3VZC

Crystal structure of Sphingosine Kinase 1 with inhibitor

Functional Information from GO Data

Chain	GOid	namespace	contents
A	0000166	molecular_function	nucleotide binding
A	0000287	molecular_function	magnesium ion binding
A	0001727	molecular_function	lipid kinase activity
A	0003376	biological_process	sphingosine-1-phosphate receptor signaling pathway
A	0003677	molecular_function	DNA binding
A	0005515	molecular_function	protein binding
A	0005516	molecular_function	calmodulin binding
A	0005524	molecular_function	ATP binding
A	0005634	cellular_component	nucleus
A	0005654	cellular_component	nucleoplasm
A	0005737	cellular_component	cytoplasm
A	0005829	cellular_component	cytosol
A	0005886	cellular_component	plasma membrane
A	0005905	cellular_component	clathrin-coated pit
A	0006473	biological_process	protein acetylation
A	0006629	biological_process	lipid metabolic process
A	0006670	biological_process	sphingosine metabolic process
A	0008289	molecular_function	lipid binding
A	0008481	molecular_function	sphingosine kinase activity
A	0010008	cellular_component	endosome membrane
A	0010468	biological_process	regulation of gene expression
A	0010803	biological_process	regulation of tumor necrosis factor-mediated signaling pathway
A	0016301	molecular_function	kinase activity
A	0016407	molecular_function	acetyltransferase activity
A	0016740	molecular_function	transferase activity
A	0019722	biological_process	calcium-mediated signaling
A	0030100	biological_process	regulation of endocytosis
A	0030139	cellular_component	endocytic vesicle
A	0030148	biological_process	sphingolipid biosynthetic process
A	0030307	biological_process	positive regulation of cell growth
A	0030335	biological_process	positive regulation of cell migration
A	0031398	biological_process	positive regulation of protein ubiquitination
A	0031410	cellular_component	cytoplasmic vesicle
A	0031901	cellular_component	early endosome membrane
A	0032740	biological_process	positive regulation of interleukin-17 production
A	0034248	biological_process	regulation of amide metabolic process
A	0034612	biological_process	response to tumor necrosis factor
A	0035556	biological_process	intracellular signal transduction
A	0035924	biological_process	cellular response to vascular endothelial growth factor stimulus
A	0038036	molecular_function	sphingosine-1-phosphate receptor activity
A	0043066	biological_process	negative regulation of apoptotic process
A	0045202	cellular_component	synapse
A	0045766	biological_process	positive regulation of angiogenesis
A	0045931	biological_process	positive regulation of mitotic cell cycle
A	0045987	biological_process	positive regulation of smooth muscle contraction
A	0046512	biological_process	sphingosine biosynthetic process
A	0046521	biological_process	sphingoid catabolic process
A	0046890	biological_process	regulation of lipid biosynthetic process
A	0048146	biological_process	positive regulation of fibroblast proliferation
A	0050764	biological_process	regulation of phagocytosis
A	0051049	biological_process	regulation of transport
A	0051092	biological_process	positive regulation of NF-kappaB transcription factor activity
A	0051239	biological_process	regulation of multicellular organismal process
A	0051721	molecular_function	protein phosphatase 2A binding
A	0071363	biological_process	cellular response to growth factor stimulus
A	0098793	cellular_component	presynapse
A	0150077	biological_process	regulation of neuroinflammatory response
A	1900060	biological_process	negative regulation of ceramide biosynthetic process
A	1900745	biological_process	positive regulation of p38MAPK cascade
A	1901224	biological_process	positive regulation of non-canonical NF-kappaB signal transduction
A	1903978	biological_process	regulation of microglial cell activation
A	1905364	biological_process	regulation of endosomal vesicle fusion
B	0000166	molecular_function	nucleotide binding
B	0000287	molecular_function	magnesium ion binding
B	0001727	molecular_function	lipid kinase activity
B	0003376	biological_process	sphingosine-1-phosphate receptor signaling pathway
B	0003677	molecular_function	DNA binding
B	0005515	molecular_function	protein binding
B	0005516	molecular_function	calmodulin binding
B	0005524	molecular_function	ATP binding
B	0005634	cellular_component	nucleus
B	0005654	cellular_component	nucleoplasm
B	0005737	cellular_component	cytoplasm
B	0005829	cellular_component	cytosol
B	0005886	cellular_component	plasma membrane
B	0005905	cellular_component	clathrin-coated pit
