Hum. Genet. 103:295-303(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 4), AND TISSUE SPECIFICITY.
RC TISSUE=Brain;
RX PubMed=21824145; DOI=10.1111/j.1471-4159.2011.07420.x;
RA Domingues S.C., Henriques A.G., Fardilha M., da Cruz E Silva E.F.,
RA da Cruz E Silva O.A.;
RT "Identification and characterization of a neuronal enriched novel
RT transcript encoding the previously described p60Fe65 isoform.";
RL J. Neurochem. 119:1086-1098(2011).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 3; 4 AND 6).
RC TISSUE=Caudate nucleus, and Cerebellum;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 5).
RC TISSUE=Fetal brain;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16554811; DOI=10.1038/nature04632;
RA Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K.,
RA Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T.,
RA Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G.,
RA Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C.,
RA Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A.,
RA Hattori M., Rogers J., Lander E.S., Sakaki Y.;
RT "Human chromosome 11 DNA sequence and analysis including novel gene
RT identification.";
RL Nature 440:497-500(2006).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Uterus;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [9]
RP FUNCTION, INTERACTION WITH ABL1, SUBCELLULAR LOCATION, PHOSPHORYLATION AT
RP TYR-547 BY ABL1, AND MUTAGENESIS OF TYR-117; TYR-234; TYR-269; TYR-270;
RP TYR-403; TYR-467; 269-TYR--TRP-271; TYR-546; TYR-547 AND TYR-658.
RX PubMed=15031292; DOI=10.1074/jbc.m311479200;
RA Perkinton M.S., Standen C.L., Lau K.F., Kesavapany S., Byers H.L., Ward M.,
RA McLoughlin D.M., Miller C.C.;
RT "The c-Abl tyrosine kinase phosphorylates the Fe65 adaptor protein to
RT stimulate Fe65/amyloid precursor protein nuclear signaling.";
RL J. Biol. Chem. 279:22084-22091(2004).
RN [10]
RP SUBCELLULAR LOCATION, AND INTERACTION WITH NEK6.
RX PubMed=17512906; DOI=10.1016/j.bbrc.2007.04.203;
RA Lee E.J., Hyun S.H., Chun J., Kang S.S.;
RT "Human NIMA-related kinase 6 is one of the Fe65 WW domain binding
RT proteins.";
RL Biochem. Biophys. Res. Commun. 358:783-788(2007).
RN [11]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH APP.
RX PubMed=18468999; DOI=10.1074/jbc.m801827200;
RA Nakaya T., Kawai T., Suzuki T.;
RT "Regulation of FE65 nuclear translocation and function by amyloid beta-
RT protein precursor in osmotically stressed cells.";
RL J. Biol. Chem. 283:19119-19131(2008).
RN [12]
RP FUNCTION, SUBCELLULAR LOCATION, PHOSPHORYLATION AT TYR-547, INTERACTION
RP WITH RASD1, AND MUTAGENESIS OF TYR-547.
RX PubMed=18922798; DOI=10.1074/jbc.m801874200;
RA Lau K.-F., Chan W.-M., Perkinton M.S., Tudor E.L., Chang R.C.C.,
RA Chan H.-Y., McLoughlin D.M., Miller C.C.J.;
RT "Dexras1 interacts with FE65 to regulate FE65-amyloid precursor protein-
RT dependent transcription.";
RL J. Biol. Chem. 283:34728-34737(2008).
RN [13]
RP FUNCTION, AND INTERACTION WITH H2AX AND MAPK8.
RX PubMed=19234442; DOI=10.1038/nature07849;
RA Cook P.J., Ju B.G., Telese F., Wang X., Glass C.K., Rosenfeld M.G.;
RT "Tyrosine dephosphorylation of H2AX modulates apoptosis and survival
RT decisions.";
RL Nature 458:591-596(2009).
RN [14]
RP FUNCTION, INTERACTION WITH SET AND TSHZ3, IDENTIFICATION IN A TRIMERIC
RP COMPLEX WITH HDAC1 AND TSHZ3, CHROMATIN-BINDING, SUBCELLULAR LOCATION, AND
RP TISSUE SPECIFICITY.
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 [15]
RP INTERACTION WITH RNF157, UBIQUITINATION BY RNF157, AND FUNCTION.
