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P51693 (APLP1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 141. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·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
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length650 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 By similarity. 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. Ref.5

The gamma-CTF peptide, C30, is a potent enhancer of neuronal apoptosis By similarity. Ref.5

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 By similarity. 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 By similarity. Ref.7 Ref.11

Subcellular location

Cell membrane; Single-pass type I membrane protein.

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

Tissue specificity

Expressed in the cerebral cortex where it is localized to the postsynaptic density (PSD). Ref.5

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-620 by caspase-3 By similarity.

N- and O-glycosylated. O-glycosylation with core 1 or possibly core 8 glycans. Glycosylation on Ser-227 is the preferred site to Thr-228. Ref.10

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
   Coding sequence diversityAlternative splicing
   DiseaseNeurodegeneration
   DomainSignal
Transmembrane
Transmembrane helix
   LigandCopper
Heparin-binding
Metal-binding
Zinc
   PTMGlycoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processadenylate cyclase-inhibiting G-protein coupled receptor signaling pathway

Inferred by curator PubMed 16531006. Source: BHF-UCL

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 direct assay PubMed 16531006. Source: BHF-UCL

endocytosis

Inferred from electronic annotation. Source: UniProtKB-KW

extracellular matrix organization

Inferred from electronic annotation. Source: Ensembl

forebrain development

Inferred from electronic annotation. Source: Ensembl

mRNA polyadenylation

Inferred from electronic annotation. Source: Ensembl

negative regulation of cAMP biosynthetic process

Inferred from direct assay PubMed 16531006. Source: BHF-UCL

nervous system development

Traceable author statement Ref.2. Source: ProtInc

organ morphogenesis

Traceable author statement Ref.2. Source: ProtInc

regulation of translation

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentGolgi apparatus

Inferred from electronic annotation. Source: Ensembl

basement membrane

Traceable author statement Ref.2. Source: ProtInc

integral component of membrane

Inferred from electronic annotation. Source: UniProtKB-KW

perinuclear region of cytoplasm

Inferred from direct assay PubMed 16531006. Source: BHF-UCL

plasma membrane

Inferred from direct assay PubMed 16531006. Source: BHF-UCL

   Molecular_functionalpha-2A adrenergic receptor binding

Inferred from physical interaction PubMed 16531006. Source: BHF-UCL

alpha-2B adrenergic receptor binding

Inferred from physical interaction PubMed 16531006. Source: BHF-UCL

alpha-2C adrenergic receptor binding

Inferred from physical interaction PubMed 16531006. Source: BHF-UCL

heparin binding

Inferred from electronic annotation. Source: UniProtKB-KW

identical protein binding

Inferred from physical interaction PubMed 16193067. Source: IntAct

protein binding

Inferred from physical interaction PubMed 16169070PubMed 16193067PubMed 21293490. Source: IntAct

transition metal ion binding

Inferred from electronic annotation. Source: InterPro

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P51693-1)

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.
Isoform 2 (identifier: P51693-2)

The sequence of this isoform differs from the canonical sequence as follows:
     517-517: D → DA

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 3838 Potential
Chain39 – 650612Amyloid-like protein 1
PRO_0000000203
Peptide621 – 65030C30 By similarity
PRO_0000000204

Regions

Topological domain39 – 580542Extracellular Potential
Transmembrane581 – 60323Helical; Potential
Topological domain604 – 65047Cytoplasmic Potential
Region158 – 17821Copper-binding By similarity
Region204 – 2118Zinc-binding
Region285 – 30521O-glycosylated at three sites
Region310 – 34233Heparin-binding By similarity
Region410 – 44132Heparin-binding By similarity
Region442 – 45918Collagen-binding By similarity
Region632 – 64918Interaction with DAB1 By similarity
Region636 – 65015Interaction with DAB2 By similarity
Motif604 – 61512Basolateral sorting signal By similarity
Motif640 – 6434Clathrin-binding Potential
Motif640 – 6434NPXY motif; contains endocytosis signal
Compositional bias241 – 2477Poly-Glu
Compositional bias264 – 2685Poly-Glu

Sites

Site1671Required for Cu(2+) reduction By similarity
Site620 – 6212Cleavage; by caspase-3 By similarity

Amino acid modifications

Glycosylation2151O-linked (GalNAc...) Ref.9
Glycosylation2271O-linked (GalNAc...) Probable
Glycosylation2281O-linked (GalNAc...) Probable
Glycosylation3371N-linked (GlcNAc...) Potential
Glycosylation4611N-linked (GlcNAc...) Potential
Glycosylation5511N-linked (GlcNAc...) Potential

