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Protein

Beta-amyloid-like protein

Gene

apl-1

Organism
Caenorhabditis elegans
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Required for normal developmental progression throughout all life stages (PubMed:18262516, PubMed:22466039). Specifically required for the molt stage during all larval transitions and morphogenesis (PubMed:18262516, PubMed:17267616, PubMed:22466039). May act with heterochronic genes, including members of the let-7 family, to regulate larval stage to adult transition (PubMed:18262516). Acts in multiple pathways to influence daf-12 and daf-16 activity to in turn regulate physiological and reproductive processes such as body size and egg-laying (PubMed:22466039). May play a role in neurotransmission (PubMed:20862215).4 Publications

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei382 – 3821Heparin1 Publication

GO - Molecular functioni

GO - Biological processi

  • body morphogenesis Source: WormBase
  • cell differentiation Source: UniProtKB-KW
  • ecdysis, collagen and cuticulin-based cuticle Source: WormBase
  • nematode larval development Source: WormBase
  • nervous system development Source: UniProtKB-KW
Complete GO annotation...

Keywords - Molecular functioni

Developmental protein

Keywords - Biological processi

Differentiation, Neurogenesis

Enzyme and pathway databases

ReactomeiR-CEL-114608. Platelet degranulation.

Names & Taxonomyi

Protein namesi
Recommended name:
Beta-amyloid-like proteinCurated
Gene namesi
Name:apl-1Imported
ORF Names:C42D8.8Imported
OrganismiCaenorhabditis elegans
Taxonomic identifieri6239 [NCBI]
Taxonomic lineageiEukaryotaMetazoaEcdysozoaNematodaChromadoreaRhabditidaRhabditoideaRhabditidaePeloderinaeCaenorhabditis
Proteomesi
  • UP000001940 Componenti: Chromosome X

Organism-specific databases

WormBaseiC42D8.8a; CE04209; WBGene00000149; apl-1.
C42D8.8b; CE27845; WBGene00000149; apl-1.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini22 – 621600ExtracellularSequence analysisAdd
BLAST
Transmembranei622 – 64221HelicalSequence analysisAdd
BLAST
Topological domaini643 – 68644CytoplasmicSequence analysisAdd
BLAST

GO - Cellular componenti

  • cytoplasmic vesicle Source: WormBase
  • early endosome Source: UniProtKB-SubCell
  • integral component of membrane Source: UniProtKB-KW
  • neuronal cell body Source: WormBase
  • neuron projection Source: WormBase
Complete GO annotation...

Keywords - Cellular componenti

Amyloid, Endosome, Membrane

Pathology & Biotechi

Disruption phenotypei

Larval lethality during the L1 stage, with the formation of vacuoles in syncytial hypoderm, organ morphology defects, and molting defects (PubMed:17267616, PubMed:20862215). RNAi-mediated knockdown results in a reduced body size, transparent appearance, sluggish movement and insensitivity to touch (PubMed:18262516, PubMed:20862215). Delayed development and a molting defect that begins at the L3 to L4 larval stage transition and continues through to transition from the L4 larval stage to the young adult stage (PubMed:20862215). Increased sensitivity to acetylcholine inhibition (PubMed:20862215). Increased pharyngeal pumping (PubMed:11896189).4 Publications

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi252 – 2521N → A: Reduced heparin binding. 1 Publication
Mutagenesisi254 – 2541H → A: Reduced heparin binding. 1 Publication
Mutagenesisi254 – 2541H → P: Reduced heparin binding. 1 Publication
Mutagenesisi348 – 3481D → C: Results in destabilized protein structure; when associated with C-368 and K-377. 1 Publication
Mutagenesisi368 – 3681S → C: Results in destabilized protein structure; when associated with C-348 and K-377. 1 Publication
Mutagenesisi374 – 3741R → A: Reduced heparin binding; when associated with A-378. 1 Publication
Mutagenesisi377 – 3771E → K in yn32: Results in lethality and destabilized protein structure. 2 Publications
Mutagenesisi378 – 3781K → A: Reduced heparin binding; when associated with A-374. 1 Publication
Mutagenesisi382 – 3821H → A: Moderately reduced heparin binding. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 2121Sequence analysisAdd
BLAST
Chaini22 – 686665Beta-amyloid-like proteinCuratedPRO_0000000201Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi42 ↔ 65By similarity
Disulfide bondi76 ↔ 119By similarity
Glycosylationi84 – 841N-linked (GlcNAc...)Sequence analysis
Disulfide bondi101 ↔ 108By similarity
Disulfide bondi135 ↔ 1952 Publications
Disulfide bondi146 ↔ 1822 Publications
Disulfide bondi160 ↔ 1942 Publications
Glycosylationi201 – 2011N-linked (GlcNAc...)Sequence analysis
Glycosylationi249 – 2491N-linked (GlcNAc...)1 Publication
Glycosylationi417 – 4171N-linked (GlcNAc...)Sequence analysis

Post-translational modificationi

Extracellular region is proteolytically cleaved.1 Publication

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

EPDiQ10651.
PaxDbiQ10651.
PRIDEiQ10651.

