UniProtKB - Q9UKG1 (DP13A_HUMAN)
DCC-interacting protein 13-alpha
APPL1
Functioni
GO - Molecular functioni
- beta-tubulin binding Source: UniProtKB
- identical protein binding Source: IntAct
- phosphatidylinositol binding Source: UniProtKB
- phosphatidylserine binding Source: UniProtKB
- protein-containing complex binding Source: UniProtKB
- protein homodimerization activity Source: UniProtKB
- protein kinase B binding Source: BHF-UCL
GO - Biological processi
- adiponectin-activated signaling pathway Source: UniProtKB
- cell cycle Source: UniProtKB-KW
- cellular response to hepatocyte growth factor stimulus Source: UniProtKB
- extrinsic apoptotic signaling pathway in absence of ligand Source: Reactome
- insulin receptor signaling pathway Source: UniProtKB
- negative regulation of Fc-gamma receptor signaling pathway involved in phagocytosis Source: UniProtKB
- positive regulation of cytokine production involved in inflammatory response Source: UniProtKB
- positive regulation of glucose import Source: UniProtKB
- positive regulation of macropinocytosis Source: UniProtKB
- positive regulation of melanin biosynthetic process Source: UniProtKB
- protein import into nucleus Source: UniProtKB
- regulation of fibroblast migration Source: UniProtKB
- regulation of G1/S transition of mitotic cell cycle Source: UniProtKB
- regulation of glucose import Source: BHF-UCL
- regulation of innate immune response Source: UniProtKB
- regulation of protein localization to plasma membrane Source: BHF-UCL
- regulation of toll-like receptor 4 signaling pathway Source: UniProtKB
- signaling Source: GO_Central
- signal transduction Source: UniProtKB
- transforming growth factor beta receptor signaling pathway Source: UniProtKB
Keywordsi
Biological process | Cell cycle |
Enzyme and pathway databases
PathwayCommonsi | Q9UKG1 |
Reactomei | R-HSA-418889, Caspase activation via Dependence Receptors in the absence of ligand |
SignaLinki | Q9UKG1 |
SIGNORi | Q9UKG1 |
Protein family/group databases
MoonDBi | Q9UKG1, Curated |
Names & Taxonomyi
Protein namesi | Recommended name: DCC-interacting protein 13-alphaCuratedShort name: Dip13-alpha1 Publication Alternative name(s): Adapter protein containing PH domain, PTB domain and leucine zipper motif 1Curated |
Gene namesi | |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
EuPathDBi | HostDB:ENSG00000157500.10 |
HGNCi | HGNC:24035, APPL1 |
MIMi | 604299, gene |
neXtProti | NX_Q9UKG1 |
Subcellular locationi
Nucleus
- Nucleus 3 Publications
Endosome
- Early endosome membrane 3 Publications; Peripheral membrane protein 1 Publication
- Endosome 1 Publication
Other locations
Note: Early endosomal membrane-bound and nuclear. Translocated into the nucleus upon release from endosomal membranes following internalization of EGF.1 Publication
Cytosol
- cytosol Source: BHF-UCL
Endosome
- early endosome Source: UniProtKB
- early endosome membrane Source: UniProtKB-SubCell
- endosome Source: UniProtKB
- endosome membrane Source: UniProtKB
- macropinosome Source: UniProtKB
Extracellular region or secreted
- extracellular exosome Source: UniProtKB
Nucleus
- nucleus Source: UniProtKB
Plasma Membrane
- plasma membrane Source: UniProtKB
Other locations
- cytoplasm Source: UniProtKB
- cytoplasmic vesicle Source: UniProtKB
- early phagosome Source: UniProtKB
- intracellular vesicle Source: UniProtKB
- membrane Source: UniProtKB
- ruffle Source: UniProtKB
- vesicle membrane Source: BHF-UCL
Keywords - Cellular componenti
Cell projection, Cytoplasm, Cytoplasmic vesicle, Endosome, Membrane, NucleusPathology & Biotechi
