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UniProtKB/Swiss-Prot P22735 (TGM1_HUMAN)
Last modified
November 3, 2009.
Version 107.
History...
Clusters with 100%,
90%,
50% identity |
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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 |
| ||||
| 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 | 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 | |
| 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.15 Ref.16 Ref.17 Ref.19 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.18 Defects in TGM1 are a cause of autosomal recessive congenital ichthyosis (ARCI) [MIM:242300]. A clinically heterogeneous group of cornification disorders. The clinical hallmark is epidermal scaling, but patients may also have collodion membrane at birth, ectropion, eclabium, alopecia, palmo-plantar hyperkeratosis, hypohidrosis, and/or variable erythema. ARCI is classically divided into lamellar ichthyosis and non-bullous congenital ichthyosiform erythroderma. |
| 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
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.15 Ref.9 | VAR_015220 | |||||
| Natural variant | 53 | 1 | C → S in ARCI. | VAR_058638 | |||||
| Natural variant | 94 | 1 | G → D in ARCI. | VAR_058639 | |||||
| Natural variant | 102 | 1 | D → V in LI1. Ref.19 | VAR_020918 | |||||
| Natural variant | 126 | 1 | R → C in ARCI. | VAR_058640 | |||||
| Natural variant | 126 | 1 | R → H in ARCI. | VAR_058641 | |||||
| Natural variant | 132 | 1 | D → N: dbSNP rs2229462. | VAR_029268 | |||||
| Natural variant | 134 | 1 | Y → C in ARCI. | VAR_058642 | |||||
| Natural variant | 142 | 1 | R → C in ARCI. | VAR_058643 | |||||
| Natural variant | 142 | 1 | R → H in LI1. Ref.16 Ref.17 | VAR_007476 | |||||
| Natural variant | 142 | 1 | R → P in ARCI. | VAR_058644 | |||||
| Natural variant | 143 | 1 | R → C in LI1 and NCIE. Ref.17 | VAR_007477 | |||||
| Natural variant | 143 | 1 | R → H in LI1. Ref.16 | VAR_007478 | |||||
| Natural variant | 144 | 1 | G → E in ARCI. | VAR_058645 | |||||
| Natural variant | 144 | 1 | G → R in ARCI. | VAR_058646 | |||||
| Natural variant | 160 | 1 | S → C in ARCI. | VAR_058647 | |||||
| Natural variant | 205 | 1 | L → Q in ARCI. | VAR_058648 | |||||
| Natural variant | 209 | 1 | V → F in ARCI. | VAR_058649 | |||||
| Natural variant | 218 | 1 | G → S in LI1. Ref.17 | VAR_007479 | |||||
| Natural variant | 225 | 1 | R → H in ARCI. | VAR_058650 | |||||
| Natural variant | 225 | 1 | R → P in ARCI. | VAR_058651 | |||||
| Natural variant | 243 | 1 | I → S in ARCI. | VAR_058652 | |||||
| Natural variant | 249 | 1 | P → L in ARCI. | VAR_058653 | |||||
| Natural variant | 264 | 1 | R → Q in ARCI. | VAR_058654 | |||||
| Natural variant | 264 | 1 | R → W in ARCI. | VAR_058655 | |||||
| Natural variant | 272 | 1 | S → P in ARCI. | VAR_058656 | |||||
| Natural variant | 276 | 1 | Y → N in ARCI. | VAR_058657 | |||||
| Natural variant | 278 | 1 | G → R in ARCI. | VAR_058658 | |||||
| Natural variant | 285 | 1 | E → K in ARCI. | VAR_058659 | |||||
| Natural variant | 286 | 1 | R → Q in ARCI. | VAR_058660 | |||||
| Natural variant | 289 | 1 | N → T in LI1. Ref.19 | VAR_020919 | |||||
| Natural variant | 293 | 1 | F → V in ARCI. | VAR_058661 | |||||
| Natural variant | 304 | 1 | I → F in ARCI. | VAR_058662 | |||||
| Natural variant | 307 | 1 | R → G in ARCI. | VAR_058663 | |||||
| Natural variant | 307 | 1 | R → W in LI1. Ref.19 | VAR_020920 | |||||
| Natural variant | 315 | 1 | R → C in ARCI. | VAR_058664 | |||||
| Natural variant | 315 | 1 | R → H in ARCI. | VAR_058665 | |||||
| Natural variant | 315 | 1 | R → L in ARCI. | VAR_058666 | |||||
| Natural variant | 323 | 1 | R → Q in LI1. Ref.15 | VAR_015221 | |||||
| Natural variant | 323 | 1 | R → W in ARCI. | VAR_058667 | |||||
| Natural variant | 330 | 1 | N → H in ARCI. | VAR_058668 | |||||
| Natural variant | 331 | 1 | S → P in ARCI. | VAR_058669 | |||||
| Natural variant | 342 | 1 | W → R in ARCI. | VAR_058670 | |||||
| Natural variant | 358 | 1 | S → R in ARCI. | VAR_058671 | |||||
| Natural variant | 359 | 1 | V → M in ARCI. | VAR_058672 | |||||
| Natural variant | 365 | 1 | Y → D in ARCI. | VAR_058673 | |||||
