Seroatlas · Human Serome Atlas

HUWE1

E3 ubiquitin-protein ligase HUWE1

Also known as: HUWE1_HUMAN, Ib772, KIAA0312, UREB1

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

Protein identityUniProt · HPA

UniProt accession: Q7Z6Z7
Gene: HUWE1
Ensembl: ENSG00000086758
Chromosome: X
Canonical length: 4374 aa
Protein class: Cancer-related genes, Disease related genes, Enzymes, Human disease related genes, Metabolic proteins, Potential drug targets, Predicted intracellular proteins, Predicted membrane proteins
Subcellular location: Nucleoplasm,Cytosol,Mid piece,Principal piece,End piece

OverviewNCBI Gene

This gene encodes a protein containing a C-terminal HECT (E6AP type E3 ubiquitin protein ligase) domain that functions as an E3 ubiquitin ligase. The encoded protein is required for the ubiquitination and subsequent degradation of the anti-apoptotic protein Mcl1 (myeloid cell leukemia sequence 1 (BCL2-related)). This protein also ubiquitinates the p53 tumor suppressor, core histones, and DNA polymerase beta. Mutations in this gene are associated with Turner type X-linked syndromic cognitive disability. [provided by RefSeq, Aug 2013]

Canonical amino-acid sequenceUniProt

4374 residues, UniProt reviewed canonical sequence.

