KEGG   PATHWAY: hsa05016Help
Entry
hsa05016                    Pathway                                

Name
Huntington's disease - Homo sapiens (human)
Description
Huntington disease (HD) is an autosomal-dominant neurodegenerative disorder that primarily affects medium spiny striatal neurons (MSN). The symptoms are choreiform, involuntary movements, personality changes and dementia. HD is caused by a CAG repeat expansion in the IT15gene, which results in a long stretch of polyglutamine close to the amino-terminus of the HD protein huntingtin (Htt). Mutant Htt (mHtt) has effects both in the cytoplasm and in the nucleus. In the cytoplasm, full-length mHtt can interfere with BDNF vesicular transport on microtubules. This mutant protein also may lead to abnormal endocytosis and secretion in neurons, because normal Htt form a complex with the proteins Hip1, clathrin and AP2 that are involved in endocytosis. In addition, mHtt affects Ca2+ signaling by sensitizing InsP3R1 to activation by InsP3, stimulating NMDAR activity, and destabilizing mitochondrial Ca2+ handling. The mHtt translocates to the nucleus, where it forms intranuclear inclusions. Nuclear toxicity is believed to be caused by interference with gene transcription, leading to loss of transcription of neuroprotective molecules such as BDNF. While mHtt binds to p53 and upregulates levels of nuclear p53 as well as p53 transcriptional activity. Augmented p53 mediates mitochondrial dysfunction.
Class
Human Diseases; Neurodegenerative diseases
BRITE hierarchy
Pathway map
Huntington's disease
hsa05016

All organismsOrtholog table
Module
RNA polymerase II, eukaryotes [PATH:hsa05016]
Disease
H00059  
Huntington's disease (HD)
Organism
Homo sapiens (human) [GN:hsa]
Gene
1211  
CLTA; clathrin light chain A [KO:K04644]
1212  
CLTB; clathrin light chain B [KO:K04645]
1213  
CLTC; clathrin heavy chain [KO:K04646]
8218  
CLTCL1; clathrin heavy chain like 1 [KO:K04646]
3092  
HIP1; huntingtin interacting protein 1 [KO:K04559]
161  
AP2A2; adaptor related protein complex 2 alpha 2 subunit [KO:K11824]
160  
AP2A1; adaptor related protein complex 2 alpha 1 subunit [KO:K11824]
163  
AP2B1; adaptor related protein complex 2 beta 1 subunit [KO:K11825]
1173  
AP2M1; adaptor related protein complex 2 mu 1 subunit [KO:K11826]
1175  
AP2S1; adaptor related protein complex 2 sigma 1 subunit [KO:K11827]
3064  
HTT; huntingtin [KO:K04533]
55081  
IFT57; intraflagellar transport 57 [KO:K04638]
841  
CASP8; caspase 8 [KO:K04398] [EC:3.4.22.61]
836  
CASP3; caspase 3 [KO:K02187] [EC:3.4.22.56]
2915  
GRM5; glutamate metabotropic receptor 5 [KO:K04604]
2776  
GNAQ; G protein subunit alpha q [KO:K04634]
23236  
PLCB1; phospholipase C beta 1 [KO:K05858] [EC:3.1.4.11]
5330  
PLCB2; phospholipase C beta 2 [KO:K05858] [EC:3.1.4.11]
5331  
PLCB3; phospholipase C beta 3 [KO:K05858] [EC:3.1.4.11]
5332  
PLCB4; phospholipase C beta 4 [KO:K05858] [EC:3.1.4.11]
2902  
GRIN1; glutamate ionotropic receptor NMDA type subunit 1 [KO:K05208]
