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AFDN (afadin, adherens junction formation factor)

Written1997-12Jean-Loup Huret
Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France
Updated2018-12Jean Loup Huret, Philippe Dessen
jean-loup.huret@atlasgeneticsoncology.org (JLH); UMR 1170 INSERM, Gustave Roussy, 114 rue Edouard Vaillant, 94805 Villejuif 94805, France (PHD)

Abstract Afadin, the protein coded by AFDN (6q27), also known as AF6 or MLLT4, is a cytoskeletal and junction-associated protein that links nectins, transmembrane proteins, to the F-actin (actin cytoskeleton) in a type of cell-cell junctions: the adherens junctions (AJs). Afadin plays an important role in AJs integrity and apical-basal polarity. There is growing evidence of it's role in carcinogenesis.

Keywords Afadin; AFDN; AF6; MLLT4; Cytoskeleton; Cell-cell junctions; Adherens junctions; Apical-basal polarity; Epithelial-mesenchymal transition; Tight junctions; Mitotic spindle orientation; Migration; Nectin; Actin; Acute myeloid leukemia; Breast cancer; Colon cancer; Pancreatic cancer; Endometrial cancer; Gastric cancer; Osteosarcoma; Neurone synapse.

(Note : for Links provided by Atlas : click)

Identity

Alias_namesMLLT4
myeloid/lymphoid or mixed-lineage leukemia
Alias_symbol (synonym)AF-6
AF6
Other aliasMLLT4 (myeloid/lymphoid or mixed-lineage leukemia; translocated to, 4)
AF6 (ALL1 fused gene from chromosome 6)
l-afadin
HGNC (Hugo) AFDN
LocusID (NCBI) 4301
Atlas_Id 6
Location 6q27  [Link to chromosome band 6q27]
Location_base_pair Starts at 167827635 and ends at 167972020 bp from pter ( according to hg19-Feb_2009)  [Mapping AFDN.png]
 
  Figure 1 Localization of AFDN (also called AF6 or MLLT4) - Courtesy Mariano Rocchi.
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)
BCL6 (3q27.3) / AFDN (6q27)KMT2A (11q23.3) / AFDN (6q27)MBTPS2 (Xp22.12) / AFDN (6q27)
AFDN (6q27) / EXOC6B (2p13.2)AFDN (6q27) / KCNAB1 (3q25.31)AFDN (6q27) / KMT2A (11q23.3)
AFDN (6q27) / AFDN (6q27)AFDN (6q27) / SASH1 (6q24.3)AFDN (6q27) / TMEM151B (6p21.1)
AFDN (6q27) / UNC93A (6q27)PLA2G2A (1p36.13) / AFDN (6q27)SASH1 (6q24.3) / AFDN (6q27)

DNA/RNA

Description The AFDN gene, located on 6q27, has a genomic size of 145,030 bases and encodes for several transcripts on the position chr6:167826991-167972020 in the + strand.
Transcription According to RefSeq, there are 3 transcripts (see below) and an anti-sens (NR_027906)
AFDN at chr6:167826991-167972020 - (NM_001207008) afadin isoform 1: 7,459 bp
AFDN at chr6:167826991-167965113 - (NM_001040000) afadin isoform 2: 7,629 bp
AFDN at chr6:167827635-167972020 - (NM_001291964) afadin isoform 4: 7,750 bp PSEUDOGENE

