Seroatlas · Human Serome Atlas

HTT

Huntingtin

Also known as: HD, HD_HUMAN, IT15

Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene

Protein identityUniProt · HPA

UniProt accession: P42858
Gene: HTT
Ensembl: ENSG00000197386
Chromosome: 4
Canonical length: 3142 aa
Protein class: Disease related genes, Human disease related genes, Plasma proteins, Predicted intracellular proteins, Predicted membrane proteins
Subcellular location: Nucleoplasm,Cytosol

OverviewNCBI Gene

Huntingtin is a disease gene linked to Huntington's disease, a neurodegenerative disorder characterized by loss of striatal neurons. This is thought to be caused by an expanded, unstable trinucleotide repeat in the huntingtin gene, which translates as a polyglutamine repeat in the protein product. A fairly broad range of trinucleotide repeats (9-35) has been identified in normal controls, and repeat numbers in excess of 40 have been described as pathological. The huntingtin locus is large, spanning 180 kb and consisting of 67 exons. The huntingtin gene is widely expressed and is required for normal development. It is expressed as 2 alternatively polyadenylated forms displaying different relative abundance in various fetal and adult tissues. The larger transcript is approximately 13.7 kb and is expressed predominantly in adult and fetal brain whereas the smaller transcript of approximately 10.3 kb is more widely expressed. The genetic defect leading to Huntington's disease may not necessarily eliminate transcription, but may confer a new property on the mRNA or alter the function of the protein. One candidate is the huntingtin-associated protein-1, highly expressed in brain, which has increased affinity for huntingtin protein with expanded polyglutamine repeats. This gene contains an upstream open reading frame in the 5' UTR that inhibits expression of the huntingtin gene product through translational repression. [provided by RefSeq, Jul 2016]

Canonical amino-acid sequenceUniProt

3142 residues, UniProt reviewed canonical sequence.

