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Protein

Amyloid beta A4 precursor protein-binding family A member 1

Gene

Apba1

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Putative function in synaptic vesicle exocytosis by binding to Munc18-1, an essential component of the synaptic vesicle exocytotic machinery. May modulate processing of the beta-amyloid precursor protein (APP) and hence formation of beta-AAP.

GO - Molecular functioni

  • beta-amyloid binding Source: RGD
  • PDZ domain binding Source: RGD
  • phosphatidylinositol-4,5-bisphosphate binding Source: RGD
  • protein complex binding Source: RGD

GO - Biological processi

  • protein complex assembly Source: InterPro
  • protein transport Source: UniProtKB-KW
  • synaptic vesicle exocytosis Source: RGD
Complete GO annotation...

Keywords - Biological processi

Protein transport, Transport

Names & Taxonomyi

Protein namesi
Recommended name:
Amyloid beta A4 precursor protein-binding family A member 1
Alternative name(s):
Adapter protein X11alpha
Neuron-specific X11 protein
Neuronal Munc18-1-interacting protein 1
Short name:
Mint-1
Gene namesi
Name:Apba1
Synonyms:Mint1, X11
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Unplaced

Organism-specific databases

RGDi620844. Apba1.

Subcellular locationi

Isoform 2 :

GO - Cellular componenti

  • cytosol Source: GOC
  • dendritic spine Source: CACAO
  • Golgi apparatus Source: UniProtKB-SubCell
  • nucleus Source: UniProtKB-SubCell
  • perinuclear region of cytoplasm Source: UniProtKB-SubCell
  • plasma membrane Source: RGD
  • protein complex Source: RGD
  • synaptic vesicle Source: InterPro
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Golgi apparatus, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi633 – 6331Y → E: Enhanced APP binding and beta-amyloid production. 1 Publication
Mutagenesisi633 – 6331Y → F: No change in APP binding. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 839839Amyloid beta A4 precursor protein-binding family A member 1PRO_0000064615Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei79 – 791PhosphoserineBy similarity
Modified residuei243 – 2431PhosphoserineCombined sources
Modified residuei247 – 2471PhosphoserineCombined sources
Modified residuei249 – 2491PhosphoserineCombined sources
Modified residuei264 – 2641PhosphoserineCombined sources
Modified residuei281 – 2811PhosphoserineBy similarity
Modified residuei306 – 3061PhosphothreonineBy similarity
Modified residuei314 – 3141PhosphoserineCombined sources
Modified residuei369 – 3691PhosphoserineBy similarity
Modified residuei372 – 3721PhosphothreonineBy similarity
Modified residuei403 – 4031PhosphoserineBy similarity
Modified residuei405 – 4051PhosphoserineBy similarity
Modified residuei410 – 4101PhosphoserineBy similarity
Modified residuei570 – 5701PhosphoserineCombined sources

Keywords - PTMi

Phosphoprotein

Proteomic databases

PaxDbiO35430.
PRIDEiO35430.

PTM databases

iPTMnetiO35430.
PhosphoSiteiO35430.

Expressioni

Tissue specificityi

Brain. Detected in the cerebellum, hippocampus, olfactory system, piriform and entorhinal cortex, supraoptic nucleus of the hypothalamus, substantia nigra, and other mesencephalic areas.

Interactioni

Subunit structurei

Part of a multimeric complex containing Munc18-1 and syntaxin-1. Also part of the brain-specific heterotrimeric complex LIN-10/X11-alpha, LIN-2/CASK, and LIN7. Binds to the cytoplasmic domain of amyloid protein (APP) (By similarity). Interacts (via PDZ 1 and 2 domains) with FSPB (By similarity). Isoform 2 interacts (via its truncated PID domain) with active, GTP-bound RAB6A and RAB6B (By similarity).By similarity

Binary interactionsi

WithEntry#Exp.IntActNotes
Stx1aP328513EBI-704760,EBI-539720
Stxbp1P617655EBI-704760,EBI-1029097

GO - Molecular functioni

  • PDZ domain binding Source: RGD
  • protein complex binding Source: RGD

Protein-protein interaction databases

BioGridi249774. 7 interactions.
IntActiO35430. 3 interactions.
MINTiMINT-102360.
STRINGi10116.ENSRNOP00000020123.

Chemistry

BindingDBiO35430.