Protein

 
  Figure 2 Afadin protein
Description The AFDN gene codes for the afadin protein.
From N-term to C-term, afadin possess two Ras-association (RA) domains, a forkhead-associated (FHA) domain, a DIL domain (responsible for actin stress fiber formation (Saito et al., 2015)), a PDZ domain (responsible for binding the cytoplasmic C-terminus of nectins; where TJP1 (ZO-1) also binds (Kuriyama et al., 1996)), three proline-rich (PR) domains, one of which interacts with USP9X (FAM): (aa 1130-1612) (Hock et al., 199; Taya et al., 1998), and an F-actin-binding domain (see Figure 2).
PDZ domain (PDZ): GLGF (glycine-leucine-glycine-phenylalanine): IITVTLKKQNGMGLSIVAAKGAGQDKLGIYVKSVVKGGAADVDGRLAAGDQLLSVDGRSLVGLSQERAAELMTRTSSVVTLEVAKQG (Prasad et al., 1993).
Phosphorylation sites: KERQRLFSQG (aa 1792-1801 according to UniProt). There is an AKT phosphorylation site at Ser1718 in l-Afadin (large variant, see below). Phosphorylation of l-Afadin by AKT at Ser1718 promotes nuclear localization, which enhances migration and perturbs cell to cell adhesion (Ellol et al. 2014).
Afadin has many splice variants, in particular two of them: the larger l-afadin and the smaller s-afadin. s-Afadin lacks the F-actin-binding domain and the third proline-rich domain. These variants are made of 1612 to 1816 amino acids (aa) according to UniProt, or 1655 and 1829 aa according to others (see Figure 2).
l-Afadin links nectins to actin filaments (F-actin). Through its PDZ domain, l-Afadin binds to the nectin conserved motif of four amino acid residues (Glu/Ala-X-Tyr-Val) (except for nectin-4), and F-actin through its F-actin-binding domain. Afadin binds nectins ( NECTIN1, NECTIN2, NECTIN3, NECTIN4), but not nectin-like molecules (Necls: CADM1, CADM2, CADM3, CADM4, PVR) (Review in Ogita and Takai, 2006).
Afadin forms homodimer.
The 3 main isoforms produced by alternative splicing are:
Canonic sequence (Isoform 4, identifier: P55196-4). 1,824 amino acids; 206,804 Da.
s-afadin (Isoform 1, identifier: P55196-2); 1,612 aa; 182,000 Da. Compared to the canonical sequence, are missing aa: 139, 393-407, 1605-1628, 1629-1824.
l-afadin (Isoform 2, identifier: P55196-1); 1,816 aa; 205,605 Da. Compared to the canonical sequence, are missing aa: 139, 393-407, 1048-1048, 1747-1824.
Expression L-afadin is widely expressed in epithelial cells, while s-afadin expression is restricted to the brain (Buchert et al., 2007)
Localisation Afadin is mainly located at the cell junctions named adherens junctions. s-afadin is able to localize both to the plasma membrane or to the nucleus while l-afadin was said to be unable to localize to the nucleus (Buchert et al., 2007).
 