>P42858|HTT
     1  MATLEKLMKA FESLKSFQQQ QQQQQQQQQQ QQQQQQQQPP PPPPPPPPPQ LPQPPPQAQP
    61  LLPQPQPPPP PPPPPPGPAV AEEPLHRPKK ELSATKKDRV NHCLTICENI VAQSVRNSPE
   121  FQKLLGIAME LFLLCSDDAE SDVRMVADEC LNKVIKALMD SNLPRLQLEL YKEIKKNGAP
   181  RSLRAALWRF AELAHLVRPQ KCRPYLVNLL PCLTRTSKRP EESVQETLAA AVPKIMASFG
   241  NFANDNEIKV LLKAFIANLK SSSPTIRRTA AGSAVSICQH SRRTQYFYSW LLNVLLGLLV
   301  PVEDEHSTLL ILGVLLTLRY LVPLLQQQVK DTSLKGSFGV TRKEMEVSPS AEQLVQVYEL
   361  TLHHTQHQDH NVVTGALELL QQLFRTPPPE LLQTLTAVGG IGQLTAAKEE SGGRSRSGSI
   421  VELIAGGGSS CSPVLSRKQK GKVLLGEEEA LEDDSESRSD VSSSALTASV KDEISGELAA
   481  SSGVSTPGSA GHDIITEQPR SQHTLQADSV DLASCDLTSS ATDGDEEDIL SHSSSQVSAV
   541  PSDPAMDLND GTQASSPISD SSQTTTEGPD SAVTPSDSSE IVLDGTDNQY LGLQIGQPQD
   601  EDEEATGILP DEASEAFRNS SMALQQAHLL KNMSHCRQPS DSSVDKFVLR DEATEPGDQE
   661  NKPCRIKGDI GQSTDDDSAP LVHCVRLLSA SFLLTGGKNV LVPDRDVRVS VKALALSCVG
   721  AAVALHPESF FSKLYKVPLD TTEYPEEQYV SDILNYIDHG DPQVRGATAI LCGTLICSIL
   781  SRSRFHVGDW MGTIRTLTGN TFSLADCIPL LRKTLKDESS VTCKLACTAV RNCVMSLCSS
   841  SYSELGLQLI IDVLTLRNSS YWLVRTELLE TLAEIDFRLV SFLEAKAENL HRGAHHYTGL
   901  LKLQERVLNN VVIHLLGDED PRVRHVAAAS LIRLVPKLFY KCDQGQADPV VAVARDQSSV
   961  YLKLLMHETQ PPSHFSVSTI TRIYRGYNLL PSITDVTMEN NLSRVIAAVS HELITSTTRA
  1021  LTFGCCEALC LLSTAFPVCI WSLGWHCGVP PLSASDESRK SCTVGMATMI LTLLSSAWFP
  1081  LDLSAHQDAL ILAGNLLAAS APKSLRSSWA SEEEANPAAT KQEEVWPALG DRALVPMVEQ
  1141  LFSHLLKVIN ICAHVLDDVA PGPAIKAALP SLTNPPSLSP IRRKGKEKEP GEQASVPLSP
  1201  KKGSEASAAS RQSDTSGPVT TSKSSSLGSF YHLPSYLKLH DVLKATHANY KVTLDLQNST
  1261  EKFGGFLRSA LDVLSQILEL ATLQDIGKCV EEILGYLKSC FSREPMMATV CVQQLLKTLF
  1321  GTNLASQFDG LSSNPSKSQG RAQRLGSSSV RPGLYHYCFM APYTHFTQAL ADASLRNMVQ
  1381  AEQENDTSGW FDVLQKVSTQ LKTNLTSVTK NRADKNAIHN HIRLFEPLVI KALKQYTTTT
  1441  CVQLQKQVLD LLAQLVQLRV NYCLLDSDQV FIGFVLKQFE YIEVGQFRES EAIIPNIFFF
  1501  LVLLSYERYH SKQIIGIPKI IQLCDGIMAS GRKAVTHAIP ALQPIVHDLF VLRGTNKADA
  1561  GKELETQKEV VVSMLLRLIQ YHQVLEMFIL VLQQCHKENE DKWKRLSRQI ADIILPMLAK
  1621  QQMHIDSHEA LGVLNTLFEI LAPSSLRPVD MLLRSMFVTP NTMASVSTVQ LWISGILAIL
  1681  RVLISQSTED IVLSRIQELS FSPYLISCTV INRLRDGDST STLEEHSEGK QIKNLPEETF
  1741  SRFLLQLVGI LLEDIVTKQL KVEMSEQQHT FYCQELGTLL MCLIHIFKSG MFRRITAAAT
  1801  RLFRSDGCGG SFYTLDSLNL RARSMITTHP ALVLLWCQIL LLVNHTDYRW WAEVQQTPKR
  1861  HSLSSTKLLS PQMSGEEEDS DLAAKLGMCN REIVRRGALI LFCDYVCQNL HDSEHLTWLI
  1921  VNHIQDLISL SHEPPVQDFI SAVHRNSAAS GLFIQAIQSR CENLSTPTML KKTLQCLEGI
  1981  HLSQSGAVLT LYVDRLLCTP FRVLARMVDI LACRRVEMLL AANLQSSMAQ LPMEELNRIQ
  2041  EYLQSSGLAQ RHQRLYSLLD RFRLSTMQDS LSPSPPVSSH PLDGDGHVSL ETVSPDKDWY
  2101  VHLVKSQCWT RSDSALLEGA ELVNRIPAED MNAFMMNSEF NLSLLAPCLS LGMSEISGGQ
  2161  KSALFEAARE VTLARVSGTV QQLPAVHHVF QPELPAEPAA YWSKLNDLFG DAALYQSLPT
  2221  LARALAQYLV VVSKLPSHLH LPPEKEKDIV KFVVATLEAL SWHLIHEQIP LSLDLQAGLD
  2281  CCCLALQLPG LWSVVSSTEF VTHACSLIYC VHFILEAVAV QPGEQLLSPE RRTNTPKAIS
  2341  EEEEEVDPNT QNPKYITAAC EMVAEMVESL QSVLALGHKR NSGVPAFLTP LLRNIIISLA
  2401  RLPLVNSYTR VPPLVWKLGW SPKPGGDFGT AFPEIPVEFL QEKEVFKEFI YRINTLGWTS
  2461  RTQFEETWAT LLGVLVTQPL VMEQEESPPE EDTERTQINV LAVQAITSLV LSAMTVPVAG
  2521  NPAVSCLEQQ PRNKPLKALD TRFGRKLSII RGIVEQEIQA MVSKRENIAT HHLYQAWDPV
  2581  PSLSPATTGA LISHEKLLLQ INPERELGSM SYKLGQVSIH SVWLGNSITP LREEEWDEEE
  2641  EEEADAPAPS SPPTSPVNSR KHRAGVDIHS CSQFLLELYS RWILPSSSAR RTPAILISEV
  2701  VRSLLVVSDL FTERNQFELM YVTLTELRRV HPSEDEILAQ YLVPATCKAA AVLGMDKAVA
  2761  EPVSRLLEST LRSSHLPSRV GALHGVLYVL ECDLLDDTAK QLIPVISDYL LSNLKGIAHC
  2821  VNIHSQQHVL VMCATAFYLI ENYPLDVGPE FSASIIQMCG VMLSGSEEST PSIIYHCALR
  2881  GLERLLLSEQ LSRLDAESLV KLSVDRVNVH SPHRAMAALG LMLTCMYTGK EKVSPGRTSD
  2941  PNPAAPDSES VIVAMERVSV LFDRIRKGFP CEARVVARIL PQFLDDFFPP QDIMNKVIGE
  3001  FLSNQQPYPQ FMATVVYKVF QTLHSTGQSS MVRDWVMLSL SNFTQRAPVA MATWSLSCFF
  3061  VSASTSPWVA AILPHVISRM GKLEQVDVNL FCLVATDFYR HQIEEELDRR AFQSVLEVVA
  3121  APGSPYHRLL TCLRNVHKVT TC