Structurei

Secondary structure

1
839
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi460 – 47718Combined sources
Helixi481 – 49313Combined sources
Beta strandi517 – 53216Combined sources
Turni533 – 5353Combined sources
Beta strandi538 – 5436Combined sources
Helixi544 – 5463Combined sources
Beta strandi547 – 5537Combined sources
Beta strandi556 – 5638Combined sources
Beta strandi587 – 5959Combined sources
Helixi599 – 61416Combined sources
Helixi615 – 6173Combined sources
Helixi625 – 6273Combined sources
Helixi630 – 63910Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
4DBBX-ray1.90A453-643[»]
ProteinModelPortaliO35430.
SMRiO35430. Positions 455-623, 657-839.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini459 – 645187PIDPROSITE-ProRule annotationAdd
BLAST
Domaini658 – 74487PDZ 1PROSITE-ProRule annotationAdd
BLAST
Domaini749 – 82476PDZ 2PROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni227 – 31589Munc-18-1 bindingAdd
BLAST
Regioni375 – 43864LIN-2/CASK bindingAdd
BLAST
Regioni628 – 64316Autoinhibitory helix linkerAdd
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi40 – 6526Pro-richAdd
BLAST
Compositional biasi67 – 715Poly-Glu
Compositional biasi295 – 33137Pro-richAdd
BLAST
Compositional biasi370 – 45485Pro-richAdd
BLAST

Domaini

Composed of an N-terminal domain that binds Munc18-1 and LIN-2/CASK, a middle phosphotyrosine-binding domain (PID/PTB) that mediates binding with the cytoplasmic domain of the beta-amyloid precursor protein, and two C-terminal PDZ domains thought to attach proteins to the plasma membrane.By similarity
The autoinhibitory helix linker occludes the APP binding site.
The PID domain, truncated by 11 amino acids, as observed in isoform 2, but not full-length, mediates the interaction with RAB6A.By similarity

Sequence similaritiesi

Contains 2 PDZ (DHR) domains.PROSITE-ProRule annotation
Contains 1 PID domain.PROSITE-ProRule annotation

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiKOG3605. Eukaryota.
ENOG410XSBD. LUCA.
HOGENOMiHOG000033981.
HOVERGENiHBG050523.
InParanoidiO35430.
KOiK04531.
PhylomeDBiO35430.

Family and domain databases

Gene3Di2.30.29.30. 1 hit.
2.30.42.10. 2 hits.
InterProiIPR030530. Apba1.
IPR001478. PDZ.
IPR011993. PH_dom-like.
IPR006020. PTB/PI_dom.
[Graphical view]
PANTHERiPTHR12345:SF14. PTHR12345:SF14. 1 hit.
PfamiPF00595. PDZ. 2 hits.
PF00640. PID. 1 hit.
[Graphical view]
SMARTiSM00228. PDZ. 2 hits.
SM00462. PTB. 1 hit.
[Graphical view]
SUPFAMiSSF50156. SSF50156. 2 hits.
SSF50729. SSF50729. 1 hit.
PROSITEiPS50106. PDZ. 2 hits.
PS01179. PID. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: O35430-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MNHLEGSAEV EVADEAPGGE VNESVEADLE HPEVEEEQQP SPPPPAGHAP
60 70 80 90 100
EDHRAHPAPP PPPPPQEEEE ERGECLARSA STESGFHNHT DTAEGDVLAA
110 120 130 140 150
ARDGYEAERA QDADDESAYA VQYRPEAEEY TEQAEAEHAE AAQRRALPNH
160 170 180 190 200
LHFHSLEHEE AMNAAYSGYV YTHRLFHRAE DEPYAEPYAD YGGLQEHVYE
210 220 230 240 250
EIGDAPELEA RDGLRLYERE RDEAAAYRQE ALGARLHHYD ERSDGESDSP
260 270 280 290 300
EKEAEFAPYP RMDSYEQEED IDQIVAEVKQ SMSSQSLDKA AEDMPEAEQD
310 320 330 340 350
LERAPTPGGG HPDSPGLPAP AGQQQRVVGT PGGSEVGQRY SKEKRDAISL
360 370 380 390 400
AIKDIKEAIE EVKTRTIRSP YTPDEPKEPI WVMRQDISPT RDCDDQRPVD
410 420 430 440 450
GDSPSPGSSS PLGAESSITP LHPGDPTEAS TNKESRKSLA SFPTYVEVPG
460 470 480 490 500
PCDPEDLIDG IIFAANYLGS TQLLSDKTPS KNVRMMQAQE AVSRIKTAQK
510 520 530 540 550
LAKSRKKAPE GESQPMTEVD LFISTQRIKV LNADTQEPMM DHPLRTISYI
560 570 580 590 600
ADIGNIVVLM ARRRMPRSNS QENVEASHPS QDAKRQYKMI CHVFESEDAQ
610 620 630 640 650
LIAQSIGQAF SVAYQEFLRA NGINPEDLSQ KEYSDLLNTQ DMYNDDLIHF
660 670 680 690 700
SKSENCKDVF IEKQKGEILG VVIVESGWGS ILPTVIIANM MHGGPAEKSG
710 720 730 740 750
KLNIGDQIMS INGTSLVGLP LSTCQSIIKG LKNQSRVKLN IVRCPPVTTV
760 770 780 790 800
LIRRPDLRYQ LGFSVQNGII CSLMRGGIAE RGGVRVGHRI IEINGQSVVA
810 820 830
TPHEKIVHIL SNAVGEIHMK TMPAAMYRLL TAQEQPVYI
Length:839
Mass (Da):92,654
Last modified:January 1, 1998 - v1
Checksum:i57F6EEA458376CAD
GO
Isoform 2 (identifier: O35430-2) [UniParc]FASTAAdd to basket

Also known as: Mint1_826

The sequence of this isoform differs from the canonical sequence as follows:
     497-507: Missing.