  Figure 3 Nectin/Afadin: nectin activations.
Function Epithelial cells contain three types of cell-cell junction: tight junctions, localized in the apex of the cells, adherens junctions (AJs), and desmosomes.
Adherens junctions: two types of cell adhesion molecules (CAMs), cadherins and nectins, interact with actin filaments (F-actin). They interact through their cytoplasmic domain to form adherens junctions.
Cadherins and nectins: In epithelial cells, β-catenin ( CTNNB1) directly binds to cadherins and links it to the actin cytoskeleton through &alpha-catenin (CTNNA1, CTNNA2, CTNNA3), while nectins are linked to the actin cytoskeleton through afadin (Tachibana et al., 2000; Ogita and Takai, 2006) (see Figure 4).
Nectins first activate SRC. Activated SRC then activates/phosphorylates FARP2, and VAV2. SRC also activates RABGEF1 (also known as Rap1) through CRK and RAPGEF1 (C3G).
Activated RABGEF1 (Rap1) also activates FARP2, which activates CDC42 40012. Activated CDC42 induces the activation of VAV2, followed by the activation of RAC1 (RAC) (see Figure 3).
Activated RABGEF1 (Rap1) is essential for down-regulation of Rho signaling and actin stress fiber dissolution (Birukova et al., 2013).
Some of the downstream effectors for VAV2 and RAC1 are actin filaments (F-actin)-binding proteins.
Nectins associate with cadherins through the interaction of afadin with &alpha-catenin and: a ponsin ( SORBS1) - vinculin (VCL) unit, an SSX2IP (ADIP) - a-actinin ( ACTN1, ACTN2 and ACTN3) unit, and a LMO7 - a-actinin unit (see Figure 4). RABGEF1 (Rap1) activates afadin to interacts with CTNND1 (p120 catenin) and strengthens its binding to E-cadherin ( CDH1), which results in reduced E-cadherin endocytosis (Bégay-Müller et al., 2002; Kooistra et al. 2007; Sakisaka et al., 2007 ; Birukova et al., 2013; Takeichi 2014)
Tight junctions/role of ZO-1 Afadin also associates transiently with tight junction protein TJP1 (ZO-1). ZO-1 is a member of F-actin-binding ZO proteins, which bind CAMs of tight junctions (TJs) such as claudins, occludin ( OCLN), and junctional adhesion molecules (JAMs) and link them to the actin cytoskeleton (Sakisaka et al., 2007) (see Figure 4). Occludin, EPHA2, a transmembrane tyrosine kinase receptor, and afadin also cooperate in tight junction organization (Perez White et al., 2017). Afadin is therefore a peripheral component of tight junctions in epithelial cells. The binding of claudins to tight junction proteins (or zonula occludens ZOs) and afadin and other proteins constitutes a step in cellular signal transduction (Zhang et al., 2018).
Apico-basal polarization/role of Par-3: PARD3 (Par-3), Par-6 and atypical protein kinase C (PRKCI) are required for apico-basal polarization of epithelial cells. Nectin-1 and nectin-3, but not nectin-2, bind the PDZ domain of Par-3 (Rakotomamonjy et al., 2017)
1- Par-3 regulates association of afadin with trans-interacting nectin and the formation of AJs;
2- Par-3 regulates E-cadherin-induced activation of Rac and formation of AJs;
3- Par-3 and afadin cooperatively regulate nectin-induced formation of TJs (Sakisaka et al 2007)
Migration Afadin is localized at cell-cell contact sites in mesangial cells. Afadin forms a complex with CTNNB1 (β-catenin) in cultured mesangial cells and Afadin regulates migratory polarity (Tsurumi et al., 2016). Afadin is required for the maintenance of the radial glial scaffold for neuronal migration during cortical development (Yamamoto et al., 2015b).
Mitotic spindle orientation Afadin is required for mitotic spindle orientation and correct epithelial morphogenesis (Carminati et al., 2016). Afadin orients the mitotic spindle and is required for lumen continuity in developing renal tubules by orienting the mitotic spindle during cell division (Gao et al., 2017). Afadin controls cell polarization and mitotic spindle orientation in developing cortical radial glia (Rakotomamonjy et al., 2017).
Actin polymerization/profilin profilin plays an important role in actin polymerization. Profilin 1 and Profilin 2 (PFN1 and PFN2) are afadin-binding protein (Boettner B et al., 2000)
MAPK cascade Afadin interacts with HRAS, KRAS, and NRAS GTPases and the Ras-related RAP1A leading to MAPK activation (Yamamoto et al., 1997). MRAS, whose GTP/GDP cycle is sensitive to the Ras GEFs, SOS1 42355, and RASGRF1 43453 (GRF1) and to RASA1 (p120 RASGAP) interacts with Afadin (Quilliam et al. 1999). RRAS, RRAS2 also interact with Afadin (Linnemann et al., 1999). Afadin also acts downstream of EGFR-Ras and provides a link from EGFR to cytoskeletal elements in the cell motility process (Gaengel and Mlodzik 2003).
Ubiquitination Afadin is a substrate of the USP9X deubiquitinating enzyme. USP9X can release ubiquitin from Afadin (Taya et al., 1998).
Ephrin receptors Eph receptor tyrosine kinases are membrane-bound proteins implicated in cell migration and intercellular communication during embryonic development, regulating cell pattern formation during organogenesis. EPHA7, EPHB2, EPHB3, and EPHB6 interact with Afadin. Afadin is phosphorylated specifically by EPHB3 and EPHB2 (Hock et al., 1998)
 