2904  
GRIN2B; glutamate ionotropic receptor NMDA type subunit 2B [KO:K05210]
3708  
ITPR1; inositol 1,4,5-trisphosphate receptor type 1 [KO:K04958]
1742  
DLG4; discs large homolog 4 [KO:K11828]
7052  
TGM2; transglutaminase 2 [KO:K05625] [EC:2.3.2.13]
5978  
REST; RE1 silencing transcription factor [KO:K09222]
25942  
SIN3A; SIN3 transcription regulator family member A [KO:K11644]
23186  
RCOR1; REST corepressor 1 [KO:K11829]
3065  
HDAC1; histone deacetylase 1 [KO:K06067] [EC:3.5.1.98]
3066  
HDAC2; histone deacetylase 2 [KO:K06067] [EC:3.5.1.98]
5430  
POLR2A; polymerase (RNA) II subunit A [KO:K03006] [EC:2.7.7.6]
5431  
POLR2B; polymerase (RNA) II subunit B [KO:K03010] [EC:2.7.7.6]
5432  
POLR2C; polymerase (RNA) II subunit C [KO:K03011]
5433  
POLR2D; polymerase (RNA) II subunit D [KO:K03012]
5434  
POLR2E; polymerase (RNA) II subunit E [KO:K03013]
5435  
POLR2F; polymerase (RNA) II subunit F [KO:K03014]
5436  
POLR2G; polymerase (RNA) II subunit G [KO:K03015]
5437  
POLR2H; polymerase (RNA) II subunit H [KO:K03016]
5438  
POLR2I; polymerase (RNA) II subunit I [KO:K03017]
5441  
POLR2L; polymerase (RNA) II subunit L [KO:K03007]
5439  
POLR2J; polymerase (RNA) II subunit J [KO:K03008]
548644  
POLR2J3; polymerase (RNA) II subunit J3 [KO:K03008]
246721  
POLR2J2; polymerase (RNA) II subunit J2 [KO:K03008]
5440  
POLR2K; polymerase (RNA) II subunit K [KO:K03009]
627  
BDNF; brain-derived neurotrophic factor [KO:K04355]
1639  
DCTN1; dynactin subunit 1 [KO:K04648]
10540  
DCTN2; dynactin subunit 2 [KO:K10424]
51164  
DCTN4; dynactin subunit 4 [KO:K10426]
9001  
HAP1; huntingtin-associated protein 1 [KO:K04647]
25981  
DNAH1; dynein axonemal heavy chain 1 [KO:K10408]
55567  
DNAH3; dynein axonemal heavy chain 3 [KO:K10408]
146754  
DNAH2; dynein axonemal heavy chain 2 [KO:K10408]
56171  
DNAH7; dynein axonemal heavy chain 7 [KO:K10408]
1767  
DNAH5; dynein axonemal heavy chain 5 [KO:K10408]
1768  
DNAH6; dynein axonemal heavy chain 6 [KO:K10408]
1770  
DNAH9; dynein axonemal heavy chain 9 [KO:K10408]
8701  
DNAH11; dynein axonemal heavy chain 11 [KO:K10408]
201625  
DNAH12; dynein axonemal heavy chain 12 [KO:K10408]
127602  
DNAH14; dynein axonemal heavy chain 14 [KO:K10408]
1769  
DNAH8; dynein axonemal heavy chain 8 [KO:K10408]
196385  
DNAH10; dynein axonemal heavy chain 10 [KO:K10408]
8632  
DNAH17; dynein axonemal heavy chain 17 [KO:K10408]
7802  
DNALI1; dynein axonemal light intermediate chain 1 [KO:K10410]
27019  
DNAI1; dynein axonemal intermediate chain 1 [KO:K10409]
64446  
DNAI2; dynein axonemal intermediate chain 2 [KO:K11143]
83544  
DNAL1; dynein axonemal light chain 1 [KO:K10411]
10126  
DNAL4; dynein axonemal light chain 4 [KO:K10412]
1387  
CREBBP; CREB binding protein [KO:K04498] [EC:2.3.1.48]
2033  
EP300; E1A binding protein p300 [KO:K04498] [EC:2.3.1.48]
6875  
TAF4B; TATA-box binding protein associated factor 4b [KO:K03129]
6874  
TAF4; TATA-box binding protein associated factor 4 [KO:K03129]
