Q9H4E7 · DEFI6_HUMAN
- ProteinDifferentially expressed in FDCP 6 homolog
- GeneDEF6
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids631 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Phosphatidylinositol 3,4,5-trisphosphate-dependent guanine nucleotide exchange factor (GEF) which plays a role in the activation of Rho GTPases RAC1, RhoA and CDC42 (PubMed:12651066, PubMed:15023524).
Can regulate cell morphology in cooperation with activated RAC1 (By similarity).
Involved in immune homeostasis by ensuring proper trafficking and availability of T-cell regulator CTLA-4 at T-cell surface (PubMed:31308374).
Plays a role in Th2 (T helper cells) development and/or activation, perhaps by interfering with ZAP70 signaling (By similarity).
Can regulate cell morphology in cooperation with activated RAC1 (By similarity).
Involved in immune homeostasis by ensuring proper trafficking and availability of T-cell regulator CTLA-4 at T-cell surface (PubMed:31308374).
Plays a role in Th2 (T helper cells) development and/or activation, perhaps by interfering with ZAP70 signaling (By similarity).
GO annotations
all annotations | all molecular function | virus receptor activity | dna binding | rna binding | cytoskeletal motor activity | catalytic activity | gtpase activity | structural molecule activity | transporter activity | cytoskeletal protein binding | lipid binding | cyclase activity | antioxidant activity | oxidoreductase activity | transferase activity | hydrolase activity | lyase activity | isomerase activity | ligase activity | protein tag activity | cargo receptor activity | histone binding | protein folding chaperone | translation regulator activity | nutrient reservoir activity | receptor ligand activity | molecular transducer activity | molecular adaptor activity | toxin activity | cell adhesion mediator activity | molecular function regulator activity | virus coreceptor activity | catalytic activity, acting on a protein | catalytic activity, acting on dna | catalytic activity, acting on rna | molecular carrier activity | transcription regulator activity | general transcription initiation factor activity | molecular sensor activity | molecular sequestering activity | atp-dependent activity | other molecular function | all biological process | mitotic cell cycle | cytokinesis | cytoplasmic translation | immune system process | muscle system process | circulatory system process | renal system process | respiratory system process | carbohydrate metabolic process | generation of precursor metabolites and energy | dna replication | dna repair | dna recombination | chromatin organization | dna-templated transcription | regulation of dna-templated transcription | trna metabolic process | protein folding | protein glycosylation | amino acid metabolic process | modified amino acid metabolic process | lipid metabolic process | vitamin metabolic process | sulfur compound metabolic process | intracellular protein transport | nucleocytoplasmic transport | autophagy | inflammatory response | mitochondrion organization | cytoskeleton organization | microtubule-based movement | peroxisome organization | lysosome organization | chromosome segregation | cell adhesion | establishment or maintenance of cell polarity | programmed cell death | photosynthesis | mrna metabolic process | snrna metabolic process | vesicle-mediated transport | reproductive process | digestive system process | signaling | cell differentiation | protein catabolic process | extracellular matrix organization | regulatory ncrna-mediated gene silencing | telomere organization | cell junction organization | wound healing | ribosome biogenesis | cilium organization | anatomical structure development | cell motility | nervous system process | endocrine process | protein maturation | transmembrane transport | nucleobase-containing small molecule metabolic process | hepaticobiliary system process | membrane organization | protein-containing complex assembly | cell wall organization or biogenesis | nitrogen cycle metabolic process | protein localization to plasma membrane | defense response to other organism | detoxification | meiotic nuclear division | mitotic nuclear division | mitochondrial gene expression | carbohydrate derivative metabolic process | other biological process | all cellular component | nuclear chromosome | extracellular region | extracellular space | cell wall | nucleus | nuclear envelope | nucleoplasm | chromosome | nucleolus | mitochondrion | lysosome | endosome | vacuole | peroxisome | endoplasmic reticulum | golgi apparatus | lipid droplet | microtubule organizing center | cytosol | ribosome | cytoskeleton | plasma membrane | cilium | plastid | thylakoid | external encapsulating structure | extracellular matrix | cytoplasmic vesicle | organelle | other cellular component | |||
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Aspect | Term | |
---|---|---|
Cellular Component | cytoplasm | |
Cellular Component | cytoskeleton | |
Cellular Component | cytosol | |
Cellular Component | filopodium | |
Cellular Component | membrane | |
Cellular Component | nucleoplasm | |
Cellular Component | nucleus | |
Cellular Component | perinuclear region of cytoplasm | |
Cellular Component | plasma membrane | |
Molecular Function | guanyl-nucleotide exchange factor activity | |
Biological Process | regulation of small GTPase mediated signal transduction | |
Biological Process | vesicle-mediated transport to the plasma membrane |
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameDifferentially expressed in FDCP 6 homolog
- Short namesDEF-6
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionQ9H4E7
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Keywords
- Cellular component
Disease & Variants
Involvement in disease
Immunodeficiency 87 and autoimmunity (IMD87)
- Note
- DescriptionAn autosomal recessive disorder with onset in infancy or early childhood. It is characterized by increased susceptibility to infections, often Epstein-Barr virus, as well as lymphadenopathy or autoimmune manifestations, predominantly hemolytic anemia. The disorder results primarily from defects in T-cell function.