RX PubMed=25342469; DOI=10.1038/cdd.2014.163;
RA Matz A., Lee S.J., Schwedhelm-Domeyer N., Zanini D., Holubowska A.,
RA Kannan M., Farnworth M., Jahn O., Goepfert M.C., Stegmueller J.;
RT "Regulation of neuronal survival and morphology by the E3 ubiquitin ligase
RT RNF157.";
RL Cell Death Differ. 22:626-642(2015).
RN [16]
RP FUNCTION, INTERACTION WITH KAT5, ACETYLATION AT LYS-204 AND LYS-701, AND
RP MUTAGENESIS OF LYS-204 AND LYS-701.
RX PubMed=33938178; DOI=10.1515/hsz-2020-0279;
RA Probst S., Riese F., Kaegi L., Krueger M., Russi N., Nitsch R.M.,
RA Konietzko U.;
RT "Lysine acetyltransferase Tip60 acetylates the APP adaptor Fe65 to increase
RT its transcriptional activity.";
RL Biol. Chem. 402:481-499(2021).
RN [17]
RP X-RAY CRYSTALLOGRAPHY (1.33 ANGSTROMS) OF 253-289 IN COMPLEX WITH ENAH.
RX PubMed=17686488; DOI=10.1016/j.jmb.2007.06.064;
RA Meiyappan M., Birrane G., Ladias J.A.A.;
RT "Structural basis for polyproline recognition by the FE65 WW domain.";
RL J. Mol. Biol. 372:970-980(2007).
RN [18]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 534-667 IN COMPLEX WITH APP.
RX PubMed=18833287; DOI=10.1038/embor.2008.188;
RA Radzimanowski J., Simon B., Sattler M., Beyreuther K., Sinning I., Wild K.;
RT "Structure of the intracellular domain of the amyloid precursor protein in
RT complex with Fe65-PTB2.";
RL EMBO Rep. 9:1134-1140(2008).
RN [19]
RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 366-505.
RX PubMed=18550529; DOI=10.1074/jbc.m800861200;
RA Radzimanowski J., Ravaud S., Schlesinger S., Koch J., Beyreuther K.,
RA Sinning I., Wild K.;
RT "Crystal structure of the human Fe65-PTB1 domain.";
RL J. Biol. Chem. 283:23113-23120(2008).
CC -!- FUNCTION: Transcription coregulator that can have both coactivator and
CC corepressor functions (PubMed:15031292, PubMed:18468999,
CC PubMed:18922798, PubMed:25342469, PubMed:33938178). Adapter protein
CC that forms a transcriptionally active complex with the gamma-secretase-
CC derived amyloid precursor protein (APP) intracellular domain
CC (PubMed:15031292, PubMed:18468999, PubMed:18922798, PubMed:25342469).
CC Plays a central role in the response to DNA damage by translocating to
CC the nucleus and inducing apoptosis (PubMed:15031292, PubMed:18468999,
CC PubMed:18922798, PubMed:25342469). May act by specifically recognizing
CC and binding histone H2AX phosphorylated on 'Tyr-142' (H2AXY142ph) at
CC double-strand breaks (DSBs), recruiting other pro-apoptosis factors
CC such as MAPK8/JNK1 (PubMed:19234442). Required for histone H4
CC acetylation at double-strand breaks (DSBs) (PubMed:19234442). Its
CC ability to specifically bind modified histones and chromatin modifying
CC enzymes such as KAT5/TIP60, probably explains its transcription
CC activation activity (PubMed:33938178). Functions in association with
CC TSHZ3, SET and HDAC factors as a transcriptional repressor, that
CC inhibits the expression of CASP4 (PubMed:19343227). Associates with
CC chromatin in a region surrounding the CASP4 transcriptional start
CC site(s) (PubMed:19343227). Involved in hippocampal neurite branching
CC and neuromuscular junction formation, as a result plays a role in
CC spatial memory functioning (By similarity). Plays a role in the
CC maintenance of lens transparency (By similarity). May play a role in
CC muscle cell strength (By similarity). {ECO:0000250|UniProtKB:Q9QXJ1,
CC ECO:0000269|PubMed:15031292, ECO:0000269|PubMed:18468999,
CC ECO:0000269|PubMed:18922798, ECO:0000269|PubMed:19234442,
CC ECO:0000269|PubMed:19343227, ECO:0000269|PubMed:25342469,
CC ECO:0000269|PubMed:33938178}.
