P42858 (HD_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Huntingtin

Alternative name(s):
Huntington disease protein
Short name=HD protein

Gene names

Name:	HTT
Synonyms:	HD, IT15

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	3142 AA.
Sequence status	Complete.
Protein existence	Evidence 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. Ref.9 Ref.10 Ref.11 Ref.12 Ref.15 Ref.19
Subcellular location	Cytoplasm. Nucleus. Note: The mutant Huntingtin protein colocalizes with AKAP8L in the nuclear matrix of Huntington's disease neurons. Ref.7 Ref.14
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.14
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.25
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	Defects in HTT are the cause of Huntington disease (HD) [MIM:143100]. HD is an autosomal dominant 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 and symptoms progressively worsen leading to death in 10 to 20 years. Onset and clinical course depend on the degree of poly-Gln repeat expansion, longer expansions resulting in earlier onset and more severe clinical manifestations. HD affects 1 in 10,000 individuals of European origin. Neuropathology of Huntington disease displays a distinctive pattern with loss of neurons, especially in the caudate and putamen (striatum).
Sequence similarities	Belongs to the huntingtin family. Contains 10 HEAT repeats.

Ontologies

Keywords
Biological process	Apoptosis
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Polymorphism Triplet repeat expansion
Disease	Disease mutation Neurodegeneration
Domain	Repeat
PTM	Acetylation Phosphoprotein Ubl conjugation
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	Golgi organization Inferred from mutant phenotype. Source: UniProtKB apoptotic process Inferred from electronic annotation. Source: UniProtKB-KW establishment of mitotic spindle orientation Inferred from mutant phenotype. Source: UniProtKB organ development Inferred from Biological aspect of Ancestor. Source: RefGenome regulation of protein phosphatase type 2A activity Inferred from mutant phenotype. Source: dictyBase retrograde vesicle-mediated transport, Golgi to ER Inferred from mutant phenotype. Source: UniProtKB vesicle transport along microtubule Inferred from mutant phenotype. Source: UniProtKB
Cellular component	Golgi apparatus Inferred from direct assay. Source: UniProtKB autophagic vacuole Inferred from direct assay. Source: UniProtKB axon Inferred from direct assay. Source: UniProtKB cytoplasmic vesicle membrane Inferred from direct assay. Source: UniProtKB cytosol Inferred from direct assay. Source: UniProtKB dendrite Inferred from direct assay. Source: UniProtKB endoplasmic reticulum Inferred from direct assay. Source: UniProtKB late endosome Inferred from direct assay. Source: UniProtKB membrane fraction Inferred from direct assay. Source: UniProtKB nucleus Inferred from direct assay Ref.13. Source: UniProtKB protein complex Inferred from direct assay. Source: UniProtKB
Molecular function	beta-tubulin binding Inferred from direct assay. Source: UniProtKB dynactin binding Inferred from physical interaction. Source: UniProtKB dynein intermediate chain binding Inferred from direct assay. Source: UniProtKB p53 binding Inferred from physical interaction. Source: UniProtKB transcription factor binding Inferred from Biological aspect of Ancestor. Source: RefGenome
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
CHD3	Q12873	3	EBI-466029,EBI-523590
CRMP1	Q14194	2	EBI-466029,EBI-473101
ECH1	Q13011	2	EBI-466029,EBI-711968
FEZ1	Q99689	3	EBI-466029,EBI-396435
GIT1	Q9Y2X7	10	EBI-466029,EBI-466061
IKBKAP	O95163	4	EBI-466029,EBI-347559
KIAA1377	Q9P2H0	2	EBI-466029,EBI-473176
MED31	Q9Y3C7	3	EBI-466029,EBI-394707
MTSS1	O43312	3	EBI-466029,EBI-473954
NBR1	Q14596	3	EBI-466029,EBI-742698
PFN2	P35080	4	EBI-466029,EBI-473138
PIAS4	Q8N2W9	3	EBI-466029,EBI-473160
PRPF40A	O75400	3	EBI-466029,EBI-473291
SH3GL3	Q99963	4	EBI-466029,EBI-473910
TCERG1	O14776	3	EBI-466029,EBI-473271
TP53	P04637	4	EBI-466029,EBI-366083
WDFY3	Q8IZQ1	11	EBI-466029,EBI-1569256
XRCC6	P12956	3	EBI-466029,EBI-353208

