Literature summary for 2.7.1.183 extracted from

Zhu, Q.; Venzke, D.; Walimbe, A.S.; Anderson, M.E.; Fu, Q.; Kinch, L.N.; Wang, W.; Chen, X.; Grishin, N.V.; Huang, N.; Yu, L.; Dixon, J.E.; Campbell, K.P.; Xiao, J.
Structure of protein O-mannose kinase reveals a unique active site architecture (2016), eLife, 5, e22238 .

Search for more literature for 2.7.1.183

Cloned(Commentary)

Cloned (Comment)	Organism
gene POMK, recombinant expression of enzyme mutants in POMK knockout cells	Danio rerio

Crystallization (Commentary)

Crystallization (Comment)	Organism
purified enzyme POMK in complex with Mg2+ ions, ADP, aluminum fluoride, and the GalNAc-beta3-GlcNAc-beta4-Man trisaccharide substrate, X-ray diffraction structure determination and analysis at 2.0 A resolution	Danio rerio

Protein Variants

Protein Variants	Comment	Organism
A230E	site-directed mutagenesis, inactive mutant	Homo sapiens
C203A/C244A	site-directed mutagenesis, inactive mutant	Homo sapiens
D118A	site-directed mutagenesis, the mutant shows reduced activity compared to wild-type enzyme	Homo sapiens
D204A	site-directed mutagenesis, the mutant shows reduced activity compared to wild-type enzyme	Homo sapiens
D227A	site-directed mutagenesis, inactive mutant	Homo sapiens
D229G	site-directed mutagenesis, the mutant's activity is unaltered compared to wild-type enzyme	Homo sapiens
D229G/G122E	site-directed mutagenesis, inactive mutant	Danio rerio
D229G/G122E	site-directed mutagenesis, the mutant shows highly reduced activity compared to wild-type enzyme	Homo sapiens
K210A	site-directed mutagenesis, the mutation impairs the catalytic activity	Homo sapiens
K93A	site-directed mutagenesis, the mutation of this Lys in HsPOMK to Gly completely abolished kinase activity	Homo sapiens
K93G/S108K	site-directed mutagenesis, the catalytic activity is restored in the double mutant, which reinstalls the Lys in strand beta3. In fact, this mutant, having both the Gly-rich loop and the beta3 Lys restored, has enhanced kinase activity in vitro compared to the wild-type enzyme	Homo sapiens
L72A	site-directed mutagenesis	Danio rerio
additional information	disease-causing mutations, overview	Homo sapiens
additional information	generation of POMK knockout cells	Danio rerio
Q214A	site-directed mutagenesis, the mutant shows reduced activity compared to wild-type enzyme	Homo sapiens
Q258R	site-directed mutagenesis, inactive mutant	Homo sapiens
V302D	site-directed mutagenesis, inactive mutant	Homo sapiens

Localization

Localization	Comment	Organism	GeneOntology No.	Textmining
membrane	Homo sapiens POMK (HsPOMK) contains a type II transmembrane (TM) domain and a lumenal kinase domain	Homo sapiens	16020	-

Metals/Ions

Metals/Ions	Comment	Organism	Structure
Mg2+	required	Homo sapiens
Mg2+	required	Danio rerio

Natural Substrates/ Products (Substrates)

