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P42858

- HD_HUMAN

UniProt

P42858 - HD_HUMAN

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Protein

Huntingtin

Gene
HTT, HD, IT15
Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5 - Experimental evidence at protein leveli

Functioni

May play a role in microtubule-mediated transport or vesicle function.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei511 – 5122Cleavage; by apopain Reviewed prediction
Sitei528 – 5292Cleavage; by apopain Reviewed prediction
Sitei550 – 5512Cleavage; by apopain Reviewed prediction
Sitei587 – 5882Cleavage; by apopain Reviewed prediction

GO - Molecular functioni

  1. beta-tubulin binding Source: UniProtKB
  2. diazepam binding Source: Ensembl
  3. dynactin binding Source: UniProtKB
  4. dynein intermediate chain binding Source: UniProtKB
  5. identical protein binding Source: IntAct
  6. p53 binding Source: UniProtKB
  7. protein binding Source: UniProtKB
  8. transcription factor binding Source: RefGenome

GO - Biological processi

  1. anterior/posterior pattern specification Source: Ensembl
  2. axon cargo transport Source: Ensembl
  3. cell aging Source: Ensembl
  4. citrulline metabolic process Source: Ensembl
  5. determination of adult lifespan Source: Ensembl
  6. dopamine receptor signaling pathway Source: Ensembl
  7. endoplasmic reticulum organization Source: Ensembl
  8. endosomal transport Source: Ensembl
  9. ER to Golgi vesicle-mediated transport Source: Ensembl
  10. establishment of mitotic spindle orientation Source: UniProtKB
  11. Golgi organization Source: UniProtKB
  12. grooming behavior Source: Ensembl
  13. hormone metabolic process Source: Ensembl
  14. insulin secretion Source: Ensembl
  15. iron ion homeostasis Source: Ensembl
  16. lactate biosynthetic process from pyruvate Source: Ensembl
  17. L-glutamate import Source: Ensembl
  18. locomotory behavior Source: Ensembl
  19. negative regulation of extrinsic apoptotic signaling pathway Source: UniProtKB
  20. negative regulation of neuron apoptotic process Source: Ensembl
  21. neural plate formation Source: Ensembl
  22. neuron apoptotic process Source: Ensembl
  23. neuron development Source: Ensembl
  24. olfactory lobe development Source: Ensembl
  25. organ development Source: RefGenome
  26. paraxial mesoderm formation Source: Ensembl
  27. protein import into nucleus Source: Ensembl
  28. quinolinate biosynthetic process Source: Ensembl
  29. regulation of mitochondrial membrane permeability Source: Ensembl
  30. regulation of mitochondrial membrane potential Source: Ensembl
  31. regulation of protein phosphatase type 2A activity Source: dictyBase
  32. regulation of synaptic plasticity Source: Ensembl
  33. response to calcium ion Source: Ensembl
  34. retrograde vesicle-mediated transport, Golgi to ER Source: UniProtKB
  35. social behavior Source: Ensembl
  36. spermatogenesis Source: Ensembl
  37. striatum development Source: Ensembl
  38. urea cycle Source: Ensembl
  39. vesicle transport along microtubule Source: UniProtKB
  40. visual learning Source: Ensembl
Complete GO annotation...

Keywords - Biological processi

Apoptosis

Enzyme and pathway databases

SignaLinkiP42858.

Names & Taxonomyi

Protein namesi
Recommended name:
Huntingtin
Alternative name(s):
Huntington disease protein
Short name:
HD protein
Gene namesi
Name:HTT
Synonyms:HD, IT15
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 4

Organism-specific databases

HGNCiHGNC:4851. HTT.

Subcellular locationi

Cytoplasm. Nucleus
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.3 Publications

GO - Cellular componenti

  1. autophagic vacuole Source: UniProtKB
  2. axon Source: UniProtKB
  3. cytoplasm Source: UniProtKB
  4. cytoplasmic vesicle membrane Source: UniProtKB
  5. cytosol Source: UniProtKB
  6. dendrite Source: UniProtKB
  7. endoplasmic reticulum Source: UniProtKB
  8. Golgi apparatus Source: UniProtKB
  9. inclusion body Source: Ensembl
  10. late endosome Source: UniProtKB
  11. mitochondrion Source: GOC
  12. nucleus Source: UniProtKB
  13. protein complex Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Involvement in diseasei

Huntington disease (HD) [MIM:143100]: A 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.
Note: The disease is caused by mutations affecting the gene represented in this entry.

