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P42858 (HD_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 147. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Huntingtin
Alternative name(s):
Huntington disease protein
Short name=HD protein
Gene names
Name:HTT
Synonyms:HD, IT15
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length3142 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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

Subunit structure

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. Ref.9 Ref.10 Ref.11 Ref.12 Ref.14 Ref.16 Ref.20

Subcellular location

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. Ref.7 Ref.14 Ref.15

Tissue specificity

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. Ref.15

Domain

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. Ref.28

Post-translational modification

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.

Polymorphism

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.

Involvement in disease

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.

Sequence similarities

Belongs to the huntingtin family.

Contains 5 HEAT repeats.

Ontologies

Keywords
   Biological processApoptosis
   Cellular componentCytoplasm
Nucleus
   Coding sequence diversityPolymorphism
Triplet repeat expansion
   DiseaseDisease mutation
Neurodegeneration
   DomainRepeat
   PTMAcetylation
Phosphoprotein
Ubl conjugation
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processER to Golgi vesicle-mediated transport

Inferred from electronic annotation. Source: Ensembl

Golgi organization

Inferred from mutant phenotype PubMed 20515468. Source: UniProtKB

L-glutamate import

Inferred from electronic annotation. Source: Ensembl

anterior/posterior pattern specification

Inferred from electronic annotation. Source: Ensembl

axon cargo transport

Inferred from electronic annotation. Source: Ensembl

cell aging

Inferred from electronic annotation. Source: Ensembl

citrulline metabolic process

Inferred from electronic annotation. Source: Ensembl

determination of adult lifespan

Inferred from electronic annotation. Source: Ensembl

dopamine receptor signaling pathway

Inferred from electronic annotation. Source: Ensembl

endoplasmic reticulum organization

Inferred from electronic annotation. Source: Ensembl

endosomal transport

Inferred from electronic annotation. Source: Ensembl

establishment of mitotic spindle orientation

Inferred from mutant phenotype PubMed 20696378. Source: UniProtKB

grooming behavior

Inferred from electronic annotation. Source: Ensembl

hormone metabolic process

Inferred from electronic annotation. Source: Ensembl

insulin secretion

Inferred from electronic annotation. Source: Ensembl

iron ion homeostasis

Inferred from electronic annotation. Source: Ensembl

lactate biosynthetic process from pyruvate

Inferred from electronic annotation. Source: Ensembl

locomotory behavior

Inferred from electronic annotation. Source: Ensembl

negative regulation of extrinsic apoptotic signaling pathway

Inferred from mutant phenotype PubMed 19240112. Source: UniProtKB

negative regulation of neuron apoptotic process

Inferred from electronic annotation. Source: Ensembl

neural plate formation

Inferred from electronic annotation. Source: Ensembl

neuron apoptotic process

Inferred from electronic annotation. Source: Ensembl

neuron development

Inferred from electronic annotation. Source: Ensembl

olfactory lobe development

Inferred from electronic annotation. Source: Ensembl

organ development

Inferred from Biological aspect of Ancestor. Source: RefGenome

paraxial mesoderm formation

Inferred from electronic annotation. Source: Ensembl

protein import into nucleus

Inferred from electronic annotation. Source: Ensembl

quinolinate biosynthetic process

Inferred from electronic annotation. Source: Ensembl

regulation of mitochondrial membrane permeability

Inferred from electronic annotation. Source: Ensembl

regulation of mitochondrial membrane potential

Inferred from electronic annotation. Source: Ensembl

regulation of protein export from nucleus

