UniProtKB - Q10651 (A4_CAEEL)
Protein
Amyloid-beta-like protein
Gene
apl-1
Organism
Caenorhabditis elegans
Status
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 key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Binding sitei | 382 | Heparin1 Publication | 1 |
GO - Molecular functioni
- heparin binding Source: InterPro
- transition metal ion binding Source: InterPro
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 function | Developmental protein |
Biological process | Differentiation, Neurogenesis |
Enzyme and pathway databases
Reactomei | R-CEL-114608, Platelet degranulation R-CEL-381426, Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs) R-CEL-416476, G alpha (q) signalling events R-CEL-8957275, Post-translational protein phosphorylation R-CEL-9609523, Insertion of tail-anchored proteins into the endoplasmic reticulum membrane |
Names & Taxonomyi
Protein namesi | Recommended name: Amyloid-beta-like proteinCurated |
Gene namesi | Name:apl-1Imported ORF Names:C42D8.8Imported |
Organismi | Caenorhabditis elegans |
Taxonomic identifieri | 6239 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Ecdysozoa › Nematoda › Chromadorea › Rhabditida › Rhabditina › Rhabditomorpha › Rhabditoidea › Rhabditidae › Peloderinae › Caenorhabditis |
Proteomesi |
|
Organism-specific databases
WormBasei | C42D8.8a ; CE04209 ; WBGene00000149 ; apl-1 C42D8.8b ; CE27845 ; WBGene00000149 ; apl-1 |
Subcellular locationi
Endosome
- Early endosome 1 Publication
Other locations
- Membrane Curated; Single-pass type I membrane protein Curated
Endosome
- early endosome Source: UniProtKB-SubCell
Other locations
- cytoplasmic vesicle Source: WormBase
- integral component of membrane Source: UniProtKB-KW
- neuron projection Source: WormBase
- neuronal cell body Source: WormBase
Topology
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Topological domaini | 22 – 621 | ExtracellularSequence analysisAdd BLAST | 600 | |
Transmembranei | 622 – 642 | HelicalSequence analysisAdd BLAST | 21 | |
Topological domaini | 643 – 686 | CytoplasmicSequence analysisAdd BLAST | 44 |
Keywords - Cellular componenti
Amyloid, Endosome, MembranePathology & 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 key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 252 | N → A: Reduced heparin binding. 1 Publication | 1 | |
Mutagenesisi | 254 | H → A: Reduced heparin binding. 1 Publication | 1 | |
Mutagenesisi | 254 | H → P: Reduced heparin binding. 1 Publication | 1 | |
Mutagenesisi | 348 | D → C: Results in destabilized protein structure; when associated with C-368 and K-377. 1 Publication | 1 | |
Mutagenesisi | 368 | S → C: Results in destabilized protein structure; when associated with C-348 and K-377. 1 Publication | 1 | |
Mutagenesisi | 374 | R → A: Reduced heparin binding; when associated with A-378. 1 Publication | 1 | |
Mutagenesisi | 377 | E → K in yn32: Results in lethality and destabilized protein structure. 2 Publications | 1 | |
Mutagenesisi | 378 | K → A: Reduced heparin binding; when associated with A-374. 1 Publication | 1 | |
Mutagenesisi | 382 | H → A: Moderately reduced heparin binding. 1 Publication | 1 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Signal peptidei | 1 – 21 | Sequence analysisAdd BLAST | 21 | |
ChainiPRO_0000000201 | 22 – 686 | Amyloid-beta-like proteinCuratedAdd BLAST | 665 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Disulfide bondi | 42 ↔ 65 | PROSITE-ProRule annotation | ||
Disulfide bondi | 76 ↔ 119 | PROSITE-ProRule annotation | ||
Glycosylationi | 84 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Disulfide bondi | 101 ↔ 108 | PROSITE-ProRule annotation | ||
Disulfide bondi | 135 ↔ 195 | PROSITE-ProRule annotation2 Publications | ||
Disulfide bondi | 146 ↔ 182 | PROSITE-ProRule annotation2 Publications | ||
Disulfide bondi | 160 ↔ 194 | PROSITE-ProRule annotation2 Publications | ||
Glycosylationi | 201 | N-linked (GlcNAc...) asparagineSequence analysis | 1 | |
Glycosylationi | 249 | N-linked (GlcNAc...) asparagine1 Publication | 1 | |
Glycosylationi | 417 | N-linked (GlcNAc...) asparagineSequence analysis | 1 |
Post-translational modificationi
Extracellular region is proteolytically cleaved.1 Publication
Keywords - PTMi
Disulfide bond, GlycoproteinProteomic databases
EPDi | Q10651 |
PaxDbi | Q10651 |
PeptideAtlasi | Q10651 |
PTM databases
iPTMneti | Q10651 |
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
Bgeei | WBGene00000149, Expressed in pharyngeal muscle cell (C elegans) and 4 other tissues |
Interactioni
Subunit structurei
Interacts (via cytoplasmic domain) with feh-1 (via PID 2 domain).