Note: This isoform interacts with RAB6 GTPases.By similarity
Show »
Length:828
Mass (Da):91,413
Checksum:iFE72D6DE098CFC27
GO

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei497 – 50711Missing in isoform 2. CuratedVSP_053520Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF029105 mRNA. Translation: AAC05303.1.
RefSeqiNP_113967.1. NM_031779.2. [O35430-1]
UniGeneiRn.54819.

Genome annotation databases

GeneIDi83589.
KEGGirno:83589.
UCSCiRGD:620844. rat. [O35430-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF029105 mRNA. Translation: AAC05303.1.
RefSeqiNP_113967.1. NM_031779.2. [O35430-1]
UniGeneiRn.54819.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
4DBBX-ray1.90A453-643[»]
ProteinModelPortaliO35430.
SMRiO35430. Positions 455-623, 657-839.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi249774. 7 interactions.
IntActiO35430. 3 interactions.
MINTiMINT-102360.
STRINGi10116.ENSRNOP00000020123.

Chemistry

BindingDBiO35430.

PTM databases

iPTMnetiO35430.
PhosphoSiteiO35430.

Proteomic databases

PaxDbiO35430.
PRIDEiO35430.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi83589.
KEGGirno:83589.
UCSCiRGD:620844. rat. [O35430-1]

Organism-specific databases

CTDi320.
RGDi620844. Apba1.

Phylogenomic databases

eggNOGiKOG3605. Eukaryota.
ENOG410XSBD. LUCA.
HOGENOMiHOG000033981.
HOVERGENiHBG050523.
InParanoidiO35430.
KOiK04531.
PhylomeDBiO35430.

Miscellaneous databases

PROiO35430.

Family and domain databases

Gene3Di2.30.29.30. 1 hit.
2.30.42.10. 2 hits.
InterProiIPR030530. Apba1.
IPR001478. PDZ.
IPR011993. PH_dom-like.
IPR006020. PTB/PI_dom.
[Graphical view]
PANTHERiPTHR12345:SF14. PTHR12345:SF14. 1 hit.
PfamiPF00595. PDZ. 2 hits.
PF00640. PID. 1 hit.
[Graphical view]
SMARTiSM00228. PDZ. 2 hits.
SM00462. PTB. 1 hit.
[Graphical view]
SUPFAMiSSF50156. SSF50156. 2 hits.
SSF50729. SSF50729. 1 hit.
PROSITEiPS50106. PDZ. 2 hits.
PS01179. PID. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Mints, Munc18-interacting proteins in synaptic vesicle exocytosis."
    Okamoto M., Suedhof T.C.
    J. Biol. Chem. 272:31459-31464(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
    Tissue: Brain.
  2. "A tripartite protein complex with the potential to couple synaptic vesicle exocytosis to cell adhesion in brain."
    Butz S., Okamoto M., Suedhof T.C.
    Cell 94:773-782(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH CASK AND LIN7.
    Tissue: Testis.
  3. "An X11alpha/FSBP complex represses transcription of the GSK3beta gene promoter."
    Lau K.F., Perkinton M.S., Rodriguez L., McLoughlin D.M., Miller C.C.
    NeuroReport 21:761-766(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBCELLULAR LOCATION, INTERACTION WITH FSBP.
  4. "Quantitative maps of protein phosphorylation sites across 14 different rat organs and tissues."
    Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C., Olsen J.V.
    Nat. Commun. 3:876-876(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-243; SER-247; SER-249; SER-264; SER-314 AND SER-570, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  5. "Autoinhibition of Mint1 adaptor protein regulates amyloid precursor protein binding and processing."
    Matos M.F., Xu Y., Dulubova I., Otwinowski Z., Richardson J.M., Tomchick D.R., Rizo J., Ho A.
    Proc. Natl. Acad. Sci. U.S.A. 109:3802-3807(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 453-643, AUTOINHIBITORY DOMAIN, MUTAGENESIS OF TYR-633, INTERACTION WITH APP.

Entry informationi

Entry nameiAPBA1_RAT
AccessioniPrimary (citable) accession number: O35430
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: January 1, 1998
Last modified: June 8, 2016
This is version 110 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.