Inferred from mutant phenotype Ref.14. Source: UniProtKB

regulation of protein phosphatase type 2A activity

Inferred from mutant phenotype PubMed 21562226. Source: dictyBase

regulation of synaptic plasticity

Inferred from electronic annotation. Source: Ensembl

response to calcium ion

Inferred from electronic annotation. Source: Ensembl

retrograde vesicle-mediated transport, Golgi to ER

Inferred from mutant phenotype PubMed 20515468. Source: UniProtKB

social behavior

Inferred from electronic annotation. Source: Ensembl

spermatogenesis

Inferred from electronic annotation. Source: Ensembl

striatum development

Inferred from electronic annotation. Source: Ensembl

urea cycle

Inferred from electronic annotation. Source: Ensembl

vesicle transport along microtubule

Inferred from mutant phenotype PubMed 20515468. Source: UniProtKB

visual learning

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentGolgi apparatus

Inferred from direct assay PubMed 15837803. Source: UniProtKB

autophagic vacuole

Inferred from direct assay PubMed 17704510. Source: UniProtKB

axon

Inferred from direct assay PubMed 7748555. Source: UniProtKB

cytoplasm

Inferred from direct assay PubMed 15064418Ref.14PubMed 7748555. Source: UniProtKB

cytoplasmic vesicle membrane

Inferred from direct assay PubMed 7748555. Source: UniProtKB

cytosol

Inferred from direct assay PubMed 20515468. Source: UniProtKB

dendrite

Inferred from direct assay PubMed 7748555. Source: UniProtKB

endoplasmic reticulum

Inferred from direct assay PubMed 17704510. Source: UniProtKB

inclusion body

Inferred from electronic annotation. Source: Ensembl

late endosome

Inferred from direct assay PubMed 17704510. Source: UniProtKB

mitochondrion

Inferred from electronic annotation. Source: GOC

nucleus

Inferred from direct assay Ref.13Ref.14PubMed 17704510. Source: UniProtKB

protein complex

Inferred from direct assay PubMed 18922795. Source: UniProtKB

   Molecular_functionbeta-tubulin binding

Inferred from direct assay PubMed 11870213. Source: UniProtKB

diazepam binding

Inferred from electronic annotation. Source: Ensembl

dynactin binding

Inferred from physical interaction PubMed 18922795. Source: UniProtKB

dynein intermediate chain binding

Inferred from direct assay PubMed 20515468. Source: UniProtKB

identical protein binding

Inferred from physical interaction PubMed 22119730PubMed 23275563. Source: IntAct

p53 binding

Inferred from physical interaction PubMed 10823891. Source: UniProtKB

transcription factor binding

Inferred from Biological aspect of Ancestor. Source: RefGenome

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

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
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
ZDHHC17Q8IUH52EBI-466029,EBI-524753
ZFC3H1G3V1X12EBI-466029,EBI-6448783
ZFYVE19Q96K213EBI-466029,EBI-6448240
ZMAT2Q96NC02EBI-466029,EBI-2682299

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 31423142Huntingtin
PRO_0000083942

Regions

Repeat204 – 24138HEAT 1
Repeat246 – 28338HEAT 2
Repeat316 – 36045HEAT 3
Repeat802 – 83938HEAT 4
Repeat902 – 94039HEAT 5
Region3 – 1311Sufficient for interaction with TPR
Motif2395 – 240410Nuclear export signal By similarity
Compositional bias18 – 3821Poly-Gln
Compositional bias39 – 4911Poly-Pro
Compositional bias63 – 7816Poly-Pro
Compositional bias1437 – 14404Poly-Thr
Compositional bias2341 – 23455Poly-Glu
Compositional bias2638 – 26436Poly-Glu

Sites

Site511 – 5122Cleavage; by apopain Potential
Site528 – 5292Cleavage; by apopain Potential
Site550 – 5512Cleavage; by apopain Potential
Site587 – 5882Cleavage; by apopain Potential

Amino acid modifications

Modified residue91N6-acetyllysine Ref.26
Modified residue1761N6-acetyllysine Ref.26
Modified residue2341N6-acetyllysine Ref.26
Modified residue3431N6-acetyllysine Ref.26
Modified residue4111Phosphoserine Ref.21
Modified residue4321Phosphoserine Ref.23
Modified residue4421N6-acetyllysine Ref.26
Modified residue11791Phosphoserine; by CDK5 Ref.17
Modified residue11991Phosphoserine; by CDK5 Ref.17
Modified residue18701Phosphoserine Ref.19 Ref.21 Ref.24
Modified residue18741Phosphoserine Ref.21 Ref.23 Ref.24

