Reactome: A Curated Pathway Database
THIS SITE IS USED FOR CURATION AND TESTING
IT IS NOT STABLE, IS LINKED TO AN INCOMPLETE DATA SET, AND IS NOT MONITORED FOR PERFORMANCE. WE STRONGLY RECOMMEND THE USE OF OUR PUBLIC SITE

Query author contributions in Reactome

Reactome depends on collaboration between our curation team and outside experts to assemble and peer-review its pathway modules. The integration of ORCID within Reactome enables us to meet a key challenge with authoring, curating and reviewing biological information by incentivizing and crediting the external experts that contribute their expertise and time to the Reactome curation process. More information is available at ORCID and Reactome.

If you have an ORCID ID that is not listed on this page, please forward this information to us and we will update your Reactome pathway records.

Name Email address

Details on Person UniProt:P42858 HTT

Class:IdReferenceGeneProduct:56424
_chainChangeLogchain:1-3142 added on Sat February 7 2015;chain:551-584 for 56424 added on Fri August 9 2019
_displayNameUniProt:P42858 HTT
_timestamp2025-05-21 21:05:44
chainchain:1-3142
chain:551-584
checksumA267509E84D52F0D
commentFUNCTION May play a role in microtubule-mediated transport or vesicle function.FUNCTION Promotes the formation of autophagic vesicles.SUBUNIT Interacts with PFN1 (PubMed:18573880). Interacts through its N-terminus with PRPF40A (PubMed:9700202). Interacts with PQBP1 (PubMed:10332029). Interacts with SETD2 (PubMed:10958656, PubMed:11461154, PubMed:9700202). Interacts with SH3GLB1 (By similarity). Interacts with SYVN (PubMed:17141218). Interacts with TPR; the interaction is inhibited by forms of Huntingtin with expanded polyglutamine stretch (PubMed:15654337). Interacts with ZDHHC13 (via ANK repeats) (PubMed:26198635). Interacts with ZDHHC17 (via ANK repeats) (PubMed:26198635, PubMed:28757145, PubMed:28882895). Interacts with F8A1/F8A2/F8A3 (PubMed:16476778, PubMed:29466333). Found in a complex with F8A1/F8A2/F8A3, HTT and RAB5A; mediates the recruitment of HTT by RAB5A (PubMed:16476778).INTERACTION The mutant Huntingtin protein colocalizes with AKAP8L in the nuclear matrix of Huntington disease neurons. Shuttles between cytoplasm and nucleus in a Ran GTPase-independent manner (PubMed:15654337). Recruits onto early endosomes in a Rab5- and HAP40-dependent fashion (PubMed:16476778).SUBCELLULAR LOCATION Expressed in the brain cortex (at protein level). Widely expressed with the highest level of expression in the brain (nerve fibers, varicosities, and nerve endings). In the brain, the regions where it can be mainly found are the cerebellar cortex, the neocortex, the striatum, and the hippocampal formation.DOMAIN The N-terminal Gln-rich and Pro-rich domain has great conformational flexibility and is likely to exist in a fluctuating equilibrium of alpha-helical, random coil, and extended conformations.PTM Cleaved by caspases downstream of the polyglutamine stretch (PubMed:10770929, PubMed:29802276, PubMed:8696339, PubMed:9535906). The resulting N-terminal fragments are cytotoxic and provokes apoptosis (PubMed:10770929).PTM Forms with expanded polyglutamine expansion are specifically ubiquitinated by SYVN1, which promotes their proteasomal degradation.PTM Phosphorylation at Ser-1179 and Ser-1199 by CDK5 in response to DNA damage in nuclei of neurons protects neurons against polyglutamine expansion as well as DNA damage mediated toxicity.PTM Myristoylated at Gly-551, following proteolytic cleavage at Asp-550.POLYMORPHISM The poly-Gln region of HTT is highly polymorphic (10 to 35 repeats) in the normal population and is expanded to about 36-120 repeats in Huntington disease patients. The repeat length usually increases in successive generations, but also contracts on occasion. The adjacent poly-Pro region is also polymorphic and varies between 7-12 residues. Polyglutamine expansion leads to elevated susceptibility to apopain cleavage and likely result in accelerated neuronal apoptosis (PubMed:8696339).DISEASE The disease is caused by variants affecting the gene represented in this entry.DISEASE The disease is caused by variants affecting the gene represented in this entry.SIMILARITY Belongs to the huntingtin family.ONLINE INFORMATION Huntingtin entry
descriptionrecommendedName: Huntingtin alternativeName: Huntington disease protein shortName: HD protein component recommendedName: Huntingtin, myristoylated N-terminal fragment /component
geneNameHTT
HD
IT15
identifierP42858
isSequenceChangedFALSE
keyword3D-structure
Acetylation
Apoptosis
Cytoplasm
Cytoplasmic vesicle
Disease variant
Endosome
Intellectual disability
Lipoprotein
Myristate
Neurodegeneration
Nucleus
Phosphoprotein
Proteomics identification
Reference proteome
Repeat
Triplet repeat expansion
Ubl conjugation
modified[InstanceEdit:9836292] Weiser, Joel, 2023-05-25
[InstanceEdit:9852000] Weiser, Joel, 2023-11-03
[InstanceEdit:9917590] Weiser, Joel, 2024-08-09
[InstanceEdit:9926675] Weiser, Joel, 2024-11-03
[InstanceEdit:9948485] Weiser, Joel, 2025-05-21
nameHTT
referenceDatabase[ReferenceDatabase:2] UniProt
referenceGene[ReferenceDNASequence:9002381] ENSEMBL:ENSG00000197386 HTT [Homo sapiens]
secondaryIdentifierHD_HUMAN
Q9UQB7
sequenceLength3142
species[Species:48887] Homo sapiens
(referenceEntity)[EntityWithAccessionedSequence:201605] HTT [cytosol] [Homo sapiens]
[EntityWithAccessionedSequence:9023590] HTT [nucleoplasm] [Homo sapiens]
[Change default viewing format]
No pathways have been reviewed or authored by UniProt:P42858 HTT (56424)