Gene content
Symbol	FHIT ( by HUGO)
Name	Fragile Histidine Triad
Category	Tumor suppressor gene
Alias	Fragile Histidine Triad Diadenosine 5' 5'''-P1 P3-Triphosphate Hydrolase AP3Aase AP3A Hydrolase FRA3B Fragile Histidine Triad Gene bis(5'-adenosyl)-triphosphatase dinucleosidetriphosphatase Tumor Suppressor Protein Dinucleosidetriphosphatase EC 3.6.1.29 Fragile Histidine Triad Protein
Cytogenetic band	NCBI: 3p14.2    Ensembl: 3p14.2
Protein information	FHIT_HUMAN Size: 147 amino acids Mass: 16858 Da Subunit: Homodimer. Interacts with UBE2I. Interacts with MDM2. Interacts with CTNNB1. Identified in a complex with CTNNB1 and LEF1 Mass spectrometry: Mass=16733; Method=MALDI; Range=2-147; Source=PubMed:15007172; Selected PDB 3D structures from [IMAGE] and Proteopedia [IMAGE] for FHIT (see all 8): 1FHI (3D) [IMAGE] 1FIT (3D) [IMAGE] 2FHI (3D) [IMAGE] 2FIT (3D) [IMAGE] 3FIT (3D) [IMAGE] 4FIT (3D) [IMAGE] Tissue specificity: Low levels expressed in all tissues tested. Phospho-FHIT observed in liver and kidney, but not in brain and lung. Phospho-FHIT undetected in all tested human tumor cell lines [IMAGE] Pathway & Disease-focused RT2 Profiler PCR Arrays including FHIT: Oncoge Function: Cleaves P(1)-P(3)-bis(5'-adenosyl) triphosphate (Ap3A) to yield AMP and ADP. Can also hydrolyze P(1)-P(4)-bis(5'-adenosyl) tetraphosphate (Ap4A), but has extremely low activity with ATP. Modulates transcriptional activation by CTNNB1 and thereby contributes to regulate the expression of genes essential for cell proliferation and survival, such as CCND1 and BIRC5. Plays a role in the induction of apoptosis via SRC and AKT1 signaling pathways. Inhibits MDM2-mediated proteasomal degradation of p53/TP53 and thereby plays a role in p53/TP53-mediated apoptosis. Induction of apoptosis depends on the ability of FHIT to bind P(1)-P(3)-bis(5'-adenosyl) triphosphate or related compounds, but does not require its catalytic activity. Functions as tumor suppressor                        Cleaves P(1)-P(3)-bis(5'-adenosyl) triphosphate (Ap3A) to yield AMP and ADP. Can also hydrolyze P(1)-P(4)-bis(5'-adenosyl) tetraphosphate (Ap4A), but has extremely low activity with ATP. Modulates transcriptional activation by CTNNB1 and thereby contributes to regulate the expression of genes essential for cell proliferation and survival, such as CCND1 and BIRC5. Plays a role in the induction of apoptosis via SRC and AKT1 signaling pathways. Inhibits MDM2-mediated proteasomal degradation of p53/TP53 and thereby plays a role in p53/TP53-mediated apoptosis. Induction of apoptosis depends on the ability of FHIT to bind P(1)-P(3)-bis(5'-adenosyl) triphosphate or related compounds, but does not require its catalytic activity. Functions as tumor suppressor Catalytic activity: P(1)-P(3)-bis(5'-adenosyl) triphosphate + H(2)O = ADP + AMP Similarity: Contains 1 HIT domain [IMAGE]

Protein Domain/Family
Source	ID	Domain	Name	Type
InterPro	IPR001310	Histidine_triad_HIT	Histidine triad (HIT) protein	Family
Blocks	IPB001310	Histidine triad (HIT) protein	Histidine triad (HIT) protein

Gene Ontology
Type	Term	Evidence	Source	Pub
Biological Process	negative regulation of proteasomal ubiquitin-dependent protein catabolic process	IMP	GOA	15313915
	nucleotide metabolic process	TAS	GOA	8794732
	purine nucleotide metabolic process	IDA	GOA	9323207
Cellular Component	cytoplasm	IDA	GOA	15007172
	cytosol	IDA	GOA	15313915
Molecular Function	bis(5'-adenosyl)-triphosphatase activity	IDA	GOA	8794732
	catalytic activity	TAS	GOA	8598045
	hydrolase activity	IDA	GOA	8794732
	identical protein binding	IPI	GOA	16189514
	protein binding	IPI	GOA	18319262
	ubiquitin protein ligase binding	IPI	GOA	15313915

Disorder & Mutation
Source	Disease
SWISS-PROT	Note=A chromosomal aberration involving FHIT has been found in a lymphoblastoid cell line established from a family with renal cell carcinoma and thyroid carcinoma. Translocation t(3;8)(p14.2;q24.1) with RNF139. Although the 3p14.2 breakpoint has been shown to interrupt FHIT in its 5-prime non-coding region, it is unlikely that FHIT is causally related to renal or other malignancies
SWISS-PROT	Note=Associated with digestive tract cancers. Numerous tumor types are found to have aberrant forms of FHIT protein due to deletions in a coding region of chromosome 3p14.2 including the fragile site locus FRA3B

FHIT cross reference
PubMed OMIM Entrez Gene NCKU SNP Nucleotide UniProt Genome Data Viewer HomoloGene