CC -!- SUBUNIT: Component of a complex, at least composed of APBB1,
CC RASD1/DEXRAS1 and APP (PubMed:18922798, PubMed:18833287,
CC PubMed:18468999). Interacts (via PID domain 2) with APP (with the
CC intracellular domain of the amyloid-beta precursor protein)
CC (PubMed:18833287, PubMed:18468999). Interacts (via PID domain 2) with
CC RASD1/DEXRAS1; impairs the transcription activation activity
CC (PubMed:18922798). Interacts (via PID domain 1) with KAT5/TIP60
CC (PubMed:33938178). 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
CC (PubMed:17686488). Interacts with MAPK8 (PubMed:19234442). Interacts
CC (via PID domain 1) with TSHZ3 (via homeobox domain) (PubMed:19343227).
CC Interacts with SET (PubMed:19343227). Found in a trimeric complex with
CC HDAC1 and TSHZ3; the interaction between HDAC1 and APBB1 is mediated by
CC TSHZ3 (PubMed:19343227). Interacts (via WWW domain) with NEK6
CC (PubMed:17512906). Interacts (via WWW domain) with ABL1
CC (PubMed:15031292). Interacts with RNF157 (PubMed:25342469).
CC {ECO:0000250|UniProtKB:Q9QXJ1, ECO:0000269|PubMed:15031292,
CC ECO:0000269|PubMed:17512906, ECO:0000269|PubMed:17686488,
CC ECO:0000269|PubMed:18468999, ECO:0000269|PubMed:18833287,
CC ECO:0000269|PubMed:18922798, ECO:0000269|PubMed:19234442,
CC ECO:0000269|PubMed:19343227, ECO:0000269|PubMed:25342469,
CC ECO:0000269|PubMed:33938178}.
CC -!- INTERACTION:
CC O00213; P05067: APP; NbExp=7; IntAct=EBI-81694, EBI-77613;
CC O00213; P05067-4: APP; NbExp=5; IntAct=EBI-81694, EBI-302641;
CC O00213; P62330: ARF6; NbExp=9; IntAct=EBI-81694, EBI-638181;
CC O00213; P00533: EGFR; NbExp=4; IntAct=EBI-81694, EBI-297353;
CC O00213; P04626: ERBB2; NbExp=2; IntAct=EBI-81694, EBI-641062;
CC O00213; Q07954: LRP1; NbExp=4; IntAct=EBI-81694, EBI-1046087;
CC O00213; Q02563: Sv2a; Xeno; NbExp=3; IntAct=EBI-81694, EBI-466194;
CC O00213-2; P05067: APP; NbExp=6; IntAct=EBI-13307975, EBI-77613;
CC O00213-2; Q86YB2: DHX8; NbExp=3; IntAct=EBI-13307975, EBI-14405236;
CC O00213-2; Q8NFZ0: FBH1; NbExp=3; IntAct=EBI-13307975, EBI-724767;
CC O00213-2; Q92993: KAT5; NbExp=3; IntAct=EBI-13307975, EBI-399080;
CC O00213-2; O15116: LSM1; NbExp=3; IntAct=EBI-13307975, EBI-347619;
CC O00213-2; Q14141: SEPTIN6; NbExp=3; IntAct=EBI-13307975, EBI-745901;
CC O00213-2; Q99720-4: SIGMAR1; NbExp=3; IntAct=EBI-13307975, EBI-25831036;
CC O00213-2; O95416: SOX14; NbExp=3; IntAct=EBI-13307975, EBI-9087806;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:18468999}.
CC Cytoplasm {ECO:0000269|PubMed:18468999}. Nucleus
CC {ECO:0000269|PubMed:15031292, ECO:0000269|PubMed:18468999,
CC ECO:0000269|PubMed:18922798, ECO:0000269|PubMed:19343227}. Cell
CC projection, growth cone {ECO:0000250|UniProtKB:P46933}. Nucleus speckle
CC {ECO:0000269|PubMed:17512906}. Note=Colocalizes with TSHZ3 in axonal
CC growth cone (By similarity). Colocalizes with TSHZ3 in the nucleus
CC (PubMed:19343227). In normal conditions, it mainly localizes to the
CC cytoplasm, while a small fraction is tethered to the cell membrane via
CC its interaction with APP (PubMed:18468999). Following exposure to DNA
CC damaging agents, it is released from cell membrane and translocates to
CC the nucleus (PubMed:18468999). Nuclear translocation is under the
CC regulation of APP (PubMed:18468999). Colocalizes with NEK6 at the
CC nuclear speckles (PubMed:17512906). Phosphorylation at Ser-610 by SGK1
CC promotes its localization to the nucleus (By similarity).