Keywords - Diseasei

Disease mutation, Neurodegeneration

Organism-specific databases

MIMi143100. phenotype.
Orphaneti399. Huntington disease.
248111. Juvenile Huntington disease.
PharmGKBiPA164741646.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 31423142HuntingtinPRO_0000083942Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei9 – 91N6-acetyllysine1 Publication
Modified residuei176 – 1761N6-acetyllysine1 Publication
Modified residuei234 – 2341N6-acetyllysine1 Publication
Modified residuei343 – 3431N6-acetyllysine1 Publication
Modified residuei411 – 4111Phosphoserine1 Publication
Modified residuei432 – 4321Phosphoserine1 Publication
Modified residuei442 – 4421N6-acetyllysine1 Publication
Modified residuei1179 – 11791Phosphoserine; by CDK51 Publication
Modified residuei1199 – 11991Phosphoserine; by CDK51 Publication
Modified residuei1870 – 18701Phosphoserine3 Publications
Modified residuei1874 – 18741Phosphoserine3 Publications

Post-translational modificationi

Cleaved by apopain downstream of the polyglutamine stretch. The resulting N-terminal fragment is cytotoxic and provokes apoptosis.
Forms with expanded polyglutamine expansion are specifically ubiquitinated by SYVN1, which promotes their proteasomal degradation.
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.

Keywords - PTMi

Acetylation, Phosphoprotein, Ubl conjugation

Proteomic databases

MaxQBiP42858.
PaxDbiP42858.
PRIDEiP42858.

PTM databases

PhosphoSiteiP42858.

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

ArrayExpressiP42858.
BgeeiP42858.
CleanExiHS_HTT.
GenevestigatoriP42858.

Organism-specific databases

HPAiCAB002756.
HPA026114.

