Details for: DEF6

Gene ID: 50619

Symbol: DEF6

Ensembl ID: ENSG00000023892

Description: DEF6 guanine nucleotide exchange factor

Associated with

Cells (max top 100)

(Cell Significance Index and respective Thresholds are uniquely calculated using our advanced thresholding algorithms to reveal cell-specific gene markers)

  • Cell Name: polychromatophilic erythroblast (CL0000550)
    Fold Change: 75.7979
    Cell Significance Index: -11.7900
  • Cell Name: mucosal type mast cell (CL0000485)
    Fold Change: 35.7655
    Cell Significance Index: -14.5300
  • Cell Name: embryonic stem cell (CL0002322)
    Fold Change: 34.1548
    Cell Significance Index: -14.0700
  • Cell Name: peripheral blood mononuclear cell (CL2000001)
    Fold Change: 31.3967
    Cell Significance Index: -16.1500
  • Cell Name: hematopoietic oligopotent progenitor cell (CL0002032)
    Fold Change: 25.1140
    Cell Significance Index: -6.3700
  • Cell Name: ciliated cell of the bronchus (CL0002332)
    Fold Change: 15.8472
    Cell Significance Index: -15.1300
  • Cell Name: orthochromatic erythroblast (CL0000552)
    Fold Change: 9.6111
    Cell Significance Index: -11.8500
  • Cell Name: CD8-positive, alpha-beta regulatory T cell (CL0000795)
    Fold Change: 4.3628
    Cell Significance Index: -13.4000
  • Cell Name: hepatic pit cell (CL2000054)
    Fold Change: 4.2219
    Cell Significance Index: 11.3100
  • Cell Name: stromal cell of bone marrow (CL0010001)
    Fold Change: 3.0879
    Cell Significance Index: -12.1900
  • Cell Name: CD4-positive, alpha-beta memory T cell, CD45RO-positive (CL0001204)
    Fold Change: 2.7958
    Cell Significance Index: 82.1100
  • Cell Name: epidermal Langerhans cell (CL0002457)
    Fold Change: 1.5444
    Cell Significance Index: -3.3800
  • Cell Name: intestinal crypt stem cell of small intestine (CL0009017)
    Fold Change: 1.3042
    Cell Significance Index: 27.7800
  • Cell Name: colon goblet cell (CL0009039)
    Fold Change: 1.2915
    Cell Significance Index: 127.7600
  • Cell Name: epithelial cell of small intestine (CL0002254)
    Fold Change: 1.2379
    Cell Significance Index: 201.3400
  • Cell Name: tuft cell of colon (CL0009041)
    Fold Change: 1.0182
    Cell Significance Index: 919.3600
  • Cell Name: early pro-B cell (CL0002046)
    Fold Change: 0.7557
    Cell Significance Index: 48.7600
  • Cell Name: basal epithelial cell of tracheobronchial tree (CL0002329)
    Fold Change: 0.6548
    Cell Significance Index: 18.3000
  • Cell Name: gut absorptive cell (CL0000677)
    Fold Change: 0.5817
    Cell Significance Index: 34.9200
  • Cell Name: neutrophil progenitor cell (CL0000834)
    Fold Change: 0.5099
    Cell Significance Index: 13.6400
  • Cell Name: CD14-positive, CD16-negative classical monocyte (CL0002057)
    Fold Change: 0.4945
    Cell Significance Index: 9.1400
  • Cell Name: tonsil germinal center B cell (CL2000006)
    Fold Change: 0.4682
    Cell Significance Index: 55.2200
  • Cell Name: conjunctival epithelial cell (CL1000432)
    Fold Change: 0.4042
