CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-007605
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 Huntingtin 
Protein Synonyms/Alias
 Huntington disease protein; HD protein 
Gene Name
 HTT 
Gene Synonyms/Alias
 HD; IT15 
Created Date
 July 27, 2013 
Organism
 Homo sapiens (Human) 
NCBI Taxa ID
 9606 
Lysine Modification
Position
Peptide
Type
References
6**MATLEKLMKAFESsumoylation[1, 2]
9ATLEKLMKAFESLKSacetylation[3]
9ATLEKLMKAFESLKSsumoylation[1, 2]
15MKAFESLKSFQQQQQsumoylation[1, 2]
89EEPLHRPKKELSATKsumoylation[2]
176ELYKEIKKNGAPRSLacetylation[3]
234TLAAAVPKIMASFGNacetylation[3]
253NEIKVLLKAFIANLKubiquitination[4]
343GSFGVTRKEMEVSPSacetylation[3]
438CSPVLSRKQKGKVLLacetylation[5]
667ENKPCRIKGDIGQSTubiquitination[4]
698SFLLTGGKNVLVPDRubiquitination[4]
813DCIPLLRKTLKDESSubiquitination[4]
902HHYTGLLKLQERVLNubiquitination[4, 6]
937SLIRLVPKLFYKCDQubiquitination[4]
941LVPKLFYKCDQGQADubiquitination[4, 7, 8]
1121EANPAATKQEEVWPAubiquitination[6]
1262DLQNSTEKFGGFLRSubiquitination[9, 10]
1337GLSSNPSKSQGRAQRubiquitination[4, 6]
1402QKVSTQLKTNLTSVTubiquitination[4, 8, 9, 10]
1410TNLTSVTKNRADKNAubiquitination[4, 6, 8]
1431LFEPLVIKALKQYTTubiquitination[6, 8, 9, 10, 11]
1730LEEHSEGKQIKNLPEubiquitination[6]
1733HSEGKQIKNLPEETFubiquitination[4]
1867RHSLSSTKLLSPQMSubiquitination[6]
1885EDSDLAAKLGMCNREubiquitination[4]
1972STPTMLKKTLQCLEGubiquitination[4]
2337ERRTNTPKAISEEEEubiquitination[6]
2417RVPPLVWKLGWSPKPubiquitination[9, 10]
2537QPRNKPLKALDTRFGubiquitination[4]
2564EIQAMVSKRENIATHubiquitination[4, 6]
2757AAVLGMDKAVAEPVSubiquitination[4]
2901LDAESLVKLSVDRVNubiquitination[4]
2967VLFDRIRKGFPCEARubiquitination[4]
Reference
 [1] SUMO modification of Huntingtin and Huntington's disease pathology.
 Steffan JS, Agrawal N, Pallos J, Rockabrand E, Trotman LC, Slepko N, Illes K, Lukacsovich T, Zhu YZ, Cattaneo E, Pandolfi PP, Thompson LM, Marsh JL.
 Science. 2004 Apr 2;304(5667):100-4. [PMID: 15064418]
 [2] Rhes, a striatal specific protein, mediates mutant-huntingtin cytotoxicity.
 Subramaniam S, Sixt KM, Barrow R, Snyder SH.
 Science. 2009 Jun 5;324(5932):1327-30. [PMID: 19498170]
 [3] Mass spectrometric identification of novel lysine acetylation sites in huntingtin.
 Cong X, Held JM, DeGiacomo F, Bonner A, Chen JM, Schilling B, Czerwieniec GA, Gibson BW, Ellerby LM.
 Mol Cell Proteomics. 2011 Oct;10(10):M111.009829. [PMID: 21685499]
 [4] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
 Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
 Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961]
 [5] Acetylation targets mutant huntingtin to autophagosomes for degradation.
 Jeong H, Then F, Melia TJ Jr, Mazzulli JR, Cui L, Savas JN, Voisine C, Paganetti P, Tanese N, Hart AC, Yamamoto A, Krainc D.
