KEGG   PATHWAY: hsa05016
Entry
hsa05016                    Pathway                                
Name
Huntington 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 IT15 gene, which results in a long stretch of polyglutamine (polyQ) close to the amino-terminus of the HD protein huntingtin (Htt). Mutant Htt (mHtt) has effects both in the cytoplasm and in the nucleus. Full-length huntingtin is cleaved by proteases in the cytoplasm, leading to the formation of cytoplasmic and neuritic aggregates. mHtt also alters vesicular transport and recycling, causes cytosolic and mitochondrial Ca2+  overload, triggers endoplasmic reticulum stress through proteasomal dysfunction, and impairs autophagy function, increasing neuronal death susceptibility. N-terminal fragments containing the polyQ strech translocate to the nucleus where they impair transcription and induce neuronal death.
Class
Human Diseases; Neurodegenerative disease
Pathway map
hsa05016  Huntington disease
hsa05016

Network
nt06461  Huntington disease
nt06466  Pathways of neurodegeneration
  Element
N00977  Mutation-caused aberrant Htt to retrograde axonal transport
N00979  Mutation-caused aberrant Htt to anterograde axonal transport
N00980  Mutation-caused aberrant Htt to REST-mediated transcriptional repression
N00981  Mutation-caused aberrant Htt to CREB-mediated transcription
N00982  Mutation-caused aberrant Htt to p53-mediated transcription
N00983  Mutation-caused aberrant Htt to extrinsic apoptotic pathway
N00985  Mutation-caused aberrant Htt to mGluR5-Ca2+ -apoptotic pathway
N00986  Mutation-caused aberrant Htt to VGCC-Ca2+ -apoptotic pathway
N00987  Mutation-caused aberrant Htt to transport of calcium
N00989  Mutation-caused aberrant Htt to electron transfer in Complex II
N00991  Mutation-caused aberrant Htt to electron transfer in Complex III
N00992  Mutation-caused aberrant Htt to TNF-JNK signaling pathway
N00993  Mutation-caused aberrant Htt to autophagy-vesicle nucleation
N01061  Mutation-caused aberrant Htt to 26S proteasome-mediated protein degradation
Disease
H00059  Huntington disease
Drug
D12012  Tominersen sodium (JAN)
D12013  Tominersen (USAN/INN)
D12970  Votoplam (USAN/INN)
Organism
Homo sapiens (human) [GN:hsa]
Gene
100532726  NDUFC2-KCTD14; NADH dehydrogenase [ubiquinone] 1 subunit C2, isoform 2 isoform 2 [KO:K03968]
10105  PPIF; peptidyl-prolyl cis-trans isomerase F, mitochondrial precursor [KO:K09565] [EC:5.2.1.8]
10120  ACTR1B; beta-centractin [KO:K16575]
10121  ACTR1A; alpha-centractin [KO:K16575]
10126  DNAL4; dynein axonemal light chain 4 [KO:K10412]
10213  PSMD14; 26S proteasome non-ATPase regulatory subunit 14 [KO:K03030]
10376  TUBA1B; tubulin alpha-1B chain [KO:K07374]
10381  TUBB3; tubulin beta-3 chain isoform 1 [KO:K07375]
10382  TUBB4A; tubulin beta-4A chain isoform 3 [KO:K07375]
10383  TUBB4B; tubulin beta-4B chain [KO:K07375]
10476  ATP5PD; ATP synthase peripheral stalk subunit d, mitochondrial isoform a [KO:K02138]
10488  CREB3; cyclic AMP-responsive element-binding protein 3 [KO:K09048]
10540  DCTN2; dynactin subunit 2 isoform 3 [KO:K10424]
10671  DCTN6; dynactin subunit 6 [KO:K10428]
107984365  [KO:K03948]
10891  PPARGC1A; peroxisome proliferator-activated receptor gamma coactivator 1-alpha isoform 2 [KO:K07202]
10975  UQCR11; cytochrome b-c1 complex subunit 10 [KO:K00420]
11047  ADRM1; proteasomal ubiquitin receptor ADRM1 isoform 1 [KO:K06691]
11258  DCTN3; dynactin subunit 3 isoform 1 [KO:K10425]
112714  TUBA3E; tubulin alpha-3E chain [KO:K07374]
113457  TUBA3D; tubulin alpha-3D chain [KO:K07374]
1173  AP2M1; AP-2 complex subunit mu isoform a [KO:K11826]
1175  AP2S1; AP-2 complex subunit sigma isoform AP17 [KO:K11827]
1211  CLTA; clathrin light chain A isoform b [KO:K04644]