  Figure 4 Afadin in adherens junctions ( AJ) and tight junctions ( TJ)
Homology Homologs of the AFDN gene: The AFDN gene is conserved in chimpanzee, Rhesus monkey, dog, cow, mouse, rat, chicken, zebrafish, C.elegans, and frog (Orthologs from Annotation Pipeline: 201 organisms have orthologs with human gene AFDN).

Implicated in

Note AFDN is implicated in a few translocations and/or fusion genes, in particular in the t(6;11) seen in leukemia (see Figure 5).
Down regulation of afadin appears to drive to carcinogenesis in a number of cancer types.
  
Entity t(6;11)(q27;q23)/AML --> KMT2A/AFDN
Disease Acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) of children and adults. Translocation t(6;11) represent about 5% of acute leukemia with 11q23/KMT2A rearrangement and is more frequent in AML than in ALL (Prasad et al., 1993; review in Huret 2018).
Prognosis The prognosis is poor.
Cytogenetics may be overlooked; The t(6;11) is the sole abnormality in most cases, but may be accompanied with, +8, +19 and+21.
Hybrid/Mutated Gene 5' KMT2A- 3' AFDN
Abnormal Protein NH2-term KMT2A (with the AT hook and DNA binding motifs) is fused to most of AFDN. KMT2A/AFDN, through constitutive self-association and in cooperation with the histone-methyltransferase DOT1L, activates aberrant gene expression (Deshpande et al., 2013). KMT2A/AFDN directly upregulates BHLHE41 (SHARP1) by DOT1L. SHARP1 binds to transcriptionally active chromatin. Suppression of SHARP1 induces robust apoptosis. The circadian clock transcription factor SHARP1 as an oncogenic target in KMT2A/AFDN cells (Numata et al., 2018). AFDN is expressed in the cytoplasm of normal cells and controls RAS levels. By contrast, in KMT2A/AFDN localize in the nucleus, leading to aberrant activation of RAS and of its downstream targets (Joh et al. 1997).
  
  
Entity Breast carcinoma
Note In breast cancer, loss of afadin protein expression induces cell migration and cell invasion (Yamamoto et al., 2015a), and is associated with adverse prognosis (Letessier et al., 2007; Fournier et al., 2011). Afadin loss of expression (in 15% of breast carcinoma) is also associated with an increased risk of metastatic relapse (Fournier et al., 2011).
The nuclear localization of L-Afadin, regulated by phosphorylation at Ser1718 by the Akt pathway, is clinically relevant for breast cancer progression (Ellol et al. 2014).
The fusion gene AFDN/ KCNAB1 has been found in breast adenocarcinoma (Yoshihara et al., 2015).
The fusion gene AFDN/ HMGCLL1 has also been found in breast adenocarcinoma (Hu et al. 2018).
  
  
Entity Uterus cancer
Note Afadin expression was significantly associated with myometrial invasion and high histological grade in uterine corpus endometrial carcinoma (Yamamoto et al., 2015a).
The fusion gene ATG5/AFDN has been found in uterine carcinosarcoma (Hu et al. 2018).
  
  
Entity Ovarian serous cystadenocarcinoma
Note The fusion gene AFDN/ UNC93A has been found in ovarian serous cystadenocarcinoma (Yoshihara et al., 2015).
  
  
Entity Prostate adenocarcinoma
Note The fusion gene AFDN/ EXOC6B has been found in prostate adenocarcinoma (Yoshihara et al., 2015).
The fusion gene AFDN/ SYK has also been found in prostate adenocarcinoma (Hu et al. 2018).
  
