APBA3_HUMAN
ID APBA3_HUMAN Reviewed; 575 AA.
AC O96018; O60483; Q9UPZ2;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1999, sequence version 1.
DT 03-AUG-2022, entry version 174.
DE RecName: Full=Amyloid-beta A4 precursor protein-binding family A member 3;
DE AltName: Full=Adapter protein X11gamma;
DE AltName: Full=Neuron-specific X11L2 protein;
DE AltName: Full=Neuronal Munc18-1-interacting protein 3;
DE Short=Mint-3;
GN Name=APBA3; Synonyms=MINT3, X11L2;
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].
RC TISSUE=Brain;
RX PubMed=10049767; DOI=10.1006/bbrc.1999.0265;
RA Tanahashi H., Tabira T.;
RT "X11L2, a new member of X11 protein family interacts with Alzheimer's beta-
RT amyloid precursor protein.";
RL Biochem. Biophys. Res. Commun. 255:663-667(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15057824; DOI=10.1038/nature02399;
RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E.,
RA Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A.,
RA Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S.,
RA Carrano A.V., Caoile C., Chan Y.M., Christensen M., Cleland C.A.,
RA Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J.,
RA Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M.,
RA Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W.,
RA Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V.,
RA Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D.,
RA McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I.,
RA Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L.,
RA Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A.,
RA She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M.,
RA Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J.,
RA Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E.,
RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M.,
RA Rubin E.M., Lucas S.M.;
RT "The DNA sequence and biology of human chromosome 19.";
RL Nature 428:529-535(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Lung;
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 [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 207-575.
RX PubMed=10574372; DOI=10.1097/00001756-199908200-00025;
RA Tanahashi H., Tabira T.;
RT "Genomic organization of the human X11L2 gene (APBA3), a third member of
RT the X11 protein family interacting with Alzheimer's beta-amyloid precursor
RT protein.";
RL NeuroReport 10:2575-2578(1999).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 472-575.
RX PubMed=9860131; DOI=10.1016/s0171-9335(98)80103-9;
RA Okamoto M., Suedhof T.C.;
RT "Mint 3: a ubiquitous mint isoform that does not bind to munc18-1 or -2.";
RL Eur. J. Cell Biol. 77:161-165(1998).
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the
RT kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-372, VARIANT [LARGE SCALE
RP ANALYSIS] ARG-376, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [8]
RP FUNCTION, INTERACTION WITH HIF1AN, AND SUBCELLULAR LOCATION.
RX PubMed=19726677; DOI=10.1074/jbc.m109.019216;
RA Sakamoto T., Seiki M.;
RT "Mint3 enhances the activity of hypoxia-inducible factor-1 (HIF-1) in
RT macrophages by suppressing the activity of factor inhibiting HIF-1.";
RL J. Biol. Chem. 284:30350-30359(2009).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19369195; DOI=10.1074/mcp.m800588-mcp200;
RA Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G.,
RA Mann M., Daub H.;
RT "Large-scale proteomics analysis of the human kinome.";
RL Mol. Cell. Proteomics 8:1751-1764(2009).
RN [10]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-11, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [12]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [13]
RP INTERACTION WITH NECAB3.
RX PubMed=26948053; DOI=10.1038/srep22784;
RA Nakaoka H.J., Hara T., Yoshino S., Kanamori A., Matsui Y., Shimamura T.,
RA Sato H., Murakami Y., Seiki M., Sakamoto T.;
RT "NECAB3 promotes activation of hypoxia-inducible factor-1 during normoxia
RT and enhances tumourigenicity of cancer cells.";
RL Sci. Rep. 6:22784-22784(2016).
RN [14]
RP STRUCTURE BY NMR OF 387-569.
RG RIKEN structural genomics initiative (RSGI);
RT "Solution structure of the PDZ domain of amyloid beta A4 precursor protein-
RT binding family A member 3.";
RL Submitted (APR-2008) to the PDB data bank.
