APBA2_HUMAN
ID APBA2_HUMAN Reviewed; 749 AA.
AC Q99767; E9PGI4; O60571; Q5XKC0;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 30-MAY-2000, sequence version 3.
DT 03-AUG-2022, entry version 185.
DE RecName: Full=Amyloid-beta A4 precursor protein-binding family A member 2;
DE AltName: Full=Adapter protein X11beta;
DE AltName: Full=Neuron-specific X11L protein;
DE AltName: Full=Neuronal Munc18-1-interacting protein 2;
DE Short=Mint-2;
GN Name=APBA2; Synonyms=MINT2, X11L;
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] (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=9614075; DOI=10.1074/jbc.273.24.14761;
RA Borg J.-P., Yang Y., De Taddeo-Borg M., Margolis B., Turner R.S.;
RT "The X11alpha protein slows cellular amyloid precursor protein processing
RT and reduces Abeta40 and Abeta42 secretion.";
RL J. Biol. Chem. 273:14761-14766(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=9890987; DOI=10.1074/jbc.274.4.2243;
RA Tomita S., Ozaki T., Taru H., Oguchi S., Takeda S., Yagi Y., Sakiyama S.,
RA Kirino Y., Suzuki T.;
RT "Interaction of a neuron-specific protein containing PDZ domains with
RT Alzheimer's amyloid precursor protein.";
RL J. Biol. Chem. 274:2243-2254(1999).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16572171; DOI=10.1038/nature04601;
RA Zody M.C., Garber M., Sharpe T., Young S.K., Rowen L., O'Neill K.,
RA Whittaker C.A., Kamal M., Chang J.L., Cuomo C.A., Dewar K.,
RA FitzGerald M.G., Kodira C.D., Madan A., Qin S., Yang X., Abbasi N.,
RA Abouelleil A., Arachchi H.M., Baradarani L., Birditt B., Bloom S.,
RA Bloom T., Borowsky M.L., Burke J., Butler J., Cook A., DeArellano K.,
RA DeCaprio D., Dorris L. III, Dors M., Eichler E.E., Engels R., Fahey J.,
RA Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G., Johnson E.,
RA Jones C., Kamat A., Kaur A., Locke D.P., Madan A., Munson G., Jaffe D.B.,
RA Lui A., Macdonald P., Mauceli E., Naylor J.W., Nesbitt R., Nicol R.,
RA O'Leary S.B., Ratcliffe A., Rounsley S., She X., Sneddon K.M.B.,
RA Stewart S., Sougnez C., Stone S.M., Topham K., Vincent D., Wang S.,
RA Zimmer A.R., Birren B.W., Hood L., Lander E.S., Nusbaum C.;
RT "Analysis of the DNA sequence and duplication history of human chromosome
RT 15.";
RL Nature 440:671-675(2006).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND VARIANT PRO-311.
RC TISSUE=Ovary;
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 [5]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 532-749 (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=9395480; DOI=10.1074/jbc.272.50.31459;
RA Okamoto M., Suedhof T.C.;
RT "Mints, Munc18-interacting proteins in synaptic vesicle exocytosis.";
RL J. Biol. Chem. 272:31459-31464(1997).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 532-749 (ISOFORM 1).
RC TISSUE=Brain;
RX PubMed=9110174; DOI=10.1101/gr.7.4.353;
RA Yu W., Andersson B., Worley K.C., Muzny D.M., Ding Y., Liu W.,
RA Ricafrente J.Y., Wentland M.A., Lennon G., Gibbs R.A.;
RT "Large-scale concatenation cDNA sequencing.";
RL Genome Res. 7:353-358(1997).
RN [7]
RP INTERACTION WITH NECAB3.
RC TISSUE=Brain;
RX PubMed=10833507; DOI=10.1074/jbc.c000302200;
RA Lee D.-S., Tomita S., Kirino Y., Suzuki T.;
RT "Regulation of X11L-dependent amyloid precursor protein metabolism by XB51,
RT a novel X11L-binding protein.";
RL J. Biol. Chem. 275:23134-23138(2000).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-11 AND SER-208, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=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).
CC -!- FUNCTION: Putative function in synaptic vesicle exocytosis by binding
CC to STXBP1, an essential component of the synaptic vesicle exocytotic
CC machinery. May modulate processing of the amyloid-beta precursor
CC protein (APP) and hence formation of APP-beta.
