Kindlin-3 is a 667 amino acid protein that localizes to both the cell membrane and the cytoplasm and contains one PH domain and one FERM domain. Expressed at high levels in lymph node tissue and at lower levels in spleen, thymus, stomach, placenta, lung, testis and small intestine, Kindlin-3 is thought to be involved in cell adhesion events and may play a role in apoptosis. Kindlin-3 is overexpressed in B-cell malignancies, suggesting that, via its ability to affect cell adhesion, Kindlin-3 may participate in tumor transformation and metastasis. Two isforms of Kindlin-3, designated short and long, exist due to alternative splicing events.
Function:
Plays a central role in cell adhesion in hematopoietic cells. Acts by activating the integrin beta-1-3 (ITGB1, ITGB2 and ITGB3). Required for integrin-mediated platelet adhesion and leukocyte adhesion to endothelial cells. Required for activation of integrin beta-2 (ITGB2) in polymorphonuclear granulocytes (PMNs).
Isoform 2 may act as a repressor of NF-kappa-B and apoptosis.
Subcellular Location:
Cell projection; podosome. Present in the F-actin surrounding ring structure of podosomes, which are specialized adhesion structures of hematopoietic cells.
Tissue Specificity:
Highly expressed in lymph node. Expressed in thymus, spleen and leukocytes. Weakly expressed in placenta, small intestine, stomach, testis and lung. Overexpressed in B-cell malignancies.
DISEASE:
Defects in FERMT3 are the cause of leukocyte adhesion deficiency type 3 (LAD3) [MIM:612168]; also called leukocyte adhesion deficiency 1 variant (LAD1v). LAD3 is a rare syndrome characterized by infections without pus formation in the presence of a leukocytosis combined with a Glanzmann-type bleeding disorder, resulting from a hematopoietic defect in integrin activation. Symptoms arise from an inability to activate the integrins expressed on hematopoietic cells, including platelets and leukocytes.
Similarity:
Belongs to the kindlin family.
Contains 1 FERM domain.
Contains 1 PH domain.
SWISS:
Q86UX7
Gene ID:
83706
Database links:
Entrez Gene: 83706 Human
Entrez Gene: 525159 Cow
Entrez Gene: 108101 Mouse
Entrez Gene: 309186 Rat
Omim: 607901 Human
SwissProt: Q32LP0 Cow
SwissProt: Q86UX7 Human
SwissProt: Q8K1B8 Mouse
|
|
