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 24-JAN-2024, entry version 182. 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. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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; 64. DR IntAct; O96018; 42. DR MINT; O96018; -. DR STRING; 9606.ENSP00000315136; -. DR GlyGen; O96018; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; O96018; -. DR PhosphoSitePlus; O96018; -. DR BioMuta; APBA3; -. DR EPD; O96018; -. DR jPOST; O96018; -. DR MassIVE; O96018; -. DR MaxQB; O96018; -. DR PaxDb; 9606-ENSP00000315136; -. DR PeptideAtlas; O96018; -. DR ProteomicsDB; 51210; -. DR Pumba; O96018; -. DR Antibodypedia; 23338; 190 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 AGR; HGNC:580; -. 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; HCEECPP; -. DR OrthoDB; 2881953at2759; -. 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; 13 hits in 1150 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 171 other cell types or tissues. 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 CDD; cd00992; PDZ_signaling; 2. DR CDD; cd01208; PTB_X11; 1. DR Gene3D; 2.30.42.10; -; 2. DR Gene3D; 2.30.29.30; Pleckstrin-homology domain (PH domain)/Phosphotyrosine-binding domain (PTB); 1. 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; AMYLOID-BETA A4 PRECURSOR PROTEIN-BINDING FAMILY A MEMBER 3; 1. DR PANTHER; PTHR12345; SYNTENIN RELATED; 1. DR Pfam; PF00595; PDZ; 2. DR Pfam; PF00640; PID; 1. DR SMART; SM00228; PDZ; 2. DR SMART; SM00462; PTB; 1. DR SUPFAM; SSF50156; PDZ domain-like; 2. DR SUPFAM; SSF50729; PH domain-like; 1. DR PROSITE; PS50106; PDZ; 2. DR PROSITE; PS01179; PID; 1. DR Genevisible; O96018; HS. 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 //