>Q7Z6Z7|HUWE1
     1  MKVDRTKLKK TPTEAPADCR ALIDKLKVCN DEQLLLELQQ IKTWNIGKCE LYHWVDLLDR
    61  FDGILADAGQ TVENMSWMLV CDRPEREQLK MLLLAVLNFT ALLIEYSFSR HLYSSIEHLT
   121  TLLASSDMQV VLAVLNLLYV FSKRSNYITR LGSDKRTPLL TRLQHLAESW GGKENGFGLA
   181  ECCRDLHMMK YPPSATTLHF EFYADPGAEV KIEKRTTSNT LHYIHIEQLD KISESPSEIM
   241  ESLTKMYSIP KDKQMLLFTH IRLAHGFSNH RKRLQAVQAR LHAISILVYS NALQESANSI
   301  LYNGLIEELV DVLQITDKQL MEIKAASLRT LTSIVHLERT PKLSSIIDCT GTASYHGFLP
   361  VLVRNCIQAM IDPSMDPYPH QFATALFSFL YHLASYDAGG EALVSCGMME ALLKVIKFLG
   421  DEQDQITFVT RAVRVVDLIT NLDMAAFQSH SGLSIFIYRL EHEVDLCRKE CPFVIKPKIQ
   481  RPNTTQEGEE METDMDGVQC IPQRAALLKS MLNFLKKAIQ DPAFSDGIRH VMDGSLPTSL
   541  KHIISNAEYY GPSLFLLATE VVTVFVFQEP SLLSSLQDNG LTDVMLHALL IKDVPATREV
   601  LGSLPNVFSA LCLNARGLQS FVQCQPFERL FKVLLSPDYL PAMRRRRSSD PLGDTASNLG
   661  SAVDELMRHQ PTLKTDATTA IIKLLEEICN LGRDPKYICQ KPSIQKADGT ATAPPPRSNH
   721  AAEEASSEDE EEEEVQAMQS FNSTQQNETE PNQQVVGTEE RIPIPLMDYI LNVMKFVESI
   781  LSNNTTDDHC QEFVNQKGLL PLVTILGLPN LPIDFPTSAA CQAVAGVCKS ILTLSHEPKV
   841  LQEGLLQLDS ILSSLEPLHR PIESPGGSVL LRELACAGNV ADATLSAQAT PLLHALTAAH
   901  AYIMMFVHTC RVGQSEIRSI SVNQWGSQLG LSVLSKLSQL YCSLVWESTV LLSLCTPNSL
   961  PSGCEFGQAD MQKLVPKDEK AGTTQGGKRS DGEQDGAAGS MDASTQGLLE GIGLDGDTLA
  1021  PMETDEPTAS DSKGKSKITP AMAARIKQIK PLLSASSRLG RALAELFGLL VKLCVGSPVR
  1081  QRRSHHAAST TTAPTPAARS TASALTKLLT KGLSWQPPPY TPTPRFRLTF FICSVGFTSP
  1141  MLFDERKYPY HLMLQKFLCS GGHNALFETF NWALSMGGKV PVSEGLEHSD LPDGTGEFLD
  1201  AWLMLVEKMV NPTTVLESPH SLPAKLPGGV QNFPQFSALR FLVVTQKAAF TCIKNLWNRK
  1261  PLKVYGGRMA ESMLAILCHI LRGEPVIRER LSKEKEGSRG EEDTGQEEGG SRREPQVNQQ
  1321  QLQQLMDMGF TREHAMEALL NTSTMEQATE YLLTHPPPIM GGVVRDLSMS EEDQMMRAIA
  1381  MSLGQDIPMD QRAESPEEVA CRKEEEERKA REKQEEEEAK CLEKFQDADP LEQDELHTFT
  1441  DTMLPGCFHL LDELPDTVYR VCDLIMTAIK RNGADYRDMI LKQVVNQVWE AADVLIKAAL
  1501  PLTTSDTKTV SEWISQMATL PQASNLATRI LLLTLLFEEL KLPCAWVVES SGILNVLIKL
  1561  LEVVQPCLQA AKEQKEVQTP KWITPVLLLI DFYEKTAISS KRRAQMTKYL QSNSNNWRWF
  1621  DDRSGRWCSY SASNNSTIDS AWKSGETSVR FTAGRRRYTV QFTTMVQVNE ETGNRRPVML
  1681  TLLRVPRLNK NSKNSNGQEL EKTLEESKEM DIKRKENKGN DTPLALESTN TEKETSLEET
  1741  KIGEILIQGL TEDMVTVLIR ACVSMLGVPV DPDTLHATLR LCLRLTRDHK YAMMFAELKS
  1801  TRMILNLTQS SGFNGFTPLV TLLLRHIIED PCTLRHTMEK VVRSAATSGA GSTTSGVVSG
  1861  SLGSREINYI LRVLGPAACR NPDIFTEVAN CCIRIALPAP RGSGTASDDE FENLRIKGPN
  1921  AVQLVKTTPL KPSPLPVIPD TIKEVIYDML NALAAYHAPE EADKSDPKPG VMTQEVGQLL
  1981  QDMGDDVYQQ YRSLTRQSSD FDTQSGFSIN SQVFAADGAS TETSASGTSQ GEASTPEESR
  2041  DGKKDKEGDR ASEEGKQKGK GSKPLMPTST ILRLLAELVR SYVGIATLIA NYSYTVGQSE
  2101  LIKEDCSVLA FVLDHLLPHT QNAEDKDTPA LARLFLASLA AAGSGTDAQV ALVNEVKAAL
  2161  GRALAMAEST EKHARLQAVM CIISTIMESC PSTSSFYSSA TAKTQHNGMN NIIRLFLKKG
  2221  LVNDLARVPH SLDLSSPNMA NTVNAALKPL ETLSRIVNQP SSLFGSKSAS SKNKSEQDAQ
  2281  GASQDSSSNQ QDPGEPGEAE VQEEDHDVTQ TEVADGDIMD GEAETDSVVI AGQPEVLSSQ
  2341  EMQVENELED LIDELLERDG GSGNSTIIVS RSGEDESQED VLMDEAPSNL SQASTLQANR
  2401  EDSMNILDPE DEEEHTQEED SSGSNEDEDD SQDEEEEEEE DEEDDQEDDE GEEGDEDDDD
  2461  DGSEMELDED YPDMNASPLV RFERFDREDD LIIEFDNMFS SATDIPPSPG NIPTTHPLMV
  2521  RHADHSSLTL GSGSSTTRLT QGIGRSQRTL RQLTANTGHT IHVHYPGNRQ PNPPLILQRL
  2581  LGPSAAADIL QLSSSLPLQS RGRARLLVGN DDVHIIARSD DELLDDFFHD QSTATSQAGT
  2641  LSSIPTALTR WTEECKVLDA ESMHDCVSVV KVSIVNHLEF LRDEELEERR EKRRKQLAEE
  2701  ETKITDKGKE DKENRDQSAQ CTASKSNDST EQNLSDGTPM PDSYPTTPSS TDAATSESKE
  2761  TLGTLQSSQQ QPTLPTPPAL GEVPQELQSP AGEGGSSTQL LMPVEPEELG PTRPSGEAET
  2821  TQMELSPAPT ITSLSPERAE DSDALTAVSS QLEGSPMDTS SLASCTLEEA VGDTSAAGSS
  2881  EQPRAGSSTP GDAPPAVAEV QGRSDGSGES AQPPEDSSPP ASSESSSTRD SAVAISGADS
  2941  RGILEEPLPS TSSEEEDPLA GISLPEGVDP SFLAALPDDI RREVLQNQLG IRPPTRTAPS
  3001  TNSSAPAVVG NPGVTEVSPE FLAALPPAIQ EEVLAQQRAE QQRRELAQNA SSDTPMDPVT
  3061  FIQTLPSDLR RSVLEDMEDS VLAVMPPDIA AEAQALRREQ EARQRQLMHE RLFGHSSTSA
  3121  LSAILRSPAF TSRLSGNRGV QYTRLAVQRG GTFQMGGSSS HNRPSGSNVD TLLRLRGRLL
  3181  LDHEALSCLL VLLFVDEPKL NTSRLHRVLR NLCYHAQTRH WVIRSLLSIL QRSSESELCI
  3241  ETPKLTTSEE KGKKSSKSCG SSSHENRPLD LLHKMESKSS NQLSWLSVSM DAALGCRTNI
  3301  FQIQRSGGRK HTEKHASGGS TVHIHPQAAP VVCRHVLDTL IQLAKVFPSH FTQQRTKETN
  3361  CESDRERGNK ACSPCSSQSS SSGICTDFWD LLVKLDNMNV SRKGKNSVKS VPVSAGGEGE
  3421  TSPYSLEASP LGQLMNMLSH PVIRRSSLLT EKLLRLLSLI SIALPENKVS EAQANSGSGA
  3481  SSTTTATSTT STTTTTAAST TPTPPTAPTP VTSAPALVAA TAISTIVVAA STTVTTPTTA
  3541  TTTVSISPTT KGSKSPAKVS DGGSSSTDFK MVSSGLTENQ LQLSVEVLTS HSCSEEGLED
  3601  AANVLLQLSR GDSGTRDTVL KLLLNGARHL GYTLCKQIGT LLAELREYNL EQQRRAQCET
  3661  LSPDGLPEEQ PQTTKLKGKM QSRFDMAENV VIVASQKRPL GGRELQLPSM SMLTSKTSTQ
  3721  KFFLRVLQVI IQLRDDTRRA NKKAKQTGRL GSSGLGSASS IQAAVRQLEA EADAIIQMVR
  3781  EGQRARRQQQ AATSESSQSE ASVRREESPM DVDQPSPSAQ DTQSIASDGT PQGEKEKEER
  3841  PPELPLLSEQ LSLDELWDML GECLKELEES HDQHAVLVLQ PAVEAFFLVH ATERESKPPV
  3901  RDTRESQLAH IKDEPPPLSP APLTPATPSS LDPFFSREPS SMHISSSLPP DTQKFLRFAE
  3961  THRTVLNQIL RQSTTHLADG PFAVLVDYIR VLDFDVKRKY FRQELERLDE GLRKEDMAVH
  4021  VRRDHVFEDS YRELHRKSPE EMKNRLYIVF EGEEGQDAGG LLREWYMIIS REMFNPMYAL
  4081  FRTSPGDRVT YTINPSSHCN PNHLSYFKFV GRIVAKAVYD NRLLECYFTR SFYKHILGKS
  4141  VRYTDMESED YHFYQGLVYL LENDVSTLGY DLTFSTEVQE FGVCEVRDLK PNGANILVTE
  4201  ENKKEYVHLV CQMRMTGAIR KQLAAFLEGF YEIIPKRLIS IFTEQELELL ISGLPTIDID
  4261  DLKSNTEYHK YQSNSIQIQW FWRALRSFDQ ADRAKFLQFV TGTSKVPLQG FAALEGMNGI
  4321  QKFQIHRDDR STDRLPSAHT CFNQLDLPAY ESFEKLRHML LLAIQECSEG FGLA