CC -!- FUNCTION: May modulate processing of the amyloid-beta precursor protein
CC (APP) and hence formation of APP-beta. May enhance the activity of
CC HIF1A in macrophages by inhibiting the activity of HIF1AN.
CC {ECO:0000269|PubMed:19726677}.
CC -!- SUBUNIT: Binds to the cytoplasmic domain of amyloid protein (APP) in
CC vivo. Interacts with HIF1AN (via N-terminus). Interacts with NECAB3;
CC seems to mediate the interaction between NECAB3 and HIF1AN.
CC {ECO:0000269|PubMed:19726677, ECO:0000269|PubMed:26948053}.
CC -!- INTERACTION:
CC O96018; P05067: APP; NbExp=3; IntAct=EBI-6115839, EBI-77613;
CC O96018; Q9NWT6: HIF1AN; NbExp=6; IntAct=EBI-6115839, EBI-745632;
CC O96018; Q96P71: NECAB3; NbExp=2; IntAct=EBI-6115839, EBI-5773009;
CC O96018; Q96P71-2: NECAB3; NbExp=4; IntAct=EBI-6115839, EBI-15098952;
CC O96018; Q92844: TANK; NbExp=2; IntAct=EBI-6115839, EBI-356349;
CC O96018; A7MCY6: TBKBP1; NbExp=2; IntAct=EBI-6115839, EBI-359969;
CC O96018; Q9QYP6: Azi2; Xeno; NbExp=2; IntAct=EBI-6115839, EBI-6115874;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, perinuclear region
CC {ECO:0000269|PubMed:19726677}.
CC -!- TISSUE SPECIFICITY: Expressed in all tissues examined with lower levels
CC in brain and testis.
CC -!- DOMAIN: Composed of an N-terminal domain, a middle phosphotyrosine-
CC binding domain (PID/PTB) that mediates binding with the cytoplasmic
CC domain of the amyloid-beta precursor protein, and two C-terminal PDZ
CC domains thought to attach proteins to the plasma membrane.
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DR EMBL; AB021638; BAA74430.1; -; mRNA.
DR EMBL; AC005954; AAC72275.1; -; Genomic_DNA.
DR EMBL; BC086306; AAH86306.1; -; mRNA.
DR EMBL; AB023431; BAA83094.1; -; Genomic_DNA.
DR EMBL; AF029110; AAC17979.1; -; mRNA.
DR CCDS; CCDS12110.1; -.
DR PIR; JG0181; JG0181.
DR RefSeq; NP_004877.1; NM_004886.3.
DR PDB; 2YT7; NMR; -; A=390-483.
DR PDB; 2YT8; NMR; -; A=483-569.
DR PDB; 5UWS; X-ray; 2.40 A; D=55-72.
DR PDBsum; 2YT7; -.
DR PDBsum; 2YT8; -.
DR PDBsum; 5UWS; -.
DR AlphaFoldDB; O96018; -.
DR SMR; O96018; -.
DR BioGRID; 114920; 65.
DR IntAct; O96018; 44.
DR MINT; O96018; -.
DR STRING; 9606.ENSP00000315136; -.
DR iPTMnet; O96018; -.
DR PhosphoSitePlus; O96018; -.
DR BioMuta; APBA3; -.
DR EPD; O96018; -.
DR jPOST; O96018; -.
DR MassIVE; O96018; -.
DR MaxQB; O96018; -.
DR PaxDb; O96018; -.
DR PeptideAtlas; O96018; -.
DR PRIDE; O96018; -.
DR ProteomicsDB; 51210; -.
DR Antibodypedia; 23338; 168 antibodies from 28 providers.
DR DNASU; 9546; -.
DR Ensembl; ENST00000316757.4; ENSP00000315136.2; ENSG00000011132.12.
DR GeneID; 9546; -.
DR KEGG; hsa:9546; -.
DR MANE-Select; ENST00000316757.4; ENSP00000315136.2; NM_004886.4; NP_004877.1.
DR UCSC; uc002lyp.2; human.
