TGM2

Protein identityUniProt · HPA

UniProt accession

P21980

Gene

TGM2

Ensembl

ENSG00000198959

Chromosome

20

Canonical length

687 aa

Protein class

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

Subcellular location

Plasma membrane,Cytosol

Secretome location

Secreted to extracellular matrix

Quaternary structure

Homooligomer

OverviewNCBI Gene

Transglutaminases are enzymes that catalyze the crosslinking of proteins by epsilon-gamma glutamyl lysine isopeptide bonds. While the primary structure of transglutaminases is not conserved, they all have the same amino acid sequence at their active sites and their activity is calcium-dependent. The protein encoded by this gene acts as a monomer, is induced by retinoic acid, and appears to be involved in apoptosis. Finally, the encoded protein is the autoantigen implicated in celiac disease. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]

Canonical amino-acid sequenceUniProt

687 residues, UniProt reviewed canonical sequence.

>P21980|TGM2
     1  MAEELVLERC DLELETNGRD HHTADLCREK LVVRRGQPFW LTLHFEGRNY EASVDSLTFS
    61  VVTGPAPSQE AGTKARFPLR DAVEEGDWTA TVVDQQDCTL SLQLTTPANA PIGLYRLSLE
   121  ASTGYQGSSF VLGHFILLFN AWCPADAVYL DSEEERQEYV LTQQGFIYQG SAKFIKNIPW
   181  NFGQFEDGIL DICLILLDVN PKFLKNAGRD CSRRSSPVYV GRVVSGMVNC NDDQGVLLGR
   241  WDNNYGDGVS PMSWIGSVDI LRRWKNHGCQ RVKYGQCWVF AAVACTVLRC LGIPTRVVTN
   301  YNSAHDQNSN LLIEYFRNEF GEIQGDKSEM IWNFHCWVES WMTRPDLQPG YEGWQALDPT
   361  PQEKSEGTYC CGPVPVRAIK EGDLSTKYDA PFVFAEVNAD VVDWIQQDDG SVHKSINRSL
   421  IVGLKISTKS VGRDEREDIT HTYKYPEGSS EEREAFTRAN HLNKLAEKEE TGMAMRIRVG
   481  QSMNMGSDFD VFAHITNNTA EEYVCRLLLC ARTVSYNGIL GPECGTKYLL NLNLEPFSEK
   541  SVPLCILYEK YRDCLTESNL IKVRALLVEP VINSYLLAER DLYLENPEIK IRILGEPKQK
   601  RKLVAEVSLQ NPLPVALEGC TFTVEGAGLT EEQKTVEIPD PVEAGEEVKV RMDLLPLHMG
   661  LHKLVVNFES DKLKAVKGFR NVIIGPA

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against TGM2 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

Cell surface

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.22

Highest tissue expression

776 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about TGM2.

Disease | ImmuneIEDB

Conditions an epitope on TGM2 was assayed in.

• celiac disease B cell

Disease | AutoantibodyPubMed

Conditions in which antibodies against TGM2 are reported. Each links to that disease's full target list.

• Celiac Disease 816
• Diabetes Mellitus, Type 1 98
• Thyroiditis, Autoimmune 13
• Crohn Disease 10
• Inflammatory Bowel Diseases 10
• Arthritis, Rheumatoid 8
• Glomerulonephritis, IGA 8
• Arthritis, Juvenile 6
• COVID-19 6
• Sjogren's Syndrome 6
• Graves Disease 5
• Liver Cirrhosis 5
• Liver Cirrhosis, Biliary 5
• Lupus Erythematosus, Systemic 5
• Schizophrenia 5
• Addison Disease 4
• Anemia 4
• Ataxia 4
• Colitis, Ulcerative 4
• Hashimoto Disease 4

Showing 20 of 43 — disease pages carrying at least 10 antigens.

ReferencesPubMed · IEDB

Publications for TGM2 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. IEDB — curated epitope assays from the Immune Epitope Database (Vita et al., Nucleic Acids Research 2019). 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)

1.19

gnomAD pLI

0

gnomAD missense Z

0.54

DepMap mean gene effect

0.11

DepMap dependency class

none

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

• apoptotic cell clearance
• bone development
• branching involved in salivary gland morphogenesis
• cellular response to cocaine
• cellular response to dopamine
• cellular response to serotonin
• negative regulation of endoplasmic reticulum calcium ion concentration
• peptide cross-linking
• phospholipase C-activating G protein-coupled receptor signaling pathway
• positive regulation of apoptotic process
• positive regulation of cell adhesion
• positive regulation of GTPase activity
• positive regulation of mitochondrial calcium ion concentration
• positive regulation of neurogenesis
• positive regulation of small GTPase mediated signal transduction
• positive regulation of sprouting angiogenesis
• protein deamination
• protein homooligomerization
• proteolysis
• regulation of apoptotic process
• salivary gland cavitation
• regulation of apoptotic cell clearance

Molecular functions

• calcium ion binding
• GTP binding
• peptidase activity
• protein-glutamine gamma-glutamyltransferase activity
• histone dopaminyltransferase activity
• histone serotonyltransferase activity
• peptide histaminyltransferase activity
• peptide noradrenalinyltransferase activity
• protein-glutamine glutaminase activity

Cellular components

• chromatin
• cytosol
• endoplasmic reticulum
• extracellular exosome
• extracellular matrix
• focal adhesion
• mitochondrion
• nucleosome
• nucleus
• perinuclear region of cytoplasm
• plasma membrane

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

• Acetylation
• Acyltransferase
• Calcium
• Cell membrane
• Chromosome
• Cytoplasm
• Disulfide bond
• Extracellular matrix
• GTP-binding
• Hydrolase
• Isopeptide bond
• Membrane
• Metal-binding
• Mitochondrion
• Nucleotide-binding
• Nucleus
• Phosphoprotein
• Protease
• S-nitrosylation
• Secreted
• Transferase

InteractionsUniProt · HPA

Protein binding partners of TGM2 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• PLCD1
• ADGRG1
• FN1
• RELA