387332  
TBPL2; TATA-box binding protein like 2 [KO:K03120]
9519  
TBPL1; TATA-box binding protein like 1 [KO:K03120]
6908  
TBP; TATA-box binding protein [KO:K03120]
6667  
SP1; Sp1 transcription factor [KO:K04684]
1385  
CREB1; cAMP responsive element binding protein 1 [KO:K05870]
10488  
CREB3; cAMP responsive element binding protein 3 [KO:K09048]
90993  
CREB3L1; cAMP responsive element binding protein 3-like 1 [KO:K09048]
64764  
CREB3L2; cAMP responsive element binding protein 3-like 2 [KO:K09048]
84699  
CREB3L3; cAMP responsive element binding protein 3-like 3 [KO:K09048]
148327  
CREB3L4; cAMP responsive element binding protein 3-like 4 [KO:K09048]
9586  
CREB5; cAMP responsive element binding protein 5 [KO:K09047]
10891  
PPARGC1A; PPARG coactivator 1 alpha [KO:K07202]
5468  
PPARG; peroxisome proliferator activated receptor gamma [KO:K08530]
7019  
TFAM; transcription factor A, mitochondrial [KO:K11830]
4899  
NRF1; nuclear respiratory factor 1 [KO:K11831]
6647  
SOD1; superoxide dismutase 1, soluble [KO:K04565] [EC:1.15.1.1]
6648  
SOD2; superoxide dismutase 2, mitochondrial [KO:K04564] [EC:1.15.1.1]
7350  
UCP1; uncoupling protein 1 [KO:K08769]
7157  
TP53; tumor protein p53 [KO:K04451]
581  
BAX; BCL2 associated X protein [KO:K02159]
27113  
BBC3; BCL2 binding component 3 [KO:K10132]
4723  
NDUFV1; NADH:ubiquinone oxidoreductase core subunit V1 [KO:K03942] [EC:1.6.99.3 1.6.5.3]
4729  
NDUFV2; NADH:ubiquinone oxidoreductase core subunit V2 [KO:K03943] [EC:1.6.99.3 1.6.5.3]
4731  
NDUFV3; NADH:ubiquinone oxidoreductase subunit V3 [KO:K03944]
4694  
NDUFA1; NADH:ubiquinone oxidoreductase subunit A1 [KO:K03945]
4695  
NDUFA2; NADH:ubiquinone oxidoreductase subunit A2 [KO:K03946]
4696  
NDUFA3; NADH:ubiquinone oxidoreductase subunit A3 [KO:K03947]
4697  
NDUFA4; NDUFA4, mitochondrial complex associated [KO:K03948]
56901  
NDUFA4L2; NADH dehydrogenase (ubiquinone) 1 alpha subcomplex, 4-like 2 [KO:K03948]
4698  
NDUFA5; NADH:ubiquinone oxidoreductase subunit A5 [KO:K03949]
4700  
NDUFA6; NADH:ubiquinone oxidoreductase subunit A6 [KO:K03950]
4701  
NDUFA7; NADH:ubiquinone oxidoreductase subunit A7 [KO:K03951]
4702  
NDUFA8; NADH:ubiquinone oxidoreductase subunit A8 [KO:K03952]
4704  
NDUFA9; NADH:ubiquinone oxidoreductase subunit A9 [KO:K03953]
4705  
NDUFA10; NADH:ubiquinone oxidoreductase subunit A10 [KO:K03954]
4706  
NDUFAB1; NADH:ubiquinone oxidoreductase subunit AB1 [KO:K03955]
126328  
NDUFA11; NADH:ubiquinone oxidoreductase subunit A11 [KO:K03956]
55967  
NDUFA12; NADH:ubiquinone oxidoreductase subunit A12 [KO:K11352]
51079  
NDUFA13; NADH:ubiquinone oxidoreductase subunit A13 [KO:K11353]
4707  
NDUFB1; NADH:ubiquinone oxidoreductase subunit B1 [KO:K03957]
4708  
NDUFB2; NADH:ubiquinone oxidoreductase subunit B2 [KO:K03958]
4709  
NDUFB3; NADH:ubiquinone oxidoreductase subunit B3 [KO:K03959]
4710  
NDUFB4; NADH:ubiquinone oxidoreductase subunit B4 [KO:K03960]
4711  
