APBB3_HUMAN
ID APBB3_HUMAN Reviewed; 486 AA.
AC O95704; B3KQN9; Q08AG4; Q96Q18; Q9BYD4; Q9NYX6; Q9NYX7; Q9NYX8;
DT 11-JAN-2001, integrated into UniProtKB/Swiss-Prot.
DT 30-NOV-2010, sequence version 2.
DT 03-AUG-2022, entry version 171.
DE RecName: Full=Amyloid-beta A4 precursor protein-binding family B member 3;
DE AltName: Full=Protein Fe65-like 2;
DE Short=Fe65L2;
GN Name=APBB3 {ECO:0000312|HGNC:HGNC:20708};
GN Synonyms=FE65L2 {ECO:0000312|HGNC:HGNC:20708};
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 [MRNA] (ISOFORMS I AND II), INTERACTION WITH APP; APLP1
RP AND APLP2, AND VARIANT ARG-231.
RC TISSUE=Brain;
RX PubMed=10081969; DOI=10.1016/s0304-3940(98)00995-1;
RA Tanahashi H.;
RT "Molecular cloning of human Fe65L2 and its interaction with the Alzheimer's
RT beta-amyloid precursor protein.";
RL Neurosci. Lett. 261:143-146(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT ARG-231.
RX PubMed=10329396; DOI=10.1006/bbrc.1999.0639;
RA Tanahashi H., Tabira T.;
RT "Genome structure and chromosomal mapping of the gene for Fe65L2
RT interacting with Alzheimer's beta-amyloid precursor protein.";
RL Biochem. Biophys. Res. Commun. 258:385-389(1999).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS I-214 AND I-245), SUBCELLULAR
RP LOCATION, AND TISSUE SPECIFICITY.
RC TISSUE=Brain;
RX PubMed=12153398; DOI=10.1042/bj20020562;
RA Tanahashi H., Tabira T.;
RT "Characterization of an amyloid precursor protein-binding protein Fe65L2
RT and its novel isoforms lacking phosphotyrosine-interaction domains.";
RL Biochem. J. 367:687-695(2002).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS I; II; III AND IV), AND VARIANT
RP ARG-231.
RA Mao Y.M., Xie Y., Sun Z., Chen X.M., Ying K., Dai J.L., Lin S., Wu C.Q.,
RA Li Y.;
RT "Molecular cloning of the full-length cDNA and novel splicing isoforms of
RT Fe65L2 gene.";
RL Submitted (JAN-2000) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM II), AND VARIANT ARG-231.
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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT ARG-231.
RX PubMed=15372022; DOI=10.1038/nature02919;
RA Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S.,
RA Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M.,
RA She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S.,
RA Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M.,
RA Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M.,
RA Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T.,
RA Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A.,
RA Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R.,
RA Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L.,
RA Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N.,
RA Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J.,
RA Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A.,
RA Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M.;
RT "The DNA sequence and comparative analysis of human chromosome 5.";
RL Nature 431:268-274(2004).
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 II).
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 STRUCTURE BY NMR OF 30-61.
RG RIKEN structural genomics initiative (RSGI);
RT "Solution structure of the WW domain from the human amyloid beta A4
RT precursor protein-binding family B member 3, APBB3.";
RL Submitted (APR-2008) to the PDB data bank.
CC -!- FUNCTION: May modulate the internalization of amyloid-beta precursor
CC protein.
CC -!- SUBUNIT: Interacts with APP (via intracellular domain)
CC (PubMed:10081969). Interacts with APLP1 and APLP2 (via intracellular
CC domain) (PubMed:10081969). {ECO:0000269|PubMed:10081969}.
CC -!- INTERACTION:
CC O95704; P05067: APP; NbExp=5; IntAct=EBI-286427, EBI-77613;
CC O95704; Q9UN19: DAPP1; NbExp=2; IntAct=EBI-286427, EBI-3918199;
CC O95704; P00533: EGFR; NbExp=2; IntAct=EBI-286427, EBI-297353;
CC O95704; P27986-2: PIK3R1; NbExp=3; IntAct=EBI-286427, EBI-9090282;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:12153398}. Nucleus
CC {ECO:0000269|PubMed:12153398}.
