Fhit fragile histidine triad gene [Mus musculus (house mouse)] - Gene

Summary

Official Symbol: Fhitprovided by MGI
Official Full Name: fragile histidine triad geneprovided by MGI
Primary source: MGI:MGI:1277947
See related: Ensembl:ENSMUSG00000060579 AllianceGenome:MGI:1277947
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Mus musculus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
Also known as: Fra14A2
Summary: This gene encodes a member of the HIT family of proteins that are characterized by the presence of a histidine triad sequence. The encoded protein is a diadenosine triphosphate hydrolase enzyme that cleaves the P(1)-P(3)-bis(5'-adenosyl) triphosphate (Ap3A) to yield AMP and ADP. This locus is very fragile and has been found to be altered in different types of cancers. Mice lacking the encoded protein display increased susceptibility to spontaneous and induced tumors. Ectopic expression of the encoded protein in such knockout mice inhibits tumor development. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Apr 2015]
Expression: Ubiquitous expression in kidney adult (RPKM 2.4), liver E18 (RPKM 1.8) and 27 other tissues See more
Orthologs: human all
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Genomic context

Location:: 14 A1; 14 5.61 cM

Exon count:: 14

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCm39 (GCF_000001635.27)	14	NC_000080.7 (11307718..12919681)
108.20200622	previous assembly	GRCm38.p6 (GCF_000001635.26)	14	NC_000080.6 (9550092..11162061, complement)

Chromosome 14 - NC_000080.7 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: Mouse ENCODE transcriptome data
Description: RNA profiling data sets generated by the Mouse ENCODE project.
BioProject: PRJNA66167
Publication: PMID 25409824
Analysis date: n/a

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Fhit loss and subsequent thymidine kinase 1 inactivation, combined with selective pressures, leads to neoplasia-associated alterations in genes and gene expression patterns in vitro and in vivo
Title: Fhit loss-associated initiation and progression of neoplasia in vitro.
Fhit-deficiency mutation signature also resembles a C>T and T>C mutation signature reported for human papillary kidney cancers and a similar signature recently reported for esophageal and bladder cancers, cancers that are frequently Fhit deficient.
Title: Exome-wide single-base substitutions in tissues and derived cell lines of the constitutive Fhit knockout mouse.
Fhit deficiency-induced global genome instability promotes mutation and clonal expansion
Title: Fhit deficiency-induced global genome instability promotes mutation and clonal expansion.
Fhit delocalizes annexin A4 from plasma membrane to cytosol and sensitizes lung cancer cells to paclitaxel.
Title: Fhit delocalizes annexin a4 from plasma membrane to cytosol and sensitizes lung cancer cells to paclitaxel.
FHIT gene is a "caretaker gene" necessary for maintenance of genome stability.
Title: Common chromosome fragile sites in human and murine epithelial cells and FHIT/FRA3B loss-induced global genome instability.
Loss of Fhit expression contributes to cell transformation.
Title: Characterization of the role of Fhit in suppression of DNA damage.
Defects in Fhit expression may promote MHC-I down-regulation in cancer cells and allow escape from immunosurveillance.
Title: The tumour suppressor Fhit positively regulates MHC class I expression on cancer cells.
the extent of tumor susceptibility due to Nit1 and Fhit deficiency is additive
Title: Nit1 and Fhit tumor suppressor activities are additive.
reduced oxidative stress, coupled with efficient but not error-free DNA damage repair, allows unscheduled long-term survival of genotoxin-exposed Fhit-deficient hematopoietic stem cells carrying deleterious mutations
Title: Fhit-deficient hematopoietic stem cells survive hydroquinone exposure carrying precancerous changes.
tumor-like microdeletions in FHIT/FRA3B are induced by replication stress
Title: Replication stress induces tumor-like microdeletions in FHIT/FRA3B.