B	0006473	biological_process	protein acetylation
B	0006629	biological_process	lipid metabolic process
B	0006670	biological_process	sphingosine metabolic process
B	0008289	molecular_function	lipid binding
B	0008481	molecular_function	sphingosine kinase activity
B	0010008	cellular_component	endosome membrane
B	0010468	biological_process	regulation of gene expression
B	0010803	biological_process	regulation of tumor necrosis factor-mediated signaling pathway
B	0016301	molecular_function	kinase activity
B	0016407	molecular_function	acetyltransferase activity
B	0016740	molecular_function	transferase activity
B	0019722	biological_process	calcium-mediated signaling
B	0030100	biological_process	regulation of endocytosis
B	0030139	cellular_component	endocytic vesicle
B	0030148	biological_process	sphingolipid biosynthetic process
B	0030307	biological_process	positive regulation of cell growth
B	0030335	biological_process	positive regulation of cell migration
B	0031398	biological_process	positive regulation of protein ubiquitination
B	0031410	cellular_component	cytoplasmic vesicle
B	0031901	cellular_component	early endosome membrane
B	0032740	biological_process	positive regulation of interleukin-17 production
B	0034248	biological_process	regulation of amide metabolic process
B	0034612	biological_process	response to tumor necrosis factor
B	0035556	biological_process	intracellular signal transduction
B	0035924	biological_process	cellular response to vascular endothelial growth factor stimulus
B	0038036	molecular_function	sphingosine-1-phosphate receptor activity
B	0043066	biological_process	negative regulation of apoptotic process
B	0045202	cellular_component	synapse
B	0045766	biological_process	positive regulation of angiogenesis
B	0045931	biological_process	positive regulation of mitotic cell cycle
B	0045987	biological_process	positive regulation of smooth muscle contraction
B	0046512	biological_process	sphingosine biosynthetic process
B	0046521	biological_process	sphingoid catabolic process
B	0046890	biological_process	regulation of lipid biosynthetic process
B	0048146	biological_process	positive regulation of fibroblast proliferation
B	0050764	biological_process	regulation of phagocytosis
B	0051049	biological_process	regulation of transport
B	0051092	biological_process	positive regulation of NF-kappaB transcription factor activity
B	0051239	biological_process	regulation of multicellular organismal process
B	0051721	molecular_function	protein phosphatase 2A binding
B	0071363	biological_process	cellular response to growth factor stimulus
B	0098793	cellular_component	presynapse
B	0150077	biological_process	regulation of neuroinflammatory response
B	1900060	biological_process	negative regulation of ceramide biosynthetic process
B	1900745	biological_process	positive regulation of p38MAPK cascade
B	1901224	biological_process	positive regulation of non-canonical NF-kappaB signal transduction
B	1903978	biological_process	regulation of microglial cell activation
B	1905364	biological_process	regulation of endosomal vesicle fusion
C	0000166	molecular_function	nucleotide binding
C	0000287	molecular_function	magnesium ion binding
C	0001727	molecular_function	lipid kinase activity
C	0003376	biological_process	sphingosine-1-phosphate receptor signaling pathway
C	0003677	molecular_function	DNA binding
C	0005515	molecular_function	protein binding
C	0005516	molecular_function	calmodulin binding
C	0005524	molecular_function	ATP binding
C	0005634	cellular_component	nucleus
C	0005654	cellular_component	nucleoplasm
C	0005737	cellular_component	cytoplasm
C	0005829	cellular_component	cytosol
C	0005886	cellular_component	plasma membrane
C	0005905	cellular_component	clathrin-coated pit
C	0006473	biological_process	protein acetylation
C	0006629	biological_process	lipid metabolic process
C	0006670	biological_process	sphingosine metabolic process
C	0008289	molecular_function	lipid binding
C	0008481	molecular_function	sphingosine kinase activity
C	0010008	cellular_component	endosome membrane
C	0010468	biological_process	regulation of gene expression
C	0010803	biological_process	regulation of tumor necrosis factor-mediated signaling pathway
C	0016301	molecular_function	kinase activity
C	0016407	molecular_function	acetyltransferase activity
C	0016740	molecular_function	transferase activity
C	0019722	biological_process	calcium-mediated signaling
C	0030100	biological_process	regulation of endocytosis
C	0030139	cellular_component	endocytic vesicle