PTM databases

iPTMnetiQ10651.

Expressioni

Tissue specificityi

Expressed in the head, pharynx, spermatheca, uterus, vulva, tail and ventral neurons (PubMed:18262516). Specifically expressed in nerve ring interneurons, the ventral cord, socket and amphids in the head, with strong expression in junctional cells, including the pharyngeal intestinal valve and uterine seam junction, and the excretory cell and weak expression in epidermal epithelial cells, including hyp7 cells, vulval cells, rectal valve cells, pharyngeal arcade cells and the tail hypodermis (PubMed:20862215).2 Publications

Developmental stagei

Similar expression pattern in larval and adult cells with expression in neuronal, muscle, hypodermal and supporting cells (PubMed:17267616). Temporally expressed in seam cells from the middle of larval stage L4 and throughout adult stages (PubMed:18262516).2 Publications

Interactioni

Subunit structurei

Interacts (via cytoplasmic domain) with feh-1 (via PID 2 domain).1 Publication

Protein-protein interaction databases

BioGridi45718. 1 interaction.
DIPiDIP-25431N.
MINTiMINT-1128886.
STRINGi6239.C42D8.8a.2.

Structurei

Secondary structure

1
686
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi136 – 1416Combined sources
Helixi149 – 16214Combined sources
Beta strandi172 – 1787Combined sources
Beta strandi187 – 1959Combined sources
Helixi243 – 2464Combined sources
Helixi253 – 29240Combined sources
Helixi294 – 35865Combined sources
Helixi362 – 39332Combined sources
Helixi395 – 3995Combined sources
Helixi402 – 42120Combined sources
Turni422 – 4254Combined sources
Helixi427 – 4304Combined sources
Turni431 – 4333Combined sources
Helixi434 – 44815Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2M05NMR-A135-197[»]
3K66X-ray2.70A240-478[»]
3K6BX-ray2.80A240-478[»]
ProteinModelPortaliQ10651.
SMRiQ10651. Positions 36-197, 240-456.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ10651.

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni252 – 2554Heparin-binding1 Publication

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi676 – 6794Clathrin-bindingSequence analysis

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi205 – 22824Asp-richAdd
BLAST

Sequence similaritiesi

Belongs to the APP family.Curated

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG3540. Eukaryota.
ENOG410ZW2A. LUCA.
GeneTreeiENSGT00530000063252.
HOGENOMiHOG000272569.
InParanoidiQ10651.
KOiK04520.
OMAiNELDERY.
PhylomeDBiQ10651.

Family and domain databases

Gene3Di3.30.1490.140. 1 hit.
3.90.570.10. 1 hit.
InterProiIPR008155. 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.
IPR019543. APP_amyloid_C.
[Graphical view]
PfamiPF10515. APP_amyloid. 1 hit.
PF12924. APP_Cu_bd. 1 hit.
PF12925. APP_E2. 1 hit.
PF02177. APP_N. 1 hit.
[Graphical view]
PRINTSiPR00203. AMYLOIDA4.
SMARTiSM00006. A4_EXTRA. 1 hit.
[Graphical view]
SUPFAMiSSF109843. SSF109843. 1 hit.
SSF56491. SSF56491. 1 hit.
SSF89811. SSF89811. 1 hit.
PROSITEiPS00319. A4_EXTRA. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