Interactioni

Subunit structurei

Binds SH3GLB1 By similarity. Interacts through its N-terminus with PRPF40A. Interacts with PQBP1, SETD2 and SYVN. Interacts with PFN1. Interacts with TPR; the interaction is inhibited by forms of Huntingtin with expanded polyglutamine stretch.7 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
itself3EBI-466029,EBI-466029
ARHGAP24Q8N2643EBI-466029,EBI-988764
BAZ1AQ9NRL24EBI-466029,EBI-927511
CHD3Q128733EBI-466029,EBI-523590
COPB1P536183EBI-466029,EBI-359063
CREBBPQ927932EBI-466029,EBI-81215
CRMP1Q141942EBI-466029,EBI-473101
CTNNB1P352225EBI-466029,EBI-491549
DCTN2Q135616EBI-466029,EBI-715074
DNAJC11Q9NVH13EBI-466029,EBI-1055336
DNAJC21Q5F1R66EBI-466029,EBI-2654581
DNAJC4Q9NNZ33EBI-466029,EBI-4397791
DNALI1O146453EBI-466029,EBI-395638
DNM1Q051933EBI-466029,EBI-713135
DYNC1H1Q142043EBI-466029,EBI-356015
ECH1Q130112EBI-466029,EBI-711968
ERCC6LQ2NKX82EBI-466029,EBI-1042535
EVLQ9UI08-22EBI-466029,EBI-6448852
FEZ1Q996895EBI-466029,EBI-396435
FNBP4Q8N3X16EBI-466029,EBI-310600
FTLP027922EBI-466029,EBI-713279
GIT1Q9Y2X710EBI-466029,EBI-466061
GOLPH3LQ9H4A52EBI-466029,EBI-4403434
GTF3C3Q9Y5Q93EBI-466029,EBI-1054873
HAP1P54257-24EBI-466029,EBI-9392340
HEY2Q9UBP52EBI-466029,EBI-750630
HIP1O002914EBI-466029,EBI-473886
HIST1H3DP684312EBI-466029,EBI-79722
HMG20AQ9NP662EBI-466029,EBI-740641
IKBKAPO951634EBI-466029,EBI-347559
JAKMIP1Q96N164EBI-466029,EBI-2680803
KIAA1377Q9P2H02EBI-466029,EBI-473176
LDOC1O957515EBI-466029,EBI-740738
MAGEB6Q8N7X42EBI-466029,EBI-6447163
MBD1Q9UIS92EBI-466029,EBI-867196
MED15Q96RN53EBI-466029,EBI-394506
MED31Q9Y3C73EBI-466029,EBI-394707
MKRN2Q9H0003EBI-466029,EBI-2341005
MRE11AP499595EBI-466029,EBI-396513
MRFAP1L1Q96HT83EBI-466029,EBI-748896
MTSS1O433123EBI-466029,EBI-473954
NBR1Q145963EBI-466029,EBI-742698
NCOR1O753763EBI-466029,EBI-347233
NME4O007462EBI-466029,EBI-744871
NUPL1Q9BVL24EBI-466029,EBI-2811583
OPTNQ96CV97EBI-466029,EBI-748974
OSTF1Q928825EBI-466029,EBI-1051152
P4HA1P136745EBI-466029,EBI-1237386
PACSIN1Q9BY113EBI-466029,EBI-721769
PAK2Q131772EBI-466029,EBI-1045887
PFN2P350804EBI-466029,EBI-473138
PIAS4Q8N2W93EBI-466029,EBI-473160
PIBF1Q8WXW33EBI-466029,EBI-2558770
PIK3R1P279867EBI-466029,EBI-79464
PIK3R2O004596EBI-466029,EBI-346930
PIK3R3Q925696EBI-466029,EBI-79893
PKMP146183EBI-466029,EBI-353408
PPARGP372314EBI-466029,EBI-781384
PRPF40AO7540015EBI-466029,EBI-473291
RNF20Q5VTR23EBI-466029,EBI-2372238
RNF40O751503EBI-466029,EBI-744408
RPL4P365782EBI-466029,EBI-348313
SETD2Q9BYW24EBI-466029,EBI-945869
SH3GL3Q999639EBI-466029,EBI-473910
SNCAP378404EBI-466029,EBI-985879
SORBS1Q9BX664EBI-466029,EBI-433642
SRGAP1Q7Z6B74EBI-466029,EBI-2481729
SRGAP2O750443EBI-466029,EBI-1051034
SRGAP3O432954EBI-466029,EBI-368166
SRRTQ9BXP53EBI-466029,EBI-712721
TACC1O754104EBI-466029,EBI-624237
TANKQ928443EBI-466029,EBI-356349
TCERG1O147769EBI-466029,EBI-473271
TP53P046374EBI-466029,EBI-366083
TRAFD1O145455EBI-466029,EBI-1396921
UBAC1Q9BSL15EBI-466029,EBI-749370
UBE2KP610863EBI-466029,EBI-473850
USP9XQ930088EBI-466029,EBI-302524
WACQ9BTA95EBI-466029,EBI-749118
WBP4O755543EBI-466029,EBI-7251981
WDFY3Q8IZQ110EBI-466029,EBI-1569256
XAGE3Q8WTP93EBI-466029,EBI-6448284
XRCC6P129563EBI-466029,EBI-353208
ZDHHC17Q8IUH512EBI-466029,EBI-524753
ZFC3H1G3V1X12EBI-466029,EBI-6448783
ZFYVE19Q96K213EBI-466029,EBI-6448240
ZMAT2Q96NC02EBI-466029,EBI-2682299

Protein-protein interaction databases

BioGridi109314. 184 interactions.
DIPiDIP-32492N.
IntActiP42858. 334 interactions.
MINTiMINT-133355.
STRINGi9606.ENSP00000347184.

Structurei

Secondary structure

1
3142
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi6 – 1712

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2D3Xmodel-A199-325[»]
2LD0NMR-A1-17[»]
2LD2NMR-A1-17[»]
3IO4X-ray3.63A/B/C1-64[»]
3IO6X-ray3.70A/B/C1-64[»]
3IORX-ray3.60A/B/C1-64[»]
3IOTX-ray3.50A/B/C1-64[»]
3IOUX-ray3.70A/B/C1-64[»]
3IOVX-ray3.70A/B/C1-64[»]
3IOWX-ray3.50A/B/C1-64[»]
3LRHX-ray2.60B/D/F/H/J/L/N/P5-18[»]
4FE8X-ray3.00A/B/C1-64[»]
4FEBX-ray2.80A/B/C1-64[»]
4FECX-ray3.00A/B/C1-64[»]
4FEDX-ray2.81A/B/C1-64[»]
ProteinModelPortaliP42858.