    Cell Significance Index: 5.5200
  • Cell Name: DN3 thymocyte (CL0000807)
    Fold Change: 0.3800
    Cell Significance Index: 3.8100
  • Cell Name: microfold cell of epithelium of small intestine (CL1000353)
    Fold Change: 0.2648
    Cell Significance Index: 18.3100
  • Cell Name: basal cell of prostate epithelium (CL0002341)
    Fold Change: 0.2616
    Cell Significance Index: 7.1200
  • Cell Name: T-helper 22 cell (CL0001042)
    Fold Change: 0.2543
    Cell Significance Index: 0.7800
  • Cell Name: bladder urothelial cell (CL1001428)
    Fold Change: 0.2374
    Cell Significance Index: 12.3300
  • Cell Name: hair follicular keratinocyte (CL2000092)
    Fold Change: 0.2247
    Cell Significance Index: 99.3600
  • Cell Name: basal cell of urothelium (CL1000486)
    Fold Change: 0.1958
    Cell Significance Index: 24.0700
  • Cell Name: intermediate cell of urothelium (CL4030055)
    Fold Change: 0.1807
    Cell Significance Index: 32.5700
  • Cell Name: paneth cell of epithelium of small intestine (CL1000343)
    Fold Change: 0.1385
    Cell Significance Index: 3.0000
  • Cell Name: L2/3-6 intratelencephalic projecting glutamatergic neuron (CL4023040)
    Fold Change: 0.0882
    Cell Significance Index: 17.6900
  • Cell Name: enteroendocrine cell of colon (CL0009042)
    Fold Change: 0.0769
    Cell Significance Index: 14.6400
  • Cell Name: sebum secreting cell (CL0000317)
    Fold Change: 0.0682
    Cell Significance Index: 4.8200
  • Cell Name: enterocyte of epithelium of small intestine (CL1000334)
    Fold Change: 0.0665
    Cell Significance Index: 1.9200
  • Cell Name: acinar cell of salivary gland (CL0002623)
    Fold Change: 0.0641
    Cell Significance Index: 2.9900
  • Cell Name: enteroendocrine cell of small intestine (CL0009006)
    Fold Change: 0.0564
    Cell Significance Index: 1.4100
  • Cell Name: pancreatic acinar cell (CL0002064)
    Fold Change: 0.0529
    Cell Significance Index: 9.0400
  • Cell Name: obsolete caudal ganglionic eminence derived GABAergic cortical interneuron (CL4023070)
    Fold Change: 0.0446
    Cell Significance Index: 16.0000
  • Cell Name: neoplastic cell (CL0001063)
    Fold Change: 0.0353
    Cell Significance Index: 7.0100
  • Cell Name: enterocyte of epithelium of large intestine (CL0002071)
    Fold Change: 0.0320
    Cell Significance Index: 1.4500
  • Cell Name: GABAergic interneuron (CL0011005)
    Fold Change: 0.0319
    Cell Significance Index: 22.0600
  • Cell Name: indirect pathway medium spiny neuron (CL4023029)
    Fold Change: 0.0185
    Cell Significance Index: 0.8200
  • Cell Name: pigmented epithelial cell (CL0000529)
    Fold Change: 0.0052
    Cell Significance Index: 9.7600
  • Cell Name: cell in vitro (CL0001034)
    Fold Change: 0.0038
    Cell Significance Index: 2.0500
  • Cell Name: anterior lens cell (CL0002223)
    Fold Change: -0.0035
    Cell Significance Index: -6.4200
  • Cell Name: lens epithelial cell (CL0002224)
    Fold Change: -0.0050
    Cell Significance Index: -7.7100
  • Cell Name: placental villous trophoblast (CL2000060)
