Q6PFW1 · VIP1_HUMAN
- ProteinInositol hexakisphosphate and diphosphoinositol-pentakisphosphate kinase 1
- GenePPIP5K1
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids1433 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Bifunctional inositol kinase that acts in concert with the IP6K kinases IP6K1, IP6K2 and IP6K3 to synthesize the diphosphate group-containing inositol pyrophosphates diphosphoinositol pentakisphosphate, PP-InsP5, and bis-diphosphoinositol tetrakisphosphate, (PP)2-InsP4. PP-InsP5 and (PP)2-InsP4, also respectively called InsP7 and InsP8, regulate a variety of cellular processes, including apoptosis, vesicle trafficking, cytoskeletal dynamics, exocytosis, insulin signaling and neutrophil activation. Phosphorylates inositol hexakisphosphate (InsP6) at position 1 to produce PP-InsP5 which is in turn phosphorylated by IP6Ks to produce (PP)2-InsP4. Alternatively, phosphorylates PP-InsP5 at position 1, produced by IP6Ks from InsP6, to produce (PP)2-InsP4. Activated when cells are exposed to hyperosmotic stress.
Catalytic activity
- 1D-myo-inositol hexakisphosphate + ATP = 1-diphospho-1D-myo-inositol 2,3,4,5,6-pentakisphosphate + ADPThis reaction proceeds in the forward direction.
Kinetics
KM | SUBSTRATE | pH | TEMPERATURE[C] | NOTES | EVIDENCE | |
---|---|---|---|---|---|---|
0.12 μM | InsP6 | |||||
0.1 μM | InsP7 |
Vmax | pH | TEMPERATURE[C] | NOTES | EVIDENCE | |
---|---|---|---|---|---|
0.03 nmol/min/mg | with InsP6 as substrate | ||||
0.13 nmol/min/mg | with InsP7 as substrate |
The catalytic efficiency is 80 folds higher for 5-PP-InsP5 (InsP7) compared to InsP6.
Features
Showing features for binding site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Binding site | 64-65 | substrate | ||||
Sequence: KK | ||||||
Binding site | 145 | ATP (UniProtKB | ChEBI) | ||||
Sequence: R | ||||||
Binding site | 198 | ATP (UniProtKB | ChEBI) | ||||
Sequence: K | ||||||
Binding site | 205 | ATP (UniProtKB | ChEBI) | ||||
Sequence: H | ||||||
Binding site | 224 | ATP (UniProtKB | ChEBI) | ||||
Sequence: R | ||||||
Binding site | 224-225 | substrate | ||||
Sequence: RK | ||||||
Binding site | 248-251 | ATP (UniProtKB | ChEBI) | ||||
Sequence: EEFM | ||||||
Binding site | 257-259 | ATP (UniProtKB | ChEBI) | ||||
Sequence: DVK | ||||||
Binding site | 259 | substrate | ||||
Sequence: K | ||||||
Binding site | 273 | substrate | ||||
Sequence: R | ||||||
Binding site | 275 | ATP (UniProtKB | ChEBI) | ||||
Sequence: S | ||||||
Binding site | 320 | ATP (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Binding site | 332-334 | ATP (UniProtKB | ChEBI) | ||||
Sequence: DVN | ||||||
Binding site | 337-340 | substrate | ||||
Sequence: SFVK |
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | cytosol | |
Cellular Component | plasma membrane | |
Molecular Function | ATP binding | |
Molecular Function | diphosphoinositol-pentakisphosphate kinase activity | |
Molecular Function | inositol heptakisphosphate kinase activity | |
Molecular Function | inositol hexakisphosphate 1-kinase activity | |
Molecular Function | inositol hexakisphosphate 3-kinase activity | |
Molecular Function | inositol hexakisphosphate 5-kinase activity | |
Molecular Function | inositol hexakisphosphate kinase activity | |
Molecular Function | inositol-1,3,4,5,6-pentakisphosphate kinase activity | |
Biological Process | inositol metabolic process | |
Biological Process | inositol phosphate biosynthetic process | |
Biological Process | inositol phosphate metabolic process |
Keywords
- Molecular function
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameInositol hexakisphosphate and diphosphoinositol-pentakisphosphate kinase 1
- 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 accessionQ6PFW1
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Note: Relocalizes to the plasma membrane upon activation of the PtdIns 3-kinase pathway.
Keywords
- Cellular component
Disease & Variants
Features
Showing features for mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 399 | Decreases 8-fold the affinity for PtdIns(3,4,5)P3. | ||||
Sequence: R → A | ||||||
Mutagenesis | 417 | Decreases 16-fold the affinity for PtdIns(3,4,5)P3. | ||||
Sequence: R → A |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 622 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 (large scale data), modified residue.