CC -!- SUBCELLULAR LOCATION: [Isoform I-214]: Nucleus.
CC -!- SUBCELLULAR LOCATION: [Isoform I-245]: Nucleus.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=6;
CC Name=II;
CC IsoId=O95704-1; Sequence=Displayed;
CC Name=I;
CC IsoId=O95704-2; Sequence=VSP_006799;
CC Name=III;
CC IsoId=O95704-3; Sequence=VSP_006800;
CC Name=IV;
CC IsoId=O95704-4; Sequence=VSP_006801;
CC Name=I-214;
CC IsoId=O95704-5; Sequence=VSP_047811, VSP_047813;
CC Name=I-245;
CC IsoId=O95704-6; Sequence=VSP_047812, VSP_047814;
CC -!- TISSUE SPECIFICITY: Expressed in various tissues, highest expression in
CC brain. {ECO:0000269|PubMed:12153398}.
CC -!- MISCELLANEOUS: [Isoform I-214]: Increased expression upon apoptotic
CC stimuli. {ECO:0000305}.
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DR EMBL; AB018247; BAA35188.1; -; mRNA.
DR EMBL; AB024745; BAA78674.1; -; Genomic_DNA.
DR EMBL; AB049618; BAB40806.1; -; mRNA.
DR EMBL; AB061224; BAB71767.1; -; mRNA.
DR EMBL; AF224708; AAF65172.1; -; mRNA.
DR EMBL; AF224709; AAF65173.1; -; mRNA.
DR EMBL; AF224710; AAF65174.1; -; mRNA.
DR EMBL; AF224711; AAF65175.1; -; mRNA.
DR EMBL; AK075280; BAG52101.1; -; mRNA.
DR EMBL; AC011399; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC116353; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471062; EAW62041.1; -; Genomic_DNA.
DR EMBL; BC125187; AAI25188.1; -; mRNA.
DR CCDS; CCDS4227.1; -. [O95704-4]
DR CCDS; CCDS4228.1; -. [O95704-3]
DR CCDS; CCDS4229.1; -. [O95704-1]
DR CCDS; CCDS47279.1; -. [O95704-2]
DR RefSeq; NP_006042.3; NM_006051.3. [O95704-4]
DR RefSeq; NP_573418.2; NM_133172.2. [O95704-3]
DR RefSeq; NP_573419.2; NM_133173.2. [O95704-1]
DR RefSeq; NP_573420.2; NM_133174.2. [O95704-2]
DR PDB; 2DYQ; X-ray; 3.10 A; A=281-417.
DR PDB; 2YSC; NMR; -; A=30-61.
DR PDBsum; 2DYQ; -.
DR PDBsum; 2YSC; -.
DR AlphaFoldDB; O95704; -.
DR SMR; O95704; -.
DR BioGRID; 115593; 26.
DR IntAct; O95704; 24.
DR MINT; O95704; -.
DR STRING; 9606.ENSP00000346378; -.
DR iPTMnet; O95704; -.
DR PhosphoSitePlus; O95704; -.
DR BioMuta; APBB3; -.
DR MassIVE; O95704; -.
DR PaxDb; O95704; -.
DR PeptideAtlas; O95704; -.
DR PRIDE; O95704; -.
DR ProteomicsDB; 51002; -. [O95704-1]
DR ProteomicsDB; 51003; -. [O95704-2]
DR ProteomicsDB; 51004; -. [O95704-3]
DR ProteomicsDB; 51005; -. [O95704-4]
DR ProteomicsDB; 77814; -.
DR ProteomicsDB; 79619; -.
DR Antibodypedia; 1613; 192 antibodies from 23 providers.
DR DNASU; 10307; -.
