Reviewed, UniProtKB/Swiss-Prot P22735 (TGM1_HUMAN)

Names and origin

Protein names

Recommended name:
    Protein-glutamine gamma-glutamyltransferase K
    EC=2.3.2.13
Alternative name(s):
    Transglutaminase K
      Short name=TGase K
      Short name=TGK
      Short name=TG(K)
    Transglutaminase-1
    Epidermal TGase

Gene names

Name:	TGM1
Synonyms:	KTG

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

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

Protein attributes

Sequence length	817 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Catalyzes the cross-linking of proteins and the conjugation of polyamines to proteins. Responsible for cross-linking epidermal proteins during formation of the stratum corneum.
Catalytic activity	Protein glutamine + alkylamine = protein N(5)-alkylglutamine + NH3.
Cofactor	Binds 1 calcium ion per subunit.
Subcellular location	Membrane; Lipid-anchor.
Post-translational modification	The membrane anchorage region possesses a cluster of five cysteines within which fatty acid(s) may become thioester-linked. It is subject to phorbol ester-stimulated phosphorylation and is hypersensitive to proteolysis, which releases the enzyme in a soluble form.
Involvement in disease	Defects in TGM1 are the cause of ichthyosis lamellar type 1 (LI1) [MIM:242300]. LI is a non-bullous ichthyosis, a skin disorder characterized by abnormal cornification of the epidermis. It is one the most severe forms of ichthyoses apparent at birth and persisting throughout life. LI patients are born encased in a tight, shiny, translucent covering called collodion membrane. Over the first weeks of life, the collodion membrane is gradually replaced by generalized large, dark brown, plate-like scales with minimal to no erythroderma. Tautness of facial skin commonly results in ectropion, eclabium and scarring alopecia of the scalp. Common complications are severe heat intolerance and recurrent ear infections. Ref.14 Ref.15 Ref.16 Ref.18 Defects in TGM1 are a cause of non-bullous congenital ichthyosiform erythroderma (NCIE) [MIM:242100]. NCIE is a non-bullous ichthyosis, a skin disorder characterized by abnormal cornification of the epidermis. Most affected individuals are born with a tight, shiny, translucent covering called collodion membrane. The collodion membrane subsequently evolves into generalized scaling and intense redness of the skin. Clinical features are milder than in lamellar ichthyoses and demonstrate a greater variability in the intensity of erythema, size and type of scales. In contrast to lamellar ichthyoses, scales are usually white, fine and powdery, and palms and soles are severely affected. Patients suffer from palmoplantar keratoderma, often with painful fissures, digital contractures, and loss of pulp volume. Ref.17
Sequence similarities	Belongs to the transglutaminase superfamily. Transglutaminase family.
Sequence caution	The sequence AAA61166.1 differs from that shown. Reason: Frameshift at position 16. The sequence M86360 differs from that shown. Reason: Frameshift at positions 16, 421 and 651.

