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Protein

Amyloid-beta-like protein

Gene

apl-1

Organism
Caenorhabditis elegans
Status
Reviewed-Annotation score: -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). Acts with heterochronic genes, including members of the let-7 family, to regulate larval stage to adult transition (PubMed:18262516, PubMed:28933985). Acts synergistically with acn-1 in let-7 regulated postembryonic cell division of hypodermal seam cells (PubMed:28933985). 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).5 Publications

Miscellaneous

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

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei382Heparin1 Publication1

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

Keywordsi

Molecular functionDevelopmental protein
Biological processDifferentiation, Neurogenesis

Enzyme and pathway databases

ReactomeiR-CEL-114608 Platelet degranulation
R-CEL-3000178 ECM proteoglycans
R-CEL-381426 Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)
R-CEL-8957275 Post-translational protein phosphorylation

Names & Taxonomyi

Protein namesi
Recommended name:
Amyloid-beta-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

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini22 – 621ExtracellularSequence analysisAdd BLAST600
Transmembranei622 – 642HelicalSequence analysisAdd BLAST21
Topological domaini643 – 686CytoplasmicSequence analysisAdd BLAST44

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). In a let-7 mutant background, partial suppression of the let-7 bursting vulva phenotype (PubMed:28933985). Double RNAi-mediated knockdown with acn-1 in a let-7 mutant background leads to complete suppression of the heterochronic seam cell defects (PubMed:28933985).5 Publications

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi252N → A: Reduced heparin binding. 1 Publication1
Mutagenesisi254H → A: Reduced heparin binding. 1 Publication1
Mutagenesisi254H → P: Reduced heparin binding. 1 Publication1
Mutagenesisi348D → C: Results in destabilized protein structure; when associated with C-368 and K-377. 1 Publication1
Mutagenesisi368S → C: Results in destabilized protein structure; when associated with C-348 and K-377. 1 Publication1
Mutagenesisi374R → A: Reduced heparin binding; when associated with A-378. 1 Publication1
Mutagenesisi377E → K in yn32: Results in lethality and destabilized protein structure. 2 Publications1
Mutagenesisi378K → A: Reduced heparin binding; when associated with A-374. 1 Publication1
Mutagenesisi382H → A: Moderately reduced heparin binding. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 21Sequence analysisAdd BLAST21
ChainiPRO_000000020122 – 686Amyloid-beta-like proteinCuratedAdd BLAST665

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi42 ↔ 65By similarity
Disulfide bondi76 ↔ 119By similarity
Glycosylationi84N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi101 ↔ 108By similarity
Disulfide bondi135 ↔ 1952 Publications
Disulfide bondi146 ↔ 1822 Publications
Disulfide bondi160 ↔ 1942 Publications
Glycosylationi201N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi249N-linked (GlcNAc...) asparagine1 Publication1
Glycosylationi417N-linked (GlcNAc...) asparagineSequence analysis1

Post-translational modificationi

Extracellular region is proteolytically cleaved.1 Publication

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

EPDiQ10651
PaxDbiQ10651
PeptideAtlasiQ10651
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, PubMed:28933985).3 Publications

Gene expression databases

BgeeiWBGene00000149

Interactioni

Subunit structurei

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

Protein-protein interaction databases

BioGridi45718, 1 interactor
DIPiDIP-25431N
IntActiQ10651, 1 interactor
STRINGi6239.C42D8.8a.2

Structurei

Secondary structure

1686
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi136 – 141Combined sources6
Helixi149 – 162Combined sources14
Beta strandi172 – 178Combined sources7
Beta strandi187 – 195Combined sources9
Helixi243 – 246Combined sources4
Helixi253 – 292Combined sources40
Helixi294 – 358Combined sources65
Helixi362 – 393Combined sources32
Helixi395 – 399Combined sources5
Helixi402 – 421Combined sources20
Turni422 – 425Combined sources4
Helixi427 – 430Combined sources4
Turni431 – 433Combined sources3
Helixi434 – 448Combined sources15

3D structure databases

ProteinModelPortaliQ10651
SMRiQ10651
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ10651

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni252 – 255Heparin-binding1 Publication4

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi676 – 679Clathrin-bindingSequence analysis4

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi205 – 228Asp-richAdd BLAST24

Sequence similaritiesi

Belongs to the APP family.Curated

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG3540 Eukaryota
ENOG410ZW2A LUCA
GeneTreeiENSGT00530000063252
HOGENOMiHOG000272569
InParanoidiQ10651
KOiK04520
OMAiREVCSEQ
OrthoDBiEOG091G0UW4
PhylomeDBiQ10651

Family and domain databases

Gene3Di1.20.120.770, 1 hit
2.30.29.30, 1 hit
3.30.1490.140, 1 hit
3.90.570.10, 1 hit
InterProiView protein in InterPro
IPR036669 Amyloid_Cu-bd_sf
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
IPR036454 Amyloid_glyco_heparin-bd_sf
IPR019543 APP_amyloid_C
IPR036176 E2_sf
IPR011993 PH-like_dom_sf
PANTHERiPTHR23103 PTHR23103, 1 hit
PfamiView protein in Pfam
PF10515 APP_amyloid, 1 hit
PF12924 APP_Cu_bd, 1 hit
PF12925 APP_E2, 1 hit
PF02177 APP_N, 1 hit
PRINTSiPR00203 AMYLOIDA4
SMARTiView protein in SMART
SM00006 A4_EXTRA, 1 hit
SUPFAMiSSF109843 SSF109843, 1 hit
SSF56491 SSF56491, 1 hit
SSF89811 SSF89811, 1 hit
PROSITEiView protein in PROSITE
PS00319 A4_EXTRA, 1 hit

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 differs from that shown. Reason: Erroneous initiation.Curated

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_000017538 – 539Missing in isoform b. Curated2

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

Similar proteinsi

Entry informationi

Entry nameiA4_CAEEL
AccessioniPrimary (citable) accession number: Q10651
Secondary accession number(s): Q18583, Q95ZX1
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 2, 2002
Last sequence update: May 2, 2002
Last modified: July 18, 2018
This is version 137 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programCaenorhabditis annotation project

Miscellaneousi

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

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