 Cell. 2009 Apr 3;137(1):60-72. [PMID: 19345187]
 [6] Systematic and quantitative assessment of the ubiquitin-modified proteome.
 Kim W, Bennett EJ, Huttlin EL, Guo A, Li J, Possemato A, Sowa ME, Rad R, Rush J, Comb MJ, Harper JW, Gygi SP.
 Mol Cell. 2011 Oct 21;44(2):325-40. [PMID: 21906983]
 [7] Methods for quantification of in vivo changes in protein ubiquitination following proteasome and deubiquitinase inhibition.
 Udeshi ND, Mani DR, Eisenhaure T, Mertins P, Jaffe JD, Clauser KR, Hacohen N, Carr SA.
 Mol Cell Proteomics. 2012 May;11(5):148-59. [PMID: 22505724]
 [8] Integrated proteomic analysis of post-translational modifications by serial enrichment.
 Mertins P, Qiao JW, Patel J, Udeshi ND, Clauser KR, Mani DR, Burgess MW, Gillette MA, Jaffe JD, Carr SA.
 Nat Methods. 2013 Jul;10(7):634-7. [PMID: 23749302]
 [9] A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles.
 Wagner SA, Beli P, Weinert BT, Nielsen ML, Cox J, Mann M, Choudhary C.
 Mol Cell Proteomics. 2011 Oct;10(10):M111.013284. [PMID: 21890473]
 [10] hCKSAAP_UbSite: improved prediction of human ubiquitination sites by exploiting amino acid pattern and properties.
 Chen Z, Zhou Y, Song J, Zhang Z.
 Biochim Biophys Acta. 2013 Aug;1834(8):1461-7. [PMID: 23603789]
 [11] Systems-wide analysis of ubiquitylation dynamics reveals a key role for PAF15 ubiquitylation in DNA-damage bypass.
 Povlsen LK, Beli P, Wagner SA, Poulsen SL, Sylvestersen KB, Poulsen JW, Nielsen ML, Bekker-Jensen S, Mailand N, Choudhary C.
 Nat Cell Biol. 2012 Oct;14(10):1089-98. [PMID: 23000965] 
Functional Description
 May play a role in microtubule-mediated transport or vesicle function. 
Sequence Annotation
 REPEAT 204 241 HEAT 1.
 REPEAT 246 283 HEAT 2.
 REPEAT 316 360 HEAT 3.
 REPEAT 802 839 HEAT 4.
 REPEAT 902 940 HEAT 5.
 REGION 3 13 Sufficient for interaction with TPR.
 MOTIF 2395 2404 Nuclear export signal (By similarity).
 MOD_RES 9 9 N6-acetyllysine.
 MOD_RES 176 176 N6-acetyllysine.
 MOD_RES 234 234 N6-acetyllysine.
 MOD_RES 343 343 N6-acetyllysine.
 MOD_RES 411 411 Phosphoserine.
 MOD_RES 419 419 Phosphoserine (By similarity).
 MOD_RES 432 432 Phosphoserine.
 MOD_RES 442 442 N6-acetyllysine.
 MOD_RES 1179 1179 Phosphoserine; by CDK5.
 MOD_RES 1199 1199 Phosphoserine; by CDK5.
 MOD_RES 1870 1870 Phosphoserine.
 MOD_RES 1874 1874 Phosphoserine.  
