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Huntington's disease [HD] protein (huntingtin) or IT15 protein

Function: - basically unknown, involved in: a) clathrin mediated endocytosis b) vesicle transport processes in axons c) post-synaptic density organization d) dendrite morphology e) transcriptional regulation f) anti-apoptosis - interactions [6]: a) huntingtin interacting protein 1 - interaction inhibited by triplet CAG expansion b) huntingtin associated protein 1 - interaction enhanced by triplet CAG expansion c) protein kinase C & casein kinase substrate in neurons 1 d) PSD-95 e) p53 f) NF kappa B g) grb2 h) RasGAP i) Sin3A j) Sp1 k) alpha-adaptin C l) SH3GL3 m) Fip2 n) CBP o) Akt/PKB p) RASD2 (Rhes) Expression: - widely expressed in brain & peripheral tissues - expressed in neurons & to a lesser extent glia throughout the brain Pathology: - trinucleotide repeat expansion of the triplet CAG in gene for huntingtin seen in Huntington's disease; mutant huntingtin thus contains a repeat expansion of 30-200 glutamine residues (Gln) - neuronal damage in Huntinton disease may be related to nuclear translocation of the N-terminal fragment of huntintin in association with GAPDH [8] - RASD2 (Rhes)- dependent sumoylation of huntingtin renders huntingtin cytotoxic; striatal-specific expression of RASD2 may expain specificity of Huntington's disease pathology for striatum [9] Laboratory: - HTT genotyping - HTT gene CAG repeats - HTT gene mutation Comparative biology: - huntingtin gene inactivation in mice causes early embryonic lethality - developmental abnormalities associated with reduced levels are most prominant in forebrain & midbrain - mice with CAG expanded huntingtin did not show these abnormalities [5]

Related

histone-lysine N-methyltransferase SETD2 (SET domain-containing protein 2, hSET2, Huntingtin-interacting protein HYPB, Huntingtin yeast partner B, Huntingtin-interacting protein 1, HIF-1, p231HBP, SETD2, HIF1, HYPB, KIAA1732, SET2, HSPC069) huntingtin-associated protein 1; HAP-1; neuroan 1 (HAP1, HAP2, HLP1) huntingtin-interacting protein 1; HIP-1 (HIP1) huntingtin-interacting protein HYPM (huntingtin yeast partner M, CXorf27, HYPM) Huntington's disease; Huntington's chorea (progressive hereditary chorea) Interesting Transcript 15 gene (IT15) or Huntingtin gene palmitoyltransferase ZDHHC13 (zinc finger DHHC domain-containing protein 13, DHHC-13, huntingtin-interacting protein 14-related protein, HIP14-related protein, huntingtin-interacting protein HIP3RP, NF-kappa-B-activating protein 209, MAPK-activating protein PM03ZDHHC13, ZDHHC13, HIP14L, HIP3RP) palmitoyltransferase ZDHHC17 (zinc finger DHHC domain-containing protein 17, DHHC-17, huntingtin-interacting protein 14, huntingtin-interacting protein 3, huntingtin-interacting protein HYPH, NF-kappa-B-activating protein 205, MAPK-activating protein PM11, ZDHHC17, HIP14, HIP3, KIAA0946, HSPC294) trinucleotide repeat (expansion)

General

other protein

Properties

COMPARTMENT: cytoplasm CELL: neuron MOTIF: glutamine-rich region {18-40} MOTIF: glutamine residue (23) proline residue {41-51} (11) proline residue {65-80} (16) HEAT repeat {205-329} proteolytic site {513-514} proteolytic site {530-531} proteolytic site {552-553} proteolytic site {589-590} HEAT repeat {745-942} glutamate residue {2343-2347} (5) glutamate residue {2640-2645} (6) leucine zipper FOR-BINDING-VIA: leucine zipper LEUCINES: 4

Database Correlations

OMIM 143100 UniProt P42858 Entrez Gene 3064

References

  1. HD Collaborative A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington's disease chromosomes. The Huntington's Disease Collaborative Research Group. Cell. 1993 Mar 26;72(6):971-83. PMID: 8458085
  2. Morell V. Huntington's gene finally found. Science. 1993 Apr 2;260(5104):28-30. No abstract available. PMID: 8465196
  3. Little P. Huntington's disease. The end of the beginning. Nature. 1993 Apr 1;362(6419):408-9. No abstract available. PMID: 8464469
  4. Ross CA, McInnis MG, Margolis RL, Li SH. Genes with triplet repeats: candidate mediators of neuropsychiatric disorders. Trends Neurosci. 1993 Jul;16(7):254-60. Review. PMID: 7689767
  5. White JK, Auerbach W, Duyao MP, Vonsattel JP, Gusella JF, Joyner AL, MacDonald ME. Huntingtin is required for neurogenesis and is not impaired by the Huntington's disease CAG expansion. Nat Genet. 1997 Dec;17(4):404-10. PMID: 9398841
  6. Harjes P, Wanker EE. The hunt for huntingtin function: interaction partners tell many different stories. Trends Biochem Sci. 2003 Aug;28(8):425-33. Review. PMID: 12932731
  7. Entrez Gene :accession 3064
  8. Sedlak TW, Snyder SH. Messenger molecules and cell death: therapeutic implications. JAMA. 2006 Jan 4;295(1):81-9. PMID: 16391220
  9. Subramaniam S et al Rhes, a Striatal Specific Protein, Mediates Mutant- Huntingtin Cytotoxicity Science. 2009 Jun 5;324(5932):1327-1330. PMID: 19498170 DOI: 10.1126/science.1172871

Component-of

diphenhydramine/huntingtin/hydrocodone/phenylephrine