Panther Pathway: P00029 Huntington's disease is associated with a mutant polyglutamine expansion in the huntingtin gene. Wild-type huntingtin protein is normally involved in vesicle endocytosis, regulation of calcium channels via the PSD-95 complex, and inhibition of apoptosis via BDNF. Mutant, polyglutamine expanded huntingtin may lose these functions, as well as gain toxicity via stimulation of apoptosis, regulation of gene transcription via p53, and abnormal calcium-mediated signal transduction pathways. Medline=11724916 Medline=12569151 Medline=12932731 Medline=14526190 PMID: 11724916 PMID: 12569151 PMID: 12932731 PMID: 14526190 4.0 s6 PROTEIN p1 s6 PROTEIN p2 8 s14 PROTEIN p7 s14 PROTEIN p2 s53 PROTEIN p2 s70 PROTEIN p34 s70 PROTEIN p1 s70 PROTEIN p35 s70 PROTEIN p36 s75 PROTEIN p37 s75 PROTEIN p1 s75 PROTEIN p38 s94 PROTEIN p2 s94 PROTEIN p40 s95 PROTEIN p2 s95 PROTEIN p40 s104 PROTEIN p1 s104 PROTEIN p43 s106 PROTEIN p43 s106 PROTEIN p44 s121 PROTEIN p49 s121 PROTEIN p50 s121 PROTEIN p51 s121 PROTEIN p48 s121 PROTEIN p1 s136 PROTEIN p1 s136 PROTEIN p58 s136 PROTEIN p56 s136 PROTEIN p55 s136 PROTEIN p57 s153 PROTEIN p52 s166 PROTEIN p52 s166 PROTEIN p43 s166 PROTEIN p53 s166 PROTEIN p54 s166 PROTEIN p1 s166 PROTEIN p60 8 s176 PROTEIN p62 s176 PROTEIN p63 s176 PROTEIN p1 s186 PROTEIN p68 s186 ION GDP s187 PROTEIN p68 s215 PROTEIN p11 s215 PROTEIN p7 s215 PROTEIN p10 s215 PROTEIN p1 s215 PROTEIN p48 s215 PROTEIN p69 s225 PROTEIN p1 s225 PROTEIN p48 s50 PROTEIN p27 s50 PROTEIN p17 s229 PROTEIN p41 s229 PROTEIN p42 Long Name: Actin-related protein 2 and 3 complex Synonym: Synonym not specified Accession: P00811 s166 PROTEIN p59 s153 PROTEIN p43 s187 ION GTP s53 PROTEIN p28 SQUARE_CLOSEUP_NORTH SQUARE_CLOSEUP_NORTHEAST OVAL OVAL inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive active inactive inactive inactive inactive active active inactive inactive inactive inactive inactive active inactive active inactive active inactive active inactive active inactive inactive inactive inactive inactive inactive active inactive active inactive active inactive inactive inactive inactive inactive active inactive inactive inactive inactive inactive inactive inactive inactive active inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive active inactive inactive active inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive inactive Wilson Christina SRI International Synapse of striatal medium spiny neuron Nucleus Mitochondrion Endocytosed vesicle Long Name: Huntingtin Synonym: Synonym not specified Accession: P00766 inside PROTEIN p1 Long Name: Brain-derived neurotrophic factor Synonym: Synonym not specified Accession: P00795 inside PROTEIN p4 Long Name: Caspase 3 Synonym: Synonym not specified Accession: P00812 inside PROTEIN p3 Long Name: Kainate receptor Synonym: Synonym not specified Accession: P00796 transmembrane PROTEIN p10 Long Name: N-methyl-d-aspartate receptor Synonym: Synonym not specified Accession: P00778 transmembrane PROTEIN p11 Long Name: Long Name: Ca2+ Synonym: Synonym not specified Accession: U05300 inside ION Ca_super_2+_endsuper Long Name: Long Name: Ca2+ Synonym: Synonym not specified Accession: U05300 inside ION Ca_super_2+_endsuper Long Name: Mitogen activated protein kinase kinase 4 Synonym: MEK4,MKK4 Accession: P00787 inside PROTEIN p13 Long Name: Mitogen activated protein kinase kinase 7 Synonym: MKK7 Accession: P00784 inside PROTEIN p14 Long Name: Stress signalling kinase 1 Synonym: Synonym not specified Accession: P00792 inside PROTEIN p15 Long Name: c-Jun N-terminal kinase 2 Synonym: Synonym not specified Accession: P00799 inside PROTEIN p16 Long Name: c-Jun Synonym: Synonym not specified Accession: P00776 inside PROTEIN p17 Long Name: c-Jun Synonym: Synonym not specified Accession: P00776 inside PROTEIN p17 Long Name: Truncated Htt Synonym: Synonym not specified Accession: P00761 inside PROTEIN p19 Long Name: Disease-associated mutant huntingtin containing polyglutamine expansion Synonym: Synonym not specified Accession: P00800 inside PROTEIN p2 Long Name: Disease-associated mutant huntingtin containing polyglutamine expansion Synonym: Synonym not specified Accession: P00800 inside PROTEIN p2 8 Long Name: Long Name: Long name not specified Synonym: Synonym not specified Accession: U05292 Heterodimer Member Info: Htt#PROTEIN#Huntingtin#P00766##;PolyQ Htt#PROTEIN#Disease-associated mutant huntingtin containing polyglutamine expansion#P00800## inside COMPLEX Complex_br_(Htt/PolyQ Htt) Long Name: Long Name: Long name not specified Synonym: Synonym not specified Accession: U05296 Heterodimer Member Info: PSD-95#PROTEIN#Postsynaptic density 95#P00789##;PolyQ Htt#PROTEIN#Disease-associated mutant huntingtin containing polyglutamine expansion#P00800## inside COMPLEX Complex_br_(PSD-95/PolyQ Htt) Long Name: Disease-associated mutant huntingtin containing polyglutamine expansion Synonym: Synonym not specified Accession: P00800 inside PROTEIN p2 Long Name: Thymoma Viral Proto-Oncogene 1 Synonym: PKB,PKB/Akt,Pkb alpha Accession: P00805 inside PROTEIN p20 Long Name: Protein fragment Synonym: Synonym not specified Accession: P00791 inside PROTEIN p22 Long Name: Caspase 6 Synonym: Synonym not specified Accession: P00809 inside PROTEIN p23 Long Name: Calpain Synonym: Synonym not specified Accession: P00788 inside PROTEIN p24 Long Name: Iron Synonym: Synonym not specified Accession: U02360 inside ION Iron Long Name: Mixed lineage kinase 2 Synonym: MAPKKK10 Accession: P00764 inside PROTEIN p12 Long Name: Mixed lineage kinase 2 Synonym: MAPKKK10 Accession: P00764 inside PROTEIN p12 Long Name: Long Name: Ca2+ Synonym: Synonym not specified Accession: U05300 inside ION Ca_super_2+_endsuper Long Name: Cytochrome c Synonym: Synonym not specified Accession: P00785 inside PROTEIN p25 Long Name: Apoptotic protease activating factor-1 Synonym: Synonym not specified Accession: P00768 inside PROTEIN p26 Long Name: Oxidative stress Synonym: Synonym not specified Accession: U02357 inside PHENOTYPE