Natural variations

Alternative sequence5171D → DA in isoform 2.
VSP_039100

Experimental info

Mutagenesis4261H → A: Reduced affinity for heparin. Reduces homodimerization. Ref.11
Mutagenesis4291R → A: Strongly reduced affinity for heparin. Strongly reduced homodimerization. Ref.11
Mutagenesis4331H → A: Reduced affinity for heparin. Reduces homodimerization. Ref.11
Sequence conflict481A → P in AAB96331. Ref.1
Sequence conflict781P → S in BC013850. Ref.4

Secondary structure

.................. 650
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified February 22, 2003. Version 3.
Checksum: B95F0F4D1C5CBAC7

FASTA65072,176
        10         20         30         40         50         60 
MGPASPAARG LSRRPGQPPL PLLLPLLLLL LRAQPAIGSL AGGSPGAAEA PGSAQVAGLC 

        70         80         90        100        110        120 
GRLTLHRDLR TGRWEPDPQR SRRCLRDPQR VLEYCRQMYP ELQIARVEQA TQAIPMERWC 

       130        140        150        160        170        180 
GGSRSGSCAH PHHQVVPFRC LPGEFVSEAL LVPEGCRFLH QERMDQCESS TRRHQEAQEA 

       190        200        210        220        230        240 
CSSQGLILHG SGMLLPCGSD RFRGVEYVCC PPPGTPDPSG TAVGDPSTRS WPPGSRVEGA 

       250        260        270        280        290        300 
EDEEEEESFP QPVDDYFVEP PQAEEEEETV PPPSSHTLAV VGKVTPTPRP TDGVDIYFGM 

       310        320        330        340        350        360 
PGEISEHEGF LRAKMDLEER RMRQINEVMR EWAMADNQSK NLPKADRQAL NEHFQSILQT 

       370        380        390        400        410        420 
LEEQVSGERQ RLVETHATRV IALINDQRRA ALEGFLAALQ ADPPQAERVL LALRRYLRAE 

       430        440        450        460        470        480 
QKEQRHTLRH YQHVAAVDPE KAQQMRFQVH THLQVIEERV NQSLGLLDQN PHLAQELRPQ 

       490        500        510        520        530        540 
IQELLHSEHL GPSELEAPAP GGSSEDKGGL QPPDSKDDTP MTLPKGSTEQ DAASPEKEKM 

       550        560        570        580        590        600 
NPLEQYERKV NASVPRGFPF HSSEIQRDEL APAGTGVSRE AVSGLLIMGA GGGSLIVLSM 

       610        620        630        640        650 
LLLRRKKPYG AISHGVVEVD PMLTLEEQQL RELQRHGYEN PTYRFLEERP 

« Hide

Isoform 2 [UniParc].

Checksum: EEF2FB97BDDF6A66
Show »

