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Protein

DCC-interacting protein 13-beta

Gene

APPL2

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

Functioni

Required for the regulation of cell proliferation in response to extracellular signals mediated by an early endosomal compartment. Links Rab5 to nuclear signal transduction.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei234 – 235Breakpoint for chromosomal translocation1 Publication2

GO - Biological processi

  • cell cycle Source: UniProtKB-KW
  • cell proliferation Source: UniProtKB
  • signal transduction Source: UniProtKB
Complete GO annotation...

Keywords - Biological processi

Cell cycle

Names & Taxonomyi

Protein namesi
Recommended name:
DCC-interacting protein 13-beta
Short name:
Dip13-beta
Alternative name(s):
Adapter protein containing PH domain, PTB domain and leucine zipper motif 2
Gene namesi
Name:APPL2
Synonyms:DIP13B
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 12

Organism-specific databases

HGNCiHGNC:18242. APPL2.

Subcellular locationi

GO - Cellular componenti

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

Keywords - Cellular componenti

Endosome, Membrane, Nucleus

Pathology & Biotechi

Involvement in diseasei

A chromosomal aberration involving APPL2/DIP13B is found in patients with chromosome 22q13.3 deletion syndrome. Translocation t(12;22)(q24.1;q13.3) with SHANK3/PSAP2 (PubMed:11431708).

Organism-specific databases

DisGeNETi55198.
OpenTargetsiENSG00000136044.
PharmGKBiPA164741199.

Polymorphism and mutation databases

BioMutaiAPPL2.
DMDMi160419148.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000799871 – 664DCC-interacting protein 13-betaAdd BLAST664

Proteomic databases

EPDiQ8NEU8.
MaxQBiQ8NEU8.
PaxDbiQ8NEU8.
PeptideAtlasiQ8NEU8.
PRIDEiQ8NEU8.

PTM databases

iPTMnetiQ8NEU8.
PhosphoSitePlusiQ8NEU8.

Expressioni

Tissue specificityi

High levels in brain, heart, kidney and skeletal muscle.1 Publication

Gene expression databases

BgeeiENSG00000136044.
CleanExiHS_APPL2.
ExpressionAtlasiQ8NEU8. baseline and differential.
GenevisibleiQ8NEU8. HS.

Organism-specific databases

HPAiHPA039688.
HPA043925.

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 subunits of the NuRD/MeCP1 complex.

Binary interactionsi

WithEntry#Exp.IntActNotes
APPL1Q9UKG19EBI-741261,EBI-741243
CRADDP785603EBI-741261,EBI-520375
MAPRE3Q9UPY83EBI-741261,EBI-726739
RAB22AQ9UL266EBI-741261,EBI-399456
RAB5CP511485EBI-741261,EBI-1054923
SUV39H2Q9H5I14EBI-741261,EBI-723127

Protein-protein interaction databases

BioGridi120495. 32 interactors.
IntActiQ8NEU8. 30 interactors.
MINTiMINT-5005458.
STRINGi9606.ENSP00000258530.

Structurei

Secondary structure

1664
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi9 – 11Combined sources3
Turni12 – 14Combined sources3
Helixi17 – 70Combined sources54
Helixi80 – 110Combined sources31
Helixi112 – 148Combined sources37
Beta strandi152 – 154Combined sources3
Helixi157 – 217Combined sources61
Helixi220 – 254Combined sources35
Helixi259 – 261Combined sources3
Helixi266 – 269Combined sources4
Beta strandi281 – 288Combined sources8
Beta strandi291 – 293Combined sources3
Beta strandi296 – 305Combined sources10
Beta strandi308 – 312Combined sources5
Beta strandi320 – 324Combined sources5
Beta strandi329 – 333Combined sources5
Beta strandi341 – 345Combined sources5
Beta strandi351 – 356Combined sources6
Helixi360 – 373Combined sources14

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4H8SX-ray3.50A/B/C/D2-384[»]
5C5BX-ray2.90B/D1-375[»]
ProteinModelPortaliQ8NEU8.
SMRiQ8NEU8.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini277 – 375PHPROSITE-ProRule annotationAdd BLAST99
Domaini488 – 637PIDPROSITE-ProRule annotationAdd BLAST150

Region

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

Sequence similaritiesi

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

Phylogenomic databases

eggNOGiKOG0521. Eukaryota.
KOG3536. Eukaryota.
ENOG410ZISK. LUCA.
GeneTreeiENSGT00710000106752.
HOGENOMiHOG000285988.
HOVERGENiHBG051394.
InParanoidiQ8NEU8.
KOiK20132.
OMAiFAHGQIN.
OrthoDBiEOG091G08AV.
PhylomeDBiQ8NEU8.
TreeFamiTF328669.