Oxidative_br_stress Long Name: Gene transcription Synonym: Synonym not specified Accession: U02352 inside PHENOTYPE Gene_br_transcription Long Name: Disease-associated mutant huntingtin containing polyglutamine expansion Synonym: Synonym not specified Accession: P00800 inside PROTEIN p2 Long Name: CREB binding protein Synonym: Synonym not specified Accession: P00777 inside PROTEIN p28 Long Name: Long Name: Long name not specified Synonym: Synonym not specified Accession: U05284 Heterodimer Member Info: CBP#PROTEIN#CREB binding protein#P00777##;PolyQ Htt#PROTEIN#Disease-associated mutant huntingtin containing polyglutamine expansion#P00800## inside COMPLEX Complex_br_(CBP/PolyQ Htt) Long Name: Disease-associated mutant huntingtin containing polyglutamine expansion Synonym: Synonym not specified Accession: P00800 inside PROTEIN p2 8 Long Name: P53 tumor suppressor phosphoprotein Synonym: TP53 Accession: P00797 inside PROTEIN p29 Long Name: Long Name: Long name not specified Synonym: Synonym not specified Accession: U05285 Heterodimer Member Info: Htt#PROTEIN#Huntingtin#P00766##;TBP#PROTEIN#Tata binding protein#P00779##;Sp1#PROTEIN#Sp1#P00803##;TAFII130#PROTEIN#TAFII130#P00806## inside COMPLEX Complex_br_(Sp1/Htt/_br_TAFII130/TBP) Long Name: Long Name: Long name not specified Synonym: Synonym not specified Accession: U05282 Heterodimer Member Info: Htt#PROTEIN#Huntingtin#P00766##;N-CoR#PROTEIN#Nuclear receptor co-repressor#P00770##;Sin3A#PROTEIN#Sin3A#P00771## inside COMPLEX Complex_br_(N-CoR/Htt/_br_Sin3A) Long Name: Truncated Htt Synonym: Synonym not specified Accession: P00761 inside PROTEIN p19 8 Long Name: Membrane depolarization Synonym: Synonym not specified Accession: U02354 inside PHENOTYPE Membrane_br_depolarization Long Name: Long Name: Long name not specified Synonym: Synonym not specified Accession: U05290 Heterodimer Member Info: PolyQ Htt#PROTEIN#Disease-associated mutant huntingtin containing polyglutamine expansion#P00800##;GAPDH#PROTEIN#Glyceraldehyde-3-phosphate dehydrogenase#P00810#G3PD# inside COMPLEX Complex_br_(PolyQ Htt/GAPDH) Long Name: Long Name: Long name not specified Synonym: Synonym not specified Accession: U05283 Heterodimer Member Info: PolyQ Htt#PROTEIN#Disease-associated mutant huntingtin containing polyglutamine expansion#P00800##;GAPDH#PROTEIN#Glyceraldehyde-3-phosphate dehydrogenase#P00810#G3PD# inside COMPLEX Complex_br_(PolyQ Htt/GAPDH) Long Name: Glyceraldehyde-3-phosphate dehydrogenase Synonym: G3PD Accession: P00810 inside PROTEIN p40 Long Name: Glyceraldehyde-3-phosphate dehydrogenase Synonym: G3PD Accession: P00810 inside PROTEIN p40 Long Name: Apoptosis Synonym: Synonym not specified Accession: U02353 inside PHENOTYPE Apoptosis Long Name: Huntington interacting protein-1 Synonym: Synonym not specified Accession: P00765 inside PROTEIN p43 Long Name: Long Name: Long name not specified Synonym: Synonym not specified Accession: U05295 Heterodimer Member Info: Hip-1#PROTEIN#Huntington interacting protein-1#P00765##;Htt#PROTEIN#Huntingtin#P00766## inside