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Protein

Protein-glutamine gamma-glutamyltransferase E

Gene

TGM3

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Catalyzes the calcium-dependent formation of isopeptide cross-links between glutamine and lysine residues in various proteins, as well as the conjugation of polyamines to proteins. Involved in the formation of the cornified envelope (CE), a specialized component consisting of covalent cross-links of proteins beneath the plasma membrane of terminally differentiated keratinocytes. Catalyzes small proline-rich proteins (SPRR1 and SPRR2) and LOR cross-linking to form small interchain oligomers, which are further cross-linked by TGM1 onto the growing CE scaffold (By similarity). In hair follicles, involved in cross-linking structural proteins to hardening the inner root sheath.By similarity

Catalytic activityi

Protein glutamine + alkylamine = protein N(5)-alkylglutamine + NH3.PROSITE-ProRule annotation2 Publications

Cofactori

Ca2+2 PublicationsNote: Binds 3 Ca2+ cations per subunit. Binds 1 Ca2+ as a zymogen, and binds 2 more Ca2+ cations, or other divalent metal cations, after proteolytic processing.2 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi222Calcium 1; via carbonyl oxygen2 Publications1
Metal bindingi225Calcium 12 Publications1
Metal bindingi227Calcium 1; via carbonyl oxygen2 Publications1
Metal bindingi228Calcium 12 Publications1
Metal bindingi230Calcium 1; via carbonyl oxygen2 Publications1
Active sitei273PROSITE-ProRule annotation1
Metal bindingi302Calcium 22 Publications1
Metal bindingi304Calcium 22 Publications1
Metal bindingi306Calcium 22 Publications1
Metal bindingi308Calcium 2; via carbonyl oxygen2 Publications1
Metal bindingi325Calcium 22 Publications1
Active sitei331PROSITE-ProRule annotation1
Active sitei354PROSITE-ProRule annotation1
Metal bindingi394Calcium 32 Publications1
Metal bindingi416Calcium 3; via carbonyl oxygen2 Publications1
Metal bindingi444Calcium 32 Publications1
Metal bindingi449Calcium 32 Publications1

GO - Molecular functioni

  • calcium ion binding Source: UniProtKB
  • catalytic activity Source: UniProtKB
  • protein-glutamine gamma-glutamyltransferase activity Source: UniProtKB
  • transferase activity, transferring acyl groups Source: UniProtKB

GO - Biological processi

  • cell envelope organization Source: UniProtKB
  • cellular protein modification process Source: UniProtKB
  • hair follicle morphogenesis Source: UniProtKB
  • keratinization Source: UniProtKB-KW
  • keratinocyte differentiation Source: UniProtKB
  • peptide cross-linking Source: UniProtKB
  • protein tetramerization Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Acyltransferase, Transferase

Keywords - Biological processi

Keratinization

Keywords - Ligandi

Calcium, Metal-binding

Enzyme and pathway databases

BioCyciZFISH:HS04931-MONOMER.
BRENDAi2.3.2.13. 2681.

Names & Taxonomyi

Protein namesi
Recommended name:
Protein-glutamine gamma-glutamyltransferase E (EC:2.3.2.13)
Alternative name(s):
Transglutaminase E
Short name:
TG(E)
Short name:
TGE
Short name:
TGase E
Transglutaminase-3
Short name:
TGase-3
Cleaved into the following 2 chains:
Gene namesi
Name:TGM3
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 20

Organism-specific databases

HGNCiHGNC:11779. TGM3.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
  • extracellular exosome Source: UniProtKB
  • extrinsic component of cytoplasmic side of plasma membrane Source: UniProtKB
Complete GO annotation...

Pathology & Biotechi

Organism-specific databases

DisGeNETi7053.
OpenTargetsiENSG00000125780.
PharmGKBiPA36492.

Chemistry databases

ChEMBLiCHEMBL3363.
DrugBankiDB00130. L-Glutamine.

Polymorphism and mutation databases

BioMutaiTGM3.
DMDMi257051080.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemoved1 Publication
ChainiPRO_00000336522 – 467Protein-glutamine gamma-glutamyltransferase E 50 kDa catalytic chainAdd BLAST466
ChainiPRO_0000033653468 – 693Protein-glutamine gamma-glutamyltransferase E 27 kDa non-catalytic chainAdd BLAST226

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylalanine1 Publication1
Modified residuei111PhosphotyrosineCombined sources1
Modified residuei112PhosphothreonineCombined sources1

Post-translational modificationi

Activated by proteolytic processing. In vitro activation is commonly achieved by cleavage with dispase, a neutral bacterial protease. Dispase cleavage site was proposed to lie between Ser-470 and Ser-471 (PubMed:8099584) or between Pro-465 and Phe-466 (PubMed:16565075). Physiological activation may be catalyzed by CTSL and, to a lesser extent, by CTSS, but not by CTSB, CTSD nor CTSV (PubMed:16565075).2 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei467 – 468Cleavage; by CTSL2

Keywords - PTMi

Acetylation, Phosphoprotein, Zymogen

Proteomic databases

EPDiQ08188.
MaxQBiQ08188.
PaxDbiQ08188.
PeptideAtlasiQ08188.
PRIDEiQ08188.
TopDownProteomicsiQ08188.