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 3142

3142

Huntingtin

PRO_0000083942

Regions

Repeat

204 – 241

38

HEAT 1

Repeat

246 – 283

38

HEAT 2

Repeat

316 – 360

45

HEAT 3

Repeat

802 – 839

38

HEAT 4

Repeat

902 – 940

39

HEAT 5

Motif

2395 – 2404

10

Nuclear export signal By similarity

Compositional bias

18 – 38

21

Poly-Gln

Compositional bias

39 – 49

11

Poly-Pro

Compositional bias

63 – 78

16

Poly-Pro

Compositional bias

1437 – 1440

4

Poly-Thr

Compositional bias

2341 – 2345

5

Poly-Glu

Compositional bias

2638 – 2643

6

Poly-Glu

Sites

Site

511 – 512

2

Cleavage; by apopain Potential

Site

528 – 529

2

Cleavage; by apopain Potential

Site

550 – 551

2

Cleavage; by apopain Potential

Site

587 – 588

2

Cleavage; by apopain Potential

Amino acid modifications

Modified residue

9

1

N6-acetyllysine Ref.24

Modified residue

176

1

N6-acetyllysine Ref.24

Modified residue

234

1

N6-acetyllysine Ref.24

Modified residue

343

1

N6-acetyllysine Ref.24

Modified residue

411

1

Phosphoserine Ref.20

Modified residue

419

1

Phosphoserine Ref.17 Ref.21

Modified residue

432

1

Phosphoserine Ref.17 Ref.21 Ref.22

Modified residue

442

1

N6-acetyllysine Ref.24

Modified residue

1179

1

Phosphoserine; by CDK5 Ref.16 Ref.18

Modified residue

1199

1

Phosphoserine; by CDK5 Ref.16 Ref.18 Ref.21

Modified residue

1870

1

Phosphoserine Ref.18 Ref.20 Ref.21

Modified residue

1874

1

Phosphoserine Ref.20 Ref.21 Ref.22

Natural variations

Natural variant

18

1

Q → QQQ.

VAR_005268

Natural variant

893

1

G → R.
Corresponds to variant rs363075 [ dbSNP | Ensembl ].

VAR_060170

Natural variant

1064

1

V → I.
Corresponds to variant rs35892913 [ dbSNP | Ensembl ].

VAR_060171

Natural variant

1091

1

I → M.
Corresponds to variant rs1143646 [ dbSNP | Ensembl ].

VAR_060172

Natural variant

1173

1

T → A.
Corresponds to variant rs3025843 [ dbSNP | Ensembl ].

VAR_060173

Natural variant

1260

1

T → M.
Corresponds to variant rs34315806 [ dbSNP | Ensembl ].

VAR_060174

Natural variant

1382

1

E → A.
Corresponds to variant rs3025837 [ dbSNP | Ensembl ].

VAR_054017

Natural variant

1385

1

N → H.
Corresponds to variant rs3025837 [ dbSNP | Ensembl ].

VAR_060175

Natural variant

1720

1

T → N.
Corresponds to variant rs363125 [ dbSNP | Ensembl ].

VAR_060176

Natural variant

2113

1

D → Y.
Corresponds to variant rs1143648 [ dbSNP | Ensembl ].

VAR_060177

Natural variant

2309

1

Y → H.
Corresponds to variant rs362331 [ dbSNP | Ensembl ].

VAR_060178

Natural variant

2786

1

V → I. Ref.6
Corresponds to variant rs362272 [ dbSNP | Ensembl ].

VAR_060179

Experimental info

Sequence conflict

823

1

C → S in BAA36753. Ref.2

Secondary structure

1

.

.

3142

Helix Strand Turn

Details...