Miscellaneous databases

EvolutionaryTraceiP42858.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Repeati204 – 24138HEAT 1Add
BLAST
Repeati246 – 28338HEAT 2Add
BLAST
Repeati316 – 36045HEAT 3Add
BLAST
Repeati802 – 83938HEAT 4Add
BLAST
Repeati902 – 94039HEAT 5Add
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni3 – 1311Sufficient for interaction with TPRAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi2395 – 240410Nuclear export signal By similarity

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi18 – 3821Poly-GlnAdd
BLAST
Compositional biasi39 – 4911Poly-ProAdd
BLAST
Compositional biasi63 – 7816Poly-ProAdd
BLAST
Compositional biasi1437 – 14404Poly-Thr
Compositional biasi2341 – 23455Poly-Glu
Compositional biasi2638 – 26436Poly-Glu

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.
Contains 5 HEAT repeats.

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiNOG82191.
HOGENOMiHOG000082472.
HOVERGENiHBG005953.
InParanoidiP42858.
KOiK04533.
OMAiSDQVFIG.
OrthoDBiEOG7JQBMD.
PhylomeDBiP42858.
TreeFamiTF323608.

Family and domain databases

Gene3Di1.25.10.10. 4 hits.
InterProiIPR011989. ARM-like.
IPR016024. ARM-type_fold.
IPR000091. Huntingtin.
IPR028426. Huntingtin_fam.
IPR024613. Huntingtin_middle-repeat.
[Graphical view]
PANTHERiPTHR10170. PTHR10170. 1 hit.
PfamiPF12372. DUF3652. 2 hits.
[Graphical view]
PRINTSiPR00375. HUNTINGTIN.
SUPFAMiSSF48371. SSF48371. 6 hits.

Sequencei

Sequence statusi: Complete.