1212  CLTB; clathrin light chain B isoform b [KO:K04645]
1213  CLTC; clathrin heavy chain 1 isoform 1 [KO:K04646]
125965  COX6B2; cytochrome c oxidase subunit 6B2 [KO:K02267]
126328  NDUFA11; NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 11 isoform 1 [KO:K03956]
127602  DNAH14; dynein axonemal heavy chain 14 isoform 2 [KO:K10408]
1327  COX4I1; cytochrome c oxidase subunit 4 isoform 1, mitochondrial isoform 1 precursor [KO:K02263]
1329  COX5B; cytochrome c oxidase subunit 5B, mitochondrial precursor [KO:K02265]
1337  COX6A1; cytochrome c oxidase subunit 6A1, mitochondrial [KO:K02266]
1339  COX6A2; cytochrome c oxidase subunit 6A2, mitochondrial precursor [KO:K02266]
1340  COX6B1; cytochrome c oxidase subunit 6B1 [KO:K02267]
1345  COX6C; cytochrome c oxidase subunit 6C [KO:K02268]
1346  COX7A1; cytochrome c oxidase subunit 7A1, mitochondrial precursor [KO:K02270]
1347  COX7A2; cytochrome c oxidase subunit 7A2, mitochondrial [KO:K02270]
1349  COX7B; cytochrome c oxidase subunit 7B, mitochondrial precursor [KO:K02271]
1350  COX7C; cytochrome c oxidase subunit 7C, mitochondrial precursor [KO:K02272]
1351  COX8A; cytochrome c oxidase subunit 8A, mitochondrial [KO:K02273]
1385  CREB1; cyclic AMP-responsive element-binding protein 1 isoform A [KO:K05870]
1387  CREBBP; CREB-binding protein isoform a [KO:K04498] [EC:2.3.1.48]
143471  PSMA8; proteasome subunit alpha-type 8 isoform 1 [KO:K02731] [EC:3.4.25.1]
146754  DNAH2; dynein axonemal heavy chain 2 isoform 1 [KO:K10408]
147700  KLC3; kinesin light chain 3 [KO:K10407]
148327  CREB3L4; cyclic AMP-responsive element-binding protein 3-like protein 4 isoform 1 [KO:K09048]
1537  CYC1; cytochrome c1, heme protein, mitochondrial precursor [KO:K00413]
160  AP2A1; AP-2 complex subunit alpha-1 isoform 1 [KO:K11824]
161  AP2A2; AP-2 complex subunit alpha-2 isoform 2 [KO:K11824]
163  AP2B1; AP-2 complex subunit beta isoform b [KO:K11825]
1639  DCTN1; dynactin subunit 1 isoform 1 [KO:K04648]
170712  COX7B2; cytochrome c oxidase subunit 7B2, mitochondrial precursor [KO:K02271]
1742  DLG4; disks large homolog 4 isoform 4 [KO:K11828]
1767  DNAH5; dynein axonemal heavy chain 5 [KO:K10408]
1768  DNAH6; dynein axonemal heavy chain 6 [KO:K10408]
1769  DNAH8; dynein axonemal heavy chain 8 isoform 2 [KO:K10408]
1770  DNAH9; dynein axonemal heavy chain 9 isoform 2 [KO:K10408]
196385  DNAH10; dynein axonemal heavy chain 10 isoform 1 [KO:K10408]
201625  DNAH12; dynein axonemal heavy chain 12 isoform 2 [KO:K10408]
203068  TUBB; tubulin beta chain isoform b [KO:K07375]
2033  EP300; histone acetyltransferase p300 isoform 1 [KO:K04498] [EC:2.3.1.48]
2081  ERN1; serine/threonine-protein kinase/endoribonuclease IRE1 precursor [KO:K08852] [EC:2.7.11.1 3.1.26.-]
22863  ATG14; beclin 1-associated autophagy-related key regulator [KO:K17889]
23130  ATG2A; autophagy-related protein 2 homolog A isoform 1 [KO:K17906]
23186  RCOR1; REST corepressor 1 [KO:K11829]
23236  PLCB1; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform a [KO:K05858] [EC:3.1.4.11]
246721  POLR2J2; DNA-directed RNA polymerase II subunit RPB11-b1 [KO:K03008]
2475  MTOR; serine/threonine-protein kinase mTOR isoform 1 [KO:K07203] [EC:2.7.11.1]
257202  GPX6; glutathione peroxidase 6 precursor [KO:K00432] [EC:1.11.1.9]
25942  SIN3A; paired amphipathic helix protein Sin3a [KO:K11644]
25981  DNAH1; dynein axonemal heavy chain 1 [KO:K10408]
260334  TUBB8B; tubulin beta 8B isoform 1 [KO:K07375]
26100  WIPI2; WD repeat domain phosphoinositide-interacting protein 2 isoform a [KO:K17908]
27019  DNAI1; dynein axonemal intermediate chain 1 isoform 1 [KO:K10409]
27089  UQCRQ; cytochrome b-c1 complex subunit 8 [KO:K00418]
27113  BBC3; bcl-2-binding component 3 isoform 1 [KO:K10132]
2776  GNAQ; guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