Ontologies

Keywords
Biological process	Keratinization
Cellular component	Membrane
Coding sequence diversity	Polymorphism
Disease	Disease mutation Ichthyosis
Ligand	Calcium Metal-binding
Molecular function	Acyltransferase Transferase
PTM	Lipoprotein Phosphoprotein
Gene Ontology (GO)
Biological process	cell envelope organization Traceable author statement. Source: UniProtKB keratinization Inferred from electronic annotation. Source: UniProtKB-KW keratinocyte differentiation Inferred from direct assay. Source: UniProtKB peptide cross-linking Inferred from electronic annotation. Source: InterPro
Cellular component	cornified envelope Traceable author statement. Source: UniProtKB intrinsic to membrane Inferred from direct assay. Source: UniProtKB
Molecular function	acyltransferase activity Inferred from electronic annotation. Source: UniProtKB-KW calcium ion binding Inferred from electronic annotation. Source: UniProtKB-KW protein binding Inferred from physical interaction. Source: UniProtKB protein-glutamine gamma-glutamyltransferase activity Inferred from direct assay. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 817	817	Protein-glutamine gamma-glutamyltransferase K		PRO_0000213701
Regions
	Region	1 – 100	100	Membrane anchorage region
Sites
	Active site	377	1	By similarity
	Active site	436	1	By similarity
	Active site	459	1	By similarity
	Metal binding	499	1	Calcium By similarity
	Metal binding	501	1	Calcium By similarity
	Metal binding	548	1	Calcium By similarity
	Metal binding	553	1	Calcium By similarity
Amino acid modifications
	Modified residue	68	1	Phosphoserine By similarity
	Modified residue	92	1	Phosphoserine By similarity
	Modified residue	95	1	Phosphoserine By similarity
Natural variations
	Natural variant	42	1	S → Y in LI1. Ref.14		VAR_015220
	Natural variant	102	1	D → V in LI1. Ref.18		VAR_020918
	Natural variant	132	1	D → N: dbSNP rs2229462.		VAR_029268
	Natural variant	142	1	R → H in LI1. Ref.15 Ref.16		VAR_007476
	Natural variant	143	1	R → C in LI1 and NCIE.		VAR_007477
	Natural variant	143	1	R → H in LI1. Ref.15 Ref.16		VAR_007478
	Natural variant	218	1	G → S in LI1. Ref.16		VAR_007479
	Natural variant	289	1	N → T in LI1. Ref.18		VAR_020919
	Natural variant	307	1	R → W in LI1. Ref.18		VAR_020920
	Natural variant	323	1	R → Q in LI1. Ref.14		VAR_015221
	Natural variant	372	1	V → I		VAR_055374
	Natural variant	379	1	V → L in LI1 and NCIE.		VAR_007480
	Natural variant	389	1	R → H in NCIE. Ref.17		VAR_015222
	Natural variant	396	1	R → L in NCIE.		VAR_007481
	Natural variant	518	1	V → M: dbSNP rs35312232.		VAR_052550
	Natural variant	607	1	R → C: dbSNP rs2229464.		VAR_052551
	Natural variant	755	1	S → L: dbSNP rs35926651.		VAR_052552
	Natural variant	802	1	D → V: dbSNP rs2228337.		VAR_024660
Experimental info
	Sequence conflict	119 – 120	2	Missing in M86360. Ref.5
	Sequence conflict	301	1	C → A in AAA61156. Ref.4
	Sequence conflict	508	1	Q → H in M86360. Ref.5
	Sequence conflict	551	1	D → E in M86360. Ref.5
	Sequence conflict	554	1	R → A in AAA61166. Ref.3
	Sequence conflict	669	1	V → I in AAA61166. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	P22735-1 [UniParc]. Last modified January 4, 2005. Version 4. Checksum: 4732F28234F5D5F1	FASTA	817	89,787
	10 20 30 40 50 60 MMDGPRSDVG RWGGNPLQPP TTPSPEPEPE PDGRSRRGGG RSFWARCCGC CSCRNAADDD 70 80 90 100 110 120 WGPEPSDSRG RGSSSGTRRP GSRGSDSRRP VSRGSGVNAA GDGTIREGML VVNGVDLLSS 130 140 150 160 170 180 RSDQNRREHH TDEYEYDELI VRRGQPFHML LLLSRTYESS DRITLELLIG NNPEVGKGTH 190 200 210 220 230 240 VIIPVGKGGS GGWKAQVVKA SGQNLNLRVH TSPNAIIGKF QFTVRTQSDA GEFQLPFDPR 250 260 270 280 290 300 NEIYILFNPW CPEDIVYVDH EDWRQEYVLN ESGRIYYGTE AQIGERTWNY GQFDHGVLDA 310 320 330 340 350 360 CLYILDRRGM PYGGRGDPVN VSRVISAMVN SLDDNGVLIG NWSGDYSRGT NPSAWVGSVE 370 380 390 400 410 420 ILLSYLRTGY SVPYGQCWVF AGVTTTVLRC LGLATRTVTN FNSAHDTDTS LTMDIYFDEN 430 440 450 460 470 480 MKPLEHLNHD SVWNFHVWND CWMKRPDLPS GFDGWQVVDA TPQETSSGIF CCGPCSVESI 490 500 510 520 530 540 KNGLVYMKYD TPFIFAEVNS DKVYWQRQDD GSFKIVYVEE KAIGTLIVTK AISSNMREDI 550 560 570 580 590 600 TYLYKHPEGS DAERKAVETA AAHGSKPNVY ANRGSAEDVA MQVEAQDAVM GQDLMVSVML 610 620 630 640 650 660 INHSSSRRTV KLHLYLSVTF YTGVSGTIFK ETKKEVELAP GASDRVTMPV AYKEYRPHLV 670 680 690 700 710 720 DQGAMLLNVS GHVKESGQVL AKQHTFRLRT PDLSLTLLGA AVVGQECEVQ IVFKNPLPVT 730 740 750 760 770 780 LTNVVFRLEG SGLQRPKILN VGDIGGNETV TLRQSFVPVR PGPRQLIASL DSPQLSQVHG 790 800 810 VIQVDVAPAP GDGGFFSDAG GDSHLGETIP MASRGGA

