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FLASH GENE

Symbol

TFPI2

contributors: mct - updated : 23-12-2014

HGNC name	tissue factor pathway inhibitor 2
HGNC id	11761

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

DNA

TYPE	functioning gene
STRUCTURE	4.32 kb     5 Exon(s)

10 Kb 5' upstream gene genomic sequence study

regulatory sequence	Promoter
	cytosine-phosphate-guanine/HTF
	Binding site   transcription factor
text structure	high GC-rich content without canonical TATA and CAAT boxes but three transcription initiation sites
	promoter exhibiting typical features of a housekeeping gene
	several putative binding sites for transcription factors were identified (MyoD, LYF1, NF-Y, GATA, oct-1, AP-1, Sp1, NF1, NF-kappa B and egr-1)

MAPPING

cloned

Y

linked

status

provisional

RNA

TRANSCRIPTS	type	messenger

text	Identification of a human TFPI-2 splice variant that is upregulated in human tumor tissues

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_006528 5 splicing 1203 variant 1 26 235 - 2007 17352822 variant 2 - splicing 289 variant 2 - 96 variant upregulated in human tumor tissues 2007 17352822 variant generated by splicing of: complete exon 2 15 nucleotides of exon 3 6 nucleotides of intron 3 7 nucleotides of exon 4 complete exon 5

EXPRESSION

Type

widely

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 vessel       highly Digestive liver       lowly   stomach       moderately Reproductive female system placenta     predominantly Respiratory lung       moderately Urinary kidney       moderately Visual eye       moderately

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Connective adipose     moderately Epithelial barrier/lining     lowly

cells

System Cell Pubmed Species Stage Rna symbol Cardiovascular endothelial cell

cell lineage

cell lines

fluid/secretion

at STAGE

physiological period

embryo, pregnancy

Text	placenta, maternal serum, heart, pancreas, embryonic tissue, umbilical cord

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	three tandem Kunitz-type (58AA motif containing three intrachain disulfide bonds) domains
	22 AA signal peptide
	eighteen cysteines
	two canomical N-linked glycosylation sites
	NLS sequence located in its Lys/Arg-rich C-terminal tail comprising residues 191-211

conjugated

GlycoP

HOMOLOGY

interspecies	homolog to rattus Tfpi2 (56.58 pc)
	homolog to murine Tfpi2 (57.48 pc)

Homologene

FAMILY

serine protease inhibitor family, Kunitz type

CATEGORY

regulatory , tumor suppressor

SUBCELLULAR LOCALIZATION	extracellular
	intracellular
	intracellular,nucleus
text	associated with the extracellular matrix (cuticle and basement membrane)
	nuclear localization of TFPI2 was also detected in a variety of endothelial cells constitutively expressing TFPI2, and TFPI2 shuttled to the nucleus by the importin system

basic FUNCTION	inhibiting strongly a wide variety of serine proteinases (trypsin, plasmin, factor XI and MMPs)
	playing a major role in cell migration and tumor invasion
	serine proteinase inhibitor that induces caspase-mediated apoptosis when offered to a variety of tumor cells
	critical for the regulation of extracellular matrix remodeling and atherosclerotic plaque stability
	Kunitz-type serine protease inhibitor, tumor suppressor gene in several types of cancer, including glioma
	Kunitz-type serine proteinase inhibitor whose expression is up-regulated by VEGFA in microvascular and umbilical vein endothelial cells (EC)

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

text	blood coagulation

PATHWAY

metabolism

signaling

a component

INTERACTION

DNA

RNA

small molecule

protein	ADAMTS1
	the proteolytic inactivation of TFPI2 by PRSS3 might represent a mechanism favoring cancer by increasing angiogenesis and vascular remodeling

cell & other

REGULATION

induced by

thrombin (thrombin induces TFPI2 expression by a mechanism involving ERK1/2 and JNK phosphorylation, leading finally to NFkB activation)

Other

TFPI2 interacting with, cleaved by and extracellular location modified by ADAMTS1

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral     --low   silencing by methylation in esophageal squamous cell carcinoma tumoral     --low   by promoter hypermethylation in nasopharyngeal carcinoma

Susceptibility

Variant & Polymorphism other	Identification of a human TFPI-2 splice variant that is upregulated in human tumor tissues

Candidate gene
Marker	may be a useful diagnostic marker for the aggressive phenotype of glial tumors
	detection of TFPI2 methylation in stool DNA may act as a useful adjunct to the noninvasive strategies for screening of colorectal cancer
Therapy target
	System Type Disorder Pubmed cancer digestive oesophagus potentially important therapeutic role for recombinant TFPI2 in the treatment of malignant esophageal carcinomas

ANIMAL & CELL MODELS