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Protein

DCC-interacting protein 13-alpha

Gene

APPL1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Adapter protein that interacts with proteins involved in different cellular signaling pathways. Required for the regulation of cell proliferation in response to extracellular signals from an early endosomal compartment. Links Rab5 to nuclear signal transduction. Involved in the regulation of the insulin receptor signaling pathway.3 Publications

GO - Molecular functioni

  • identical protein binding Source: IntAct
  • protein kinase B binding Source: BHF-UCL

GO - Biological processi

  • cell cycle Source: UniProtKB-KW
  • cell proliferation Source: UniProtKB
  • extrinsic apoptotic signaling pathway in absence of ligand Source: Reactome
  • insulin receptor signaling pathway Source: UniProtKB
  • regulation of establishment of protein localization to plasma membrane Source: BHF-UCL
  • regulation of glucose import Source: BHF-UCL
  • signal transduction Source: UniProtKB
Complete GO annotation...

Keywords - Biological processi

Cell cycle

Enzyme and pathway databases

BioCyciZFISH:ENSG00000157500-MONOMER.
ReactomeiR-HSA-418889. Ligand-independent caspase activation via DCC.
SignaLinkiQ9UKG1.
SIGNORiQ9UKG1.

Names & Taxonomyi

Protein namesi
Recommended name:
DCC-interacting protein 13-alpha
Short name:
Dip13-alpha
Alternative name(s):
Adapter protein containing PH domain, PTB domain and leucine zipper motif 1
Gene namesi
Name:APPL1
Synonyms:APPLImported, DIP13A, KIAA1428Imported
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 3

Organism-specific databases

HGNCiHGNC:24035. APPL1.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
  • cytosol Source: BHF-UCL
  • early endosome membrane Source: UniProtKB-SubCell
  • endosome membrane Source: UniProtKB
  • extracellular exosome Source: UniProtKB
  • nucleus Source: UniProtKB
  • vesicle membrane Source: BHF-UCL
Complete GO annotation...

Keywords - Cellular componenti

Endosome, Membrane, Nucleus

Pathology & Biotechi

Involvement in diseasei

Maturity-onset diabetes of the young 14 (MODY14)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA form of diabetes that is characterized by an autosomal dominant mode of inheritance, onset in childhood or early adulthood (usually before 25 years of age), a primary defect in insulin secretion and frequent insulin-independence at the beginning of the disease.
See also OMIM:616511
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_07585794D → N in MODY14; no effect on protein abundance; loss of function in insulin receptor signaling pathway. 1 PublicationCorresponds to variant rs796065047dbSNPEnsembl.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi410S → D: Decreased interaction with OCRL. 1 Publication1

Keywords - Diseasei

Diabetes mellitus, Disease mutation

Organism-specific databases

DisGeNETi26060.
MIMi616511. phenotype.
OpenTargetsiENSG00000157500.
PharmGKBiPA162376755.

Polymorphism and mutation databases

BioMutaiAPPL1.
DMDMi61213025.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000799851 – 709DCC-interacting protein 13-alphaAdd BLAST709

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei399PhosphothreonineCombined sources1
Modified residuei401PhosphoserineCombined sources1
Modified residuei410Phosphoserine; by PKA1 Publication1
Modified residuei693PhosphoserineBy similarity1
Modified residuei696PhosphoserineBy similarity1

Post-translational modificationi

Phosphorylation at Ser-410 by PKA severely impairs binding to OCRL.1 Publication

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ9UKG1.
MaxQBiQ9UKG1.
PaxDbiQ9UKG1.
PeptideAtlasiQ9UKG1.
PRIDEiQ9UKG1.

PTM databases

iPTMnetiQ9UKG1.
PhosphoSitePlusiQ9UKG1.

Expressioni

Tissue specificityi

High levels in heart, ovary, pancreas and skeletal muscle.1 Publication

Gene expression databases

BgeeiENSG00000157500.
CleanExiHS_APPL1.
ExpressionAtlasiQ9UKG1. baseline and differential.
GenevisibleiQ9UKG1. HS.

Organism-specific databases

HPAiHPA011138.

