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

Summary

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

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_000009.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

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Expression

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See details

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 Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

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.
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.
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.
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.
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.
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.
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.
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.
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.
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)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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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 more info	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)

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

NC_000009.12 Reference GRCh38.p14 Primary Assembly

Range

35812960..35815479 complement

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

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 ...
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 ...
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

NC_060933.1 Alternate T2T-CHM13v2.0

Range

35833627..35836146 complement

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_054364017.1 → XP_054219992.1 adenosine 5'-monophosphoramidase HINT2 isoform X1
XM_054364018.1 → XP_054219993.1 adenosine 5'-monophosphoramidase HINT2 isoform X2
XM_054364019.1 → XP_054219994.1 adenosine 5'-monophosphoramidase HINT2 isoform X3