Q8IV63 · VRK3_HUMAN
- ProteinSerine/threonine-protein kinase VRK3
- GeneVRK3
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids474 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Plays a role in the regulation of the cell cycle by phosphorylating the nuclear envelope protein barrier-to-autointegration factor/BAF that is required for disassembly and reassembly, respectively, of the nuclear envelope during mitosis (PubMed:25899223).
Under normal physiological conditions, negatively regulates ERK activity along with VHR/DUSP3 phosphatase in the nucleus, causing timely and transient action of ERK. Stress conditions activate CDK5 which phosphorylates VRK3 to increase VHR phosphatase activity and suppress prolonged ERK activation that causes cell death (PubMed:27346674).
For example, upon glutamate induction, promotes nuclear localization of HSP70/HSPA1A to inhibit ERK activation via VHR/DUSP3 phosphatase (PubMed:27941812).
Under normal physiological conditions, negatively regulates ERK activity along with VHR/DUSP3 phosphatase in the nucleus, causing timely and transient action of ERK. Stress conditions activate CDK5 which phosphorylates VRK3 to increase VHR phosphatase activity and suppress prolonged ERK activation that causes cell death (PubMed:27346674).
For example, upon glutamate induction, promotes nuclear localization of HSP70/HSPA1A to inhibit ERK activation via VHR/DUSP3 phosphatase (PubMed:27941812).
Catalytic activity
- ATP + L-seryl-[protein] = ADP + H+ + O-phospho-L-seryl-[protein]
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | cytoplasm | |
Cellular Component | intracellular membrane-bounded organelle | |
Cellular Component | nucleoplasm | |
Cellular Component | nucleus | |
Molecular Function | ATP binding | |
Molecular Function | protein phosphatase binding | |
Molecular Function | protein serine/threonine kinase activity | |
Biological Process | negative regulation of ERK1 and ERK2 cascade | |
Biological Process | signal transduction | |
Biological Process | skeletal muscle tissue development |
Keywords
- Molecular function
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameSerine/threonine-protein kinase VRK3
- EC number
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionQ8IV63
- Secondary accessions
Proteomes
Organism-specific databases
Disease & Variants
Features
Showing features for natural variant, mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Natural variant | VAR_041295 | 59 | in dbSNP:rs2033262 | |||
Sequence: S → F | ||||||
Natural variant | VAR_041296 | 105 | in dbSNP:rs11547882 | |||
Sequence: P → T | ||||||
Mutagenesis | 108 | Unable to be phosphorylated by CDK5. | ||||
Sequence: S → A | ||||||
Natural variant | VAR_051682 | 170 | in dbSNP:rs11547881 | |||
Sequence: S → P | ||||||
Natural variant | VAR_041297 | 171 | in dbSNP:rs11547883 | |||
Sequence: F → L | ||||||
Natural variant | VAR_051683 | 188 | in dbSNP:rs11879620 | |||
Sequence: T → A | ||||||
Mutagenesis | 203 | Complete loss of kinase activity. | ||||
Sequence: K → E | ||||||
Natural variant | VAR_041298 | 268 | in dbSNP:rs10410075 | |||
Sequence: S → L | ||||||
Natural variant | VAR_041299 | 288 | in dbSNP:rs10409482 | |||
Sequence: C → Y | ||||||
Natural variant | VAR_051684 | 304 | in dbSNP:rs35261919 | |||
Sequence: H → L | ||||||
Natural variant | VAR_041300 | 370 | in dbSNP:rs35331034 | |||
Sequence: R → C | ||||||
Natural variant | VAR_041301 | 371 | in dbSNP:rs56407496 | |||
Sequence: S → G |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 607 variants from UniProt as well as other sources including ClinVar and dbSNP.
Organism-specific databases
Miscellaneous
Chemistry
Genetic variation databases
PTM/Processing
Features
Showing features for chain, modified residue, modified residue (large scale data).
Type | ID | Position(s) | Source | Description | |||
---|---|---|---|---|---|---|---|
Chain | PRO_0000086808 | 1-474 | UniProt | Serine/threonine-protein kinase VRK3 | |||
Sequence: MISFCPDCGKSIQAAFKFCPYCGNSLPVEEHVGSQTFVNPHVSSFQGSKRGLNSSFETSPKKVKWSSTVTSPRLSLFSDGDSSESEDTLSSSERSKGSGSRPPTPKSSPQKTRKSPQVTRGSPQKTSCSPQKTRQSPQTLKRSRVTTSLEALPTGTVLTDKSGRQWKLKSFQTRDNQGILYEAAPTSTLTCDSGPQKQKFSLKLDAKDGRLFNEQNFFQRAAKPLQVNKWKKLYSTPLLAIPTCMGFGVHQDKYRFLVLPSLGRSLQSALDVSPKHVLSERSVLQVACRLLDALEFLHENEYVHGNVTAENIFVDPEDQSQVTLAGYGFAFRYCPSGKHVAYVEGSRSPHEGDLEFISMDLHKGCGPSRRSDLQSLGYCMLKWLYGFLPWTNCLPNTEDIMKQKQKFVDKPGPFVGPCGHWIRPSETLQKYLKVVMALTYEEKPPYAMLRNNLEALLQDLRVSPYDPIGLPMVP | |||||||
Modified residue | 54 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 54 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 55 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 55 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 58 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue | 59 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 59 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 71 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 75 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 78 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 82 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 82 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 83 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 83 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 85 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 90 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 104 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue | 108 | UniProt | Phosphoserine; by CDK5 | ||||
Sequence: S | |||||||
Modified residue | 115 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 119 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue | 122 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 122 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 127 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 129 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 136 | PRIDE | Phosphoserine | ||||
Sequence: S |
Post-translational modification
Phosphorylated at Ser-108 by CDK5; leading to protection of the cell against H2O2-induced apoptosis.
