MADD
Developmental stage
Expressed in fetal brain and kidney.
Isoform 7
Expressed in fetal liver.
Function
Guanyl-nucleotide exchange factor that regulates small GTPases of the Rab family (PubMed:18559336, PubMed:20937701). Converts GDP-bound inactive form of RAB27A and RAB27B to the GTP-bound active forms (PubMed:18559336, PubMed:20937701). Converts GDP-bound inactive form of RAB3A, RAB3C and RAB3D to the GTP-bound active forms, GTPases involved in synaptic vesicle exocytosis and vesicle secretion (By similarity). Plays a role in synaptic vesicle formation and in vesicle trafficking at the neuromuscular junction (By similarity). Involved in up-regulating a post-docking step of synaptic exocytosis in central synapses (By similarity). Probably by binding to the motor proteins KIF1B and KIF1A, mediates motor-dependent transport of GTP-RAB3A-positive vesicles to the presynaptic nerve terminals (By similarity). Plays a role in TNFA-mediated activation of the MAPK pathway, including ERK1/2 (PubMed:32761064). May link TNFRSF1A with MAP kinase activation (PubMed:9115275). May be involved in the regulation of TNFA-induced apoptosis (PubMed:11577081, PubMed:32761064).
Involvement in disease
DEEAH syndrome
DEEAH
An autosomal recessive disorder characterized by moderate to severe global developmental delay, impaired intellectual development, poor or absent speech, and endocrine, pancreatic exocrine and autonomic dysfunction, as well as hematologic abnormalities. Additional features include facial dysmorphism, seizures, undescended testes, and distal skeletal anomalies. Death in early childhood may occur.
None
The disease is caused by variants affecting the gene represented in this entry.
Neurodevelopmental disorder with dysmorphic facies, impaired speech, and hypotonia
NEDDISH
An autosomal recessive disorder characterized by global developmental delay, mildly to severely impaired intellectual development, poor speech and language acquisition. Some patients may have early normal development with onset of the disorder in the first years of life. More variable neurologic abnormalities include hypotonia, seizures, apnea, mild signs of autonomic or peripheral neuropathy, and autism.
None
The disease is caused by variants affecting the gene represented in this entry.
Sequence Similarities
Belongs to the MADD family.
Tissue Specificity
Expressed in testis, ovary, brain and heart (PubMed:8988362). Expressed in spleen, thymus, prostate, testis, ovary, small instestine and colon (PubMed:9115275). Expressed in liver (PubMed:9796103).
Isoform 1
Not detected in the brain, breast, kidney, lung, ovary, pancreas, testis, uterus, stomach and thyroid.
Isoform 2
Expressed in the brain, breast, kidney, lung, ovary, pancreas, testis, uterus, stomach and thyroid.
Isoform 3
Expressed in the brain, breast, kidney, lung, ovary, pancreas, testis, uterus, stomach and thyroid.
Isoform 4
Expressed in the brain, breast, kidney, lung, ovary, pancreas, testis, uterus, stomach and thyroid.
Isoform 5
Expressed in the brain, breast, kidney, lung, ovary, pancreas, testis, uterus, stomach and thyroid.
Isoform 6
Not detected in the brain, breast, kidney, lung, ovary, pancreas, testis, uterus, stomach and thyroid.
Isoform 7
Not detected in the brain, breast, kidney, lung, ovary, pancreas, testis, uterus, stomach and thyroid.
Cellular localization
- Cell membrane
- Cytoplasm
- Cell projection
- Axon
Alternative names
DENN, IG20, KIAA0358, MADD, MAP kinase-activating death domain protein, Differentially expressed in normal and neoplastic cells, Insulinoma glucagonoma clone 20, Rab3 GDP/GTP exchange factor, Rab3 GDP/GTP exchange protein, RabGEF, Rab3GEP