Contents

Search

fragile histidine triad protein; AP3A hydrolase; bis(5'-adenosyl)-triphosphatase; diadenosine 5',5'''-P1,P3-triphosphate hydrolase (FHIT)

Function: - cleaves A-5'-PPP-5'A to yield AMP & ADP - modulates transcriptional activation by CTNNB1 thus role in expression of genes essential for cell proliferation & survival, such as CCND1 & BIRC5 - role in the induction of apoptosis via SRC & AKT1 signaling - inhibits MDM2-mediated proteasomal degradation of p53/TP53 thus a role in p53/TP53-mediated apoptosis - induction of apoptosis may in part come from the mitochondrial form, which sensitizes the low-affinity Ca+2 transporters, enhancing mitochondrial Ca+2 uptake. - phosphorylation at Tyr-114 by SRC is required for induction of apoptosis - interacts with UBE2I, MDM2, CTNNB1 - identified in a complex with CTNNB1 & LEF1 - possible tumor suppressor for specific tissues Cofactor: - divalent cations - Mg+2 > Mn+2, Ca+2, Co+2 - not Zn+2, Cd+2, Ni+2 Structure: - homodimer - contains 1 HIT domain Compartment: cytoplasm, mitochondria, nucleus Expression: - low levels expressed in all tissues tested - phospho-FHIT observed in liver & kidney - phospho-FHIT not expressed in brain or lung - phospho-FHIT undetected in any tested human tumor cell lines Pathology: - chromosomal translocation t(3;8)(p14.2;q24.1) involving FHIT & RNF139 has been found in a lymphoblastoid cell line established from a family with renal cell carcinoma & thyroid carcinoma - the 3p14.2 breakpoint interrupts FHIT in its 5' non-coding region, but it is unlikely that FHIT is causally related to renal cell carcinoma or thyroid carcinoma - associated with digestive tract cancers - tumors 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 - abnormal transcripts of FHIT found in ~50% of - esophageal carcinoma - gastric carcinoma - colon carcinoma

Related

FHIT (fragile histidine triad) gene

General

human longevity protein hydrolase phosphoprotein

Properties

SIZE: entity length = 147 aa MW = 17 kD COMPARTMENT: mitochondria cytoplasm cell nucleus MOTIF: HIstidine Triad (HIT domain) {2-109} MOTIF: binding site SITE: 8-8 FOR-BINDING-OF: Substrate binding site SITE: 27-27 FOR-BINDING-OF: Substrate binding site SITE: 83-83 FOR-BINDING-OF: Substrate histidine residue {H96} binding site SITE: 98-98 FOR-BINDING-OF: Substrate Tyr phosphorylation site {Y114} Tyr phosphorylation site {Y145}

Database Correlations

OMIM 601153 UniProt P49789 Pfam PF01230 Entrez Gene 2272 Kegg hsa:2272 ENZYME 3.6.1.29

References

  1. UniProt :accession P49789
  2. UniProt PubMed refs - PMID: 16407838 - PMID: 407838 - PMID: 19622739 - PMID: 622739 - PMID: 9323207 - PMID: 15182206 - PMID: 182206 - PMID: 23207 - PMID: 15313915 - PMID: 313915
  3. Atlas of Genetics & Cytogenetics in Oncology & Haematology http://atlasgeneticsoncology.org/genes/FHITID192ch3p14.html