CC -!- SUBUNIT: Part of a multimeric complex containing STXBP1 and syntaxin-1.
CC Binds to the cytoplasmic domain of amyloid-beta protein, and to the
CC nuclear factor NF-kappa-B/p65 via its PDZ domain. Interacts with the N-
CC terminal domain of NECAB3. {ECO:0000269|PubMed:10833507}.
CC -!- INTERACTION:
CC Q99767; Q99767: APBA2; NbExp=2; IntAct=EBI-81711, EBI-81711;
CC Q99767; P05067: APP; NbExp=2; IntAct=EBI-81711, EBI-77613;
CC Q99767; O94985: CLSTN1; NbExp=2; IntAct=EBI-81711, EBI-522075;
CC Q99767-2; Q8N7X4: MAGEB6; NbExp=3; IntAct=EBI-12218351, EBI-6447163;
CC Q99767-2; A0A024R8A9: USP20; NbExp=3; IntAct=EBI-12218351, EBI-14096082;
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q99767-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q99767-2; Sequence=VSP_045692;
CC -!- TISSUE SPECIFICITY: Brain.
CC -!- DOMAIN: Composed of an N-terminal domain that binds STXBP1, a middle
CC phosphotyrosine-binding domain (PID/PTB) that mediates binding with the
CC cytoplasmic domain of the amyloid-beta precursor protein, and two C-
CC terminal PDZ 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; AF047348; AAC39767.1; -; mRNA.
DR EMBL; AB014719; BAA34734.1; -; mRNA.
DR EMBL; AC024474; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC127522; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC174469; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC082986; AAH82986.1; -; mRNA.
DR EMBL; AF029108; AAC05306.1; -; mRNA.
DR EMBL; U79255; AAB50203.1; -; mRNA.
DR CCDS; CCDS10022.1; -. [Q99767-1]
DR CCDS; CCDS45197.1; -. [Q99767-2]
DR RefSeq; NP_001123886.1; NM_001130414.1. [Q99767-2]
DR RefSeq; NP_005494.2; NM_005503.3. [Q99767-1]
DR RefSeq; XP_011519790.1; XM_011521488.2. [Q99767-1]
DR RefSeq; XP_011519791.1; XM_011521489.2. [Q99767-1]
DR RefSeq; XP_011519792.1; XM_011521490.2. [Q99767-1]
DR RefSeq; XP_011519793.1; XM_011521491.1. [Q99767-1]
DR RefSeq; XP_011519794.1; XM_011521492.2. [Q99767-1]
DR RefSeq; XP_016877590.1; XM_017022101.1.
DR RefSeq; XP_016877591.1; XM_017022102.1.
DR RefSeq; XP_016877592.1; XM_017022103.1.
DR RefSeq; XP_016877593.1; XM_017022104.1.
DR RefSeq; XP_016877594.1; XM_017022105.1.
DR RefSeq; XP_016877595.1; XM_017022106.1.
DR RefSeq; XP_016877596.1; XM_017022107.1.
DR RefSeq; XP_016877597.1; XM_017022108.1.
DR RefSeq; XP_016877598.1; XM_017022109.1.
DR RefSeq; XP_016877599.1; XM_017022110.1. [Q99767-1]
DR RefSeq; XP_016877600.1; XM_017022111.1.
DR RefSeq; XP_016877601.1; XM_017022112.1. [Q99767-1]
DR RefSeq; XP_016877602.1; XM_017022113.1.
DR RefSeq; XP_016877603.1; XM_017022114.1.
DR RefSeq; XP_016877604.1; XM_017022115.1.
DR RefSeq; XP_016877605.1; XM_017022116.1.
DR RefSeq; XP_016877606.1; XM_017022117.1.
DR AlphaFoldDB; Q99767; -.
DR SMR; Q99767; -.
DR BioGRID; 106818; 41.
DR ELM; Q99767; -.
DR IntAct; Q99767; 33.
DR MINT; Q99767; -.
DR STRING; 9606.ENSP00000453293; -.
DR TCDB; 8.A.24.2.3; the ezrin/radixin/moesin-binding phosphoprotein 50 (ebp50) family.
DR iPTMnet; Q99767; -.
