TGM2 transglutaminase 2 [Homo sapiens (human)] - Gene

Summary

Official Symbol: TGM2provided by HGNC
Official Full Name: transglutaminase 2provided by HGNC
Primary source: HGNC:HGNC:11778
See related: Ensembl:ENSG00000198959 MIM:190196; Vega:OTTHUMG00000032437
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: TGC; TG(C)
Summary: 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]
Expression: Broad expression in placenta (RPKM 177.0), endometrium (RPKM 107.6) and 16 other tissues See more
Orthologs: mouse all

Genomic context

Location:: 20q11.23

Exon count:: 14

Annotation release	Status	Assembly	Chr	Location
109	current	GRCh38.p12 (GCF_000001405.38)	20	NC_000020.11 (38127387..38166578, complement)
105	previous assembly	GRCh37.p13 (GCF_000001405.25)	20	NC_000020.10 (36756863..36794910, complement)

Chromosome 20 - NC_000020.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Jun 15 11:32:44 2016

Bibliography

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GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

Taken together, the present data suggested a potentially important role for TGM2 in the regulation of osteosarcoma chemosensitivity. TGM2 might therefore serve as a therapeutic target for osteosarcoma.
Title: TGM2 knockdown reverses cisplatin chemoresistance in osteosarcoma.
Multiple symptoms and high serum anti-tTG antibody levels correlated with mucosal damage in children with Celiac disease.
Title: Relationships between Clinical Presentation, Serology, Histology, and Duodenal Deposits of Tissue Transglutaminase Antibodies in Pediatric Celiac Disease.
A role for TG2 has been demonstrated in both endothelial tubule formation and in tubule loss, which involves its function in the regulation of TGFbeta1 and Smad signaling.
Title: The functional relationship between transglutaminase 2 and transforming growth factor β1 in the regulation of angiogenesis and endothelial-mesenchymal transition.
Production of anti-TG2 antibodies could be due to a general state of inflammation or could indicate a very early stage of a gluten-dependent pathology.
Title: Intestinal Production of Anti-Tissue Transglutaminase 2 Antibodies in Patients with Diagnosis Other Than Celiac Disease.
TG2 plays a crucial role in the proliferative process
Title: The complex role of transglutaminase 2 in glioblastoma proliferation.
A long non-coding RNA is located within the first intron of transglutaminase 2 gene. LOC107987281 lncRNA is induced when levels of TGM2 transcripts are also increased, for example after drug treatment. In addition, correlation analysis between the expression of this lncRNA and TGM2 demonstrated that occurs in relation to the development of several tumors affecting pancreas, stomach and kidney.
Title: A long non-coding RNA inside the type 2 transglutaminase gene tightly correlates with the expression of its transcriptional variants.
The results point to regulation of alternative splicing of tissue transglutaminase could account for the complex physiopathology of celiac disease.
Title: Alternative RNA splicing of leucocyte tissue transglutaminase in coeliac disease.
Our data revealed that patients with lower level of TG2 expression detected in cancer tissues had longer disease free survival and overall survival as compared to the patients with higher TG2 expression.
Title: Prognostic value of Transglutaminase 2 in non-small cell lung cancer patients.
Gluten-free diet compliance and lower antitissue transglutaminase (atTG) at diagnosis are predictors of earlier normalization of atTG levels in patients with celiac disease. Patients with type 1 diabetes mellitus are less likely to normalize atTG levels, with longer normalization time.
Title: Antitissue Transglutaminase Normalization Postdiagnosis in Children With Celiac Disease.
expression in psoriasis was higher than in normal skin
Title: Elevated transglutaminase-2 expression in the epidermis of psoriatic skin and its role in the skin lesion development.

Submit: New GeneRIF Correction See all GeneRIFs (337)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Protein interactions

Protein	Gene	Interaction	Pubs
Envelope surface glycoprotein gp120	env	Cyclosporin (CsA) treatment prevents gp120-dependent induction of apoptosis by blocking the activation of Ca(2+)-dependent effector elements such as transglutaminase (TG) proteins	PubMed
Envelope transmembrane glycoprotein gp41	env	The HIV-1 transmembrane glycoprotein gp41 is an amino acceptor and donor substrate for transglutaminase in vitro; soluble CD4 can block the transglutaminase-catalyzed incorporation of the polyamine spermidine into HIV-1 gp41	PubMed
Rev	rev	tissue transglutaminase has been proposed to interfere with HIV replication through a specific interaction with eukaryotic initiation factor 5A (eIF-5A) that inhibits Rev-mediated nuclear export of viral mRNA	PubMed
Tat	tat	Microarray analysis indicates HIV-1 Tat-induced upregulation of transglutaminase 2 (TGM2) in primary human brain microvascular endothelial cells	PubMed