COMPLEX Complex_br_(Htt/Hip-1) Long Name: Hip1 protein interactor Synonym: Synonym not specified Accession: P00794 inside PROTEIN p44 Long Name: Long Name: Long name not specified Synonym: Synonym not specified Accession: U05297 Heterodimer Member Info: Hip-1#PROTEIN#Huntington interacting protein-1#P00765##;Hippi#PROTEIN#Hip1 protein interactor#P00794## inside COMPLEX Complex_br_(Hip-1/Hippi) Long Name: Pro-caspase 8 Synonym: Synonym not specified Accession: P00767 inside PROTEIN p45 Long Name: Caspase 8 Synonym: Synonym not specified Accession: P00808 inside PROTEIN p46 Long Name: Long Name: Long name not specified Synonym: Synonym not specified Accession: U05286 Heterodimer Member Info: HAP1#PROTEIN#Huntingtin's associated protein#P00762##;Htt#PROTEIN#Huntingtin#P00766##;Dynein complex#PROTEIN#Dynein complex#P00774##;Microtubule#PROTEIN#Microtubule#P00780##;Dynactin#PROTEIN#Dynactin#P00781## transmembrane COMPLEX Complex_br_(Microtubule/Dynein_br_complex/_br_Dynactin/HAP1/_br_Htt) Long Name: Long Name: Long name not specified Synonym: Synonym not specified Accession: U05291 Heterodimer Member Info: Htt#PROTEIN#Huntingtin#P00766##;N-Wasp#PROTEIN#neural Wiskott-Aldrich syndrome protein #P00769##;PACSIN-1#PROTEIN#Protein kinase C and casein kinase substrate in neurons 1#P00802##;Synaptojanin#PROTEIN#Synaptojanin#P00804##;SH3GL3#PROTEIN#Src homology region 3-containing Grb2-like protein 3#P00813## outerSurface COMPLEX Complex_br_(Htt/SH3GL3/_br_PACSIN-1/Synaptojanin/_br_N-Wasp) Long Name: Actin-related protein 2 and 3 complex Synonym: Synonym not specified Accession: P00811 inside PROTEIN p59 Long Name: Actin Synonym: F-actin Accession: P00807 inside PROTEIN p60 Long Name: Actin Synonym: F-actin Accession: P00807 inside PROTEIN p60 8 Long Name: Long Name: Long name not specified Synonym: Synonym not specified Accession: U05289 Heterodimer Member Info: Hip-12#PROTEIN#Huntingtin interacting protein 12#P00763##;Hip-1#PROTEIN#Huntington interacting protein-1#P00765## inside COMPLEX Complex_br_(Hip-12/Hip-1) Long Name: Clathrin Synonym: Synonym not specified Accession: P00798 inside PROTEIN p53 Long Name: alpha-Adaptin Synonym: Synonym not specified Accession: P00782 inside PROTEIN p54 Long Name: Long Name: Long name not specified Synonym: Synonym not specified Accession: U05293 Heterodimer Member Info: Hip-12#PROTEIN#Huntingtin interacting protein 12#P00763##;Hip-1#PROTEIN#Huntington interacting protein-1#P00765##;Htt#PROTEIN#Huntingtin#P00766##;alpha-Adaptin#PROTEIN#alpha-Adaptin#P00782##;Clathrin#PROTEIN#Clathrin#P00798##;Actin#PROTEIN#Actin#P00807#F-actin# outerSurface COMPLEX Complex_br_(Hip-12/Hip-1/_br_Clathrin/_alpha_-Adaptin/_br_Htt/Actin) Long Name: beta-Tubulin Synonym: Synonym not specified Accession: P00790 inside PROTEIN p61 Long Name: beta-Tubulin Synonym: Synonym not specified Accession: P00790 inside PROTEIN p61 2 Long Name: Long Name: Long name not specified Synonym: Synonym not specified Accession: U05299 Heterodimer