    Fold Change: -0.0071
    Cell Significance Index: -0.1900
  • Cell Name: pro-T cell (CL0000827)
    Fold Change: -0.0090
    Cell Significance Index: -0.2300
  • Cell Name: secondary lens fiber (CL0002225)
    Fold Change: -0.0095
    Cell Significance Index: -12.9700
  • Cell Name: pulmonary alveolar epithelial cell (CL0000322)
    Fold Change: -0.0135
    Cell Significance Index: -10.2100
  • Cell Name: non-pigmented ciliary epithelial cell (CL0002304)
    Fold Change: -0.0157
    Cell Significance Index: -9.9900
  • Cell Name: pancreatic A cell (CL0000171)
    Fold Change: -0.0195
    Cell Significance Index: -14.4400
  • Cell Name: pigmented ciliary epithelial cell (CL0002303)
    Fold Change: -0.0200
    Cell Significance Index: -2.9000
  • Cell Name: kidney loop of Henle cortical thick ascending limb epithelial cell (CL1001109)
    Fold Change: -0.0215
    Cell Significance Index: -15.7700
  • Cell Name: type B pancreatic cell (CL0000169)
    Fold Change: -0.0253
    Cell Significance Index: -14.2500
  • Cell Name: ciliary muscle cell (CL1000443)
    Fold Change: -0.0322
    Cell Significance Index: -14.6300
  • Cell Name: dopaminergic neuron (CL0000700)
    Fold Change: -0.0335
    Cell Significance Index: -9.6300
  • Cell Name: direct pathway medium spiny neuron (CL4023026)
    Fold Change: -0.0386
    Cell Significance Index: -1.4600
  • Cell Name: abnormal cell (CL0001061)
    Fold Change: -0.0411
    Cell Significance Index: -4.2000
  • Cell Name: lactocyte (CL0002325)
    Fold Change: -0.0544
    Cell Significance Index: -7.0300
  • Cell Name: epithelial cell of stomach (CL0002178)
    Fold Change: -0.0611
    Cell Significance Index: -7.1200
  • Cell Name: basal cell of epidermis (CL0002187)
    Fold Change: -0.0632
    Cell Significance Index: -0.9600
  • Cell Name: stromal cell of ovary (CL0002132)
    Fold Change: -0.0684
    Cell Significance Index: -9.4000
  • Cell Name: pancreatic D cell (CL0000173)
    Fold Change: -0.0704
    Cell Significance Index: -14.8300
  • Cell Name: odontoblast (CL0000060)
    Fold Change: -0.0856
    Cell Significance Index: -10.9700
  • Cell Name: luminal adaptive secretory precursor cell of mammary gland (CL4033057)
    Fold Change: -0.0863
    Cell Significance Index: -4.0600
  • Cell Name: CD4-positive, alpha-beta thymocyte (CL0000810)
    Fold Change: -0.0934
    Cell Significance Index: -1.6100
  • Cell Name: transit amplifying cell of colon (CL0009011)
    Fold Change: -0.0952
    Cell Significance Index: -3.0500
  • Cell Name: pancreatic ductal cell (CL0002079)
    Fold Change: -0.1044
    Cell Significance Index: -11.9700
  • Cell Name: smooth muscle cell of sphincter of pupil (CL0002243)
    Fold Change: -0.1116
    Cell Significance Index: -11.6200
  • Cell Name: paneth cell of colon (CL0009009)
    Fold Change: -0.1161
    Cell Significance Index: -1.7400
  • Cell Name: cardiac muscle myoblast (CL0000513)
    Fold Change: -0.1203
    Cell Significance Index: -9.2300
  • Cell Name: fibro/adipogenic progenitor cell (CL0009099)