PTM databases

iPTMnetiQ08188.
PhosphoSitePlusiQ08188.

Expressioni

Gene expression databases

BgeeiENSG00000125780.
CleanExiHS_TGM3.
GenevisibleiQ08188. HS.

Organism-specific databases

HPAiHPA004728.

Interactioni

Subunit structurei

Consists of two polypeptide chains, which are synthesized as a precursor form of a single polypeptide.2 Publications

Protein-protein interaction databases

BioGridi112911. 23 interactors.
IntActiQ08188. 8 interactors.
MINTiMINT-7950929.
STRINGi9606.ENSP00000370867.

Chemistry databases

BindingDBiQ08188.

Structurei

Secondary structure

1693
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi6 – 10Combined sources5
Helixi13 – 19Combined sources7
Beta strandi31 – 33Combined sources3
Beta strandi38 – 46Combined sources9
Beta strandi53 – 59Combined sources7
Beta strandi61 – 63Combined sources3
Turni66 – 69Combined sources4
Beta strandi70 – 79Combined sources10
Beta strandi82 – 92Combined sources11
Beta strandi95 – 101Combined sources7
Beta strandi109 – 119Combined sources11
Beta strandi122 – 134Combined sources13
Helixi149 – 155Combined sources7
Beta strandi160 – 167Combined sources8
Beta strandi170 – 177Combined sources8
Helixi185 – 193Combined sources9
Helixi197 – 201Combined sources5
Helixi203 – 208Combined sources6
Helixi209 – 211Combined sources3
Helixi213 – 223Combined sources11
Turni227 – 229Combined sources3
Beta strandi231 – 235Combined sources5
Helixi247 – 249Combined sources3
Helixi253 – 262Combined sources10
Beta strandi268 – 271Combined sources4
Helixi273 – 287Combined sources15
Beta strandi291 – 300Combined sources10
Beta strandi305 – 313Combined sources9
Turni322 – 325Combined sources4
Beta strandi326 – 337Combined sources12
Turni341 – 343Combined sources3
Helixi345 – 347Combined sources3
Beta strandi349 – 353Combined sources5
Beta strandi356 – 359Combined sources4
Helixi372 – 377Combined sources6
Turni383 – 385Combined sources3
Helixi386 – 394Combined sources9
Beta strandi396 – 403Combined sources8
Turni404 – 407Combined sources4
Beta strandi408 – 426Combined sources19
Beta strandi433 – 435Combined sources3
Helixi437 – 440Combined sources4
Beta strandi444 – 446Combined sources3
Helixi447 – 460Combined sources14
Beta strandi482 – 489Combined sources8
Beta strandi499 – 507Combined sources9
Beta strandi509 – 511Combined sources3
Beta strandi513 – 524Combined sources12
Beta strandi530 – 543Combined sources14
Beta strandi548 – 555Combined sources8
Helixi557 – 560Combined sources4
Turni561 – 563Combined sources3
Beta strandi569 – 577Combined sources9
Beta strandi584 – 591Combined sources8
Beta strandi597 – 603Combined sources7
Beta strandi611 – 618Combined sources8
Beta strandi621 – 623Combined sources3
Beta strandi627 – 633Combined sources7
Turni635 – 637Combined sources3
Beta strandi638 – 640Combined sources3
Beta strandi642 – 646Combined sources5
Beta strandi654 – 661Combined sources8
Beta strandi667 – 677Combined sources11
Beta strandi680 – 692Combined sources13

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1L9MX-ray2.10A/B2-693[»]
1L9NX-ray2.10A/B2-693[»]
1NUDX-ray2.70A/B2-693[»]
1NUFX-ray2.70A2-693[»]
1NUGX-ray2.40A/B2-693[»]
ProteinModelPortaliQ08188.
SMRiQ08188.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ08188.

Family & Domainsi

Sequence similaritiesi

Phylogenomic databases

eggNOGiENOG410IFMV. Eukaryota.
ENOG410XQEZ. LUCA.
GeneTreeiENSGT00760000119108.
HOVERGENiHBG004342.
InParanoidiQ08188.
KOiK05620.
OMAiMVGWNFG.
OrthoDBiEOG091G030K.
PhylomeDBiQ08188.
TreeFamiTF324278.