Natural variations

Natural variant181Q → QQQ.
VAR_005268
Natural variant8931G → R.
Corresponds to variant rs363075 [ dbSNP | Ensembl ].
VAR_060170
Natural variant10641V → I.
Corresponds to variant rs35892913 [ dbSNP | Ensembl ].
VAR_060171
Natural variant10911I → M.
Corresponds to variant rs1143646 [ dbSNP | Ensembl ].
VAR_060172
Natural variant11731T → A.
Corresponds to variant rs3025843 [ dbSNP | Ensembl ].
VAR_060173
Natural variant12601T → M.
Corresponds to variant rs34315806 [ dbSNP | Ensembl ].
VAR_060174
Natural variant13821E → A.
Corresponds to variant rs3025837 [ dbSNP | Ensembl ].
VAR_054017
Natural variant13851N → H.
Corresponds to variant rs3025837 [ dbSNP | Ensembl ].
VAR_060175
Natural variant17201T → N.
Corresponds to variant rs363125 [ dbSNP | Ensembl ].
VAR_060176
Natural variant21131D → Y.
Corresponds to variant rs1143648 [ dbSNP | Ensembl ].
VAR_060177
Natural variant23091Y → H.
Corresponds to variant rs362331 [ dbSNP | Ensembl ].
VAR_060178
Natural variant27861V → I. Ref.6
Corresponds to variant rs362272 [ dbSNP | Ensembl ].
VAR_060179

Experimental info

Sequence conflict8231C → S in BAA36753. Ref.2

Secondary structure

... 3142
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P42858 [UniParc].

Last modified May 18, 2010. Version 2.
Checksum: A267509E84D52F0D

FASTA3,142347,603
        10         20         30         40         50         60 
MATLEKLMKA FESLKSFQQQ QQQQQQQQQQ QQQQQQQQPP PPPPPPPPPQ LPQPPPQAQP 

        70         80         90        100        110        120 
LLPQPQPPPP PPPPPPGPAV AEEPLHRPKK ELSATKKDRV NHCLTICENI VAQSVRNSPE 

       130        140        150        160        170        180 
FQKLLGIAME LFLLCSDDAE SDVRMVADEC LNKVIKALMD SNLPRLQLEL YKEIKKNGAP 

       190        200        210        220        230        240 
RSLRAALWRF AELAHLVRPQ KCRPYLVNLL PCLTRTSKRP EESVQETLAA AVPKIMASFG 

       250        260        270        280        290        300 
NFANDNEIKV LLKAFIANLK SSSPTIRRTA AGSAVSICQH SRRTQYFYSW LLNVLLGLLV 

       310        320        330        340        350        360 
PVEDEHSTLL ILGVLLTLRY LVPLLQQQVK DTSLKGSFGV TRKEMEVSPS AEQLVQVYEL 

       370        380        390        400        410        420 
TLHHTQHQDH NVVTGALELL QQLFRTPPPE LLQTLTAVGG IGQLTAAKEE SGGRSRSGSI 

       430        440        450        460        470        480 
VELIAGGGSS CSPVLSRKQK GKVLLGEEEA LEDDSESRSD VSSSALTASV KDEISGELAA 

       490        500        510        520        530        540 
SSGVSTPGSA GHDIITEQPR SQHTLQADSV DLASCDLTSS ATDGDEEDIL SHSSSQVSAV 

       550        560        570        580        590        600 
PSDPAMDLND GTQASSPISD SSQTTTEGPD SAVTPSDSSE IVLDGTDNQY LGLQIGQPQD 

       610        620        630        640        650        660 
EDEEATGILP DEASEAFRNS SMALQQAHLL KNMSHCRQPS DSSVDKFVLR DEATEPGDQE 

       670        680        690        700        710        720 
NKPCRIKGDI GQSTDDDSAP LVHCVRLLSA SFLLTGGKNV LVPDRDVRVS VKALALSCVG 