| Natural variant | 366 | 1 | L → P in ARCI. | VAR_058674 | |||||
| Natural variant | 372 | 1 | V → I | VAR_055374 | |||||
| Natural variant | 379 | 1 | V → L in LI1 and NCIE. Ref.17 | VAR_007480 | |||||
| Natural variant | 382 | 1 | G → R in ARCI. | VAR_058675 | |||||
| Natural variant | 383 | 1 | V → M in ARCI. | VAR_058676 | |||||
| Natural variant | 389 | 1 | R → H in NCIE. Ref.18 | VAR_015222 | |||||
| Natural variant | 389 | 1 | R → P in ARCI. | VAR_058677 | |||||
| Natural variant | 392 | 1 | G → D in ARCI. | VAR_058678 | |||||
| Natural variant | 396 | 1 | R → H in ARCI. | VAR_058679 | |||||
| Natural variant | 396 | 1 | R → L in NCIE. Ref.17 | VAR_007481 | |||||
| Natural variant | 396 | 1 | R → S in ARCI. | VAR_058680 | |||||
| Natural variant | 401 | 1 | F → V in ARCI. | VAR_058681 | |||||
| Natural variant | 430 | 1 | D → V in ARCI. | VAR_058682 | |||||
| Natural variant | 473 | 1 | G → S in ARCI. | VAR_058683 | |||||
| Natural variant | 490 | 1 | D → G in ARCI. | VAR_058684 | |||||
| Natural variant | 518 | 1 | V → M: dbSNP rs35312232. Ref.9 | VAR_052550 | |||||
| Natural variant | 520 | 1 | E → G in ARCI. | VAR_058685 | |||||
| Natural variant | 544 | 1 | Y → C in ARCI. | VAR_058686 | |||||
| Natural variant | 607 | 1 | R → C: dbSNP rs2229464. Ref.9 | VAR_052551 | |||||
| Natural variant | 687 | 1 | R → C in ARCI. | VAR_058687 | |||||
| Natural variant | 687 | 1 | R → H in ARCI. | VAR_058688 | |||||
| Natural variant | 755 | 1 | S → L: dbSNP rs35926651. Ref.9 | VAR_052552 | |||||
| Natural variant | 764 | 1 | R → C in ARCI. | VAR_058689 | |||||
| Natural variant | 802 | 1 | D → V: dbSNP rs2228337. Ref.9 | 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
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References
| « Hide '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. 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. 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] | "Transglutaminase-1 gene mutations in autosomal recessive congenital ichthyosis: summary of mutations (including 23 novel) and modeling of TGase-1." Herman M.L., Farasat S., Steinbach P.J., Wei M.H., Toure O., Fleckman P., Blake P., Bale S.J., Toro J.R. Hum. Mutat. 30:537-547(2009) [PubMed: 19241467] [Abstract] Cited for: REVIEW ON VARIANTS. |
| [15] | "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. |
| [16] | "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. |
| [17] | "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. |
| [18] | "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. |
| [19] | "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. |
Cross-references
Sequence databases | |
|---|---|
| M55183 mRNA. Translation: AAA59474.1. D90287 mRNA. Translation: BAA14329.1. M62925 mRNA. Translation: AAA61166.1. Frameshift. M83230 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... |
Protein-protein interaction databases | |
| STRING | P22735. |
PTM databases | |
| PhosphoSite | P22735. |
Proteomic databases | |
| PeptideAtlas | P22735. |
| PRIDE | P22735. |
Genome annotation databases | |
| Ensembl | ENST00000206765; ENSP00000206765; ENSG00000092295; Homo sapiens. [Genome view] |
| GeneID | 7051. |
| KEGG | hsa:7051. |
| UCSC | uc001wod.1. human. |
Organism-specific databases | |
| CTD | 7051. |
| 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 | CGCCSCR. |
Enzyme and pathway databases | |
| BRENDA | 2.3.2.13. 247. |
Gene expression databases | |
| ArrayExpress | P22735. |
| Bgee | P22735. |
| CleanEx | HS_TGM1. |
| Genevestigator | P22735. |
| 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 |
| ||||||||
| 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. | ||||||||
Relevant documents
| Human chromosome 14 Human chromosome 14: entries, gene names and cross-references to MIM |
| Human entries with polymorphisms or disease mutations List of human entries with polymorphisms or disease mutations |
| Human polymorphisms and disease mutations Index of human polymorphisms and disease mutations |
| MIM cross-references Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot |
| SIMILARITY comments Index of protein domains and families |

Clusters with


