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FLASH GENE

Symbol

FERMT2

contributors: mct/pgu - updated : 27-06-2017

HGNC name	fermitin family homolog 2 (Drosophila)
HGNC id	15767

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_006832 15 - 3351 NP_006823 77 680 - 2008 18997731 NM_001134999 16 - 3372 NP_001128471 78.5 687 - 2008 18997731 NM_001135000 15 - 2161 NP_001128472 72.3 633 - 2008 18997731

EXPRESSION

Type	ubiquitous

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Cardiovascular heart       highly Digestive intestine large intestine colon     Endocrine pancreas         Reproductive female system ovary         male system prostate       Respiratory lung         Skin/Tegument skin         Urinary kidney

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Connective interstitial dermis   highly Muscular striatum cardiac   highly

cell lineage

cell lines

fluid/secretion

at STAGE

physiological period

pregnancy

cell cycle

cell cycle, G1, S

Text

placenta

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	N terminus of kindlin-2 (K2-N), with a conserved positively charged surface that binds to membrane enriched with negatively charged phosphatidylinositol-(4,5)-bisphosphate
	a pleckstrin homology (PH) domain
	two C-terminal FERM domains, similar with that of talin

HOMOLOGY

interspecies	ortholog to C.elegans UNC-112
	ortholog to murine Plekhc1

intraspecies

homolog to URP1,URP2

Homologene

FAMILY

kindlin family

CATEGORY

adhesion , regulatory

SUBCELLULAR LOCALIZATION	plasma membrane
	intracellular
	intracellular,cytoplasm,cytosolic
	intracellular,nucleus,nucleoplasm
text	localizes to cell–ECM-adhesion sites

basic FUNCTION	playing an indispensable role for proper control of cell shape change
	being a novel and essential element of bidirectional integrin signaling
	regulator of integrin activation and functions as a coactivator
	required for talin-induced integrin activation, and is a novel and essential element of bidirectional integrin signaling
	novel integrin adaptor protein important for muscle differentiation, and critical regulator of myocyte elongation
	cytoplasmic component of cell/ECM adhesions that bind to beta-integrin cytoplasmic tails directly and cooperate with talin in integrin activation
	essential role for integrin signalling and cell/ECM adhesion regulation
	essential component of the intercalated disc, that is necessary for cytoskeletal organization at sites of membrane attachment, and required for vertebrate myocardial formation and function
	integrin adaptor protein important for muscle differentiation, and critical regulator of myocyte elongation
	focal adhesion proteins implicated in integrin activation
	physiological role for kindlin-2 in skin fibroblasts under normal steady-state conditions and during tissue regeneration
	important functions of kindlin-2 in the regulation of podocyte-matrix adhesion and matrix deposition
	focal adhesion protein that regulate integrin signaling
	governs RAC1 activation, which controls osteoblast function, and is a critical mediator for osteoblast physiology
	capable of promoting integrin activation, but such ability is significantly reduced for its membrane-binding defective mutant
	potential membrane-binding function of its ubiquitin-like domain, which is likely common for all kindlins to promote their localization to the plasma membrane and control integrin activation
	FBLIM1 may work in concert with its binding partners FERMT2 and filamin in bone
	SRC, FERMT2 and FBLIM1 together constitute a positive feedback loop that controls SRC activity and regulates integrin-mediated cellular functions
	is a focal adhesion protein that regulates the activation of integrins
	in Pancreatic stellate cells (PSCs) promoted the progression of pancreatic cancer

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

text	actin cytoskeleton organization and biogenesis

PATHWAY

metabolism

signaling

a component

INTERACTION

DNA

RNA

small molecule

protein	FBLP1
	interact with many components of cell-ECM adhesions, such as migfilin and integrin-linked kinase to promote cytoskeletal reorganization
	interacts directly with the focal-adhesion proteins ILK and migfilin
	binds directly to the C terminal region of beta integrin cytoplasmic tails and exerts intergrin-specific activation effects
	interacts with multiple phosphoinositides, preferentially with phosphatidylinositol 3,4,5-trisphosphate
	FERMT2 and filamin, which directly bind FBLIM1, have been implicated in regulation of bone remodeling
	regulatory loop between FERMT2 and GLI1, an effector of Hedgehog signaling pathway (FERMT2 is transcriptionally downregulated via GLI1 occupancy on the FERMT2 promoter)
	FERMT2 is a novel ACTN2-interacting protein and plays an important role in the regulation of cardiac structure and function

cell & other

REGULATION

induced by

serum in diploid fibroblast cell line

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral     --over   in breast tumors constitutional         resulting in early embryonic lethality tumoral         in leiomyomas compared with normal myometrium tumoral     --low   greatly decreased in leiomyosarcomas tumoral     --over   in malignant mesothelioma, and heightened expression of Kindlin-2 might contribute to tumor progression

Susceptibility

to sporadic Alzheimer disease (SAD)

Variant & Polymorphism SNP	rs17125944 in FERMT2 is associated with sporadic AD (SAD) patients

Candidate gene
Marker
Therapy target
	System Type Disorder Pubmed cancer reproductive prostate targeting the FERMT2-GLI1 feedback loop may facilitate the killing of prostate cancer cells

ANIMAL & CELL MODELS