FASTA65172,247

References

« Hide 'large scale' references
[1]"Human amyloid precursor-like protein 1 -- cDNA cloning, ectopic expression in COS-7 cells and identification of soluble forms in the cerebrospinal fluid."
Paliga K., Peraus G., Kreger S., Duwrrwang U., Hesse L., Multhaup G., Masters C.L., Beyreuther K., Weidemann A.
Eur. J. Biochem. 250:354-363(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]"Structure of the human amyloid-precursor-like protein gene APLP1 at 19q13.1."
Lenkkeri U., Kestila M., Lamerdin J.E., McCready P., Adamson A., Olsen A., Tryggvason K.
Hum. Genet. 102:192-196(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1).
[3]"The DNA sequence and biology of human chromosome 19."
Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E., Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A., Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S., Carrano A.V. expand/collapse author list , Caoile C., Chan Y.M., Christensen M., Cleland C.A., Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M., Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V., Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D., McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I., Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L., Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E., Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M., Rubin E.M., Lucas S.M.
Nature 428:529-535(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]"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] (ISOFORMS 1 AND 2).
Tissue: Brain and Ovary.
[5]"Selective localization of amyloid precursor-like protein 1 in the cerebral cortex postsynaptic density."
Kim T.-W., Wu K., Xu J.-L., McAuliffe G., Tanzi R.E., Wasco W., Black I.B.
Brain Res. Mol. Brain Res. 32:36-44(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: POSSIBLE FUNCTION, TISSUE SPECIFICITY.
[6]"The amyloid beta-protein precursor and its mammalian homologues. Evidence for a zinc-modulated heparin-binding superfamily."
Bush A.I., Pettingell W.H. Jr., de Paradis M., Tanzi R.E., Wasco W.
J. Biol. Chem. 269:26618-26621(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: HEPARIN AND ZINC-BINDING.
[7]"Interaction of a neuron-specific protein containing PDZ domains with Alzheimer's amyloid precursor protein."
Tomita S., Ozaki T., Taru H., Oguchi S., Takeda S., Yagi Y., Sakiyama S., Kirino Y., Suzuki T.
J. Biol. Chem. 274:2243-2254(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH APBA2.
[8]"Evidence for a copper-binding superfamily of the amyloid precursor protein."
Simons A., Ruppert T., Schmidt C., Schlicksupp A., Pipkorn R., Reed J., Masters C.L., White A.R., Cappai R., Beyreuther K., Bayer T.A., Multhaup G.
Biochemistry 41:9310-9320(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: EXTRACELLULAR COPPER-BINDING.
[9]"Enrichment of glycopeptides for glycan structure and attachment site identification."
Nilsson J., Rueetschi U., Halim A., Hesse C., Carlsohn E., Brinkmalm G., Larson G.
Nat. Methods 6:809-811(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT THR-215; SER-227 AND THR-228, STRUCTURE OF CARBOHYDRATES.
Tissue: Cerebrospinal fluid.
[10]"LC-MS/MS characterization of O-glycosylation sites and glycan structures of human cerebrospinal fluid glycoproteins."
Halim A., Ruetschi U., Larson G., Nilsson J.
J. Proteome Res. 12:573-584(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: GLYCOSYLATION, IDENTIFICATION BY MASS SPECTROMETRY.
[11]"The E2 Domains of APP and APLP1 Share a Conserved Mode of Dimerization."
Lee S., Xue Y., Hu J., Wang Y., Liu X., Demeler B., Ha Y.
Biochemistry 50:5453-5464(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.11 ANGSTROMS) OF 285-499, HEPARIN-BINDING, MUTAGENESIS OF HIS-426; ARG-429 AND HIS-433, SUBUNIT.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U48437 mRNA. Translation: AAB96331.1.
AD000864 Genomic DNA. Translation: AAB50173.1.
BC012889 mRNA. Translation: AAH12889.1.
BC013850 mRNA. No translation available.
CCDSCCDS32997.1. [P51693-2]
RefSeqNP_001019978.1. NM_001024807.1. [P51693-2]
NP_005157.1. NM_005166.3. [P51693-1]
UniGeneHs.74565.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
3PMRX-ray2.11A/B285-499[»]
3Q7GX-ray2.30A/B285-494[»]
3Q7LX-ray2.20A/B285-494[»]
3QMKX-ray2.21A/B285-494[»]
ProteinModelPortalP51693.
SMRP51693. Positions 55-211, 292-489.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid106830. 45 interactions.
DIPDIP-30846N.
IntActP51693. 42 interactions.
MINTMINT-1395075.
STRING9606.ENSP00000221891.

PTM databases

PhosphoSiteP51693.

Polymorphism databases

DMDM28558769.

Proteomic databases

PaxDbP51693.
PRIDEP51693.

Protocols and materials databases

DNASU333.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000221891; ENSP00000221891; ENSG00000105290. [P51693-2]
GeneID333.
KEGGhsa:333.
UCSCuc002oce.3. human. [P51693-1]
uc002ocf.3. human. [P51693-2]

Organism-specific databases

CTD333.
GeneCardsGC19P036359.
HGNCHGNC:597. APLP1.
HPAHPA028971.
MIM104775. gene.
neXtProtNX_P51693.
PharmGKBPA24884.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG289770.
HOGENOMHOG000232190.
HOVERGENHBG000051.
InParanoidP51693.
KOK05639.
OMAMLLPCGS.
PhylomeDBP51693.
TreeFamTF317274.

Gene expression databases

ArrayExpressP51693.
BgeeP51693.
CleanExHS_APLP1.
GenevestigatorP51693.

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. human.
EvolutionaryTraceP51693.
GeneWikiAPLP1.
GenomeRNAi333.
NextBio1377.
PROP51693.
SOURCESearch...

Entry information

Entry nameAPLP1_HUMAN
AccessionPrimary (citable) accession number: P51693
Secondary accession number(s): O00113, Q96A92
Entry history
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: February 22, 2003
Last modified: July 9, 2014
This is version 141 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human chromosome 19

Human chromosome 19: entries, gene names and cross-references to MIM