CC {ECO:0000250|UniProtKB:P46933, ECO:0000269|PubMed:17512906,
CC ECO:0000269|PubMed:18468999, ECO:0000269|PubMed:19343227}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=6;
CC Name=1;
CC IsoId=O00213-1; Sequence=Displayed;
CC Name=2;
CC IsoId=O00213-2; Sequence=VSP_011658;
CC Name=3;
CC IsoId=O00213-3; Sequence=VSP_045326, VSP_045327, VSP_011658;
CC Name=4; Synonyms=p60Fe65;
CC IsoId=O00213-4; Sequence=VSP_047459;
CC Name=5;
CC IsoId=O00213-5; Sequence=VSP_045326, VSP_045327;
CC Name=6;
CC IsoId=O00213-6; Sequence=VSP_054709;
CC -!- TISSUE SPECIFICITY: Highly expressed in brain; strongly reduced in
CC post-mortem elderly subjects with Alzheimer disease.
CC {ECO:0000269|PubMed:19343227}.
CC -!- TISSUE SPECIFICITY: [Isoform 4]: Expressed preferentially in the brain.
CC {ECO:0000269|PubMed:21824145}.
CC -!- PTM: Phosphorylation at Ser-610 by SGK1 promotes its localization to
CC the nucleus (By similarity). Phosphorylated following nuclear
CC translocation (PubMed:15031292, PubMed:18922798). Phosphorylation at
CC Tyr-547 by ABL1 enhances transcriptional activation activity and
CC reduces the affinity for RASD1/DEXRAS1 (PubMed:15031292,
CC PubMed:18922798). {ECO:0000250|UniProtKB:P46933,
CC ECO:0000269|PubMed:15031292, ECO:0000269|PubMed:18922798}.
CC -!- PTM: Acetylation at Lys-204 and Lys-701 by KAT5 promotes its
CC transcription activator activity. {ECO:0000269|PubMed:33938178}.
CC -!- PTM: Polyubiquitination by RNF157 leads to degradation by the
CC proteasome (PubMed:25342469). {ECO:0000269|PubMed:25342469}.
CC -!- SEQUENCE CAUTION:
CC Sequence=CAD98057.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; L77864; AAB93631.1; -; mRNA.
DR EMBL; AF029234; AAC79942.1; -; Genomic_DNA.
DR EMBL; AF047835; AAC79942.1; JOINED; Genomic_DNA.
DR EMBL; EF103274; ABL07489.3; -; mRNA.
DR EMBL; AK293550; BAH11531.1; -; mRNA.
DR EMBL; AK293554; BAH11532.1; -; mRNA.
DR EMBL; AK293643; BAH11554.1; -; mRNA.
DR EMBL; AK295241; BAH12016.1; -; mRNA.
DR EMBL; BX538185; CAD98057.1; ALT_INIT; mRNA.
DR EMBL; AC068733; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC084337; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471064; EAW68723.1; -; Genomic_DNA.
DR EMBL; CH471064; EAW68724.1; -; Genomic_DNA.
DR EMBL; BC010854; AAH10854.1; -; mRNA.
DR CCDS; CCDS31410.1; -. [O00213-2]
DR CCDS; CCDS58114.1; -. [O00213-3]
DR CCDS; CCDS66015.1; -. [O00213-4]
DR CCDS; CCDS66016.1; -. [O00213-6]
DR CCDS; CCDS66017.1; -. [O00213-5]
DR CCDS; CCDS66018.1; -. [O00213-1]
DR RefSeq; NP_001155.1; NM_001164.4. [O00213-1]
DR RefSeq; NP_001244248.1; NM_001257319.2. [O00213-5]
DR RefSeq; NP_001244249.1; NM_001257320.2. [O00213-4]
DR RefSeq; NP_001244250.1; NM_001257321.2. [O00213-4]
DR RefSeq; NP_001244252.1; NM_001257323.2. [O00213-3]
DR RefSeq; NP_001244254.1; NM_001257325.2. [O00213-6]
DR RefSeq; NP_001244255.1; NM_001257326.2. [O00213-4]
DR RefSeq; NP_663722.1; NM_145689.2. [O00213-2]
DR RefSeq; XP_011518342.1; XM_011520040.2.
DR RefSeq; XP_016873130.1; XM_017017641.1.