2876  GPX1; glutathione peroxidase 1 isoform 1 [KO:K00432] [EC:1.11.1.9]
2877  GPX2; glutathione peroxidase 2 [KO:K00432] [EC:1.11.1.9]
2878  GPX3; glutathione peroxidase 3 isoform 1 precursor [KO:K00432] [EC:1.11.1.9]
2880  GPX5; epididymal secretory glutathione peroxidase isoform 1 precursor [KO:K00432] [EC:1.11.1.9]
2882  GPX7; glutathione peroxidase 7 precursor [KO:K00432] [EC:1.11.1.9]
2890  GRIA1; glutamate receptor 1 isoform 1 precursor [KO:K05197]
2891  GRIA2; glutamate receptor 2 isoform 1 precursor [KO:K05198]
2892  GRIA3; glutamate receptor 3 isoform 2 precursor [KO:K05199]
2893  GRIA4; glutamate receptor 4 isoform 1 precursor [KO:K05200]
2902  GRIN1; glutamate receptor ionotropic, NMDA 1 isoform GluN1-1a precursor [KO:K05208]
2904  GRIN2B; glutamate receptor ionotropic, NMDA 2B isoform a precursor [KO:K05210]
291  SLC25A4; ADP/ATP translocase 1 [KO:K05863]
2915  GRM5; metabotropic glutamate receptor 5 isoform a precursor [KO:K04604]
292  SLC25A5; ADP/ATP translocase 2 [KO:K05863]
293  SLC25A6; ADP/ATP translocase 3 [KO:K05863]
29796  UQCR10; cytochrome b-c1 complex subunit 9 isoform a [KO:K00419]
29982  NRBF2; nuclear receptor-binding factor 2 isoform 1 [KO:K21246]
3064  HTT; huntingtin isoform 1 [KO:K04533]
3065  HDAC1; histone deacetylase 1 [KO:K06067] [EC:3.5.1.98]
3066  HDAC2; histone deacetylase 2 [KO:K06067] [EC:3.5.1.98]
30849  PIK3R4; phosphoinositide 3-kinase regulatory subunit 4 [KO:K08333] [EC:2.7.11.1]
3092  HIP1; huntingtin-interacting protein 1 isoform 1 [KO:K04559]
317  APAF1; apoptotic protease-activating factor 1 isoform c [KO:K02084]
341947  COX8C; cytochrome c oxidase subunit 8C, mitochondrial [KO:K02273]
347688  TUBB8; tubulin beta-8 chain isoform 1 [KO:K07375]
347733  TUBB2B; tubulin beta-2B chain [KO:K07375]
3708  ITPR1; inositol 1,4,5-trisphosphate-gated calcium channel ITPR1 isoform 4 [KO:K04958]
374291  NDUFS7; NADH dehydrogenase [ubiquinone] iron-sulfur protein 7, mitochondrial isoform 1 [KO:K03940] [EC:7.1.1.2]
3766  KCNJ10; ATP-sensitive inward rectifier potassium channel 10 [KO:K05003]
3798  KIF5A; kinesin heavy chain isoform 5A isoform 1 [KO:K10396] [EC:5.6.1.3]
3799  KIF5B; kinesin-1 heavy chain [KO:K10396] [EC:5.6.1.3]
3800  KIF5C; kinesin heavy chain isoform 5C [KO:K10396] [EC:5.6.1.3]
3831  KLC1; kinesin light chain 1 isoform 2 [KO:K10407]
387332  TBPL2; TATA box-binding protein-like 2 [KO:K03120]
4217  MAP3K5; mitogen-activated protein kinase kinase kinase 5 isoform 2 [KO:K04426] [EC:2.7.11.25]
4294  MAP3K10; mitogen-activated protein kinase kinase kinase 10 [KO:K04418] [EC:2.7.11.25]
440567  UQCRHL; cytochrome b-c1 complex subunit 6-like, mitochondrial [KO:K00416]
441925  BECN2; beclin-2 [KO:K08334]
4508  ATP6; ATP synthase F0 subunit 6 [KO:K02126]
4509  ATP8; ATP synthase F0 subunit 8 [KO:K02125]
4512  COX1; cytochrome c oxidase subunit I [KO:K02256] [EC:7.1.1.9]
4513  COX2; cytochrome c oxidase subunit II [KO:K02261]
4514  COX3; cytochrome c oxidase subunit III [KO:K02262]
4519  CYTB; cytochrome b [KO:K00412]
4535  ND1; NADH dehydrogenase subunit 1 [KO:K03878] [EC:7.1.1.2]
4536  ND2; NADH dehydrogenase subunit 2 [KO:K03879] [EC:7.1.1.2]
4537  ND3; NADH dehydrogenase subunit 3 [KO:K03880] [EC:7.1.1.2]
4538  ND4; NADH dehydrogenase subunit 4 [KO:K03881] [EC:7.1.1.2]
4539  ND4L; NADH dehydrogenase subunit 4L [KO:K03882] [EC:7.1.1.2]
4540  ND5; NADH dehydrogenase subunit 5 [KO:K03883] [EC:7.1.1.2]
4541  ND6; NADH dehydrogenase subunit 6 [KO:K03884] [EC:7.1.1.2]
4694  NDUFA1; NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 1 [KO:K03945]
4695  NDUFA2; NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 2 isoform 1 [KO:K03946]
4696  NDUFA3; NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 3 [KO:K03947]
