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FHIT fragile histidine triad diadenosine triphosphatase [ Homo sapiens (human) ]

Gene ID: 2272, updated on 2-Nov-2024

Summary

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Official Symbol
FHITprovided by HGNC
Official Full Name
fragile histidine triad diadenosine triphosphataseprovided by HGNC
Primary source
HGNC:HGNC:3701
See related
Ensembl:ENSG00000189283 MIM:601153; AllianceGenome:HGNC:3701
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
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Genomic context

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See FHIT in Genome Data Viewer
Location:
3p14.2
Exon count:
17
Annotation release Status Assembly Chr Location
RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 3 NC_000003.12 (59747277..61251452, complement)
RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 3 NC_060927.1 (59787636..61294609, complement)
RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 3 NC_000003.11 (59733003..61237126, complement)

Chromosome 3 - NC_000003.12Genomic Context describing neighboring genes Neighboring gene CFAP20DC divergent transcript Neighboring gene Sharpr-MPRA regulatory region 3507 Neighboring gene ReSE screen-validated silencer GRCh37_chr3:59599597-59599768 Neighboring gene SNRPB2 pseudogene 1 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr3:59703433-59704161 Neighboring gene hCG1813818 Neighboring gene MED14-independent group 3 enhancer GRCh37_chr3:59784329-59785528 Neighboring gene H3K27ac hESC enhancer GRCh37_chr3:59793929-59794564 Neighboring gene H3K27ac hESC enhancer GRCh37_chr3:59795199-59795832 Neighboring gene H3K27ac hESC enhancer GRCh37_chr3:59795833-59796466 Neighboring gene P300/CBP strongly-dependent group 1 enhancer GRCh37_chr3:59803658-59804857 Neighboring gene uncharacterized LOC105377113 Neighboring gene uncharacterized LOC105377112 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 14494 Neighboring gene ReSE screen-validated silencer GRCh37_chr3:60040744-60040947 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 20017 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 20018 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 20019 Neighboring gene uncharacterized LOC107986015 Neighboring gene ReSE screen-validated silencer GRCh37_chr3:60349391-60349588 Neighboring gene origin of replication at fragile site FRA3B Neighboring gene NANOG hESC enhancer GRCh37_chr3:60645689-60646190 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr3:60657785-60658608 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr3:60655264-60656034 Neighboring gene MTERF1 pseudogene 1 Neighboring gene microRNA 548bb Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr3:60758024-60758879 Neighboring gene peptidylprolyl isomerase A pseudogene 70 Neighboring gene small nucleolar RNA U3 Neighboring gene TMED2 pseudogene 1 Neighboring gene P300/CBP strongly-dependent group 1 enhancer GRCh37_chr3:60921018-60922217 Neighboring gene MED14-independent group 3 enhancer GRCh37_chr3:60938928-60940127 Neighboring gene uncharacterized LOC124906244 Neighboring gene uncharacterized LOC105377111 Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chr3:61015791-61016990 Neighboring gene MED14-independent group 3 enhancer GRCh37_chr3:61027375-61028574 Neighboring gene Sharpr-MPRA regulatory region 1919 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr3:61127340-61127863 Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr3:61126817-61127339 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 20020 Neighboring gene Sharpr-MPRA regulatory region 15147 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 20022 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 20023 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 20024 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 20025 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 20026 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 20027 Neighboring gene Sharpr-MPRA regulatory region 9847 Neighboring gene uncharacterized LOC124909387 Neighboring gene uncharacterized LOC105377114 Neighboring gene uncharacterized LOC105377115 Neighboring gene Sharpr-MPRA regulatory region 1523

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: HPA RNA-seq normal tissues 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 Apr 4 07:08:55 2018

Bibliography

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Related articles in PubMed

  1. Fragile histidine triad (FHIT) gene is overexpressed in colorectal cancer. Wierzbicki PM, et al. J Physiol Pharmacol, 2009 Oct. PMID 20083853
  2. Association of 5'-CpG island hypermethylation of the FHIT gene with lung cancer in southern-central Chinese population. Li W, et al. Cancer Biol Ther, 2010 Nov 15. PMID 20814237
  3. Restoration of fragile histidine triad (FHIT) expression inhibits cell growth and induces apoptosis in cutaneous T-cell lymphoma cell line. Song X, et al. Cancer Invest, 2010 Dec. PMID 20690795
  4. Homozygous deletion but not mutation of exons 5 and 8 of the fragile histidine triad (FHIT) gene is associated with features of differentiated thyroid carcinoma. Yin DT, et al. Ann Clin Lab Sci, 2010 Summer. PMID 20689140
  5. Contig array CGH at 3p14.2 points to the FRA3B/FHIT common fragile region as the target gene in diffuse large B-cell lymphoma. Kameoka Y, et al. Oncogene, 2004 Dec 2. PMID 15480422

