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
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
109.20200815	current	GRCh38.p13 (GCF_000001405.39)	20	NC_000020.11 (38127385..38166508, 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 Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

MiR-532-3p suppresses colorectal cancer progression by disrupting the ETS1/TGM2 axis-mediated Wnt/beta-catenin signaling.
Title: MiR-532-3p suppresses colorectal cancer progression by disrupting the ETS1/TGM2 axis-mediated Wnt/β-catenin signaling.
glycolysis-mediated TG2 induction and tissue fibrosis is associated with experimental pulmonary hypertension, heart failure, and hyperglycemia
Title: Glycolysis regulated transglutaminase 2 activation in cardiopulmonary fibrogenic remodeling.
The data indicates that AFF1 inhibits adipogenic differentiation by regulating the transcription of TGM2.
Title: AFF1 inhibits adipogenic differentiation via targeting TGM2 transcription.
TG2 potentially presents a novel target for therapeutic intervention that can support available multiple sclerosis therapies targeting lymphocyte infiltration
Title: Tissue Transglutaminase Appears in Monocytes and Macrophages but Not in Lymphocytes in White Matter Multiple Sclerosis Lesions.
transglutaminase 2 expression induced by all-trans retinoic acid treatment reprograms inflammatory signaling networks governed by nuclear factor kappa-light-chain-enhancer of activated B-cell activation, resulting in overexpression of TNF-alpha and IL-1beta in differentiating APL cells, suggesting that atypically expressed transglutaminase 2 is a promising target for leukemia treatment.
Title: Transglutaminase 2 programs differentiating acute promyelocytic leukemia cells in all-trans retinoic acid treatment to inflammatory stage through NF-κB activation.
MicroRNA214 suppresses the viability, migration and invasion of human colorectal carcinoma cells via targeting TGM2.
Title: MicroRNA‑214 suppresses the viability, migration and invasion of human colorectal carcinoma cells via targeting transglutaminase 2.
This study shows a significant gene dose effect in terms of tTGA level at diagnosis, but no significant association between HLA-DQB1*02 allele dose and the clinical outcomes in Celiac disease.
Title: HLA-DQ2 homozygosis increases tTGA levels at diagnosis but does not influence the clinical phenotype of coeliac disease: A multicentre study.
Significantly increased concentration in endometrial cancer (EC) as compared to healthy controls were found in case of CD44 antigen (CD44) , epithelial cell adhesion molecule (EpCAM) and transglutaminase 2 (TGM2).
Title: CD44, TGM2 and EpCAM as novel plasma markers in endometrial cancer diagnosis.
REVIEW: Tissue transglutaminase in the pathogenesis of heart failure
Title: Tissue transglutaminase in the pathogenesis of heart failure.
the anti-inflammatory mechanism that prevents neutrophils from adhering to endothelial cells is identified with TG2 S-nitrosylation at the endothelial cell-blood interface.
Title: Endothelial cell-surface tissue transglutaminase inhibits neutrophil adhesion by binding and releasing nitric oxide.

Submit: New GeneRIF Correction See all GeneRIFs (356)

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

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: 230 organisms have orthologs with human gene TGM2
Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
GTP binding	IEA Inferred from Electronic Annotation more info
identical protein 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	IBA Inferred from Biological aspect of Ancestor more info	PubMed
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
peptide cross-linking	IBA Inferred from Biological aspect of Ancestor more info	PubMed
peptide cross-linking	IDA Inferred from Direct Assay 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
salivary gland cavitation	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
collagen-containing extracellular matrix	HDA more info	PubMed
colocalizes_with 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	IBA Inferred from Biological aspect of Ancestor more info	PubMed
mitochondrion	IDA Inferred from Direct Assay more info	PubMed
plasma membrane	IDA Inferred from Direct Assay more info

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_001323316.2 → 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_001323317.2 → NP_001310246.1 protein-glutamine gamma-glutamyltransferase 2 isoform c

Status: REVIEWED

Source sequence(s)

AK295775, AL031651, BQ011237

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_001323318.2 → NP_001310247.1 protein-glutamine gamma-glutamyltransferase 2 isoform d

Status: REVIEWED

Source sequence(s)

AK300292, AL031651, BQ011237, EU794665, HY030430

UniProtKB/TrEMBL

B4DTN7, V9HWG3
NM_004613.4 → 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, BQ011237, BQ430537, BQ938957, HY030430

Consensus CDS

CCDS13302.1

UniProtKB/Swiss-Prot

P21980

UniProtKB/TrEMBL

V9HWG3

Related

ENSP00000355330.2, ENST00000361475.7

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_198951.3 → 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, AL031651, BC003551, HY030430

UniProtKB/Swiss-Prot

P21980

Related

ENST00000468262.5

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 Updated Annotation Release 109.20200815

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

Reference GRCh38.p13 Primary Assembly

Genomic

NC_000020.11 Reference GRCh38.p13 Primary Assembly

Range

38127385..38166508 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