NDUFB5; NADH:ubiquinone oxidoreductase subunit B5 [KO:K03961]
4712  
NDUFB6; NADH:ubiquinone oxidoreductase subunit B6 [KO:K03962]
4713  
NDUFB7; NADH:ubiquinone oxidoreductase subunit B7 [KO:K03963]
4714  
NDUFB8; NADH:ubiquinone oxidoreductase subunit B8 [KO:K03964]
4715  
NDUFB9; NADH:ubiquinone oxidoreductase subunit B9 [KO:K03965]
4716  
NDUFB10; NADH:ubiquinone oxidoreductase subunit B10 [KO:K03966]
54539  
NDUFB11; NADH:ubiquinone oxidoreductase subunit B11 [KO:K11351]
4719  
NDUFS1; NADH:ubiquinone oxidoreductase core subunit S1 [KO:K03934] [EC:1.6.99.3 1.6.5.3]
4720  
NDUFS2; NADH:ubiquinone oxidoreductase core subunit S2 [KO:K03935] [EC:1.6.99.3 1.6.5.3]
4722  
NDUFS3; NADH:ubiquinone oxidoreductase core subunit S3 [KO:K03936] [EC:1.6.99.3 1.6.5.3]
4724  
NDUFS4; NADH:ubiquinone oxidoreductase subunit S4 [KO:K03937]
4725  
NDUFS5; NADH:ubiquinone oxidoreductase subunit S5 [KO:K03938]
4726  
NDUFS6; NADH:ubiquinone oxidoreductase subunit S6 [KO:K03939]
374291  
NDUFS7; NADH:ubiquinone oxidoreductase core subunit S7 [KO:K03940] [EC:1.6.99.3 1.6.5.3]
4728  
NDUFS8; NADH:ubiquinone oxidoreductase core subunit S8 [KO:K03941] [EC:1.6.99.3 1.6.5.3]
4717  
NDUFC1; NADH:ubiquinone oxidoreductase subunit C1 [KO:K03967]
4718  
NDUFC2; NADH:ubiquinone oxidoreductase subunit C2 [KO:K03968]
NDUFC2-KCTD14; NDUFC2-KCTD14 readthrough [KO:K03968]
6389  
SDHA; succinate dehydrogenase complex flavoprotein subunit A [KO:K00234] [EC:1.3.5.1]
6390  
SDHB; succinate dehydrogenase complex iron sulfur subunit B [KO:K00235] [EC:1.3.5.1]
6391  
SDHC; succinate dehydrogenase complex subunit C [KO:K00236]
6392  
SDHD; succinate dehydrogenase complex subunit D [KO:K00237]
7386  
UQCRFS1; ubiquinol-cytochrome c reductase, Rieske iron-sulfur polypeptide 1 [KO:K00411] [EC:1.10.2.2]
4519  
CYTB; cytochrome b [KO:K00412]
1537  
CYC1; cytochrome c1 [KO:K00413]
7384  
UQCRC1; ubiquinol-cytochrome c reductase core protein I [KO:K00414]
7385  
UQCRC2; ubiquinol-cytochrome c reductase core protein II [KO:K00415]
7388  
UQCRH; ubiquinol-cytochrome c reductase hinge protein [KO:K00416]
440567  
UQCRHL; ubiquinol-cytochrome c reductase hinge protein like [KO:K00416]
7381  
UQCRB; ubiquinol-cytochrome c reductase binding protein [KO:K00417]
27089  
UQCRQ; ubiquinol-cytochrome c reductase complex III subunit VII [KO:K00418]
29796  
UQCR10; ubiquinol-cytochrome c reductase, complex III subunit X [KO:K00419]
10975  
UQCR11; ubiquinol-cytochrome c reductase, complex III subunit XI [KO:K00420]
4514  
COX3; cytochrome c oxidase III [KO:K02262]
4512  
COX1; cytochrome c oxidase subunit I [KO:K02256] [EC:1.9.3.1]
4513  
COX2; cytochrome c oxidase subunit II [KO:K02261]
84701  
COX4I2; cytochrome c oxidase subunit 4I2 [KO:K02263]
1327  
COX4I1; cytochrome c oxidase subunit 4I1 [KO:K02263]
9377  
COX5A; cytochrome c oxidase subunit 5A [KO:K02264]
1329  
COX5B; cytochrome c oxidase subunit 5B [KO:K02265]
1337  
COX6A1; cytochrome c oxidase subunit 6A1 [KO:K02266]
1339  
COX6A2; cytochrome c oxidase subunit 6A2 [KO:K02266]