Submit: New GeneRIF Correction See all GeneRIFs (17)

Variation

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Alleles

Alleles of this type are documented at Mouse Genome Informatics (MGI)

Endonuclease-mediated (2)
Targeted (2) 1 citation

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

PMC18303P1 (e-PCR)
- UniSTS:271684

D14Mit229 (e-PCR), detects polymorphism
- UniSTS:127345

16.MMHAP12FRF7.seq (e-PCR)
- UniSTS:123294

NoName (e-PCR)
- UniSTS:225186

NoName (e-PCR)
- UniSTS:224436

AI591601 (e-PCR)
- UniSTS:164544

D14Mit132 (e-PCR), detects polymorphism
- UniSTS:116417

AF047699 (e-PCR)
- UniSTS:163546

Gene Ontology Provided by MGI

Function	Evidence Code	Pubs
enables adenosine 5'-monophosphoramidase activity	ISO Inferred from Sequence Orthology more info
enables adenylylsulfatase activity	ISO Inferred from Sequence Orthology more info
enables adenylylsulfate-ammonia adenylyltransferase activity	ISO Inferred from Sequence Orthology more info
enables bis(5'-adenosyl)-triphosphatase activity	IBA Inferred from Biological aspect of Ancestor more info
enables bis(5'-adenosyl)-triphosphatase activity	ISO Inferred from Sequence Orthology more info
enables bis(5'-adenosyl)-triphosphatase activity	ISS Inferred from Sequence or Structural Similarity more info	PubMed
enables catalytic activity	IEA Inferred from Electronic Annotation more info
enables hydrolase activity	IEA Inferred from Electronic Annotation more info
enables identical protein binding	ISO Inferred from Sequence Orthology more info
enables nickel cation binding	ISO Inferred from Sequence Orthology more info
enables nucleotide binding	IEA Inferred from Electronic Annotation more info
enables transferase activity	IEA Inferred from Electronic Annotation more info
enables ubiquitin protein ligase binding	IBA Inferred from Biological aspect of Ancestor more info
enables ubiquitin protein ligase binding	ISO Inferred from Sequence Orthology more info

Process	Evidence Code	Pubs
acts_upstream_of_or_within DNA replication	IDA Inferred from Direct Assay more info	PubMed
acts_upstream_of_or_within apoptotic process	IEA Inferred from Electronic Annotation more info
involved_in diadenosine triphosphate catabolic process	IBA Inferred from Biological aspect of Ancestor more info
involved_in diadenosine triphosphate catabolic process	ISO Inferred from Sequence Orthology more info
involved_in diadenosine triphosphate catabolic process	ISS Inferred from Sequence or Structural Similarity more info	PubMed
involved_in intrinsic apoptotic signaling pathway by p53 class mediator	IBA Inferred from Biological aspect of Ancestor more info
involved_in intrinsic apoptotic signaling pathway by p53 class mediator	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of proteasomal ubiquitin-dependent protein catabolic process	IBA Inferred from Biological aspect of Ancestor more info
involved_in negative regulation of proteasomal ubiquitin-dependent protein catabolic process	ISO Inferred from Sequence Orthology more info
involved_in purine nucleotide metabolic process	IBA Inferred from Biological aspect of Ancestor more info
involved_in purine nucleotide metabolic process	ISO Inferred from Sequence Orthology more info

Component	Evidence Code	Pubs
is_active_in cytoplasm	IBA Inferred from Biological aspect of Ancestor more info
located_in cytoplasm	IDA Inferred from Direct Assay more info	PubMed
located_in cytoplasm	ISO Inferred from Sequence Orthology more info
located_in cytosol	ISO Inferred from Sequence Orthology more info
located_in fibrillar center	ISO Inferred from Sequence Orthology more info
located_in mitochondrion	IEA Inferred from Electronic Annotation more info
is_active_in nucleus	IBA Inferred from Biological aspect of Ancestor more info
is_active_in plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in plasma membrane	ISO Inferred from Sequence Orthology more info

General protein information

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Preferred Names: bis(5'-adenosyl)-triphosphatase