4697  COXFA4; cytochrome c oxidase subunit NDUFA4 [KO:K03948]
4698  NDUFA5; NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 5 isoform 1 [KO:K03949]
4700  NDUFA6; NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 6 [KO:K03950]
4701  NDUFA7; NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 7 [KO:K03951]
4702  NDUFA8; NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 8 isoform 1 [KO:K03952]
4704  NDUFA9; NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 9, mitochondrial precursor [KO:K03953]
4705  NDUFA10; NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 10, mitochondrial isoform 1 precursor [KO:K03954]
4706  NDUFAB1; acyl carrier protein, mitochondrial precursor [KO:K03955]
4707  NDUFB1; NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 1 [KO:K03957]
4708  NDUFB2; NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 2, mitochondrial precursor [KO:K03958]
4709  NDUFB3; NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 3 [KO:K03959]
4710  NDUFB4; NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 4 isoform 1 [KO:K03960]
4711  NDUFB5; NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 5, mitochondrial isoform 1 precursor [KO:K03961]
4712  NDUFB6; NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 6 isoform 1 [KO:K03962]
4713  NDUFB7; NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 7 [KO:K03963]
4714  NDUFB8; NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 8, mitochondrial isoform 1 precursor [KO:K03964]
4715  NDUFB9; NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 9 isoform 1 [KO:K03965]
4716  NDUFB10; NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 10 [KO:K03966]
4717  NDUFC1; NADH dehydrogenase [ubiquinone] 1 subunit C1, mitochondrial precursor [KO:K03967]
4718  NDUFC2; NADH dehydrogenase [ubiquinone] 1 subunit C2 isoform 1 [KO:K03968]
4719  NDUFS1; NADH-ubiquinone oxidoreductase 75 kDa subunit, mitochondrial isoform 1 precursor [KO:K03934] [EC:7.1.1.2]
4720  NDUFS2; NADH dehydrogenase [ubiquinone] iron-sulfur protein 2, mitochondrial isoform 1 precursor [KO:K03935] [EC:7.1.1.2]
4722  NDUFS3; NADH dehydrogenase [ubiquinone] iron-sulfur protein 3, mitochondrial precursor [KO:K03936] [EC:7.1.1.2]
4723  NDUFV1; NADH dehydrogenase [ubiquinone] flavoprotein 1, mitochondrial isoform 1 precursor [KO:K03942] [EC:7.1.1.2]
4724  NDUFS4; NADH dehydrogenase [ubiquinone] iron-sulfur protein 4, mitochondrial isoform 1 precursor [KO:K03937]
4725  NDUFS5; NADH dehydrogenase [ubiquinone] iron-sulfur protein 5 [KO:K03938]
4726  NDUFS6; NADH dehydrogenase [ubiquinone] iron-sulfur protein 6, mitochondrial precursor [KO:K03939]
4728  NDUFS8; NADH dehydrogenase [ubiquinone] iron-sulfur protein 8, mitochondrial precursor [KO:K03941] [EC:7.1.1.2]
4729  NDUFV2; NADH dehydrogenase [ubiquinone] flavoprotein 2, mitochondrial precursor [KO:K03943] [EC:7.1.1.2]
4731  NDUFV3; NADH dehydrogenase [ubiquinone] flavoprotein 3, mitochondrial isoform b precursor [KO:K03944]
4899  NRF1; nuclear respiratory factor 1 isoform 1 [KO:K11831]
493869  GPX8; probable glutathione peroxidase 8 isoform a [KO:K00432] [EC:1.11.1.9]
498  ATP5F1A; ATP synthase F(1) complex subunit alpha, mitochondrial isoform a precursor [KO:K02132]
506  ATP5F1B; ATP synthase F(1) complex subunit beta, mitochondrial precursor [KO:K02133] [EC:7.1.2.2]
509  ATP5F1C; ATP synthase F(1) complex subunit gamma, mitochondrial isoform L (liver) precursor [KO:K02136]
51079  NDUFA13; NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 13 [KO:K11353]
51164  DCTN4; dynactin subunit 4 isoform b [KO:K10426]
513  ATP5F1D; ATP synthase F(1) complex subunit delta, mitochondrial precursor [KO:K02134]
514  ATP5F1E; ATP synthase F(1) complex subunit epsilon, mitochondrial [KO:K02135]
