Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

Q03157 (APLP1_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 129. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Amyloid-like protein 1

Short name=APLP
Short name=APLP-1

Cleaved into the following chain:

  1. C30
Gene names
Name:Aplp1
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length653 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

May play a role in postsynaptic function. The C-terminal gamma-secretase processed fragment, ALID1, activates transcription activation through APBB1 (Fe65) binding. Couples to JIP signal transduction through C-terminal binding. May interact with cellular G-protein signaling pathways. Can regulate neurite outgrowth through binding to components of the extracellular matrix such as heparin and collagen I.

The gamma-CTF peptide, C30, is a potent enhancer of neuronal apoptosis By similarity.

Subunit structure

Monomer and homodimer. Heparin binding promotes homodimerization. Binds, via its C-terminus, to the PID domain of several cytoplasmic proteins, including APBB and APBA family members, MAPK8IP1 and Dab1 By similarity. Binding to Dab1 inhibits its serine phosphorylation. Interacts with CPEB1. Interacts (via NPXY motif) with DAB2 (via PID domain); the interaction is impaired by tyrosine phosphorylation of the NPXY motif. Interacts (via NPXY motif) with DAB1. Ref.4 Ref.5 Ref.6 Ref.7 Ref.8 Ref.9

Subcellular location

Cell membrane; Single-pass type I membrane protein.

C30: Cytoplasm. Note: C-terminally processed in the Golgi complex.

Domain

The NPXY sequence motif found in many tyrosine-phosphorylated proteins is required for the specific binding of the PID domain. However, additional amino acids either N- or C-terminal to the NPXY motif are often required for complete interaction. The NPXY site is also involved in clathrin-mediated endocytosis.

Post-translational modification

Proteolytically cleaved by caspases during neuronal apoptosis. Cleaved, in vitro, at Asp-623 by caspase-3 By similarity. Ref.7

N- and O-glycosylated.

Miscellaneous

Binds zinc and copper in the extracellular domain. Zinc-binding increases heparin binding. No Cu2+ reducing activity with copper-binding.

Sequence similarities

Belongs to the APP family.

Ontologies

Keywords
   Biological processApoptosis
Cell adhesion
Endocytosis
   Cellular componentCell membrane
Cytoplasm
Membrane
   DiseaseNeurodegeneration
   DomainSignal
Transmembrane
Transmembrane helix
   LigandCopper
Heparin-binding
Metal-binding
Zinc
   PTMGlycoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processapoptotic process

Inferred from electronic annotation. Source: UniProtKB-KW

cell adhesion

Inferred from electronic annotation. Source: UniProtKB-KW

cellular response to norepinephrine stimulus

Inferred from electronic annotation. Source: Ensembl

endocytosis

Inferred from electronic annotation. Source: UniProtKB-KW

extracellular matrix organization

Inferred from genetic interaction PubMed 15385965. Source: MGI

forebrain development

Inferred from genetic interaction PubMed 15385965. Source: MGI

mRNA polyadenylation

Inferred from direct assay Ref.9. Source: MGI

negative regulation of cAMP biosynthetic process

Inferred from electronic annotation. Source: Ensembl

regulation of translation

Inferred from direct assay Ref.9. Source: MGI

   Cellular_componentGolgi apparatus

Inferred from direct assay Ref.1. Source: UniProtKB

integral component of membrane

Traceable author statement Ref.4. Source: UniProtKB

membrane

Inferred from direct assay Ref.9. Source: MGI

perinuclear region of cytoplasm

Inferred from electronic annotation. Source: Ensembl

plasma membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular_functionheparin binding

Inferred from electronic annotation. Source: UniProtKB-KW

transition metal ion binding

Inferred from electronic annotation. Source: InterPro

Complete GO annotation...

