UniProt functional annotation for Q08188



	UniProt functional annotation for Q08188

UniProt code: Q08188.

Organism: Homo sapiens (Human).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.

Function: 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. {ECO:0000250}.

Catalytic activity: Reaction=L-glutaminyl-[protein] + L-lysyl-[protein] = [protein]-L- lysyl-N(6)-5-L-glutamyl-[protein] + NH4(+); Xref=Rhea:RHEA:54816, Rhea:RHEA-COMP:9752, Rhea:RHEA-COMP:10207, Rhea:RHEA-COMP:14005, ChEBI:CHEBI:28938, ChEBI:CHEBI:29969, ChEBI:CHEBI:30011, ChEBI:CHEBI:138370; EC=2.3.2.13; Evidence={ECO:0000255|PROSITE- ProRule:PRU10024, ECO:0000269|PubMed:11980702, ECO:0000269|PubMed:12679341, ECO:0000269|PubMed:27866708};

Cofactor: Name=Ca(2+); Xref=ChEBI:CHEBI:29108; Evidence={ECO:0000269|PubMed:11980702, ECO:0000269|PubMed:12679341}; Note=Binds 3 Ca(2+) cations per subunit. Binds 1 Ca(2+) as a zymogen, and binds 2 more Ca(2+) cations, or other divalent metal cations, after proteolytic processing. {ECO:0000269|PubMed:11980702, ECO:0000269|PubMed:12679341};

Subunit: Consists of two polypeptide chains, which are synthesized as a precursor form of a single polypeptide. {ECO:0000269|PubMed:11980702, ECO:0000269|PubMed:12679341}.

Subcellular location: Cytoplasm {ECO:0000269|PubMed:27866708}.

Ptm: 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). {ECO:0000269|PubMed:16565075, ECO:0000269|PubMed:8099584}.

Disease: Uncombable hair syndrome 2 (UHS2) [MIM:617251]: A form of uncombable hair syndrome, a condition characterized by scalp hair that is impossible to comb due to the haphazard arrangement of the hair bundles. A characteristic morphologic feature is a triangular to reniform to heart shape on cross-sections, and a groove, canal or flattening along the entire length of the hair. Most individuals are affected early in childhood and the hair takes on a spun-glass appearance with the hair becoming dry, curly, glossy, lighter in color, and progressively uncombable. The hair growth rate can range from slow to normal, and the condition improves with age. {ECO:0000269|PubMed:27866708}. Note=The disease is caused by variants affecting the gene represented in this entry.

Similarity: Belongs to the transglutaminase superfamily. Transglutaminase family. {ECO:0000305}.

Annotations taken from UniProtKB at the EBI.


Organism:		Homo sapiens (Human).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.



Function:		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. {ECO:0000250}.


Catalytic activity:		Reaction=L-glutaminyl-[protein] + L-lysyl-[protein] = [protein]-L- lysyl-N(6)-5-L-glutamyl-[protein] + NH4(+); Xref=Rhea:RHEA:54816, Rhea:RHEA-COMP:9752, Rhea:RHEA-COMP:10207, Rhea:RHEA-COMP:14005, ChEBI:CHEBI:28938, ChEBI:CHEBI:29969, ChEBI:CHEBI:30011, ChEBI:CHEBI:138370; EC=2.3.2.13; Evidence={ECO:0000255\|PROSITE- ProRule:PRU10024, ECO:0000269\|PubMed:11980702, ECO:0000269\|PubMed:12679341, ECO:0000269\|PubMed:27866708};
Cofactor:		Name=Ca(2+); Xref=ChEBI:CHEBI:29108; Evidence={ECO:0000269\|PubMed:11980702, ECO:0000269\|PubMed:12679341}; Note=Binds 3 Ca(2+) cations per subunit. Binds 1 Ca(2+) as a zymogen, and binds 2 more Ca(2+) cations, or other divalent metal cations, after proteolytic processing. {ECO:0000269\|PubMed:11980702, ECO:0000269\|PubMed:12679341};
Subunit:		Consists of two polypeptide chains, which are synthesized as a precursor form of a single polypeptide. {ECO:0000269\|PubMed:11980702, ECO:0000269\|PubMed:12679341}.
Subcellular location:		Cytoplasm {ECO:0000269\|PubMed:27866708}.
Ptm:		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). {ECO:0000269\|PubMed:16565075, ECO:0000269\|PubMed:8099584}.
Disease:		Uncombable hair syndrome 2 (UHS2) [MIM:617251]: A form of uncombable hair syndrome, a condition characterized by scalp hair that is impossible to comb due to the haphazard arrangement of the hair bundles. A characteristic morphologic feature is a triangular to reniform to heart shape on cross-sections, and a groove, canal or flattening along the entire length of the hair. Most individuals are affected early in childhood and the hair takes on a spun-glass appearance with the hair becoming dry, curly, glossy, lighter in color, and progressively uncombable. The hair growth rate can range from slow to normal, and the condition improves with age. {ECO:0000269\|PubMed:27866708}. Note=The disease is caused by variants affecting the gene represented in this entry.
Similarity:		Belongs to the transglutaminase superfamily. Transglutaminase family. {ECO:0000305}.