C	0030148	biological_process	sphingolipid biosynthetic process
C	0030307	biological_process	positive regulation of cell growth
C	0030335	biological_process	positive regulation of cell migration
C	0031398	biological_process	positive regulation of protein ubiquitination
C	0031410	cellular_component	cytoplasmic vesicle
C	0031901	cellular_component	early endosome membrane
C	0032740	biological_process	positive regulation of interleukin-17 production
C	0034248	biological_process	regulation of amide metabolic process
C	0034612	biological_process	response to tumor necrosis factor
C	0035556	biological_process	intracellular signal transduction
C	0035924	biological_process	cellular response to vascular endothelial growth factor stimulus
C	0038036	molecular_function	sphingosine-1-phosphate receptor activity
C	0043066	biological_process	negative regulation of apoptotic process
C	0045202	cellular_component	synapse
C	0045766	biological_process	positive regulation of angiogenesis
C	0045931	biological_process	positive regulation of mitotic cell cycle
C	0045987	biological_process	positive regulation of smooth muscle contraction
C	0046512	biological_process	sphingosine biosynthetic process
C	0046521	biological_process	sphingoid catabolic process
C	0046890	biological_process	regulation of lipid biosynthetic process
C	0048146	biological_process	positive regulation of fibroblast proliferation
C	0050764	biological_process	regulation of phagocytosis
C	0051049	biological_process	regulation of transport
C	0051092	biological_process	positive regulation of NF-kappaB transcription factor activity
C	0051239	biological_process	regulation of multicellular organismal process
C	0051721	molecular_function	protein phosphatase 2A binding
C	0071363	biological_process	cellular response to growth factor stimulus
C	0098793	cellular_component	presynapse
C	0150077	biological_process	regulation of neuroinflammatory response
C	1900060	biological_process	negative regulation of ceramide biosynthetic process
C	1900745	biological_process	positive regulation of p38MAPK cascade
C	1901224	biological_process	positive regulation of non-canonical NF-kappaB signal transduction
C	1903978	biological_process	regulation of microglial cell activation
C	1905364	biological_process	regulation of endosomal vesicle fusion
D	0000166	molecular_function	nucleotide binding
D	0000287	molecular_function	magnesium ion binding
D	0001727	molecular_function	lipid kinase activity
D	0003376	biological_process	sphingosine-1-phosphate receptor signaling pathway
D	0003677	molecular_function	DNA binding
D	0005515	molecular_function	protein binding
D	0005516	molecular_function	calmodulin binding
D	0005524	molecular_function	ATP binding
D	0005634	cellular_component	nucleus
D	0005654	cellular_component	nucleoplasm
D	0005737	cellular_component	cytoplasm
D	0005829	cellular_component	cytosol
D	0005886	cellular_component	plasma membrane
D	0005905	cellular_component	clathrin-coated pit
D	0006473	biological_process	protein acetylation
D	0006629	biological_process	lipid metabolic process
D	0006670	biological_process	sphingosine metabolic process
D	0008289	molecular_function	lipid binding
D	0008481	molecular_function	sphingosine kinase activity
D	0010008	cellular_component	endosome membrane
D	0010468	biological_process	regulation of gene expression
D	0010803	biological_process	regulation of tumor necrosis factor-mediated signaling pathway
D	0016301	molecular_function	kinase activity
D	0016407	molecular_function	acetyltransferase activity
D	0016740	molecular_function	transferase activity
D	0019722	biological_process	calcium-mediated signaling
D	0030100	biological_process	regulation of endocytosis
D	0030139	cellular_component	endocytic vesicle
D	0030148	biological_process	sphingolipid biosynthetic process
D	0030307	biological_process	positive regulation of cell growth
D	0030335	biological_process	positive regulation of cell migration
D	0031398	biological_process	positive regulation of protein ubiquitination
D	0031410	cellular_component	cytoplasmic vesicle
D	0031901	cellular_component	early endosome membrane
D	0032740	biological_process	positive regulation of interleukin-17 production
D	0034248	biological_process	regulation of amide metabolic process
D	0034612	biological_process	response to tumor necrosis factor
D	0035556	biological_process	intracellular signal transduction
D	0035924	biological_process	cellular response to vascular endothelial growth factor stimulus