Go to the HIV-1, Human Interaction Database

Pathways from BioSystems

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Huntington's disease, organism-specific biosystem (from KEGG)
Huntington's disease, organism-specific biosystemHuntington disease (HD) is an autosomal-dominant neurodegenerative disorder that primarily affects medium spiny striatal neurons (MSN). The symptoms are choreiform, involuntary movements, personality...
Huntington's disease, conserved biosystem (from KEGG)
Huntington's disease, conserved biosystemHuntington disease (HD) is an autosomal-dominant neurodegenerative disorder that primarily affects medium spiny striatal neurons (MSN). The symptoms are choreiform, involuntary movements, personality...
Thromboxane A2 receptor signaling, organism-specific biosystem (from Pathway Interaction Database)
Thromboxane A2 receptor signaling, organism-specific biosystem
Thromboxane A2 receptor signaling

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

WI-20127 (e-PCR)
- UniSTS:67654

SHGC-12855 (e-PCR)
- UniSTS:1896

RH45330 (e-PCR)
- UniSTS:69997

D20S1009 (e-PCR)
- UniSTS:67217

D20S543E (e-PCR)
- UniSTS:72654

TGM2_2385 (e-PCR)
- UniSTS:281055

Homology

Homologs of the TGM2 gene: The TGM2 gene is conserved in chimpanzee, dog, cow, mouse, rat, chicken, zebrafish, and frog.
Orthologs from Annotation Pipeline: 200 organisms have orthologs with human gene TGM2
The Hierarchical Catalog of Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
GTP binding	IEA Inferred from Electronic Annotation more info
metal ion binding	IEA Inferred from Electronic Annotation more info
protein binding	IPI Inferred from Physical Interaction more info	PubMed
protein domain specific binding	IEA Inferred from Electronic Annotation more info
protein-glutamine gamma-glutamyltransferase activity	IMP Inferred from Mutant Phenotype more info	PubMed
protein-glutamine gamma-glutamyltransferase activity	ISS Inferred from Sequence or Structural Similarity more info

Process	Evidence Code	Pubs
apoptotic cell clearance	IDA Inferred from Direct Assay more info	PubMed
blood vessel remodeling	IEA Inferred from Electronic Annotation more info
branching involved in salivary gland morphogenesis	IEA Inferred from Electronic Annotation more info
isopeptide cross-linking via N6-(L-isoglutamyl)-L-lysine	IEA Inferred from Electronic Annotation more info
negative regulation of endoplasmic reticulum calcium ion concentration	IMP Inferred from Mutant Phenotype more info	PubMed
positive regulation of I-kappaB kinase/NF-kappaB signaling	IEA Inferred from Electronic Annotation more info
positive regulation of apoptotic process	IMP Inferred from Mutant Phenotype more info	PubMed
positive regulation of cell adhesion	ISS Inferred from Sequence or Structural Similarity more info
positive regulation of cytosolic calcium ion concentration involved in phospholipase C-activating G protein-coupled signaling pathway	IEA Inferred from Electronic Annotation more info
positive regulation of inflammatory response	IEA Inferred from Electronic Annotation more info
positive regulation of mitochondrial calcium ion concentration	IMP Inferred from Mutant Phenotype more info	PubMed
positive regulation of smooth muscle cell proliferation	IEA Inferred from Electronic Annotation more info
protein homooligomerization	IEA Inferred from Electronic Annotation more info
salivary gland cavitation	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
collagen-containing extracellular matrix	HDA more info	PubMed
cytosol	IDA Inferred from Direct Assay more info	PubMed
endoplasmic reticulum	IEA Inferred from Electronic Annotation more info
extracellular exosome	HDA more info	PubMed
focal adhesion	HDA more info	PubMed
intrinsic component of plasma membrane	IDA Inferred from Direct Assay more info	PubMed
intrinsic component of plasma membrane	IMP Inferred from Mutant Phenotype more info	PubMed
mitochondrion	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: protein-glutamine gamma-glutamyltransferase 2

Names: C polypeptide, protein-glutamine-gamma-glutamyltransferase; TGase C; TGase H; TGase-2; tissue transglutaminase; transglutaminase C; transglutaminase H

NP_001310245.1

EC 2.3.2.13

NP_001310246.1

EC 2.3.2.13

NP_001310247.1

EC 2.3.2.13

NP_004604.2

EC 2.3.2.13

NP_945189.1

EC 2.3.2.13

XP_011527330.1

EC 2.3.2.13

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_001323316.1 → NP_001310245.1 protein-glutamine gamma-glutamyltransferase 2 isoform a