Keyword
 3D-structure; Acetylation; Apoptosis; Complete proteome; Cytoplasm; Disease mutation; Neurodegeneration; Nucleus; Phosphoprotein; Polymorphism; Reference proteome; Repeat; Triplet repeat expansion; Ubl conjugation. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 3142 AA 
Protein Sequence
MATLEKLMKA FESLKSFQQQ QQQQQQQQQQ QQQQQQQQPP PPPPPPPPPQ LPQPPPQAQP 60
LLPQPQPPPP PPPPPPGPAV AEEPLHRPKK ELSATKKDRV NHCLTICENI VAQSVRNSPE 120
FQKLLGIAME LFLLCSDDAE SDVRMVADEC LNKVIKALMD SNLPRLQLEL YKEIKKNGAP 180
RSLRAALWRF AELAHLVRPQ KCRPYLVNLL PCLTRTSKRP EESVQETLAA AVPKIMASFG 240
NFANDNEIKV LLKAFIANLK SSSPTIRRTA AGSAVSICQH SRRTQYFYSW LLNVLLGLLV 300
PVEDEHSTLL ILGVLLTLRY LVPLLQQQVK DTSLKGSFGV TRKEMEVSPS AEQLVQVYEL 360
TLHHTQHQDH NVVTGALELL QQLFRTPPPE LLQTLTAVGG IGQLTAAKEE SGGRSRSGSI 420
VELIAGGGSS CSPVLSRKQK GKVLLGEEEA LEDDSESRSD VSSSALTASV KDEISGELAA 480
SSGVSTPGSA GHDIITEQPR SQHTLQADSV DLASCDLTSS ATDGDEEDIL SHSSSQVSAV 540
PSDPAMDLND GTQASSPISD SSQTTTEGPD SAVTPSDSSE IVLDGTDNQY LGLQIGQPQD 600
EDEEATGILP DEASEAFRNS SMALQQAHLL KNMSHCRQPS DSSVDKFVLR DEATEPGDQE 660
NKPCRIKGDI GQSTDDDSAP LVHCVRLLSA SFLLTGGKNV LVPDRDVRVS VKALALSCVG 720
AAVALHPESF FSKLYKVPLD TTEYPEEQYV SDILNYIDHG DPQVRGATAI LCGTLICSIL 780
SRSRFHVGDW MGTIRTLTGN TFSLADCIPL LRKTLKDESS VTCKLACTAV RNCVMSLCSS 840
SYSELGLQLI IDVLTLRNSS YWLVRTELLE TLAEIDFRLV SFLEAKAENL HRGAHHYTGL 900
LKLQERVLNN VVIHLLGDED PRVRHVAAAS LIRLVPKLFY KCDQGQADPV VAVARDQSSV 960
YLKLLMHETQ PPSHFSVSTI TRIYRGYNLL PSITDVTMEN NLSRVIAAVS HELITSTTRA 1020
LTFGCCEALC LLSTAFPVCI WSLGWHCGVP PLSASDESRK SCTVGMATMI LTLLSSAWFP 1080
LDLSAHQDAL ILAGNLLAAS APKSLRSSWA SEEEANPAAT KQEEVWPALG DRALVPMVEQ 1140
LFSHLLKVIN ICAHVLDDVA PGPAIKAALP SLTNPPSLSP IRRKGKEKEP GEQASVPLSP 1200
KKGSEASAAS RQSDTSGPVT TSKSSSLGSF YHLPSYLKLH DVLKATHANY KVTLDLQNST 1260
EKFGGFLRSA LDVLSQILEL ATLQDIGKCV EEILGYLKSC FSREPMMATV CVQQLLKTLF 1320
GTNLASQFDG LSSNPSKSQG RAQRLGSSSV RPGLYHYCFM APYTHFTQAL ADASLRNMVQ 1380
AEQENDTSGW FDVLQKVSTQ LKTNLTSVTK NRADKNAIHN HIRLFEPLVI KALKQYTTTT 1440
CVQLQKQVLD LLAQLVQLRV NYCLLDSDQV FIGFVLKQFE YIEVGQFRES EAIIPNIFFF 1500
LVLLSYERYH SKQIIGIPKI IQLCDGIMAS GRKAVTHAIP ALQPIVHDLF VLRGTNKADA 1560
GKELETQKEV VVSMLLRLIQ YHQVLEMFIL VLQQCHKENE DKWKRLSRQI ADIILPMLAK 1620
