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O43548 (TGM5_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 131. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Protein-glutamine gamma-glutamyltransferase 5

EC=2.3.2.13
Alternative name(s):
Transglutaminase X
Short name=TG(X)
Short name=TGX
Short name=TGase X
Transglutaminase-5
Short name=TGase-5
Gene names
Name:TGM5
Synonyms:TGMX
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length720 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Catalyzes the cross-linking of proteins and the conjugation of polyamines to proteins. Contributes to the formation of the cornified cell envelope of keratinocytes.

Catalytic activity

Protein glutamine + alkylamine = protein N(5)-alkylglutamine + NH3.

Cofactor

Binds 1 calcium ion per subunit By similarity.

Subcellular location

Cytoplasm. Note: Associated with intermediate filaments. Ref.4

Tissue specificity

Expressed in foreskin keratinocytes.

Induction

By 12-O-tetradecanoylphorbol-13-acetate (TPA) and calcium in NHEK cells. Ref.4

Involvement in disease

Peeling skin syndrome, acral type (APSS) [MIM:609796]: A non-inflammatory and localized form of peeling skin syndrome, a genodermatosis characterized by the continuous shedding of the outer layers of the epidermis. In APSS patients, skin peeling is painless and strictly limited to the dorsa of the hands and feet. It is accompanied by painless erythema and spontaneous non-scarring healing. Ultrastructural and histological analysis shows a level of blistering high in the epidermis at the stratum granulosum-stratum corneum junction.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.5

Sequence similarities

Belongs to the transglutaminase superfamily. Transglutaminase family.

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform Long (identifier: O43548-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform Short (identifier: O43548-2)

The sequence of this isoform differs from the canonical sequence as follows:
     64-145: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed Ref.4
Chain2 – 720719Protein-glutamine gamma-glutamyltransferase 5
PRO_0000213713

Sites

Active site2781 By similarity
Active site3371 By similarity
Active site3601 By similarity
Metal binding4001Calcium By similarity
Metal binding4021Calcium By similarity
Metal binding4481Calcium By similarity
Metal binding4531Calcium By similarity

Amino acid modifications

Modified residue21N-acetylalanine Ref.4

Natural variations

Alternative sequence64 – 14582Missing in isoform Short.
VSP_006415
Natural variant671P → S. Ref.2
VAR_013248
Natural variant1091T → M. Ref.5
Corresponds to variant rs113463533 [ dbSNP | Ensembl ].
VAR_025848
Natural variant1131G → C in APSS; completely abolishes the enzyme activity. Ref.5
Corresponds to variant rs112292549 [ dbSNP | Ensembl ].
VAR_025849
Natural variant3521A → G. Ref.2
Corresponds to variant rs28756768 [ dbSNP | Ensembl ].
VAR_013249
Natural variant5041V → M.
Corresponds to variant rs7171797 [ dbSNP | Ensembl ].
VAR_052564
Natural variant5211Q → R.
Corresponds to variant rs35985214 [ dbSNP | Ensembl ].
VAR_052565

Sequences

Sequence LengthMass (Da)Tools
Isoform Long [UniParc].

Last modified January 23, 2007. Version 4.
Checksum: 9CF68884B48BAE1C

FASTA72080,778
        10         20         30         40         50         60 
MAQGLEVALT DLQSSRNNVR HHTEEITVDH LLVRRGQAFN LTLYFRNRSF QPGLDNIIFV 

        70         80         90        100        110        120 
VETGPLPDLA LGTRAVFSLA RHHSPSPWIA WLETNGATST EVSLCAPPTA AVGRYLLKIH 

       130        140        150        160        170        180 
IDSFQGSVTA YQLGEFILLF NPWCPEDAVY LDSEPQRQEY VMNDYGFIYQ GSKNWIRPCP 

       190        200        210        220        230        240 
WNYGQFEDKI IDICLKLLDK SLHFQTDPAT DCALRGSPVY VSRVVCAMIN SNDDNGVLNG 

       250        260        270        280        290        300 
NWSENYTDGA NPAEWTGSVA ILKQWNATGC QPVRYGQCWV FAAVMCTVMR CLGIPTRVIT 

       310        320        330        340        350        360 
NFDSGHDTDG NLIIDEYYDN TGRILGNKKK DTIWNFHVWN ECWMARKDLP PAYGGWQVLD 

       370        380        390        400        410        420 
ATPQEMSNGV YCCGPASVRA IKEGEVDLNY DTPFVFSMVN ADCMSWLVQG GKEQKLHQDT 

       430        440        450        460        470        480 
SSVGNFISTK SIQSDERDDI TENYKYEEGS LQERQVFLKA LQKLKARSFH GSQRGAELQP 

       490        500        510        520        530        540 
SRPTSLSQDS PRSLHTPSLR PSDVVQVSLK FKLLDPPNMG QDICFVLLAL NMSSQFKDLK 

       550        560        570        580        590        600 
VNLSAQSLLH DGSPLSPFWQ DTAFITLSPK EAKTYPCKIS YSQYSQYLST DKLIRISALG 

       610        620        630        640        650        660 
EEKSSPEKIL VNKIITLSYP SITINVLGAA VVNQPLSIQV IFSNPLSEQV EDCVLTVEGS 

       670        680        690        700        710        720 
GLFKKQQKVF LGVLKPQHQA SIILETVPFK SGQRQIQANM RSNKFKDIKG YRNVYVDFAL 

« Hide

Isoform Short [UniParc].

