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UniProtKB - P42858 (HD_HUMAN)
Protein
Huntingtin
Gene
HTT
Organism
Homo sapiens (Human)
Status
Functioni
May play a role in microtubule-mediated transport or vesicle function.
Promotes the formation of autophagic vesicles.
1 PublicationGO - Molecular functioni
- beta-tubulin binding Source: UniProtKB
- dynactin binding Source: UniProtKB
- dynein intermediate chain binding Source: UniProtKB
- heat shock protein binding Source: CAFA
- identical protein binding Source: IntAct
- kinase binding Source: ParkinsonsUK-UCL
- p53 binding Source: UniProtKB
- profilin binding Source: UniProtKB
- transmembrane transporter binding Source: UniProtKB
GO - Biological processi
- apoptotic process Source: UniProtKB-KW
- establishment of mitotic spindle orientation Source: UniProtKB
- Golgi organization Source: UniProtKB
- microtubule-based transport Source: GO_Central
- negative regulation of extrinsic apoptotic signaling pathway Source: UniProtKB
- positive regulation of aggrephagy Source: ParkinsonsUK-UCL
- positive regulation of apoptotic process Source: CAFA
- positive regulation of autophagy of mitochondrion Source: ParkinsonsUK-UCL
- positive regulation of cilium assembly Source: SYSCILIA_CCNET
- positive regulation of inositol 1,4,5-trisphosphate-sensitive calcium-release channel activity Source: UniProtKB
- positive regulation of lipophagy Source: ParkinsonsUK-UCL
- protein destabilization Source: CAFA
- regulation of CAMKK-AMPK signaling cascade Source: ARUK-UCL
- regulation of cAMP-dependent protein kinase activity Source: ARUK-UCL
- regulation of phosphoprotein phosphatase activity Source: dictyBase
- retrograde vesicle-mediated transport, Golgi to endoplasmic reticulum Source: UniProtKB
- vesicle transport along microtubule Source: UniProtKB
- vocal learning Source: AgBase
Keywordsi
| Biological process | Apoptosis |
Enzyme and pathway databases
| PathwayCommonsi | P42858 |
| Reactomei | R-HSA-9022692, Regulation of MECP2 expression and activity |
| SignaLinki | P42858 |
| SIGNORi | P42858 |
Protein family/group databases
| MoonDBi | P42858, Predicted |
Names & Taxonomyi
| Protein namesi | Recommended name: HuntingtinAlternative name(s): Huntington disease protein Short name: HD protein Cleaved into the following chain: |
| Gene namesi | Name:HTT Synonyms:HD, IT15 |
| Organismi | Homo sapiens (Human) |
| Taxonomic identifieri | 9606 [NCBI] |
| Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
| Proteomesi |
|
Organism-specific databases
| HGNCi | HGNC:4851, HTT |
| MIMi | 613004, gene |
| neXtProti | NX_P42858 |
| VEuPathDBi | HostDB:ENSG00000197386 |
Subcellular locationi
Endosome
- Early endosome 1 Publication
Cytoplasm and Cytosol
- Cytoplasm 3 Publications
Nucleus
- Nucleus 2 Publications
Note: 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).2 Publications
Other locations
- autophagosome 1 Publication
Cytoskeleton
- centriole Source: SYSCILIA_CCNET
Cytosol
- cytosol Source: UniProtKB
- postsynaptic cytosol Source: SynGO
- presynaptic cytosol Source: SynGO
Endoplasmic reticulum
- endoplasmic reticulum Source: UniProtKB
Endosome
- early endosome Source: UniProtKB
- late endosome Source: UniProtKB
Golgi apparatus
- Golgi apparatus Source: UniProtKB
Nucleus
- nucleoplasm Source: HPA
- nucleus Source: UniProtKB
Other locations
- autophagosome Source: UniProtKB
- axon Source: UniProtKB
- cytoplasm Source: UniProtKB
- cytoplasmic vesicle membrane Source: UniProtKB
- dendrite Source: UniProtKB
- inclusion body Source: CAFA
- perinuclear region of cytoplasm Source: CAFA
- protein-containing complex Source: UniProtKB
Keywords - Cellular componenti
Cytoplasm, Cytoplasmic vesicle, Endosome, NucleusPathology & Biotechi
Involvement in diseasei
Huntington disease (HD)1 Publication
The disease is caused by variants affecting the gene represented in this entry.
Disease descriptionA neurodegenerative disorder characterized by involuntary movements (chorea), general motor impairment, psychiatric disorders and dementia. Onset of the disease occurs usually in the third or fourth decade of life. Onset and clinical course depend on the degree of poly-Gln repeat expansion, longer expansions resulting in earlier onset and more severe clinical manifestations. Neuropathology of Huntington disease displays a distinctive pattern with loss of neurons, especially in the caudate and putamen.
Related information in OMIMLopes-Maciel-Rodan syndrome (LOMARS)2 Publications
The disease is caused by variants affecting the gene represented in this entry.