1 PublicationProtein-protein interaction databases
BioGRIDi | 45718, 4 interactors |
DIPi | DIP-25431N |
STRINGi | 6239.C42D8.8a |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details3D structure databases
BMRBi | Q10651 |
SMRi | Q10651 |
ModBasei | Search... |
PDBe-KBi | Search... |
Miscellaneous databases
EvolutionaryTracei | Q10651 |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 32 – 197 | E1PROSITE-ProRule annotationAdd BLAST | 166 | |
Domaini | 240 – 440 | E2PROSITE-ProRule annotationAdd BLAST | 201 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 32 – 125 | GFLD subdomainPROSITE-ProRule annotationAdd BLAST | 94 | |
Regioni | 133 – 197 | CuBD subdomainPROSITE-ProRule annotationAdd BLAST | 65 | |
Regioni | 252 – 255 | Heparin-binding1 Publication | 4 |
Motif
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Motifi | 674 – 679 | YENPXY motifBy similarity | 6 |
Compositional bias
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Compositional biasi | 205 – 228 | Asp-richAdd BLAST | 24 |
Domaini
The NPXY motif mediates the interaction with clathrin.Sequence analysis
Sequence similaritiesi
Belongs to the APP family.PROSITE-ProRule annotation
Keywords - Domaini
Signal, Transmembrane, Transmembrane helixPhylogenomic databases
eggNOGi | KOG3540, Eukaryota |
GeneTreei | ENSGT00530000063252 |
InParanoidi | Q10651 |
OMAi | IIDEPAS |
OrthoDBi | 953529at2759 |
PhylomeDBi | Q10651 |
Family and domain databases
Gene3Di | 1.20.120.770, 1 hit 2.30.29.30, 1 hit 3.30.1490.140, 1 hit 3.90.570.10, 1 hit |
InterProi | View 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 IPR015849, Amyloid_glyco_heparin-bd IPR036454, Amyloid_glyco_heparin-bd_sf IPR019745, Amyloid_glyco_intracell_CS IPR019543, APP_amyloid_C IPR019744, APP_CUBD_CS IPR036176, E2_sf IPR011993, PH-like_dom_sf |
PANTHERi | PTHR23103, PTHR23103, 1 hit |
Pfami | View protein in Pfam PF10515, APP_amyloid, 1 hit PF12924, APP_Cu_bd, 1 hit PF12925, APP_E2, 1 hit PF02177, APP_N, 1 hit |
PRINTSi | PR00203, AMYLOIDA4 |
SMARTi | View protein in SMART SM00006, A4_EXTRA, 1 hit |
SUPFAMi | SSF109843, SSF109843, 1 hit SSF56491, SSF56491, 1 hit SSF89811, SSF89811, 1 hit |
PROSITEi | View protein in PROSITE PS00319, APP_CUBD, 1 hit PS51869, APP_E1, 1 hit PS51870, APP_E2, 1 hit PS00320, APP_INTRA, 1 hit |
s (2)i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
This entry describes 2 produced by isoformsialternative splicing. AlignAdd to basketIsoform a (identifier: Q10651-1) [UniParc]FASTAAdd to basket
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
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
Sequence cautioni
The sequence AAC46470 differs from that shown. Reason: Erroneous initiation.Curated
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_000017 | 538 – 539 | Missing in isoform b. Curated | 2 |
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. |
PIRi | T15795 |
RefSeqi | NP_508870.3, NM_076469.5 [Q10651-1] NP_508871.1, NM_076470.4 [Q10651-2] |
Genome annotation databases
EnsemblMetazoai | C42D8.8a.1; C42D8.8a.1; WBGene00000149 [Q10651-1] C42D8.8b.1; C42D8.8b.1; WBGene00000149 [Q10651-2] |
GeneIDi | 180783 |
KEGGi | cel:CELE_C42D8.8 |
