APBA1_RAT
ID APBA1_RAT Reviewed; 839 AA.
AC O35430;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-JAN-1998, sequence version 1.
DT 25-MAY-2022, entry version 144.
DE RecName: Full=Amyloid-beta A4 precursor protein-binding family A member 1;
DE AltName: Full=Adapter protein X11alpha;
DE AltName: Full=Neuron-specific X11 protein;
DE AltName: Full=Neuronal Munc18-1-interacting protein 1;
DE Short=Mint-1;
GN Name=Apba1; Synonyms=Mint1, X11;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (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 [2]
RP INTERACTION WITH CASK AND LIN7.
RC TISSUE=Testis;
RX PubMed=9753324; DOI=10.1016/s0092-8674(00)81736-5;
RA Butz S., Okamoto M., Suedhof T.C.;
RT "A tripartite protein complex with the potential to couple synaptic vesicle
RT exocytosis to cell adhesion in brain.";
RL Cell 94:773-782(1998).
RN [3]
RP SUBCELLULAR LOCATION, AND INTERACTION WITH FSBP.
RX PubMed=20531236; DOI=10.1097/wnr.0b013e32833bfca0;
RA Lau K.F., Perkinton M.S., Rodriguez L., McLoughlin D.M., Miller C.C.;
RT "An X11alpha/FSBP complex represses transcription of the GSK3beta gene
RT promoter.";
RL NeuroReport 21:761-766(2010).
RN [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-243; SER-247; SER-249;
RP SER-264; SER-286; SER-314 AND SER-570, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
RN [5]
RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 453-643, AUTOINHIBITORY DOMAIN,
RP MUTAGENESIS OF TYR-633, AND INTERACTION WITH APP.
RX PubMed=22355143; DOI=10.1073/pnas.1119075109;
RA Matos M.F., Xu Y., Dulubova I., Otwinowski Z., Richardson J.M.,
RA Tomchick D.R., Rizo J., Ho A.;
RT "Autoinhibition of Mint1 adaptor protein regulates amyloid precursor
RT protein binding and processing.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:3802-3807(2012).
CC -!- FUNCTION: Putative function in synaptic vesicle exocytosis by binding
CC to Munc18-1, 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 Munc18-1 and syntaxin-
CC 1. Component of the brain-specific heterotrimeric complex (LIN-10-LIN-
CC 2-LIN-7 complex) composed of at least APBA1, CASK, and LIN7, which
CC associates with the motor protein KIF17 to transport vesicles along
CC microtubules (By similarity). Within the complex, interacts (via PDZ
CC domain) with the motor protein KIF17; the interaction is direct and is
CC required for association of KIF17 with the cargo that is to be
CC transported (By similarity). Binds to the cytoplasmic domain of amyloid
CC protein (APP) (By similarity). Interacts (via PDZ 1 and 2 domains) with
CC FSPB (By similarity). Isoform 2 interacts (via its truncated PID
CC domain) with active, GTP-bound RAB6A and RAB6B (By similarity).
CC {ECO:0000250, ECO:0000250|UniProtKB:B2RUJ5}.
CC -!- INTERACTION:
CC O35430; P32851: Stx1a; NbExp=3; IntAct=EBI-704760, EBI-539720;
CC O35430; P61765: Stxbp1; NbExp=5; IntAct=EBI-704760, EBI-1029097;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Cytoplasm, perinuclear
CC region {ECO:0000250}. Nucleus {ECO:0000269|PubMed:20531236}. Note=Only
CC a small proportion of the protein is nuclear.
CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Golgi apparatus {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=O35430-1; Sequence=Displayed;
CC Name=2; Synonyms=Mint1_826;
CC IsoId=O35430-2; Sequence=VSP_053520;
CC -!- TISSUE SPECIFICITY: Brain. Detected in the cerebellum, hippocampus,
CC olfactory system, piriform and entorhinal cortex, supraoptic nucleus of
CC the hypothalamus, substantia nigra, and other mesencephalic areas.
CC -!- DOMAIN: Composed of an N-terminal domain that binds Munc18-1 and LIN-
CC 2/CASK, a middle phosphotyrosine-binding domain (PID/PTB) that mediates
CC binding with the cytoplasmic domain of the amyloid-beta precursor
CC protein, and two C-terminal PDZ domains thought to attach proteins to
CC the plasma membrane. {ECO:0000250}.
CC -!- DOMAIN: The autoinhibitory helix linker occludes the APP binding site.
CC -!- DOMAIN: The PID domain, truncated by 11 amino acids, as observed in
CC isoform 2, but not full-length, mediates the interaction with RAB6A.