Family and domain databases

Gene3Di2.30.29.30. 2 hits.
InterProiIPR011993. 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]

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q8NEU8-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MPAVDKLLLE EALQDSPQTR SLLSVFEEDA GTLTDYTNQL LQAMQRVYGA
60 70 80 90 100
QNEMCLATQQ LSKQLLAYEK QNFALGKGDE EVISTLHYFS KVVDELNLLH
110 120 130 140 150
TELAKQLADT MVLPIIQFRE KDLTEVSTLK DLFGLASNEH DLSMAKYSRL
160 170 180 190 200
PKKKENEKVK TEVGKEVAAA RRKQHLSSLQ YYCALNALQY RKQMAMMEPM
210 220 230 240 250
IGFAHGQINF FKKGAEMFSK RMDSFLSSVA DMVQSIQVEL EAEAEKMRVS
260 270 280 290 300
QQELLSVDES VYTPDSDVAA PQINRNLIQK AGYLNLRNKT GLVTTTWERL
310 320 330 340 350
YFFTQGGNLM CQPRGAVAGG LIQDLDNCSV MAVDCEDRRY CFQITTPNGK
360 370 380 390 400
SGIILQAESR KENEEWICAI NNISRQIYLT DNPEAVAIKL NQTALQAVTP
410 420 430 440 450
ITSFGKKQES SCPSQNLKNS EMENENDKIV PKATASLPEA EELIAPGTPI
460 470 480 490 500
QFDIVLPATE FLDQNRGSRR TNPFGETEDE SFPEAEDSLL QQMFIVRFLG
510 520 530 540 550
SMAVKTDSTT EVIYEAMRQV LAARAIHNIF RMTESHLMVT SQSLRLIDPQ
560 570 580 590 600
TQVSRANFEL TSVTQFAAHQ ENKRLVGFVI RVPESTGEES LSTYIFESNS
610 620 630 640 650
EGEKICYAIN LGKEIIEVQK DPEALAQLML SIPLTNDGKY VLLNDQPDDD
660
DGNPNEHRGA ESEA
Length:664
Mass (Da):74,493
Last modified:October 23, 2007 - v3
Checksum:i359404B1CBA813DB
GO
Isoform 2 (identifier: Q8NEU8-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-43: Missing.

Note: No experimental confirmation available.
Show »
Length:621
Mass (Da):69,746
Checksum:i17C12D12E6225086
GO
Isoform 3 (identifier: Q8NEU8-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     138-138: N → NDVCLFL

Note: No experimental confirmation available.
Show »
Length:670
Mass (Da):75,184
Checksum:iD805FD692E06644B
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti295T → A (PubMed:14702039).Curated1
Sequence conflicti448T → A (PubMed:14702039).Curated1
Sequence conflicti528N → S in BAH12496 (PubMed:14702039).Curated1
Sequence conflicti575L → P in BAH12397 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_021505433A → V.2 PublicationsCorresponds to variant rs2272495dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0447711 – 43Missing in isoform 2. 1 PublicationAdd BLAST43
Alternative sequenceiVSP_044772138N → NDVCLFL in isoform 3. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY113704 mRNA. Translation: AAM55530.1.
AK001521 mRNA. No translation available.
AK296610 mRNA. Translation: BAH12397.1.
AK297100 mRNA. Translation: BAH12496.1.
AC016257 Genomic DNA. No translation available.
AC078874 Genomic DNA. No translation available.
BC033731 mRNA. Translation: AAH33731.1.
CCDSiCCDS58275.1. [Q8NEU8-2]
CCDS58276.1. [Q8NEU8-3]
CCDS9101.1. [Q8NEU8-1]
RefSeqiNP_001238833.1. NM_001251904.1. [Q8NEU8-3]
NP_001238834.1. NM_001251905.1. [Q8NEU8-2]
NP_060641.2. NM_018171.3. [Q8NEU8-1]
XP_016875041.1. XM_017019552.1. [Q8NEU8-2]
XP_016875042.1. XM_017019553.1. [Q8NEU8-2]
UniGeneiHs.506603.