- See alsoMIM:619573
Natural variants in IMD87
Variant ID | Position(s) | Change | Description | |
---|---|---|---|---|
VAR_086410 | 210 | Y>D | in IMD87; affects function in vesicle-mediated protein transport as shown by impaired CTLA4 trafficking to cell surface in homozygous patient T cells; severely decreased protein levels in patient T cells; increased protein degradation; dbSNP:rs2150387447 | |
VAR_086411 | 314-631 | missing | in IMD87; protein not detected in homozygous patient T cells or when the mutant is expressed in a heterologous system | |
VAR_086412 | 331 | E>K | in IMD87; affects function in vesicle-mediated protein transport as shown by impaired CTLA4 trafficking to cell surface in homozygous patient T cells; decreased interaction with RAB11A; dbSNP:rs541285645 |
Features
Showing features for mutagenesis, natural variant.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 18 | Abolishes interaction with RAC1. | ||||
Sequence: L → N | ||||||
Mutagenesis | 31-33 | Abolishes interaction with RAC1. | ||||
Sequence: LKV → NKS | ||||||
Natural variant | VAR_086410 | 210 | in IMD87; affects function in vesicle-mediated protein transport as shown by impaired CTLA4 trafficking to cell surface in homozygous patient T cells; severely decreased protein levels in patient T cells; increased protein degradation; dbSNP:rs2150387447 | |||
Sequence: Y → D | ||||||
Mutagenesis | 210 | Loss of phosphorylation by LCK and abolition of PtdInsP3 binding. | ||||
Sequence: Y → F | ||||||
Mutagenesis | 225-226 | Abolishes PtdInsP3 binding. | ||||
Sequence: KR → AA | ||||||
Mutagenesis | 230-231 | Abolishes PtdInsP3 binding. | ||||
Sequence: RR → AA | ||||||
Mutagenesis | 236 | Abolishes PtdInsP3 binding. | ||||
Sequence: R → C | ||||||
Natural variant | VAR_033193 | 287 | in dbSNP:rs2395617 | |||
Sequence: N → T | ||||||
Natural variant | VAR_086411 | 314-631 | in IMD87; protein not detected in homozygous patient T cells or when the mutant is expressed in a heterologous system | |||
Sequence: Missing | ||||||
Natural variant | VAR_086412 | 331 | in IMD87; affects function in vesicle-mediated protein transport as shown by impaired CTLA4 trafficking to cell surface in homozygous patient T cells; decreased interaction with RAB11A; dbSNP:rs541285645 | |||
Sequence: E → K | ||||||
Natural variant | VAR_033194 | 578 | in dbSNP:rs9296146 | |||
Sequence: R → H |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 556 variants from UniProt as well as other sources including ClinVar and dbSNP.
Keywords
- Disease
Organism-specific databases
Miscellaneous
Genetic variation databases
PTM/Processing
Features
Showing features for chain, modified residue, modified residue (large scale data).
