Seroatlas · Human Serome Atlas

HERC6

Probable E3 ubiquitin-protein ligase HERC6

Also known as: FLJ20637, HERC6_HUMAN

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

Protein identityUniProt · HPA

UniProt accession: Q8IVU3
Gene: HERC6
Ensembl: ENSG00000138642
Chromosome: 4
Canonical length: 1022 aa
Protein class: Enzymes, Predicted intracellular proteins, Predicted membrane proteins
Subcellular location: Nucleoplasm,Cytosol

OverviewNCBI Gene

HERC6 belongs to the HERC family of ubiquitin ligases, all of which contain a HECT domain and at least 1 RCC1 (MIM 179710)-like domain (RLD). The 350-amino acid HECT domain is predicted to catalyze the formation of a thioester with ubiquitin before transferring it to a substrate, and the RLD is predicted to act as a guanine nucleotide exchange factor for small G proteins (Hochrainer et al., 2005 [PubMed 15676274]).[supplied by OMIM, Mar 2008]

Canonical amino-acid sequenceUniProt

1022 residues, UniProt reviewed canonical sequence.

>Q8IVU3|HERC6
     1  MYFCWGADSR ELQRRRTAGS PGAELLQAAS GERHSLLLLT NHRVLSCGDN SRGQLGRRGA
    61  QRGELPEPIQ ALETLIVDLV SCGKEHSLAV CHKGRVFAWG AGSEGQLGIG EFKEISFTPK
   121  KIMTLNDIKI IQVSCGHYHS LALSKDSQVF SWGKNSHGQL GLGKEFPSQA SPQRVRSLEG
   181  IPLAQVAAGG AHSFALSLCG TSFGWGSNSA GQLALSGRNV PVQSNKPLSV GALKNLGVVY
   241  ISCGDAHTAV LTQDGKVFTF GDNRSGQLGY SPTPEKRGPQ LVERIDGLVS QIDCGSYHTL
   301  AYVHTTGQVV SFGHGPSDTS KPTHPEALTE NFDISCLISA EDFVDVQVKH IFAGTYANFV
   361  TTHQDTSSTR APGKTLPEIS RISQSMAEKW IAVKRRSTEH EMAKSEIRMI FSSPACLTAS
   421  FLKKRGTGET TSIDVDLEMA RDTFKKLTKK EWISSMITTC LEDDLLRALP CHSPHQEALS
   481  VFLLLPECPV MHDSKNWKNL VVPFAKAVCE MSKQSLQVLK KCWAFLQESS LNPLIQMLKA
   541  AIISQLLHQT KTEQDHCNVK ALLGMMKELH KVNKANCRLP ENTFNINELS NLLNFYIDRG
   601  RQLFRDNHLI PAETPSPVIF SDFPFIFNSL SKIKLLQADS HIKMQMSEKK AYMLMHETIL
   661  QKKDEFPPSP RFILRVRRSR LVKDALRQLS QAEATDFCKV LVVEFINEIC PESGGVSSEF
   721  FHCMFEEMTK PEYGMFMYPE MGSCMWFPAK PKPEKKRYFL FGMLCGLSLF NLNVANLPFP
   781  LALYKKLLDQ KPSLEDLKEL SPRLGKSLQE VLDDAADDIG DALCIRFSIH WDQNDVDLIP
   841  NGISIPVDQT NKRDYVSKYI DYIFNVSVKA VYEEFQRGFY RVCEKEILRH FYPEELMTAI
   901  IGNTDYDWKQ FEQNSKYEQG YQKSHPTIQL FWKAFHKLTL DEKKKFLFFL TGRDRLHARG
   961  IQKMEIVFRC PETFSERDHP TSITCHNILS LPKYSTMERM EEALQVAINN NRGFVSPMLT
  1021  QS

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against HERC6 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): 0.25
Highest tissue expression: 29 nTPM

Expression across tissuesHPA

Tissue

salivary gland: 29 nTPM
esophagus: 20 nTPM
cervix: 12 nTPM
thymus: 12 nTPM
ovary: 11 nTPM
vagina: 11 nTPM

Single-cell type

esophageal apical cells: 94 nCPM
esophageal suprabasal cells: 54 nCPM
pituitary stem cells: 48 nCPM
oligodendrocyte progenitor cells: 46 nCPM
retinal bipolar cells: 43 nCPM
salivary duct cells: 39 nCPM

Immune cell

MAIT T-cell: 13 nTPM
T-reg: 13 nTPM
memory CD4 T-cell: 8.9 nTPM
non-classical monocyte: 7.5 nTPM
naive CD4 T-cell: 6.9 nTPM
gdT-cell: 6.4 nTPM

Brain region

spinal cord: 20 nTPM
medulla oblongata: 13 nTPM
cerebral cortex: 12 nTPM
hypothalamus: 11 nTPM
pons: 10 nTPM
basal ganglia: 9.3 nTPM

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): 0.89
gnomAD pLI: 0
gnomAD missense Z: 1.16
DepMap mean gene effect: 0.03
DepMap dependency class: selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

Molecular functions

ubiquitin protein ligase activity

Cellular components

Protein domainsUniProt · Pfam · InterPro

KeywordsUniProt

Antibody and autoantibody relevanceSeroatlas analysis

Seroatlas reads HERC6 as an antibody target. Whether an autoantibody or antibody against HERC6 could matter depends on whether native HERC6 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.

HERC6 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 HERC6 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.

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