InnateDB Protein
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IDBP-473513.3
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Last Modified
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2014-10-13 [Report errors or provide feedback]
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Gene Symbol
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FHIT
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Protein Name
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fragile histidine triad gene
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Synonyms
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AP3Aase; FRA3B;
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Species
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Homo sapiens
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Ensembl Protein
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ENSP00000418582
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InnateDB Gene
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IDBG-42471 (FHIT)
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Protein Structure
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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}.
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Subcellular Localization |
Cytoplasm. Mitochondrion. Nucleus.
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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}.
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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.
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Comments |
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Number of Interactions
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This gene and/or its encoded proteins are associated with 15 experimentally validated interaction(s) in this database.
Experimentally validated |
Total |
15
[view]
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Protein-Protein |
13
[view]
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Protein-DNA |
2
[view]
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Protein-RNA |
0
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DNA-DNA |
0
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RNA-RNA |
0
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DNA-RNA |
0
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Molecular Function |
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Biological Process |
GO:0006163
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purine nucleotide metabolic process
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GO:0006351
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transcription, DNA-templated
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GO:0006355
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regulation of transcription, DNA-templated
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GO:0009117
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nucleotide metabolic process
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GO:0032435
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negative regulation of proteasomal ubiquitin-dependent protein catabolic process
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GO:0072332
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intrinsic apoptotic signaling pathway by p53 class mediator
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Cellular Component |
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PDB ID |
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InterPro |
IPR001310
Histidine triad (HIT) protein
IPR011146
HIT-like domain
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PFAM |
PF01230
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PRINTS |
PR00332
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PIRSF |
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SMART |
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TIGRFAMs |
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Modification |
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SwissProt |
P49789
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PhosphoSite |
PhosphoSite-P49789
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TrEMBL |
Q71VB2
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UniProt Splice Variant |
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Entrez Gene |
2272
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UniGene |
Hs.655995
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RefSeq |
NP_002003
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HUGO |
HGNC:3701
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OMIM |
601153
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CCDS |
CCDS2894
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HPRD |
03096
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IMGT |
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EMBL |
AC093418
AC093556
AC096917
AC097357
AC098480
AC099536
AC099780
AC104164
AC132808
AC138071
AF020503
AF023460
AF152363
AF152364
AF152365
AK289824
AY625256
BC032336
CH471055
DQ120721
DQ416126
DQ666923
DQ865132
DQ865133
DQ865134
EF183457
EF183458
EF183459
EF183461
EF183462
EF183463
EF183464
EF186677
KJ534835
U46922
U76267
U76268
U76269
U76270
U76271
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GenPept |
AAA99013
AAB52539
AAB84098
AAB97515
AAH32336
AAT37530
AAZ23623
ABD93871
ABG02275
ABI15740
ABI15741
ABI15742
ABM65879
ABM66086
ABM66087
ABM66088
ABM66090
ABM66091
ABM66092
ABM66093
AHW56475
BAF82513
EAW65393
EAW65394
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