Involvement in diseasei
Maturity-onset diabetes of the young 14 (MODY14)1 Publication
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_075857 | 94 | D → N in MODY14; no effect on protein abundance; loss of function in insulin receptor signaling pathway. 1 PublicationCorresponds to variant dbSNP:rs796065047EnsemblClinVar. | 1 |
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 410 | S → D: Decreased interaction with OCRL. 1 Publication | 1 |
Keywords - Diseasei
Diabetes mellitus, Disease mutationOrganism-specific databases
DisGeNETi | 26060 |
GeneReviewsi | APPL1 |
MalaCardsi | APPL1 |
MIMi | 616511, phenotype |
OpenTargetsi | ENSG00000157500 |
Orphaneti | 552, MODY |
PharmGKBi | PA162376755 |
Miscellaneous databases
Pharosi | Q9UKG1, Tbio |
Polymorphism and mutation databases
BioMutai | APPL1 |
DMDMi | 61213025 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000079985 | 1 – 709 | DCC-interacting protein 13-alphaAdd BLAST | 709 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 399 | PhosphothreonineCombined sources | 1 | |
Modified residuei | 401 | PhosphoserineCombined sources | 1 | |
Modified residuei | 410 | Phosphoserine; by PKA1 Publication | 1 | |
Modified residuei | 693 | PhosphoserineBy similarity | 1 | |
Modified residuei | 696 | PhosphoserineBy similarity | 1 |
Post-translational modificationi
Keywords - PTMi
PhosphoproteinProteomic databases
EPDi | Q9UKG1 |
jPOSTi | Q9UKG1 |
MassIVEi | Q9UKG1 |
MaxQBi | Q9UKG1 |
PaxDbi | Q9UKG1 |
PeptideAtlasi | Q9UKG1 |
PRIDEi | Q9UKG1 |
ProteomicsDBi | 84785 |
PTM databases
iPTMneti | Q9UKG1 |
PhosphoSitePlusi | Q9UKG1 |
Expressioni
Tissue specificityi
Gene expression databases
Bgeei | ENSG00000157500, Expressed in calcaneal tendon and 233 other tissues |
ExpressionAtlasi | Q9UKG1, baseline and differential |
Genevisiblei | Q9UKG1, HS |
Organism-specific databases
HPAi | ENSG00000157500, Low tissue specificity |
Interactioni
Subunit structurei
Homodimer (PubMed:18034774). Binds RAB5A/Rab5 through an N-terminal domain. This interaction is essential for its recruitment to endosomal membranes as well as its role in cell proliferation (PubMed:15016378). Binds DCC and the catalytic domain of the inactive form of AKT2 through its PID domain (PubMed:10490823, PubMed:12011067). Binds PIK3CA and subunits of the NuRD/MeCP1 complex (PubMed:10490823, PubMed:15016378).
Interacts with OCRL and INPP5B (PubMed:21666675, PubMed:17765681, PubMed:20133602, PubMed:21233288).
Interacts with NTRK2 (By similarity).
Interacts with APPL2; interaction is independent of follicle stimulating hormone stimulation; interaction is decreased by adiponectin in a time-dependent manner (PubMed:17030088, PubMed:18034774, PubMed:19661063).
Forms a complex with APPL2 and RUVBL2 (PubMed:19433865).
Forms a complex comprising APPL2, RUVBL2, CTNNB1, HDAC1 and HDAC2; interaction reduces interaction between CTNNB1, HDAC1, HDAC2 and RUVBL2 leading to the decrease of deacetylase activity of this complex; affects the recruitment of repressive complexes to the Wnt target genes (PubMed:19433865).
Interacts with ANXA2 (PubMed:21645192).
Interacts with TGFBR1; interaction is TGF beta dependent; mediates trafficking of the TGFBR1 from the endosomes to the nucleus via microtubules in a TRAF6-dependent manner (PubMed:26583432).
Interacts with PRKCZ (PubMed:26583432).
Interacts with PIK3R1 and APPL2 (By similarity).
Interacts with ADIPOR1; ADIPOQ enhances this interaction; inhibites adiponectin-stimulated binding of APPL2 to ADIPOR1 (By similarity).