1340  
COX6B1; cytochrome c oxidase subunit 6B1 [KO:K02267]
125965  
COX6B2; cytochrome c oxidase subunit 6B2 [KO:K02267]
1345  
COX6C; cytochrome c oxidase subunit 6C [KO:K02268]
1346  
COX7A1; cytochrome c oxidase subunit 7A1 [KO:K02270]
1347  
COX7A2; cytochrome c oxidase subunit 7A2 [KO:K02270]
9167  
COX7A2L; cytochrome c oxidase subunit 7A2 like [KO:K02270]
1349  
COX7B; cytochrome c oxidase subunit 7B [KO:K02271]
170712  
COX7B2; cytochrome c oxidase subunit 7B2 [KO:K02271]
1350  
COX7C; cytochrome c oxidase subunit 7C [KO:K02272]
341947  
COX8C; cytochrome c oxidase subunit 8C [KO:K02273]
1351  
COX8A; cytochrome c oxidase subunit 8A [KO:K02273]
498  
ATP5A1; ATP synthase, H+ transporting, mitochondrial F1 complex, alpha subunit 1, cardiac muscle [KO:K02132]
506  
ATP5B; ATP synthase, H+ transporting, mitochondrial F1 complex, beta polypeptide [KO:K02133] [EC:3.6.3.14]
509  
ATP5C1; ATP synthase, H+ transporting, mitochondrial F1 complex, gamma polypeptide 1 [KO:K02136]
513  
ATP5D; ATP synthase, H+ transporting, mitochondrial F1 complex, delta subunit [KO:K02134]
514  
ATP5E; ATP synthase, H+ transporting, mitochondrial F1 complex, epsilon subunit [KO:K02135]
4508  
ATP6; ATP synthase F0 subunit 6 [KO:K02126]
515  
ATP5F1; ATP synthase, H+ transporting, mitochondrial Fo complex subunit B1 [KO:K02127]
516  
ATP5G1; ATP synthase, H+ transporting, mitochondrial Fo complex subunit C1 (subunit 9) [KO:K02128]
517  
ATP5G2; ATP synthase, H+ transporting, mitochondrial Fo complex subunit C2 (subunit 9) [KO:K02128]
518  
ATP5G3; ATP synthase, H+ transporting, mitochondrial Fo complex subunit C3 (subunit 9) [KO:K02128]
10476  
ATP5H; ATP synthase, H+ transporting, mitochondrial Fo complex subunit D [KO:K02138]
539  
ATP5O; ATP synthase, H+ transporting, mitochondrial F1 complex, O subunit [KO:K02137]
522  
ATP5J; ATP synthase, H+ transporting, mitochondrial Fo complex subunit F6 [KO:K02131]
4509  
ATP8; ATP synthase F0 subunit 8 [KO:K02125]
7416  
VDAC1; voltage dependent anion channel 1 [KO:K05862]
7417  
VDAC2; voltage dependent anion channel 2 [KO:K15040]
7419  
VDAC3; voltage dependent anion channel 3 [KO:K15041]
291  
SLC25A4; solute carrier family 25 member 4 [KO:K05863]
292  
SLC25A5; solute carrier family 25 member 5 [KO:K05863]
293  
SLC25A6; solute carrier family 25 member 6 [KO:K05863]
83447  
SLC25A31; solute carrier family 25 member 31 [KO:K05863]
10105  
PPIF; peptidylprolyl isomerase F [KO:K09565] [EC:5.2.1.8]
54205  
CYCS; cytochrome c, somatic [KO:K08738]
317  
APAF1; apoptotic peptidase activating factor 1 [KO:K02084]
842  
CASP9; caspase 9 [KO:K04399] [EC:3.4.22.62]
2876  
GPX1; glutathione peroxidase 1 [KO:K00432] [EC:1.11.1.9]
Compound
C00025  
L-Glutamate
C00076  
Calcium cation
C01245  
D-myo-Inositol 1,4,5-trisphosphate
Reference
  Authors
Landles C, Bates GP
  Title
Huntingtin and the molecular pathogenesis of Huntington's disease. Fourth in molecular medicine review series.