Binary interactions

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 3737 Potential
Chain38 – 653616Amyloid-like protein 1
PRO_0000000205
Peptide624 – 65330C30 By similarity
PRO_0000000206

Regions

Topological domain38 – 583546Extracellular Potential
Transmembrane584 – 60623Helical; Potential
Topological domain607 – 65347Cytoplasmic Potential
Region157 – 17721Copper-binding
Region203 – 2108Zinc-binding By similarity
Region313 – 34533Heparin-binding By similarity
Region413 – 44432Heparin-binding By similarity
Region445 – 46218Collagen-binding By similarity
Region635 – 65117Interaction with DAB1
Region639 – 65315Interaction with DAB2
Motif607 – 61812Basolateral sorting signal By similarity
Motif643 – 6464NPXY motif; contains endocytosis signal
Compositional bias263 – 2719Poly-Glu
Compositional bias535 – 5384Poly-Ser
Compositional bias601 – 6066Poly-Leu

Sites

Site1661Required for Cu(2+) reduction By similarity
Site623 – 6242Cleavage; by caspase-3 By similarity

Amino acid modifications

Glycosylation4641N-linked (GlcNAc...) Potential
Glycosylation5541N-linked (GlcNAc...) Potential

Experimental info

Mutagenesis6411Y → G: Reduced binding of APBB1. Ref.7
Sequence conflict181P → PP in AAH21877. Ref.2

Sequences

Sequence LengthMass (Da)Tools
Q03157 [UniParc].

Last modified October 1, 1993. Version 1.
Checksum: 56516DC3EA40E4B0

FASTA65372,751
        10         20         30         40         50         60 
MGPTSPAARG QGRRWRPPLP LLLPLSLLLL RAQLAVGNLA VGSPSAAEAP GSAQVAGLCG 

        70         80         90        100        110        120 
RLTLHRDLRT GRWEPDPQRS RRCLLDPQRV LEYCRQMYPE LHIARVEQAA QAIPMERWCG 

       130        140        150        160        170        180 
GTRSGRCAHP HHEVVPFHCL PGEFVSEALL VPEGCRFLHQ ERMDQCESST RRHQEAQEAC 

       190        200        210        220        230        240 
SSQGLILHGS GMLLPCGSDR FRGVEYVCCP PPATPNPSGM AAGDPSTRSW PLGGRAEGGE 

       250        260        270        280        290        300 
DEEEVESFPQ PVDDYFVEPP QAEEEEEEEE ERAPPPSSHT PVMVSRVTPT PRPTDGVDVY 

       310        320        330        340        350        360 
FGMPGEIGEH EGFLRAKMDL EERRMRQINE VMREWAMADS QSKNLPKADR QALNEHFQSI 

       370        380        390        400        410        420 
LQTLEEQVSG ERQRLVETHA TRVIALINDQ RRAALEGFLA ALQGDPPQAE RVLMALRRYL 

       430        440        450        460        470        480 
RAEQKEQRHT LRHYQHVAAV DPEKAQQMRF QVQTHLQVIE ERMNQSLGLL DQNPHLAQEL 

       490        500        510        520        530        540 
RPQIQELLLA EHLGPSELDA SVPGSSSEDK GSLQPPESKD DPPVTLPKGS TDQESSSSGR 

       550        560        570        580        590        600 
EKLTPLEQYE QKVNASAPRG FPFHSSDIQR DELAPSGTGV SREALSGLLI MGAGGGSLIV 