Genome annotation databases

EnsembliENST00000258530; ENSP00000258530; ENSG00000136044. [Q8NEU8-1]
ENST00000539978; ENSP00000444472; ENSG00000136044. [Q8NEU8-2]
ENST00000551662; ENSP00000446917; ENSG00000136044. [Q8NEU8-3]
GeneIDi55198.
KEGGihsa:55198.
UCSCiuc001tlf.2. human. [Q8NEU8-1]

Keywords - Coding sequence diversityi

Alternative splicing, Chromosomal rearrangement, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY113704 mRNA. Translation: AAM55530.1.
AK001521 mRNA. No translation available.
AK296610 mRNA. Translation: BAH12397.1.
AK297100 mRNA. Translation: BAH12496.1.
AC016257 Genomic DNA. No translation available.
AC078874 Genomic DNA. No translation available.
BC033731 mRNA. Translation: AAH33731.1.
CCDSiCCDS58275.1. [Q8NEU8-2]
CCDS58276.1. [Q8NEU8-3]
CCDS9101.1. [Q8NEU8-1]
RefSeqiNP_001238833.1. NM_001251904.1. [Q8NEU8-3]
NP_001238834.1. NM_001251905.1. [Q8NEU8-2]
NP_060641.2. NM_018171.3. [Q8NEU8-1]
XP_016875041.1. XM_017019552.1. [Q8NEU8-2]
XP_016875042.1. XM_017019553.1. [Q8NEU8-2]
UniGeneiHs.506603.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4H8SX-ray3.50A/B/C/D2-384[»]
5C5BX-ray2.90B/D1-375[»]
ProteinModelPortaliQ8NEU8.
SMRiQ8NEU8.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi120495. 32 interactors.
IntActiQ8NEU8. 30 interactors.
MINTiMINT-5005458.
STRINGi9606.ENSP00000258530.

PTM databases

iPTMnetiQ8NEU8.
PhosphoSitePlusiQ8NEU8.

Polymorphism and mutation databases

BioMutaiAPPL2.
DMDMi160419148.

Proteomic databases

EPDiQ8NEU8.
MaxQBiQ8NEU8.
PaxDbiQ8NEU8.
PeptideAtlasiQ8NEU8.
PRIDEiQ8NEU8.

Protocols and materials databases

DNASUi55198.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000258530; ENSP00000258530; ENSG00000136044. [Q8NEU8-1]
ENST00000539978; ENSP00000444472; ENSG00000136044. [Q8NEU8-2]
ENST00000551662; ENSP00000446917; ENSG00000136044. [Q8NEU8-3]
GeneIDi55198.
KEGGihsa:55198.
UCSCiuc001tlf.2. human. [Q8NEU8-1]

Organism-specific databases

CTDi55198.
DisGeNETi55198.
GeneCardsiAPPL2.
H-InvDBHIX0010948.
HGNCiHGNC:18242. APPL2.
HPAiHPA039688.
HPA043925.
MIMi606231. gene.
neXtProtiNX_Q8NEU8.
OpenTargetsiENSG00000136044.
PharmGKBiPA164741199.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0521. Eukaryota.
KOG3536. Eukaryota.
ENOG410ZISK. LUCA.
GeneTreeiENSGT00710000106752.
HOGENOMiHOG000285988.
HOVERGENiHBG051394.
InParanoidiQ8NEU8.
KOiK20132.
OMAiFAHGQIN.
OrthoDBiEOG091G08AV.
PhylomeDBiQ8NEU8.
TreeFamiTF328669.

Miscellaneous databases

ChiTaRSiAPPL2. human.
GeneWikiiAPPL2.
GenomeRNAii55198.
PROiQ8NEU8.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000136044.
CleanExiHS_APPL2.
ExpressionAtlasiQ8NEU8. baseline and differential.
GenevisibleiQ8NEU8. HS.

Family and domain databases

Gene3Di2.30.29.30. 2 hits.
InterProiIPR011993. 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 nameiDP13B_HUMAN
AccessioniPrimary (citable) accession number: Q8NEU8
Secondary accession number(s): B7Z411
, B7Z4B0, F5GZG0, F8W1P5, Q8N4R7, Q9NVL2
Entry historyi
Integrated into UniProtKB/Swiss-Prot: March 15, 2005
Last sequence update: October 23, 2007
Last modified: November 30, 2016
This is version 133 of the entry and version 3 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 12
    Human chromosome 12: 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.