  
Entity Clear cell renal cell carcinoma
Note The fusion gene AFDN/ TTLL2 has been found in clear cell renal cell carcinoma (Hu et al. 2018).
  
  
Entity Colon cancer
Note Lower expression of CFTR and/or afadin is correlated with a poor prognosis in colon cancer (Sun et al., 2014). Loss of afadin induces cell migration and cell invasion (Yamamoto et al., 2015a).
  
  
Entity Pancreatic cancer.
Note Afadin is expressed at low levels in pancreatic cancer. Depletion of Afadin promotes proliferation through upregulation of the expression of SNAIL proteins, and this requires the nuclear localization of afadin (Xu et al., 2015).
  
  
Entity Gastric cancer
Note Helicobacter pylori disrupts cell-cell junctions through down regulation of afadin and induces epithelial to mesenchymal transition (EMT) of gastric cells, leading to the acquisition of an aggressive phenotype, which can contribute to gastric carcinogenesis (Marques et al., 2018).
AFDN antisense RNA 1 ( AFDN-AS1) is significantly downregulated in gastric cancer and a predictor of a poor prognosis (Lai et al., 2017).
Prognosis
  
  
Entity Low grade glioma
Note The fusion gene AFDN/ SASH1 has been found in low grade glioma (Yoshihara et al., 2015).
  
  
Entity osteosarcoma
Note High expression of CLDN2 (claudin2) induces high expression of afadin, which results in silencing of the MAPK signaling pathway and inhibits the metastasis phenotype in osteosarcoma cells (Zhang et al., 2018).
  
  
Entity Lung squamous cell carcinoma
Note The fusion gene AFDN/ GMDS has been found in squamous cell carcinoma of the lung (Hu et al. 2018).
  
  
Entity Neurone synapse and nucleus
Note Afadin signaling at synapses contributes to activity-dependent spine morphogenic activity. Following stimulation by 17β-estradiol, afadin locates to both synapses and the nucleus. Accumulation of afadin in the nucleus induces phosphorylation of kinases MAPK3 / MAPK1 (pERK1/2), phosphorylation of RPS6KA1 (p90RSK) that can directly phosphorylate histone H3 at serine 10 (H3S10p.). This in turn contributes to long term alterations in synapse structure (VanLeeuwen et al., 2014; Sellers et al., 2018).
  

Breakpoints

 
  Figure 5 ADFN fusion partners.

To be noted

TARGET THERAPY
Targeting the DVL2 - FOXE1 -Snail signalling axis may thus represent a promising therapeutic strategy (Xu et al., 2015)
Exposure of KMT2A/AFDN -rearranged AML blasts to tipifarnib, a RAS inhibitor, leads to cell autophagy and apoptosis, thus supporting RAS targeting as a novel potential therapy (Manara et al. 2014).

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PMID 9722616
 
Afadin is localized at cell-cell contact sites in mesangial cells and regulates migratory polarity
Tsurumi H, Kurihara H, Miura K, Tanego A, Ohta Y, Igarashi T, Oka A, Horita S, Hattori M, Harita Y
Lab Invest 2016 Jan;96(1):49-59
PMID 26568295
 
Coordinated nuclear and synaptic shuttling of afadin promotes spine plasticity and histone modifications
VanLeeuwen JE, Rafalovich I, Sellers K, Jones KA, Griffith TN, Huda R, Miller RJ, Srivastava DP, Penzes P
J Biol Chem 2014 Apr 11;289(15):10831-42
PMID 24567331
 
Loss of polarity protein AF6 promotes pancreatic cancer metastasis by inducing Snail expression
Xu Y, Chang R, Peng Z, Wang Y, Ji W, Guo J, Song L, Dai C, Wei W, Wu Y, Wan X, Shao C, Zhan L
Nat Commun 2015 May 26;6:7184
PMID 26013125
 