D	0038036	molecular_function	sphingosine-1-phosphate receptor activity
D	0043066	biological_process	negative regulation of apoptotic process
D	0045202	cellular_component	synapse
D	0045766	biological_process	positive regulation of angiogenesis
D	0045931	biological_process	positive regulation of mitotic cell cycle
D	0045987	biological_process	positive regulation of smooth muscle contraction
D	0046512	biological_process	sphingosine biosynthetic process
D	0046521	biological_process	sphingoid catabolic process
D	0046890	biological_process	regulation of lipid biosynthetic process
D	0048146	biological_process	positive regulation of fibroblast proliferation
D	0050764	biological_process	regulation of phagocytosis
D	0051049	biological_process	regulation of transport
D	0051092	biological_process	positive regulation of NF-kappaB transcription factor activity
D	0051239	biological_process	regulation of multicellular organismal process
D	0051721	molecular_function	protein phosphatase 2A binding
D	0071363	biological_process	cellular response to growth factor stimulus
D	0098793	cellular_component	presynapse
D	0150077	biological_process	regulation of neuroinflammatory response
D	1900060	biological_process	negative regulation of ceramide biosynthetic process
D	1900745	biological_process	positive regulation of p38MAPK cascade
D	1901224	biological_process	positive regulation of non-canonical NF-kappaB signal transduction
D	1903978	biological_process	regulation of microglial cell activation
D	1905364	biological_process	regulation of endosomal vesicle fusion
E	0000166	molecular_function	nucleotide binding
E	0000287	molecular_function	magnesium ion binding
E	0001727	molecular_function	lipid kinase activity
E	0003376	biological_process	sphingosine-1-phosphate receptor signaling pathway
E	0003677	molecular_function	DNA binding
E	0005515	molecular_function	protein binding
E	0005516	molecular_function	calmodulin binding
E	0005524	molecular_function	ATP binding
E	0005634	cellular_component	nucleus
E	0005654	cellular_component	nucleoplasm
E	0005737	cellular_component	cytoplasm
E	0005829	cellular_component	cytosol
E	0005886	cellular_component	plasma membrane
E	0005905	cellular_component	clathrin-coated pit
E	0006473	biological_process	protein acetylation
E	0006629	biological_process	lipid metabolic process
E	0006670	biological_process	sphingosine metabolic process
E	0008289	molecular_function	lipid binding
E	0008481	molecular_function	sphingosine kinase activity
E	0010008	cellular_component	endosome membrane
E	0010468	biological_process	regulation of gene expression
E	0010803	biological_process	regulation of tumor necrosis factor-mediated signaling pathway
E	0016301	molecular_function	kinase activity
E	0016407	molecular_function	acetyltransferase activity
E	0016740	molecular_function	transferase activity
E	0019722	biological_process	calcium-mediated signaling
E	0030100	biological_process	regulation of endocytosis
E	0030139	cellular_component	endocytic vesicle
E	0030148	biological_process	sphingolipid biosynthetic process
E	0030307	biological_process	positive regulation of cell growth
E	0030335	biological_process	positive regulation of cell migration
E	0031398	biological_process	positive regulation of protein ubiquitination
E	0031410	cellular_component	cytoplasmic vesicle
E	0031901	cellular_component	early endosome membrane
E	0032740	biological_process	positive regulation of interleukin-17 production
E	0034248	biological_process	regulation of amide metabolic process
E	0034612	biological_process	response to tumor necrosis factor
E	0035556	biological_process	intracellular signal transduction
E	0035924	biological_process	cellular response to vascular endothelial growth factor stimulus
E	0038036	molecular_function	sphingosine-1-phosphate receptor activity
E	0043066	biological_process	negative regulation of apoptotic process
E	0045202	cellular_component	synapse
E	0045766	biological_process	positive regulation of angiogenesis
E	0045931	biological_process	positive regulation of mitotic cell cycle
E	0045987	biological_process	positive regulation of smooth muscle contraction
E	0046512	biological_process	sphingosine biosynthetic process
E	0046521	biological_process	sphingoid catabolic process
E	0046890	biological_process	regulation of lipid biosynthetic process
E	0048146	biological_process	positive regulation of fibroblast proliferation
E	0050764	biological_process	regulation of phagocytosis
E	0051049	biological_process	regulation of transport