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

Isoform a (identifier: Q10651-1) [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
MTVGKLMIGL LIPILVATVY AEGSPAGSKR HEKFIPMVAF SCGYRNQYMT
60 70 80 90 100
EEGSWKTDDE RYATCFSGKL DILKYCRKAY PSMNITNIVE YSHEVSISDW
110 120 130 140 150
CREEGSPCKW THSVRPYHCI DGEFHSEALQ VPHDCQFSHV NSRDQCNDYQ
160 170 180 190 200
HWKDEAGKQC KTKKSKGNKD MIVRSFAVLE PCALDMFTGV EFVCCPNDQT
210 220 230 240 250
NKTDVQKTKE DEDDDDDEDD AYEDDYSEES DEKDEEEPSS QDPYFKIANW
260 270 280 290 300
TNEHDDFKKA EMRMDEKHRK KVDKVMKEWG DLETRYNEQK AKDPKGAEKF
310 320 330 340 350
KSQMNARFQK TVSSLEEEHK RMRKEIEAVH EERVQAMLNE KKRDATHDYR
360 370 380 390 400
QALATHVNKP NKHSVLQSLK AYIRAEEKDR MHTLNRYRHL LKADSKEAAA
410 420 430 440 450
YKPTVIHRLR YIDLRINGTL AMLRDFPDLE KYVRPIAVTY WKDYRDEVSP
460 470 480 490 500
DISVEDSELT PIIHDDEFSK NAKLDVKAPT TTAKPVKETD NAKVLPTEAS
510 520 530 540 550
DSEEEADEYY EDEDDEQVKK TPDMKKKVKV VDIKPKEIKV TIEEEKKAPK
560 570 580 590 600
LVETSVQTDD EDDDEDSSSS TSSESDEDED KNIKELRVDI EPIIDEPASF
610 620 630 640 650
YRHDKLIQSP EVERSASSVF QPYVLASAMF ITAICIIAFA ITNARRRRAM
660 670 680
RGFIEVDVYT PEERHVAGMQ VNGYENPTYS FFDSKA
Length:686
Mass (Da):79,435
Last modified:May 2, 2002 - v2
Checksum:iA0816858FDD48608
GO
Isoform b (identifier: Q10651-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     538-539: Missing.

Note: No experimental confirmation available.
Show »
Length:684
Mass (Da):79,193
Checksum:i2E86C4ABD2CD0C59
GO

Sequence cautioni

The sequence AAC46470.1 differs from that shown. Reason: Erroneous initiation. Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei538 – 5392Missing in isoform b. CuratedVSP_000017

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
FO080659 Genomic DNA. Translation: CCD65568.1.
FO080659 Genomic DNA. Translation: CCD65569.1.
U00240 mRNA. Translation: AAC46470.1. Different initiation.
PIRiT15795.
RefSeqiNP_508870.3. NM_076469.5. [Q10651-1]
NP_508871.1. NM_076470.4. [Q10651-2]
UniGeneiCel.6164.

Genome annotation databases

EnsemblMetazoaiC42D8.8a; C42D8.8a; WBGene00000149. [Q10651-1]
GeneIDi180783.
KEGGicel:CELE_C42D8.8.
UCSCiC42D8.8a. c. elegans. [Q10651-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
FO080659 Genomic DNA. Translation: CCD65568.1.
FO080659 Genomic DNA. Translation: CCD65569.1.
U00240 mRNA. Translation: AAC46470.1. Different initiation.
PIRiT15795.
RefSeqiNP_508870.3. NM_076469.5. [Q10651-1]
NP_508871.1. NM_076470.4. [Q10651-2]
UniGeneiCel.6164.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2M05NMR-A135-197[»]
3K66X-ray2.70A240-478[»]
3K6BX-ray2.80A240-478[»]
ProteinModelPortaliQ10651.
SMRiQ10651. Positions 36-197, 240-456.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi45718. 1 interaction.
DIPiDIP-25431N.
MINTiMINT-1128886.
STRINGi6239.C42D8.8a.2.

PTM databases

iPTMnetiQ10651.

Proteomic databases

EPDiQ10651.
PaxDbiQ10651.
PRIDEiQ10651.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsemblMetazoaiC42D8.8a; C42D8.8a; WBGene00000149. [Q10651-1]
GeneIDi180783.
KEGGicel:CELE_C42D8.8.
UCSCiC42D8.8a. c. elegans. [Q10651-1]

Organism-specific databases

CTDi180783.
WormBaseiC42D8.8a; CE04209; WBGene00000149; apl-1.
C42D8.8b; CE27845; WBGene00000149; apl-1.

Phylogenomic databases

eggNOGiKOG3540. Eukaryota.
ENOG410ZW2A. LUCA.
GeneTreeiENSGT00530000063252.
HOGENOMiHOG000272569.
InParanoidiQ10651.
KOiK04520.
OMAiNELDERY.
PhylomeDBiQ10651.

Enzyme and pathway databases

ReactomeiR-CEL-114608. Platelet degranulation.

Miscellaneous databases

EvolutionaryTraceiQ10651.
NextBioi910936.
PROiQ10651.