Natural Substrates	Organism	Comment (Nat. Sub.)	Natural Products	Comment (Nat. Pro.)	Rev.	Reac.
ATP + 3-O-[N-acetyl-beta-D-galactosaminyl-(1->3)-N-acetyl-beta-D-glucosaminyl-(1->4)-alpha-D-mannosyl]-L-seryl-[protein]	Homo sapiens	-	ADP + 3-O-[N-acetyl-beta-D-galactosaminyl-(1->3)-N-acetyl-beta-D-glucosaminyl-(1->4)-6-O-phosphono-alpha-D-mannosyl]-L-seryl-[protein]	-	?
ATP + 3-O-[N-acetyl-beta-D-galactosaminyl-(1->3)-N-acetyl-beta-D-glucosaminyl-(1->4)-alpha-D-mannosyl]-L-seryl-[protein]	Danio rerio	-	ADP + 3-O-[N-acetyl-beta-D-galactosaminyl-(1->3)-N-acetyl-beta-D-glucosaminyl-(1->4)-6-O-phosphono-alpha-D-mannosyl]-L-seryl-[protein]	-	?
ATP + 3-O-[N-acetyl-beta-D-galactosaminyl-(1->3)-N-acetyl-beta-D-glucosaminyl-(1->4)-alpha-D-mannosyl]-L-threonyl-[protein]	Homo sapiens	-	ADP + 3-O-[N-acetyl-beta-D-galactosaminyl-(1->3)-N-acetyl-beta-D-glucosaminyl-(1->4)-6-O-phosphono-alpha-D-mannosyl]-L-threonyl-[protein]	-	?
ATP + 3-O-[N-acetyl-beta-D-galactosaminyl-(1->3)-N-acetyl-beta-D-glucosaminyl-(1->4)-alpha-D-mannosyl]-L-threonyl-[protein]	Danio rerio	-	ADP + 3-O-[N-acetyl-beta-D-galactosaminyl-(1->3)-N-acetyl-beta-D-glucosaminyl-(1->4)-6-O-phosphono-alpha-D-mannosyl]-L-threonyl-[protein]	-	?

Organism

Organism	UniProt	Comment	Textmining
Danio rerio	Q5U3W1	-	-
Homo sapiens	Q9H5K3	-	-

Posttranslational Modification

Posttranslational Modification	Comment	Organism
glycoprotein	there are four potential N-linked glycosylation sites in the HsPOMK kinase domain: Asn67, Asn165, Asn220, and Asn235	Homo sapiens
no glycoprotein	no glycosylation site is present in DrPOMK	Danio rerio

Substrates and Products (Substrate)

Substrates	Comment Substrates	Organism	Products	Comment (Products)	Rev.	Reac.
ATP + 3-O-[N-acetyl-beta-D-galactosaminyl-(1->3)-N-acetyl-beta-D-glucosaminyl-(1->4)-alpha-D-mannosyl]-L-seryl-[protein]	-	Homo sapiens	ADP + 3-O-[N-acetyl-beta-D-galactosaminyl-(1->3)-N-acetyl-beta-D-glucosaminyl-(1->4)-6-O-phosphono-alpha-D-mannosyl]-L-seryl-[protein]	-	?
ATP + 3-O-[N-acetyl-beta-D-galactosaminyl-(1->3)-N-acetyl-beta-D-glucosaminyl-(1->4)-alpha-D-mannosyl]-L-seryl-[protein]	-	Danio rerio	ADP + 3-O-[N-acetyl-beta-D-galactosaminyl-(1->3)-N-acetyl-beta-D-glucosaminyl-(1->4)-6-O-phosphono-alpha-D-mannosyl]-L-seryl-[protein]	-	?
ATP + 3-O-[N-acetyl-beta-D-galactosaminyl-(1->3)-N-acetyl-beta-D-glucosaminyl-(1->4)-alpha-D-mannosyl]-L-threonyl-[protein]	-	Homo sapiens	ADP + 3-O-[N-acetyl-beta-D-galactosaminyl-(1->3)-N-acetyl-beta-D-glucosaminyl-(1->4)-6-O-phosphono-alpha-D-mannosyl]-L-threonyl-[protein]	-	?
ATP + 3-O-[N-acetyl-beta-D-galactosaminyl-(1->3)-N-acetyl-beta-D-glucosaminyl-(1->4)-alpha-D-mannosyl]-L-threonyl-[protein]	-	Danio rerio	ADP + 3-O-[N-acetyl-beta-D-galactosaminyl-(1->3)-N-acetyl-beta-D-glucosaminyl-(1->4)-6-O-phosphono-alpha-D-mannosyl]-L-threonyl-[protein]	-	?
additional information	enzyme POMK can efficiently phosphorylate the GalNAc-beta3-GlcNAc-b4-Man trisaccharide. GalNAc-beta3-GlcNAc-beta4-Man is recognized by a surface groove, and the GalNAc-beta3-GlcNAc moiety mediates the majority of interactions with POMK	Homo sapiens	?	-	-
additional information	enzyme POMK can efficiently phosphorylate the GalNAc-beta3-GlcNAc-beta4-Man trisaccharide. GalNAc-beta3-GlcNAc-beta4-Man is recognized by a surface groove, and the GalNAc-beta3-GlcNAc moiety mediates the majority of interactions with POMK. POMK specifically recognizes GalNAc-beta3-GlcNAc-beta4-mannose	Danio rerio	?	-	-