E	0051092	biological_process	positive regulation of NF-kappaB transcription factor activity
E	0051239	biological_process	regulation of multicellular organismal process
E	0051721	molecular_function	protein phosphatase 2A binding
E	0071363	biological_process	cellular response to growth factor stimulus
E	0098793	cellular_component	presynapse
E	0150077	biological_process	regulation of neuroinflammatory response
E	1900060	biological_process	negative regulation of ceramide biosynthetic process
E	1900745	biological_process	positive regulation of p38MAPK cascade
E	1901224	biological_process	positive regulation of non-canonical NF-kappaB signal transduction
E	1903978	biological_process	regulation of microglial cell activation
E	1905364	biological_process	regulation of endosomal vesicle fusion
F	0000166	molecular_function	nucleotide binding
F	0000287	molecular_function	magnesium ion binding
F	0001727	molecular_function	lipid kinase activity
F	0003376	biological_process	sphingosine-1-phosphate receptor signaling pathway
F	0003677	molecular_function	DNA binding
F	0005515	molecular_function	protein binding
F	0005516	molecular_function	calmodulin binding
F	0005524	molecular_function	ATP binding
F	0005634	cellular_component	nucleus
F	0005654	cellular_component	nucleoplasm
F	0005737	cellular_component	cytoplasm
F	0005829	cellular_component	cytosol
F	0005886	cellular_component	plasma membrane
F	0005905	cellular_component	clathrin-coated pit
F	0006473	biological_process	protein acetylation
F	0006629	biological_process	lipid metabolic process
F	0006670	biological_process	sphingosine metabolic process
F	0008289	molecular_function	lipid binding
F	0008481	molecular_function	sphingosine kinase activity
F	0010008	cellular_component	endosome membrane
F	0010468	biological_process	regulation of gene expression
F	0010803	biological_process	regulation of tumor necrosis factor-mediated signaling pathway
F	0016301	molecular_function	kinase activity
F	0016407	molecular_function	acetyltransferase activity
F	0016740	molecular_function	transferase activity
F	0019722	biological_process	calcium-mediated signaling
F	0030100	biological_process	regulation of endocytosis
F	0030139	cellular_component	endocytic vesicle
F	0030148	biological_process	sphingolipid biosynthetic process
F	0030307	biological_process	positive regulation of cell growth
F	0030335	biological_process	positive regulation of cell migration
F	0031398	biological_process	positive regulation of protein ubiquitination
F	0031410	cellular_component	cytoplasmic vesicle
F	0031901	cellular_component	early endosome membrane
F	0032740	biological_process	positive regulation of interleukin-17 production
F	0034248	biological_process	regulation of amide metabolic process
F	0034612	biological_process	response to tumor necrosis factor
F	0035556	biological_process	intracellular signal transduction
F	0035924	biological_process	cellular response to vascular endothelial growth factor stimulus
F	0038036	molecular_function	sphingosine-1-phosphate receptor activity
F	0043066	biological_process	negative regulation of apoptotic process
F	0045202	cellular_component	synapse
F	0045766	biological_process	positive regulation of angiogenesis
F	0045931	biological_process	positive regulation of mitotic cell cycle
F	0045987	biological_process	positive regulation of smooth muscle contraction
F	0046512	biological_process	sphingosine biosynthetic process
F	0046521	biological_process	sphingoid catabolic process
F	0046890	biological_process	regulation of lipid biosynthetic process
F	0048146	biological_process	positive regulation of fibroblast proliferation
F	0050764	biological_process	regulation of phagocytosis
F	0051049	biological_process	regulation of transport
F	0051092	biological_process	positive regulation of NF-kappaB transcription factor activity
F	0051239	biological_process	regulation of multicellular organismal process
F	0051721	molecular_function	protein phosphatase 2A binding
F	0071363	biological_process	cellular response to growth factor stimulus
F	0098793	cellular_component	presynapse
F	0150077	biological_process	regulation of neuroinflammatory response
F	1900060	biological_process	negative regulation of ceramide biosynthetic process
F	1900745	biological_process	positive regulation of p38MAPK cascade
F	1901224	biological_process	positive regulation of non-canonical NF-kappaB signal transduction
F	1903978	biological_process	regulation of microglial cell activation
F	1905364	biological_process	regulation of endosomal vesicle fusion