Family and domain databases

Gene3Di2.60.40.10. 3 hits.
3.90.260.10. 1 hit.
InterProiIPR023608. Gln_gamma-glutamylTfrase_euk.
IPR013783. Ig-like_fold.
IPR014756. Ig_E-set.
IPR002931. Transglutaminase-like.
IPR013808. Transglutaminase_AS.
IPR008958. Transglutaminase_C.
IPR001102. Transglutaminase_N.
[Graphical view]
PANTHERiPTHR11590. PTHR11590. 1 hit.
PfamiPF00927. Transglut_C. 2 hits.
PF01841. Transglut_core. 1 hit.
PF00868. Transglut_N. 1 hit.
[Graphical view]
PIRSFiPIRSF000459. TGM_EBP42. 1 hit.
SMARTiSM00460. TGc. 1 hit.
[Graphical view]
SUPFAMiSSF49309. SSF49309. 2 hits.
SSF81296. SSF81296. 1 hit.
PROSITEiPS00547. TRANSGLUTAMINASES. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q08188-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MAALGVQSIN WQTAFNRQAH HTDKFSSQEL ILRRGQNFQV LMIMNKGLGS
60 70 80 90 100
NERLEFIVST GPYPSESAMT KAVFPLSNGS SGGWSAVLQA SNGNTLTISI
110 120 130 140 150
SSPASAPIGR YTMALQIFSQ GGISSVKLGT FILLFNPWLN VDSVFMGNHA
160 170 180 190 200
EREEYVQEDA GIIFVGSTNR IGMIGWNFGQ FEEDILSICL SILDRSLNFR
210 220 230 240 250
RDAATDVASR NDPKYVGRVL SAMINSNDDN GVLAGNWSGT YTGGRDPRSW
260 270 280 290 300
NGSVEILKNW KKSGFSPVRY GQCWVFAGTL NTALRSLGIP SRVITNFNSA
310 320 330 340 350
HDTDRNLSVD VYYDPMGNPL DKGSDSVWNF HVWNEGWFVR SDLGPSYGGW
360 370 380 390 400
QVLDATPQER SQGVFQCGPA SVIGVREGDV QLNFDMPFIF AEVNADRITW
410 420 430 440 450
LYDNTTGKQW KNSVNSHTIG RYISTKAVGS NARMDVTDKY KYPEGSDQER
460 470 480 490 500
QVFQKALGKL KPNTPFAATS SMGLETEEQE PSIIGKLKVA GMLAVGKEVN
510 520 530 540 550
LVLLLKNLSR DTKTVTVNMT AWTIIYNGTL VHEVWKDSAT MSLDPEEEAE
560 570 580 590 600
HPIKISYAQY EKYLKSDNMI RITAVCKVPD ESEVVVERDI ILDNPTLTLE
610 620 630 640 650
VLNEARVRKP VNVQMLFSNP LDEPVRDCVL MVEGSGLLLG NLKIDVPTLG
660 670 680 690
PKEGSRVRFD ILPSRSGTKQ LLADFSCNKF PAIKAMLSID VAE
Length:693
Mass (Da):76,632
Last modified:September 1, 2009 - v4
Checksum:iEAFAC0C9A8AA5FD6
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti58 – 59VS → DT in AAA61155 (PubMed:8099584).Curated2
Sequence conflicti251N → G in AAA61155 (PubMed:8099584).Curated1
Sequence conflicti324S → G in BAF84040 (PubMed:14702039).Curated1
Sequence conflicti346S → P in AAA61155 (PubMed:8099584).Curated1
Sequence conflicti674D → G in BAF84040 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_04006713T → K.6 PublicationsCorresponds to variant rs214803dbSNPEnsembl.1
Natural variantiVAR_040068163I → L.1 PublicationCorresponds to variant rs6048066dbSNPEnsembl.1
Natural variantiVAR_040069249S → N.1 PublicationCorresponds to variant rs214814dbSNPEnsembl.1
Natural variantiVAR_040070562K → R.1 PublicationCorresponds to variant rs1042617dbSNPEnsembl.1
Natural variantiVAR_040071654G → R.5 PublicationsCorresponds to variant rs214830dbSNPEnsembl.1
Natural variantiVAR_055360687L → M.1 PublicationCorresponds to variant rs45581032dbSNPEnsembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L10386 mRNA. Translation: AAA61155.1.
AK290324 mRNA. Translation: BAF83013.1.
AK291351 mRNA. Translation: BAF84040.1.
AK315236 mRNA. Translation: BAG37663.1.
EF102483 Genomic DNA. Translation: ABK41960.1.
AL031678 Genomic DNA. Translation: CAB37633.1.
CH471133 Genomic DNA. Translation: EAX10601.1.
CH471133 Genomic DNA. Translation: EAX10602.1.
BC109075 mRNA. Translation: AAI09076.1.
BC109076 mRNA. Translation: AAI09077.1.
CCDSiCCDS33435.1.
PIRiA45991.
RefSeqiNP_003236.3. NM_003245.3.
UniGeneiHs.2022.