Status: REVIEWED

Source sequence(s)

AL031651, BQ011237, DB064707

Consensus CDS

CCDS13302.1

UniProtKB/Swiss-Prot

P21980

UniProtKB/TrEMBL

V9HWG3

Conserved Domains (4) summary

smart00460
Location:269 → 361

TGc; Transglutaminase/protease-like homologues

COG1305
Location:271 → 369

YebA; Transglutaminase-like enzyme, putative cysteine protease [Posttranslational modification, protein turnover, chaperones]

pfam00868
Location:6 → 120

Transglut_N; Transglutaminase family

pfam00927
Location:587 → 686

Transglut_C; Transglutaminase family, C-terminal ig like domain
NM_001323317.1 → NP_001310246.1 protein-glutamine gamma-glutamyltransferase 2 isoform c

Status: REVIEWED

Source sequence(s)

AK295775, AL031651, BG772156, BQ011237, HY030430

UniProtKB/TrEMBL

B4DIT7

Conserved Domains (4) summary

smart00460
Location:188 → 280

TGc; Transglutaminase/protease-like homologues

COG1305
Location:190 → 288

YebA; Transglutaminase-like enzyme, putative cysteine protease [Posttranslational modification, protein turnover, chaperones]

pfam00868
Location:6 → 63

Transglut_N; Transglutaminase family

pfam00927
Location:506 → 605

Transglut_C; Transglutaminase family, C-terminal ig like domain
NM_001323318.1 → NP_001310247.1 protein-glutamine gamma-glutamyltransferase 2 isoform d

Status: REVIEWED

Source sequence(s)

AK300292, AL031651, BG772156, BQ011237, EU794665, HY030430

UniProtKB/TrEMBL

B4DTN7, V9HWG3
NM_004613.3 → NP_004604.2 protein-glutamine gamma-glutamyltransferase 2 isoform a

See identical proteins and their annotated locations for NP_004604.2

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (a). Both variants 1 and 5 encode the same isoform (a).

Source sequence(s)

AK126508, AL031651, BC003551, BG772156, BQ011237, BQ430537, BQ938957, HY030430

Consensus CDS

CCDS13302.1

UniProtKB/Swiss-Prot

P21980

UniProtKB/TrEMBL

V9HWG3

Related

ENSP00000355330.2, OTTHUMP00000030960, ENST00000361475.6, OTTHUMT00000079151

Conserved Domains (4) summary

smart00460
Location:269 → 361

TGc; Transglutaminase/protease-like homologues

COG1305
Location:271 → 369

YebA; Transglutaminase-like enzyme, putative cysteine protease [Posttranslational modification, protein turnover, chaperones]

pfam00868
Location:6 → 120

Transglut_N; Transglutaminase family

pfam00927
Location:587 → 686

Transglut_C; Transglutaminase family, C-terminal ig like domain
NM_198951.2 → NP_945189.1 protein-glutamine gamma-glutamyltransferase 2 isoform b

See identical proteins and their annotated locations for NP_945189.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) differs in the 3' UTR and coding region compared to variant 1. The resulting isoform (b) is shorter and has a unique C-terminus compared to isoform a.

Source sequence(s)

AA493184, BC003551, BG772156, HY030430

UniProtKB/Swiss-Prot

P21980

Conserved Domains (3) summary

smart00460
Location:269 → 361

TGc; Transglutaminase/protease-like homologues

pfam00868
Location:4 → 122

Transglut_N; Transglutaminase family

pfam00927
Location:473 → 538

Transglut_C; Transglutaminase family, C-terminal ig like domain

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 109 details...

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p12 Primary Assembly

Genomic

NC_000020.11 Reference GRCh38.p12 Primary Assembly

Range

38127387..38166578 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_011529028.1 → XP_011527330.1 protein-glutamine gamma-glutamyltransferase 2 isoform X1

See identical proteins and their annotated locations for XP_011527330.1

UniProtKB/Swiss-Prot

P21980

UniProtKB/TrEMBL

V9HWG3

Conserved Domains (4) summary

smart00460
Location:269 → 361

TGc; Transglutaminase/protease-like homologues

COG1305
Location:271 → 369

YebA; Transglutaminase-like enzyme, putative cysteine protease [Posttranslational modification, protein turnover, chaperones]

pfam00868
Location:6 → 120

Transglut_N; Transglutaminase family

pfam00927
Location:587 → 686

Transglut_C; Transglutaminase family, C-terminal ig like domain