Q03157 (APLP1_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Amyloid-like protein 1
Short name=APLP
Short name=APLP-1

Cleaved into the following chain:

1. C30

Gene names

Name:

Aplp1

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	653 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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 process	Apoptosis Cell adhesion Endocytosis
Cellular component	Cell membrane Cytoplasm Membrane
Disease	Neurodegeneration
Domain	Signal Transmembrane Transmembrane helix
Ligand	Copper Heparin-binding Metal-binding Zinc
PTM	Glycoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	apoptotic 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: Compara 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: Compara regulation of translation Inferred from direct assay Ref.9. Source: MGI
Cellular_component	Golgi apparatus Inferred from direct assay Ref.1. Source: UniProtKB integral to membrane Traceable author statement Ref.4. Source: UniProtKB perinuclear region of cytoplasm Inferred from electronic annotation. Source: Compara plasma membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	heparin binding Inferred from electronic annotation. Source: UniProtKB-KW transition metal ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
App	P12023	4	EBI-399929,EBI-78814
Dab1	P97318	4	EBI-399929,EBI-81680

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 37	37	Potential
	Chain	38 – 653	616	Amyloid-like protein 1		PRO_0000000205
	Peptide	624 – 653	30	C30 By similarity		PRO_0000000206
Regions
	Topological domain	38 – 583	546	Extracellular Potential
	Transmembrane	584 – 606	23	Helical; Potential
	Topological domain	607 – 653	47	Cytoplasmic Potential
	Region	157 – 177	21	Copper-binding
	Region	203 – 210	8	Zinc-binding By similarity
	Region	313 – 345	33	Heparin-binding By similarity
	Region	413 – 444	32	Heparin-binding By similarity
	Region	445 – 462	18	Collagen-binding By similarity
	Region	635 – 651	17	Interaction with DAB1
	Region	639 – 653	15	Interaction with DAB2
	Motif	607 – 618	12	Basolateral sorting signal By similarity
	Motif	643 – 646	4	NPXY motif; contains endocytosis signal
	Compositional bias	263 – 271	9	Poly-Glu
	Compositional bias	535 – 538	4	Poly-Ser
	Compositional bias	601 – 606	6	Poly-Leu
Sites
	Site	166	1	Required for Cu(2+) reduction By similarity
	Site	623 – 624	2	Cleavage; by caspase-3 By similarity
Amino acid modifications
	Glycosylation	464	1	N-linked (GlcNAc...) Potential
	Glycosylation	554	1	N-linked (GlcNAc...) Potential
Experimental info
	Mutagenesis	641	1	Y → G: Reduced binding of APBB1. Ref.7
	Sequence conflict	18	1	P → PP in AAH21877. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Q03157 [UniParc]. Last modified October 1, 1993. Version 1. Checksum: 56516DC3EA40E4B0	FASTA	653	72,751
	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

References

	« Hide 'large scale' referencesShow '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.
IPI	IPI00129249.
PIR	A46362.
RefSeq	NP_031493.2. NM_007467.3.
UniGene	Mm.2381.
3D structure databases
ProteinModelPortal	Q03157.
SMR	Q03157. Positions 54-145, 148-210, 295-488.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q03157. 9 interactions.
MINT	MINT-1177110.
PTM databases
PhosphoSite	Q03157.
Proteomic databases
PaxDb	Q03157.
PRIDE	Q03157.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000006828; ENSMUSP00000006828; ENSMUSG00000006651.
GeneID	11803.
KEGG	mmu:11803.
UCSC	uc009gek.1. mouse.
Organism-specific databases
CTD	333.
MGI	MGI:88046. Aplp1.
Phylogenomic databases
eggNOG	NOG289770.
GeneTree	ENSGT00530000063252.
HOVERGEN	HBG000051.
InParanoid	Q03157.
KO	K05639.
Gene expression databases
Bgee	Q03157.
CleanEx	MM_APLP1.
Genevestigator	Q03157.
GermOnline	ENSMUSG00000006651. Mus musculus.
Family and domain databases
Gene3D	3.30.1490.140. 1 hit. 3.90.570.10. 1 hit.
InterPro	IPR008155. 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]
Pfam	PF10515. APP_amyloid. 1 hit. PF12924. APP_Cu_bd. 1 hit. PF12925. APP_E2. 1 hit. PF02177. APP_N. 1 hit. [Graphical view]
PRINTS	PR00203. AMYLOIDA4.
SMART	SM00006. A4_EXTRA. 1 hit. [Graphical view]
SUPFAM	SSF56491. A4_extra. 1 hit. SSF89811. Amyloid_glyco_Cu-bd. 1 hit. SSF109843. SSF109843. 1 hit.
PROSITE	PS00319. A4_EXTRA. 1 hit. PS00320. A4_INTRA. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	APLP1. mouse.
NextBio	279655.
SOURCE	Search...

Entry information

Entry name

APLP1_MOUSE

Accession

Primary (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:	May 1, 2013
This is version 120 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program