    Fold Change: -0.1210
    Cell Significance Index: -6.1200
  • Cell Name: progenitor cell of mammary luminal epithelium (CL0009116)
    Fold Change: -0.1307
    Cell Significance Index: -9.7400
  • Cell Name: mature alpha-beta T cell (CL0000791)
    Fold Change: -0.1339
    Cell Significance Index: -0.7300
  • Cell Name: hippocampal granule cell (CL0001033)
    Fold Change: -0.1388
    Cell Significance Index: -9.3300
  • Cell Name: foveolar cell of stomach (CL0002179)
    Fold Change: -0.1419
    Cell Significance Index: -0.9300
  • Cell Name: cortical cell of adrenal gland (CL0002097)
    Fold Change: -0.1439
    Cell Significance Index: -3.8600
  • Cell Name: medial ganglionic eminence derived interneuron (CL4023063)
    Fold Change: -0.1459
    Cell Significance Index: -2.0900
  • Cell Name: retinal progenitor cell (CL0002672)
    Fold Change: -0.1575
    Cell Significance Index: -8.8400
  • Cell Name: eye photoreceptor cell (CL0000287)
    Fold Change: -0.1757
    Cell Significance Index: -11.0800
  • Cell Name: neuron associated cell (CL0000095)
    Fold Change: -0.1760
    Cell Significance Index: -7.2100
  • Cell Name: hematopoietic cell (CL0000988)
    Fold Change: -0.1928
    Cell Significance Index: -2.8200
  • Cell Name: intestinal tuft cell (CL0019032)
    Fold Change: -0.1964
    Cell Significance Index: -12.0400
  • Cell Name: kidney loop of Henle descending limb epithelial cell (CL1001021)
    Fold Change: -0.2045
    Cell Significance Index: -16.2000
  • Cell Name: glycinergic neuron (CL1001509)
    Fold Change: -0.2065
    Cell Significance Index: -10.8400
  • Cell Name: intestinal epithelial cell (CL0002563)
    Fold Change: -0.2241
    Cell Significance Index: -2.3200
  • Cell Name: forebrain neuroblast (CL1000042)
    Fold Change: -0.2283
    Cell Significance Index: -14.0300
  • Cell Name: lung endothelial cell (CL1001567)
    Fold Change: -0.2565
    Cell Significance Index: -13.3600
  • Cell Name: eukaryotic cell (CL0000255)
    Fold Change: -0.2780
    Cell Significance Index: -12.0900
  • Cell Name: L5 extratelencephalic projecting glutamatergic cortical neuron (CL4023041)
    Fold Change: -0.2963
    Cell Significance Index: -10.3800
  • Cell Name: Hofbauer cell (CL3000001)
    Fold Change: -0.3017
    Cell Significance Index: -2.4600
  • Cell Name: lymphoid lineage restricted progenitor cell (CL0000838)
    Fold Change: -0.3022
    Cell Significance Index: -3.8300
  • Cell Name: stratified epithelial cell (CL0000079)
    Fold Change: -0.3253
    Cell Significance Index: -11.9400
  • Cell Name: corticothalamic-projecting glutamatergic cortical neuron (CL4023013)
    Fold Change: -0.3391
    Cell Significance Index: -10.8000
  • Cell Name: corneal epithelial cell (CL0000575)
    Fold Change: -0.3407
    Cell Significance Index: -4.8500
  • Cell Name: small intestine goblet cell (CL1000495)
    Fold Change: -0.3429
    Cell Significance Index: -12.0500
  • Cell Name: L6b glutamatergic cortical neuron (CL4023038)
    Fold Change: -0.3470
    Cell Significance Index: -11.3600

