CDD Conserved Protein Domain Family: FERM_C

cd13205: FERM_C_fermitin

FERM domain C-lobe of the Fermitin family

Fermitin functions as a mediator of integrin inside-out signalling. The recruitment of Fermitin proteins and Talin to the membrane mediates the terminal event of integrin signalling, via interaction with integrin beta subunits. Fermatin has FERM domain interrupted with a pleckstrin homology (PH) domain. Fermitin family homologs (Fermt1, 2, and 3, also known as Kindlins) are each encoded by a different gene. In mammalian studies, Fermt1 is generally expressed in epithelial cells, Fermt2 is expressed inmuscle tissues, and Fermt3 is expressed in hematopoietic lineages. Specifically Fermt2 is expressed in smooth and striated muscle tissues in mice and in the somites (a trunk muscle precursor) and neural crest in Xenopus embryos. As such it has been proposed that Fermt2 plays a role in cardiomyocyte and neural crest differentiation. Expression of mammalian Fermt3 is associated with hematopoietic lineages: the anterior ventral blood islands, vitelline veins, and early myeloid cells. In Xenopus embryos this expression, also include the notochord and cement gland. The FERM domain has a cloverleaf tripart structure composed of: (1) FERM_N (A-lobe or F1); (2) FERM_M (B-lobe, or F2); and (3) FERM_C (C-lobe or F3). This cd is not included in the C-lobe hierarchy based on its position in the tree. One thing to note is that unlike the other members of the C-lobe hierarchy it contains 2 FERM M domains which might also reflect a difference in its evolutionary history. The C-lobe/F3 within the FERM domain is part of the PH domain family. The FERM domain is found in the cytoskeletal-associated proteins such as ezrin, moesin, radixin, 4.1R, and merlin. These proteins provide a link between the membrane and cytoskeleton and are involved in signal transduction pathways. The FERM domain is also found in protein tyrosine phosphatases (PTPs), the tyrosine kinases FAK and JAK, in addition to other proteins involved in signaling. This domain is structurally similar to the PH and PTB domains and consequently is capable of binding to both peptides and phospholipids at different sites.

Feature 1 # #### Q9BQL6 564 EFGLTYYLVRFkg--sKKDDILGVSyNRLIKIDaatgipvTTWRFtNIKQWNVNWETRQVVIEfdQNVFTAFTCLSADCK 641 human NP_506628 608 EHGIHYFIVRFrn--aRKAELVAVAvNRLAKLNmdngeslKTWRFaNMKKWHVNWEIRHLKIQf-EDEDIEFKPLSADCK 684 nematode NP_957198 527 DFGISYFMVRFkg--sRKDEVLGIAnNRLIRIDlgvgdvvKTWRYnNMRQWNVNWDIRQVAIEfdGNINIAFGCVNADCK 604 zebrafish AAH82672 568 EFGLAYYIVRFrg--sKKDDLLGVShNRLIRIDiatkdpiTTWRFsSMKQWNVNWEKREVAIEfdQNISIAFMSQSANCK 645 African clawed ... XP_784927 590 EYGITFFVVRThg--tRKDELLGLAyNRMIKMDintgdlqKTWRYsTMTHWNVNWETRELIIGm-EDEQIQMACLTCDCK 666 purple urchin XP_415024 564 EFGLSYYIVRFkg--sKKEDVLGVSyNRLIRIDiatgdpiTTWRFsTMKQWNVNWEIRQVGIEfdQNVSVAFTCLSADCK 641 chicken XP_001628628 525 EFGVSHFIVRFrsdkpKKEEILGIAfNRIMRIDastreaiKTWRYsVMRAWNVNWETREMIVQc-EDEMIAFNCVSADIK 603 starlet sea ane... XP_002411717 567 EFGISLFVVRFsg--sKKEELLGVAfNRLMRMElstgdhiKTWRFnTMKAWNVNWEVKQMMVQfeEEPHVAFACLSADCK 644 black-legged tick XP_002590896 559 EFGITHFVVRFrg--nKKEDLLGVAfNRIMRMDlhtgdalKTWRYnSMKHWNVNWEVKEVLVQf-EDEQVSFACLSADCK 635 Florida lancelet EFX74788 585 EYGVSLFVVKFmg--qRKEELLGVAfNRLMRMDlttgdhiKTWRYnTMKAWNVNWEVKHMMVQf-EEESVIFSCLSADCK 661 common water flea

Feature 1 # # ## Q9BQL6 642 IVHEYIGGYIFLST 655 human NP_506628 685 VVHEFIGGYIFLSM 698 nematode NP_957198 605 VVHEYIGGYIFMST 618 zebrafish AAH82672 646 IVHEYIGGYIFLST 659 African clawed frog XP_784927 667 IVHEYIGGSIFLAL 680 purple urchin XP_415024 642 IIHEHIGGYIFLST 655 chicken XP_001628628 604 AVHEFIGGYIFLSM 617 starlet sea anemone XP_002411717 645 TVHEFIGGYIFLSM 658 black-legged tick XP_002590896 636 IVHEFIGGYIFNSM 649 Florida lancelet EFX74788 662 VVHEFIGGYIFLSM 675 common water flea

Conserved Protein Domain FamilyFERM_C_fermitin

Conserved Protein Domain Family
FERM_C_fermitin