Disease descriptionAn autosomal recessive neurodevelopmental disorder characterized by developmental regression in infancy, delayed psychomotor development, severe intellectual disability, and cerebral and cerebellar atrophy. Additional features include swallowing problems, dystonia, bradykinesia, and continuous manual stereotypies without chorea. Some patients manifest seizures.
Related information in OMIM| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Natural variantiVAR_079026 | 703 | P → L in LOMARS. 1 PublicationCorresponds to variant dbSNP:rs768047421Ensembl. | 1 | |
| Natural variantiVAR_079027 | 2717 | F → L in LOMARS. 1 PublicationCorresponds to variant dbSNP:rs1085307052Ensembl. | 1 |
Mutagenesis
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Mutagenesisi | 495 | I → A: Inhibits interaction with ZDHHC13 and ZDHHC17. 1 Publication | 1 | |
| Mutagenesisi | 498 – 499 | QP → AA: Abolishes interaction with ZDHHC17. 1 Publication | 2 | |
| Mutagenesisi | 498 | Q → A: Inhibits interaction with ZDHHC13 and ZDHHC17. 1 Publication | 1 | |
| Mutagenesisi | 499 | P → A: Inhibits interaction with ZDHHC13 and ZDHHC17. 1 Publication | 1 | |
| Mutagenesisi | 511 | D → A: Loss of proteolytic cleavage. 1 Publication | 1 | |
| Mutagenesisi | 528 | D → A: No effect on proteolytic cleavage. 1 Publication | 1 | |
| Mutagenesisi | 550 | D → E: Loss of proteolytic cleavage. Loss of myristoylation. 1 Publication | 1 | |
| Mutagenesisi | 551 | G → A: Loss of myristoylation. 2 Publications | 1 | |
| Mutagenesisi | 551 | G → S: Loss of myristoylation. 1 Publication | 1 | |
| Mutagenesisi | 584 | D → A: Loss of proteolytic cleavage. 1 Publication | 1 |
Keywords - Diseasei
Disease variant, Mental retardation, NeurodegenerationOrganism-specific databases
| DisGeNETi | 3064 |
| GeneReviewsi | HTT |
| MalaCardsi | HTT |
| MIMi | 143100, phenotype 617435, phenotype |
| OpenTargetsi | ENSG00000197386 |
| Orphaneti | 399, Huntington disease 248111, Juvenile Huntington disease |
| PharmGKBi | PA164741646 |
Miscellaneous databases
| Pharosi | P42858, Tchem |
Chemistry databases
| ChEMBLi | CHEMBL5514 |
| DrugBanki | DB09130, Copper |
Genetic variation databases
| BioMutai | HTT |
| DMDMi | 296434520 |
PTM / Processingi
Molecule processing
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| ChainiPRO_0000083942 | 1 – 3142 | HuntingtinAdd BLAST | 3142 | |
| ChainiPRO_0000447477 | 551 – 584 | Huntingtin, myristoylated N-terminal fragmentAdd BLAST | 34 |
Amino acid modifications
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Modified residuei | 9 | N6-acetyllysine1 Publication | 1 | |
| Modified residuei | 176 | N6-acetyllysine1 Publication | 1 | |
| Modified residuei | 234 | N6-acetyllysine1 Publication | 1 | |
| Modified residuei | 343 | N6-acetyllysine1 Publication | 1 | |
| Modified residuei | 411 | PhosphoserineCombined sources | 1 | |
| Modified residuei | 417 | PhosphoserineBy similarity | 1 | |
| Modified residuei | 419 | PhosphoserineBy similarity | 1 | |
| Modified residuei | 432 | PhosphoserineCombined sources | 1 | |
| Modified residuei | 442 | N6-acetyllysine1 Publication | 1 | |
| Lipidationi | 551 | N-myristoyl glycine2 Publications | 1 | |
| Modified residuei | 640 | PhosphoserineCombined sources | 1 | |
| Modified residuei | 643 | PhosphoserineCombined sources | 1 | |
| Modified residuei | 1179 | Phosphoserine; by CDK51 Publication | 1 | |
| Modified residuei | 1199 | Phosphoserine; by CDK5Combined sources1 Publication | 1 | |
