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Q9UKG1 (DP13A_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 119. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:APPL1
Synonyms:APPL, DIP13A, KIAA1428
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length709 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Required for the regulation of cell proliferation in response to extracellular signals from an early endosomal compartment. Links Rab5 to nuclear signal transduction. Ref.1 Ref.6

Subunit structure

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. Ref.1 Ref.2 Ref.6 Ref.7 Ref.11 Ref.14 Ref.15

Subcellular location

Early endosome membrane; Peripheral membrane protein. Nucleus. Note: Early endosomal membrane-bound and nuclear. Translocated into the nucleus upon release from endosomal membranes following internalization of EGF. Ref.6 Ref.11

Tissue specificity

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

Domain

Overexpression of an N-terminal domain (residues 1-319) or a C-terminal region (residues 273-709) has a proapoptotic effect. Ref.6

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 (Ref.15).

Post-translational modification

Phosophorylation at Ser-410 by PKA severely impairs binding to OCRL.

Sequence similarities

Contains 1 PH domain.

Contains 1 PID domain.

Ontologies

Keywords
   Biological processCell cycle
   Cellular componentEndosome
Membrane
Nucleus
   Coding sequence diversityPolymorphism
   DomainCoiled coil
   PTMPhosphoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processapoptotic process

Traceable author statement. Source: Reactome

cell cycle

Inferred from electronic annotation. Source: UniProtKB-KW

cell proliferation

Inferred from direct assay Ref.6. Source: UniProtKB

insulin receptor signaling pathway

Traceable author statement PubMed 17848569. Source: BHF-UCL

positive regulation of apoptotic process

Traceable author statement. Source: Reactome

regulation of apoptotic process

Traceable author statement. Source: Reactome

regulation of establishment of protein localization to plasma membrane

Inferred from mutant phenotype PubMed 17848569. Source: BHF-UCL

regulation of glucose import

Inferred from mutant phenotype PubMed 17848569. Source: BHF-UCL

signal transduction

Traceable author statement Ref.1. Source: UniProtKB

   Cellular_componentcytoplasm

Inferred by curator Ref.1. Source: UniProtKB

cytosol

Inferred from direct assay PubMed 17848569. Source: BHF-UCL

early endosome membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

endosome membrane

Inferred from direct assay Ref.6. Source: UniProtKB

extracellular vesicular exosome

Inferred from direct assay PubMed 19056867. Source: UniProt

nucleus

Inferred from direct assay Ref.6. Source: UniProtKB

vesicle membrane

Inferred from direct assay PubMed 17848569. Source: BHF-UCL

   Molecular_functionidentical protein binding

Inferred from physical interaction PubMed 17581628. Source: IntAct

protein binding

Inferred from physical interaction Ref.1Ref.2Ref.6Ref.14. Source: UniProtKB

protein kinase B binding

Inferred from physical interaction PubMed 17848569. Source: BHF-UCL

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 709709DCC-interacting protein 13-alpha
PRO_0000079985

Regions

Domain277 – 37599PH
Domain496 – 656161PID
Region1 – 428428Required for RAB5A binding Ref.6
Coiled coil215 – 25945 Potential
Coiled coil621 – 67353 Potential
Motif403 – 41412F&H

Amino acid modifications

Modified residue3991Phosphothreonine Ref.9
Modified residue4011Phosphoserine Ref.12
Modified residue4101Phosphoserine; by PKA Ref.7

Natural variations

Natural variant1081A → V.
Corresponds to variant rs4381906 [ dbSNP | Ensembl ].
VAR_050958
Natural variant6431E → Q in a breast cancer sample; somatic mutation. Ref.17
VAR_035909
Natural variant7001E → G.
Corresponds to variant rs11544593 [ dbSNP | Ensembl ].
VAR_050959

Secondary structure

......................................................... 709
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q9UKG1 [UniParc].

