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    HINT2 histidine triad nucleotide binding protein 2 [ Homo sapiens (human) ]

    Gene ID: 84681, updated on 2-Nov-2024

    Summary

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    Official Symbol
    HINT2provided by HGNC
    Official Full Name
    histidine triad nucleotide binding protein 2provided by HGNC
    Primary source
    HGNC:HGNC:18344
    See related
    Ensembl:ENSG00000137133 MIM:609997; AllianceGenome:HGNC:18344
    Gene type
    protein coding
    RefSeq status
    VALIDATED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    HIT-17
    Summary
    Histidine triad proteins, such as HINT2, are nucleotide hydrolases and transferases that act on the alpha-phosphate of ribonucleotides (Brenner, 2002 [PubMed 12119013]).[supplied by OMIM, Mar 2008]
    Expression
    Ubiquitous expression in kidney (RPKM 37.3), fat (RPKM 32.0) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See HINT2 in Genome Data Viewer
    Location:
    9p13.3
    Exon count:
    6
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 9 NC_000009.12 (35812960..35815479, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 9 NC_060933.1 (35833627..35836146, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 9 NC_000009.11 (35812957..35815039, complement)

    Chromosome 9 - NC_000009.12Genomic Context describing neighboring genes Neighboring gene MED14-independent group 3 enhancer GRCh37_chr9:35752887-35754086 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 19879 Neighboring gene RGP1 homolog, RAB6A GEF complex partner 1 Neighboring gene microseminoprotein, prostate associated Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 19880 Neighboring gene natriuretic peptide receptor 2 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr9:35811777-35812333 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 19881 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 28338 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 19882 Neighboring gene sperm associated antigen 8 Neighboring gene family with sequence similarity 221 member B Neighboring gene ATAC-STARR-seq lymphoblastoid active region 28339 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 19883 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr9:35829817-35830317 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr9:35835675-35836588 Neighboring gene transmembrane protein 8B Neighboring gene ATAC-STARR-seq lymphoblastoid active region 28340 Neighboring gene Sharpr-MPRA regulatory region 825 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr9:35846373-35847248 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 28341 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 28342 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 28343 Neighboring gene olfactory receptor family 13 subfamily E member 1 pseudogene

    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. Histidine triad nucleotide-binding protein 2: From basic science to clinical implications. Yao J, et al. Biochem Pharmacol, 2023 Jun. PMID 37004779
    2. Hint2, a mitochondrial apoptotic sensitizer down-regulated in hepatocellular carcinoma. Martin J, et al. Gastroenterology, 2006 Jun. PMID 16762638, Free PMC Article
    3. Structural characterization of human histidine triad nucleotide-binding protein 2, a member of the histidine triad superfamily. Maize KM, et al. FEBS J, 2013 Jul. PMID 23659632, Free PMC Article
    4. Biochemical, crystallographic and biophysical characterization of histidine triad nucleotide-binding protein 2 with different ligands including a non-hydrolyzable analog of Ap4A. Dolot R, et al. Biochim Biophys Acta Gen Subj, 2021 Nov. PMID 34329705
    5. HINT2 downregulation promotes colorectal carcinoma migration and metastasis. Li W, et al. Oncotarget, 2017 Feb 21. PMID 28088787, Free PMC Article

    See all (42) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Histidine triad nucleotide-binding protein 2: From basic science to clinical implications.
      Title: Histidine triad nucleotide-binding protein 2: From basic science to clinical implications.
    2. Biochemical, crystallographic and biophysical characterization of histidine triad nucleotide-binding protein 2 with different ligands including a non-hydrolyzable analog of Ap4A.
      Title: Biochemical, crystallographic and biophysical characterization of histidine triad nucleotide-binding protein 2 with different ligands including a non-hydrolyzable analog of Ap4A.
    3. Histidine triad nucleotide-binding proteins HINT1 and HINT2 share similar substrate specificities and little affinity for the signaling dinucleotide Ap4A.
      Title: Histidine triad nucleotide-binding proteins HINT1 and HINT2 share similar substrate specificities and little affinity for the signaling dinucleotide Ap4A.
    4. Multivariate analyses revealed that tumor size and HINT2 expression are risk factors for Hepatocellular carcinoma recurrence. HINT2 is down-regulated in Hepatocellular carcinoma, and low HINT2 expression predicts earlier tumor recurrence. HINT2 expression may serve as a prognostic indicator of recurrence in Hepatocellular carcinoma.
      Title: Clinical significance of down-regulated HINT2 in hepatocellular carcinoma.
    5. Decreased electron transfer and oxidative phosphorylation capacity in the absence of HINT-2.
      Title: The histidine triad nucleotide-binding protein 2 (HINT-2) positively regulates hepatocellular energy metabolism.
    6. Authors deduced that HINT2 triggers apoptosis in pancreatic cancer cells by regulating mitochondrial Ca(2+) influx through the mitochondrial calcium uniporter (MCU). Authors found that HINT2 can sensitize BxPC-3 and L3.6pl cells to gemcitabine-induced apoptosis and that gemcitabine up-regulates HINT2 expression.
      Title: HINT2 triggers mitochondrial Ca(2+) influx by regulating the mitochondrial Ca(2+) uniporter (MCU) complex and enhances gemcitabine apoptotic effect in pancreatic cancer.
    7. HINT2 downregulation depended on hypoxia inducible factor (HIF)-2alpha-mediated transcriptional activation of zinc finger E-box-binding homeobox 1 (ZEB1). These results suggest that HINT2 downregulation promotes HIF-2alpha expression, which induces EMT and enhances CRC cell migration and invasion.
      Title: HINT2 downregulation promotes colorectal carcinoma migration and metastasis.
    8. Low HINT2 expression is associated with low response to therapy in endometrial cancer.
      Title: Progesterone enhances calcitriol antitumor activity by upregulating vitamin D receptor expression and promoting apoptosis in endometrial cancer cells.
    9. X-ray crystal structure of human HINT2 with and without bound AMP.
      Title: Structural characterization of human histidine triad nucleotide-binding protein 2, a member of the histidine triad superfamily.
    10. Observational study of gene-disease association. (HuGE Navigator)
      Title: Genetic variants in nuclear-encoded mitochondrial genes influence AIDS progression.
    Submit: New GeneRIF Correction See all GeneRIFs (11)