       730        740        750        760        770        780 
AAVALHPESF FSKLYKVPLD TTEYPEEQYV SDILNYIDHG DPQVRGATAI LCGTLICSIL 

       790        800        810        820        830        840 
SRSRFHVGDW MGTIRTLTGN TFSLADCIPL LRKTLKDESS VTCKLACTAV RNCVMSLCSS 

       850        860        870        880        890        900 
SYSELGLQLI IDVLTLRNSS YWLVRTELLE TLAEIDFRLV SFLEAKAENL HRGAHHYTGL 

       910        920        930        940        950        960 
LKLQERVLNN VVIHLLGDED PRVRHVAAAS LIRLVPKLFY KCDQGQADPV VAVARDQSSV 

       970        980        990       1000       1010       1020 
YLKLLMHETQ PPSHFSVSTI TRIYRGYNLL PSITDVTMEN NLSRVIAAVS HELITSTTRA 

      1030       1040       1050       1060       1070       1080 
LTFGCCEALC LLSTAFPVCI WSLGWHCGVP PLSASDESRK SCTVGMATMI LTLLSSAWFP 

      1090       1100       1110       1120       1130       1140 
LDLSAHQDAL ILAGNLLAAS APKSLRSSWA SEEEANPAAT KQEEVWPALG DRALVPMVEQ 

      1150       1160       1170       1180       1190       1200 
LFSHLLKVIN ICAHVLDDVA PGPAIKAALP SLTNPPSLSP IRRKGKEKEP GEQASVPLSP 

      1210       1220       1230       1240       1250       1260 
KKGSEASAAS RQSDTSGPVT TSKSSSLGSF YHLPSYLKLH DVLKATHANY KVTLDLQNST 

      1270       1280       1290       1300       1310       1320 
EKFGGFLRSA LDVLSQILEL ATLQDIGKCV EEILGYLKSC FSREPMMATV CVQQLLKTLF 

      1330       1340       1350       1360       1370       1380 
GTNLASQFDG LSSNPSKSQG RAQRLGSSSV RPGLYHYCFM APYTHFTQAL ADASLRNMVQ 

      1390       1400       1410       1420       1430       1440 
AEQENDTSGW FDVLQKVSTQ LKTNLTSVTK NRADKNAIHN HIRLFEPLVI KALKQYTTTT 

      1450       1460       1470       1480       1490       1500 
CVQLQKQVLD LLAQLVQLRV NYCLLDSDQV FIGFVLKQFE YIEVGQFRES EAIIPNIFFF 

      1510       1520       1530       1540       1550       1560 
LVLLSYERYH SKQIIGIPKI IQLCDGIMAS GRKAVTHAIP ALQPIVHDLF VLRGTNKADA 

      1570       1580       1590       1600       1610       1620 
GKELETQKEV VVSMLLRLIQ YHQVLEMFIL VLQQCHKENE DKWKRLSRQI ADIILPMLAK 

      1630       1640       1650       1660       1670       1680 
QQMHIDSHEA LGVLNTLFEI LAPSSLRPVD MLLRSMFVTP NTMASVSTVQ LWISGILAIL 

      1690       1700       1710       1720       1730       1740 
RVLISQSTED IVLSRIQELS FSPYLISCTV INRLRDGDST STLEEHSEGK QIKNLPEETF 

      1750       1760       1770       1780       1790       1800 
SRFLLQLVGI LLEDIVTKQL KVEMSEQQHT FYCQELGTLL MCLIHIFKSG MFRRITAAAT 

      1810       1820       1830       1840       1850       1860 
RLFRSDGCGG SFYTLDSLNL RARSMITTHP ALVLLWCQIL LLVNHTDYRW WAEVQQTPKR 

      1870       1880       1890       1900       1910       1920 
HSLSSTKLLS PQMSGEEEDS DLAAKLGMCN REIVRRGALI LFCDYVCQNL HDSEHLTWLI 

      1930       1940       1950       1960       1970       1980 
VNHIQDLISL SHEPPVQDFI SAVHRNSAAS GLFIQAIQSR CENLSTPTML KKTLQCLEGI 

