InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: FHIT

Summary

InnateDB Protein

IDBP-42473.5

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

FHIT

Protein Name

fragile histidine triad gene

Synonyms

AP3Aase; FRA3B;

Species

Homo sapiens

Ensembl Protein

ENSP00000342087

InnateDB Gene

IDBG-42471 (FHIT)

Protein Structure

UniProt Annotation

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, it may in part come from the mitochondrial form, which sensitizes the low- affinity Ca(2+) transporters, enhancing mitochondrial calcium uptake. Functions as tumor suppressor. {ECO:0000269PubMed:12574506, ECO:0000269PubMed:15313915, ECO:0000269PubMed:16407838, ECO:0000269PubMed:18077326, ECO:0000269PubMed:19622739, ECO:0000269PubMed:8794732, ECO:0000269PubMed:9323207}.

Subcellular Localization

Cytoplasm. Mitochondrion. Nucleus.

Disease Associations

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. {ECO:0000269PubMed:15007172}.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. {ECO:0000269PubMed:15007172}.

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.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 15 experimentally validated interaction(s) in this database.

Experimentally validated
Total	15 [view]
Protein-Protein	13 [view]
Protein-DNA	2 [view]
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Gene Ontology

Molecular Function

Accession	GO Term
GO:0000166	nucleotide binding
GO:0003824	catalytic activity
GO:0005515	protein binding
GO:0016787	hydrolase activity
GO:0031625	ubiquitin protein ligase binding
GO:0042802	identical protein binding
GO:0047710	bis(5'-adenosyl)-triphosphatase activity

Biological Process

GO:0006163	purine nucleotide metabolic process
GO:0006351	transcription, DNA-templated
GO:0006355	regulation of transcription, DNA-templated
GO:0009117	nucleotide metabolic process
GO:0032435	negative regulation of proteasomal ubiquitin-dependent protein catabolic process
GO:0072332	intrinsic apoptotic signaling pathway by p53 class mediator