CC {ECO:0000250}.
CC -!- MISCELLANEOUS: [Isoform 2]: This isoform interacts with RAB6 GTPases.
CC {ECO:0000250}.
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DR EMBL; AF029105; AAC05303.1; -; mRNA.
DR RefSeq; NP_113967.1; NM_031779.2. [O35430-1]
DR PDB; 4DBB; X-ray; 1.90 A; A=453-643.
DR PDB; 6KMH; X-ray; 2.40 A; C/D=338-397.
DR PDBsum; 4DBB; -.
DR PDBsum; 6KMH; -.
DR AlphaFoldDB; O35430; -.
DR BMRB; O35430; -.
DR SMR; O35430; -.
DR BioGRID; 249774; 7.
DR CORUM; O35430; -.
DR ELM; O35430; -.
DR IntAct; O35430; 3.
DR MINT; O35430; -.
DR STRING; 10116.ENSRNOP00000020123; -.
DR BindingDB; O35430; -.
DR CarbonylDB; O35430; -.
DR iPTMnet; O35430; -.
DR PhosphoSitePlus; O35430; -.
DR PaxDb; O35430; -.
DR PeptideAtlas; O35430; -.
DR PRIDE; O35430; -.
DR GeneID; 83589; -.
DR KEGG; rno:83589; -.
DR UCSC; RGD:620844; rat. [O35430-1]
DR CTD; 320; -.
DR RGD; 620844; Apba1.
DR eggNOG; KOG3605; Eukaryota.
DR InParanoid; O35430; -.
DR OrthoDB; 436779at2759; -.
DR PhylomeDB; O35430; -.
DR Reactome; R-RNO-212676; Dopamine Neurotransmitter Release Cycle.
DR PRO; PR:O35430; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0043197; C:dendritic spine; IDA:CACAO.
DR GO; GO:0098978; C:glutamatergic synapse; ISO:RGD.
DR GO; GO:0005794; C:Golgi apparatus; IEA:UniProtKB-SubCell.
DR GO; GO:0016020; C:membrane; ISO:RGD.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; IDA:RGD.
DR GO; GO:0048787; C:presynaptic active zone membrane; ISO:RGD.
DR GO; GO:0032991; C:protein-containing complex; IDA:RGD.
DR GO; GO:0098685; C:Schaffer collateral - CA1 synapse; ISO:RGD.
DR GO; GO:0008021; C:synaptic vesicle; IEA:InterPro.
DR GO; GO:0001540; F:amyloid-beta binding; IPI:RGD.
DR GO; GO:0030165; F:PDZ domain binding; IPI:RGD.
DR GO; GO:0005546; F:phosphatidylinositol-4,5-bisphosphate binding; IDA:RGD.
DR GO; GO:0044877; F:protein-containing complex binding; IDA:RGD.
DR GO; GO:0007268; P:chemical synaptic transmission; ISO:RGD.
DR GO; GO:0014051; P:gamma-aminobutyric acid secretion; ISO:RGD.
DR GO; GO:0014047; P:glutamate secretion; ISO:RGD.
DR GO; GO:0001701; P:in utero embryonic development; ISO:RGD.
DR GO; GO:0006886; P:intracellular protein transport; ISO:RGD.
DR GO; GO:0007626; P:locomotory behavior; ISO:RGD.
DR GO; GO:0035264; P:multicellular organism growth; ISO:RGD.
DR GO; GO:0065003; P:protein-containing complex assembly; IEA:InterPro.
DR GO; GO:0010468; P:regulation of gene expression; ISO:RGD.
DR GO; GO:2000300; P:regulation of synaptic vesicle exocytosis; ISO:RGD.
DR GO; GO:0016079; P:synaptic vesicle exocytosis; TAS:RGD.
DR Gene3D; 2.30.29.30; -; 1.
DR Gene3D; 2.30.42.10; -; 2.
DR InterPro; IPR030530; Apba1.
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:SF14; PTHR12345:SF14; 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; Alternative splicing; Cytoplasm; Golgi apparatus; Nucleus;
KW Phosphoprotein; Protein transport; Reference proteome; Repeat; Transport.