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Primary structure of keratinocyte transglutaminase." Phillips M.A., Stewart B.E., Qin Q., Chakravarty R., Floyd E.E., Jetten A.M., Rice R.H. Proc. Natl. Acad. Sci. U.S.A. 87:9333-9337(1990) [PubMed: 1979171] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Molecular cloning of human epidermal transglutaminase cDNA from keratinocytes in culture." Yamanishi K., Liew F.M., Konishi K., Yasuno H., Doi H., Hirano J., Fukushima S. Biochem. Biophys. Res. Commun. 175:906-913(1991) [PubMed: 1673840] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Keratinocyte.
[3]	"The complete amino acid sequence of the human transglutaminase K enzyme deduced from the nucleic acid sequences of cDNA clones." Kim H.C., Idler W.W., Kim I.-G., Han J.H., Chung S.-I., Steinert P.M. J. Biol. Chem. 266:536-539(1991) [PubMed: 1670769] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[4]	"Genomic structure of keratinocyte transglutaminase. Recruitment of new exon for modified function." Phillips M.A., Stewart B.E., Rice R.H. J. Biol. Chem. 267:2282-2286(1992) [PubMed: 1346394] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Tissue: Placenta.
[5]	"Structure and organization of the human transglutaminase 1 gene." Kim I.-G., McBride O.W., Wang M., Kim S.-Y., Idler W.W., Steinert P.M. J. Biol. Chem. 267:7710-7717(1992) [PubMed: 1348508] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[6]	"Structure of the gene for human transglutaminase 1." Yamanishi K., Inazawa J., Liew F., Nonomura K., Ariyama T., Yasuno H., Abe T., Doi H., Hirano J., Fukushima S. J. Biol. Chem. 267:17858-17863(1992) [PubMed: 1381356] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Tissue: Placenta.
[7]	"Organization and evolution of the human epidermal keratinocyte transglutaminase I gene." Polakowska R.R., Eickbush T., Falciano V., Razvi F., Goldsmith L.A. Proc. Natl. Acad. Sci. U.S.A. 89:4476-4480(1992) [PubMed: 1350092] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Tissue: Placenta.
[8]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Oesophagus.
[9]	NIEHS SNPs program Submitted (MAY-2006) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS TYR-42; ILE-372; MET-518; CYS-607; LEU-755 AND VAL-802.
[10]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[11]	"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]. Tissue: Skin.
[12]	"Isolation of cDNA for human epidermal type I transglutaminase." Polakowska R., Herting E., Goldsmith L.A. J. Invest. Dermatol. 96:285-288(1991) [PubMed: 1704039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 6-551.
[13]	"Type I keratinocyte transglutaminase: expression in human skin and psoriasis." Schroeder W., Thacher S., Stewart-Galetka S., Annarella M., Chema D., Sicliano M., Davies P., Tang H.Y., Sowa B., Duvic M. J. Invest. Dermatol. 99:27-34(1992) [PubMed: 1351505] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 375-817. Tissue: Skin.
[14]	"Mutations of keratinocyte transglutaminase in lamellar ichthyosis." Huber M., Rettler I., Bernasconi K., Frenk E., Lavrijsen S.P.M., Ponec M., Bon A., Lautenschlager S., Schorderet D.F., Hohl D. Science 267:525-528(1995) [PubMed: 7824952] [Abstract] Cited for: VARIANTS LI1 TYR-42 AND GLN-323.
[15]	"Mutations in the gene for transglutaminase 1 in autosomal recessive lamellar ichthyosis." Russell L.J., Digiovanna J.J., Rogers G.R., Steinert P.M., Hashem N., Compton J.G., Bale S.J. Nat. Genet. 9:279-283(1995) [PubMed: 7773290] [Abstract] Cited for: VARIANTS LI1 HIS-142 AND HIS-143.
[16]	"Transglutaminase 1 mutations in autosomal recessive congenital ichthyosis: private and recurrent mutations in an isolated population." Laiho E., Ignatius J., Mikkola H., Yee V.C., Teller D.C., Niemi K.-M., Saarialho-Kere U., Kere J., Palotie A. Am. J. Hum. Genet. 61:529-538(1997) [PubMed: 9326318] [Abstract] Cited for: VARIANTS LI1/NCIE HIS-142; CYS-143; SER-218; LEU-379 AND LEU-396.
[17]	"Novel mutations of TGM1 in a child with congenital ichthyosiform erythroderma." Akiyama M., Takizawa Y., Kokaji T., Shimizu H. Br. J. Dermatol. 144:401-407(2001) [PubMed: 11251583] [Abstract] Cited for: VARIANT NCIE HIS-389.
[18]	"Novel mutations of the transglutaminase 1 gene in lamellar ichthyosis." Yang J.M., Ahn K.S., Cho M.O., Yoneda K., Lee C.H., Lee J.H., Lee E.S., Candi E., Melino G., Ahvazi B., Steinert P.M. J. Invest. Dermatol. 117:214-218(2001) [PubMed: 11511296] [Abstract] Cited for: VARIANTS LI1 VAL-102; THR-289 AND TRP-307.
+	Additional computationally mapped references.

