TGM6

Protein identityUniProt · HPA

UniProt accession

O95932

Gene

TGM6

Ensembl

ENSG00000166948

Chromosome

20

Canonical length

706 aa

Protein class

Disease related genes, Enzymes, Human disease related genes, Metabolic proteins, Potential drug targets, Predicted intracellular proteins

OverviewNCBI Gene

The protein encoded by this gene belongs to the transglutaminase superfamily. It catalyzes the cross-linking of proteins and the conjugation of polyamines to proteins. Mutations in this gene are associated with spinocerebellar ataxia type 35 (SCA35). Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2011]

Canonical amino-acid sequenceUniProt

706 residues, UniProt reviewed canonical sequence.

>O95932|TGM6
     1  MAGIRVTKVD WQRSRNGAAH HTQEYPCPEL VVRRGQSFSL TLELSRALDC EEILIFTMET
    61  GPRASEALHT KAVFQTSELE RGEGWTAARE AQMEKTLTVS LASPPSAVIG RYLLSIRLSS
   121  HRKHSNRRLG EFVLLFNPWC AEDDVFLASE EERQEYVLSD SGIIFRGVEK HIRAQGWNYG
   181  QFEEDILNIC LSILDRSPGH QNNPATDVSC RHNPIYVTRV ISAMVNSNND RGVVQGQWQG
   241  KYGGGTSPLH WRGSVAILQK WLKGRYKPVK YGQCWVFAGV LCTVLRCLGI ATRVVSNFNS
   301  AHDTDQNLSV DKYVDSFGRT LEDLTEDSMW NFHVWNESWF ARQDLGPSYN GWQVLDATPQ
   361  EESEGVFRCG PASVTAIREG DVHLAHDGPF VFAEVNADYI TWLWHEDESR ERVYSNTKKI
   421  GRCISTKAVG SDSRVDITDL YKYPEGSRKE RQVYSKAVNR LFGVEASGRR IWIRRAGGRC
   481  LWRDDLLEPA TKPSIAGKFK VLEPPMLGHD LRLALCLANL TSRAQRVRVN LSGATILYTR
   541  KPVAEILHES HAVRLGPQEE KRIPITISYS KYKEDLTEDK KILLAAMCLV TKGEKLLVEK
   601  DITLEDFITI KVLGPAMVGV AVTVEVTVVN PLIERVKDCA LMVEGSGLLQ EQLSIDVPTL
   661  EPQERASVQF DITPSKSGPR QLQVDLVSPH FPDIKGFVIV HVATAK

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against TGM6 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)

0.23

Highest tissue expression

0.4 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about TGM6.

Disease | AllUniProt

Conditions TGM6 is implicated in, by any mechanism.

• Spinocerebellar ataxia 35 (SCA35) MIM:613908

Disease | GeneticClinVar

10 pathogenic / likely-pathogenic of 554 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Spinocerebellar ataxia type 35
• TGM6-related disorder

Disease | AutoantibodyPubMed

Conditions in which antibodies against TGM6 are reported. Each links to that disease's full target list.

• Celiac Disease 6
• Ataxia 3
• Cerebellar Ataxia 3

ReferencesPubMed · IEDB

Publications for TGM6 from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.

Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.

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)

1.37

gnomAD pLI

0

gnomAD missense Z

-0.82

DepMap mean gene effect

0.03

DepMap dependency class

none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 2% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Molecular functions

• metal ion binding
• protein-glutamine gamma-glutamyltransferase activity

Cellular components

• cytoplasm

Protein domainsUniProt · Pfam · InterPro

• Transglutaminase, N-terminal
• Transglutaminase-like
• Transglutaminase, C-terminal
• Immunoglobulin-like fold
• Transglutaminase, active site
• Immunoglobulin E-set
• Protein-glutamine gamma-glutamyltransferase, animal
• Transglutaminase, C-terminal domain superfamily
• Transglutaminase-like superfamily
• Papain-like cysteine peptidase superfamily
• Protein-glutamine gamma-glutamyltransferases
• Transglutaminase family
• Transglutaminase family, C-terminal ig like domain
• Transglutaminase-like superfamily

KeywordsUniProt

• Acyltransferase
• Calcium
• Cytoplasm
• Metal-binding
• Neurodegeneration
• Spinocerebellar ataxia
• Transferase