Names: AP3A hydrolase; AP3Aase; adenosine 5'-monophosphoramidase FHIT; adenylylsulfatase; adenylylsulfate-ammonia adenylyltransferase; diadenosine 5',5'''-P1,P3-triphosphate hydrolase; dinucleosidetriphosphatase; fragile histidine triad protein

NP_001295214.1

EC 2.7.7.51

EC 3.6.1.29

EC 3.6.2.1

NP_001295215.1

EC 2.7.7.51

EC 3.6.1.29

EC 3.6.2.1

NP_001347070.1

EC 2.7.7.51

EC 3.6.1.29

EC 3.6.2.1

NP_001411365.1

EC 2.7.7.51

EC 3.6.1.29

EC 3.6.2.1

NP_001411366.1

EC 2.7.7.51

EC 3.6.1.29

EC 3.6.2.1

NP_034340.1

EC 2.7.7.51

EC 3.6.1.29

EC 3.6.2.1

XP_006517987.1

EC 2.7.7.51

EC 3.6.1.29

EC 3.6.2.1

XP_036014355.1

EC 2.7.7.51

EC 3.6.1.29

EC 3.6.2.1

XP_036014356.1

EC 2.7.7.51

EC 3.6.1.29

EC 3.6.2.1

XP_036014357.1

EC 2.7.7.51

EC 3.6.1.29

EC 3.6.2.1

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_001308285.2 → NP_001295214.1 bis(5'-adenosyl)-triphosphatase isoform 1

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longest transcript and encodes the longer isoform (1).

Source sequence(s)

AC154197, AC154570, AC154708, AC159306, CT485999

Consensus CDS

CCDS79263.1

UniProtKB/TrEMBL

E9PZ91

Related

ENSMUSP00000124017.2, ENSMUST00000160340.8

Conserved Domains (1) summary

cd01275
Location:68 → 187

FHIT; FHIT (fragile histidine family): FHIT proteins, related to the HIT family carry a motif HxHxH/Qxx (x, is a hydrophobic amino acid), On the basis of sequence, substrate specificity, structure, evolution and mechanism, HIT proteins are classified into ...
NM_001308286.2 → NP_001295215.1 bis(5'-adenosyl)-triphosphatase isoform 2

See identical proteins and their annotated locations for NP_001295215.1

Status: REVIEWED

Description

Transcript Variant: This variant (3) differs in the 5' UTR, represents the use of an alternate promoter and uses a downstream start codon compared to variant 1. It encodes isoform 2 which has a shorter N-terminus compared to isoform 1. Both variants 2, 3 and 4 encode the same protein (isoform 2).

Source sequence(s)

AC154570, AC159306, CT485999

Consensus CDS

CCDS49400.1

UniProtKB/Swiss-Prot

O89106, Q6URW5, Q91VL1

UniProtKB/TrEMBL

E9PVU9

Related

ENSMUSP00000123874.2, ENSMUST00000161302.8

Conserved Domains (1) summary

cd01275
Location:5 → 124

FHIT; FHIT (fragile histidine family): FHIT proteins, related to the HIT family carry a motif HxHxH/Qxx (x, is a hydrophobic amino acid), On the basis of sequence, substrate specificity, structure, evolution and mechanism, HIT proteins are classified into ...
NM_001360141.2 → NP_001347070.1 bis(5'-adenosyl)-triphosphatase isoform 2

Status: REVIEWED

Source sequence(s)

AC105071, AC154197, AC154570, AC154708, AC159306, CT485999

Consensus CDS

CCDS49400.1

UniProtKB/Swiss-Prot

O89106, Q6URW5, Q91VL1

UniProtKB/TrEMBL

E9PVU9

Related

ENSMUSP00000124957.2, ENSMUST00000161895.8

Conserved Domains (1) summary

cd01275
Location:5 → 124

FHIT; FHIT (fragile histidine family): FHIT proteins, related to the HIT family carry a motif HxHxH/Qxx (x, is a hydrophobic amino acid), On the basis of sequence, substrate specificity, structure, evolution and mechanism, HIT proteins are classified into ...
NM_001424436.1 → NP_001411365.1 bis(5'-adenosyl)-triphosphatase isoform 2