Interactioni

Subunit structurei

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. Binds DCC and the catalytic domain of the inactive form of AKT2 through its PID domain. Binds PIK3CA and subunits of the NuRD/MeCP1 complex. Interacts with OCRL and INPP5B.7 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
itself7EBI-741243,EBI-741243
ACTN2P356092EBI-741243,EBI-77797
ADIPOR1Q96A546EBI-741243,EBI-1632076
Adipor1Q91VH13EBI-741243,EBI-992398From a different organism.
ADIPOR2Q86V243EBI-741243,EBI-1769445
AKT1P317492EBI-741243,EBI-296087
APPL2Q8NEU89EBI-741243,EBI-741261
DSTQ030013EBI-741243,EBI-310758
DYSFO759232EBI-741243,EBI-2799016
EGFRP005332EBI-741243,EBI-297353
FARS2O953635EBI-741243,EBI-2513774
HDAC1Q135472EBI-741243,EBI-301834
HDAC3O153792EBI-741243,EBI-607682
MAGEA9BP433623EBI-741243,EBI-10209139
MEOX1P502213EBI-741243,EBI-2864512
RAB21Q9UL2510EBI-741243,EBI-1056039
RAB5AP2033917EBI-741243,EBI-399437
RHEBL1Q8TAI73EBI-741243,EBI-746555
RTCBQ9Y3I03EBI-741243,EBI-2107208
SYNE2Q8WXH03EBI-741243,EBI-2372294
TRAF2Q129332EBI-741243,EBI-355744
UBE2OQ9C0C95EBI-741243,EBI-2339946

GO - Molecular functioni

  • identical protein binding Source: IntAct
  • protein kinase B binding Source: BHF-UCL

Protein-protein interaction databases

BioGridi117522. 68 interactors.
DIPiDIP-29322N.
IntActiQ9UKG1. 85 interactors.
MINTiMINT-1177965.
STRINGi9606.ENSP00000288266.

Structurei

Secondary structure

1709
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi9 – 11Combined sources3
Turni12 – 14Combined sources3
Helixi16 – 66Combined sources51
Helixi67 – 70Combined sources4
Helixi81 – 110Combined sources30
Helixi112 – 120Combined sources9
Helixi122 – 151Combined sources30
Beta strandi152 – 154Combined sources3
Helixi157 – 217Combined sources61
Helixi220 – 257Combined sources38
Helixi259 – 261Combined sources3
Beta strandi262 – 265Combined sources4
Turni268 – 270Combined sources3
Beta strandi281 – 286Combined sources6
Beta strandi298 – 305Combined sources8
Beta strandi308 – 312Combined sources5
Beta strandi320 – 324Combined sources5
Beta strandi329 – 333Combined sources5
Beta strandi339 – 345Combined sources7
Beta strandi348 – 350Combined sources3
Beta strandi354 – 356Combined sources3
Helixi360 – 374Combined sources15
Beta strandi499 – 512Combined sources14
Helixi519 – 534Combined sources16
Beta strandi542 – 555Combined sources14
Turni557 – 559Combined sources3
Beta strandi562 – 567Combined sources6
Helixi568 – 570Combined sources3
Beta strandi571 – 577Combined sources7
Beta strandi580 – 590Combined sources11
Beta strandi600 – 610Combined sources11
Helixi612 – 629Combined sources18
Helixi634 – 643Combined sources10

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2EJ8X-ray1.84A/B492-644[»]
2ELAX-ray2.00A/B493-646[»]
2ELBX-ray2.60A1-376[»]
2Q12X-ray1.79A5-265[»]
2Q13X-ray2.05A5-385[»]
2Z0NX-ray1.95A1-275[»]
2Z0OX-ray2.58A1-385[»]
5C5BX-ray2.90A/C5-375[»]
ProteinModelPortaliQ9UKG1.
SMRiQ9UKG1.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ9UKG1.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini277 – 375PHPROSITE-ProRule annotationAdd BLAST99
Domaini496 – 656PIDPROSITE-ProRule annotationAdd BLAST161

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 428Required for RAB5A bindingAdd BLAST428

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili215 – 259Sequence analysisAdd BLAST45
Coiled coili621 – 673Sequence analysisAdd BLAST53

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi403 – 414F&HAdd BLAST12

Domaini

Overexpression of an N-terminal domain (residues 1-319) or a C-terminal region (residues 273-709) has a proapoptotic effect.1 Publication
The F&H motif, an approximately 12-13 amino-acid sequence centered around Phe and His residues, is essential for binding to OCRL and INPP5B.1 Publication

Sequence similaritiesi

Contains 1 PH domain.PROSITE-ProRule annotation
Contains 1 PID domain.PROSITE-ProRule annotation

Keywords - Domaini

Coiled coil

Phylogenomic databases

eggNOGiKOG0521. Eukaryota.
KOG3536. Eukaryota.
ENOG410ZWZQ. LUCA.
GeneTreeiENSGT00710000106752.
HOGENOMiHOG000285988.
HOVERGENiHBG051394.
InParanoidiQ9UKG1.
KOiK08733.
OMAiSDVETMQ.
OrthoDBiEOG091G08AV.
PhylomeDBiQ9UKG1.
TreeFamiTF328669.