| Modified residuei | 1870 | PhosphoserineCombined sources | 1 | |
| Modified residuei | 1874 | PhosphoserineCombined sources | 1 |
Post-translational modificationi
Cleaved by caspases downstream of the polyglutamine stretch (PubMed:8696339, PubMed:9535906, PubMed:10770929, PubMed:29802276). The resulting N-terminal fragments are cytotoxic and provokes apoptosis (PubMed:10770929).4 Publications
Forms with expanded polyglutamine expansion are specifically ubiquitinated by SYVN1, which promotes their proteasomal degradation.1 Publication
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.1 Publication
Myristoylated at Gly-551, following proteolytic cleavage at Asp-550.2 Publications
Sites
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Sitei | 511 – 512 | Cleavage; by caspase-31 Publication | 2 | |
| Sitei | 528 – 529 | Cleavage; by caspase-3Sequence analysis | 2 | |
| Sitei | 550 – 551 | Cleavage; by caspase-31 Publication | 2 | |
| Sitei | 584 – 585 | Cleavage; by caspase-61 Publication | 2 | |
| Sitei | 587 – 588 | Cleavage; by caspase-3Sequence analysis | 2 |
Keywords - PTMi
Acetylation, Lipoprotein, Myristate, Phosphoprotein, Ubl conjugationProteomic databases
| EPDi | P42858 |
| jPOSTi | P42858 |
| MassIVEi | P42858 |
| MaxQBi | P42858 |
| PaxDbi | P42858 |
| PeptideAtlasi | P42858 |
| PRIDEi | P42858 |
| ProteomicsDBi | 55561 |
PTM databases
| GlyGeni | P42858, 3 sites, 1 O-linked glycan (3 sites) |
| iPTMneti | P42858 |
| MetOSitei | P42858 |
| PhosphoSitePlusi | P42858 |
| SwissPalmi | P42858 |
Expressioni
Tissue specificityi
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.1 Publication
Gene expression databases
| Bgeei | ENSG00000197386, Expressed in sural nerve and 180 other tissues |
| ExpressionAtlasi | P42858, baseline and differential |
| Genevisiblei | P42858, HS |
Organism-specific databases
| HPAi | ENSG00000197386, Low tissue specificity |
Interactioni
Subunit structurei
Interacts with PFN1 (PubMed:18573880).
Interacts through its N-terminus with PRPF40A (PubMed:9700202).
Interacts with PQBP1 (PubMed:10332029).
Interacts with SETD2 (PubMed:9700202, PubMed:10958656, PubMed:11461154).
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:28882895, PubMed:28757145).
Interacts with F8A1/F8A2/F8A3 (PubMed:29466333, PubMed:16476778).
Found in a complex with F8A1/F8A2/F8A3, HTT and RAB5A; mediates the recruitment of HTT by RAB5A (PubMed:16476778).
By similarity12 PublicationsBinary interactionsi
P42858
GO - Molecular functioni
- beta-tubulin binding Source: UniProtKB
- dynactin binding Source: UniProtKB
- dynein intermediate chain binding Source: UniProtKB
- heat shock protein binding Source: CAFA
- identical protein binding Source: IntAct
- kinase binding Source: ParkinsonsUK-UCL
- p53 binding Source: UniProtKB
- profilin binding Source: UniProtKB
- transmembrane transporter binding Source: UniProtKB
Protein-protein interaction databases
| BioGRIDi | 109314, 394 interactors |
| CORUMi | P42858 |
| DIPi | DIP-32492N |
| ELMi | P42858 |
| IntActi | P42858, 1108 interactors |
| MINTi | P42858 |
| STRINGi | 9606.ENSP00000347184 |
Chemistry databases
| BindingDBi | P42858 |
Miscellaneous databases
| RNActi | P42858, protein |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details3D structure databases
| BMRBi | P42858 |
| SMRi | P42858 |
| ModBasei | Search... |
| PDBe-KBi | Search... |
Miscellaneous databases
| EvolutionaryTracei | P42858 |
Family & Domainsi
Domains and Repeats
