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FHIT fragile histidine triad [ Homo sapiens (human) ]

Gene ID: 2272, updated on 3-Nov-2018

Summary

Official Symbol
FHITprovided by HGNC
Official Full Name
fragile histidine triadprovided by HGNC
Primary source
HGNC:HGNC:3701
See related
Ensembl:ENSG00000189283 MIM:601153; Vega:OTTHUMG00000158591
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
FRA3B; AP3Aase
Summary
The protein encoded by this gene is a P1-P3-bis(5'-adenosyl) triphosphate hydrolase involved in purine metabolism. This gene encompasses the common fragile site FRA3B on chromosome 3, where carcinogen-induced damage can lead to translocations and aberrant transcripts. In fact, aberrant transcripts from this gene have been found in about half of all esophageal, stomach, and colon carcinomas. The encoded protein is also a tumor suppressor, as loss of its activity results in replication stress and DNA damage. [provided by RefSeq, Aug 2017]
Expression
Ubiquitous expression in gall bladder (RPKM 2.2), lymph node (RPKM 1.6) and 25 other tissues See more
Orthologs

Genomic context

See FHIT in Genome Data Viewer
Location:
3p14.2
Exon count:
20
Annotation release Status Assembly Chr Location
109 current GRCh38.p12 (GCF_000001405.38) 3 NC_000003.12 (59747278..61251474, complement)
105 previous assembly GRCh37.p13 (GCF_000001405.25) 3 NC_000003.11 (59735036..61237133, complement)

Chromosome 3 - NC_000003.12Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC105377110 Neighboring gene small nuclear ribonucleoprotein polypeptide B2 pseudogene Neighboring gene hCG1813818 Neighboring gene uncharacterized LOC105377113 Neighboring gene uncharacterized LOC105377112 Neighboring gene uncharacterized LOC107986015 Neighboring gene origin of replication at fragile site FRA3B Neighboring gene transcription termination factor 1, mitochondrial-like Neighboring gene transmembrane p24 trafficking protein 2 pseudogene Neighboring gene microRNA 548bb Neighboring gene peptidylprolyl isomerase A pseudogene 70 Neighboring gene peptidylprolyl isomerase A pseudogene 71 Neighboring gene uncharacterized LOC105377111 Neighboring gene uncharacterized LOC105377114 Neighboring gene uncharacterized LOC105377115 Neighboring gene uncharacterized LOC107986016 Neighboring gene protein tyrosine phosphatase, receptor type G

Genomic regions, transcripts, and products

Expression

  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Jun 15 11:32:44 2016

Bibliography

GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

Phenotypes

Copy number response

Description
Copy number response
Triplosensitivity

No evidence available (Last evaluated (2018-10-24)

ClinGen Genome Curation PagePubMed
Haploinsufficency

No evidence available (Last evaluated (2018-10-24)

ClinGen Genome Curation PagePubMed

NHGRI GWAS Catalog

Description
A genome-wide association study (GWAS) for bronchopulmonary dysplasia.
NHGRI GWA Catalog
A genome-wide association study provides evidence for association of chromosome 8p23 (MYP10) and 10q21.1 (MYP15) with high myopia in the French Population.
NHGRI GWA Catalog
Gene-age interactions in blood pressure regulation: a large-scale investigation with the CHARGE, Global BPgen, and ICBP Consortia.
NHGRI GWA Catalog
Genetic variants associated with breast size also influence breast cancer risk.
NHGRI GWA Catalog
Genome wide study of maternal and parent-of-origin effects on the etiology of orofacial clefts.
NHGRI GWA Catalog
Genome-wide association scan of quantitative traits for attention deficit hyperactivity disorder identifies novel associations and confirms candidate gene associations.
NHGRI GWA Catalog
Genome-wide association studies of pit-and-fissure- and smooth-surface caries in permanent dentition.
NHGRI GWA Catalog
Genome-wide association study of d-amphetamine response in healthy volunteers identifies putative associations, including cadherin 13 (CDH13).
NHGRI GWA Catalog
Genome-wide association study of maternal and inherited loci for conotruncal heart defects.
NHGRI GWA Catalog
Genome-wide association study of recurrent early-onset major depressive disorder.
NHGRI GWA Catalog
Genome-wide joint SNP and CNV analysis of aortic root diameter in African Americans: the HyperGEN study.
NHGRI GWA Catalog
Genome-wide mapping for clinically relevant predictors of lamotrigine- and phenytoin-induced hypersensitivity reactions.
NHGRI GWA Catalog
Genome-wide pharmacogenomic study of citalopram-induced side effects in STAR*D.
NHGRI GWA Catalog
Variants in several genomic regions associated with asperger disorder.
NHGRI GWA Catalog