DR PDB; 2E45; NMR; -; A=241-290.
DR PDB; 2HO2; X-ray; 1.33 A; A=253-289.
DR PDB; 2IDH; X-ray; 2.28 A; A/B/C/D/E/F/G/H=253-289.
DR PDB; 2OEI; X-ray; 1.35 A; A=253-289.
DR PDB; 3D8D; X-ray; 2.20 A; A/B=366-505.
DR PDB; 3D8E; X-ray; 2.80 A; A/B/C/D=366-505.
DR PDB; 3D8F; X-ray; 2.70 A; A/B/C/D=366-505.
DR PDB; 3DXC; X-ray; 2.10 A; A/C=534-667.
DR PDB; 3DXD; X-ray; 2.20 A; A/C=534-667.
DR PDB; 3DXE; X-ray; 2.00 A; A/C=534-667.
DR PDB; 5NQH; X-ray; 2.60 A; A/B/C/D=534-667.
DR PDBsum; 2E45; -.
DR PDBsum; 2HO2; -.
DR PDBsum; 2IDH; -.
DR PDBsum; 2OEI; -.
DR PDBsum; 3D8D; -.
DR PDBsum; 3D8E; -.
DR PDBsum; 3D8F; -.
DR PDBsum; 3DXC; -.
DR PDBsum; 3DXD; -.
DR PDBsum; 3DXE; -.
DR PDBsum; 5NQH; -.
DR AlphaFoldDB; O00213; -.
DR BMRB; O00213; -.
DR SMR; O00213; -.
DR BioGRID; 106819; 161.
DR CORUM; O00213; -.
DR DIP; DIP-30903N; -.
DR ELM; O00213; -.
DR IntAct; O00213; 167.
DR MINT; O00213; -.
DR STRING; 9606.ENSP00000477213; -.
DR GlyGen; O00213; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; O00213; -.
DR PhosphoSitePlus; O00213; -.
DR BioMuta; APBB1; -.
DR EPD; O00213; -.
DR jPOST; O00213; -.
DR MassIVE; O00213; -.
DR MaxQB; O00213; -.
DR PaxDb; O00213; -.
DR PeptideAtlas; O00213; -.
DR PRIDE; O00213; -.
DR ProteomicsDB; 47783; -. [O00213-1]
DR ProteomicsDB; 47784; -. [O00213-2]
DR ProteomicsDB; 6474; -.
DR Antibodypedia; 23808; 415 antibodies from 39 providers.
DR DNASU; 322; -.
DR Ensembl; ENST00000299402.10; ENSP00000299402.6; ENSG00000166313.20. [O00213-2]
DR Ensembl; ENST00000311051.7; ENSP00000311912.3; ENSG00000166313.20. [O00213-2]
DR Ensembl; ENST00000530885.5; ENSP00000433338.1; ENSG00000166313.20. [O00213-3]
DR Ensembl; ENST00000608394.5; ENSP00000476442.1; ENSG00000166313.20. [O00213-4]
DR Ensembl; ENST00000608645.5; ENSP00000476646.1; ENSG00000166313.20. [O00213-4]
DR Ensembl; ENST00000608655.5; ENSP00000476846.1; ENSG00000166313.20. [O00213-5]
DR Ensembl; ENST00000608704.5; ENSP00000476871.1; ENSG00000166313.20. [O00213-4]
DR Ensembl; ENST00000609331.5; ENSP00000477069.1; ENSG00000166313.20. [O00213-6]
DR Ensembl; ENST00000609360.6; ENSP00000477213.1; ENSG00000166313.20. [O00213-1]
DR GeneID; 322; -.
DR KEGG; hsa:322; -.
DR MANE-Select; ENST00000609360.6; ENSP00000477213.1; NM_001164.5; NP_001155.1.
DR UCSC; uc001mdb.4; human. [O00213-1]
DR CTD; 322; -.
DR DisGeNET; 322; -.
DR GeneCards; APBB1; -.
DR HGNC; HGNC:581; APBB1.
DR HPA; ENSG00000166313; Tissue enhanced (brain).
DR MalaCards; APBB1; -.
DR MIM; 602709; gene.
DR neXtProt; NX_O00213; -.
DR OpenTargets; ENSG00000166313; -.
DR PharmGKB; PA24873; -.
DR VEuPathDB; HostDB:ENSG00000166313; -.
DR eggNOG; ENOG502QT08; Eukaryota.