UCSCi | C42D8.8a, c. elegans [Q10651-1] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
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. |
PIRi | T15795 |
RefSeqi | NP_508870.3, NM_076469.5 [Q10651-1] NP_508871.1, NM_076470.4 [Q10651-2] |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
2M05 | NMR | - | A | 135-197 | [»] | |
3K66 | X-ray | 2.70 | A | 240-478 | [»] | |
3K6B | X-ray | 2.80 | A | 240-478 | [»] | |
BMRBi | Q10651 | |||||
SMRi | Q10651 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 45718, 4 interactors |
DIPi | DIP-25431N |
STRINGi | 6239.C42D8.8a |
PTM databases
iPTMneti | Q10651 |
Proteomic databases
EPDi | Q10651 |
PaxDbi | Q10651 |
PeptideAtlasi | Q10651 |
Genome annotation databases
EnsemblMetazoai | C42D8.8a.1; C42D8.8a.1; WBGene00000149 [Q10651-1] C42D8.8b.1; C42D8.8b.1; WBGene00000149 [Q10651-2] |
GeneIDi | 180783 |
KEGGi | cel:CELE_C42D8.8 |
UCSCi | C42D8.8a, c. elegans [Q10651-1] |
Organism-specific databases
CTDi | 180783 |
WormBasei | C42D8.8a ; CE04209 ; WBGene00000149 ; apl-1 C42D8.8b ; CE27845 ; WBGene00000149 ; apl-1 |
Phylogenomic databases
eggNOGi | KOG3540, Eukaryota |
GeneTreei | ENSGT00530000063252 |
InParanoidi | Q10651 |
OMAi | IIDEPAS |
OrthoDBi | 953529at2759 |
PhylomeDBi | Q10651 |
Enzyme and pathway databases
Reactomei | R-CEL-114608, Platelet degranulation R-CEL-381426, Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs) R-CEL-416476, G alpha (q) signalling events R-CEL-8957275, Post-translational protein phosphorylation R-CEL-9609523, Insertion of tail-anchored proteins into the endoplasmic reticulum membrane |
Miscellaneous databases
EvolutionaryTracei | Q10651 |
PROi | PR:Q10651 |
Gene expression databases
Bgeei | WBGene00000149, Expressed in pharyngeal muscle cell (C elegans) and 4 other tissues |
Family and domain databases
Gene3Di | 1.20.120.770, 1 hit 2.30.29.30, 1 hit 3.30.1490.140, 1 hit 3.90.570.10, 1 hit |
InterProi | View 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 IPR015849, Amyloid_glyco_heparin-bd IPR036454, Amyloid_glyco_heparin-bd_sf IPR019745, Amyloid_glyco_intracell_CS IPR019543, APP_amyloid_C IPR019744, APP_CUBD_CS IPR036176, E2_sf IPR011993, PH-like_dom_sf |
PANTHERi | PTHR23103, PTHR23103, 1 hit |
Pfami | View protein in Pfam PF10515, APP_amyloid, 1 hit PF12924, APP_Cu_bd, 1 hit PF12925, APP_E2, 1 hit PF02177, APP_N, 1 hit |
PRINTSi | PR00203, AMYLOIDA4 |
SMARTi | View protein in SMART SM00006, A4_EXTRA, 1 hit |
SUPFAMi | SSF109843, SSF109843, 1 hit SSF56491, SSF56491, 1 hit SSF89811, SSF89811, 1 hit |
PROSITEi | View protein in PROSITE PS00319, APP_CUBD, 1 hit PS51869, APP_E1, 1 hit PS51870, APP_E2, 1 hit PS00320, APP_INTRA, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | A4_CAEEL | |
Accessioni | Q10651Primary (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: | April 7, 2021 | |
This is version 153 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Caenorhabditis annotation project |
Miscellaneousi
Keywords - Technical termi
3D-structure, Reference proteomeDocuments
- Caenorhabditis elegans
Caenorhabditis elegans: entries, gene names and cross-references to WormBase - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families