Status: REVIEWED

Source sequence(s)

AC105071, AC154197, AC154570, AC154708, AC159306, CT485999

UniProtKB/Swiss-Prot

O89106, Q6URW5, Q91VL1
NM_001424437.1 → NP_001411366.1 bis(5'-adenosyl)-triphosphatase isoform 2

Status: REVIEWED

Source sequence(s)

AC154570, AC154708, AC159306, CT485999

UniProtKB/Swiss-Prot

O89106, Q6URW5, Q91VL1
NM_010210.4 → NP_034340.1 bis(5'-adenosyl)-triphosphatase isoform 2

See identical proteins and their annotated locations for NP_034340.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) lacks an alternate exon in the 5' UTR, lacks a portion of the 5' coding region, and uses a downstream start codon compared to variant 1. It encodes isoform 2 which has a shorter N-terminus compared to isoform 1. Variants 2, 3 and 4 encode the same protein (isoform 2).

Source sequence(s)

AC154197, AC154570, AC154708, AC159306, CT485999

Consensus CDS

CCDS49400.1

UniProtKB/Swiss-Prot

O89106, Q6URW5, Q91VL1

UniProtKB/TrEMBL

E9PVU9

Related

ENSMUSP00000124073.2, ENSMUST00000162278.8

Conserved Domains (1) summary

cd01275
Location:5 → 124

FHIT; FHIT (fragile histidine family): FHIT proteins, related to the HIT family carry a motif HxHxH/Qxx (x, is a hydrophobic amino acid), On the basis of sequence, substrate specificity, structure, evolution and mechanism, HIT proteins are classified into ...

RefSeqs of Annotated Genomes: GCF_000001635.27-RS_2024_02

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCm39 C57BL/6J

Genomic

NC_000080.7 Reference GRCm39 C57BL/6J

Range

11307718..12919681

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_036158463.1 → XP_036014356.1 bis(5'-adenosyl)-triphosphatase isoform X3

UniProtKB/Swiss-Prot

O89106, Q6URW5, Q91VL1

UniProtKB/TrEMBL

E9PVU9

Conserved Domains (1) summary

cd01275
Location:5 → 124

FHIT; FHIT (fragile histidine family): FHIT proteins, related to the HIT family carry a motif HxHxH/Qxx (x, is a hydrophobic amino acid), On the basis of sequence, substrate specificity, structure, evolution and mechanism, HIT proteins are classified into ...
XM_036158464.1 → XP_036014357.1 bis(5'-adenosyl)-triphosphatase isoform X3

UniProtKB/Swiss-Prot

O89106, Q6URW5, Q91VL1

UniProtKB/TrEMBL

E9PVU9

Conserved Domains (1) summary

cd01275
Location:5 → 124

FHIT; FHIT (fragile histidine family): FHIT proteins, related to the HIT family carry a motif HxHxH/Qxx (x, is a hydrophobic amino acid), On the basis of sequence, substrate specificity, structure, evolution and mechanism, HIT proteins are classified into ...
XM_006517924.1 → XP_006517987.1 bis(5'-adenosyl)-triphosphatase isoform X2

Conserved Domains (1) summary

cd01275
Location:40 → 159

FHIT; FHIT (fragile histidine family): FHIT proteins, related to the HIT family carry a motif HxHxH/Qxx (x, is a hydrophobic amino acid), On the basis of sequence, substrate specificity, structure, evolution and mechanism, HIT proteins are classified into ...
XM_036158462.1 → XP_036014355.1 bis(5'-adenosyl)-triphosphatase isoform X1

UniProtKB/TrEMBL

E9PZ91

Conserved Domains (1) summary

cd01275
Location:68 → 187

FHIT; FHIT (fragile histidine family): FHIT proteins, related to the HIT family carry a motif HxHxH/Qxx (x, is a hydrophobic amino acid), On the basis of sequence, substrate specificity, structure, evolution and mechanism, HIT proteins are classified into ...