  Journal
EMBO Rep 5:958-63 (2004)
Reference
  Authors
Borrell-Pages M, Zala D, Humbert S, Saudou F
  Title
Huntington's disease: from huntingtin function and dysfunction to therapeutic strategies.
  Journal
Cell Mol Life Sci 63:2642-60 (2006)
Reference
  Authors
Bossy-Wetzel E, Petrilli A, Knott AB
  Title
Mutant huntingtin and mitochondrial dysfunction.
  Journal
Trends Neurosci 31:609-16 (2008)
Reference
  Authors
Cattaneo E, Zuccato C, Tartari M
  Title
Normal huntingtin function: an alternative approach to Huntington's disease.
  Journal
Nat Rev Neurosci 6:919-30 (2005)
Reference
  Authors
Bezprozvanny I, Hayden MR
  Title
Deranged neuronal calcium signaling and Huntington disease.
  Journal
Biochem Biophys Res Commun 322:1310-7 (2004)
Reference
  Authors
Sawa A, Tomoda T, Bae BI
  Title
Mechanisms of neuronal cell death in Huntington's disease.
  Journal
Cytogenet Genome Res 100:287-95 (2003)
Reference
  Authors
Ross CA.
  Title
Polyglutamine pathogenesis: emergence of unifying mechanisms for Huntington's disease and related disorders.
  Journal
Neuron 35:819-22 (2002)
Reference
  Authors
Ross CA
  Title
Huntington's disease: new paths to pathogenesis.
  Journal
Cell 118:4-7 (2004)
Reference
  Authors
Tang TS, Slow E, Lupu V, Stavrovskaya IG, Sugimori M, Llinas R, Kristal BS, Hayden MR, Bezprozvanny I
  Title
Disturbed Ca2+ signaling and apoptosis of medium spiny neurons in Huntington's disease.
  Journal
Proc Natl Acad Sci U S A 102:2602-7 (2005)
Reference
  Authors
Mattson MP.
  Title
Accomplices to neuronal death.
  Journal
Nature 415:377-9 (2002)
Reference
  Authors
McGill JK, Beal MF
  Title
PGC-1alpha, a new therapeutic target in Huntington's disease?
  Journal
Cell 127:465-8 (2006)
Reference
  Authors
La Spada AR, Morrison RS
  Title
The power of the dark side: Huntington's disease protein and p53 form a deadly alliance.
  Journal
Neuron 47:1-3 (2005)
Reference
  Authors
Lesort M, Chun W, Tucholski J, Johnson GV
  Title
Does tissue transglutaminase play a role in Huntington's disease?
  Journal
Neurochem Int 40:37-52 (2002)
Reference
  Authors
Bae BI, Xu H, Igarashi S, Fujimuro M, Agrawal N, Taya Y, Hayward SD, Moran TH, Montell C, Ross CA, Snyder SH, Sawa A
  Title
p53 mediates cellular dysfunction and behavioral abnormalities in Huntington's disease.
  Journal
Neuron 47:29-41 (2005)
Reference
  Authors
Li SH, Cheng AL, Zhou H, Lam S, Rao M, Li H, Li XJ
  Title
Interaction of Huntington disease protein with transcriptional activator Sp1.
  Journal
Mol Cell Biol 22:1277-87 (2002)
KO pathway
 

DBGET integrated database retrieval system