515  ATP5PB; ATP synthase peripheral stalk subunit b, mitochondrial precursor [KO:K02127]
516  ATP5MC1; ATP synthase F(0) complex subunit C1, mitochondrial precursor [KO:K02128]
517  ATP5MC2; ATP synthase F(0) complex subunit C2, mitochondrial isoform c precursor [KO:K02128]
518  ATP5MC3; ATP synthase F(0) complex subunit C3, mitochondrial isoform A precursor [KO:K02128]
51807  TUBA8; tubulin alpha-8 chain isoform 1 [KO:K07374]
522  ATP5PF; ATP synthase peripheral stalk subunit F6, mitochondrial isoform a precursor [KO:K02131]
5289  PIK3C3; phosphatidylinositol 3-kinase catalytic subunit type 3 isoform 1 [KO:K00914] [EC:2.7.1.137]
5330  PLCB2; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform 1 [KO:K05858] [EC:3.1.4.11]
5331  PLCB3; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 isoform 1 [KO:K05858] [EC:3.1.4.11]
5332  PLCB4; 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform b [KO:K05858] [EC:3.1.4.11]
539  ATP5PO; ATP synthase peripheral stalk subunit OSCP, mitochondrial precursor [KO:K02137]
54205  CYCS; cytochrome c [KO:K08738]
5430  POLR2A; DNA-directed RNA polymerase II subunit RPB1 [KO:K03006] [EC:2.7.7.6]
5431  POLR2B; DNA-directed RNA polymerase II subunit RPB2 isoform 1 [KO:K03010] [EC:2.7.7.6]
5432  POLR2C; DNA-directed RNA polymerase II subunit RPB3 [KO:K03011]
5433  POLR2D; DNA-directed RNA polymerase II subunit RPB4 [KO:K03012]
5434  POLR2E; DNA-directed RNA polymerases I, II, and III subunit RPABC1 isoform a [KO:K03013]
5435  POLR2F; DNA-directed RNA polymerases I, II, and III subunit RPABC2 isoform 1 [KO:K03014]
5436  POLR2G; DNA-directed RNA polymerase II subunit RPB7 [KO:K03015]
5437  POLR2H; DNA-directed RNA polymerases I, II, and III subunit RPABC3 isoform 2 [KO:K03016]
5438  POLR2I; DNA-directed RNA polymerase II subunit RPB9 [KO:K03017]
5439  POLR2J; DNA-directed RNA polymerase II subunit RPB11-a isoform 1 [KO:K03008]
5440  POLR2K; DNA-directed RNA polymerases I, II, and III subunit RPABC4 [KO:K03009]
5441  POLR2L; DNA-directed RNA polymerases I, II, and III subunit RPABC5 [KO:K03007]
54539  NDUFB11; NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 11, mitochondrial isoform 2 [KO:K11351]
5468  PPARG; peroxisome proliferator-activated receptor gamma isoform 2 [KO:K08530]
548644  POLR2J3; DNA-directed RNA polymerase II subunit RPB11-b2 [KO:K03008]
55062  WIPI1; WD repeat domain phosphoinositide-interacting protein 1 isoform a [KO:K17908]
55081  IFT57; intraflagellar transport protein 57 homolog [KO:K04638]
55102  ATG2B; autophagy-related protein 2 homolog B [KO:K17906]
55567  DNAH3; dynein axonemal heavy chain 3 isoform 1 [KO:K10408]
55626  AMBRA1; activating molecule in BECN1-regulated autophagy protein 1 isoform 5 [KO:K17985]
55860  ACTR10; actin-related protein 10 [KO:K16576]
55967  NDUFA12; NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 12 isoform a [KO:K11352]
5599  MAPK8; mitogen-activated protein kinase 8 isoform alpha2 [KO:K04440] [EC:2.7.11.24]
5601  MAPK9; mitogen-activated protein kinase 9 isoform alpha2 [KO:K04440] [EC:2.7.11.24]
5602  MAPK10; mitogen-activated protein kinase 10 isoform 1 [KO:K04440] [EC:2.7.11.24]
5609  MAP2K7; dual specificity mitogen-activated protein kinase kinase 7 isoform 3 [KO:K04431] [EC:2.7.12.2]
56171  DNAH7; dynein axonemal heavy chain 7 [KO:K10408]
5682  PSMA1; proteasome subunit alpha type-1 isoform 2 [KO:K02725] [EC:3.4.25.1]
5683  PSMA2; proteasome subunit alpha type-2 [KO:K02726] [EC:3.4.25.1]
5684  PSMA3; proteasome subunit alpha type-3 isoform 1 [KO:K02727] [EC:3.4.25.1]
5685  PSMA4; proteasome subunit alpha type-4 isoform 1 [KO:K02728] [EC:3.4.25.1]
5686  PSMA5; proteasome subunit alpha type-5 isoform 1 [KO:K02729] [EC:3.4.25.1]
5687  PSMA6; proteasome subunit alpha type-6 isoform a [KO:K02730] [EC:3.4.25.1]