      1990       2000       2010       2020       2030       2040 
HLSQSGAVLT LYVDRLLCTP FRVLARMVDI LACRRVEMLL AANLQSSMAQ LPMEELNRIQ 

      2050       2060       2070       2080       2090       2100 
EYLQSSGLAQ RHQRLYSLLD RFRLSTMQDS LSPSPPVSSH PLDGDGHVSL ETVSPDKDWY 

      2110       2120       2130       2140       2150       2160 
VHLVKSQCWT RSDSALLEGA ELVNRIPAED MNAFMMNSEF NLSLLAPCLS LGMSEISGGQ 

      2170       2180       2190       2200       2210       2220 
KSALFEAARE VTLARVSGTV QQLPAVHHVF QPELPAEPAA YWSKLNDLFG DAALYQSLPT 

      2230       2240       2250       2260       2270       2280 
LARALAQYLV VVSKLPSHLH LPPEKEKDIV KFVVATLEAL SWHLIHEQIP LSLDLQAGLD 

      2290       2300       2310       2320       2330       2340 
CCCLALQLPG LWSVVSSTEF VTHACSLIYC VHFILEAVAV QPGEQLLSPE RRTNTPKAIS 

      2350       2360       2370       2380       2390       2400 
EEEEEVDPNT QNPKYITAAC EMVAEMVESL QSVLALGHKR NSGVPAFLTP LLRNIIISLA 

      2410       2420       2430       2440       2450       2460 
RLPLVNSYTR VPPLVWKLGW SPKPGGDFGT AFPEIPVEFL QEKEVFKEFI YRINTLGWTS 

      2470       2480       2490       2500       2510       2520 
RTQFEETWAT LLGVLVTQPL VMEQEESPPE EDTERTQINV LAVQAITSLV LSAMTVPVAG 

      2530       2540       2550       2560       2570       2580 
NPAVSCLEQQ PRNKPLKALD TRFGRKLSII RGIVEQEIQA MVSKRENIAT HHLYQAWDPV 

      2590       2600       2610       2620       2630       2640 
PSLSPATTGA LISHEKLLLQ INPERELGSM SYKLGQVSIH SVWLGNSITP LREEEWDEEE 

      2650       2660       2670       2680       2690       2700 
EEEADAPAPS SPPTSPVNSR KHRAGVDIHS CSQFLLELYS RWILPSSSAR RTPAILISEV 

      2710       2720       2730       2740       2750       2760 
VRSLLVVSDL FTERNQFELM YVTLTELRRV HPSEDEILAQ YLVPATCKAA AVLGMDKAVA 

      2770       2780       2790       2800       2810       2820 
EPVSRLLEST LRSSHLPSRV GALHGVLYVL ECDLLDDTAK QLIPVISDYL LSNLKGIAHC 

      2830       2840       2850       2860       2870       2880 
VNIHSQQHVL VMCATAFYLI ENYPLDVGPE FSASIIQMCG VMLSGSEEST PSIIYHCALR 

      2890       2900       2910       2920       2930       2940 
GLERLLLSEQ LSRLDAESLV KLSVDRVNVH SPHRAMAALG LMLTCMYTGK EKVSPGRTSD 

      2950       2960       2970       2980       2990       3000 
PNPAAPDSES VIVAMERVSV LFDRIRKGFP CEARVVARIL PQFLDDFFPP QDIMNKVIGE 

      3010       3020       3030       3040       3050       3060 
FLSNQQPYPQ FMATVVYKVF QTLHSTGQSS MVRDWVMLSL SNFTQRAPVA MATWSLSCFF 

      3070       3080       3090       3100       3110       3120 
VSASTSPWVA AILPHVISRM GKLEQVDVNL FCLVATDFYR HQIEEELDRR AFQSVLEVVA 