Type | ID | Position(s) | Source | Description | |||
---|---|---|---|---|---|---|---|
Chain | PRO_0000294522 | 1-631 | UniProt | Differentially expressed in FDCP 6 homolog | |||
Sequence: MALRKELLKSIWYAFTALDVEKSGKVSKSQLKVLSHNLYTVLHIPHDPVALEEHFRDDDDGPVSSQGYMPYLNKYILDKVEEGAFVKEHFDELCWTLTAKKNYRADSNGNSMLSNQDAFRLWCLFNFLSEDKYPLIMVPDEVEYLLKKVLSSMSLEVSLGELEELLAQEAQVAQTTGGLSVWQFLELFNSGRCLRGVGRDTLSMAIHEVYQELIQDVLKQGYLWKRGHLRRNWAERWFQLQPSCLCYFGSEECKEKRGIIPLDAHCCVEVLPDRDGKRCMFCVKTANRTYEMSASDTRQRQEWTAAIQMAIRLQAEGKTSLHKDLKQKRREQREQRERRRAAKEEELLRLQQLQEEKERKLQELELLQEAQRQAERLLQEEEERRRSQHRELQQALEGQLREAEQARASMQAEMELKEEEAARQRQRIKELEEMQQRLQEALQLEVKARRDEESVRIAQTRLLEEEEEKLKQLMQLKEEQERYIERAQQEKEELQQEMAQQSRSLQQAQQQLEEVRQNRQRADEDVEAAQRKLRQASTNVKHWNVQMNRLMHPIEPGDKRPVTSSSFSGFQPPLLAHRDSSLKRLTRWGSQGNRTPSPNSNEQQKSLNGGDEAPAPASTPQEDKLDPAPEN | |||||||
Modified residue | 210 | UniProt | Phosphotyrosine | ||||
Sequence: Y | |||||||
Modified residue | 225 | UniProt | N6-acetyllysine | ||||
Sequence: K | |||||||
Modified residue (large scale data) | 387 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 580 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 581 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 590 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 590 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 595 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue (large scale data) | 597 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 600 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 606 | PRIDE | Phosphoserine | ||||
Sequence: S |
Post-translational modification
Tyrosine-phosphorylated by tyrosine-protein kinase LCK in response to T-cell activation.
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
Broadly expressed in the immune system. Highly expressed in T cells (PubMed:31308374).
Gene expression databases
Organism-specific databases
Interaction
Subunit
Interacts with ZAP70 (By similarity).
Interacts with IRF4, activated RAC1 and F-actin. Both the phosphorylated and non-phosphorylated forms bind phosphatidylinositol 3,4,5-trisphosphate (PtdInsP3). Interacts with RAB11A (PubMed:31308374).
Interacts with IRF4, activated RAC1 and F-actin. Both the phosphorylated and non-phosphorylated forms bind phosphatidylinositol 3,4,5-trisphosphate (PtdInsP3). Interacts with RAB11A (PubMed:31308374).
Binary interactions
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for domain, region, compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Domain | 216-312 | PH | ||||
Sequence: DVLKQGYLWKRGHLRRNWAERWFQLQPSCLCYFGSEECKEKRGIIPLDAHCCVEVLPDRDGKRCMFCVKTANRTYEMSASDTRQRQEWTAAIQMAIR | ||||||
Region | 318-341 | Disordered | ||||
Sequence: KTSLHKDLKQKRREQREQRERRRA | ||||||
Region | 397-417 | Disordered | ||||
Sequence: EGQLREAEQARASMQAEMELK | ||||||
Region | 494-631 | Disordered | ||||
Sequence: LQQEMAQQSRSLQQAQQQLEEVRQNRQRADEDVEAAQRKLRQASTNVKHWNVQMNRLMHPIEPGDKRPVTSSSFSGFQPPLLAHRDSSLKRLTRWGSQGNRTPSPNSNEQQKSLNGGDEAPAPASTPQEDKLDPAPEN | ||||||
Compositional bias | 498-515 | Polar residues | ||||
Sequence: MAQQSRSLQQAQQQLEEV | ||||||
Compositional bias | 516-531 | Basic and acidic residues | ||||
Sequence: RQNRQRADEDVEAAQR | ||||||
Compositional bias | 585-608 | Polar residues | ||||
Sequence: LTRWGSQGNRTPSPNSNEQQKSLN |
Domain
The PH domain is essential for phosphatidylinositol 3,4,5-trisphosphate binding.
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length631
- Mass (Da)73,910
- Last updated2001-03-01 v1
- Checksum466A9A3D6D5CB8D8
Computationally mapped potential isoform sequences
There are 3 potential isoforms mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
H0Y7V7 | H0Y7V7_HUMAN | DEF6 | 594 | ||
A0A8V8TNX4 | A0A8V8TNX4_HUMAN | DEF6 | 141 | ||
A0A8V8TMY0 | A0A8V8TMY0_HUMAN | DEF6 | 146 |
Features
Showing features for compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Compositional bias | 498-515 | Polar residues | ||||
Sequence: MAQQSRSLQQAQQQLEEV | ||||||
Compositional bias | 516-531 | Basic and acidic residues | ||||
Sequence: RQNRQRADEDVEAAQR | ||||||
Compositional bias | 585-608 | Polar residues | ||||
Sequence: LTRWGSQGNRTPSPNSNEQQKSLN |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AY241694 EMBL· GenBank· DDBJ | AAO91767.1 EMBL· GenBank· DDBJ | mRNA | ||
AJ276095 EMBL· GenBank· DDBJ | CAC08450.1 EMBL· GenBank· DDBJ | mRNA | ||
Z97832 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. |