Web resources

GeneReviews

NIEHS-SNPs

Cross-references

Sequence databases
EMBLGenBankDDBJ	M55183 mRNA. Translation: AAA59474.1. D90287 mRNA. Translation: BAA14329.1. M62925 mRNA. Translation: AAA61166.1. Frameshift. M83230 , M83227, M83228, M83229 Genomic DNA. Translation: AAA61156.1. M86360 Genomic DNA. No translation available. D10353 Genomic DNA. Translation: BAA34203.1. M98447 Genomic DNA. Translation: AAA96667.1. AK315843 mRNA. Translation: BAF98734.1. DQ640500 Genomic DNA. Translation: ABF70204.1. CH471078 Genomic DNA. Translation: EAW66047.1. BC034699 mRNA. Translation: AAH34699.1. X57974 mRNA. Translation: CAA41040.1.
IPI	IPI00305622.
PIR	TGHUM1. A43401.
RefSeq	NP_000350.1.
UniGene	Hs.508950
3D structure databases
HSSP	HSSP built from PDB template 1QRK based on UniProtKB P00488.
ModBase	Search...
PTM databases
PhosphoSite	P22735.
Proteomic databases
PeptideAtlas	P22735.
PRIDE	P22735.
Genome annotation databases
Ensembl	ENSG00000092295. Homo sapiens. [Contig view]
GeneID	7051.
KEGG	hsa:7051.
Organism-specific databases
GeneCards	GC14M023788.
H-InvDB	HIX0026666.
HGNC	HGNC:11777. TGM1.
HPA	CAB015159.
MIM	190195. gene. 242100. phenotype. 242300. phenotype.
Orphanet	79394. Erythroderma, congenital ichthyosiform, nonbullous. 313. Ichthyosis, lamellar.
PharmGKB	PA36490.
GenAtlas	Search...
Phylogenomic databases
HOGENOM	P22735.
HOVERGEN	P22735.
OMA	P22735. CGCCSCR.
Enzyme and pathway databases
BRENDA	2.3.2.13. 247.
Gene expression databases
ArrayExpress	P22735.
Bgee	P22735.
CleanEx	HS_TGM1.
GermOnline	ENSG00000092295. 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. 1 hit.
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	27569.
SOURCE	Search...

Entry information

Entry name

TGM1_HUMAN

Accession

Primary (citable) accession number: P22735
Secondary accession number(s): Q197M4

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 1, 1991
Last sequence update:	January 4, 2005
Last modified:	June 16, 2009
This is version 101 of the entry and version 4 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)