DR CTD; 9546; -.
DR DisGeNET; 9546; -.
DR GeneCards; APBA3; -.
DR HGNC; HGNC:580; APBA3.
DR HPA; ENSG00000011132; Low tissue specificity.
DR MIM; 604262; gene.
DR neXtProt; NX_O96018; -.
DR OpenTargets; ENSG00000011132; -.
DR PharmGKB; PA24872; -.
DR VEuPathDB; HostDB:ENSG00000011132; -.
DR eggNOG; KOG3605; Eukaryota.
DR GeneTree; ENSGT00940000160384; -.
DR HOGENOM; CLU_013563_2_0_1; -.
DR InParanoid; O96018; -.
DR OMA; YPAPQEV; -.
DR OrthoDB; 436779at2759; -.
DR PhylomeDB; O96018; -.
DR TreeFam; TF315245; -.
DR PathwayCommons; O96018; -.
DR Reactome; R-HSA-6794361; Neurexins and neuroligins.
DR SignaLink; O96018; -.
DR SIGNOR; O96018; -.
DR BioGRID-ORCS; 9546; 12 hits in 1074 CRISPR screens.
DR ChiTaRS; APBA3; human.
DR EvolutionaryTrace; O96018; -.
DR GeneWiki; APBA3; -.
DR GenomeRNAi; 9546; -.
DR Pharos; O96018; Tbio.
DR PRO; PR:O96018; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; O96018; protein.
DR Bgee; ENSG00000011132; Expressed in pancreatic ductal cell and 170 other tissues.
DR Genevisible; O96018; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0043197; C:dendritic spine; IBA:GO_Central.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0001540; F:amyloid-beta binding; IBA:GO_Central.
DR GO; GO:0019899; F:enzyme binding; IPI:UniProtKB.
DR GO; GO:0004857; F:enzyme inhibitor activity; IDA:UniProtKB.
DR GO; GO:0007268; P:chemical synaptic transmission; IBA:GO_Central.
DR GO; GO:0001701; P:in utero embryonic development; IEA:Ensembl.
DR GO; GO:0043086; P:negative regulation of catalytic activity; IDA:UniProtKB.
DR GO; GO:0015031; P:protein transport; IEA:UniProtKB-KW.
DR GO; GO:0010468; P:regulation of gene expression; IEA:Ensembl.
DR Gene3D; 2.30.29.30; -; 1.
DR Gene3D; 2.30.42.10; -; 2.
DR InterPro; IPR030531; Apba3.
DR InterPro; IPR001478; PDZ.
DR InterPro; IPR036034; PDZ_sf.
DR InterPro; IPR011993; PH-like_dom_sf.
DR InterPro; IPR006020; PTB/PI_dom.
DR PANTHER; PTHR12345:SF9; PTHR12345:SF9; 1.
DR Pfam; PF00595; PDZ; 2.
DR Pfam; PF00640; PID; 1.
DR SMART; SM00228; PDZ; 2.
DR SMART; SM00462; PTB; 1.
DR SUPFAM; SSF50156; SSF50156; 2.
DR PROSITE; PS50106; PDZ; 2.
DR PROSITE; PS01179; PID; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Cytoplasm; Phosphoprotein; Protein transport;
KW Reference proteome; Repeat; Transport.
FT CHAIN 1..575
FT /note="Amyloid-beta A4 precursor protein-binding family A
FT member 3"
FT /id="PRO_0000064620"
FT DOMAIN 217..381
FT /note="PID"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00148"
FT DOMAIN 394..480
FT /note="PDZ 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00143"
FT DOMAIN 485..560
FT /note="PDZ 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00143"
FT REGION 1..50
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 118..211
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 215..364
FT /note="Required for interaction with NECAB3"
FT /evidence="ECO:0000269|PubMed:26948053"
FT COMPBIAS 161..176
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0007744|PubMed:22814378"
FT MOD_RES 11
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 171
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O70248"
FT MOD_RES 372
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT VARIANT 154
FT /note="W -> L (in dbSNP:rs35932323)"
FT /id="VAR_050666"
FT VARIANT 276
FT /note="K -> T (in dbSNP:rs3746119)"
FT /id="VAR_020134"
FT VARIANT 376
FT /note="C -> R (in dbSNP:rs8102086)"
FT /evidence="ECO:0007744|PubMed:18669648"
FT /id="VAR_047952"
FT VARIANT 527
FT /note="I -> F (in dbSNP:rs1045236)"
FT /id="VAR_011822"
FT CONFLICT 505
FT /note="I -> IVRPRPLAPGWGGRAALSTAPEQPPPLSRAPLFLPQ (in Ref.