Impairment of radial glial scaffold-dependent neuronal migration and formation of double cortex by genetic ablation of afadin
Yamamoto H, Mandai K, Konno D, Maruo T, Matsuzaki F, Takai Y
Brain Res 2015 Sep 16;1620:139-52
PMID 25988834
 
The Ras target AF-6 interacts with ZO-1 and serves as a peripheral component of tight junctions in epithelial cells
Yamamoto T, Harada N, Kano K, Taya S, Canaani E, Matsuura Y, Mizoguchi A, Ide C, Kaibuchi K
J Cell Biol 1997 Nov 3;139(3):785-95
PMID 9348294
 
The landscape and therapeutic relevance of cancer-associated transcript fusions
Yoshihara K, Wang Q, Torres-Garcia W, Zheng S, Vegesna R, Kim H, Verhaak RG
Oncogene 2015 Sep 10;34(37):4845-54
PMID 25500544
 
CLDN2 inhibits the metastasis of osteosarcoma cells via down-regulating the afadin/ERK signaling pathway
Zhang X, Wang H, Li Q, Li T
Cancer Cell Int 2018 Oct 17;18:160
PMID 30349422
 

Citation

This paper should be referenced as such :
Huret JL, Dessen P
AFDN (afadin, adherens junction formation factor);
Atlas Genet Cytogenet Oncol Haematol. in press
On line version : http://AtlasGeneticsOncology.org/Genes/AF6ID6.html
History of this paper:
Huret, JL. MLLT4 (myeloid/lymphoid or mixed-lineage leukemia (trithorax); translocated to, 4). Atlas Genet Cytogenet Oncol Haematol. 1997;1(2):56-57.
http://documents.irevues.inist.fr/bitstream/handle/2042/32049/12-1997-AF6ID6.pdf


Other Leukemias implicated (Data extracted from papers in the Atlas) [ 3 ]
  11q23 rearrangements (KMT2A) in therapy related leukaemias
t(6;11)(q27;q23) KMT2A/AFDN
t(6;11)(q27;q23) AFDN/KMT2A