Ubiquitinated by RNF144A.
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Interaction
Subunit
Interacts with DUSP3 (PubMed:27346674, PubMed:27941812).
Interacts with RAN. Interacts with HSP70/HSPA1A (PubMed:27941812).
Interacts with RAN. Interacts with HSP70/HSPA1A (PubMed:27941812).
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | Q8IV63 | MAX P61244 | 2 | EBI-1058605, EBI-751711 |
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for compositional bias, region, motif, domain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Compositional bias | 41-85 | Polar residues | ||||
Sequence: HVSSFQGSKRGLNSSFETSPKKVKWSSTVTSPRLSLFSDGDSSES | ||||||
Region | 41-152 | Disordered | ||||
Sequence: HVSSFQGSKRGLNSSFETSPKKVKWSSTVTSPRLSLFSDGDSSESEDTLSSSERSKGSGSRPPTPKSSPQKTRKSPQVTRGSPQKTSCSPQKTRQSPQTLKRSRVTTSLEAL | ||||||
Motif | 49-64 | Nuclear localization signal | ||||
Sequence: KRGLNSSFETSPKKVK | ||||||
Compositional bias | 92-152 | Polar residues | ||||
Sequence: SERSKGSGSRPPTPKSSPQKTRKSPQVTRGSPQKTSCSPQKTRQSPQTLKRSRVTTSLEAL | ||||||
Domain | 166-457 | Protein kinase | ||||
Sequence: WKLKSFQTRDNQGILYEAAPTSTLTCDSGPQKQKFSLKLDAKDGRLFNEQNFFQRAAKPLQVNKWKKLYSTPLLAIPTCMGFGVHQDKYRFLVLPSLGRSLQSALDVSPKHVLSERSVLQVACRLLDALEFLHENEYVHGNVTAENIFVDPEDQSQVTLAGYGFAFRYCPSGKHVAYVEGSRSPHEGDLEFISMDLHKGCGPSRRSDLQSLGYCMLKWLYGFLPWTNCLPNTEDIMKQKQKFVDKPGPFVGPCGHWIRPSETLQKYLKVVMALTYEEKPPYAMLRNNLEALL |
Sequence similarities
Phylogenomic databases
Family and domain databases
Sequence & Isoforms
- Sequence statusComplete
This entry describes 3 isoforms produced by Alternative splicing.
Q8IV63-1
This isoform has been chosen as the canonical sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
- Name1
- Length474
- Mass (Da)52,881
- Last updated2003-10-10 v2
- Checksum86B9B91050A7F0CC
Q8IV63-2
- Name2
Q8IV63-3
- Name3
- Differences from canonical
- 47-96: Missing
Computationally mapped potential isoform sequences
There are 11 potential isoforms mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
M0R164 | M0R164_HUMAN | VRK3 | 72 | ||
M0R025 | M0R025_HUMAN | VRK3 | 182 | ||
M0R073 | M0R073_HUMAN | VRK3 | 362 | ||
M0R3H2 | M0R3H2_HUMAN | VRK3 | 117 | ||
M0R200 | M0R200_HUMAN | VRK3 | 197 | ||
M0QXV1 | M0QXV1_HUMAN | VRK3 | 150 | ||
M0QXD7 | M0QXD7_HUMAN | VRK3 | 169 | ||
M0QX88 | M0QX88_HUMAN | VRK3 | 177 | ||
M0QZ79 | M0QZ79_HUMAN | VRK3 | 112 | ||
M0QYA8 | M0QYA8_HUMAN | VRK3 | 406 | ||
M0QYG0 | M0QYG0_HUMAN | VRK3 | 247 |
Features
Showing features for compositional bias, alternative sequence, sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Compositional bias | 41-85 | Polar residues | ||||
Sequence: HVSSFQGSKRGLNSSFETSPKKVKWSSTVTSPRLSLFSDGDSSES | ||||||
Alternative sequence | VSP_043409 | 47-96 | in isoform 3 | |||
Sequence: Missing | ||||||
Compositional bias | 92-152 | Polar residues | ||||
Sequence: SERSKGSGSRPPTPKSSPQKTRKSPQVTRGSPQKTSCSPQKTRQSPQTLKRSRVTTSLEAL | ||||||
Sequence conflict | 161 | in Ref. 2; AAP47180 | ||||
Sequence: K → E | ||||||
Alternative sequence | VSP_008544 | 407-412 | in isoform 2 | |||
Sequence: FVDKPG → LPWDSF | ||||||
Alternative sequence | VSP_008545 | 413-474 | in isoform 2 | |||
Sequence: Missing |
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AB031052 EMBL· GenBank· DDBJ | BAA90769.1 EMBL· GenBank· DDBJ | mRNA | ||
AF514788 EMBL· GenBank· DDBJ | AAP47180.1 EMBL· GenBank· DDBJ | mRNA | ||
AK292918 EMBL· GenBank· DDBJ | BAF85607.1 EMBL· GenBank· DDBJ | mRNA | ||
AK303010 EMBL· GenBank· DDBJ | BAG64141.1 EMBL· GenBank· DDBJ | mRNA | ||
AC011452 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
BC023556 EMBL· GenBank· DDBJ | AAH23556.1 EMBL· GenBank· DDBJ | mRNA | ||
BC095449 EMBL· GenBank· DDBJ | AAH95449.1 EMBL· GenBank· DDBJ | mRNA |