DR GeneTree; ENSGT00390000000002; -.
DR HOGENOM; CLU_021196_0_0_1; -.
DR InParanoid; O00213; -.
DR OMA; NDNSRVG; -.
DR OrthoDB; 437627at2759; -.
DR PhylomeDB; O00213; -.
DR TreeFam; TF314331; -.
DR PathwayCommons; O00213; -.
DR Reactome; R-HSA-5693565; Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks.
DR SignaLink; O00213; -.
DR SIGNOR; O00213; -.
DR BioGRID-ORCS; 322; 7 hits in 1078 CRISPR screens.
DR ChiTaRS; APBB1; human.
DR EvolutionaryTrace; O00213; -.
DR GeneWiki; APBB1; -.
DR GenomeRNAi; 322; -.
DR Pharos; O00213; Tbio.
DR PRO; PR:O00213; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; O00213; protein.
DR Bgee; ENSG00000166313; Expressed in right hemisphere of cerebellum and 160 other tissues.
DR ExpressionAtlas; O00213; baseline and differential.
DR Genevisible; O00213; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:HPA.
DR GO; GO:0030426; C:growth cone; IDA:UniProtKB.
DR GO; GO:0030027; C:lamellipodium; IDA:UniProtKB.
DR GO; GO:0016607; C:nuclear speck; IEA:UniProtKB-SubCell.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0045202; C:synapse; IDA:UniProtKB.
DR GO; GO:0001540; F:amyloid-beta binding; IBA:GO_Central.
DR GO; GO:0003682; F:chromatin binding; IDA:UniProtKB.
DR GO; GO:0042393; F:histone binding; IPI:UniProtKB.
DR GO; GO:0050750; F:low-density lipoprotein particle receptor binding; TAS:ARUK-UCL.
DR GO; GO:0070064; F:proline-rich region binding; IPI:UniProtKB.
DR GO; GO:0003713; F:transcription coactivator activity; TAS:ARUK-UCL.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; IPI:UniProtKB.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0007409; P:axonogenesis; NAS:UniProtKB.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; IDA:UniProtKB.
DR GO; GO:0006325; P:chromatin organization; IEA:UniProtKB-KW.
DR GO; GO:0043967; P:histone H4 acetylation; ISS:UniProtKB.
DR GO; GO:1902807; P:negative regulation of cell cycle G1/S phase transition; ISS:UniProtKB.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IGI:ARUK-UCL.
DR GO; GO:0043065; P:positive regulation of apoptotic process; IDA:UniProtKB.
DR GO; GO:0050714; P:positive regulation of protein secretion; TAS:ARUK-UCL.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; TAS:ARUK-UCL.
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:0007165; P:signal transduction; NAS:UniProtKB.
DR GO; GO:0006939; P:smooth muscle contraction; ISS:UniProtKB.
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 3D-structure; Acetylation; Activator; Alternative splicing; Apoptosis;
KW Cell membrane; Cell projection; Chromatin regulator; Cytoplasm; DNA damage;
KW Membrane; Nucleus; Phosphoprotein; Reference proteome; Repeat; Repressor;
KW Transcription; Transcription regulation; Ubl conjugation.