External links

Nomenclature
HGNC (Hugo)AFDN   7137
Cards
AtlasAF6ID6
Entrez_Gene (NCBI)AFDN  4301  afadin, adherens junction formation factor
AliasesAF6; MLL-AF6; MLLT4; l-afadin
GeneCards (Weizmann)AFDN
Ensembl hg19 (Hinxton)ENSG00000130396 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000130396 [Gene_View]  ENSG00000130396 [Sequence]  chr6:167827635-167972020 [Contig_View]  AFDN [Vega]
ICGC DataPortalENSG00000130396
TCGA cBioPortalAFDN
AceView (NCBI)AFDN
Genatlas (Paris)AFDN
WikiGenes4301
SOURCE (Princeton)AFDN
Genetics Home Reference (NIH)AFDN
Genomic and cartography
GoldenPath hg38 (UCSC)AFDN  -     chr6:167827635-167972020 +  6q27   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)AFDN  -     6q27   [Description]    (hg19-Feb_2009)
EnsemblAFDN - 6q27 [CytoView hg19]  AFDN - 6q27 [CytoView hg38]
Mapping of homologs : NCBIAFDN [Mapview hg19]  AFDN [Mapview hg38]
OMIM159559   
Gene and transcription
Genbank (Entrez)AB209420 AB621809 AF085836 AI271860 AK055689
RefSeq transcript (Entrez)NM_001040000 NM_001040001 NM_001207008 NM_001291964 NM_001366319 NM_001366320 NM_001366321 NM_005936
RefSeq genomic (Entrez)
Consensus coding sequences : CCDS (NCBI)AFDN
Cluster EST : UnigeneHs.741785 [ NCBI ]
CGAP (NCI)Hs.741785
Alternative Splicing GalleryENSG00000130396
Gene ExpressionAFDN [ NCBI-GEO ]   AFDN [ EBI - ARRAY_EXPRESS ]   AFDN [ SEEK ]   AFDN [ MEM ]
Gene Expression Viewer (FireBrowse)AFDN [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevestigatorExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)4301
GTEX Portal (Tissue expression)AFDN
Human Protein AtlasENSG00000130396-AFDN [pathology]   [cell]   [tissue]
Protein : pattern, domain, 3D structure
UniProt/SwissProtP55196   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtP55196  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProP55196
Splice isoforms : SwissVarP55196
PhosPhoSitePlusP55196
Domaine pattern : Prosite (Expaxy)DILUTE (PS51126)    PDZ (PS50106)    RA (PS50200)   
Domains : Interpro (EBI)Afadin    CBD_Afadin    Dilute_dom    FHA_dom    PDZ    PDZ_sf    RA_dom    SMAD_FHA_dom_sf    Ubiquitin-like_domsf   
Domain families : Pfam (Sanger)DIL (PF01843)    FHA (PF00498)    PDZ (PF00595)    RA (PF00788)   
Domain families : Pfam (NCBI)pfam01843    pfam00498    pfam00595    pfam00788   
Domain families : Smart (EMBL)DIL (SM01132)  FHA (SM00240)  PDZ (SM00228)  RA (SM00314)  
Conserved Domain (NCBI)AFDN
DMDM Disease mutations4301
Blocks (Seattle)AFDN
PDB (RSDB)1T2M    1XZ9    2AIN    2EXG    5A6C   
PDB Europe1T2M    1XZ9    2AIN    2EXG    5A6C   
PDB (PDBSum)1T2M    1XZ9    2AIN    2EXG    5A6C   
PDB (IMB)1T2M    1XZ9    2AIN    2EXG    5A6C   
Structural Biology KnowledgeBase1T2M    1XZ9    2AIN    2EXG    5A6C   
SCOP (Structural Classification of Proteins)1T2M    1XZ9    2AIN    2EXG    5A6C   
CATH (Classification of proteins structures)1T2M    1XZ9    2AIN    2EXG    5A6C   
SuperfamilyP55196
Human Protein Atlas [tissue]ENSG00000130396-AFDN [tissue]
Peptide AtlasP55196
HPRD01164
IPIIPI00398718   IPI00216505   IPI00023461   IPI00759546   IPI01014668   IPI00953593   IPI00479469   IPI00965424   IPI00640210   IPI00643785   IPI00829971   IPI00966597   IPI00966568   IPI00967991   IPI00966289   IPI00967110   
Protein Interaction databases
DIP (DOE-UCLA)P55196
IntAct (EBI)P55196
FunCoupENSG00000130396
BioGRIDAFDN
STRING (EMBL)AFDN
ZODIACAFDN
Ontologies - Pathways
QuickGOP55196
