MDFIC
Domain
The cysteine-rich C-terminus is involved in its granular distribution in the cytoplasm. The cysteine-rich C-terminus mediates protein-protein interactions, including interaction with HIV-1 Tat, transcription factors, AXIN1, CCNT1 (PubMed:12192039, PubMed:12944466, PubMed:16260749).
Function
Required to control the activity of various transcription factors through their sequestration in the cytoplasm. Retains nuclear Zic proteins ZIC1, ZIC2 and ZIC3 in the cytoplasm and inhibits their transcriptional activation (By similarity). Modulates the expression from both cellular and viral promoters. Down-regulates Tat-dependent transcription of the human immunodeficiency virus type 1 (HIV-1) LTR by interacting with HIV-1 Tat and Rev and impairing their nuclear import, probably by rendering the NLS domains inaccessible to importin-beta (PubMed:12944466, PubMed:16260749, Ref.6). Also stimulates activation of human T-cell leukemia virus type I (HTLV-I) LTR (PubMed:10671520). Binds to the axin complex, resulting in an increase in the level of free beta-catenin (PubMed:12192039). Affects axin regulation of the WNT and JNK signaling pathways (PubMed:12192039). Has a role in the development of lymphatic vessel valves. It is required to promote lymphatic endothelial cell migration, in a process that involves down-regulation of integrin beta 1 activation and control of cell adhesion to the extracellular matrix (By similarity) (PubMed:35235341).
Involvement in disease
Lymphatic malformation 12
LMPHM12
A form of primary lymphedema, a disease characterized by swelling of body parts due to developmental anomalies and functional defects of the lymphatic system. Patients with lymphedema may suffer from recurrent local infections. LMPHM12 is an autosomal recessive, severe form often resulting in fetal or perinatal demise. It is characterized by dysfunction of core collecting lymphatic vessels, including the thoracic duct and cisterna chyli, non-immune hydrops fetalis, chylothorax, pleural effusions, and chylous ascites.
None
The disease is caused by variants affecting the gene represented in this entry.
Sequence Similarities
Belongs to the MDFI family.
Tissue Specificity
Expressed in lymphatic tissues. Detected in the spleen, thymus, peripheral blood leukocytes as well as prostate, uterus and small intestine. Expressed in lymphatic endothelial cells (PubMed:35235341).
Cellular localization
- Isoform 1
- Nucleus
- Nucleolus
- Also shows a granular distribution in the cytoplasm.
- Isoform 2
- Cytoplasm
- Cell membrane
- Single-pass membrane protein
- Secreted
Alternative names
MyoD family inhibitor domain-containing protein, I-mfa domain-containing protein, hIC, MDFIC