HINT1

Last updated
HINT1
Protein HINT1 PDB 1av5.png
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases HINT1 , HINT, NMAN, PKCI-1, PRKCNH1, histidine triad nucleotide binding protein 1
External IDs OMIM: 601314 MGI: 1321133 HomoloGene: 3904 GeneCards: HINT1
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_005340

NM_008248

RefSeq (protein)

NP_005331

NP_032274

Location (UCSC) Chr 5: 131.16 – 131.22 Mb Chr 11: 54.87 – 54.87 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Histidine triad nucleotide-binding protein 1 also known as adenosine 5'-monophosphoramidase is an enzyme that in humans is encoded by the HINT1 gene. [5] [6]

HINT1 hydrolyzes purine nucleotide phosphoramidates with a single phosphate group. [7] In addition, functions as scaffolding protein that modulates transcriptional activation. [8]

It is a haploinsufficient tumor suppressor gene that inhibits the Wnt/β-catenin pathway in colon cancer cells and microphthalmia-associated transcription factor (MITF) activity in human mast cells. [9] [10] In the LysRS-Ap4A-MITF signaling pathway, HINT1 inhibits the MITF transcriptional activity by direct association. Upon pathway activation, HINT1 is released from MITF by diadenosine tetraphosphate (Ap4A), produced by LysRS. [10] [11]

See also

Related Research Articles

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ACVR1C

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Cyclin-dependent kinase 4 Human protein

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Transforming protein RhoA Protein-coding gene in the species Homo sapiens

Transforming protein RhoA, also known as Ras homolog family member A (RhoA), is a small GTPase protein in the Rho family of GTPases that in humans is encoded by the RHOA gene. While the effects of RhoA activity are not all well known, it is primarily associated with cytoskeleton regulation, mostly actin stress fibers formation and actomyosin contractility. It acts upon several effectors. Among them, ROCK1 and DIAPH1 are the best described. RhoA, and the other Rho GTPases, are part of a larger family of related proteins known as the Ras superfamily, a family of proteins involved in the regulation and timing of cell division. RhoA is one of the oldest Rho GTPases, with homologues present in the genomes since 1.5 billion years. As a consequence, RhoA is somehow involved in many cellular processes which emerged throughout evolution. RhoA specifically is regarded as a prominent regulatory factor in other functions such as the regulation of cytoskeletal dynamics, transcription, cell cycle progression and cell transformation.

Histidine kinase

Histidine kinases (HK) are multifunctional, and in non-animal kingdoms, typically transmembrane, proteins of the transferase class of enzymes that play a role in signal transduction across the cellular membrane. The vast majority of HKs are homodimers that exhibit autokinase, phosphotransfer, and phosphatase activity. HKs can act as cellular receptors for signaling molecules in a way analogous to tyrosine kinase receptors (RTK). Multifunctional receptor molecules such as HKs and RTKs typically have portions on the outside of the cell that bind to hormone- or growth factor-like molecules, portions that span the cell membrane, and portions within the cell that contain the enzymatic activity. In addition to kinase activity, the intracellular domains typically have regions that bind to a secondary effector molecule or complex of molecules that further propagate signal transduction within the cell. Distinct from other classes of protein kinases, HKs are usually parts of a two-component signal transduction mechanisms in which HK transfers a phosphate group from ATP to a histidine residue within the kinase, and then to an aspartate residue on the receiver domain of a response regulator protein. More recently, the widespread existence of protein histidine phosphorylation distinct from that of two-component histidine kinases has been recognised in human cells. In marked contrast to Ser, Thr and Tyr phosphorylation, the analysis of phosphorylated Histidine using standard biochemical and mass spectrometric approaches is much more challenging, and special procedures and separation techniques are required for their preservation alongside classical Ser, Thr and Tyr phosphorylation on proteins isolated from human cells.

PIM1

Proto-oncogene serine/threonine-protein kinase Pim-1 is an enzyme that in humans is encoded by the PIM1 gene.

PRKCH

Protein kinase C eta type is an enzyme that in humans is encoded by the PRKCH gene.

DYRK1A Protein-coding gene in the species Homo sapiens

Dual specificity tyrosine-phosphorylation-regulated kinase 1A is an enzyme that in humans is encoded by the DYRK1A gene. Alternative splicing of this gene generates several transcript variants differing from each other either in the 5' UTR or in the 3' coding region. These variants encode at least five different isoforms.

IKBKE

Inhibitor of nuclear factor kappa-B kinase subunit epsilon also known as I-kappa-B kinase epsilon or IKK-epsilon is an enzyme that in humans is encoded by the IKBKE gene.