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this specific cell.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Cell ID: Standard Cell Ontology term used for mapping and comparing cells across experiments. Ensures consistency in analyzing cellular functions across tissues.
Fold Change: Represents the ratio of the current Cell Significance Index to the Cell Significance Index Threshold, indicating how much the gene expression has changed compared to a baseline.
Cell Significance Index: Reflects how strongly a gene is expressed in this cell type. Calculated using techniques like effect size estimation and bootstrapping for reliability.

Other Information

**Key Characteristics:** DEF6 is a member of the Dbl family of GEFs, which are characterized by their ability to stimulate the exchange of GDP for GTP in small GTPases. The human DEF6 gene (ENSG00000023892) is highly expressed in various cell types, including polychromatophilic erythroblasts, mucosal-type mast cells, embryonic stem cells, and hematopoietic oligopotent progenitor cells. The protein product of the DEF6 gene, DEFI6_HUMAN, shares high sequence homology with Differentially expressed in FDCP 6 homolog, a protein involved in the regulation of cytoskeletal dynamics. **Pathways and Functions:** DEF6 plays a critical role in regulating the activity of small GTPases, which are key regulators of cellular signaling and structure. The guanine nucleotide exchange factor activity of DEF6 is involved in the activation of Cdc42, Rac1, Rac2, RhoA, RhoB, and RhoC, leading to the regulation of various cellular processes, including: 1. **Cytoskeleton organization:** DEF6 regulates the dynamics of the cytoskeleton, including the formation of filopodia and the organization of the actin cytoskeleton. 2. **Cell migration and invasion:** The activation of Rac1 and RhoA by DEF6 is essential for cell migration and invasion, processes that are critical in the development and progression of various diseases, including cancer. 3. **Cell signaling:** DEF6 regulates the activity of small GTPases, which are involved in the transmission of signals from the cell surface to the nucleus, influencing gene expression and cellular behavior. 4. **Vesicle-mediated transport:** DEF6 is involved in the regulation of vesicle-mediated transport to the plasma membrane, a process that is critical for the secretion of proteins and lipids. **Clinical Significance:** The dysregulation of DEF6 and its downstream signaling pathways has been implicated in various diseases, including: 1. **Cancer:** The aberrant activation of Rac1 and RhoA by DEF6 has been observed in various types of cancer, including breast cancer, lung cancer, and colon cancer. 2. **Neurological disorders:** The dysregulation of DEF6 and its downstream signaling pathways has been implicated in neurological disorders, including Alzheimer's disease and Parkinson's disease. 3. **Immunological disorders:** The dysregulation of DEF6 and its downstream signaling pathways has been implicated in immunological disorders, including autoimmune diseases and inflammatory disorders. In conclusion, DEF6 is a critical regulator of small GTPases, which play essential roles in various cellular processes, including cytoskeleton organization, cell migration and invasion, cell signaling, and vesicle-mediated transport. The dysregulation of DEF6 and its downstream signaling pathways has been implicated in various diseases, highlighting the importance of further research into the mechanisms of DEF6 and its role in human disease.

Genular Protein ID: 2798612504

Symbol: DEFI6_HUMAN

Name: Differentially expressed in FDCP 6 homolog

UniProtKB Accession Codes:

Q9H4E7 Q86VF4

Database IDs:

AGR 1 AlphaFoldDB 1 Antibodypedia 1 Bgee 1 BioGRID 1 BioGRID-ORCS 1 BioMuta 1 CCDS 1 CDD 1 CTD 1 ChiTaRS 1 DMDM 1 DNASU 1 DisGeNET 1 EMBL 3 Ensembl 1 ExpressionAtlas 1 GO 12 Gene3D 1 GeneCards 1 GeneTree 1 GeneWiki 1 GenomeRNAi 1 HGNC 1 HOGENOM 1 HPA 1 InParanoid 1 IntAct 1 InterPro 3 KEGG 1 MANE-Select 1 MIM 3 MalaCards 1 MassIVE 1 MetOSite 1 NCBI Taxonomy 1 OMA 1 OpenTargets 1 OrthoDB 1 PANTHER 2 PRO 1 PROSITE 1 PathwayCommons 1 PaxDb 1 PeptideAtlas 1 Pfam 1 PharmGKB 1 Pharos 1 PhosphoSitePlus 1 PhylomeDB 1 Proteomes 1 ProteomicsDB 1 Pumba 1 RNAct 1 Reactome 4 RefSeq 1 SIGNOR 1 SMART 1 SMR 1 STRING 1 SUPFAM 2 SignaLink 1 TreeFam 1 UCSC 1 VEuPathDB 1 eggNOG 1 iPTMnet 1 jPOST 1 neXtProt 1

Citations:

PubMed ID: 12651066

Title: Molecular cloning of IBP, a SWAP-70 homologous GEF, which is highly expressed in the immune system.

PubMed ID: 12651066

DOI: 10.1016/s0198-8859(03)00024-7

PubMed ID: 15023524

Title: DEF6, a novel PH-DH-like domain protein, is an upstream activator of the Rho GTPases Rac1, Cdc42, and RhoA.

PubMed ID: 15023524

DOI: 10.1016/j.yexcr.2003.12.004

PubMed ID: 14574404

Title: The DNA sequence and analysis of human chromosome 6.