HIV-1 interactions

Protein interactions

Protein Gene Interaction Pubs
Tat tat HIV-1 Tat-fused fragile histidine triad (FHIT) can robustly inhibit growth and induce apoptosis of human hepatocellular carcinoma cells PubMed

Go to the HIV-1, Human Interaction Database

Pathways from BioSystems

  • Non-small cell lung cancer, organism-specific biosystem (from KEGG)
    Non-small cell lung cancer, organism-specific biosystemLung cancer is a leading cause of cancer death among men and women in industrialized countries. Non-small-cell lung cancer (NSCLC) accounts for approximately 85% of lung cancer and represents a heter...
  • Non-small cell lung cancer, conserved biosystem (from KEGG)
    Non-small cell lung cancer, conserved biosystemLung cancer is a leading cause of cancer death among men and women in industrialized countries. Non-small-cell lung cancer (NSCLC) accounts for approximately 85% of lung cancer and represents a heter...
  • Purine metabolism, organism-specific biosystem (from KEGG)
    Purine metabolism, organism-specific biosystem
    Purine metabolism
  • Purine metabolism, conserved biosystem (from KEGG)
    Purine metabolism, conserved biosystem
    Purine metabolism
  • Small cell lung cancer, organism-specific biosystem (from KEGG)
    Small cell lung cancer, organism-specific biosystemLung cancer is a leading cause of cancer death among men and women in industrialized countries. Small cell lung carcinoma (SCLC) is a highly aggressive neoplasm, which accounts for approximately 25% ...
  • Small cell lung cancer, conserved biosystem (from KEGG)
    Small cell lung cancer, conserved biosystemLung cancer is a leading cause of cancer death among men and women in industrialized countries. Small cell lung carcinoma (SCLC) is a highly aggressive neoplasm, which accounts for approximately 25% ...

Interactions

Products Interactant Other Gene Complex Source Pubs Description

General gene information

Markers

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
bis(5'-adenosyl)-triphosphatase activity IDA
Inferred from Direct Assay
more info
PubMed 
catalytic activity TAS
Traceable Author Statement
more info
PubMed 
hydrolase activity IDA
Inferred from Direct Assay
more info
PubMed 
identical protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
nucleotide binding IEA
Inferred from Electronic Annotation
more info
 
protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
ubiquitin protein ligase binding IPI
Inferred from Physical Interaction
more info
PubMed 
Component Evidence Code Pubs
cytoplasm IDA
Inferred from Direct Assay
more info
PubMed 
cytosol IDA
Inferred from Direct Assay
more info
PubMed 
fibrillar center IDA
Inferred from Direct Assay
more info
 
mitochondrion IEA
Inferred from Electronic Annotation
more info
 
plasma membrane IDA
Inferred from Direct Assay
more info
 

General protein information

Preferred Names
bis(5'-adenosyl)-triphosphatase
Names
AP3A hydrolase
diadenosine 5',5'''-P1,P3-triphosphate hydrolase
dinucleosidetriphosphatase
NP_001159715.1
NP_001307828.1
NP_001307829.1
NP_001307830.1
NP_001341518.1
NP_001341519.1
NP_002003.1
XP_016861369.1
XP_016861370.1
XP_016861371.1
XP_016861372.1
XP_016861373.1
XP_016861374.1
XP_016861375.1

NCBI Reference Sequences (RefSeq)

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.

Genomic

  1. NG_007551.2 RefSeqGene

    Range
    4999..1509182
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_001166243.2NP_001159715.1  bis(5'-adenosyl)-triphosphatase isoform 1

    See identical proteins and their annotated locations for NP_001159715.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2), as well as variants 1, 3, and 4, encodes isoform 1.
    Source sequence(s)
    AC132808, BC032336, DB477833
    Consensus CDS
    CCDS2894.1
    UniProtKB/Swiss-Prot
    P49789
    UniProtKB/TrEMBL
    A0A024R366
    Related
    ENSP00000417557.1, OTTHUMP00000213128, ENST00000476844.5, OTTHUMT00000351424
    Conserved Domains (1) summary
    cd01275
    Location:5124
    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 ...
  2. NM_001320899.1NP_001307828.1  bis(5'-adenosyl)-triphosphatase isoform 1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3), as well as variants 1, 2, and 4, encodes isoform 1.
    Source sequence(s)
    AC132808, AK289824, DB477833
    Consensus CDS
    CCDS2894.1
    UniProtKB/Swiss-Prot
    P49789
    UniProtKB/TrEMBL
    A0A024R366
    Related
    ENSP00000417480.1, OTTHUMP00000213224, ENST00000468189.5, OTTHUMT00000351648
    Conserved Domains (1) summary
    cd01275
    Location:5124
    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 ...
  3. NM_001320900.1NP_001307829.1  bis(5'-adenosyl)-triphosphatase isoform 1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (4), as well as variants 1-3, encodes isoform 1.
    Source sequence(s)
    AC096917, AC097357, AC098480, AC099536, AC099780, AC132808, AC138071
    Consensus CDS
    CCDS2894.1
    UniProtKB/Swiss-Prot
    P49789
    UniProtKB/TrEMBL
    A0A024R366
    Conserved Domains (1) summary
    cd01275
    Location:5124
    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 ...
  4. NM_001320901.1NP_001307830.1  bis(5'-adenosyl)-triphosphatase isoform 2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (5) encodes a protein with a shorter N-terminus than isoform 1.
    Source sequence(s)
    AC099780, AC132808, BE246370, DB131595
    Conserved Domains (1) summary
    cl00228
    Location:468
    HIT_like; HIT family: HIT (Histidine triad) proteins, named for a motif related to the sequence HxHxH/Qxx (x, a hydrophobic amino acid), are a superfamily of nucleotide hydrolases and transferases, which act on the alpha-phosphate of ribonucleotides. On the basis ...
  5. NM_001354589.1NP_001341518.1  bis(5'-adenosyl)-triphosphatase isoform 3