TNK2

Activated CDC42 kinase 1, also known as ACK1, is an enzyme that in humans is encoded by the TNK2 gene. TNK2 gene encodes a non-receptor tyrosine kinase, ACK1, that binds to multiple receptor tyrosine kinases e.g. EGFR, MERTK, AXL, HER2 and insulin receptor (IR). ACK1 also interacts with Cdc42Hs in its GTP-bound form and inhibits both the intrinsic and GTPase-activating protein (GAP)-stimulated GTPase activity of Cdc42Hs. This binding is mediated by a unique sequence of 47 amino acids C-terminal to an SH3 domain. The protein may be involved in a regulatory mechanism that sustains the GTP-bound active form of Cdc42Hs and which is directly linked to a tyrosine phosphorylation signal transduction pathway. Several alternatively spliced transcript variants have been identified from this gene, but the full-length nature of only two transcript variants has been determined.

ARHGEF6

Rho guanine nucleotide exchange factor 6 is a protein that, in humans, is encoded by the ARHGEF6 gene.

PIAS3

E3 SUMO-protein ligase PIAS3 is an enzyme that in humans is encoded by the PIAS3 gene.

KARS (gene)

Lysyl-tRNA synthetase is an enzyme that in humans is encoded by the KARS gene.

MKNK1

MAP kinase-interacting serine/threonine-protein kinase 1 is an enzyme that in humans is encoded by the MKNK1 gene.

NUAK1

NUAK family SNF1-like kinase 1 also known as AMPK-related protein kinase 5 (ARK5) is an enzyme that in humans is encoded by the NUAK1 gene.

GNA11

Guanine nucleotide-binding protein subunit alpha-11 is a protein that in humans is encoded by the GNA11 gene. Together with GNAQ, it functions as a Gq alpha subunit.

TFAP2C

Transcription factor AP-2 gamma also known as AP2-gamma is a protein that in humans is encoded by the TFAP2C gene. AP2-gamma is a member of the activating protein 2 family of transcription factors.

Diadenosine tetraphosphate or Ap4A is a putative alarmone, ubiquitous in nature being common to everything from bacteria to humans. It is made up of two adenosines joined together by a 5′-5′ linked chain of four phosphates. Adenosine polyphosphates are capable of inducing multiple physiological effects.

HINT2

Histidine triad nucleotide binding protein 2 (HINT2) is a mitochondrial protein that in humans is encoded by the HINT2 gene on chromosome 9. This protein is an AMP-lysine hydrolase and phosphoamidase and may contribute to tumor suppression.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000169567 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000020267 - Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. Brzoska PM, Chen H, Levin NA, Kuo WL, Collins C, Fu KK, Gray JW, Christman MF (Feb 1997). "Cloning, mapping, and in vivo localization of a human member of the PKCI-1 protein family (PRKCNH1)". Genomics. 36 (1): 151–6. doi:10.1006/geno.1996.0435. PMID   8812426.
  6. "Entrez Gene: HINT1 histidine triad nucleotide binding protein 1".
  7. Strom A, Tong CL, Wagner CR (May 2020). "Histidine triad nucleotide-binding proteins HINT1 and HINT2 share similar substrate specificities and little affinity for the signaling dinucleotide Ap4A". FEBS Letters. 594 (10): 1497–1505. doi:10.1002/1873-3468.13745. PMID   31990367. S2CID   210933742.
  8. "P49773: HINT1 (human)". UniProt.
  9. Wang L, Li H, Zhang Y, Santella RM, Weinstein IB (Apr 2009). "HINT1 inhibits beta-catenin/TCF4, USF2 and NFkappaB activity in human hepatoma cells". Int J Cancer. 124 (7): 1526–34. doi:10.1002/ijc.24072. PMC   2667231 . PMID   19089909.
  10. 1 2 Lee YN, Nechushtan H, Figov N, Razin E (Feb 2004). "The function of lysyl-tRNA synthetase and Ap4A as signaling regulators of MITF activity in FcepsilonRI-activated mast cells". Immunity. 20 (2): 145–51. doi: 10.1016/S1074-7613(04)00020-2 . PMID   14975237.
  11. Yannay-Cohen N, Carmi-Levy I, Kay G, Yang CM, Han JM, Kemeny DM, Kim S, Nechushtan H, Razin E (June 2009). "LysRS serves as a key signaling molecule in the immune response by regulating gene expression". Mol Cell. 34 (5): 603–11. doi: 10.1016/j.molcel.2009.05.019 . PMID   19524539.

Further reading