P42858-1 [UniParc]FASTAAdd to Basket

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MATLEKLMKA FESLKSFQQQ QQQQQQQQQQ QQQQQQQQPP PPPPPPPPPQ     50
LPQPPPQAQP LLPQPQPPPP PPPPPPGPAV AEEPLHRPKK ELSATKKDRV 100
NHCLTICENI VAQSVRNSPE FQKLLGIAME LFLLCSDDAE SDVRMVADEC 150
LNKVIKALMD SNLPRLQLEL YKEIKKNGAP RSLRAALWRF AELAHLVRPQ 200
KCRPYLVNLL PCLTRTSKRP EESVQETLAA AVPKIMASFG NFANDNEIKV 250
LLKAFIANLK SSSPTIRRTA AGSAVSICQH SRRTQYFYSW LLNVLLGLLV 300
PVEDEHSTLL ILGVLLTLRY LVPLLQQQVK DTSLKGSFGV TRKEMEVSPS 350
AEQLVQVYEL TLHHTQHQDH NVVTGALELL QQLFRTPPPE LLQTLTAVGG 400
IGQLTAAKEE SGGRSRSGSI VELIAGGGSS CSPVLSRKQK GKVLLGEEEA 450
LEDDSESRSD VSSSALTASV KDEISGELAA SSGVSTPGSA GHDIITEQPR 500
SQHTLQADSV DLASCDLTSS ATDGDEEDIL SHSSSQVSAV PSDPAMDLND 550
GTQASSPISD SSQTTTEGPD SAVTPSDSSE IVLDGTDNQY LGLQIGQPQD 600
EDEEATGILP DEASEAFRNS SMALQQAHLL KNMSHCRQPS DSSVDKFVLR 650
DEATEPGDQE NKPCRIKGDI GQSTDDDSAP LVHCVRLLSA SFLLTGGKNV 700
LVPDRDVRVS VKALALSCVG AAVALHPESF FSKLYKVPLD TTEYPEEQYV 750
SDILNYIDHG DPQVRGATAI LCGTLICSIL SRSRFHVGDW MGTIRTLTGN 800
TFSLADCIPL LRKTLKDESS VTCKLACTAV RNCVMSLCSS SYSELGLQLI 850
IDVLTLRNSS YWLVRTELLE TLAEIDFRLV SFLEAKAENL HRGAHHYTGL 900
LKLQERVLNN VVIHLLGDED PRVRHVAAAS LIRLVPKLFY KCDQGQADPV 950
VAVARDQSSV YLKLLMHETQ PPSHFSVSTI TRIYRGYNLL PSITDVTMEN 1000
NLSRVIAAVS HELITSTTRA LTFGCCEALC LLSTAFPVCI WSLGWHCGVP 1050
PLSASDESRK SCTVGMATMI LTLLSSAWFP LDLSAHQDAL ILAGNLLAAS 1100
APKSLRSSWA SEEEANPAAT KQEEVWPALG DRALVPMVEQ LFSHLLKVIN 1150
ICAHVLDDVA PGPAIKAALP SLTNPPSLSP IRRKGKEKEP GEQASVPLSP 1200
KKGSEASAAS RQSDTSGPVT TSKSSSLGSF YHLPSYLKLH DVLKATHANY 1250
KVTLDLQNST EKFGGFLRSA LDVLSQILEL ATLQDIGKCV EEILGYLKSC 1300
FSREPMMATV CVQQLLKTLF GTNLASQFDG LSSNPSKSQG RAQRLGSSSV 1350
RPGLYHYCFM APYTHFTQAL ADASLRNMVQ AEQENDTSGW FDVLQKVSTQ 1400
LKTNLTSVTK NRADKNAIHN HIRLFEPLVI KALKQYTTTT CVQLQKQVLD 1450
LLAQLVQLRV NYCLLDSDQV FIGFVLKQFE YIEVGQFRES EAIIPNIFFF 1500
LVLLSYERYH SKQIIGIPKI IQLCDGIMAS GRKAVTHAIP ALQPIVHDLF 1550
VLRGTNKADA GKELETQKEV VVSMLLRLIQ YHQVLEMFIL VLQQCHKENE 1600
DKWKRLSRQI ADIILPMLAK QQMHIDSHEA LGVLNTLFEI LAPSSLRPVD 1650
MLLRSMFVTP NTMASVSTVQ LWISGILAIL RVLISQSTED IVLSRIQELS 1700
FSPYLISCTV INRLRDGDST STLEEHSEGK QIKNLPEETF SRFLLQLVGI 1750
LLEDIVTKQL KVEMSEQQHT FYCQELGTLL MCLIHIFKSG MFRRITAAAT 1800
RLFRSDGCGG SFYTLDSLNL RARSMITTHP ALVLLWCQIL LLVNHTDYRW 1850
WAEVQQTPKR HSLSSTKLLS PQMSGEEEDS DLAAKLGMCN REIVRRGALI 1900
LFCDYVCQNL HDSEHLTWLI VNHIQDLISL SHEPPVQDFI SAVHRNSAAS 1950
GLFIQAIQSR CENLSTPTML KKTLQCLEGI HLSQSGAVLT LYVDRLLCTP 2000
FRVLARMVDI LACRRVEMLL AANLQSSMAQ LPMEELNRIQ EYLQSSGLAQ 2050
RHQRLYSLLD RFRLSTMQDS LSPSPPVSSH PLDGDGHVSL ETVSPDKDWY 2100
VHLVKSQCWT RSDSALLEGA ELVNRIPAED MNAFMMNSEF NLSLLAPCLS 2150
LGMSEISGGQ KSALFEAARE VTLARVSGTV QQLPAVHHVF QPELPAEPAA 2200
YWSKLNDLFG DAALYQSLPT LARALAQYLV VVSKLPSHLH LPPEKEKDIV 2250
KFVVATLEAL SWHLIHEQIP LSLDLQAGLD CCCLALQLPG LWSVVSSTEF 2300
VTHACSLIYC VHFILEAVAV QPGEQLLSPE RRTNTPKAIS EEEEEVDPNT 2350
QNPKYITAAC EMVAEMVESL QSVLALGHKR NSGVPAFLTP LLRNIIISLA 2400
RLPLVNSYTR VPPLVWKLGW SPKPGGDFGT AFPEIPVEFL QEKEVFKEFI 2450
YRINTLGWTS RTQFEETWAT LLGVLVTQPL VMEQEESPPE EDTERTQINV 2500
LAVQAITSLV LSAMTVPVAG NPAVSCLEQQ PRNKPLKALD TRFGRKLSII 2550
RGIVEQEIQA MVSKRENIAT HHLYQAWDPV PSLSPATTGA LISHEKLLLQ 2600
INPERELGSM SYKLGQVSIH SVWLGNSITP LREEEWDEEE EEEADAPAPS 2650
SPPTSPVNSR KHRAGVDIHS CSQFLLELYS RWILPSSSAR RTPAILISEV 2700
VRSLLVVSDL FTERNQFELM YVTLTELRRV HPSEDEILAQ YLVPATCKAA 2750
AVLGMDKAVA EPVSRLLEST LRSSHLPSRV GALHGVLYVL ECDLLDDTAK 2800
QLIPVISDYL LSNLKGIAHC VNIHSQQHVL VMCATAFYLI ENYPLDVGPE 2850
FSASIIQMCG VMLSGSEEST PSIIYHCALR GLERLLLSEQ LSRLDAESLV 2900
KLSVDRVNVH SPHRAMAALG LMLTCMYTGK EKVSPGRTSD PNPAAPDSES 2950
VIVAMERVSV LFDRIRKGFP CEARVVARIL PQFLDDFFPP QDIMNKVIGE 3000
FLSNQQPYPQ FMATVVYKVF QTLHSTGQSS MVRDWVMLSL SNFTQRAPVA 3050
MATWSLSCFF VSASTSPWVA AILPHVISRM GKLEQVDVNL FCLVATDFYR 3100
HQIEEELDRR AFQSVLEVVA APGSPYHRLL TCLRNVHKVT TC 3142
Length:3,142
Mass (Da):347,603
Last modified:May 18, 2010 - v2
Checksum:iA267509E84D52F0D
GO