FT CHAIN 1..710
FT /note="Amyloid beta precursor protein binding family B
FT member 1"
FT /id="PRO_0000076049"
FT DOMAIN 253..285
FT /note="WW"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00224"
FT DOMAIN 370..509
FT /note="PID 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00148"
FT DOMAIN 542..699
FT /note="PID 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00148"
FT REGION 1..24
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 131..254
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 276..299
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 340..365
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1..17
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 152..175
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 208..249
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 204
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000269|PubMed:33938178"
FT MOD_RES 517
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9QXJ1"
FT MOD_RES 547
FT /note="Phosphotyrosine; by ABL1"
FT /evidence="ECO:0000269|PubMed:15031292,
FT ECO:0000269|PubMed:18922798"
FT MOD_RES 610
FT /note="Phosphoserine; by SGK1"
FT /evidence="ECO:0000250|UniProtKB:P46933"
FT MOD_RES 701
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000269|PubMed:33938178"
FT VAR_SEQ 1..259
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:21824145"
FT /id="VSP_047459"
FT VAR_SEQ 1..240
FT /note="MSVPSSLSQSAINANSHGGPALSLPLPLHAAHNQLLNAKLQATAVGPKDLRS
FT AMGEGGGPEPGPANAKWLKEGQNQLRRAATAHRDQNRNVTLTLAEEASQEPEMAPLGPK
FT GLIHLYSELELSAHNAANRGLRGPGLIISTQEQGPDEGEEKAAGEAEEEEEDDDDEEEE
FT EDLSSPPGLPEPLESVEAPPRPQALTDGPREHSKSASLLFGMRNSAASDEDSSWATLSQ
FT GSPSYGSPEDT -> MTQMR (in isoform 6)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_054709"
FT VAR_SEQ 1..213
FT /note="Missing (in isoform 3 and isoform 5)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:17974005"
FT /id="VSP_045326"
FT VAR_SEQ 214..240
FT /note="NSAASDEDSSWATLSQGSPSYGSPEDT -> MSAMFSQDFFLAIILQDSSA
FT (in isoform 3 and isoform 5)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:17974005"
FT /id="VSP_045327"
FT VAR_SEQ 462..463
FT /note="Missing (in isoform 2 and isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_011658"
FT VARIANT 327
FT /note="M -> V (in dbSNP:rs1800423)"
FT /id="VAR_014444"
FT VARIANT 396
FT /note="N -> S (in dbSNP:rs1800425)"
FT /id="VAR_014445"
FT MUTAGEN 117
FT /note="Y->F: No effect on phosphorylation by ABL1."
FT /evidence="ECO:0000269|PubMed:15031292"
FT MUTAGEN 204
FT /note="K->Q: Mimics acetylation; leading to increased
FT transcription activator activity; when associated with Q-
FT 701."
FT /evidence="ECO:0000269|PubMed:33938178"
FT MUTAGEN 204
FT /note="K->R: Abolished acetylation by KAT5, leading to
FT decreased transcription activator activity; when associated
FT with R-701."
FT /evidence="ECO:0000269|PubMed:33938178"
FT MUTAGEN 234
FT /note="Y->F: No effect on phosphorylation by ABL1."
FT /evidence="ECO:0000269|PubMed:15031292"
FT MUTAGEN 269..271
FT /note="YYW->AAA: Impairs transcriptional activation and
FT inhibits binding to ABL1."
FT /evidence="ECO:0000269|PubMed:15031292"
FT MUTAGEN 269
FT /note="Y->F: No effect on phosphorylation by ABL1."
FT /evidence="ECO:0000269|PubMed:15031292"
FT MUTAGEN 270
FT /note="Y->F: No effect on phosphorylation by ABL1."
FT /evidence="ECO:0000269|PubMed:15031292"
FT MUTAGEN 403
FT /note="Y->F: No effect on phosphorylation by ABL1."
FT /evidence="ECO:0000269|PubMed:15031292"
FT MUTAGEN 467
FT /note="Y->F: No effect on phosphorylation by ABL1."
FT /evidence="ECO:0000269|PubMed:15031292"
FT MUTAGEN 546
FT /note="Y->F: No effect on phosphorylation by ABL1."
FT /evidence="ECO:0000269|PubMed:15031292"
FT MUTAGEN 547
FT /note="Y->F: Abrogates phosphorylation and stimulation of
FT transcription by ABL1, and increases the interaction with
FT RASD1/DEXRAS1."
FT /evidence="ECO:0000269|PubMed:15031292,
FT ECO:0000269|PubMed:18922798"
FT MUTAGEN 658
FT /note="Y->F: No effect on phosphorylation by ABL1."
FT /evidence="ECO:0000269|PubMed:15031292"
FT MUTAGEN 701
FT /note="K->Q: Mimics acetylation; leading to increased
FT transcription activator activity; when associated with Q-
FT 204."
FT /evidence="ECO:0000269|PubMed:33938178"
FT MUTAGEN 701
FT /note="K->R: Abolished acetylation by KAT5, leading to
FT decreased transcription activator activity; when associated
FT with R-204."