See all (356) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Integrated analysis of FHIT gene alterations in cancer.
    Title: Integrated analysis of FHIT gene alterations in cancer.
  2. Expression of Tumor Suppressor FHIT Is Regulated by the LINC00173-SNAIL Axis in Human Lung Adenocarcinoma.
    Title: Expression of Tumor Suppressor FHIT Is Regulated by the LINC00173-SNAIL Axis in Human Lung Adenocarcinoma.
  3. The Rosetta Stone Hypothesis-Based Interaction of the Tumor Suppressor Proteins Nit1 and Fhit.
    Title: The Rosetta Stone Hypothesis-Based Interaction of the Tumor Suppressor Proteins Nit1 and Fhit.
  4. Investigation of the expression levels of CDH1, FHIT, PTEN, and TTPAL genes in colorectal tumors.
    Title: Investigation of the expression levels of CDH1, FHIT, PTEN, and TTPAL genes in colorectal tumors.
  5. System analysis of FHIT in LUAD and LUSC: The expression, prognosis, gene regulation network, and regulation targets.
    Title: System analysis of FHIT in LUAD and LUSC: The expression, prognosis, gene regulation network, and regulation targets.
  6. Germinal epimutation of Fragile Histidine Triad (FHIT) gene is associated with progression to acute and chronic adult T-cell leukemia diseases.
    Title: Germinal epimutation of Fragile Histidine Triad (FHIT) gene is associated with progression to acute and chronic adult T-cell leukemia diseases.
  7. rs73092672 allele T is significantly associated with the higher risk of breast cancer incidence.
    Title: rs73092672 allele T is significantly associated with the higher risk of breast cancer incidence.
  8. Locus-specific transcription silencing at the FHIT gene suppresses replication stress-induced copy number variant formation and associated replication delay.
    Title: Locus-specific transcription silencing at the FHIT gene suppresses replication stress-induced copy number variant formation and associated replication delay.
  9. Fhit induces the reciprocal suppressions between Lin28/Let-7 and miR-17/92miR.
    Title: Fhit induces the reciprocal suppressions between Lin28/Let-7 and miR-17/92miR.
  10. Relationship between Methylation of FHIT and CDH13 Gene Promoter Region and Liver Cancer.
    Title: Relationship between Methylation of FHIT and CDH13 Gene Promoter Region and Liver Cancer.
Submit: New GeneRIF Correction See all GeneRIFs (270)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

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

EBI GWAS Catalog

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

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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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 PubChem

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Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables adenosine 5'-monophosphoramidase activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables adenylylsulfatase activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables adenylylsulfate-ammonia adenylyltransferase activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables bis(5'-adenosyl)-triphosphatase activity IBA
Inferred from Biological aspect of Ancestor
more info
  
enables bis(5'-adenosyl)-triphosphatase activity IDA
Inferred from Direct Assay
more info
 PubMed 
enables identical protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables nucleotide binding IEA
Inferred from Electronic Annotation
more info
  
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables ubiquitin protein ligase binding IBA
Inferred from Biological aspect of Ancestor
more info
  
enables ubiquitin protein ligase binding IPI
Inferred from Physical Interaction
more info
 PubMed 
Process Evidence Code Pubs
involved_in diadenosine triphosphate catabolic process IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in diadenosine triphosphate catabolic process IDA
Inferred from Direct Assay
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 IMP
Inferred from Mutant Phenotype
more info
 PubMed 
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 IMP
Inferred from Mutant Phenotype
more info
 PubMed 
involved_in purine nucleotide metabolic process IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in purine nucleotide metabolic process IDA
Inferred from Direct Assay
more info
 PubMed 
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 cytosol IDA
Inferred from Direct Assay
more info
 PubMed 
located_in fibrillar center IDA
Inferred from Direct Assay
more info
  
located_in mitochondrion HTP PubMed 
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 IDA
Inferred from Direct Assay
more info
  

General protein information

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Preferred Names
bis(5'-adenosyl)-triphosphatase
Names
AP3A hydrolase
adenosine 5'-monophosphoramidase FHIT
adenylylsulfatase
adenylylsulfate-ammonia adenylyltransferase
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

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.

Genomic

  1. NG_007551.2 RefSeqGene

    Range
    5008..1509183
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_001166243.3 → NP_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
    A2IAS9, A2IAT0, A2IAT6, A8K1A9, P49789, Q45QG9, Q6IU12
    Related
    ENSP00000417557.1, ENST00000476844.5
    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 ...

  2. NM_001320899.2 → NP_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
    A2IAS9, A2IAT0, A2IAT6, A8K1A9, P49789, Q45QG9, Q6IU12
    Related
    ENSP00000417480.1, ENST00000468189.5
    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 ...

  3. NM_001320900.2 → NP_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
    A2IAS9, A2IAT0, A2IAT6, A8K1A9, P49789, Q45QG9, Q6IU12
    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 ...

  4. NM_001320901.2 → NP_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)
    AC132808, BE246370, DB131595
    Conserved Domains (1) summary
    cl00228
    Location:4 → 68
    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_001354589.2 → NP_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:5 → 92
    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_001354590.2 → NP_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:5 → 92
    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_002012.4 → NP_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
    A2IAS9, A2IAT0, A2IAT6, A8K1A9, P49789, Q45QG9, Q6IU12
    Related
    ENSP00000418582.1, ENST00000492590.6
    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 ...

RNA

  1. NR_135491.2 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_148921.2 RNA Sequence

    Status: REVIEWED

    Source sequence(s)
    AC096917, AC097357, AC104164, AC138071

  3. NR_148922.2 RNA Sequence

    Status: REVIEWED

    Source sequence(s)
    AC096917, AC097357, AC138071

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

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

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000003.12 Reference GRCh38.p14 Primary Assembly

    Range
    59747277..61251452 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060927.1 Alternate T2T-CHM13v2.0

    Range
    59787636..61294609 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
P49789.3 GenPept UniProtKB/Swiss-Prot:P49789

Gene LinkOut

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