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.

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti18 – 181Q → QQQ.
VAR_005268
Natural varianti893 – 8931G → R.
Corresponds to variant rs363075 [ dbSNP | Ensembl ].
VAR_060170
Natural varianti1064 – 10641V → I.
Corresponds to variant rs35892913 [ dbSNP | Ensembl ].
VAR_060171
Natural varianti1091 – 10911I → M.
Corresponds to variant rs1143646 [ dbSNP | Ensembl ].
VAR_060172
Natural varianti1173 – 11731T → A.
Corresponds to variant rs3025843 [ dbSNP | Ensembl ].
VAR_060173
Natural varianti1260 – 12601T → M.
Corresponds to variant rs34315806 [ dbSNP | Ensembl ].
VAR_060174
Natural varianti1382 – 13821E → A.
Corresponds to variant rs3025837 [ dbSNP | Ensembl ].
VAR_054017
Natural varianti1385 – 13851N → H.
Corresponds to variant rs3025837 [ dbSNP | Ensembl ].
VAR_060175
Natural varianti1720 – 17201T → N.
Corresponds to variant rs363125 [ dbSNP | Ensembl ].
VAR_060176
Natural varianti2113 – 21131D → Y.
Corresponds to variant rs1143648 [ dbSNP | Ensembl ].
VAR_060177
Natural varianti2309 – 23091Y → H.
Corresponds to variant rs362331 [ dbSNP | Ensembl ].
VAR_060178
Natural varianti2786 – 27861V → I.1 Publication
Corresponds to variant rs362272 [ dbSNP | Ensembl ].
VAR_060179

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti823 – 8231C → S in BAA36753. 1 Publication

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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.
PIRiA46068.
RefSeqiNP_002102.4. NM_002111.7.
UniGeneiHs.518450.

Genome annotation databases

EnsembliENST00000355072; ENSP00000347184; ENSG00000197386.
GeneIDi3064.
KEGGihsa:3064.
UCSCiuc021xkv.1. human.

Polymorphism databases

DMDMi296434520.

Keywords - Coding sequence diversityi

Polymorphism, Triplet repeat expansion

Cross-referencesi

Web resourcesi

Wikipedia

Huntingtin entry

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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_002111.7.
UniGenei Hs.518450.

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
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 [» ]
ProteinModelPortali P42858.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 109314. 184 interactions.
DIPi DIP-32492N.
IntActi P42858. 334 interactions.
MINTi MINT-133355.
STRINGi 9606.ENSP00000347184.

Chemistry

ChEMBLi CHEMBL5514.

PTM databases

PhosphoSitei P42858.

Polymorphism databases

DMDMi 296434520.

Proteomic databases

MaxQBi P42858.
PaxDbi P42858.
PRIDEi P42858.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000355072 ; ENSP00000347184 ; ENSG00000197386 .
GeneIDi 3064.
KEGGi hsa:3064.
UCSCi uc021xkv.1. human.

Organism-specific databases

CTDi 3064.
GeneCardsi GC04P003076.
GeneReviewsi HTT.
HGNCi HGNC:4851. HTT.
HPAi CAB002756.
HPA026114.
MIMi 143100. phenotype.
613004. gene.
neXtProti NX_P42858.
Orphaneti 399. Huntington disease.
248111. Juvenile Huntington disease.
PharmGKBi PA164741646.
GenAtlasi Search...

Phylogenomic databases

eggNOGi NOG82191.
HOGENOMi HOG000082472.
HOVERGENi HBG005953.
InParanoidi P42858.
KOi K04533.
OMAi SDQVFIG.
OrthoDBi EOG7JQBMD.
PhylomeDBi P42858.
TreeFami TF323608.

