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FLASH GENE

Symbol

GSN

contributors: mct/npt/pgu - updated : 06-05-2014

HGNC name	gelsolin (amyloidosis, Finnish type)
HGNC id	4620

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

DNA

TYPE	functioning gene
STRUCTURE	64.74 kb     18 Exon(s)

10 Kb 5' upstream gene genomic sequence study

MAPPING

cloned

Y

linked

Y

status

confirmed

Map	cen - D9S29 - TNC - D9S154 - D9S41 - D9S26 - D9S21 /D9S103 - GSN - D9S49 - D9S60 ,AK1 AK1 - D9S61 - qter

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_000177 - - 2719 NP_000168 83 782 - 2009 19666512 secreted form NM_198252 18 - 2685 NP_937895 81 731 - 2009 19666512 cytoplasmic form NM_001127664 19 - 2764 NP_001121136 - 731 - 2009 19666512 NM_001127663 19 - 2797 NP_001121135 - 731 - 2009 19666512 NM_001127665 19 - 2759 NP_001121137 - 731 - 2009 19666512 NM_001127666 19 - 2756 NP_001121138 - 742 - 2009 19666512 NM_001127667 19 - 2747 NP_001121139 - 742 - 2009 19666512 NM_001127662 17 - 2592 NP_001121134 - 731 - 2009 19666512 NM_001258029 - - 2579 NP_001244958 - 748 - 2009 19666512 NM_001258030 - - 2656 NP_001244959 - 739 - 2009 19666512

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 Digestive intestine small intestine     highly   mouth       highly Hearing/Equilibrium ear outer       Homo sapiens Nervous nerve cranial nerve     highly

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Connective adipose     highly

cells

System Cell Pubmed Species Stage Rna symbol Blood/Hematopoietic platelet Hearing / Equilibrium hair cell receptor Homo sapiens Lymphoid/Immune macrophage Nervous Schawnn cell Homo sapiens

cell lineage
cell lines
fluid/secretion	plasma

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	two tandem homologous halves, each containing a three-fold segmental repeat,
	the N half representing a Ca2+ insensitive, PIP2 sensitive severing site
	the C half, a Ca2+ dependent actin binding and capping site, separated by a linker cleaved by caspase 3
	six gelsolin-like repeats

HOMOLOGY

intraspecies

homolog to villin

Homologene

FAMILY

villin/gelsolin family

CATEGORY

regulatory , structural protein

SUBCELLULAR LOCALIZATION	extracellular
	intracellular
	intracellular,cytoplasm,cytosolic
	intracellular,cytoplasm,cytoskeleton

basic FUNCTION	implicated in actin remodeling in growing and in apoptotic cells
	can promote the assembly of monomers into filaments (nucleation) as well as sever filaments already formed
	with calponin are reported to play signaling roles in addition to their better-characterized actin-binding properties and it is possible that the GCC regulates both of these functions
	calcium-regulated actin severing and capping protein, having biological role in cardiac remodeling
	important contributor to heart failure progression through novel mechanisms of HIF-1alpha and DNase I activation and downregulation of antiapoptotic survival factors
	required for macrophage recruitment during remyelination of the peripheral nervous system
	plays a role in the actin polymerization complex of hair cell stereocilia
	ACSL1 and gelsolin are oppositely regulated in adipogenesis and lipogenesis
	regulate dynamic actin filament organization by severing and capping
	also regulates cell morphology, differentiation, movement, and apoptosis

CELLULAR PROCESS	cell life, cell death/apoptosis
	cell organization/biogenesis
	cell communication

PHYSIOLOGICAL PROCESS

text	putatively recycling filaments at the leading edge of motile cells

PATHWAY

metabolism

signaling

a component	form a tight gelsolin:calponin complex (GCC)
	FHL1 exists as part of a complex that binds with PDLIM1, GSN and ACTN1
	part of the whirlin complex

INTERACTION

DNA

RNA

small molecule

protein	binds to actin and to fibronectin
	can physically interact with TP53
	GSN associates with the N-terminus of STXN4 to regulate insulin granule exocytosis
	induces cardiomyocyte hypertrophy and NPPB expression via MAPK14 signaling and GATA4 transcriptional factor activation

cell & other

REGULATION

activated by

hypoxia (hypoxia stimulates expression of CAPG and GSN via HIF1A-dependent and -independent pathways, respectively, and this up-regulation may contribute to the increased motility of pulmonary artery smooth muscle cells under hypoxia)

Other	calcium Ca2+ and polyphosphoinositide 4,5-biphosphate (PIP2)-regulated
	cleaved by CASP3 to form a potential effector of morphologic change during apoptosis

ASSOCIATED DISORDERS

corresponding disease(s)

CAAG

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function constitutional     --over   is highly expressed in murine and human hearts after myocardial infarction and is associated with progression of heart failure tumoral     --low   in pancreatic cancer and enhanced targeting of gelsolin to the ubiquitin-proteasome pathway is an important contributing factor for this effect tumoral     --low   in breast cancer tissues and is linked with metastasis development and death in patients constitutional       loss of function inactivation of gelsolin during sperm capacitation occurs by its binding to PIP(2) and tyrosine phosphorylation by SRC

Susceptibility

Variant & Polymorphism

Candidate gene	for malignant pleural mesothelioma
Marker	CSF-gelsolin level might reflect the alteration of gelsolin in brain tissue of epileptic patients and CSF-gelsolin seems to be a potential biomarker for epilepsy
Therapy target
	System Type Disorder Pubmed cardiovascular aquired heart failure inhibition of GSN may form a novel target for heart failure therapy

ANIMAL & CELL MODELS

	GSN(-/-) mice have a surprisingly lower mortality, markedly reduced hypertrophy, smaller late infarct size, less interstitial fibrosis, and improved cardiac function when compared with GSN(+/+) mice
	in Gsn(-/-) mice, emigration of newly generated cells from the subventricular zone into the olfactory bulb was slowed