FT 5; AAC17979)"
FT /evidence="ECO:0000305"
FT HELIX 57..65
FT /evidence="ECO:0007829|PDB:5UWS"
FT STRAND 393..398
FT /evidence="ECO:0007829|PDB:2YT7"
FT STRAND 407..411
FT /evidence="ECO:0007829|PDB:2YT7"
FT STRAND 415..418
FT /evidence="ECO:0007829|PDB:2YT7"
FT STRAND 421..426
FT /evidence="ECO:0007829|PDB:2YT7"
FT HELIX 433..435
FT /evidence="ECO:0007829|PDB:2YT7"
FT STRAND 443..449
FT /evidence="ECO:0007829|PDB:2YT7"
FT HELIX 457..466
FT /evidence="ECO:0007829|PDB:2YT7"
FT TURN 467..469
FT /evidence="ECO:0007829|PDB:2YT7"
FT STRAND 470..477
FT /evidence="ECO:0007829|PDB:2YT7"
FT STRAND 483..490
FT /evidence="ECO:0007829|PDB:2YT8"
FT STRAND 493..495
FT /evidence="ECO:0007829|PDB:2YT8"
FT STRAND 498..502
FT /evidence="ECO:0007829|PDB:2YT8"
FT STRAND 505..509
FT /evidence="ECO:0007829|PDB:2YT8"
FT HELIX 515..518
FT /evidence="ECO:0007829|PDB:2YT8"
FT STRAND 525..529
FT /evidence="ECO:0007829|PDB:2YT8"
FT HELIX 539..548
FT /evidence="ECO:0007829|PDB:2YT8"
FT STRAND 551..558
FT /evidence="ECO:0007829|PDB:2YT8"
FT HELIX 560..566
FT /evidence="ECO:0007829|PDB:2YT8"
SQ SEQUENCE 575 AA; 61454 MW; 3B910CC74C5F3840 CRC64;
MDFPTISRSP SGPPAMDLEG PRDILVPSED LTPDSQWDPM PGGPGSLSRM ELDESSLQEL
VQQFEALPGD LVGPSPGGAP CPLHIATGHG LASQEIADAH GLLSAEAGRD DLLGLLHCEE
CPPSQTGPEE PLEPAPRLLQ PPEDPDEDSD SPEWVEGASA EQEGSRSSSS SPEPWLETVP
LVTPEEPPAG AQSPETLASY PAPQEVPGPC DHEDLLDGVI FGARYLGSTQ LVSERNPPTS
TRMAQAREAM DRVKAPDGET QPMTEVDLFV STKRIKVLTA DSQEAMMDHA LHTISYTADI
GCVLVLMARR RLARRPAPQD HGRRLYKMLC HVFYAEDAQL IAQAIGQAFA AAYSQFLRES
GIDPSQVGVH PSPGACHLHN GDLDHFSNSD NCREVHLEKR RGEGLGVALV ESGWGSLLPT
AVIANLLHGG PAERSGALSI GDRLTAINGT SLVGLPLAAC QAAVRETKSQ TSVTLSIVHC
PPVTTAIIHR PHAREQLGFC VEDGIICSLL RGGIAERGGI RVGHRIIEIN GQSVVATPHA
RIIELLTEAY GEVHIKTMPA ATYRLLTGQE QPVYL