Last modified May 1, 2000. Version 1.
Checksum: 4CABECFCF4BB110D

FASTA70979,663
        10         20         30         40         50         60 
MPGIDKLPIE ETLEDSPQTR SLLGVFEEDA TAISNYMNQL YQAMHRIYDA QNELSAATHL 

        70         80         90        100        110        120 
TSKLLKEYEK QRFPLGGDDE VMSSTLQQFS KVIDELSSCH AVLSTQLADA MMFPITQFKE 

       130        140        150        160        170        180 
RDLKEILTLK EVFQIASNDH DAAINRYSRL SKKRENDKVK YEVTEDVYTS RKKQHQTMMH 

       190        200        210        220        230        240 
YFCALNTLQY KKKIALLEPL LGYMQAQISF FKMGSENLNE QLEEFLANIG TSVQNVRREM 

       250        260        270        280        290        300 
DSDIETMQQT IEDLEVASDP LYVPDPDPTK FPVNRNLTRK AGYLNARNKT GLVSSTWDRQ 

       310        320        330        340        350        360 
FYFTQGGNLM SQARGDVAGG LAMDIDNCSV MAVDCEDRRY CFQITSFDGK KSSILQAESK 

       370        380        390        400        410        420 
KDHEEWICTI NNISKQIYLS ENPEETAARV NQSALEAVTP SPSFQQRHES LRPAAGQSRP 

       430        440        450        460        470        480 
PTARTSSSGS LGSESTNLAA LSLDSLVAPD TPIQFDIISP VCEDQPGQAK AFGQGGRRTN 

       490        500        510        520        530        540 
PFGESGGSTK SETEDSILHQ LFIVRFLGSM EVKSDDHPDV VYETMRQILA ARAIHNIFRM 

       550        560        570        580        590        600 
TESHLLVTCD CLKLIDPQTQ VTRLTFPLPC VVLYATHQEN KRLFGFVLRT SSGRSESNLS 

       610        620        630        640        650        660 
SVCYIFESNN EGEKICDSVG LAKQIALHAE LDRRASEKQK EIERVKEKQQ KELNKQKQIE 

       670        680        690        700 
KDLEEQSRLI AASSRPNQAS SEGQFVVLSS SQSEESDLGE GGKKRESEA 

« Hide

References

« Hide 'large scale' references
[1]"Identification of a chromosome 3p14.3-21.1 gene, APPL, encoding an adaptor molecule that interacts with the oncoprotein-serine/threonine kinase AKT2."
Mitsuuchi Y., Johnson S.W., Sonoda G., Tanno S., Golemis E.A., Testa J.R.
Oncogene 18:4891-4898(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TISSUE SPECIFICITY, INTERACTION WITH AKT2 AND PIK3CA.
[2]"Mediation of the DCC apoptotic signal by DIP13 alpha."
Liu J., Yao F., Wu R., Morgan M., Thorburn A., Finley R.L. Jr., Chen Y.Q.
J. Biol. Chem. 277:26281-26285(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], INTERACTION WITH DCC.
[3]"Prediction of the coding sequences of unidentified human genes. XVI. The complete sequences of 150 new cDNA clones from brain which code for large proteins in vitro."
Nagase T., Kikuno R., Ishikawa K., Hirosawa M., Ohara O.
DNA Res. 7:65-73(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Brain.
[4]"Construction of expression-ready cDNA clones for KIAA genes: manual curation of 330 KIAA cDNA clones."
Nakajima D., Okazaki N., Yamakawa H., Kikuno R., Ohara O., Nagase T.
DNA Res. 9:99-106(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: SEQUENCE REVISION.
[5]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Testis.
[6]"APPL proteins link Rab5 to nuclear signal transduction via an endosomal compartment."
Miaczynska M., Christoforidis S., Giner A., Shevchenko A., Uttenweiler-Joseph S., Habermann B., Wilm M., Parton R.G., Zerial M.
Cell 116:445-456(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH RAB5A AND NURD/MECP1 COMPLEX, IDENTIFICATION BY MASS SPECTROMETRY.
[7]"A role of the Lowe syndrome protein OCRL in early steps of the endocytic pathway."
Erdmann K.S., Mao Y., McCrea H.J., Zoncu R., Lee S., Paradise S., Modregger J., Biemesderfer D., Toomre D., De Camilli P.
Dev. Cell 13:377-390(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH OCRL, F&H MOTIF, PHOSPHORYLATION AT SER-410.
[8]"ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage."
Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E., Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y., Gygi S.P., Elledge S.J.
Science 316:1160-1166(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Embryonic kidney.
[9]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-399, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[10]"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach."
Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.
Anal. Chem. 81:4493-4501(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[11]"Two closely related endocytic proteins that share a common OCRL-binding motif with APPL1."
Swan L.E., Tomasini L., Pirruccello M., Lunardi J., De Camilli P.
Proc. Natl. Acad. Sci. U.S.A. 107:3511-3516(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH OCRL, SUBCELLULAR LOCATION.
[12]"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis."
Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.
Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-401, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[13]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[14]"The PH domain proteins IPIP27A and B link OCRL1 to receptor recycling in the endocytic pathway."
Noakes C.J., Lee G., Lowe M.
Mol. Biol. Cell 22:606-623(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH OCRL.
[15]"Recognition of the F&H motif by the Lowe syndrome protein OCRL."
Pirruccello M., Swan L.E., Folta-Stogniew E., De Camilli P.
Nat. Struct. Mol. Biol. 18:789-795(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH OCRL, F&H MOTIF.
[16]"N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB."
Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.
Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[17]"The consensus coding sequences of human breast and colorectal cancers."
Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. expand/collapse author list , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E.
Science 314:268-274(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT [LARGE SCALE ANALYSIS] GLN-643.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF169797 mRNA. Translation: AAF04012.1.
AF424738 mRNA. Translation: AAL17835.1.
AB037849 mRNA. Translation: BAA92666.2.
BC028599 mRNA. Translation: AAH28599.1.
CCDSCCDS2882.1.
RefSeqNP_036228.1. NM_012096.2.
UniGeneHs.476415.

3D structure databases

PDBe
RCSB-PDB
PDBj
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[»]
ProteinModelPortalQ9UKG1.
SMRQ9UKG1. Positions 4-378, 499-645.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid117522. 33 interactions.
DIPDIP-29322N.
IntActQ9UKG1. 48 interactions.
MINTMINT-1177965.
STRING9606.ENSP00000288266.

PTM databases

PhosphoSiteQ9UKG1.

Polymorphism databases

DMDM61213025.

Proteomic databases

MaxQBQ9UKG1.
PaxDbQ9UKG1.
PeptideAtlasQ9UKG1.
PRIDEQ9UKG1.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000288266; ENSP00000288266; ENSG00000157500.
GeneID26060.
KEGGhsa:26060.
UCSCuc003dio.3. human.

Organism-specific databases

CTD26060.
GeneCardsGC03P057237.
HGNCHGNC:24035. APPL1.
HPAHPA011138.
MIM604299. gene.
neXtProtNX_Q9UKG1.
PharmGKBPA162376755.
HUGESearch...
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG69757.
HOGENOMHOG000285988.
HOVERGENHBG051394.
InParanoidQ9UKG1.
KOK08733.
OMASDVETMQ.
OrthoDBEOG79PJPK.
PhylomeDBQ9UKG1.
TreeFamTF328669.

Enzyme and pathway databases

ReactomeREACT_578. Apoptosis.
SignaLinkQ9UKG1.

Gene expression databases

ArrayExpressQ9UKG1.
BgeeQ9UKG1.
CleanExHS_APPL1.
GenevestigatorQ9UKG1.

Family and domain databases

Gene3D1.20.1270.60. 1 hit.
2.30.29.30. 2 hits.
InterProIPR027267. AH/BAR-dom.
IPR011993. PH_like_dom.
IPR001849. Pleckstrin_homology.
IPR006020. PTB/PI_dom.
[Graphical view]
PfamPF00640. PID. 1 hit.
[Graphical view]
SMARTSM00233. PH. 1 hit.
[Graphical view]
PROSITEPS50003. PH_DOMAIN. 1 hit.
PS01179. PID. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSAPPL1. human.
EvolutionaryTraceQ9UKG1.
GeneWikiAPPL1.
GenomeRNAi26060.
NextBio47954.
PROQ9UKG1.
SOURCESearch...

Entry information

Entry nameDP13A_HUMAN
AccessionPrimary (citable) accession number: Q9UKG1
Secondary accession number(s): Q9P2B9
Entry history
Integrated into UniProtKB/Swiss-Prot: March 15, 2005
Last sequence update: May 1, 2000
Last modified: July 9, 2014
This is version 119 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 3

Human chromosome 3: entries, gene names and cross-references to MIM