Huntingtin (HTT)

IT15; HD; Interesting Transcript 15; Huntington disease protein

SPN	O826
HGNC	4851
MGI	96067
PubMed	19748341
RGD	68337
UniProt	P42858
Wiki	Huntingtin

Huntingtin has no sequence homology with other proteins and is highly expressed in neurons and testes in humans and rodents. Huntingtin upregulates the expression of Brain Derived Neurotrophic Factor (BDNF) at the transcription level but the mechanism by which huntingtin regulated gene expression has not been determined. From immunohistochemistry, electron microscopy, and subcellular fractionation studies of the molecule, it has been found that huntingtin is primarily associated with vesicles and microtubules. These appear to indicate a functional role in cytoskeletal anchoring or transport of mitochondria. The Htt protein is involved in vesicle trafficking as it interacts with HIP1, a clathrin binding protein, to mediate endocytosis, the absorption of materials into a cell.

Reference

"A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington's disease chromosomes."
Cell 72:971-983(1993) [PubMed] [Europe PMC] [Abstract]

"Identification and characterization of the miniature pig Huntington's disease gene homolog: evidence for conservation and polymorphism in the CAG triplet repeat."
Genomics 69:72-85(2000) [PubMed] [Europe PMC] [Abstract]

"Generation and annotation of the DNA sequences of human chromosomes 2 and 4."
Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract]

"Structure and expression of the Huntington's disease gene: evidence against simple inactivation due to an expanded CAG repeat."
Somat. Cell Mol. Genet. 20:27-38(1994) [PubMed] [Europe PMC] [Abstract]

"Structural analysis of the 5' region of mouse and human Huntington disease genes reveals conservation of putative promoter region and di- and trinucleotide polymorphisms."
Genomics 25:707-715(1995) [PubMed] [Europe PMC] [Abstract]

"Differential 3' polyadenylation of the Huntington disease gene results in two mRNA species with variable tissue expression."
Hum. Mol. Genet. 2:1541-1545(1993) [PubMed] [Europe PMC] [Abstract]

"Cellular localization of the Huntington's disease protein and discrimination of the normal and mutated form."
Nat. Genet. 10:104-110(1995) [PubMed] [Europe PMC] [Abstract]

"Cleavage of huntingtin by apopain, a proapoptotic cysteine protease, is modulated by the polyglutamine tract."
Nat. Genet. 13:442-449(1996) [PubMed] [Europe PMC] [Abstract]

"Huntingtin interacts with a family of WW domain proteins."
Hum. Mol. Genet. 7:1463-1474(1998) [PubMed] [Europe PMC] [Abstract]

"PQBP-1, a novel polyglutamine tract binding protein, inhibits transcription activation by Brn-2 and affects cell survival."
Hum. Mol. Genet. 8:977-987(1999) [PubMed] [Europe PMC] [Abstract]

"Huntingtin's WW domain partners in Huntington's disease post-mortem brain fulfill genetic criteria for direct involvement in Huntington's disease pathogenesis."
Hum. Mol. Genet. 9:2175-2182(2000) [PubMed] [Europe PMC] [Abstract]

"Identification of the full-length huntingtin-interacting protein p231HBP/HYPB as a DNA-binding factor."
Mol. Cell. Neurosci. 18:68-79(2001) [PubMed] [Europe PMC] [Abstract]

"Huntingtin contains a highly conserved nuclear export signal."
Hum. Mol. Genet. 12:1393-1403(2003) [PubMed] [Europe PMC] [Abstract]

"Polyglutamine expansion of huntingtin impairs its nuclear export."
Nat. Genet. 37:198-204(2005) [PubMed] [Europe PMC] [Abstract]

"Interaction of the nuclear matrix protein NAKAP with HypA and huntingtin: implications for nuclear toxicity in Huntington's disease pathogenesis."
NeuroMolecular Med. 7:297-310(2005) [PubMed] [Europe PMC] [Abstract]

"Ubiquitin ligase Hrd1 enhances the degradation and suppresses the toxicity of polyglutamine-expanded huntingtin."
Exp. Cell Res. 313:538-550(2007) [PubMed] [Europe PMC] [Abstract]

"Phosphorylation of huntingtin by cyclin-dependent kinase 5 is induced by DNA damage and regulates wild-type and mutant huntingtin toxicity in neurons."
J. Neurosci. 27:7318-7328(2007) [PubMed] [Europe PMC] [Abstract]

"Phosphoproteome of resting human platelets."
J. Proteome Res. 7:526-534(2008) [PubMed] [Europe PMC] [Abstract]

"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle."
Mol. Cell 31:438-448(2008) [PubMed] [Europe PMC] [Abstract]

"Phosphorylation of profilin by ROCK1 regulates polyglutamine aggregation."
Mol. Cell. Biol. 28:5196-5208(2008) [PubMed] [Europe PMC] [Abstract]

"A quantitative atlas of mitotic phosphorylation."
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]

"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach."
Anal. Chem. 81:4493-4501(2009) [PubMed] [Europe PMC] [Abstract]

"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions."
Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract]

"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis."
Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract]

"Initial characterization of the human central proteome."
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]

"Mass spectrometric identification of novel lysine acetylation sites in huntingtin."
Mol. Cell. Proteomics 0:0-0(2011) [PubMed] [Europe PMC] [Abstract]

"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation."
Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract]

"An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome."
J. Proteomics 96:253-262(2014) [PubMed] [Europe PMC] [Abstract]

"Secondary structure of Huntingtin amino-terminal region."
Structure 17:1205-1212(2009) [PubMed] [Europe PMC] [Abstract]