DR PhosphoSitePlus; Q99767; -.
DR BioMuta; APBA2; -.
DR DMDM; 6226950; -.
DR EPD; Q99767; -.
DR jPOST; Q99767; -.
DR MassIVE; Q99767; -.
DR MaxQB; Q99767; -.
DR PaxDb; Q99767; -.
DR PeptideAtlas; Q99767; -.
DR PRIDE; Q99767; -.
DR ProteomicsDB; 20327; -.
DR ProteomicsDB; 78469; -. [Q99767-1]
DR Antibodypedia; 22443; 209 antibodies from 35 providers.
DR DNASU; 321; -.
DR Ensembl; ENST00000411764.5; ENSP00000409312.1; ENSG00000034053.15. [Q99767-2]
DR Ensembl; ENST00000558259.5; ENSP00000454171.1; ENSG00000034053.15. [Q99767-1]
DR Ensembl; ENST00000558330.5; ENSP00000452722.1; ENSG00000034053.15. [Q99767-2]
DR Ensembl; ENST00000558402.5; ENSP00000453293.1; ENSG00000034053.15. [Q99767-1]
DR Ensembl; ENST00000561069.5; ENSP00000453144.1; ENSG00000034053.15. [Q99767-1]
DR Ensembl; ENST00000612449.2; ENSP00000483174.1; ENSG00000276495.4. [Q99767-2]
DR Ensembl; ENST00000620457.4; ENSP00000480384.1; ENSG00000276495.4. [Q99767-1]
DR Ensembl; ENST00000631894.1; ENSP00000488107.1; ENSG00000276495.4. [Q99767-1]
DR Ensembl; ENST00000683413.1; ENSP00000507394.1; ENSG00000034053.15. [Q99767-1]
DR GeneID; 321; -.
DR KEGG; hsa:321; -.
DR MANE-Select; ENST00000683413.1; ENSP00000507394.1; NM_001353788.2; NP_001340717.1.
DR UCSC; uc001zck.4; human. [Q99767-1]
DR CTD; 321; -.
DR DisGeNET; 321; -.
DR GeneCards; APBA2; -.
DR HGNC; HGNC:579; APBA2.
DR HPA; ENSG00000034053; Tissue enhanced (brain, lymphoid tissue).
DR MIM; 602712; gene.
DR neXtProt; NX_Q99767; -.
DR OpenTargets; ENSG00000034053; -.
DR PharmGKB; PA24870; -.
DR VEuPathDB; HostDB:ENSG00000034053; -.
DR eggNOG; KOG3605; Eukaryota.
DR GeneTree; ENSGT00940000158943; -.
DR HOGENOM; CLU_013563_3_0_1; -.
DR InParanoid; Q99767; -.
DR OMA; KPLPHSC; -.
DR OrthoDB; 436779at2759; -.
DR PhylomeDB; Q99767; -.
DR TreeFam; TF315245; -.
DR PathwayCommons; Q99767; -.
DR Reactome; R-HSA-6794361; Neurexins and neuroligins.
DR SignaLink; Q99767; -.
DR SIGNOR; Q99767; -.
DR BioGRID-ORCS; 321; 12 hits in 1074 CRISPR screens.
DR ChiTaRS; APBA2; human.
DR GeneWiki; APBA2; -.
DR GenomeRNAi; 321; -.
DR Pharos; Q99767; Tbio.
DR PRO; PR:Q99767; -.
DR Proteomes; UP000005640; Chromosome 15.
DR RNAct; Q99767; protein.
DR Bgee; ENSG00000034053; Expressed in superior frontal gyrus and 97 other tissues.
DR ExpressionAtlas; Q99767; baseline and differential.
DR Genevisible; Q99767; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0043197; C:dendritic spine; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0098685; C:Schaffer collateral - CA1 synapse; IEA:Ensembl.
DR GO; GO:0008021; C:synaptic vesicle; IEA:InterPro.
DR GO; GO:0001540; F:amyloid-beta binding; IBA:GO_Central.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
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:0007626; P:locomotory behavior; IEA:Ensembl.
DR GO; GO:0035264; P:multicellular organism growth; IEA:Ensembl.
DR GO; GO:0007399; P:nervous system development; TAS:ProtInc.
DR GO; GO:0015031; P:protein transport; IEA:UniProtKB-KW.