QQMHIDSHEA LGVLNTLFEI LAPSSLRPVD MLLRSMFVTP NTMASVSTVQ LWISGILAIL 1680
RVLISQSTED IVLSRIQELS FSPYLISCTV INRLRDGDST STLEEHSEGK QIKNLPEETF 1740
SRFLLQLVGI LLEDIVTKQL KVEMSEQQHT FYCQELGTLL MCLIHIFKSG MFRRITAAAT 1800
RLFRSDGCGG SFYTLDSLNL RARSMITTHP ALVLLWCQIL LLVNHTDYRW WAEVQQTPKR 1860
HSLSSTKLLS PQMSGEEEDS DLAAKLGMCN REIVRRGALI LFCDYVCQNL HDSEHLTWLI 1920
VNHIQDLISL SHEPPVQDFI SAVHRNSAAS GLFIQAIQSR CENLSTPTML KKTLQCLEGI 1980
HLSQSGAVLT LYVDRLLCTP FRVLARMVDI LACRRVEMLL AANLQSSMAQ LPMEELNRIQ 2040
EYLQSSGLAQ RHQRLYSLLD RFRLSTMQDS LSPSPPVSSH PLDGDGHVSL ETVSPDKDWY 2100
VHLVKSQCWT RSDSALLEGA ELVNRIPAED MNAFMMNSEF NLSLLAPCLS LGMSEISGGQ 2160
KSALFEAARE VTLARVSGTV QQLPAVHHVF QPELPAEPAA YWSKLNDLFG DAALYQSLPT 2220
LARALAQYLV VVSKLPSHLH LPPEKEKDIV KFVVATLEAL SWHLIHEQIP LSLDLQAGLD 2280
CCCLALQLPG LWSVVSSTEF VTHACSLIYC VHFILEAVAV QPGEQLLSPE RRTNTPKAIS 2340
EEEEEVDPNT QNPKYITAAC EMVAEMVESL QSVLALGHKR NSGVPAFLTP LLRNIIISLA 2400
RLPLVNSYTR VPPLVWKLGW SPKPGGDFGT AFPEIPVEFL QEKEVFKEFI YRINTLGWTS 2460
RTQFEETWAT LLGVLVTQPL VMEQEESPPE EDTERTQINV LAVQAITSLV LSAMTVPVAG 2520
NPAVSCLEQQ PRNKPLKALD TRFGRKLSII RGIVEQEIQA MVSKRENIAT HHLYQAWDPV 2580
PSLSPATTGA LISHEKLLLQ INPERELGSM SYKLGQVSIH SVWLGNSITP LREEEWDEEE 2640
EEEADAPAPS SPPTSPVNSR KHRAGVDIHS CSQFLLELYS RWILPSSSAR RTPAILISEV 2700
VRSLLVVSDL FTERNQFELM YVTLTELRRV HPSEDEILAQ YLVPATCKAA AVLGMDKAVA 2760
EPVSRLLEST LRSSHLPSRV GALHGVLYVL ECDLLDDTAK QLIPVISDYL LSNLKGIAHC 2820
VNIHSQQHVL VMCATAFYLI ENYPLDVGPE FSASIIQMCG VMLSGSEEST PSIIYHCALR 2880
GLERLLLSEQ LSRLDAESLV KLSVDRVNVH SPHRAMAALG LMLTCMYTGK EKVSPGRTSD 2940
PNPAAPDSES VIVAMERVSV LFDRIRKGFP CEARVVARIL PQFLDDFFPP QDIMNKVIGE 3000
FLSNQQPYPQ FMATVVYKVF QTLHSTGQSS MVRDWVMLSL SNFTQRAPVA MATWSLSCFF 3060
VSASTSPWVA AILPHVISRM GKLEQVDVNL FCLVATDFYR HQIEEELDRR AFQSVLEVVA 3120
APGSPYHRLL TCLRNVHKVT TC 3142 
Gene Ontology
 GO:0005776; C:autophagic vacuole; IDA:UniProtKB.
 GO:0030424; C:axon; IDA:UniProtKB.
 GO:0030659; C:cytoplasmic vesicle membrane; IDA:UniProtKB.
 GO:0005829; C:cytosol; IDA:UniProtKB.
 GO:0030425; C:dendrite; IDA:UniProtKB.
 GO:0005783; C:endoplasmic reticulum; IDA:UniProtKB.
 GO:0005794; C:Golgi apparatus; IDA:UniProtKB.