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Repeati | 204 – 241 | HEAT 1Add BLAST | 38 | |
| Repeati | 246 – 283 | HEAT 2Add BLAST | 38 | |
| Repeati | 316 – 360 | HEAT 3Add BLAST | 45 | |
| Repeati | 802 – 839 | HEAT 4Add BLAST | 38 | |
| Repeati | 902 – 940 | HEAT 5Add BLAST | 39 |
Region
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Regioni | 3 – 13 | Sufficient for interaction with TPR1 PublicationAdd BLAST | 11 | |
| Regioni | 14 – 85 | DisorderedSequence analysisAdd BLAST | 72 | |
| Regioni | 447 – 469 | DisorderedSequence analysisAdd BLAST | 23 | |
| Regioni | 491 – 502 | Interaction with ZDHHC171 PublicationAdd BLAST | 12 | |
| Regioni | 517 – 583 | DisorderedSequence analysisAdd BLAST | 67 | |
| Regioni | 1176 – 1225 | DisorderedSequence analysisAdd BLAST | 50 | |
| Regioni | 2330 – 2351 | DisorderedSequence analysisAdd BLAST | 22 | |
| Regioni | 2633 – 2662 | DisorderedSequence analysisAdd BLAST | 30 |
Motif
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Motifi | 2395 – 2404 | Nuclear export signalBy similarity | 10 |
Compositional bias
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Compositional biasi | 14 – 35 | Polar residuesSequence analysisAdd BLAST | 22 | |
| Compositional biasi | 36 – 82 | Pro residuesSequence analysisAdd BLAST | 47 | |
| Compositional biasi | 531 – 583 | Polar residuesSequence analysisAdd BLAST | 53 | |
| Compositional biasi | 1205 – 1225 | Polar residuesSequence analysisAdd BLAST | 21 | |
| Compositional biasi | 2335 – 2349 | Basic and acidic residuesSequence analysisAdd BLAST | 15 |
Domaini
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.1 Publication
Sequence similaritiesi
Belongs to the huntingtin family.Curated
Keywords - Domaini
RepeatPhylogenomic databases
| eggNOGi | ENOG502QR1D, Eukaryota |
| GeneTreei | ENSGT00390000015863 |
| HOGENOMi | CLU_000428_0_0_1 |
| InParanoidi | P42858 |
| OMAi | YSWWAEV |
| OrthoDBi | 33894at2759 |
| PhylomeDBi | P42858 |
| TreeFami | TF323608 |
Family and domain databases
| Gene3Di | 1.25.10.10, 2 hits |
| InterProi | View protein in InterPro IPR011989, ARM-like IPR016024, ARM-type_fold IPR000091, Huntingtin IPR028426, Huntingtin_fam IPR024613, Huntingtin_middle-repeat |
| PANTHERi | PTHR10170, PTHR10170, 1 hit |
| Pfami | View protein in Pfam PF12372, DUF3652, 1 hit |
| PRINTSi | PR00375, HUNTINGTIN |
| SUPFAMi | SSF48371, SSF48371, 2 hits |
Sequence (1+)i
Sequence statusi: Complete.
Sequence processingi: The displayed sequence is further processed into a mature form.
This entry has 1 described isoform and 7 potential isoforms that are computationally mapped.Show allAlign All
P42858-1 [UniParc]FASTAAdd to basket
10 20 30 40 50
MATLEKLMKA FESLKSFQQQ QQQQQQQQQQ QQQQQQQQPP PPPPPPPPPQ
60 70 80 90 100
LPQPPPQAQP LLPQPQPPPP PPPPPPGPAV AEEPLHRPKK ELSATKKDRV
110 120 130 140 150
NHCLTICENI VAQSVRNSPE FQKLLGIAME LFLLCSDDAE SDVRMVADEC
160 170 180 190 200
LNKVIKALMD SNLPRLQLEL YKEIKKNGAP RSLRAALWRF AELAHLVRPQ
210 220 230 240 250
KCRPYLVNLL PCLTRTSKRP EESVQETLAA AVPKIMASFG NFANDNEIKV
260 270 280 290 300
LLKAFIANLK SSSPTIRRTA AGSAVSICQH SRRTQYFYSW LLNVLLGLLV
310 320 330 340 350
PVEDEHSTLL ILGVLLTLRY LVPLLQQQVK DTSLKGSFGV TRKEMEVSPS
360 370 380 390 400
AEQLVQVYEL TLHHTQHQDH NVVTGALELL QQLFRTPPPE LLQTLTAVGG
410 420 430 440 450
IGQLTAAKEE SGGRSRSGSI VELIAGGGSS CSPVLSRKQK GKVLLGEEEA
460 470 480 490 500
LEDDSESRSD VSSSALTASV KDEISGELAA SSGVSTPGSA GHDIITEQPR
510 520 530 540 550
SQHTLQADSV DLASCDLTSS ATDGDEEDIL SHSSSQVSAV PSDPAMDLND
560 570 580 590 600
GTQASSPISD SSQTTTEGPD SAVTPSDSSE IVLDGTDNQY LGLQIGQPQD
610 620 630 640 650
EDEEATGILP DEASEAFRNS SMALQQAHLL KNMSHCRQPS DSSVDKFVLR
660 670 680 690 700
DEATEPGDQE NKPCRIKGDI GQSTDDDSAP LVHCVRLLSA SFLLTGGKNV
710 720 730 740 750
LVPDRDVRVS VKALALSCVG AAVALHPESF FSKLYKVPLD TTEYPEEQYV
760 770 780 790 800
SDILNYIDHG DPQVRGATAI LCGTLICSIL SRSRFHVGDW MGTIRTLTGN
810 820 830 840 850
TFSLADCIPL LRKTLKDESS VTCKLACTAV RNCVMSLCSS SYSELGLQLI
860 870 880 890 900
IDVLTLRNSS YWLVRTELLE TLAEIDFRLV SFLEAKAENL HRGAHHYTGL
910 920 930 940 950
LKLQERVLNN VVIHLLGDED PRVRHVAAAS LIRLVPKLFY KCDQGQADPV
960 970 980 990 1000
VAVARDQSSV YLKLLMHETQ PPSHFSVSTI TRIYRGYNLL PSITDVTMEN
1010 1020 1030 1040 1050
NLSRVIAAVS HELITSTTRA LTFGCCEALC LLSTAFPVCI WSLGWHCGVP
1060 1070 1080 1090 1100
PLSASDESRK SCTVGMATMI LTLLSSAWFP LDLSAHQDAL ILAGNLLAAS
1110 1120 1130 1140 1150
APKSLRSSWA SEEEANPAAT KQEEVWPALG DRALVPMVEQ LFSHLLKVIN
1160 1170 1180 1190 1200
ICAHVLDDVA PGPAIKAALP SLTNPPSLSP IRRKGKEKEP GEQASVPLSP
1210 1220 1230 1240 1250
KKGSEASAAS RQSDTSGPVT TSKSSSLGSF YHLPSYLKLH DVLKATHANY
1260 1270 1280 1290 1300
KVTLDLQNST EKFGGFLRSA LDVLSQILEL ATLQDIGKCV EEILGYLKSC
1310 1320 1330 1340 1350
FSREPMMATV CVQQLLKTLF GTNLASQFDG LSSNPSKSQG RAQRLGSSSV
1360 1370 1380 1390 1400
RPGLYHYCFM APYTHFTQAL ADASLRNMVQ AEQENDTSGW FDVLQKVSTQ
1410 1420 1430 1440 1450
LKTNLTSVTK NRADKNAIHN HIRLFEPLVI KALKQYTTTT CVQLQKQVLD
1460 1470 1480 1490 1500
LLAQLVQLRV NYCLLDSDQV FIGFVLKQFE YIEVGQFRES EAIIPNIFFF
1510 1520 1530 1540 1550
LVLLSYERYH SKQIIGIPKI IQLCDGIMAS GRKAVTHAIP ALQPIVHDLF
1560 1570 1580 1590 1600
VLRGTNKADA GKELETQKEV VVSMLLRLIQ YHQVLEMFIL VLQQCHKENE
1610 1620 1630 1640 1650
DKWKRLSRQI ADIILPMLAK QQMHIDSHEA LGVLNTLFEI LAPSSLRPVD
1660 1670 1680 1690 1700
MLLRSMFVTP NTMASVSTVQ LWISGILAIL RVLISQSTED IVLSRIQELS
1710 1720 1730 1740 1750
FSPYLISCTV INRLRDGDST STLEEHSEGK QIKNLPEETF SRFLLQLVGI
1760 1770 1780 1790 1800
LLEDIVTKQL KVEMSEQQHT FYCQELGTLL MCLIHIFKSG MFRRITAAAT
1810 1820 1830 1840 1850
RLFRSDGCGG SFYTLDSLNL RARSMITTHP ALVLLWCQIL LLVNHTDYRW
1860 1870 1880 1890 1900
WAEVQQTPKR HSLSSTKLLS PQMSGEEEDS DLAAKLGMCN REIVRRGALI
1910 1920 1930 1940 1950
LFCDYVCQNL HDSEHLTWLI VNHIQDLISL SHEPPVQDFI SAVHRNSAAS
1960 1970 1980 1990 2000
GLFIQAIQSR CENLSTPTML KKTLQCLEGI HLSQSGAVLT LYVDRLLCTP
2010 2020 2030 2040 2050
FRVLARMVDI LACRRVEMLL AANLQSSMAQ LPMEELNRIQ EYLQSSGLAQ
2060 2070 2080 2090 2100
RHQRLYSLLD RFRLSTMQDS LSPSPPVSSH PLDGDGHVSL ETVSPDKDWY
2110 2120 2130 2140 2150
VHLVKSQCWT RSDSALLEGA ELVNRIPAED MNAFMMNSEF NLSLLAPCLS
2160 2170 2180 2190 2200
LGMSEISGGQ KSALFEAARE VTLARVSGTV QQLPAVHHVF QPELPAEPAA
2210 2220 2230 2240 2250
YWSKLNDLFG DAALYQSLPT LARALAQYLV VVSKLPSHLH LPPEKEKDIV
2260 2270 2280 2290 2300
KFVVATLEAL SWHLIHEQIP LSLDLQAGLD CCCLALQLPG LWSVVSSTEF
2310 2320 2330 2340 2350
VTHACSLIYC VHFILEAVAV QPGEQLLSPE RRTNTPKAIS EEEEEVDPNT
2360 2370 2380 2390 2400
QNPKYITAAC EMVAEMVESL QSVLALGHKR NSGVPAFLTP LLRNIIISLA
2410 2420 2430 2440 2450
RLPLVNSYTR VPPLVWKLGW SPKPGGDFGT AFPEIPVEFL QEKEVFKEFI
2460 2470 2480 2490 2500
YRINTLGWTS RTQFEETWAT LLGVLVTQPL VMEQEESPPE EDTERTQINV
2510 2520 2530 2540 2550
LAVQAITSLV LSAMTVPVAG NPAVSCLEQQ PRNKPLKALD TRFGRKLSII
2560 2570 2580 2590 2600
RGIVEQEIQA MVSKRENIAT HHLYQAWDPV PSLSPATTGA LISHEKLLLQ
2610 2620 2630 2640 2650
INPERELGSM SYKLGQVSIH SVWLGNSITP LREEEWDEEE EEEADAPAPS
2660 2670 2680 2690 2700
SPPTSPVNSR KHRAGVDIHS CSQFLLELYS RWILPSSSAR RTPAILISEV
2710 2720 2730 2740 2750
VRSLLVVSDL FTERNQFELM YVTLTELRRV HPSEDEILAQ YLVPATCKAA
2760 2770 2780 2790 2800
AVLGMDKAVA EPVSRLLEST LRSSHLPSRV GALHGVLYVL ECDLLDDTAK
2810 2820 2830 2840 2850
QLIPVISDYL LSNLKGIAHC VNIHSQQHVL VMCATAFYLI ENYPLDVGPE
2860 2870 2880 2890 2900
FSASIIQMCG VMLSGSEEST PSIIYHCALR GLERLLLSEQ LSRLDAESLV
2910 2920 2930 2940 2950
KLSVDRVNVH SPHRAMAALG LMLTCMYTGK EKVSPGRTSD PNPAAPDSES
2960 2970 2980 2990 3000
VIVAMERVSV LFDRIRKGFP CEARVVARIL PQFLDDFFPP QDIMNKVIGE
3010 3020 3030 3040 3050
FLSNQQPYPQ FMATVVYKVF QTLHSTGQSS MVRDWVMLSL SNFTQRAPVA
3060 3070 3080 3090 3100
MATWSLSCFF VSASTSPWVA AILPHVISRM GKLEQVDVNL FCLVATDFYR
3110 3120 3130 3140
HQIEEELDRR AFQSVLEVVA APGSPYHRLL TCLRNVHKVT TC
Computationally mapped potential isoform sequencesi
There are 7 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket| A0A7P0TA78 | A0A7P0TA78_HUMAN | Huntingtin | HTT | 3,056 | Annotation score: | ||
| A0A7P0TAC5 | A0A7P0TAC5_HUMAN | Huntingtin | HTT | 3,086 | Annotation score: | ||
| A0A7P0TAN5 | A0A7P0TAN5_HUMAN | Huntingtin | HTT | 2,880 | Annotation score: | ||
| A0A7P0Z417 | A0A7P0Z417_HUMAN | Huntingtin | HTT | 2,191 | Annotation score: | ||
| H0YA07 | H0YA07_HUMAN | Huntingtin | HTT | 112 | Annotation score: | ||
| A0A3B3ISR3 | A0A3B3ISR3_HUMAN | Huntingtin | HTT | 97 | Annotation score: | ||
| A0A3B3IU25 | A0A3B3IU25_HUMAN | Huntingtin | HTT | 75 | Annotation score: |
Experimental Info
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Sequence conflicti | 823 | C → S in BAA36753 (PubMed:11013077).Curated | 1 |
Polymorphismi
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 contracts also 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).1 Publication
Natural variant
| Feature key | Position(s) | DescriptionActions | Graphical view | Length |
|---|---|---|---|---|
| Natural variantiVAR_005268 | 18 | Q → QQQ. | 1 | |
| Natural variantiVAR_081737 | 551 | G → E Inhibits proteolytic cleavage at D-550; abolishes post-translational myristoylation; results in increased cleavage at D-511. 1 PublicationCorresponds to variant dbSNP:rs118005095Ensembl. | 1 | |
| Natural variantiVAR_079026 | 703 | P → L in LOMARS. 1 PublicationCorresponds to variant dbSNP:rs768047421Ensembl. | 1 | |
| Natural variantiVAR_060170 | 893 | G → R. Corresponds to variant dbSNP:rs363075Ensembl. | 1 | |
| Natural variantiVAR_060171 | 1064 | V → I. Corresponds to variant dbSNP:rs35892913Ensembl. | 1 | |
| Natural variantiVAR_060172 | 1091 | I → M. Corresponds to variant dbSNP:rs1143646Ensembl. | 1 | |
| Natural variantiVAR_060173 | 1173 | T → A. Corresponds to variant dbSNP:rs3025843Ensembl. | 1 | |
| Natural variantiVAR_060174 | 1260 | T → M Found in a patient with Rett syndrome-like phenotype; unknown pathological significance. 1 PublicationCorresponds to variant dbSNP:rs34315806Ensembl. | 1 | |
| Natural variantiVAR_054017 | 1382 | E → A. Corresponds to variant dbSNP:rs3025837Ensembl. | 1 | |
| Natural variantiVAR_060175 | 1385 | N → H. Corresponds to variant dbSNP:rs3025837Ensembl. | 1 | |
| Natural variantiVAR_060176 | 1720 | T → N. Corresponds to variant dbSNP:rs363125Ensembl. | 1 | |
| Natural variantiVAR_060177 | 2113 | D → Y. Corresponds to variant dbSNP:rs1143648Ensembl. | 1 | |
| Natural variantiVAR_060178 | 2309 | Y → H. Corresponds to variant dbSNP:rs362331Ensembl. | 1 | |
| Natural variantiVAR_079027 | 2717 | F → L in LOMARS. 1 PublicationCorresponds to variant dbSNP:rs1085307052Ensembl. | 1 | |
| Natural variantiVAR_060179 | 2786 | V → I1 PublicationCorresponds to variant dbSNP:rs362272Ensembl. | 1 |
Sequence databases
| Select the link destinations: EMBLi GenBanki DDBJi Links Updated | L12392 mRNA Translation: AAB38240.1 AB016794 mRNA Translation: BAA36753.1 Z49154 Genomic DNA Translation: CAA89024.1 Z49155 Genomic DNA Translation: CAA89025.1 Z49208 Genomic DNA No translation available. Z49769 Genomic DNA Translation: CAA89839.1 Z68756 Genomic DNA No translation available. Z69649 Genomic DNA No translation available. L27350 Genomic DNA No translation available. L27351 Genomic DNA No translation available. L27352 Genomic DNA No translation available. L27353 Genomic DNA No translation available. L27354 Genomic DNA No translation available. L34020 Genomic DNA No translation available. L20431 mRNA Translation: AAA52702.1 |
| PIRi | A46068 |
| RefSeqi | NP_002102.4, NM_002111.8 |
Genome annotation databases
| Ensembli | ENST00000355072; ENSP00000347184; ENSG00000197386 |
| GeneIDi | 3064 |
| KEGGi | hsa:3064 |
| UCSCi | uc062uto.1, human |
Keywords - Coding sequence diversityi
Triplet repeat expansionSimilar proteinsi
Cross-referencesi
Web resourcesi
| Wikipedia Huntingtin entry |
Sequence databases
| Select the link destinations: EMBLi GenBanki DDBJi Links Updated | L12392 mRNA Translation: AAB38240.1 AB016794 mRNA Translation: BAA36753.1 Z49154 Genomic DNA Translation: CAA89024.1 Z49155 Genomic DNA Translation: CAA89025.1 Z49208 Genomic DNA No translation available. Z49769 Genomic DNA Translation: CAA89839.1 Z68756 Genomic DNA No translation available. Z69649 Genomic DNA No translation available. L27350 Genomic DNA No translation available. L27351 Genomic DNA No translation available. L27352 Genomic DNA No translation available. L27353 Genomic DNA No translation available. L27354 Genomic DNA No translation available. L34020 Genomic DNA No translation available. L20431 mRNA Translation: AAA52702.1 |
| PIRi | A46068 |
| RefSeqi | NP_002102.4, NM_002111.8 |
3D structure databases
| Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
| 2D3X | model | - | A | 199-325 | [»] | |
| 2LD0 | NMR | - | A | 1-17 | [»] | |
| 2LD2 | NMR | - | A | 1-17 | [»] | |
| 3IO4 | X-ray | 3.63 | A/B/C | 1-64 | [»] | |
| 3IO6 | X-ray | 3.70 | A/B/C | 1-64 | [»] | |
| 3IOR | X-ray | 3.60 | A/B/C | 1-64 | [»] | |
| 3IOT | X-ray | 3.50 | A/B/C | 1-64 | [»] | |
| 3IOU | X-ray | 3.70 | A/B/C | 1-64 | [»] | |
| 3IOV | X-ray | 3.70 | A/B/C | 1-64 | [»] | |
| 3IOW | X-ray | 3.50 | A/B/C | 1-64 | [»] | |
| 3LRH | X-ray | 2.60 | B/D/F/H/J/L/N/P | 5-18 | [»] | |
| 4FE8 | X-ray | 3.00 | A/B/C | 1-64 | [»] | |
| 4FEB | X-ray | 2.80 | A/B/C | 1-64 | [»] | |
| 4FEC | X-ray | 3.00 | A/B/C | 1-64 | [»] | |
| 4FED | X-ray | 2.81 | A/B/C | 1-64 | [»] | |
| 4RAV | X-ray | 2.50 | E/F | 1-17 | [»] | |
| 6EZ8 | electron microscopy | 4.00 | A | 1-3142 | [»] | |
| 6N8C | NMR | - | A/B/C/D | 2-24 | [»] | |
| 6RMH | electron microscopy | 9.60 | A | 1-3142 | [»] | |
| 6X9O | electron microscopy | 2.60 | A | 1-3142 | [»] | |
| 6YEJ | electron microscopy | 18.20 | A | 18-3142 | [»] | |
| 7DXJ | electron microscopy | 3.60 | A | 1-3142 | [»] | |
| 7DXK | electron microscopy | 4.10 | A | 18-3142 | [»] | |
| BMRBi | P42858 | |||||
| SMRi | P42858 | |||||
| ModBasei | Search... | |||||
| PDBe-KBi | Search... | |||||
Protein-protein interaction databases
| BioGRIDi | 109314, 394 interactors |
| CORUMi | P42858 |
| DIPi | DIP-32492N |
| ELMi | P42858 |
| IntActi | P42858, 1108 interactors |
| MINTi | P42858 |
| STRINGi | 9606.ENSP00000347184 |
Chemistry databases