Enzyme and pathway databases

SignaLinki P42858.

Miscellaneous databases

ChiTaRSi HTT. human.
EvolutionaryTracei P42858.
GeneWikii Huntingtin.
GenomeRNAii 3064.
NextBioi 12121.
PROi P42858.
SOURCEi Search...

Gene expression databases

ArrayExpressi P42858.
Bgeei P42858.
CleanExi HS_HTT.
Genevestigatori P42858.

Family and domain databases

Gene3Di 1.25.10.10. 4 hits.
InterProi IPR011989. ARM-like.
IPR016024. ARM-type_fold.
IPR000091. Huntingtin.
IPR028426. Huntingtin_fam.
IPR024613. Huntingtin_middle-repeat.
[Graphical view ]
PANTHERi PTHR10170. PTHR10170. 1 hit.
Pfami PF12372. DUF3652. 2 hits.
[Graphical view ]
PRINTSi PR00375. HUNTINGTIN.
SUPFAMi SSF48371. SSF48371. 6 hits.
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  1. "A novel gene containing a trinucleotide repeat that is expanded and unstable on Huntington's disease chromosomes."
    Macdonald M., Ambrose C.M., Duyao M.P., Myers R.H., Lin C.S., Srinidhi J., Barnes G., Taylor S.A., James M., Groot N., McFarlane H., Jenkins B., Anderson M.A., Wexler N.S., Gusella J.F., Bates G.P., Baxendale S., Hummerich H.
    , Kirby S., North M., Youngman S., Mott R., Zehetner G., Sedlacek Z., Poustka A., Frischauf A.-M., Lehrach H., Buckler A.J., Church D., Doucette-Stamm L., O'Donovan M.C., Riba-Ramirez L., Shah M., Stanton V.P., Strobel S.A., Draths K.M., Wales J.L., Dervan P., Housman D.E., Altherr M., Shiang R., Thompson L., Fielder T., Wasmuth J.J., Tagle D., Valdes J., Elmer L., Allard M., Castilla L., Swaroop M., Blanchard K., Collins F.S., Snell R., Holloway T., Gillespie K., Datson N., Shaw S., Harper P.S.
    Cell 72:971-983(1993) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Tissue: Retina.
  2. "Identification and characterization of the miniature pig Huntington's disease gene homolog: evidence for conservation and polymorphism in the CAG triplet repeat."
    Matsuyama N., Hadano S., Onoe K., Osuga H., Shouguchi-Miyata J., Gondo Y., Ikeda J.-E.
    Genomics 69:72-85(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Tissue: Brain.
  3. "Generation and annotation of the DNA sequences of human chromosomes 2 and 4."
    Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H.
    , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K.
    Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  4. Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-203.
  5. "Structural analysis of the 5' region of mouse and human Huntington disease genes reveals conservation of putative promoter region and di- and trinucleotide polymorphisms."
    Lin B., Nasir J., Kalchman M.A., McDonald H., Zeisler J., Goldberg Y.P., Hayden M.R.
    Genomics 25:707-715(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-88.
  6. "Differential 3' polyadenylation of the Huntington disease gene results in two mRNA species with variable tissue expression."
    Lin B., Rommens J.M., Graham R.K., Kalchman M., Macdonald H., Nasir J., Delaney A., Goldberg Y.P., Hayden M.R.
    Hum. Mol. Genet. 2:1541-1545(1993) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 2561-3142, VARIANT ILE-2786.
    Tissue: Brain, Caudate nucleus, Frontal cortex, Muscle and Retina.
  7. "Cellular localization of the Huntington's disease protein and discrimination of the normal and mutated form."
    Trottier Y., Devys D., Imbert G., Saudou F., An I., Lutz Y., Weber C., Agid Y., Hirsch E.C., Mandel J.-L.
    Nat. Genet. 10:104-110(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBCELLULAR LOCATION.
  8. "Cleavage of huntingtin by apopain, a proapoptotic cysteine protease, is modulated by the polyglutamine tract."
    Goldberg Y.P., Nicholson D.W., Rasper D.M., Kalchman M.A., Koide H.B., Graham R.K., Bromm M., Kazemi-Esfarjani P., Thornberry N.A., Vaillancourt J.P., Hayden M.R.
    Nat. Genet. 13:442-449(1996) [PubMed] [Europe PMC] [Abstract]
    Cited for: CLEAVAGE BY APOPAIN.
  9. Cited for: INTERACTION WITH PRPF40A AND SETD2.
  10. "PQBP-1, a novel polyglutamine tract binding protein, inhibits transcription activation by Brn-2 and affects cell survival."
    Waragai M., Lammers C.-H., Takeuchi S., Imafuku I., Udagawa Y., Kanazawa I., Kawabata M., Mouradian M.M., Okazawa H.
    Hum. Mol. Genet. 8:977-987(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH PQBP1.
    Tissue: Brain.
  11. "Huntingtin's WW domain partners in Huntington's disease post-mortem brain fulfill genetic criteria for direct involvement in Huntington's disease pathogenesis."
    Passani L.A., Bedford M.T., Faber P.W., McGinnis K.M., Sharp A.H., Gusella J.F., Vonsattel J.-P., MacDonald M.E.