Genome annotation databases

EnsembliENST00000381458; ENSP00000370867; ENSG00000125780.
GeneIDi7053.
KEGGihsa:7053.
UCSCiuc002wfx.5. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Web resourcesi

NIEHS-SNPs

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L10386 mRNA. Translation: AAA61155.1.
AK290324 mRNA. Translation: BAF83013.1.
AK291351 mRNA. Translation: BAF84040.1.
AK315236 mRNA. Translation: BAG37663.1.
EF102483 Genomic DNA. Translation: ABK41960.1.
AL031678 Genomic DNA. Translation: CAB37633.1.
CH471133 Genomic DNA. Translation: EAX10601.1.
CH471133 Genomic DNA. Translation: EAX10602.1.
BC109075 mRNA. Translation: AAI09076.1.
BC109076 mRNA. Translation: AAI09077.1.
CCDSiCCDS33435.1.
PIRiA45991.
RefSeqiNP_003236.3. NM_003245.3.
UniGeneiHs.2022.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1L9MX-ray2.10A/B2-693[»]
1L9NX-ray2.10A/B2-693[»]
1NUDX-ray2.70A/B2-693[»]
1NUFX-ray2.70A2-693[»]
1NUGX-ray2.40A/B2-693[»]
ProteinModelPortaliQ08188.
SMRiQ08188.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi112911. 23 interactors.
IntActiQ08188. 8 interactors.
MINTiMINT-7950929.
STRINGi9606.ENSP00000370867.

Chemistry databases

BindingDBiQ08188.
ChEMBLiCHEMBL3363.
DrugBankiDB00130. L-Glutamine.

PTM databases

iPTMnetiQ08188.
PhosphoSitePlusiQ08188.

Polymorphism and mutation databases

BioMutaiTGM3.
DMDMi257051080.

Proteomic databases

EPDiQ08188.
MaxQBiQ08188.
PaxDbiQ08188.
PeptideAtlasiQ08188.
PRIDEiQ08188.
TopDownProteomicsiQ08188.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000381458; ENSP00000370867; ENSG00000125780.
GeneIDi7053.
KEGGihsa:7053.
UCSCiuc002wfx.5. human.

Organism-specific databases

CTDi7053.
DisGeNETi7053.
GeneCardsiTGM3.
HGNCiHGNC:11779. TGM3.
HPAiHPA004728.
MIMi600238. gene.
neXtProtiNX_Q08188.
OpenTargetsiENSG00000125780.
PharmGKBiPA36492.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IFMV. Eukaryota.
ENOG410XQEZ. LUCA.
GeneTreeiENSGT00760000119108.
HOVERGENiHBG004342.
InParanoidiQ08188.
KOiK05620.
OMAiMVGWNFG.
OrthoDBiEOG091G030K.
PhylomeDBiQ08188.
TreeFamiTF324278.

Enzyme and pathway databases

BioCyciZFISH:HS04931-MONOMER.
BRENDAi2.3.2.13. 2681.

Miscellaneous databases

ChiTaRSiTGM3. human.
EvolutionaryTraceiQ08188.
GeneWikiiTGM3.
GenomeRNAii7053.
PROiQ08188.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000125780.
CleanExiHS_TGM3.
GenevisibleiQ08188. HS.

Family and domain databases

Gene3Di2.60.40.10. 3 hits.
3.90.260.10. 1 hit.
InterProiIPR023608. Gln_gamma-glutamylTfrase_euk.
IPR013783. Ig-like_fold.
IPR014756. Ig_E-set.
IPR002931. Transglutaminase-like.
IPR013808. Transglutaminase_AS.
IPR008958. Transglutaminase_C.
IPR001102. Transglutaminase_N.
[Graphical view]
PANTHERiPTHR11590. PTHR11590. 1 hit.
PfamiPF00927. Transglut_C. 2 hits.
PF01841. Transglut_core. 1 hit.
PF00868. Transglut_N. 1 hit.
[Graphical view]
PIRSFiPIRSF000459. TGM_EBP42. 1 hit.
SMARTiSM00460. TGc. 1 hit.
[Graphical view]
SUPFAMiSSF49309. SSF49309. 2 hits.
SSF81296. SSF81296. 1 hit.
PROSITEiPS00547. TRANSGLUTAMINASES. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiTGM3_HUMAN
AccessioniPrimary (citable) accession number: Q08188
Secondary accession number(s): A8K5N6
, B2RCR6, D3DVX1, O95933, Q32ML9, Q32MM0
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 1, 1995
Last sequence update: September 1, 2009
Last modified: November 30, 2016
This is version 165 of the entry and version 4 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 20
    Human chromosome 20: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.