Subunits

Subunits	Comment	Organism
More	Homo sapiens POMK (HsPOMK) contains a type II transmembrane (TM) domain and a lumenal kinase domain	Homo sapiens

Synonyms

Synonyms	Comment	Organism
DrPOMK	-	Danio rerio
HsPOMK	-	Homo sapiens
POMK	-	Homo sapiens
POMK	-	Danio rerio
protein O-mannose kinase	-	Homo sapiens
protein O-mannose kinase	-	Danio rerio
SGK196	-	Homo sapiens
SGK196	-	Danio rerio

Cofactor

Cofactor	Comment	Organism	Structure
ATP	-	Homo sapiens
ATP	-	Danio rerio

General Information

General Information	Comment	Organism
evolution	POMK is highly conserved throughout evolution	Homo sapiens
evolution	POMK is highly conserved throughout evolution	Danio rerio
malfunction	loss of DrPOMK in Danio Rerio leads to disrupted muscle function	Danio rerio
malfunction	POMK mutations cause a spectrum of congenital and limb-girdle muscular dystrophies, including the most severe presentation known as the Walker-Warburg syndrome, which is associated with brain and eye abnormalities and death in early childhood. Disease-causing mutations, overview	Homo sapiens
metabolism	enzyme POMK plays a critical role for the biosynthesis of functional alpha-dystroglycan (alph-DG), alpha-DG is a subunit of the dystroglycan complex, and binds to basement membrane molecules such as laminin to connect the extracellular matrix with the actin cytoskeleton. alpha-DG is also a receptor for human pathogens	Homo sapiens
metabolism	enzyme POMK plays a critical role for the biosynthesis of functional alpha-dystroglycan (alph-DG), alpha-DG is a subunit of the dystroglycan complex, and binds to basement membrane molecules such as laminin to connect the extracellular matrix with the actin cytoskeleton. alpha-DG is also a receptor for human pathogens	Danio rerio
additional information	the structure of protein O-mannose kinase reveals a unique active site architecture. The active site of POMK is established by residues located in non-canonical positions and is stabilized by a disulfide bridge. Seven conserved Cys are present in POMK homologues, and six of them are involved in forming three pairs of disulfide bridges in DrPOMK. Cys53-Cys66 is located in a long loop in the backside of the N-lobe. Cys72-Cys139 connects helix alphaB and strand beta4. Cys201-Cys241 links the catalytic loop with the activation segment. Cys310 alone exists as a free cysteine and is buried in the C-lobe, not exposed to the solvent. DrPOMK kinase has a bilobal architecture. In POMK, a Ser (Ser106DrPOMK) occupies the position of the critical Lys72PKA in strand beta3. The critical role of this Lys in DrPOMK is instead served by Lys91_DrPOMK located at the beginning of strand beta2 that reaches into the active site and interacts with the phosphate groups of ADP. Another important Lys involved in nucleotide-binding is Lys208_DrPOMK located in helix alphaCL, it interacts with the AlF3 group that mimics the transition state gamma-phosphate of ATP	Danio rerio
physiological function	the 'pseudokinase' SgK196 is a protein O-mannose kinase (POMK) that catalyzes an essential phosphorylation step during biosynthesis of the laminin-binding glycan on alpha-dystroglycan	Homo sapiens
physiological function	the 'pseudokinase' SgK196 is a protein O-mannose kinase (POMK) that catalyzes an essential phosphorylation step during biosynthesis of the laminin-binding glycan on alpha-dystroglycan	Danio rerio

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Release 2023.1 (January 2023)