    Hum. Mol. Genet. 9:2175-2182(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH SETD2.
  12. "Identification of the full-length huntingtin-interacting protein p231HBP/HYPB as a DNA-binding factor."
    Rega S., Stiewe T., Chang D.-I., Pollmeier B., Esche H., Bardenheuer W., Marquitan G., Puetzer B.M.
    Mol. Cell. Neurosci. 18:68-79(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH SETD2.
  13. "Huntingtin contains a highly conserved nuclear export signal."
    Xia J., Lee D.H., Taylor J., Vandelft M., Truant R.
    Hum. Mol. Genet. 12:1393-1403(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEAR EXPORT SIGNAL.
  14. "Polyglutamine expansion of huntingtin impairs its nuclear export."
    Cornett J., Cao F., Wang C.E., Ross C.A., Bates G.P., Li S.H., Li X.J.
    Nat. Genet. 37:198-204(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH TPR, SUBCELLULAR LOCATION.
  15. "Interaction of the nuclear matrix protein NAKAP with HypA and huntingtin: implications for nuclear toxicity in Huntington's disease pathogenesis."
    Sayer J.A., Manczak M., Akileswaran L., Reddy P.H., Coghlan V.M.
    NeuroMolecular Med. 7:297-310(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
  16. "Ubiquitin ligase Hrd1 enhances the degradation and suppresses the toxicity of polyglutamine-expanded huntingtin."
    Yang H., Zhong X., Ballar P., Luo S., Shen Y., Rubinsztein D.C., Monteiro M.J., Fang S.
    Exp. Cell Res. 313:538-550(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH SYVN, UBIQUITINATION.
  17. "Phosphorylation of huntingtin by cyclin-dependent kinase 5 is induced by DNA damage and regulates wild-type and mutant huntingtin toxicity in neurons."
    Anne S.L., Saudou F., Humbert S.
    J. Neurosci. 27:7318-7328(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION AT SER-1179 AND SER-1199.
  18. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Platelet.
  19. "Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle."
    Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M.
    Mol. Cell 31:438-448(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1870, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Cervix carcinoma.
  20. "Phosphorylation of profilin by ROCK1 regulates polyglutamine aggregation."
    Shao J., Welch W.J., Diprospero N.A., Diamond M.I.
    Mol. Cell. Biol. 28:5196-5208(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH PFN1.
  21. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-411; SER-1870 AND SER-1874, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Cervix carcinoma.
  22. "Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach."
    Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.
    Anal. Chem. 81:4493-4501(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  23. "Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions."
    Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K.
    Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-432 AND SER-1874, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Leukemic T-cell.
  24. "Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis."
    Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.
    Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1870 AND SER-1874, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Cervix carcinoma.
  25. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  26. "Mass spectrometric identification of novel lysine acetylation sites in huntingtin."
    Cong X., Held J.M., Degiacomo F., Bonner A., Chen J.M., Schilling B., Czerwieniec G.A., Gibson B.W., Ellerby L.M.
    Mol. Cell. Proteomics 0:0-0(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: ACETYLATION AT LYS-9; LYS-176; LYS-234; LYS-343 AND LYS-442.
  27. "System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation."
    Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.
    Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  28. "Secondary structure of Huntingtin amino-terminal region."
    Kim M.W., Chelliah Y., Kim S.W., Otwinowski Z., Bezprozvanny I.
    Structure 17:1205-1212(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (3.5 ANGSTROMS) OF 1-64, DOMAIN.

Entry informationi

Entry nameiHD_HUMAN
AccessioniPrimary (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 3, 2014
This is version 151 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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, Complete proteome, Reference proteome

Documents

  1. Human chromosome 4
    Human chromosome 4: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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