Checksum: 8BCA7AAE9430D220
Show »

FASTA63871,919

References

« Hide 'large scale' references
[1]"Isolation of a cDNA encoding a novel member of the transglutaminase gene family from human keratinocytes. Detection and identification of transglutaminase gene products based on reverse transcription-polymerase chain reaction with degenerate primers."
Aeschlimann D., Koeller M.K., Allen-Hoffmann B.L., Mosher D.F.
J. Biol. Chem. 273:3452-3460(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS LONG AND SHORT).
Tissue: Foreskin.
[2]"Evolution of transglutaminase genes: identification of a transglutaminase gene cluster on human chromosome 15q15. Structure of the gene encoding transglutaminase X and a novel gene family member, transglutaminase Z."
Grenard P., Bates M.K., Aeschlimann D.
J. Biol. Chem. 276:33066-33078(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS SER-67 AND GLY-352.
[3]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM LONG).
[4]"Transglutaminase 5 is acetylated at the N-terminal end."
Rufini A., Vilbois F., Paradisi A., Oddi S., Tartaglione R., Leta A., Bagetta G., Guerrieri P., Finazzi-Agro' A., Melino G., Candi E.
Amino Acids 26:425-430(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 2-16, SUBCELLULAR LOCATION, ACETYLATION AT ALA-2, INDUCTION BY TPA AND CALCIUM, IDENTIFICATION BY MASS SPECTROMETRY.
[5]"A homozygous missense mutation in TGM5 abolishes epidermal transglutaminase 5 activity and causes acral peeling skin syndrome."
Cassidy A.J., van Steensel M.A.M., Steijlen P.M., van Geel M., van der Velden J., Morley S.M., Terrinoni A., Melino G., Candi E., McLean W.H.I.
Am. J. Hum. Genet. 77:909-917(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT APSS CYS-113, VARIANT MET-109, CHARACTERIZATION OF VARIANT APSS CYS-113, CHARACTERIZATION OF VARIANT MET-109.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF035960 mRNA. Translation: AAC02978.1.
AF035961 mRNA. Translation: AAC02979.1.
AF206510 expand/collapse EMBL AC list , AF206502, AF206503, AF206504, AF206505, AF206506, AF206507, AF206508, AF206509 Genomic DNA. Translation: AAF23981.1.
BC119009 mRNA. Translation: AAI19010.1.
CCDSCCDS32211.1. [O43548-2]
CCDS32212.1. [O43548-1]
RefSeqNP_004236.1. NM_004245.3. [O43548-2]
NP_963925.2. NM_201631.3. [O43548-1]
UniGeneHs.129719.

3D structure databases

ProteinModelPortalO43548.
SMRO43548. Positions 4-716.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid114742. 1 interaction.
STRING9606.ENSP00000220420.

Chemistry

DrugBankDB00130. L-Glutamine.

PTM databases

PhosphoSiteO43548.

Proteomic databases

PaxDbO43548.
PRIDEO43548.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000220420; ENSP00000220420; ENSG00000104055. [O43548-1]
ENST00000349114; ENSP00000220419; ENSG00000104055. [O43548-2]
GeneID9333.
KEGGhsa:9333.
UCSCuc001zrc.2. human. [O43548-1]
uc001zre.2. human. [O43548-2]

Organism-specific databases

CTD9333.
GeneCardsGC15M043527.
HGNCHGNC:11781. TGM5.
HPAHPA041649.
MIM603805. gene.
609796. phenotype.
neXtProtNX_O43548.
Orphanet263534. Acral peeling skin syndrome.
PharmGKBPA36494.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG293974.
HOGENOMHOG000231695.
HOVERGENHBG004342.
InParanoidO43548.
KOK05622.
OMAGVLNGNW.
OrthoDBEOG7WT40M.
PhylomeDBO43548.
TreeFamTF324278.

Gene expression databases

BgeeO43548.
CleanExHS_TGM5.
GenevestigatorO43548.

Family and domain databases

Gene3D2.60.40.10. 3 hits.
3.90.260.10. 1 hit.
InterProIPR023608. Gln_gamma-glutamylTfrase_euk.
IPR013783. Ig-like_fold.
IPR014756. Ig_E-set.
IPR002931. Transglutaminase-like.
IPR008958. Transglutaminase_C.
IPR013808. Transglutaminase_CS.
IPR001102. Transglutaminase_N.
[Graphical view]
PANTHERPTHR11590. PTHR11590. 1 hit.
PfamPF00927. Transglut_C. 2 hits.
PF01841. Transglut_core. 1 hit.
PF00868. Transglut_N. 1 hit.
[Graphical view]
PIRSFPIRSF000459. TGM_EBP42. 1 hit.
SMARTSM00460. TGc. 1 hit.
[Graphical view]
SUPFAMSSF49309. SSF49309. 2 hits.
SSF81296. SSF81296. 1 hit.
PROSITEPS00547. TRANSGLUTAMINASES. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GenomeRNAi9333.
NextBio34961.
PROO43548.
SOURCESearch...

Entry information

Entry nameTGM5_HUMAN
AccessionPrimary (citable) accession number: O43548
Secondary accession number(s): O43549, Q0VF40, Q9UEZ4
Entry history
Integrated into UniProtKB/Swiss-Prot: July 15, 1999
Last sequence update: January 23, 2007
Last modified: July 9, 2014
This is version 131 of the entry and version 4 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 15

Human chromosome 15: entries, gene names and cross-references to MIM