       610        620        630        640        650 
LSLLLLRKKK PYGTISHGVV EVDPMLTLEE QQLRELQRHG YENPTYRFLE ERP 

« Hide

References

« Hide 'large scale' references
[1]"Identification of a mouse brain cDNA that encodes a protein related to the Alzheimer disease-associated amyloid beta protein precursor."
Wasco W., Bupp K., Magendantz M., Gusella J.F., Tanzi R.E., Solomon F.
Proc. Natl. Acad. Sci. U.S.A. 89:10758-10762(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Brain.
[2]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Retina.
[3]"Regulation of amyloid protein precursor (APP) binding to collagen and mapping of the binding sites on APP and collagen type I."
Beher D., Hesse L., Masters C.L., Multhaup G.
J. Biol. Chem. 271:1613-1620(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: COLLAGEN-BINDING.
[4]"Disabled-1 binds to the cytoplasmic domain of amyloid precursor-like protein 1."
Homayouni R., Rice D.S., Sheldon M., Curran T.
J. Neurosci. 19:7507-7515(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH DAB1.
[5]"C-jun N-terminal kinase (JNK)-interacting protein-1b/islet-brain-1 scaffolds Alzheimer's amyloid precursor protein with JNK."
Matsuda S., Yasukawa T., Homma Y., Ito Y., Niikura T., Hiraki T., Hirai S., Ohno S., Kita Y., Kawasumi M., Kouyama K., Yamamoto T., Kyriakis J.M., Nishimoto I.
J. Neurosci. 21:6597-6607(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH MAPK8IP1.
[6]"Disabled-2 colocalizes with the LDLR in clathrin-coated pits and interacts with AP-2."
Morris S.M., Cooper J.A.
Traffic 2:111-123(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH DAB2.
[7]"Processing of beta-amyloid precursor-like protein-1 and -2 by gamma-secretase regulates transcription."
Scheinfeld M.H., Ghersi E., Laky K., Fowlkes B.J., D'Adamio L.
J. Biol. Chem. 277:44195-44201(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEOLYTIC PROCESSING BY GAMMA SECRETASE, INTERACTION WITH APBB1, MUTAGENESIS OF TYR-641.
[8]"Crystal structures of the Dab homology domains of mouse disabled 1 and 2."
Yun M., Keshvara L., Park C.G., Zhang Y.M., Dickerson J.B., Zheng J., Rock C.O., Curran T., Park H.W.
J. Biol. Chem. 278:36572-36581(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH DAB1.
[9]"Amyloid precursor proteins anchor CPEB to membranes and promote polyadenylation-induced translation."
Cao Q., Huang Y.-S., Kan M.-C., Richter J.D.
Mol. Cell. Biol. 25:10930-10939(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH CPEB1.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
L04538 mRNA. Translation: AAA37247.1.
BC021877 mRNA. Translation: AAH21877.1.
PIRA46362.
RefSeqNP_031493.2. NM_007467.3.
UniGeneMm.2381.

3D structure databases

ProteinModelPortalQ03157.
SMRQ03157. Positions 50-218, 295-488, 582-609.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid198153. 1 interaction.
IntActQ03157. 10 interactions.
MINTMINT-1177110.

PTM databases

PhosphoSiteQ03157.

Proteomic databases

PaxDbQ03157.
PRIDEQ03157.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000006828; ENSMUSP00000006828; ENSMUSG00000006651.
GeneID11803.
KEGGmmu:11803.
UCSCuc009gek.2. mouse.

Organism-specific databases

CTD333.
MGIMGI:88046. Aplp1.

Phylogenomic databases

eggNOGNOG289770.
GeneTreeENSGT00530000063252.
HOVERGENHBG000051.
InParanoidQ03157.
KOK05639.
OrthoDBEOG7RNJZP.
PhylomeDBQ03157.
TreeFamTF317274.

Gene expression databases

BgeeQ03157.
CleanExMM_APLP1.
GenevestigatorQ03157.

Family and domain databases

Gene3D3.30.1490.140. 1 hit.
3.90.570.10. 1 hit.
InterProIPR008155. Amyloid_glyco.
IPR011178. Amyloid_glyco_Cu-bd.
IPR024329. Amyloid_glyco_E2_domain.
IPR008154. Amyloid_glyco_extra.
IPR019744. Amyloid_glyco_extracell_CS.
IPR015849. Amyloid_glyco_heparin-bd.
IPR019745. Amyloid_glyco_intracell_CS.
IPR019543. APP_amyloid_C.
[Graphical view]
PfamPF10515. APP_amyloid. 1 hit.
PF12924. APP_Cu_bd. 1 hit.
PF12925. APP_E2. 1 hit.
PF02177. APP_N. 1 hit.
[Graphical view]
PRINTSPR00203. AMYLOIDA4.
SMARTSM00006. A4_EXTRA. 1 hit.
[Graphical view]
SUPFAMSSF109843. SSF109843. 1 hit.
SSF56491. SSF56491. 1 hit.
SSF89811. SSF89811. 1 hit.
PROSITEPS00319. A4_EXTRA. 1 hit.
PS00320. A4_INTRA. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSAPLP1. mouse.
NextBio279655.
PROQ03157.
SOURCESearch...

Entry information

Entry nameAPLP1_MOUSE
AccessionPrimary (citable) accession number: Q03157
Secondary accession number(s): Q8VC38
Entry history
Integrated into UniProtKB/Swiss-Prot: October 1, 1993
Last sequence update: October 1, 1993
Last modified: April 16, 2014
This is version 129 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot