DCC-interacting protein 13-alpha - Homo sapiens (Human)

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Reviewed, UniProtKB/Swiss-Prot Q9UKG1 (DP13A_HUMAN)

Last modified December 15, 2009. Version 78. History...

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Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents

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Names and origin

Protein names

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 names

Name:	APPL1
Synonyms:	APPL, DIP13A, KIAA1428

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

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Protein attributes

Sequence length	709 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

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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. Ref.1 Ref.6 Ref.2
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
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
Post-translational modification	Phosphorylated upon DNA damage, probably by ATM or ATR. Ref.7 Ref.8
Sequence similarities	Contains 1 PH domain. Contains 1 PID domain.

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Ontologies

Keywords
Biological process	Cell cycle
Cellular component	Endosome Membrane Nucleus
Coding sequence diversity	Polymorphism
Domain	Coiled coil
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome
Gene Ontology (GO)
Biological process	cell cycle Inferred from electronic annotation. Source: UniProtKB-KW cell proliferation Ref.6 Inferred from direct assay. Source: UniProtKB insulin receptor signaling pathway Traceable author statement. Source: UniProtKB regulation of establishment of protein localization to plasma membrane Inferred from mutant phenotype. Source: UniProtKB regulation of glucose import Inferred from mutant phenotype. Source: UniProtKB
Cellular component	cytosol Inferred from direct assay. Source: UniProtKB endosome membrane Ref.6 Inferred from direct assay. Source: UniProtKB extrinsic to membrane Inferred from electronic annotation. Source: UniProtKB-SubCell microsome Inferred from direct assay. Source: UniProtKB nucleus Ref.6 Inferred from direct assay. Source: UniProtKB vesicle membrane Inferred from direct assay. Source: UniProtKB
Molecular function	protein kinase B binding Inferred from physical interaction. Source: UniProtKB
Complete GO annotation...

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Binary interactions

With	Entry	#Exp.	IntAct	Notes
ADIPOR1	Q96A54	5	EBI-741243,EBI-1632076
Adipor1	Q91VH1	3	EBI-741243,EBI-992398	From a different organism.
ADIPOR2	Q86V24	2	EBI-741243,EBI-1769445

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Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 709

709

DCC-interacting protein 13-alpha

PRO_0000079985

Regions

Domain

277 – 375

Domain

496 – 656

161

PID

Region

1 – 428

428

Required for RAB5A binding Ref.6

Coiled coil

215 – 259

Potential

Coiled coil

621 – 673

Potential

Amino acid modifications

Modified residue

399

Phosphothreonine Ref.8

Modified residue

401

Phosphoserine Ref.8

Modified residue

691

Phosphoserine Ref.7

Natural variations

Natural variant

108

A → V: dbSNP rs4381906.

VAR_050958

Natural variant

643

E → Q in a breast cancer sample; somatic mutation. Ref.11

VAR_035909

Natural variant

700

E → G: dbSNP rs11544593.

VAR_050959

Secondary structure

709

Helix Strand Turn

Details...

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Sequences

Sequence

Length

Mass (Da)

Tools

Q9UKG1-1 [UniParc].

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

709

79,663

        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

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References

	« Hide 'large scale' referencesShow '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: 10490823] [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: 12011067] [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: 10718198] [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: 12168954] [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: 15489334] [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: 15016378] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH RAB5A AND NURD/MECP1 COMPLEX, IDENTIFICATION BY MASS SPECTROMETRY.
[7]	"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: 17525332] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-691, MASS SPECTROMETRY.
[8]	"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: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-399 AND SER-401, MASS SPECTROMETRY.
[9]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[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: 19413330] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-401, MASS SPECTROMETRY.
[11]	"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. Velculescu V.E. Science 314:268-274(2006) [PubMed: 16959974] [Abstract] Cited for: VARIANT [LARGE SCALE ANALYSIS] GLN-643.
+	Additional computationally mapped references.

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Cross-references

Sequence databases

AF169797 mRNA. Translation: AAF04012.1.
AF424738 mRNA. Translation: AAL17835.1.
AB037849 mRNA. Translation: BAA92666.2.
BC028599 mRNA. Translation: AAH28599.1.

IPI

IPI00015836.

RefSeq

NP_036228.1.

UniGene

Hs.476415

3D structure databases

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	[»]

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-29322N.

IntAct

Q9UKG1. 15 interactions.

STRING

Q9UKG1.

PTM databases

PhosphoSite

Q9UKG1.

Proteomic databases

PeptideAtlas

Q9UKG1.

PRIDE

Q9UKG1.

Genome annotation databases

Ensembl

ENST00000288266; ENSP00000288266; ENSG00000157500; Homo sapiens. [Genome view]

GeneID

26060.

KEGG

hsa:26060.

UCSC

uc003dio.1. human.

Organism-specific databases

CTD

26060.

GeneCards

GC03P057237.

H-InvDB

HIX0003392.

HGNC

HGNC:24035. APPL1.

HPA

HPA011138.

MIM

604299. gene.

HUGE

Search...

GenAtlas

Search...

Phylogenomic databases

HOGENOM

HBG447421.

HOVERGEN

Q9UKG1.

InParanoid

Q9UKG1.

OMA

DSDVETM.

OrthoDB

EOG9KPWWJ.

Enzyme and pathway databases

Pathway_Interaction_DB

ar_pathway. Coregulation of Androgen receptor activity.

Gene expression databases

ArrayExpress

Q9UKG1.

Bgee

Q9UKG1.

CleanEx

HS_APPL1.

Genevestigator

Q9UKG1.

GermOnline

ENSG00000157500. Homo sapiens.

Family and domain databases

InterPro

IPR011993. PH_type.
IPR001849. Pleckstrin_homology.
IPR006020. PTB_PID.
[Graphical view]

Gene3D

G3DSA:2.30.29.30. PH_type. 2 hits.

Pfam

PF00169. PH. 1 hit.
PF00640. PID. 1 hit.
[Graphical view]

SMART

SM00233. PH. 1 hit.
[Graphical view]

PROSITE

PS50003. PH_DOMAIN. 1 hit.
PS01179. PID. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

NextBio

47954.

SOURCE

Search...

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Entry information

Entry name

DP13A_HUMAN

Accession

Primary (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:	December 15, 2009
This is version 78 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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.

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Relevant documents

Human chromosome 3

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

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

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

SIMILARITY comments

Index of protein domains and families

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Binary interactions

With

Entry

#Exp.

IntAct

Notes

Sequence annotation (Features)

Molecule processing

Regions

Amino acid modifications

Natural variations

Secondary structure

Sequences

References

Cross-references

Sequence databases

3D structure databases

Protein-protein interaction databases

PTM databases

Proteomic databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Enzyme and pathway databases

Gene expression databases

Family and domain databases

Other Resources

Entry information

Relevant documents