Functional Information from PDB Data

site_id	AC1
Number of Residues	9
Details	BINDING SITE FOR RESIDUE UUL A 1001

Chain	Residue
A	PHE173
A	ILE174
A	VAL177
A	ASP178
A	THR196
A	MET272
A	PHE288
A	LEU299
A	PHE303

---

site_id	AC2
Number of Residues	10
Details	BINDING SITE FOR RESIDUE UUL B 1001

Chain	Residue
B	PHE173
B	ILE174
B	VAL177
B	ASP178
B	THR196
B	MET272
B	PHE288
B	LEU299
B	PHE303
B	MET306

---

site_id	AC3
Number of Residues	10
Details	BINDING SITE FOR RESIDUE UUL C 1001

Chain	Residue
C	PHE173
C	ILE174
C	VAL177
C	ASP178
C	THR196
C	MET272
C	PHE288
C	PHE303
C	MET306
C	HIS311

---

site_id	AC4
Number of Residues	10
Details	BINDING SITE FOR RESIDUE UUL D 1001

Chain	Residue
D	PHE173
D	ILE174
D	VAL177
D	ASP178
D	THR196
D	MET272
D	PHE288
D	PHE303
D	MET306
D	HIS311

---

site_id	AC5
Number of Residues	6
Details	BINDING SITE FOR RESIDUE EDO D 1002

Chain	Residue
D	MET150
D	ASN151
D	LEU264
D	HIS265
D	ARG279
D	CYS280

---

site_id	AC6
Number of Residues	9
Details	BINDING SITE FOR RESIDUE UUL E 1001

Chain	Residue
E	PHE173
E	ILE174
E	VAL177
E	ASP178
E	THR196
E	MET272
E	PHE288
E	PHE303
E	MET306

---

site_id	AC7
Number of Residues	9
Details	BINDING SITE FOR RESIDUE UUL F 1001

Chain	Residue
F	PHE173
F	ILE174
F	ASP178
F	PHE192
F	THR196
F	MET272
F	PHE288
F	PHE303
F	HIS311

---

site_id	AC8
Number of Residues	5
Details	BINDING SITE FOR RESIDUE EDO F 1002

Chain	Residue
F	MET150
F	ASN151
F	LEU264
F	ARG279
F	CYS280

---

Functional Information from SwissProt/UniProt

site_id	SWS_FT_FI1
Number of Residues	882
Details	Domain: {"description":"DAGKc","evidences":[{"source":"PROSITE-ProRule","id":"PRU00783","evidenceCode":"ECO:0000255"}]}

Chain

Residue

Details

---

site_id	SWS_FT_FI2
Number of Residues	48
Details	Motif: {"description":"Nuclear export signal 1","evidences":[{"source":"PubMed","id":"14575709","evidenceCode":"ECO:0000269"}]}

Chain

Residue

Details

---

site_id	SWS_FT_FI3
Number of Residues	48
Details	Motif: {"description":"Nuclear export signal 2","evidences":[{"source":"PubMed","id":"14575709","evidenceCode":"ECO:0000269"}]}

Chain

Residue

Details

---

site_id	SWS_FT_FI4
Number of Residues	6
Details	Active site: {"description":"Proton donor/acceptor","evidences":[{"source":"PubMed","id":"23602659","evidenceCode":"ECO:0000269"}]}

Chain

Residue

Details

---

site_id	SWS_FT_FI5
Number of Residues	102
Details	Binding site: {"evidences":[{"source":"PubMed","id":"23602659","evidenceCode":"ECO:0000269"}]}

Chain

Residue

Details

---

site_id	SWS_FT_FI6
Number of Residues	6
Details	Modified residue: {"description":"Phosphothreonine","evidences":[{"source":"PubMed","id":"18669648","evidenceCode":"ECO:0007744"}]}

Chain

Residue

Details

---