      3130       3140 
APGSPYHRLL TCLRNVHKVT TC 

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References

« Hide 'large scale' references
[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. expand/collapse author list , 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. expand/collapse author list , 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]"Structure and expression of the Huntington's disease gene: evidence against simple inactivation due to an expanded CAG repeat."
Ambrose C.M., Duyao M.P., Barnes G., Bates G.P., Lin C.S., Srinidhi J., Baxendale S., Hummerich H., Lehrach H., Altherr M., Wasmuth J., Buckler A., Church D., Housman D., Berks M., Micklem G., Durbin R., Dodge A. expand/collapse author list , Read A., Gusella J.F., Macdonald M.E.
Somat. Cell Mol. Genet. 20:27-38(1994) [PubMed] [Europe PMC] [Abstract]
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]"Huntingtin interacts with a family of WW domain proteins."
Faber P.W., Barnes G.T., Srinidhi J., Chen J., Gusella J.F., MacDonald M.E.
Hum. Mol. Genet. 7:1463-1474(1998) [PubMed] [Europe PMC] [Abstract]
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]"Phosphoproteome of resting human platelets."
Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J., Schuetz C., Walter U., Gambaryan S., Sickmann A.
J. Proteome Res. 7:526-534(2008) [PubMed] [Europe PMC] [Abstract]
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]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
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]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
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.
+Additional computationally mapped references.

Web resources

GeneReviews
Wikipedia

Huntingtin entry

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
PIRA46068.
RefSeqNP_002102.4. NM_002111.6.
UniGeneHs.518450.

3D structure databases

PDBe
RCSB PDB
PDBj
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[»]
ProteinModelPortalP42858.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid109314. 181 interactions.
DIPDIP-32492N.
IntActP42858. 333 interactions.
MINTMINT-133355.
STRING9606.ENSP00000347184.

Chemistry

ChEMBLCHEMBL5514.

PTM databases

PhosphoSiteP42858.

Polymorphism databases

DMDM296434520.

Proteomic databases

PaxDbP42858.
PRIDEP42858.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000355072; ENSP00000347184; ENSG00000197386.
GeneID3064.
KEGGhsa:3064.
UCSCuc021xkv.1. human.

Organism-specific databases

CTD3064.
GeneCardsGC04P003076.
HGNCHGNC:4851. HTT.
HPACAB002756.
HPA026114.
MIM143100. phenotype.
613004. gene.
neXtProtNX_P42858.
Orphanet399. Huntington disease.
248111. Juvenile Huntington disease.
PharmGKBPA164741646.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG82191.
HOGENOMHOG000082472.
HOVERGENHBG005953.
InParanoidP42858.
KOK04533.
OMASDQVFIG.
OrthoDBEOG7JQBMD.
PhylomeDBP42858.
TreeFamTF323608.

Enzyme and pathway databases

SignaLinkP42858.

Gene expression databases

ArrayExpressP42858.
BgeeP42858.
CleanExHS_HTT.
GenevestigatorP42858.

Family and domain databases

Gene3D1.25.10.10. 4 hits.
InterProIPR011989. ARM-like.
IPR016024. ARM-type_fold.
IPR000091. Huntingtin.
IPR028426. Huntingtin_fam.
IPR024613. Huntingtin_middle-repeat.
[Graphical view]
PANTHERPTHR10170. PTHR10170. 1 hit.
PTHR10170:SF5. PTHR10170:SF5. 1 hit.
PfamPF12372. DUF3652. 2 hits.
[Graphical view]
PRINTSPR00375. HUNTINGTIN.
SUPFAMSSF48371. SSF48371. 6 hits.
ProtoNetSearch...

Other

ChiTaRSHTT. human.
EvolutionaryTraceP42858.
GeneWikiHuntingtin.
GenomeRNAi3064.
NextBio12121.
PROP42858.
SOURCESearch...

Entry information

Entry nameHD_HUMAN
AccessionPrimary (citable) accession number: P42858
Secondary accession number(s): Q9UQB7
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1995
Last sequence update: May 18, 2010
Last modified: April 16, 2014
This is version 147 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 4

Human chromosome 4: entries, gene names and cross-references to MIM