By similarity13 PublicationsBinary interactionsi
Hide detailsQ9UKG1
GO - Molecular functioni
- beta-tubulin binding Source: UniProtKB
- identical protein binding Source: IntAct
- protein homodimerization activity Source: UniProtKB
- protein kinase B binding Source: BHF-UCL
Protein-protein interaction databases
BioGRIDi | 117522, 87 interactors |
CORUMi | Q9UKG1 |
DIPi | DIP-29322N |
ELMi | Q9UKG1 |
IntActi | Q9UKG1, 96 interactors |
MINTi | Q9UKG1 |
STRINGi | 9606.ENSP00000288266 |
Miscellaneous databases
RNActi | Q9UKG1, protein |
Structurei
Secondary structure
3D structure databases
SMRi | Q9UKG1 |
ModBasei | Search... |
PDBe-KBi | Search... |
Miscellaneous databases
EvolutionaryTracei | Q9UKG1 |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 3 – 268 | BARPROSITE-ProRule annotationAdd BLAST | 266 | |
Domaini | 277 – 375 | PHPROSITE-ProRule annotationAdd BLAST | 99 | |
Domaini | 496 – 656 | PIDPROSITE-ProRule annotationAdd BLAST | 161 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 1 – 428 | Required for RAB5A bindingAdd BLAST | 428 |
Coiled coil
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Coiled coili | 215 – 259 | Sequence analysisAdd BLAST | 45 | |
Coiled coili | 621 – 673 | Sequence analysisAdd BLAST | 53 |
Motif
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Motifi | 403 – 414 | F&HAdd BLAST | 12 |
Domaini
Keywords - Domaini
Coiled coilPhylogenomic databases
eggNOGi | KOG0521, Eukaryota KOG3536, Eukaryota |
GeneTreei | ENSGT00940000156624 |
HOGENOMi | CLU_025935_0_0_1 |
InParanoidi | Q9UKG1 |
OMAi | ENMQQTI |
OrthoDBi | 253010at2759 |
PhylomeDBi | Q9UKG1 |
TreeFami | TF328669 |
Family and domain databases
CDDi | cd07631, BAR_APPL1, 1 hit |
Gene3Di | 1.20.1270.60, 1 hit 2.30.29.30, 2 hits |
InterProi | View protein in InterPro IPR027267, AH/BAR_dom_sf IPR037929, APPL1_BAR IPR011993, PH-like_dom_sf IPR001849, PH_domain IPR006020, PTB/PI_dom |
Pfami | View protein in Pfam PF00169, PH, 1 hit PF00640, PID, 1 hit |
SMARTi | View protein in SMART SM00233, PH, 1 hit SM00462, PTB, 1 hit |
SUPFAMi | SSF103657, SSF103657, 1 hit |
PROSITEi | View protein in PROSITE PS50003, PH_DOMAIN, 1 hit PS01179, PID, 1 hit |
(1+)i Sequence
Sequence statusi: Complete.