Helix

1 – 16

16

Sequences

	Sequence		Length	Mass (Da)
	P42858 [UniParc]. Last modified May 18, 2010. Version 2. Checksum: A267509E84D52F0D	FASTA	3,142	347,603
	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

References

	« Hide 'large scale' referencesShow '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. , 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: 8458085] [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: 11013077] [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: 15815621] [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. , Read A., Gusella J.F., Macdonald M.E. Somat. Cell Mol. Genet. 20:27-38(1994) [PubMed: 8197474] [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: 7759106] [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: 7903579] [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: 7647777] [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: 8696339] [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: 9700202] [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: 10332029] [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: 10958656] [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: 11461154] [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: 12783847] [Abstract] Cited for: NUCLEAR EXPORT SIGNAL.
[14]	"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: 16391387] [Abstract] Cited for: SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[15]	"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: 17141218] [Abstract] Cited for: INTERACTION WITH SYVN, UBIQUITINATION.
[16]	"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: 17611284] [Abstract] Cited for: PHOSPHORYLATION AT SER-1179 AND SER-1199.
[17]	"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: 18088087] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-419 AND SER-432, MASS SPECTROMETRY. Tissue: Platelet.
[18]	"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: 18691976] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1179; SER-1199 AND SER-1870, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[19]	"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: 18573880] [Abstract] Cited for: INTERACTION WITH PFN1.
[20]	"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: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-411; SER-1870 AND SER-1874, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[21]	"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: 19413330] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-419; SER-432; SER-1199; SER-1870 AND SER-1874, MASS SPECTROMETRY. Tissue: Embryonic kidney.
[22]	"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: 19690332] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-432 AND SER-1874, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[23]	"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: 21269460] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[24]	"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: 21685499] [Abstract] Cited for: ACETYLATION AT LYS-9; LYS-176; LYS-234; LYS-343 AND LYS-442.
[25]	"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: 19748341] [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.

IPI

IPI00002335.

PIR

A46068.

RefSeq

NP_002102.4. NM_002111.6.

UniGene

Hs.518450.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2D3X	model	-	A	199-325	[»]
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	[»]

ProteinModelPortal

P42858.

ModBase

Search...

Protein-protein interaction databases

IntAct

P42858. 38 interactions.

MINT

MINT-133355.

STRING

P42858.

PTM databases

PhosphoSite

P42858.

Polymorphism databases

DMDM

296434520.

Proteomic databases

PRIDE

P42858.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000355072; ENSP00000347184; ENSG00000197386.

GeneID

3064.

KEGG

hsa:3064.

UCSC

uc010icr.1. human.

Organism-specific databases

CTD

3064.

GeneCards

GC04P003076.

H-InvDB

HIX0004042.

HGNC

HGNC:4851. HTT.

HPA

CAB002756.
HPA026114.

MIM

143100. phenotype.
613004. gene.

neXtProt

NX_P42858.

Orphanet

399. Huntington disease.
248111. Juvenile Huntington disease.

PharmGKB

PA164741646.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG06671.

HOGENOM

HBG356385.

HOVERGEN

HBG005953.

InParanoid

P42858.

OMA

DSEHLTW.

OrthoDB

EOG4RNB7G.

PhylomeDB

P42858.

Gene expression databases

ArrayExpress

P42858.

Bgee

P42858.

CleanEx

HS_HTT.

Genevestigator

P42858.

GermOnline

ENSG00000197386. Homo sapiens.

Family and domain databases

InterPro

IPR011989. ARM-like.
IPR016024. ARM-type_fold.
IPR000357. HEAT.
IPR000091. Huntingtin.
IPR024613. Huntingtin_middle-repeat.
[Graphical view]

Gene3D

G3DSA:1.25.10.10. ARM-like. 3 hits.

KO

K04533.

PANTHER

PTHR10170. Huntingtin. 1 hit.

Pfam

PF12372. DUF3652. 2 hits.
PF02985. HEAT. 1 hit.
[Graphical view]

PRINTS

PR00375. HUNTINGTIN.

SUPFAM

SSF48371. ARM-type_fold. 1 hit.

PROSITE

PS50077. HEAT_REPEAT. False negative.
[Graphical view]

ProtoNet

Search...

Other

NextBio

12121.

SOURCE

Search...

Entry information

Entry name

HD_HUMAN

Accession

Primary (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:	January 25, 2012
This is version 121 of the entry and version 2 of the sequence. [Complete history]

Entry status

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.