Member Info: Htt#PROTEIN#Huntingtin#P00766##;FIP-2#PROTEIN#FIP-2#P00772##;Rab8#PROTEIN#Rab8#P00783## inside COMPLEX Complex_br_(Rab8/FIP-2/_br_Htt) Long Name: GDP Synonym: Synonym not specified Accession: U02358 inside ION GDP Long Name: GTP Synonym: Synonym not specified Accession: U02356 inside ION GTP Long Name: Long Name: Rho family, small GTP binding protein Synonym: Synonym not specified Accession: U05288 Heterodimer Member Info: Rac#PROTEIN#Rac#P00775##;GDP#ION#GDP#U02358## inside COMPLEX Complex_br_(Rac/GDP) Long Name: Long Name: Long name not specified Synonym: Synonym not specified Accession: U05294 Heterodimer Member Info: Rac#PROTEIN#Rac#P00775##;GTP#ION#GTP#U02356## inside COMPLEX Complex_br_(Rac/GTP) Long Name: Long Name: Long name not specified Synonym: Synonym not specified Accession: U05281 Heterodimer Member Info: HAP1#PROTEIN#Huntingtin's associated protein#P00762##;Htt#PROTEIN#Huntingtin#P00766##;Duo#PROTEIN#Huntingtin-associated protein interacting protein#P00773#Kalirin#;NMDA receptor#PROTEIN#N-methyl-d-aspartate receptor#P00778##;PSD-95#PROTEIN#Postsynaptic density 95#P00789##;Kainate receptor#PROTEIN#Kainate receptor#P00796## transmembrane COMPLEX Complex_br_(NMDA_br_receptor/PSD-95/_br_Kainate_br_receptor/Htt/_br_HAP1/Duo) Long Name: Huntingtin-associated protein interacting protein Synonym: Kalirin Accession: P00773 inside PROTEIN p69 Long Name: Long Name: Long name not specified Synonym: Synonym not specified Accession: U05298 Heterodimer Member Info: HAP1#PROTEIN#Huntingtin's associated protein#P00762##;Htt#PROTEIN#Huntingtin#P00766## inside COMPLEX Complex_br_(Htt/HAP1) Long Name: Fos protein Synonym: c-fos Accession: P00801 inside PROTEIN p27 Long Name: Long Name: Long name not specified Synonym: Synonym not specified Accession: U05280 Heterodimer Member Info: c-Jun#PROTEIN#c-Jun#P00776##;Fos protein#PROTEIN#Fos protein#P00801#c-fos# inside COMPLEX Complex_br_(Fos protein/c-Jun) Long Name: Retrograde transport Synonym: Synonym not specified Accession: U02359 inside PHENOTYPE Retrograde_br_transport Long Name: Long Name: Long name not specified Synonym: Synonym not specified Accession: U05287 Heterodimer Member Info: ARF#PROTEIN#ADP-ribosylation factor#P00786##;Arfaptin-2#PROTEIN#Arfaptin-2#P00793#POR1# inside COMPLEX Complex_br_(Arfaptin-2/ARF) Long Name: Brain-derived neurotrophic factor Synonym: Synonym not specified Accession: G01531 inside GENE gn1 Long Name: Proline oxidase Synonym: Synonym not specified Accession: G01529 inside GENE gn2 Long Name: Bcl-2-binding component 3 Synonym: Synonym not specified Accession: G01534 inside GENE gn3 Long Name: Tumor protein p53 inducible protein 3 Synonym: Synonym not specified Accession: G01535 inside GENE gn4 Long Name: Bcl-2-associated X protein Synonym: Synonym not specified Accession: G01533 inside GENE gn5 Long Name: Polyglutamine expanded mutant huntingtin Synonym: Synonym not specified Accession: G01532 inside GENE gn6 Long Name: Huntingtin Synonym: Synonym not specified