Reviewed, UniProtKB/Swiss-Prot O43548 (TGM5_HUMAN)

Names and origin

Protein names

Recommended name:
    Protein-glutamine gamma-glutamyltransferase 5
    EC=2.3.2.13
Alternative name(s):
    Transglutaminase-5
      Short name=TGase 5
    Transglutaminase X
      Short name=TGase X
      Short name=TGX
      Short name=TG(X)

Gene names

Name:	TGM5
Synonyms:	TGMX

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	720 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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 tetradecanoylphorbolacetate (TPA) and calcium in NHEK cells. Ref.4
Involvement in disease	Defects in TGM5 are a cause of peeling skin syndrome acral type (APSS) [MIM:609796, 270300]. Peeling skin syndrome (PSS) is an autosomal recessive genodermatosis characterized by the continuous shedding of the outer layers of the epidermis from birth and throughout life. In some cases of PSS, skin peeling is accompanied by erythema, vesicular lesions, or, in rare cases, other ectodermal features, like fragile hair and nail abnormalities. Two main subtypes, noninflammatory type A and inflammatory type B, have been suggested. However, it is clear from the dermatology literature that there are additional subtypes. In some families, an acral form of PSS (APSS) has been reported, in which skin peeling is strictly limited to the dorsa of the hands and feet, and, again, ultrastructural and histological analysis shows a level of blistering high in the epidermis at the stratum granulosum-stratum corneum junction. Ref.5
Sequence similarities	Belongs to the transglutaminase superfamily. Transglutaminase family.

Ontologies

Keywords
Cellular component	Cytoplasm
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Disease mutation
Ligand	Calcium Metal-binding
Molecular function	Acyltransferase Transferase
PTM	Acetylation
Technical term	Complete proteome Direct protein sequencing
Gene Ontology (GO)
Biological process	epidermis development Ref.1 Traceable author statement. Source: ProtInc peptide cross-linking Inferred from electronic annotation. Source: InterPro
Cellular component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	acyltransferase activity Inferred from electronic annotation. Source: UniProtKB-KW calcium ion binding Inferred from electronic annotation. Source: UniProtKB-KW protein-glutamine gamma-glutamyltransferase activity Ref.1 Traceable author statement. Source: ProtInc
Complete GO annotation...

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 key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Initiator methionine	1	1	Removed Ref.4
	Chain	2 – 720	719	Protein-glutamine gamma-glutamyltransferase 5		PRO_0000213713
Sites
	Active site	278	1	By similarity
	Active site	337	1	By similarity
	Active site	360	1	By similarity
	Metal binding	400	1	Calcium By similarity
	Metal binding	402	1	Calcium By similarity
	Metal binding	448	1	Calcium By similarity
	Metal binding	453	1	Calcium By similarity
Amino acid modifications
	Modified residue	2	1	N-acetylalanine Ref.4
Natural variations
	Alternative sequence	64 – 145	82	Missing in isoform Short.		VSP_006415
	Natural variant	67	1	P → S		VAR_013248
	Natural variant	109	1	T → M		VAR_025848
	Natural variant	113	1	G → C in APSS; completely abolishes the enzyme activity. Ref.5		VAR_025849
	Natural variant	352	1	A → G: dbSNP rs28756768. Ref.2		VAR_013249
	Natural variant	504	1	V → M: dbSNP rs7171797.		VAR_052564
	Natural variant	521	1	Q → R: dbSNP rs35985214.		VAR_052565