| BindingDBi | P42858 |
| ChEMBLi | CHEMBL5514 |
| DrugBanki | DB09130, Copper |
Protein family/group databases
| MoonDBi | P42858, Predicted |
PTM databases
| GlyGeni | P42858, 3 sites, 1 O-linked glycan (3 sites) |
| iPTMneti | P42858 |
| MetOSitei | P42858 |
| PhosphoSitePlusi | P42858 |
| SwissPalmi | P42858 |
Genetic variation databases
| BioMutai | HTT |
| DMDMi | 296434520 |
Proteomic databases
| EPDi | P42858 |
| jPOSTi | P42858 |
| MassIVEi | P42858 |
| MaxQBi | P42858 |
| PaxDbi | P42858 |
| PeptideAtlasi | P42858 |
| PRIDEi | P42858 |
| ProteomicsDBi | 55561 |
Protocols and materials databases
| ABCDi | P42858, 2 sequenced antibodies |
| Antibodypediai | 3449, 799 antibodies |
| DNASUi | 3064 |
Genome annotation databases
| Ensembli | ENST00000355072; ENSP00000347184; ENSG00000197386 |
| GeneIDi | 3064 |
| KEGGi | hsa:3064 |
| UCSCi | uc062uto.1, human |
Organism-specific databases
| CTDi | 3064 |
| DisGeNETi | 3064 |
| GeneCardsi | HTT |
| GeneReviewsi | HTT |
| HGNCi | HGNC:4851, HTT |
| HPAi | ENSG00000197386, Low tissue specificity |
| MalaCardsi | HTT |
| MIMi | 143100, phenotype 613004, gene 617435, phenotype |
| neXtProti | NX_P42858 |
| OpenTargetsi | ENSG00000197386 |
| Orphaneti | 399, Huntington disease 248111, Juvenile Huntington disease |
| PharmGKBi | PA164741646 |
| VEuPathDBi | HostDB:ENSG00000197386 |
| GenAtlasi | Search... |
Phylogenomic databases
| eggNOGi | ENOG502QR1D, Eukaryota |
| GeneTreei | ENSGT00390000015863 |
| HOGENOMi | CLU_000428_0_0_1 |
| InParanoidi | P42858 |
| OMAi | YSWWAEV |
| OrthoDBi | 33894at2759 |
| PhylomeDBi | P42858 |
| TreeFami | TF323608 |
Enzyme and pathway databases
| PathwayCommonsi | P42858 |
| Reactomei | R-HSA-9022692, Regulation of MECP2 expression and activity |
| SignaLinki | P42858 |
| SIGNORi | P42858 |
Miscellaneous databases
| BioGRID-ORCSi | 3064, 27 hits in 1025 CRISPR screens |
| ChiTaRSi | HTT, human |
| EvolutionaryTracei | P42858 |
| GeneWikii | Huntingtin |
| GenomeRNAii | 3064 |
| Pharosi | P42858, Tchem |
| PROi | PR:P42858 |
| RNActi | P42858, protein |
| SOURCEi | Search... |
Gene expression databases
| Bgeei | ENSG00000197386, Expressed in sural nerve and 180 other tissues |
| ExpressionAtlasi | P42858, baseline and differential |
| Genevisiblei | P42858, HS |
Family and domain databases
| Gene3Di | 1.25.10.10, 2 hits |
| InterProi | View protein in InterPro IPR011989, ARM-like IPR016024, ARM-type_fold IPR000091, Huntingtin IPR028426, Huntingtin_fam IPR024613, Huntingtin_middle-repeat |
| PANTHERi | PTHR10170, PTHR10170, 1 hit |
| Pfami | View protein in Pfam PF12372, DUF3652, 1 hit |
| PRINTSi | PR00375, HUNTINGTIN |
| SUPFAMi | SSF48371, SSF48371, 2 hits |
| MobiDBi | Search... |
Entry informationi
| Entry namei | HD_HUMAN | |
| Accessioni | P42858Primary (citable) accession number: P42858 Secondary accession number(s): Q9UQB7 | |
| Entry historyi | Integrated into UniProtKB/Swiss-Prot: | November 1, 1995 |
| Last sequence update: | May 18, 2010 | |
| Last modified: | September 29, 2021 | |
| This is version 215 of the entry and version 2 of the sequence. See complete history. | ||
| Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
| Annotation program | Chordata Protein Annotation Program | |
| Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. | |
Miscellaneousi
Keywords - Technical termi
3D-structure, Reference proteomeDocuments
- Human chromosome 4
Human chromosome 4: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families