Family and domain databases

Gene3Di3.30.1490.140. 1 hit.
3.90.570.10. 1 hit.
InterProiIPR008155. 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.
IPR019543. APP_amyloid_C.
[Graphical view]
PfamiPF10515. APP_amyloid. 1 hit.
PF12924. APP_Cu_bd. 1 hit.
PF12925. APP_E2. 1 hit.
PF02177. APP_N. 1 hit.
[Graphical view]
PRINTSiPR00203. AMYLOIDA4.
SMARTiSM00006. A4_EXTRA. 1 hit.
[Graphical view]
SUPFAMiSSF109843. SSF109843. 1 hit.
SSF56491. SSF56491. 1 hit.
SSF89811. SSF89811. 1 hit.
PROSITEiPS00319. A4_EXTRA. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Genome sequence of the nematode C. elegans: a platform for investigating biology."
    The C. elegans sequencing consortium
    Science 282:2012-2018(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    Strain: Bristol N2.
  2. "apl-1, a Caenorhabditis elegans gene encoding a protein related to the human beta-amyloid protein precursor."
    Daigle I., Li C.
    Proc. Natl. Acad. Sci. U.S.A. 90:12045-12049(1993) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 6-686.
    Strain: Bristol N2.
  3. "feh-1 and apl-1, the Caenorhabditis elegans orthologues of mammalian Fe65 and beta-amyloid precursor protein genes, are involved in the same pathway that controls nematode pharyngeal pumping."
    Zambrano N., Bimonte M., Arbucci S., Gianni D., Russo T., Bazzicalupo P.
    J. Cell Sci. 115:1411-1422(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH FEH-1, DISRUPTION PHENOTYPE.
  4. "Proteomics reveals N-linked glycoprotein diversity in Caenorhabditis elegans and suggests an atypical translocation mechanism for integral membrane proteins."
    Kaji H., Kamiie J., Kawakami H., Kido K., Yamauchi Y., Shinkawa T., Taoka M., Takahashi N., Isobe T.
    Mol. Cell. Proteomics 6:2100-2109(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-249, IDENTIFICATION BY MASS SPECTROMETRY.
    Strain: Bristol N2.
  5. "APL-1, a Caenorhabditis elegans protein related to the human beta-amyloid precursor protein, is essential for viability."
    Hornsten A., Lieberthal J., Fadia S., Malins R., Ha L., Xu X., Daigle I., Markowitz M., O'Connor G., Plasterk R., Li C.
    Proc. Natl. Acad. Sci. U.S.A. 104:1971-1976(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, TISSUE SPECIFICITY, PROTEOLYTIC CLEAVAGE, DISRUPTION PHENOTYPE, MUTAGENESIS OF GLU-377.
  6. "The expression of the Alzheimer's amyloid precursor protein-like gene is regulated by developmental timing microRNAs and their targets in Caenorhabditis elegans."
    Niwa R., Zhou F., Li C., Slack F.J.
    Dev. Biol. 315:418-425(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, DISRUPTION PHENOTYPE.
  7. "Intracellular trafficking and synaptic function of APL-1 in Caenorhabditis elegans."
    Wiese M., Antebi A., Zheng H.
    PLoS ONE 5:3307-3314(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, DISRUPTION PHENOTYPE.
  8. "APL-1, the Alzheimer's Amyloid precursor protein in Caenorhabditis elegans, modulates multiple metabolic pathways throughout development."
    Ewald C.Y., Raps D.A., Li C.
    Genetics 191:493-507(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  9. "Structural characterization of the E2 domain of APL-1, a Caenorhabditis elegans homolog of human amyloid precursor protein, and its heparin binding site."
    Hoopes J.T., Liu X., Xu X., Demeler B., Folta-Stogniew E., Li C., Ha Y.
    J. Biol. Chem. 285:2165-2173(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 240-478 IN COMPLEX WITH HEPARIN ANALOG, MUTAGENESIS OF ASN-252; HIS-254; ASP-348; SER-368; ARG-374; GLU-377; LYS-378 AND HIS-382.
  10. "Quantification of copper binding to amyloid precursor protein domain 2 and its Caenorhabditis elegans ortholog. Implications for biological function."
    Leong S.L., Young T.R., Barnham K.J., Wedd A.G., Hinds M.G., Xiao Z., Cappai R.
    Metallomics 6:105-116(2014) [PubMed] [Europe PMC] [Abstract]
    Cited for: STRUCTURE BY NMR OF 135-197, DISULFIDE BONDS, LACK OF COPPER-BINDING.

Entry informationi

Entry nameiA4_CAEEL
AccessioniPrimary (citable) accession number: Q10651
Secondary accession number(s): Q18583, Q95ZX1
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 2, 2002
Last sequence update: May 2, 2002
Last modified: May 11, 2016
This is version 120 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programCaenorhabditis annotation project

Miscellaneousi

Miscellaneous

Lacks conserved metal-binding sites and has only weak affinity for copper in vitro.1 Publication

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Caenorhabditis elegans
    Caenorhabditis elegans: entries, gene names and cross-references to WormBase
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. 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.