PubMed ID: 14574404

DOI: 10.1038/nature02055

PubMed ID: 12923183

Title: T cell receptor engagement leads to the recruitment of IBP, a novel guanine nucleotide exchange factor, to the immunological synapse.

PubMed ID: 12923183

DOI: 10.1074/jbc.m308960200

PubMed ID: 17121847

Title: Cooperation of DEF6 with activated Rac in regulating cell morphology.

PubMed ID: 17121847

DOI: 10.1074/jbc.m605153200

PubMed ID: 19690332

Title: Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions.

PubMed ID: 19690332

DOI: 10.1126/scisignal.2000007

PubMed ID: 19608861

Title: Lysine acetylation targets protein complexes and co-regulates major cellular functions.

PubMed ID: 19608861

DOI: 10.1126/science.1175371

PubMed ID: 21269460

Title: Initial characterization of the human central proteome.

PubMed ID: 21269460

DOI: 10.1186/1752-0509-5-17

PubMed ID: 23186163

Title: Toward a comprehensive characterization of a human cancer cell phosphoproteome.

PubMed ID: 23186163

DOI: 10.1021/pr300630k

PubMed ID: 25944712

Title: N-terminome analysis of the human mitochondrial proteome.

PubMed ID: 25944712

DOI: 10.1002/pmic.201400617

PubMed ID: 31308374

Title: Human DEF6 deficiency underlies an immunodeficiency syndrome with systemic autoimmunity and aberrant CTLA-4 homeostasis.

PubMed ID: 31308374

DOI: 10.1038/s41467-019-10812-x

PubMed ID: 31578334

Title:

PubMed ID: 31578334

DOI: 10.1038/s41467-019-12454-5

PubMed ID: 32562707

Title: DEF6 deficiency, a mendelian susceptibility to EBV infection, lymphoma, and autoimmunity.

PubMed ID: 32562707

DOI: 10.1016/j.jaci.2020.05.052

Sequence Information:

  • Length: 631
  • Mass: 73910
  • Checksum: 466A9A3D6D5CB8D8
  • Sequence:
    • MALRKELLKS IWYAFTALDV EKSGKVSKSQ LKVLSHNLYT VLHIPHDPVA LEEHFRDDDD 
GPVSSQGYMP YLNKYILDKV EEGAFVKEHF DELCWTLTAK KNYRADSNGN SMLSNQDAFR 
LWCLFNFLSE DKYPLIMVPD EVEYLLKKVL SSMSLEVSLG ELEELLAQEA QVAQTTGGLS 
VWQFLELFNS GRCLRGVGRD TLSMAIHEVY QELIQDVLKQ GYLWKRGHLR RNWAERWFQL 
QPSCLCYFGS EECKEKRGII PLDAHCCVEV LPDRDGKRCM FCVKTANRTY EMSASDTRQR 
QEWTAAIQMA IRLQAEGKTS LHKDLKQKRR EQREQRERRR AAKEEELLRL QQLQEEKERK 
LQELELLQEA QRQAERLLQE EEERRRSQHR ELQQALEGQL REAEQARASM QAEMELKEEE 
AARQRQRIKE LEEMQQRLQE ALQLEVKARR DEESVRIAQT RLLEEEEEKL KQLMQLKEEQ 
ERYIERAQQE KEELQQEMAQ QSRSLQQAQQ QLEEVRQNRQ RADEDVEAAQ RKLRQASTNV 
KHWNVQMNRL MHPIEPGDKR PVTSSSFSGF QPPLLAHRDS SLKRLTRWGS QGNRTPSPNS 
NEQQKSLNGG DEAPAPASTP QEDKLDPAPE N

Database document:

This is a preview of the gene's schema. Only a few entries are kept for 'singleCellExpressions,' 'mRNAExpressions,' and other large data arrays for visualization purposes. You can zoom in with the mouse wheel for a closer view, and the text will adjust automatically if necessary. For the full schema, download it here.