Literature summary for 2.4.1.174 extracted from

Shimbo, M.; Suzuki, R.; Fuseya, S.; Sato, T.; Kiyohara, K.; Hagiwara, K.; Okada, R.; Wakui, H.; Tsunakawa, Y.; Watanabe, H.; Kimata, K.; Narimatsu, H.; Kudo, T.; Takahashi, S.
Postnatal lethality and chondrodysplasia in mice lacking both chondroitin sulfate N-acetylgalactosaminyltransferase-1 and -2 (2017), PLoS ONE, 12, e0190333 .

Search for more literature for 2.4.1.174

Cloned(Commentary)

Cloned (Comment)	Organism
gene CSGALNACT1 or t1, quantitative RT-PCR enzyme expression analysis of CS glycosyltransferases	Mus musculus
gene CSGALNACT2 or t2, quantitative RT-PCR enzyme expression analysis of CS glycosyltransferases	Mus musculus

Protein Variants

Protein Variants	Comment	Organism
additional information	generation of single knockout T1 KO mutant and of double knockout mutant Col2-DKO, a chondrocyte-specific t1::t2 KO mutant, quantitative RT-PCR analysis of knee cartilage shows no or slight t1 and t2 gene expression in Col2-DKO mice compared with wild-type mice. t1::t2 double KO mice show severe dwarfism and postnatal lethality, pgenotype, overview	Mus musculus
additional information	generation of single knockout T2 KO mutant and of double knockout mutant Col2-DKO, a chondrocyte-specific t1::t2 KO mutant, quantitative RT-PCR analysis of knee cartilage shows no or slight t1 and t2 gene expression in Col2-DKO mice compared with wild-type mice. t1::t2 double KO mice show severe dwarfism and postnatal lethality, phenotype, overview	Mus musculus

Localization

Localization	Comment	Organism	GeneOntology No.	Textmining
cell membrane	-	Mus musculus	-	-

Natural Substrates/ Products (Substrates)

Natural Substrates	Organism	Comment (Nat. Sub.)	Natural Products	Comment (Nat. Pro.)	Rev.	Reac.
UDP-N-acetyl-D-galactosamine + beta-D-glucuronyl-(1->3)-D-galactosyl-proteoglycan	Mus musculus	-	UDP + N-acetyl-D-galactosaminyl-(1->4)-beta-D-glucuronyl-(1->3)-beta-D-galactosyl-proteoglycan	-	?
UDP-N-acetyl-D-galactosamine + beta-D-glucuronyl-(1->3)-D-galactosyl-proteoglycan	Mus musculus C57BL/6	-	UDP + N-acetyl-D-galactosaminyl-(1->4)-beta-D-glucuronyl-(1->3)-beta-D-galactosyl-proteoglycan	-	?

Organism

Organism	UniProt	Comment	Textmining
Mus musculus	Q8BJQ9	gene t1	-
Mus musculus	Q8C1F4	gene t2	-
Mus musculus C57BL/6	Q8BJQ9	gene t1	-
Mus musculus C57BL/6	Q8C1F4	gene t2	-

Source Tissue

Source Tissue	Comment	Organism	Textmining
bone	quantitative gene expression and in situ hybridization of genes associated with endochondral ossification	Mus musculus	-
cartilage	knee, quantitative RT-PCR enzyme expression analysis of CSGALNACT1	Mus musculus	-
cartilage	knee, quantitative RT-PCR enzyme expression analysis of CSGALNACT2	Mus musculus	-

Substrates and Products (Substrate)

Substrates	Comment Substrates	Organism	Products	Comment (Products)	Rev.	Reac.
UDP-N-acetyl-D-galactosamine + beta-D-glucuronyl-(1->3)-D-galactosyl-proteoglycan	-	Mus musculus	UDP + N-acetyl-D-galactosaminyl-(1->4)-beta-D-glucuronyl-(1->3)-beta-D-galactosyl-proteoglycan	-	?
UDP-N-acetyl-D-galactosamine + beta-D-glucuronyl-(1->3)-D-galactosyl-proteoglycan	-	Mus musculus C57BL/6	UDP + N-acetyl-D-galactosaminyl-(1->4)-beta-D-glucuronyl-(1->3)-beta-D-galactosyl-proteoglycan	-	?