5688  PSMA7; proteasome subunit alpha type-7 [KO:K02731] [EC:3.4.25.1]
5689  PSMB1; proteasome subunit beta type-1 [KO:K02732] [EC:3.4.25.1]
5690  PSMB2; proteasome subunit beta type-2 isoform 1 [KO:K02734] [EC:3.4.25.1]
56901  COXFA4L2; NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 4-like 2 [KO:K03948]
5691  PSMB3; proteasome subunit beta type-3 [KO:K02735] [EC:3.4.25.1]
5692  PSMB4; proteasome subunit beta type-4 [KO:K02736] [EC:3.4.25.1]
5693  PSMB5; proteasome subunit beta type-5 isoform 1 [KO:K02737] [EC:3.4.25.1]
5694  PSMB6; proteasome subunit beta type-6 isoform 1 [KO:K02738] [EC:3.4.25.1]
5695  PSMB7; proteasome subunit beta type-7 precursor [KO:K02739] [EC:3.4.25.1]
5700  PSMC1; 26S proteasome regulatory subunit 4 isoform a [KO:K03062]
5701  PSMC2; 26S proteasome regulatory subunit 7 isoform 1 [KO:K03061]
5702  PSMC3; 26S proteasome regulatory subunit 6A [KO:K03065]
5704  PSMC4; 26S proteasome regulatory subunit 6B isoform 1 [KO:K03063]
5705  PSMC5; 26S proteasome regulatory subunit 8 isoform 1 [KO:K03066]
5706  PSMC6; 26S proteasome regulatory subunit 10B isoform 1 [KO:K03064]
5707  PSMD1; 26S proteasome non-ATPase regulatory subunit 1 isoform 1 [KO:K03032]
5708  PSMD2; 26S proteasome non-ATPase regulatory subunit 2 isoform 1 [KO:K03028]
5709  PSMD3; 26S proteasome non-ATPase regulatory subunit 3 [KO:K03033]
5710  PSMD4; 26S proteasome non-ATPase regulatory subunit 4 isoform 2 [KO:K03029]
5713  PSMD7; 26S proteasome non-ATPase regulatory subunit 7 [KO:K03038]
5714  PSMD8; 26S proteasome non-ATPase regulatory subunit 8 [KO:K03031]
5715  PSMD9; 26S proteasome non-ATPase regulatory subunit 9 isoform 1 [KO:K06693]
5717  PSMD11; 26S proteasome non-ATPase regulatory subunit 11 [KO:K03036]
5718  PSMD12; 26S proteasome non-ATPase regulatory subunit 12 isoform 1 [KO:K03035]
5719  PSMD13; 26S proteasome non-ATPase regulatory subunit 13 isoform 1 [KO:K03039]
581  BAX; apoptosis regulator BAX isoform alpha [KO:K02159]
5978  REST; RE1-silencing transcription factor isoform 1 [KO:K09222]
60673  ATG101; autophagy-related protein 101 [KO:K19730]
627  BDNF; neurotrophic factor BDNF precursor form isoform a preproprotein [KO:K04355]
6389  SDHA; succinate dehydrogenase [ubiquinone] flavoprotein subunit, mitochondrial isoform 1 [KO:K00234] [EC:1.3.5.1]
6390  SDHB; succinate dehydrogenase [ubiquinone] iron-sulfur subunit, mitochondrial isoform 1 precursor [KO:K00235] [EC:1.3.5.1]
6391  SDHC; succinate dehydrogenase cytochrome b560 subunit, mitochondrial isoform 1 precursor [KO:K00236]
6392  SDHD; succinate dehydrogenase [ubiquinone] cytochrome b small subunit, mitochondrial isoform a precursor [KO:K00237]
64446  DNAI2; dynein axonemal intermediate chain 2 isoform 1 [KO:K11143]
64764  CREB3L2; cyclic AMP-responsive element-binding protein 3-like protein 2 isoform 1 [KO:K09048]
64837  KLC2; kinesin light chain 2 isoform 1 [KO:K10407]
6506  SLC1A2; excitatory amino acid transporter 2 isoform 1 [KO:K05613]
6507  SLC1A3; excitatory amino acid transporter 1 isoform 1 [KO:K05614]
6647  SOD1; superoxide dismutase [Cu-Zn] [KO:K04565] [EC:1.15.1.1]
6648  SOD2; superoxide dismutase [Mn], mitochondrial isoform A precursor [KO:K04564] [EC:1.15.1.1]
6667  SP1; transcription factor Sp1 isoform a [KO:K04684]
6804  STX1A; syntaxin-1A isoform 1 [KO:K04560]
6874  TAF4; transcription initiation factor TFIID subunit 4 [KO:K03129]
6875  TAF4B; transcription initiation factor TFIID subunit 4B isoform 2 [KO:K03129]
6908  TBP; TATA-box-binding protein isoform 1 [KO:K03120]
7019  TFAM; transcription factor A, mitochondrial isoform 1 precursor [KO:K11830]
7052  TGM2; protein-glutamine gamma-glutamyltransferase 2 isoform a [KO:K05625] [EC:2.3.2.13]
7157  TP53; cellular tumor antigen p53 isoform a [KO:K04451]