FT CHAIN 1..839
FT /note="Amyloid-beta A4 precursor protein-binding family A
FT member 1"
FT /id="PRO_0000064615"
FT DOMAIN 459..645
FT /note="PID"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00148"
FT DOMAIN 658..744
FT /note="PDZ 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00143"
FT DOMAIN 749..824
FT /note="PDZ 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00143"
FT REGION 1..118
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 227..315
FT /note="Munc-18-1 binding"
FT REGION 235..346
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 362..437
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 375..438
FT /note="LIN-2/CASK binding"
FT REGION 628..643
FT /note="Autoinhibitory helix linker"
FT COMPBIAS 101..118
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 235..275
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 402..416
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 423..437
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 79
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:B2RUJ5"
FT MOD_RES 243
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 247
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 249
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 264
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 281
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:B2RUJ5"
FT MOD_RES 286
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 306
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q02410"
FT MOD_RES 314
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 369
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:B2RUJ5"
FT MOD_RES 372
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q02410"
FT MOD_RES 403
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:B2RUJ5"
FT MOD_RES 405
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:B2RUJ5"
FT MOD_RES 410
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:B2RUJ5"
FT MOD_RES 570
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT VAR_SEQ 497..507
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_053520"
FT MUTAGEN 633
FT /note="Y->E: Enhanced APP binding and amyloid-beta
FT production."
FT /evidence="ECO:0000269|PubMed:22355143"
FT MUTAGEN 633
FT /note="Y->F: No change in APP binding."
FT /evidence="ECO:0000269|PubMed:22355143"
FT HELIX 342..364
FT /evidence="ECO:0007829|PDB:6KMH"
FT STRAND 460..477
FT /evidence="ECO:0007829|PDB:4DBB"
FT HELIX 481..493
FT /evidence="ECO:0007829|PDB:4DBB"
FT STRAND 517..532
FT /evidence="ECO:0007829|PDB:4DBB"
FT TURN 533..535
FT /evidence="ECO:0007829|PDB:4DBB"
FT STRAND 538..543
FT /evidence="ECO:0007829|PDB:4DBB"
FT HELIX 544..546
FT /evidence="ECO:0007829|PDB:4DBB"
FT STRAND 547..553
FT /evidence="ECO:0007829|PDB:4DBB"
FT STRAND 556..563
FT /evidence="ECO:0007829|PDB:4DBB"
FT STRAND 587..595
FT /evidence="ECO:0007829|PDB:4DBB"
FT HELIX 599..614
FT /evidence="ECO:0007829|PDB:4DBB"
FT HELIX 615..617
FT /evidence="ECO:0007829|PDB:4DBB"
FT HELIX 625..627
FT /evidence="ECO:0007829|PDB:4DBB"
FT HELIX 630..639
FT /evidence="ECO:0007829|PDB:4DBB"
SQ SEQUENCE 839 AA; 92654 MW; 57F6EEA458376CAD CRC64;
MNHLEGSAEV EVADEAPGGE VNESVEADLE HPEVEEEQQP SPPPPAGHAP EDHRAHPAPP
PPPPPQEEEE ERGECLARSA STESGFHNHT DTAEGDVLAA ARDGYEAERA QDADDESAYA
VQYRPEAEEY TEQAEAEHAE AAQRRALPNH LHFHSLEHEE AMNAAYSGYV YTHRLFHRAE
DEPYAEPYAD YGGLQEHVYE EIGDAPELEA RDGLRLYERE RDEAAAYRQE ALGARLHHYD
ERSDGESDSP EKEAEFAPYP RMDSYEQEED IDQIVAEVKQ SMSSQSLDKA AEDMPEAEQD
LERAPTPGGG HPDSPGLPAP AGQQQRVVGT PGGSEVGQRY SKEKRDAISL AIKDIKEAIE
EVKTRTIRSP YTPDEPKEPI WVMRQDISPT RDCDDQRPVD GDSPSPGSSS PLGAESSITP
LHPGDPTEAS TNKESRKSLA SFPTYVEVPG PCDPEDLIDG IIFAANYLGS TQLLSDKTPS
KNVRMMQAQE AVSRIKTAQK LAKSRKKAPE GESQPMTEVD LFISTQRIKV LNADTQEPMM
DHPLRTISYI ADIGNIVVLM ARRRMPRSNS QENVEASHPS QDAKRQYKMI CHVFESEDAQ
LIAQSIGQAF SVAYQEFLRA NGINPEDLSQ KEYSDLLNTQ DMYNDDLIHF SKSENCKDVF
IEKQKGEILG VVIVESGWGS ILPTVIIANM MHGGPAEKSG KLNIGDQIMS INGTSLVGLP
LSTCQSIIKG LKNQSRVKLN IVRCPPVTTV LIRRPDLRYQ LGFSVQNGII CSLMRGGIAE
RGGVRVGHRI IEINGQSVVA TPHEKIVHIL SNAVGEIHMK TMPAAMYRLL TAQEQPVYI