DR Ensembl; ENST00000354402.9; ENSP00000346378.5; ENSG00000113108.20. [O95704-4]
DR Ensembl; ENST00000356738.6; ENSP00000349177.2; ENSG00000113108.20. [O95704-3]
DR Ensembl; ENST00000357560.9; ENSP00000350171.4; ENSG00000113108.20. [O95704-1]
DR Ensembl; ENST00000412920.7; ENSP00000402591.3; ENSG00000113108.20. [O95704-2]
DR Ensembl; ENST00000467078.5; ENSP00000422718.1; ENSG00000113108.20. [O95704-6]
DR Ensembl; ENST00000509914.5; ENSP00000426107.1; ENSG00000113108.20. [O95704-5]
DR GeneID; 10307; -.
DR KEGG; hsa:10307; -.
DR MANE-Select; ENST00000357560.9; ENSP00000350171.4; NM_133173.3; NP_573419.2.
DR UCSC; uc003lgd.2; human. [O95704-1]
DR CTD; 10307; -.
DR DisGeNET; 10307; -.
DR GeneCards; APBB3; -.
DR HGNC; HGNC:20708; APBB3.
DR HPA; ENSG00000113108; Tissue enhanced (brain).
DR MIM; 602711; gene.
DR neXtProt; NX_O95704; -.
DR OpenTargets; ENSG00000113108; -.
DR PharmGKB; PA134958636; -.
DR VEuPathDB; HostDB:ENSG00000113108; -.
DR eggNOG; ENOG502QR5N; Eukaryota.
DR GeneTree; ENSGT00390000000002; -.
DR HOGENOM; CLU_093354_0_0_1; -.
DR InParanoid; O95704; -.
DR OMA; LYMGILP; -.
DR PhylomeDB; O95704; -.
DR TreeFam; TF314331; -.
DR PathwayCommons; O95704; -.
DR SignaLink; O95704; -.
DR BioGRID-ORCS; 10307; 10 hits in 1075 CRISPR screens.
DR ChiTaRS; APBB3; human.
DR EvolutionaryTrace; O95704; -.
DR GeneWiki; APBB3; -.
DR GenomeRNAi; 10307; -.
DR Pharos; O95704; Tbio.
DR PRO; PR:O95704; -.
DR Proteomes; UP000005640; Chromosome 5.
DR RNAct; O95704; protein.
DR Bgee; ENSG00000113108; Expressed in right hemisphere of cerebellum and 96 other tissues.
DR ExpressionAtlas; O95704; baseline and differential.
DR Genevisible; O95704; HS.
DR GO; GO:0015629; C:actin cytoskeleton; IDA:HPA.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; IDA:ARUK-UCL.
DR GO; GO:0016020; C:membrane; IDA:ARUK-UCL.
DR GO; GO:0005634; C:nucleus; IDA:ARUK-UCL.
DR GO; GO:0001540; F:amyloid-beta binding; IBA:GO_Central.
DR GO; GO:0050750; F:low-density lipoprotein particle receptor binding; IPI:ARUK-UCL.
DR GO; GO:0050714; P:positive regulation of protein secretion; IDA:ARUK-UCL.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; IBA:GO_Central.
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; 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; Alternative splicing; Cytoplasm; Nucleus; Reference proteome;
KW Repeat.