This entry has 1 described isoform and 2 potential isoforms that are computationally mapped.Show allAlign All
10 20 30 40 50
MPGIDKLPIE ETLEDSPQTR SLLGVFEEDA TAISNYMNQL YQAMHRIYDA
60 70 80 90 100
QNELSAATHL TSKLLKEYEK QRFPLGGDDE VMSSTLQQFS KVIDELSSCH
110 120 130 140 150
AVLSTQLADA MMFPITQFKE RDLKEILTLK EVFQIASNDH DAAINRYSRL
160 170 180 190 200
SKKRENDKVK YEVTEDVYTS RKKQHQTMMH YFCALNTLQY KKKIALLEPL
210 220 230 240 250
LGYMQAQISF FKMGSENLNE QLEEFLANIG TSVQNVRREM DSDIETMQQT
260 270 280 290 300
IEDLEVASDP LYVPDPDPTK FPVNRNLTRK AGYLNARNKT GLVSSTWDRQ
310 320 330 340 350
FYFTQGGNLM SQARGDVAGG LAMDIDNCSV MAVDCEDRRY CFQITSFDGK
360 370 380 390 400
KSSILQAESK KDHEEWICTI NNISKQIYLS ENPEETAARV NQSALEAVTP
410 420 430 440 450
SPSFQQRHES LRPAAGQSRP PTARTSSSGS LGSESTNLAA LSLDSLVAPD
460 470 480 490 500
TPIQFDIISP VCEDQPGQAK AFGQGGRRTN PFGESGGSTK SETEDSILHQ
510 520 530 540 550
LFIVRFLGSM EVKSDDHPDV VYETMRQILA ARAIHNIFRM TESHLLVTCD
560 570 580 590 600
CLKLIDPQTQ VTRLTFPLPC VVLYATHQEN KRLFGFVLRT SSGRSESNLS
610 620 630 640 650
SVCYIFESNN EGEKICDSVG LAKQIALHAE LDRRASEKQK EIERVKEKQQ
660 670 680 690 700
KELNKQKQIE KDLEEQSRLI AASSRPNQAS SEGQFVVLSS SQSEESDLGE
GGKKRESEA
Computationally mapped potential isoform sequencesi
There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketC9JAB0 | C9JAB0_HUMAN | DCC-interacting protein 13-alpha | APPL1 | 133 | Annotation score: | ||
C9K0C4 | C9K0C4_HUMAN | DCC-interacting protein 13-alpha | APPL1 | 114 | Annotation score: |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_075857 | 94 | D → N in MODY14; no effect on protein abundance; loss of function in insulin receptor signaling pathway. 1 PublicationCorresponds to variant dbSNP:rs796065047EnsemblClinVar. | 1 | |
Natural variantiVAR_050958 | 108 | A → V. Corresponds to variant dbSNP:rs4381906Ensembl. | 1 | |
Natural variantiVAR_035909 | 643 | E → Q in a breast cancer sample; somatic mutation. 1 Publication | 1 | |
Natural variantiVAR_050959 | 700 | E → G. Corresponds to variant dbSNP:rs11544593Ensembl. | 1 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AF169797 mRNA Translation: AAF04012.1 AF424738 mRNA Translation: AAL17835.1 AB037849 mRNA Translation: BAA92666.2 BC028599 mRNA Translation: AAH28599.1 |
CCDSi | CCDS2882.1 |
RefSeqi | NP_036228.1, NM_012096.2 |
Genome annotation databases
Ensembli | ENST00000288266; ENSP00000288266; ENSG00000157500 ENST00000650354; ENSP00000498115; ENSG00000157500 |
GeneIDi | 26060 |
KEGGi | hsa:26060 |
UCSCi | uc003dio.4, human |
Keywords - Coding sequence diversityi
PolymorphismSimilar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AF169797 mRNA Translation: AAF04012.1 AF424738 mRNA Translation: AAL17835.1 AB037849 mRNA Translation: BAA92666.2 BC028599 mRNA Translation: AAH28599.1 |
CCDSi | CCDS2882.1 |
RefSeqi | NP_036228.1, NM_012096.2 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
2EJ8 | X-ray | 1.84 | A/B | 492-644 | [»] | |
2ELA | X-ray | 2.00 | A/B | 493-646 | [»] | |
2ELB | X-ray | 2.60 | A | 1-376 | [»] | |
2Q12 | X-ray | 1.79 | A | 5-265 | [»] | |
2Q13 | X-ray | 2.05 | A | 5-385 | [»] | |
2Z0N | X-ray | 1.95 | A | 1-275 | [»] | |
2Z0O | X-ray | 2.58 | A | 1-385 | [»] | |
5C5B | X-ray | 2.90 | A/C | 5-375 | [»] | |
SMRi | Q9UKG1 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 117522, 87 interactors |
CORUMi | Q9UKG1 |
DIPi | DIP-29322N |
ELMi | Q9UKG1 |
IntActi | Q9UKG1, 96 interactors |
MINTi | Q9UKG1 |