Accession: G01530 inside GENE gn7 inside RNA rn1 inside RNA rn2 inside RNA rn3 inside RNA rn4 inside RNA rn5 inside RNA rn6 inside RNA rn7 Long Name: Cytochrome c Synonym: Synonym not specified Accession: P00785 inside PROTEIN p25 STATE_TRANSITION a3 a4 a2 STATE_TRANSITION a2 a6 a312 HETERODIMER_ASSOCIATION 3.8999824792540494E-4,0.613236906701232 a1 a6 a9 INHIBITION a1 a5 TRANSPORT 0.42179147387808275,0.001999011724541422 a27 a30 a26 TRANSPORT 0.47416660240589126,0.002844125344563686 a29 a28 a25 STATE_TRANSITION a31 a32 a30 STATE_TRANSITION a33 a34 a32 STATE_TRANSITION a35 a36 a32 STATE_TRANSITION a37 a38 a32 STATE_TRANSITION a39 a40 a38 STATE_TRANSITION a41 a42 a40 STATE_TRANSITION a2 a45 a46 TRUNCATION 0.3969764906219684,0.23736018719296936 a1 a44 a48 a4 a49 a51 STATE_TRANSITION a50 a51 a55 STATE_TRANSITION a32 a53 a40 TRANSPORT 0.7273263903529106,6.217248937900877E-15 a54 a55 a113 TRANSPORT 0.41539998948088375,-0.002997948771890968 a56 a57 a113 STATE_TRANSITION a58 a59 a57 HETERODIMER_ASSOCIATION 0.5487634901039351,0.3130766065336559 a64 a42 a67 HETERODIMER_ASSOCIATION 0.0017394041183078635,0.37307641958493853 a69 a68 a72 STATE_TRANSITION a68 a73 STATE_TRANSITION 0.4751085520681553,0.0028244016044594034 a74 a75 a68 STATE_TRANSITION a44 a102 TRANSPORT a120 a121 a61 DISSOCIATION -0.007413074952667742,0.5263739837398376 a121 a124 a68 HETERODIMER_ASSOCIATION 0.2923405232908234,0.39386584402812996 a62 a125 a120 HETERODIMER_ASSOCIATION 0.34221574989567927,0.3772174105584032 a136 a134 a139 TRUNCATION -0.003320097808277467,0.5889808645714094 a140 a141 a142 a139 STATE_TRANSITION a174 a223 a173 STATE_TRANSITION a176 a177 a223 a240 a259 STATE_TRANSITION a224 a225 a240 STATE_TRANSITION 0.400487663446933,-9.326971586598454E-4 0.5769157966118437,-0.002795789012195682 a258 a257 a259 a254 a295 HETERODIMER_ASSOCIATION 0.6288673989513014,0.21217522052022264 a295 a21 a22 DISSOCIATION 0.5865653416996839,-4.7288132235512315E-4 0.6919681666625104,-0.06094604278445459 a295 a307 a22 a308 a25 a26 HETERODIMER_ASSOCIATION 0.28315009963856763,0.663837165561973 a134 a1 a135 HETERODIMER_ASSOCIATION 0.43608085096333227,0.40607286193089465 a177 a218 a217 a216 a201 a223 MODULATION a62 a61 PHYSICAL_STIMULATION a62 a113 PHYSICAL_STIMULATION a67 a63 INHIBITION a101 a63 PHYSICAL_STIMULATION a96 a63 PHYSICAL_STIMULATION a69 a63 TRANSCRIPTION a76 sa138 a75 TRANSCRIPTION 0.13079542477954753,-1.7462673534396345E-4 a78 sa141 a75 TRANSCRIPTION 0.45436002039775847,0.004283528811825477 a77 sa140 a75 TRANSCRIPTION a79 sa139 a75 PHYSICAL_STIMULATION 0.00828396498762407,-0.09063851781504617 a141 a5 PHYSICAL_STIMULATION a59 a5 PHYSICAL_STIMULATION a10 a5 TRANSCRIPTION a313 sa142 a1 TRANSLATION sa142 a10 TRANSCRIPTION a314 sa143 a52 TRANSLATION sa143 a1 TRANSLATION sa144 a2 TRANSCRIPTION a315 sa144 a52 PHYSICAL_STIMULATION a155 a309 PHYSICAL_STIMULATION 0.3442511168586875,-0.47512344227604064 a4 a5 PHYSICAL_STIMULATION 0.08211831209349474,-0.17907642341848107 0.9083716627927365,0.19981505333643024 a53 a5