    Status: REVIEWED

    Description
    Transcript Variant: This variant (7), as well as variant 8, encodes isoform 3.
    Source sequence(s)
    AC096917, AC097357, AC099536, AC099780, AC132808, AC138071
    Conserved Domains (1) summary
    cl00228
    Location:592
    HIT_like; HIT family: HIT (Histidine triad) proteins, named for a motif related to the sequence HxHxH/Qxx (x, a hydrophobic amino acid), are a superfamily of nucleotide hydrolases and transferases, which act on the alpha-phosphate of ribonucleotides. On the basis ...
  6. NM_001354590.1NP_001341519.1  bis(5'-adenosyl)-triphosphatase isoform 3

    Status: REVIEWED

    Description
    Transcript Variant: This variant (8), as well as variant 7, encodes isoform 3.
    Source sequence(s)
    AC096917, AC097357, AC099536, AC099780, AC132808, AC138071
    Conserved Domains (1) summary
    cl00228
    Location:592
    HIT_like; HIT family: HIT (Histidine triad) proteins, named for a motif related to the sequence HxHxH/Qxx (x, a hydrophobic amino acid), are a superfamily of nucleotide hydrolases and transferases, which act on the alpha-phosphate of ribonucleotides. On the basis ...
  7. NM_002012.3NP_002003.1  bis(5'-adenosyl)-triphosphatase isoform 1

    See identical proteins and their annotated locations for NP_002003.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) encodes the longest isoform (1). Variants 1-4 all encode the same isoform (1).
    Source sequence(s)
    AC132808, DB477833, U46922
    Consensus CDS
    CCDS2894.1
    UniProtKB/Swiss-Prot
    P49789
    UniProtKB/TrEMBL
    A0A024R366
    Related
    ENSP00000418582.1, OTTHUMP00000213225, ENST00000492590.5, OTTHUMT00000351649
    Conserved Domains (1) summary
    cd01275
    Location:5124
    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 ...

RNA

  1. NR_135491.1 RNA Sequence

    Status: REVIEWED

    Description
    Transcript Variant: This variant (6) is represented as non-coding because the predicted ORF does not meet RefSeq quality criteria.
    Source sequence(s)
    AC099780, AC132808, AK127931, BE246370
  2. NR_148921.1 RNA Sequence

    Status: REVIEWED

    Source sequence(s)
    AC096917, AC097357, AC104164, AC138071
  3. NR_148922.1 RNA Sequence

    Status: REVIEWED

    Source sequence(s)
    AC096917, AC097357, AC138071

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 109 details...Open this link in a new tab

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

Reference GRCh38.p12 Primary Assembly

Genomic

  1. NC_000003.12 Reference GRCh38.p12 Primary Assembly

    Range
    59747278..61251474 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_017005884.1XP_016861373.1  bis(5'-adenosyl)-triphosphatase isoform X4

  2. XM_017005883.1XP_016861372.1  bis(5'-adenosyl)-triphosphatase isoform X3

  3. XM_017005881.2XP_016861370.1  bis(5'-adenosyl)-triphosphatase isoform X1

  4. XM_017005882.2XP_016861371.1  bis(5'-adenosyl)-triphosphatase isoform X2

  5. XM_017005880.2XP_016861369.1  bis(5'-adenosyl)-triphosphatase isoform X1

  6. XM_017005885.2XP_016861374.1  bis(5'-adenosyl)-triphosphatase isoform X5

  7. XM_017005886.2XP_016861375.1  bis(5'-adenosyl)-triphosphatase isoform X5

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