STRINGi | 9606.ENSP00000288266 |
Protein family/group databases
MoonDBi | Q9UKG1, Curated |
PTM databases
iPTMneti | Q9UKG1 |
PhosphoSitePlusi | Q9UKG1 |
Polymorphism and mutation databases
BioMutai | APPL1 |
DMDMi | 61213025 |
Proteomic databases
EPDi | Q9UKG1 |
jPOSTi | Q9UKG1 |
MassIVEi | Q9UKG1 |
MaxQBi | Q9UKG1 |
PaxDbi | Q9UKG1 |
PeptideAtlasi | Q9UKG1 |
PRIDEi | Q9UKG1 |
ProteomicsDBi | 84785 |
Protocols and materials databases
Antibodypediai | 2775, 356 antibodies |
Genome annotation databases
Ensembli | ENST00000288266; ENSP00000288266; ENSG00000157500 ENST00000650354; ENSP00000498115; ENSG00000157500 |
GeneIDi | 26060 |
KEGGi | hsa:26060 |
UCSCi | uc003dio.4, human |
Organism-specific databases
CTDi | 26060 |
DisGeNETi | 26060 |
EuPathDBi | HostDB:ENSG00000157500.10 |
GeneCardsi | APPL1 |
GeneReviewsi | APPL1 |
HGNCi | HGNC:24035, APPL1 |
HPAi | ENSG00000157500, Low tissue specificity |
MalaCardsi | APPL1 |
MIMi | 604299, gene 616511, phenotype |
neXtProti | NX_Q9UKG1 |
OpenTargetsi | ENSG00000157500 |
Orphaneti | 552, MODY |
PharmGKBi | PA162376755 |
HUGEi | Search... |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG0521, Eukaryota KOG3536, Eukaryota |
GeneTreei | ENSGT00940000156624 |
HOGENOMi | CLU_025935_0_0_1 |
InParanoidi | Q9UKG1 |
OMAi | ENMQQTI |
OrthoDBi | 253010at2759 |
PhylomeDBi | Q9UKG1 |
TreeFami | TF328669 |
Enzyme and pathway databases
PathwayCommonsi | Q9UKG1 |
Reactomei | R-HSA-418889, Caspase activation via Dependence Receptors in the absence of ligand |
SignaLinki | Q9UKG1 |
SIGNORi | Q9UKG1 |
Miscellaneous databases
BioGRID-ORCSi | 26060, 9 hits in 847 CRISPR screens |
ChiTaRSi | APPL1, human |
EvolutionaryTracei | Q9UKG1 |
GeneWikii | APPL1 |
GenomeRNAii | 26060 |
Pharosi | Q9UKG1, Tbio |
PROi | PR:Q9UKG1 |
RNActi | Q9UKG1, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000157500, Expressed in calcaneal tendon and 233 other tissues |
ExpressionAtlasi | Q9UKG1, baseline and differential |
Genevisiblei | Q9UKG1, HS |
Family and domain databases
CDDi | cd07631, BAR_APPL1, 1 hit |
Gene3Di | 1.20.1270.60, 1 hit 2.30.29.30, 2 hits |
InterProi | View protein in InterPro IPR027267, AH/BAR_dom_sf IPR037929, APPL1_BAR IPR011993, PH-like_dom_sf IPR001849, PH_domain IPR006020, PTB/PI_dom |
Pfami | View protein in Pfam PF00169, PH, 1 hit PF00640, PID, 1 hit |
SMARTi | View protein in SMART SM00233, PH, 1 hit SM00462, PTB, 1 hit |
SUPFAMi | SSF103657, SSF103657, 1 hit |
PROSITEi | View protein in PROSITE PS50003, PH_DOMAIN, 1 hit PS01179, PID, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | DP13A_HUMAN | |
Accessioni | Q9UKG1Primary (citable) accession number: Q9UKG1 Secondary accession number(s): Q9P2B9 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | March 15, 2005 |
Last sequence update: | May 1, 2000 | |
Last modified: | December 2, 2020 | |
This is version 173 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any 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. |
Miscellaneousi
Keywords - Technical termi
3D-structure, Reference proteomeDocuments
- Human chromosome 3
Human chromosome 3: entries, gene names and cross-references to MIM - Human polymorphisms and disease mutations
Index of human polymorphisms and disease mutations - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - Human entries with polymorphisms or disease mutations
List of human entries with polymorphisms or disease mutations