Ontology : AmiGOprotein binding  nucleoplasm  cytosol  cytosol  plasma membrane  cell-cell junction  cell-cell adherens junction  cell adhesion  signal transduction  cell-cell signaling  protein C-terminus binding  nuclear speck  Ras GTPase binding  cell junction  negative regulation of cell migration  regulation of protein localization  adherens junction organization  positive regulation of GTPase activity  cell-cell contact zone  cell-cell adhesion mediated by cadherin  cadherin binding  cell adhesion molecule binding  actin filament binding  establishment of protein localization to plasma membrane  tight junction  bicellular tight junction assembly  establishment of endothelial intestinal barrier  positive regulation of cell-cell adhesion mediated by cadherin  
Ontology : EGO-EBIprotein binding  nucleoplasm  cytosol  cytosol  plasma membrane  cell-cell junction  cell-cell adherens junction  cell adhesion  signal transduction  cell-cell signaling  protein C-terminus binding  nuclear speck  Ras GTPase binding  cell junction  negative regulation of cell migration  regulation of protein localization  adherens junction organization  positive regulation of GTPase activity  cell-cell contact zone  cell-cell adhesion mediated by cadherin  cadherin binding  cell adhesion molecule binding  actin filament binding  establishment of protein localization to plasma membrane  tight junction  bicellular tight junction assembly  establishment of endothelial intestinal barrier  positive regulation of cell-cell adhesion mediated by cadherin  
NDEx NetworkAFDN
Atlas of Cancer Signalling NetworkAFDN
Wikipedia pathwaysAFDN
Orthology - Evolution
OrthoDB4301
GeneTree (enSembl)ENSG00000130396
Phylogenetic Trees/Animal Genes : TreeFamAFDN
HOGENOMP55196
Homologs : HomoloGeneAFDN
Homology/Alignments : Family Browser (UCSC)AFDN
Gene fusions - Rearrangements
Fusion : MitelmanMLLT4/EXOC6B [6q27/2p13.2]  
Fusion : MitelmanMLLT4/KCNAB1 [6q27/3q25.31]  [t(3;6)(q25;q27)]  
Fusion : MitelmanMLLT4/SASH1 [6q27/6q24.3]  [t(6;6)(q24;q27)]  
Fusion : MitelmanSASH1/MLLT4 [6q24.3/6q27]  [t(6;6)(q24;q27)]  
Fusion PortalMLLT4 6q27 EXOC6B 2p13.2 PRAD
Fusion PortalMLLT4 6q27 KCNAB1 3q25.31 BRCA
Fusion PortalMLLT4 6q27 MLL LAML
Fusion PortalMLLT4 6q27 SASH1 6q24.3 LGG
Fusion PortalMLLT4 6q27 UNC93A 6q27 OV
Fusion PortalMLL MLLT4 6q27 LAML
Fusion PortalSASH1 6q24.3 MLLT4 6q27 LGG
Fusion : TICdbKMT2A [11q23.3]  -  MLLT4 [6q27]
Fusion : QuiverAFDN
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerAFDN [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)AFDN
dbVarAFDN
ClinVarAFDN
1000_GenomesAFDN 
Exome Variant ServerAFDN
ExAC (Exome Aggregation Consortium)ENSG00000130396
GNOMAD BrowserENSG00000130396
Varsome BrowserAFDN
Genetic variants : HAPMAP4301
Genomic Variants (DGV)AFDN [DGVbeta]
DECIPHERAFDN [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisAFDN 
Mutations
ICGC Data PortalAFDN 
TCGA Data PortalAFDN 
Broad Tumor PortalAFDN
OASIS PortalAFDN [ Somatic mutations - Copy number]
Cancer Gene: CensusAFDN 
Mutations and Diseases : HGMDAFDN
intOGen PortalMLLT4
BioMutasearch AFDN
DgiDB (Drug Gene Interaction Database)AFDN
DoCM (Curated mutations)AFDN (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)AFDN (select a term)
intoGenAFDN
NCG5 (London)AFDN
Cancer3DAFDN(select the gene name)
Impact of mutations[PolyPhen2] [Provean] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Diseases
OMIM159559   
Orphanet
DisGeNETAFDN
MedgenAFDN
Genetic Testing Registry AFDN
NextProtP55196 [Medical]
TSGene4301
GENETestsAFDN
Target ValidationAFDN
Huge Navigator AFDN [HugePedia]
snp3D : Map Gene to Disease4301
BioCentury BCIQAFDN
ClinGenAFDN
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD4301
Chemical/Pharm GKB GenePA30853
Clinical trialAFDN
Miscellaneous
canSAR (ICR)AFDN (select the gene name)
Probes
Litterature
PubMed107 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMineAFDN
EVEXAFDN
GoPubMedAFDN
iHOPAFDN
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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indexed on : Fri Jan 11 13:21:07 CET 2019

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