 GO:0016234; C:inclusion body; IEA:Compara.
 GO:0005770; C:late endosome; IDA:UniProtKB.
 GO:0005634; C:nucleus; IDA:UniProtKB.
 GO:0043234; C:protein complex; IDA:UniProtKB.
 GO:0048487; F:beta-tubulin binding; IDA:UniProtKB.
 GO:0050809; F:diazepam binding; IEA:Compara.
 GO:0045505; F:dynein intermediate chain binding; IDA:UniProtKB.
 GO:0008134; F:transcription factor binding; IBA:RefGenome.
 GO:0009952; P:anterior/posterior pattern specification; IEA:Compara.
 GO:0008088; P:axon cargo transport; IEA:Compara.
 GO:0007569; P:cell aging; IEA:Compara.
 GO:0000052; P:citrulline metabolic process; IEA:Compara.
 GO:0008340; P:determination of adult lifespan; IEA:Compara.
 GO:0007212; P:dopamine receptor signaling pathway; IEA:Compara.
 GO:0007029; P:endoplasmic reticulum organization; IEA:Compara.
 GO:0016197; P:endosomal transport; IEA:Compara.
 GO:0006888; P:ER to Golgi vesicle-mediated transport; IEA:Compara.
 GO:0000132; P:establishment of mitotic spindle orientation; IMP:UniProtKB.
 GO:0007030; P:Golgi organization; IMP:UniProtKB.
 GO:0042445; P:hormone metabolic process; IEA:Compara.
 GO:0030073; P:insulin secretion; IEA:Compara.
 GO:0055072; P:iron ion homeostasis; IEA:Compara.
 GO:0051938; P:L-glutamate import; IEA:Compara.
 GO:0019244; P:lactate biosynthetic process from pyruvate; IEA:Compara.
 GO:0007626; P:locomotory behavior; IEA:Compara.
 GO:2001237; P:negative regulation of extrinsic apoptotic signaling pathway; IMP:UniProtKB.
 GO:0043524; P:negative regulation of neuron apoptotic process; IEA:Compara.
 GO:0021990; P:neural plate formation; IEA:Compara.
 GO:0051402; P:neuron apoptotic process; IEA:Compara.
 GO:0048666; P:neuron development; IEA:Compara.
 GO:0021988; P:olfactory lobe development; IEA:Compara.
 GO:0048513; P:organ development; IBA:RefGenome.
 GO:0048341; P:paraxial mesoderm formation; IEA:Compara.
 GO:0006606; P:protein import into nucleus; IEA:Compara.
 GO:0019805; P:quinolinate biosynthetic process; IEA:Compara.
 GO:0046902; P:regulation of mitochondrial membrane permeability; IEA:Compara.
 GO:0051881; P:regulation of mitochondrial membrane potential; IEA:Compara.
 GO:0046825; P:regulation of protein export from nucleus; IMP:UniProtKB.
 GO:0034047; P:regulation of protein phosphatase type 2A activity; IMP:dictyBase.
 GO:0048167; P:regulation of synaptic plasticity; IEA:Compara.
 GO:0051592; P:response to calcium ion; IEA:Compara.
 GO:0006890; P:retrograde vesicle-mediated transport, Golgi to ER; IMP:UniProtKB.
 GO:0035176; P:social behavior; IEA:Compara.
 GO:0007283; P:spermatogenesis; IEA:Compara.
 GO:0021756; P:striatum development; IEA:Compara.
 GO:0000050; P:urea cycle; IEA:Compara.
 GO:0047496; P:vesicle transport along microtubule; IMP:UniProtKB.
 GO:0008542; P:visual learning; IEA:Compara. 
Interpro
 IPR011989; ARM-like.
 IPR016024; ARM-type_fold.
 IPR000091; Huntingtin.
 IPR024613; Huntingtin_middle-repeat. 
Pfam
 PF12372; DUF3652 
SMART
  
PROSITE
 PS50077; HEAT_REPEAT 
PRINTS
 PR00375; HUNTINGTIN.