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against HTT can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability: Intracellular
Secreted: No
Transmembrane segments: 0
Mean surface accessibility (rSASA): 0
Highest tissue expression: 20 nTPM

Expression across tissuesHPA

Tissue

pancreas: 20 nTPM
cerebral cortex: 17 nTPM
cerebellum: 16 nTPM
skeletal muscle: 14 nTPM
skin: 14 nTPM
hippocampal formation: 13 nTPM

Single-cell type

cone photoreceptor cells: 350 nCPM
sertoli cells: 293 nCPM
adrenal medulla cells: 202 nCPM
retinal ganglion cells: 201 nCPM
myonuclei: 184 nCPM
pituicytes/fscs: 183 nCPM

Immune cell

non-classical monocyte: 1.5 nTPM
memory CD8 T-cell: 1.3 nTPM
T-reg: 1.2 nTPM
intermediate monocyte: 1.1 nTPM
myeloid DC: 1.1 nTPM
gdT-cell: 1 nTPM

Brain region

cerebral cortex: 58 nTPM
hippocampal formation: 58 nTPM
basal ganglia: 48 nTPM
amygdala: 48 nTPM
white matter: 48 nTPM
pons: 44 nTPM

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about HTT.

Disease | AllUniProt

Conditions HTT is implicated in, by any mechanism.

Huntington disease (HD) MIM:143100
Lopes-Maciel-Rodan syndrome (LOMARS) MIM:617435

Disease | GeneticClinVar

12 pathogenic / likely-pathogenic of 783 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

Huntington disease
Lopes-Maciel-Rodan syndrome

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance): 0.18
gnomAD pLI: 1
gnomAD missense Z: 2.78
DepMap mean gene effect: -0.16
DepMap dependency class: selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 5% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

Molecular functions

Cellular components

Protein domainsUniProt · Pfam · InterPro

Armadillo-like helical
Armadillo-type fold
Huntingtin
Huntingtin, N-terminal, HEAT repeats 2
Huntingtin family
Huntingtin, N-terminal, HEAT repeats 1
Huntingtin, bridge
Huntingtin, C-terminal HEAT repeats
Huntingtin, N-terminal HEAT
Huntingtin, bridge
Huntingtin, N-terminal HEAT 1
Huntingtin, C-terminal HEAT

KeywordsUniProt

InteractionsUniProt · HPA

Protein binding partners of HTT in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

Antibody and autoantibody relevanceSeroatlas analysis

Seroatlas reads HTT as an antibody target. Whether an autoantibody or antibody against HTT could matter depends on whether native HTT is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.

HTT is annotated as predominantly intracellular. Intracellular proteins are common autoantibody markers, becoming visible to the immune system after cell injury or altered processing, but are usually markers of disease rather than direct drivers.

Annotation status

The present source text does not explicitly label HTT as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.

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