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against HUWE1 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: 96 nTPM

Expression across tissuesHPA

Tissue

skeletal muscle: 96 nTPM
skin: 57 nTPM
cerebellum: 56 nTPM
tongue: 55 nTPM
heart muscle: 54 nTPM
ovary: 52 nTPM

Single-cell type

sertoli cells: 274 nCPM
thyrotrophs: 259 nCPM
pituicytes/fscs: 237 nCPM
corticotrophs: 233 nCPM
lactotrophs: 227 nCPM
somatotrophs: 223 nCPM

Immune cell

eosinophil: 5.2 nTPM
non-classical monocyte: 4.1 nTPM
MAIT T-cell: 4 nTPM
NK-cell: 3.9 nTPM
gdT-cell: 3.8 nTPM
plasmacytoid DC: 3.8 nTPM

Brain region

pons: 210 nTPM
midbrain: 201 nTPM
cerebral cortex: 196 nTPM
hypothalamus: 190 nTPM
hippocampal formation: 183 nTPM
cerebellum: 176 nTPM

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about HUWE1.

Disease | AllUniProt

Conditions HUWE1 is implicated in, by any mechanism.

Intellectual developmental disorder, X-linked, syndromic, Turner type (MRXST) MIM:309590

Disease | GeneticClinVar

78 pathogenic / likely-pathogenic of 2,544 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

Intellectual disability, X-linked syndromic, Turner type
HUWE1-related disorder
Intellectual disability
Inborn genetic diseases
Thyroid cancer, nonmedullary, 1

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): 0.06
gnomAD pLI: 1
gnomAD missense Z: 8.87
DepMap mean gene effect: -0.85
DepMap dependency class: common

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

HECT domain
WWE domain
UBA-like superfamily
Ubiquitin-associated domain
Armadillo-type fold
HUWE1/REV1, ubiquitin-binding motif
HECT, E3 ligase catalytic domain
WWE domain superfamily
E3 ubiquitin-protein ligase
HECT-domain (ubiquitin-transferase)
WWE domain
Ubiquitin binding region
UBA-like domain
E3 ubiquitin ligase, domain of unknown function DUF908
E3 ubiquitin ligase, domain of unknown function DUF913
HUWE1, UBA domain
Domain of Unknown Function (DUF908)
Domain of Unknown Function (DUF913)

KeywordsUniProt

InteractionsUniProt · HPA

Protein binding partners of HUWE1 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 HUWE1 as an antibody target. Whether an autoantibody or antibody against HUWE1 could matter depends on whether native HUWE1 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.

HUWE1 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 HUWE1 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.

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