Synonyms

Synonyms	Comment	Organism
chondroitin sulfate N-acetylgalactosaminyltransferase 1	-	Mus musculus
chondroitin sulfate N-acetylgalactosaminyltransferase 2	-	Mus musculus
CSGalNAcT1	-	Mus musculus
CSGALNACT2	-	Mus musculus

General Information

General Information	Comment	Organism
malfunction	impaired chndroitin sulfate (CS) content in cartilage and induction of abnormal endochondral ossification is caused by t1::t2 (CSGALNACT1/CSGALNACT2) double deficiency. DKO mice exhibit postnatal lethality, whereas t2 KO mice show normal size and skeletal development. Col2-DKO mice survive to adulthood and show severe dwarfism. Histological analysis of epiphyseal cartilage from Col2-DKO mice reveals disrupted endochondral ossification, characterized by drastic GAG reduction in the extracellular matrix. DKO cartilage has reduced chondrocyte proliferation and an increased number of apoptotic chondrocytes compared with wild-type cartilage. Conversely, primary chondrocyte cultures from Col2-DKO knee cartilage have the same proliferation rate as wild-type chondrocytes and low GAG expression levels, indicating that the chondrocytes themselves have an intact proliferative ability. Quantitative RT-PCR analysis of E18.5 cartilage shows that the expression levels of Col2a1 and Ptch1 transcripts tend to decrease in DKO compared with those in wild-type mice. Phenotype of t2 null mice, overview	Mus musculus
malfunction	t1 single knockout mice (t1 KO) exhibit slight dwarfism and a reduction in chondroitin sulfate (CS) content in cartilage compared with wild-type mice. Impaired chondroitin sulfate (CS) content in cartilage and induction of abnormal endochondral ossification is caused by t1::t2 (CSGALNACT1/CSGALNACT2) double deficiency. DKO mice exhibit postnatal lethality. Col2-DKO mice survive to adulthood and show severe dwarfism compared with t1 KO mice. Histological analysis of epiphyseal cartilage from Col2-DKO mice reveals disrupted endochondral ossification, characterized by drastic GAG reduction in the extracellular matrix. DKO cartilage has reduced chondrocyte proliferation and an increased number of apoptotic chondrocytes compared with wild-type cartilage. Conversely, primary chondrocyte cultures from Col2-DKO knee cartilage have the same proliferation rate as wild-type chondrocytes and low GAG expression levels, indicating that the chondrocytes themselves have an intact proliferative ability. Quantitative RT-PCR analysis of E18.5 cartilage shows that the expression levels of Col2a1 and Ptch1 transcripts tend to decrease in DKO compared with those in wild-type mice. The CS content in DKO cartilage is decreased compared with that in t1 KO cartilage	Mus musculus
metabolism	six glycosyltransferases are known to coordinately synthesize the backbone structure of chondroitin sulfate (CS). Two glycosyltransferases, Csgalnact1 (t1) and Csgalnact2 (t2), are critical for initiation of CS synthesis in vitro. According to an in vitro enzymatic characterization, among the six CS glycosyltransferases, only t1 and t2 possessed the ability to independently initiate CS synthesis. t1 efficiently transfers GalNAc onto the linkage tetrasaccharide in vitro, which is common to both CS and heparin sulfate/heparin, and t1 initiation activity is stronger than that of t2	Mus musculus
additional information	quantitative analysis of six CS glycosyltransferase transcripts using real-time RT-PCR	Mus musculus
physiological function	both chondroitin sulfate N-acetylgalactosaminyltransferase 1 (t1) and chondroitin sulfate N-acetylgalactosaminyltransferase 2 (t2) are necessary for chondroitin sulfate (CS) synthesis and normal chondrocyte differentiation but are not sufficient for all CS synthesis in cartilage. CS biosynthesis is initiated by the transfer of GalNAc residues to the linkage region, which consists of tetrasaccharide units of GlcUA-beta1,3-galactose (Gal)-beta1,3-Gal-beta1,4-xylose (Xyl) attached to the serine residues of the core proteins. This triggers CS elongation by alternating addition of GalNAc and GlcUA residues, which is catalyzed by six glycosyltransferases in mammals. Enzyme t1 and t2 are known to function in both initiation and elongation activity. t1 exhibits stronger initiation activity than t2, indicating that t1 has a vital role in CS synthesis initiation	Mus musculus
physiological function	both chondroitin sulfate N-acetylgalactosaminyltransferase 1 (t1) and chondroitin sulfate N-acetylgalactosaminyltransferase 2 (t2) are necessary for chondroitin sulfate (CS) synthesis and normal chondrocyte differentiation but are not sufficient for all CS synthesis in cartilage. CS biosynthesis is initiated by the transfer of GalNAc residues to the linkage region, which consists of tetrasaccharide units of GlcUA-beta1,3-galactose (Gal)-beta1,3-Gal-beta1,4-xylose (Xyl) attached to the serine residues of the core proteins. This triggers CS elongation by alternating addition of GalNAc and GlcUA residues, which is catalyzed by six glycosyltransferases in mammals. t1 and t2 are known to function in both initiation and elongation activity. Enzyme t1 exhibits stronger initiation activity than t2, indicating that t1 has a vital role in CS synthesis initiation	Mus musculus

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Release 2023.1 (January 2023)