7186  TRAF2; TNF receptor-associated factor 2 [KO:K03173] [EC:2.3.2.27]
7277  TUBA4A; tubulin alpha-4A chain isoform 1 [KO:K07374]
7278  TUBA3C; tubulin alpha-3C chain [KO:K07374]
7280  TUBB2A; tubulin beta-2A chain isoform 1 [KO:K07375]
7350  UCP1; mitochondrial brown fat uncoupling protein 1 isoform 1 [KO:K08769]
7381  UQCRB; cytochrome b-c1 complex subunit 7 isoform 1 [KO:K00417]
7384  UQCRC1; cytochrome b-c1 complex subunit 1, mitochondrial precursor [KO:K00414]
7385  UQCRC2; cytochrome b-c1 complex subunit 2, mitochondrial precursor [KO:K00415]
7386  UQCRFS1; cytochrome b-c1 complex subunit Rieske, mitochondrial [KO:K00411] [EC:7.1.1.8]
7388  UQCRH; cytochrome b-c1 complex subunit 6, mitochondrial isoform 1 precursor [KO:K00416]
7416  VDAC1; non-selective voltage-gated ion channel VDAC1 isoform 1 [KO:K05862]
7417  VDAC2; non-selective voltage-gated ion channel VDAC2 isoform 2 [KO:K15040]
7419  VDAC3; non-selective voltage-gated ion channel VDAC3 isoform 1 [KO:K15041]
774  CACNA1B; voltage-dependent N-type calcium channel subunit alpha-1B isoform 1 [KO:K04849]
7802  DNALI1; axonemal dynein light intermediate polypeptide 1 [KO:K10410]
7846  TUBA1A; tubulin alpha-1A chain isoform 1 [KO:K07374]
7979  SEM1; 26S proteasome complex subunit SEM1 isoform c [KO:K10881]
79861  TUBAL3; tubulin alpha chain-like 3 isoform 1 [KO:K07374]
81027  TUBB1; tubulin beta-1 chain [KO:K07375]
8218  CLTCL1; clathrin heavy chain 2 isoform 1 [KO:K04646]
83447  SLC25A31; ADP/ATP translocase 4 isoform 1 [KO:K05863]
83544  DNAL1; dynein axonemal light chain 1 isoform 1 [KO:K10411]
836  CASP3; caspase-3 isoform a preproprotein [KO:K02187] [EC:3.4.22.56]
8408  ULK1; serine/threonine-protein kinase ULK1 [KO:K21357] [EC:2.7.11.1]
841  CASP8; caspase-8 isoform 2 precursor [KO:K04398] [EC:3.4.22.61]
842  CASP9; caspase-9 isoform alpha precursor [KO:K04399] [EC:3.4.22.62]
84516  DCTN5; dynactin subunit 5 isoform 1 [KO:K10427]
84617  TUBB6; tubulin beta-6 chain isoform 1 [KO:K07375]
84699  CREB3L3; cyclic AMP-responsive element-binding protein 3-like protein 3 isoform a [KO:K09048]
84701  COX4I2; cytochrome c oxidase subunit 4 isoform 2, mitochondrial [KO:K02263]
84790  TUBA1C; tubulin alpha-1C chain isoform c [KO:K07374]
8632  DNAH17; dynein axonemal heavy chain 17 [KO:K10408]
8678  BECN1; beclin-1 isoform a [KO:K08334]
8701  DNAH11; dynein axonemal heavy chain 11 [KO:K10408]
89953  KLC4; kinesin light chain 4 isoform a [KO:K10407]
9001  HAP1; huntingtin-associated protein 1 isoform 3 [KO:K04647]
90993  CREB3L1; cyclic AMP-responsive element-binding protein 3-like protein 1 isoform 1 [KO:K09048]
9167  COX7A2L; cytochrome c oxidase subunit 7A2-like, mitochondrial isoform a [KO:K02270]
9377  COX5A; cytochrome c oxidase subunit 5A, mitochondrial precursor [KO:K02264]
9519  TBPL1; TATA box-binding protein-like 1 [KO:K03120]
9586  CREB5; cyclic AMP-responsive element-binding protein 5 isoform alpha [KO:K09047]
9706  ULK2; serine/threonine-protein kinase ULK2 [KO:K08269] [EC:2.7.11.1]
9776  ATG13; autophagy-related protein 13 isoform c [KO:K08331]
9821  RB1CC1; RB1-inducible coiled-coil protein 1 isoform 1 [KO:K17589]
9861  PSMD6; 26S proteasome non-ATPase regulatory subunit 6 isoform 2 [KO:K03037]
Compound
C00025  L-Glutamate
C00076  Calcium cation
C00238  Potassium cation
C01245  D-myo-Inositol 1,4,5-trisphosphate
C01330  Sodium cation
C04549  1-Phosphatidyl-1D-myo-inositol 3-phosphate
Reference
PMID:15459747
  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)
DOI:10.1038/sj.embor.7400250
Reference
PMID:17041811
  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)
DOI:10.1007/s00018-006-6242-0
Reference
PMID:18951640
  Authors
Bossy-Wetzel E, Petrilli A, Knott AB
  Title
Mutant huntingtin and mitochondrial dysfunction.