FT /evidence="ECO:0000269|PubMed:33938178"
FT CONFLICT 367
FT /note="I -> T (in Ref. 4; BAH11532)"
FT /evidence="ECO:0000305"
FT CONFLICT 493
FT /note="T -> A (in Ref. 4; BAH11532)"
FT /evidence="ECO:0000305"
FT STRAND 259..263
FT /evidence="ECO:0007829|PDB:2HO2"
FT STRAND 268..272
FT /evidence="ECO:0007829|PDB:2HO2"
FT TURN 273..275
FT /evidence="ECO:0007829|PDB:2HO2"
FT STRAND 278..281
FT /evidence="ECO:0007829|PDB:2HO2"
FT STRAND 368..379
FT /evidence="ECO:0007829|PDB:3D8D"
FT HELIX 382..385
FT /evidence="ECO:0007829|PDB:3D8D"
FT TURN 387..389
FT /evidence="ECO:0007829|PDB:3D8D"
FT HELIX 390..401
FT /evidence="ECO:0007829|PDB:3D8D"
FT STRAND 421..427
FT /evidence="ECO:0007829|PDB:3D8D"
FT STRAND 430..434
FT /evidence="ECO:0007829|PDB:3D8D"
FT TURN 436..438
FT /evidence="ECO:0007829|PDB:3D8D"
FT STRAND 441..446
FT /evidence="ECO:0007829|PDB:3D8D"
FT HELIX 447..449
FT /evidence="ECO:0007829|PDB:3D8D"
FT STRAND 452..455
FT /evidence="ECO:0007829|PDB:3D8D"
FT STRAND 458..460
FT /evidence="ECO:0007829|PDB:3D8F"
FT STRAND 464..470
FT /evidence="ECO:0007829|PDB:3D8D"
FT TURN 472..474
FT /evidence="ECO:0007829|PDB:3D8D"
FT STRAND 477..486
FT /evidence="ECO:0007829|PDB:3D8D"
FT HELIX 488..504
FT /evidence="ECO:0007829|PDB:3D8D"
FT STRAND 544..554
FT /evidence="ECO:0007829|PDB:3DXE"
FT HELIX 559..571
FT /evidence="ECO:0007829|PDB:3DXE"
FT HELIX 575..577
FT /evidence="ECO:0007829|PDB:3DXE"
FT STRAND 579..585
FT /evidence="ECO:0007829|PDB:3DXE"
FT STRAND 587..594
FT /evidence="ECO:0007829|PDB:3DXE"
FT TURN 595..597
FT /evidence="ECO:0007829|PDB:3DXE"
FT STRAND 600..605
FT /evidence="ECO:0007829|PDB:3DXE"
FT HELIX 606..608
FT /evidence="ECO:0007829|PDB:3DXE"
FT STRAND 609..614
FT /evidence="ECO:0007829|PDB:3DXE"
FT STRAND 620..628
FT /evidence="ECO:0007829|PDB:3DXE"
FT STRAND 631..641
FT /evidence="ECO:0007829|PDB:3DXE"
FT HELIX 644..665
FT /evidence="ECO:0007829|PDB:3DXE"
SQ SEQUENCE 710 AA; 77244 MW; FD4A2EF7E8D8E884 CRC64;
MSVPSSLSQS AINANSHGGP ALSLPLPLHA AHNQLLNAKL QATAVGPKDL RSAMGEGGGP
EPGPANAKWL KEGQNQLRRA ATAHRDQNRN VTLTLAEEAS QEPEMAPLGP KGLIHLYSEL
ELSAHNAANR GLRGPGLIIS TQEQGPDEGE EKAAGEAEEE EEDDDDEEEE EDLSSPPGLP
EPLESVEAPP RPQALTDGPR EHSKSASLLF GMRNSAASDE DSSWATLSQG SPSYGSPEDT
DSFWNPNAFE TDSDLPAGWM RVQDTSGTYY WHIPTGTTQW EPPGRASPSQ GSSPQEESQL
TWTGFAHGEG FEDGEFWKDE PSDEAPMELG LKEPEEGTLT FPAQSLSPEP LPQEEEKLPP
RNTNPGIKCF AVRSLGWVEM TEEELAPGRS SVAVNNCIRQ LSYHKNNLHD PMSGGWGEGK
DLLLQLEDET LKLVEPQSQA LLHAQPIISI RVWGVGRDSG RERDFAYVAR DKLTQMLKCH
VFRCEAPAKN IATSLHEICS KIMAERRNAR CLVNGLSLDH SKLVDVPFQV EFPAPKNELV
QKFQVYYLGN VPVAKPVGVD VINGALESVL SSSSREQWTP SHVSVAPATL TILHQQTEAV
LGECRVRFLS FLAVGRDVHT FAFIMAAGPA SFCCHMFWCE PNAASLSEAV QAACMLRYQK
CLDARSQAST SCLPAPPAES VARRVGWTVR RGVQSLWGSL KPKRLGAHTP