    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

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Genotypes

    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 hydrolase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables nucleotide binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in apoptotic process IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in lipid catabolic process IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in negative regulation of peptidyl-lysine acetylation IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in steroid biosynthetic process IEA
    Inferred from Electronic Annotation
    more info
    		  
    Component Evidence Code Pubs
    is_active_in cytoplasm IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in mitochondrial matrix IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in mitochondrial outer membrane TAS
    Traceable Author Statement
    more info
    		  
    located_in mitochondrion HTP PubMed 
    is_active_in mitochondrion IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in mitochondrion IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in mitochondrion ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  

    General protein information

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    Preferred Names
    adenosine 5'-monophosphoramidase HINT2
    Names
    HINT-2
    HINT-3
    HIT-17kDa
    PKCI-1-related HIT protein
    histidine triad nucleotide-binding protein 2, mitochondrial
    protein kinase C inhibitor-2

    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)

    1. NM_032593.3 → NP_115982.1  adenosine 5'-monophosphoramidase HINT2 precursor

      See identical proteins and their annotated locations for NP_115982.1

      Status: VALIDATED

      Source sequence(s)
      BC047737, BI759951, BM764627
      Consensus CDS
      CCDS6594.1
      UniProtKB/Swiss-Prot
      Q5TCW3, Q9BX68
      UniProtKB/TrEMBL
      Q53HJ8
      Related
      ENSP00000259667.5, ENST00000259667.6
      Conserved Domains (1) summary
      cd01276
      Location:53 → 155
      PKCI_related; Protein Kinase C Interacting protein related (PKCI): PKCI and related proteins belong to the ubiquitous HIT family of hydrolases that act on alpha-phosphates of ribonucleotides. The members of this subgroup have a conserved HxHxHxx motif (x is a ...

    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_000009.12 Reference GRCh38.p14 Primary Assembly

      Range
      35812960..35815479 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_024447702.2 → XP_024303470.1  adenosine 5'-monophosphoramidase HINT2 isoform X1

      Conserved Domains (1) summary
      cd01276
      Location:55 → 157
      PKCI_related; Protein Kinase C Interacting protein related (PKCI): PKCI and related proteins belong to the ubiquitous HIT family of hydrolases that act on alpha-phosphates of ribonucleotides. The members of this subgroup have a conserved HxHxHxx motif (x is a ...

    2. XM_024447703.1 → XP_024303471.1  adenosine 5'-monophosphoramidase HINT2 isoform X2

      Conserved Domains (1) summary
      cl00228
      Location:55 → 135
      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 ...

    3. XM_024447704.2 → XP_024303472.1  adenosine 5'-monophosphoramidase HINT2 isoform X3

      UniProtKB/TrEMBL
      Q53HJ8
      Related
      ENST00000461169.1
      Conserved Domains (1) summary
      cl00228
      Location:53 → 133
      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 ...

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060933.1 Alternate T2T-CHM13v2.0

      Range
      35833627..35836146 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054364017.1 → XP_054219992.1  adenosine 5'-monophosphoramidase HINT2 isoform X1

    2. XM_054364018.1 → XP_054219993.1  adenosine 5'-monophosphoramidase HINT2 isoform X2

    3. XM_054364019.1 → XP_054219994.1  adenosine 5'-monophosphoramidase HINT2 isoform X3

    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q9BX68.1 GenPept UniProtKB/Swiss-Prot:Q9BX68

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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