FT CHAIN 1..486
FT /note="Amyloid-beta A4 precursor protein-binding family B
FT member 3"
FT /id="PRO_0000076054"
FT DOMAIN 29..61
FT /note="WW"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00224"
FT DOMAIN 113..280
FT /note="PID 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00148"
FT DOMAIN 285..440
FT /note="PID 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00148"
FT VAR_SEQ 196..214
FT /note="VHIRVWGVGSSKGRDRDFA -> AVIPTDADPQYLNPWTQIL (in
FT isoform I-214)"
FT /evidence="ECO:0000303|PubMed:12153398"
FT /id="VSP_047811"
FT VAR_SEQ 210..245
FT /note="DRDFAFVASDKDSCMLKCHVFCCDVPAKAIASALHG -> SSDVDPGLLPLP
FT GPALVGEGGPSSAGTVWGESERLG (in isoform I-245)"
FT /evidence="ECO:0000303|PubMed:12153398"
FT /id="VSP_047812"
FT VAR_SEQ 210..211
FT /note="Missing (in isoform I)"
FT /evidence="ECO:0000303|PubMed:10081969, ECO:0000303|Ref.4"
FT /id="VSP_006799"
FT VAR_SEQ 210
FT /note="D -> PISAPA (in isoform III)"
FT /evidence="ECO:0000303|Ref.4"
FT /id="VSP_006800"
FT VAR_SEQ 210
FT /note="D -> DSPISAPA (in isoform IV)"
FT /evidence="ECO:0000303|Ref.4"
FT /id="VSP_006801"
FT VAR_SEQ 215..486
FT /note="Missing (in isoform I-214)"
FT /evidence="ECO:0000303|PubMed:12153398"
FT /id="VSP_047813"
FT VAR_SEQ 246..486
FT /note="Missing (in isoform I-245)"
FT /evidence="ECO:0000303|PubMed:12153398"
FT /id="VSP_047814"
FT VARIANT 165
FT /note="G -> R (in dbSNP:rs7715021)"
FT /id="VAR_029518"
FT VARIANT 231
FT /note="C -> R (in dbSNP:rs250430)"
FT /evidence="ECO:0000269|PubMed:10081969,
FT ECO:0000269|PubMed:10329396, ECO:0000269|PubMed:14702039,
FT ECO:0000269|PubMed:15372022, ECO:0000269|Ref.4"
FT /id="VAR_024702"
FT STRAND 35..40
FT /evidence="ECO:0007829|PDB:2YSC"
FT STRAND 43..51
FT /evidence="ECO:0007829|PDB:2YSC"
FT STRAND 54..57
FT /evidence="ECO:0007829|PDB:2YSC"
FT STRAND 292..304
FT /evidence="ECO:0007829|PDB:2DYQ"
FT HELIX 307..318
FT /evidence="ECO:0007829|PDB:2DYQ"
FT STRAND 327..333
FT /evidence="ECO:0007829|PDB:2DYQ"
FT STRAND 335..342
FT /evidence="ECO:0007829|PDB:2DYQ"
FT STRAND 354..358
FT /evidence="ECO:0007829|PDB:2DYQ"
FT HELIX 359..361
FT /evidence="ECO:0007829|PDB:2DYQ"
FT STRAND 362..367
FT /evidence="ECO:0007829|PDB:2DYQ"
FT STRAND 373..379
FT /evidence="ECO:0007829|PDB:2DYQ"
FT STRAND 381..383
FT /evidence="ECO:0007829|PDB:2DYQ"
FT STRAND 385..391
FT /evidence="ECO:0007829|PDB:2DYQ"
FT HELIX 397..415
FT /evidence="ECO:0007829|PDB:2DYQ"
SQ SEQUENCE 486 AA; 52585 MW; 553DFB4D8655EFA1 CRC64;
MLGKDYMLAI ILVNCDDDLW GDHSLEVEAG LPPGWRKIHD AAGTYYWHVP SGSTQWQRPT
WELGDAEDPG TGTEGIWGLR PPKGRSFSSL ESSLDRSNSL SWYGGESYIQ SMEPGAKCFA
VRSLGWVEVP EEDLAPGKSS IAVNNCIQQL AQTRSRSQPP DGAWGEGQNM LMILKKDAMS
LVNPLDHSLI HCQPLVHIRV WGVGSSKGRD RDFAFVASDK DSCMLKCHVF CCDVPAKAIA
SALHGLCAQI LSERVEVSGD ASCCSPDPIS PEDLPRQVEL LDAVSQAAQK YEALYMGTLP
VTKAMGMDVL NEAIGTLTAR GDRNAWVPTM LSVSDSLMTA HPIQAEASTE EEPLWQCPVR
LVTFIGVGRD PHTFGLIADL GRQSFQCAAF WCQPHAGGLS EAVQAACMVQ YQKCLVASAA
RGKAWGAQAR ARLRLKRTSS MDSPGGPLPL PLLKGGVGGA GATPRKRGVF SFLDAFRLKP
SLLHMP