Family and domain databases

Gene3Di1.20.1270.60. 1 hit.
2.30.29.30. 2 hits.
InterProiIPR027267. AH/BAR-dom.
IPR011993. PH_dom-like.
IPR001849. PH_domain.
IPR006020. PTB/PI_dom.
[Graphical view]
PfamiPF00169. PH. 1 hit.
PF00640. PID. 1 hit.
[Graphical view]
SMARTiSM00233. PH. 1 hit.
SM00462. PTB. 1 hit.
[Graphical view]
SUPFAMiSSF50729. SSF50729. 2 hits.
PROSITEiPS50003. PH_DOMAIN. 1 hit.
PS01179. PID. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q9UKG1-1 [UniParc]FASTAAdd to basket

« Hide

        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
Length:709
Mass (Da):79,663
Last modified:May 1, 2000 - v1
Checksum:i4CABECFCF4BB110D
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_07585794D → N in MODY14; no effect on protein abundance; loss of function in insulin receptor signaling pathway. 1 PublicationCorresponds to variant rs796065047dbSNPEnsembl.1
Natural variantiVAR_050958108A → V.Corresponds to variant rs4381906dbSNPEnsembl.1
Natural variantiVAR_035909643E → Q in a breast cancer sample; somatic mutation. 1 Publication1
Natural variantiVAR_050959700E → G.Corresponds to variant rs11544593dbSNPEnsembl.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.
CCDSiCCDS2882.1.
RefSeqiNP_036228.1. NM_012096.2.
UniGeneiHs.476415.

Genome annotation databases

EnsembliENST00000288266; ENSP00000288266; ENSG00000157500.
GeneIDi26060.
KEGGihsa:26060.
UCSCiuc003dio.4. human.

Keywords - Coding sequence diversityi

Polymorphism

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.
CCDSiCCDS2882.1.
RefSeqiNP_036228.1. NM_012096.2.
UniGeneiHs.476415.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2EJ8X-ray1.84A/B492-644[»]
2ELAX-ray2.00A/B493-646[»]
2ELBX-ray2.60A1-376[»]
2Q12X-ray1.79A5-265[»]
2Q13X-ray2.05A5-385[»]
2Z0NX-ray1.95A1-275[»]
2Z0OX-ray2.58A1-385[»]
5C5BX-ray2.90A/C5-375[»]
ProteinModelPortaliQ9UKG1.
SMRiQ9UKG1.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi117522. 68 interactors.
DIPiDIP-29322N.
IntActiQ9UKG1. 85 interactors.
MINTiMINT-1177965.
STRINGi9606.ENSP00000288266.

PTM databases

iPTMnetiQ9UKG1.
PhosphoSitePlusiQ9UKG1.

Polymorphism and mutation databases

BioMutaiAPPL1.
DMDMi61213025.

Proteomic databases

EPDiQ9UKG1.
MaxQBiQ9UKG1.
PaxDbiQ9UKG1.
PeptideAtlasiQ9UKG1.
PRIDEiQ9UKG1.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000288266; ENSP00000288266; ENSG00000157500.
GeneIDi26060.
KEGGihsa:26060.
UCSCiuc003dio.4. human.

Organism-specific databases

CTDi26060.
DisGeNETi26060.
GeneCardsiAPPL1.
HGNCiHGNC:24035. APPL1.
HPAiHPA011138.
MIMi604299. gene.
616511. phenotype.
neXtProtiNX_Q9UKG1.
OpenTargetsiENSG00000157500.
PharmGKBiPA162376755.
HUGEiSearch...
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0521. Eukaryota.
KOG3536. Eukaryota.
ENOG410ZWZQ. LUCA.
GeneTreeiENSGT00710000106752.
HOGENOMiHOG000285988.
HOVERGENiHBG051394.
InParanoidiQ9UKG1.
KOiK08733.
OMAiSDVETMQ.
OrthoDBiEOG091G08AV.
PhylomeDBiQ9UKG1.
TreeFamiTF328669.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000157500-MONOMER.
ReactomeiR-HSA-418889. Ligand-independent caspase activation via DCC.
SignaLinkiQ9UKG1.
SIGNORiQ9UKG1.

Miscellaneous databases

ChiTaRSiAPPL1. human.
EvolutionaryTraceiQ9UKG1.
GeneWikiiAPPL1.
GenomeRNAii26060.
PROiQ9UKG1.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000157500.
CleanExiHS_APPL1.
ExpressionAtlasiQ9UKG1. baseline and differential.
GenevisibleiQ9UKG1. HS.

Family and domain databases

Gene3Di1.20.1270.60. 1 hit.
2.30.29.30. 2 hits.
InterProiIPR027267. AH/BAR-dom.
IPR011993. PH_dom-like.
IPR001849. PH_domain.
IPR006020. PTB/PI_dom.
[Graphical view]
PfamiPF00169. PH. 1 hit.
PF00640. PID. 1 hit.
[Graphical view]
SMARTiSM00233. PH. 1 hit.
SM00462. PTB. 1 hit.
[Graphical view]
SUPFAMiSSF50729. SSF50729. 2 hits.
PROSITEiPS50003. PH_DOMAIN. 1 hit.
PS01179. PID. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiDP13A_HUMAN
AccessioniPrimary (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: November 30, 2016
This is version 143 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 3
    Human chromosome 3: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. 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.