DR GO; GO:0010468; P:regulation of gene expression; IEA:Ensembl.
DR GO; GO:2000300; P:regulation of synaptic vesicle exocytosis; IEA:Ensembl.
DR Gene3D; 2.30.29.30; -; 1.
DR Gene3D; 2.30.42.10; -; 2.
DR InterPro; IPR030529; Apba2.
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:SF12; PTHR12345:SF12; 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 Alternative splicing; Phosphoprotein; Protein transport;
KW Reference proteome; Repeat; Transport.
FT CHAIN 1..749
FT /note="Amyloid-beta A4 precursor protein-binding family A
FT member 2"
FT /id="PRO_0000064616"
FT DOMAIN 368..555
FT /note="PID"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00148"
FT DOMAIN 568..654
FT /note="PDZ 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00143"
FT DOMAIN 659..734
FT /note="PDZ 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00143"
FT REGION 1..94
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 130..220
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 185..270
FT /note="STXBP1-binding"
FT REGION 238..344
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 78..94
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 143..157
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 172..189
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 294..316
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 322..344
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 11
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 208
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT VAR_SEQ 406..417
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_045692"
FT VARIANT 311
FT /note="L -> P (in dbSNP:rs8040932)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_050665"
FT CONFLICT 135
FT /note="Q -> H (in Ref. 2; BAA34734)"
FT /evidence="ECO:0000305"
FT CONFLICT 163
FT /note="G -> R (in Ref. 1; AAC39767)"
FT /evidence="ECO:0000305"
FT CONFLICT 170..214
FT /note="DEPSVLEAHDQEEDGHYCASKEGYQDYYPEEANGNTGASPYRLRR -> MSP
FT PSLRPMTRKKMVTMCQQRGLPGLLPRGGQREHRRLPLPPEA (in Ref. 1;
FT AAC39767)"
FT /evidence="ECO:0000305"
FT CONFLICT 344
FT /note="E -> K (in Ref. 2; BAA34734)"
FT /evidence="ECO:0000305"
FT CONFLICT 354
FT /note="F -> L (in Ref. 2; BAA34734)"
FT /evidence="ECO:0000305"
FT CONFLICT 364..365
FT /note="ED -> KN (in Ref. 2; BAA34734)"
FT /evidence="ECO:0000305"
FT CONFLICT 604
FT /note="G -> C (in Ref. 1; AAC39767)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 749 AA; 82512 MW; C15AE9CFAEF51D85 CRC64;
MAHRKLESVG SGMLDHRVRP GPVPHSQEPE SEDMELPLEG YVPEGLELAA LRPESPAPEE
QECHNHSPDG DSSSDYVNNT SEEEDYDEGL PEEEEGITYY IRYCPEDDSY LEGMDCNGEE
YLAHSAHPVD TDECQEAVEE WTDSAGPHPH GHEAEGSQDY PDGQLPIPED EPSVLEAHDQ
EEDGHYCASK EGYQDYYPEE ANGNTGASPY RLRRGDGDLE DQEEDIDQIV AEIKMSLSMT
SITSASEASP EHGPEPGPED SVEACPPIKA SCSPSRHEAR PKSLNLLPEA KHPGDPQRGF
KPKTRTPEER LKWPHEQVCN GLEQPRKQQR SDLNGPVDNN NIPETKKVAS FPSFVAVPGP
CEPEDLIDGI IFAANYLGST QLLSERNPSK NIRMMQAQEA VSRVKRMQKA AKIKKKANSE
GDAQTLTEVD LFISTQRIKV LNADTQETMM DHALRTISYI ADIGNIVVLM ARRRMPRSAS
QDCIETTPGA QEGKKQYKMI CHVFESEDAQ LIAQSIGQAF SVAYQEFLRA NGINPEDLSQ
KEYSDIINTQ EMYNDDLIHF SNSENCKELQ LEKHKGEILG VVVVESGWGS ILPTVILANM
MNGGPAARSG KLSIGDQIMS INGTSLVGLP LATCQGIIKG LKNQTQVKLN IVSCPPVTTV
LIKRPDLKYQ LGFSVQNGII CSLMRGGIAE RGGVRVGHRI IEINGQSVVA TAHEKIVQAL
SNSVGEIHMK TMPAAMFRLL TGQETPLYI