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FLASH GENE

Symbol

TES

contributors: mct/npt/pgu - updated : 10-02-2021

HGNC name	testin LIM domain protein
HGNC id	14620

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

DNA

TYPE	functioning gene
STRUCTURE	48.30 kb     7 Exon(s)

10 Kb 5' upstream gene genomic sequence study

regulatory sequence	cytosine-phosphate-guanine/HTF
text structure	1a/7 to 7, two Cpg islands

MAPPING

cloned

Y

linked

N

status

provisional

Map	cen - [D7S486 - TES - D7S522 ] - HERVH2 - CAV2 - CAV1 - MET - D7S2460 -CAPZA2 - qter
Text	[fra7G ]

RNA

TRANSCRIPTS	type	messenger

text	three isoforms 1 and 2 from 3'utr region, 1, 2 vs 3 by alternative splice of exon 1a, (1,2), 1b (3)

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_015641 7 splicing 2799 NP_056456 48 421 - 2000 10950921 NM_152829 7 splicing 2633 NP_690042 47 412 - 2000 10950921

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         Homo sapiens

cell lineage	lymphoblastoid cells
cell lines	cancer cell lines but not in hematological malignancies cell lines
fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	a PET domain in the N-terminus
	four phosphorylation sites
	one glycosylation site
	one cytochrome C heme binding site
	three cysteine-rich LIM/double zinc finger motifs (LIM domains) at the C terminus (LIM3 domain lacking the FPPPP motif, binds to the EVH1 domain of ENAH, but not to those of VASP or EVL)(Boeda 2007)

HOMOLOGY

interspecies

homolog to murine Testin

intraspecies

homolog to SOX9

Homologene

FAMILY

prickle/espinas/testin family

CATEGORY

adhesion , transcription factor

SUBCELLULAR LOCALIZATION	plasma membrane,junction
	intracellular
	intracellular,cytoplasm,cytosolic
	intracellular,nucleus
text	putative tumor suppressor and localizes to the cytoplasm as a component of focal adhesions and cell contacts
	locates in the cytoplasm along stress fibers being recruited to focal adhesions

basic FUNCTION	transcriptional regulation through protein-protein interactions
	actin-binding protein mainly located at focal adhesions (Rotter 2005)
	atypical EVH1 binding partner and regulator specific to a single ENAH/VASP family member (Boeda 2008)
	plays a role in cell spreading and motility as well as cytoskeletal organisation, e.g. actin stress fibre assembly
	has different conformational states in different cellular compartments, and a "closed" conformational state of TES may be involved in nucleolar localization (
	novel protein partner of the CASR that regulates receptor-mediated Rho signalling, and supports CASR-dependent activation of Rho kinase
	involved in endothelial cell (EC) functions relevant to atherosclerosis
	focal adhesion protein testin is a modular scaffold and tumour suppressor
	testin region (amino acids 52-233) harbouring the PET domain interacts with the C-terminal LIM1-2 domains
	participate in the processes of tumor growth, angiogenesis, and metastasis
	expression of testin protein level correlates positively with percentage of cells in G1 phase, while overexpression can induce apoptosis and decreased colony forming ability
	TES serves likely as a crucial regulator of the hypertrophic reaction by hindering the calcineurin-dependent pathway in the heart

CELLULAR PROCESS	nucleotide, transcription, regulation
	cell organization/biogenesis

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

a component

INTERACTION

DNA

RNA

small molecule

protein	specific ENAH interacting partner
	interaction between TES and spectrin is mediated by a LIM (Lin-11, Isl-1 and Mec3) domain of TES and by the alpha10 repeat of alphaII-spectrin (Rotter 2005)
	interaction between TES and EVL (co-localization of these two proteins at focal adhesions) (Rotter 2005)
	SRY and NR5A1 co-operate to activate the human SOX9 homologous TES, a process dependent on phosphorylated NR5A1
	SOX9 activates TES, augmented by NR5A1, suggesting a mechanism for maintenance of SOX9 expression by auto-regulation
	interplay between the CASR and testin in the regulation of CASR-mediated Rho signalling with possible effects on the cytoskeleton
	TES directly interacted with calcineurin and suppressed its downstream signalling pathway

cell & other

REGULATION

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral       loss of function by hypermethylation in ovarian carcinoma tumoral   amplification     with MET oncogene in gastric cancer constitutional     --low   association between reduced TES expression and coronary artery disease tumoral   LOH     in primary gastric cancer tumoral     --low   is the most frequently methylated and silenced gene yet reported in childhood acute lymphoblastic leukaemia constitutional     --low   associate with loss by cells epithelial morphology and gain migratory and invasive properties of mesenchymal cells tumoral       loss of function in human endometrial carcinoma tumoral     --other   is aberrantly methylated in ALL

Susceptibility

Variant & Polymorphism

Candidate gene	best candidate tumor suppressor gene at 7q31
Marker
Therapy target
	System Type Disorder Pubmed cancer reproductive uterus restoration of TESTIN to be a novel therapeutic strategy for endometrial carcinoma cancer hemopathy   re-expression of TESTIN has anti-leukaemia effects which point to novel therapeutic opportunities for childhood ALL

ANIMAL & CELL MODELS