Sequences

	Sequence		Length	Mass (Da)
	Isoform Long [UniParc]. Last modified January 23, 2007. Version 4. Checksum: 9CF68884B48BAE1C	FASTA	720	80,778
	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
	Isoform Short. Checksum: 8BCA7AAE9430D220	FASTA	638	71,919
	10 20 30 40 50 60 MAQGLEVALT DLQSSRNNVR HHTEEITVDH LLVRRGQAFN LTLYFRNRSF QPGLDNIIFV 70 80 90 100 110 120 VETEDAVYLD SEPQRQEYVM NDYGFIYQGS KNWIRPCPWN YGQFEDKIID ICLKLLDKSL 130 140 150 160 170 180 HFQTDPATDC ALRGSPVYVS RVVCAMINSN DDNGVLNGNW SENYTDGANP AEWTGSVAIL 190 200 210 220 230 240 KQWNATGCQP VRYGQCWVFA AVMCTVMRCL GIPTRVITNF DSGHDTDGNL IIDEYYDNTG 250 260 270 280 290 300 RILGNKKKDT IWNFHVWNEC WMARKDLPPA YGGWQVLDAT PQEMSNGVYC CGPASVRAIK 310 320 330 340 350 360 EGEVDLNYDT PFVFSMVNAD CMSWLVQGGK EQKLHQDTSS VGNFISTKSI QSDERDDITE 370 380 390 400 410 420 NYKYEEGSLQ ERQVFLKALQ KLKARSFHGS QRGAELQPSR PTSLSQDSPR SLHTPSLRPS 430 440 450 460 470 480 DVVQVSLKFK LLDPPNMGQD ICFVLLALNM SSQFKDLKVN LSAQSLLHDG SPLSPFWQDT 490 500 510 520 530 540 AFITLSPKEA KTYPCKISYS QYSQYLSTDK LIRISALGEE KSSPEKILVN KIITLSYPSI 550 560 570 580 590 600 TINVLGAAVV NQPLSIQVIF SNPLSEQVED CVLTVEGSGL FKKQQKVFLG VLKPQHQASI 610 620 630 ILETVPFKSG QRQIQANMRS NKFKDIKGYR NVYVDFAL

References

	« Hide 'large scale' referencesShow '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: 9452468] [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: 11390390] [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: 15489334] [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: 15290349] [Abstract] Cited for: PROTEIN SEQUENCE OF 2-16, SUBCELLULAR LOCATION, ACETYLATION AT ALA-2, INDUCTION BY TPA AND CALCIUM, 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: 16380904] [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
EMBLGenBankDDBJ	AF035960 mRNA. Translation: AAC02978.1. AF035961 mRNA. Translation: AAC02979.1. AF206510 , AF206502, AF206503, AF206504, AF206505, AF206506, AF206507, AF206508, AF206509 Genomic DNA. Translation: AAF23981.1. BC119009 mRNA. Translation: AAI19010.1.
IPI	IPI00218650. IPI00873911.
RefSeq	NP_004236.1. NP_963925.2.
UniGene	Hs.129719
3D structure databases
HSSP	HSSP built from PDB template 1L9M based on UniProtKB Q08188.
ModBase	Search...
Protein-protein interaction databases
STRING	O43548.
PTM databases
PhosphoSite	O43548.
Proteomic databases
PRIDE	O43548.
Genome annotation databases
Ensembl	ENST00000220420; ENSP00000220420; ENSG00000104055; Homo sapiens. [Genome view] ENST00000349114; ENSP00000220419; ENSG00000104055; Homo sapiens. [Genome view] ENST00000396996; ENSP00000380192; ENSG00000104055; Homo sapiens. [Genome view]
GeneID	9333.
KEGG	hsa:9333.
UCSC	uc001zrd.1. human. uc001zre.1. human.
Organism-specific databases
CTD	9333.
GeneCards	GC15M041312.
H-InvDB	HIX0038074. HIX0038097.
HGNC	HGNC:11781. TGM5.
MIM	270300. phenotype. 603805. gene. 609796. phenotype.
Orphanet	817. Skin peeling syndrome.
PharmGKB	PA36494.
GenAtlas	Search...
Phylogenomic databases
HOGENOM	O43548.
HOVERGEN	O43548.
OMA	DDNGVLN.
Enzyme and pathway databases
BRENDA	2.3.2.13. 247.
Gene expression databases
ArrayExpress	O43548.
Bgee	O43548.
CleanEx	HS_TGM5.
Genevestigator	O43548.
GermOnline	ENSG00000104055. Homo sapiens.
Family and domain databases
InterPro	IPR008957. Fibronectin_typ-III-like_fold. IPR013783. Ig-like_fold. IPR002931. Transglutaminase-like. IPR008958. Transglutaminase_C. IPR013808. Transglutaminase_CS. IPR001102. Transglutaminase_N. [Graphical view]
Gene3D	G3DSA:2.60.40.30. FN_III-like. 1 hit. G3DSA:2.60.40.10. Ig-like_fold. 2 hits.
Pfam	PF00927. Transglut_C. 2 hits. PF01841. Transglut_core. 1 hit. PF00868. Transglut_N. 1 hit. [Graphical view]
SMART	SM00460. TGc. 1 hit. [Graphical view]
PROSITE	PS00547. TRANSGLUTAMINASES. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
DrugBank	DB00130. L-Glutamine.
NextBio	34961.
SOURCE	Search...

Entry information

Entry name

TGM5_HUMAN

Accession

Primary (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:	November 3, 2009
This is version 87 of the entry and version 4 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

Disclaimer

Any 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.