  Journal
Trends Neurosci 31:609-16 (2008)
DOI:10.1016/j.tins.2008.09.004
Reference
PMID:16288298
  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)
DOI:10.1038/nrn1806
Reference
PMID:15336977
  Authors
Bezprozvanny I, Hayden MR
  Title
Deranged neuronal calcium signaling and Huntington disease.
  Journal
Biochem Biophys Res Commun 322:1310-7 (2004)
DOI:10.1016/j.bbrc.2004.08.035
Reference
PMID:14526190
  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)
DOI:10.1159/000072864
Reference
PMID:12372277
  Authors
Ross CA.
  Title
Polyglutamine pathogenesis: emergence of unifying mechanisms for Huntington's disease and related disorders.
  Journal
Neuron 35:819-22 (2002)
DOI:10.1016/S0896-6273(02)00872-3
Reference
PMID:15242639
  Authors
Ross CA
  Title
Huntington's disease: new paths to pathogenesis.
  Journal
Cell 118:4-7 (2004)
DOI:10.1016/j.cell.2004.06.022
Reference
PMID:24739785
  Authors
Coffey ET
  Title
Nuclear and cytosolic JNK signalling in neurons.
  Journal
Nat Rev Neurosci 15:285-99 (2014)
DOI:10.1038/nrn3729
Reference
PMID:19525941
  Authors
Morfini GA, You YM, Pollema SL, Kaminska A, Liu K, Yoshioka K, Bjorkblom B, Coffey ET, Bagnato C, Han D, Huang CF, Banker G, Pigino G, Brady ST
  Title
Pathogenic huntingtin inhibits fast axonal transport by activating JNK3 and phosphorylating kinesin.
  Journal
Nat Neurosci 12:864-71 (2009)
DOI:10.1038/nn.2346
Reference
PMID:26920688
  Authors
Kumar P, Kumar D, Jha SK, Jha NK, Ambasta RK
  Title
Ion Channels in Neurological Disorders.
  Journal
Adv Protein Chem Struct Biol 103:97-136 (2016)
DOI:10.1016/bs.apcsb.2015.10.006
Reference
PMID:25191533
  Authors
Proft J, Weiss N
  Title
Rectifying rectifier channels in Huntington disease.
  Journal
Commun Integr Biol 7:e29410 (2014)
DOI:10.4161/cib.29410
Reference
PMID:15695335
  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)
DOI:10.1073/pnas.0409402102
Reference
PMID:29427371
  Authors
Mackay JP, Nassrallah WB, Raymond LA
  Title
Cause or compensation?-Altered neuronal Ca(2+) handling in Huntington's disease.
  Journal
CNS Neurosci Ther 24:301-310 (2018)
DOI:10.1111/cns.12817
Reference
PMID:11807533
  Authors
Mattson MP.
  Title
Accomplices to neuronal death.
  Journal
Nature 415:377-9 (2002)
DOI:10.1038/415377a
Reference
PMID:17081970
  Authors
McGill JK, Beal MF
  Title
PGC-1alpha, a new therapeutic target in Huntington's disease?
  Journal
Cell 127:465-8 (2006)
DOI:10.1016/j.cell.2006.10.023
Reference
PMID:30941017
  Authors
Intihar TA, Martinez EA, Gomez-Pastor R
  Title
Mitochondrial Dysfunction in Huntington's Disease; Interplay Between HSF1, p53 and PGC-1alpha Transcription Factors.
  Journal
Front Cell Neurosci 13:103 (2019)
DOI:10.3389/fncel.2019.00103
Reference
PMID:15996541
  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)
DOI:10.1016/j.neuron.2005.06.023
Reference
PMID:11738471
  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)
DOI:10.1016/S0197-0186(01)00059-6
Reference
PMID:15996546
  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)
DOI:10.1016/j.neuron.2005.06.005
Reference
PMID:11839795
  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)
DOI:10.1128/MCB.22.5.1277-1287.2002
Reference
PMID:25270767
  Authors
Vidal RL, Matus S, Bargsted L, Hetz C
  Title
Targeting autophagy in neurodegenerative diseases.
  Journal
Trends Pharmacol Sci 35:583-91 (2014)
DOI:10.1016/j.tips.2014.09.002
Reference
PMID:16522639
  Authors
Shibata M, Lu T, Furuya T, Degterev A, Mizushima N, Yoshimori T, MacDonald M, Yankner B, Yuan J
  Title
Regulation of intracellular accumulation of mutant Huntingtin by Beclin 1.
  Journal
J Biol Chem 281:14474-85 (2006)
DOI:10.1074/jbc.M600364200
Related
pathway
hsa00190  Oxidative phosphorylation
hsa03020  RNA polymerase
hsa03022  Basal transcription factors
hsa03050  Proteasome
hsa04020  Calcium signaling pathway
hsa04115  p53 signaling pathway
hsa04140  Autophagy - animal
hsa04141  Protein processing in endoplasmic reticulum
hsa04144  Endocytosis
hsa04210  Apoptosis
hsa04724  Glutamatergic synapse
KO pathway
ko05016   

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