Type | ID | Position(s) | Source | Description | |||
---|---|---|---|---|---|---|---|
Chain | PRO_0000315688 | 1-1433 | UniProt | Inositol hexakisphosphate and diphosphoinositol-pentakisphosphate kinase 1 | |||
Sequence: MWSLTASEGESTTAHFFLGAGDEGLGTRGIGMRPEESDSELLEDEEDEVPPEPQIIVGICAMTKKSKSKPMTQILERLCRFDYLTVVILGEDVILNEPVENWPSCHCLISFHSKGFPLDKAVAYSKLRNPFLINDLAMQYYIQDRREVYRILQEEGIDLPRYAVLNRDPARPEECNLIEGEDQVEVNGAVFPKPFVEKPVSAEDHNVYIYYPSSAGGGSQRLFRKIGSRSSVYSPESSVRKTGSYIYEEFMPTDGTDVKVYTVGPDYAHAEARKSPALDGKVERDSEGKEIRYPVMLTAMEKLVARKVCVAFKQTVCGFDLLRANGHSFVCDVNGFSFVKNSMKYYDDCAKILGNTIMRELAPQFQIPWSIPTEAEDIPIVPTTSGTMMELRCVIAIIRHGDRTPKQKMKMEVKHPRFFALFEKHGGYKTGKLKLKRPEQLQEVLDITRLLLAELEKEPGGEIEEKTGKLEQLKSVLEMYGHFSGINRKVQLTYYPHGVKASNEGQDPQRETLAPSLLLVLKWGGELTPAGRVQAEELGRAFRCMYPGGQGDYAGFPGCGLLRLHSTFRHDLKIYASDEGRVQMTAAAFAKGLLALEGELTPILVQMVKSANMNGLLDSDGDSLSSCQHRVKARLHHILQQDAPFGPEDYDQLAPTRSTSLLNSMTIIQNPVKVCDQVFALIENLTHQIRERMQDPRSVDLQLYHSETLELMLQRWSKLERDFRQKSGRYDISKIPDIYDCVKYDVQHNGSLGLQGTAELLRLSKALADVVIPQEYGISREEKLEIAVGFCLPLLRKILLDLQRTHEDESVNKLHPLCYLRYSRGVLSPGRHVRTRLYFTSESHVHSLLSVFRYGGLLDETQDAQWQRALDYLSAISELNYMTQIVIMLYEDNTQDPLSEERFHVELHFSPGVKGVEEEGSAPAGCGFRPASSENEEMKTNQGSMENLCPGKASDEPDRALQTSPQPPEGPGLPRRSPLIRNRKAGSMEVLSETSSSRPGGYRLFSSSRPPTEMKQSGLGSQCTGLFSTTVLGGSSSAPNLQDYARSHGKKLPPASLKHRDELLFVPAVKRFSVSFAKHPTNGFEGCSMVPTIYPLETLHNALSLRQVSEFLSRVCQRHTDAQAQASAALFDSMHSSQASDNPFSPPRTLHSPPLQLQQRSEKPPWYSSGPSSTVSSAGPSSPTTVDGNSQFGFSDQPSLNSHVAEEHQGLGLLQETPGSGAQELSIEGEQELFEPNQSPQVPPMETSQPYEEVSQPCQEVPDISQPCQDISEALSQPCQKVPDISQQCQENHDNGNHTCQEVPHISQPCQKSSQLCQKVSEEVCQLCLENSEEVSQPCQGVSVEVGKLVHKFHVGVGSLVQETLVEVGSPAEEIPEEVIQPYQEFSVEVGRLAQETSAINLLSQGIPEIDKPSQEFPEEIDLQAQEVPEEIN | |||||||
Modified residue (large scale data) | 475 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 944 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 944 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 963 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue (large scale data) | 964 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 977 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 987 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 987 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 1006 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 1037 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 1037 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 1073 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 1073 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 1145 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 1149 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue | 1152 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 1152 | PRIDE | Phosphoserine | ||||
Sequence: S |
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
Widely expressed, with a higher expression in skeletal muscle, heart and brain.
Gene expression databases
Organism-specific databases
Structure
Family & Domains
Features
Showing features for region, compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 382-453 | Polyphosphoinositide-binding domain | ||||
Sequence: PTTSGTMMELRCVIAIIRHGDRTPKQKMKMEVKHPRFFALFEKHGGYKTGKLKLKRPEQLQEVLDITRLLLA | ||||||
Region | 915-1020 | Disordered | ||||
Sequence: GVEEEGSAPAGCGFRPASSENEEMKTNQGSMENLCPGKASDEPDRALQTSPQPPEGPGLPRRSPLIRNRKAGSMEVLSETSSSRPGGYRLFSSSRPPTEMKQSGLG | ||||||
Compositional bias | 934-948 | Polar residues | ||||
Sequence: ENEEMKTNQGSMENL | ||||||
Compositional bias | 988-1020 | Polar residues | ||||
Sequence: MEVLSETSSSRPGGYRLFSSSRPPTEMKQSGLG | ||||||
Region | 1134-1199 | Disordered | ||||
Sequence: MHSSQASDNPFSPPRTLHSPPLQLQQRSEKPPWYSSGPSSTVSSAGPSSPTTVDGNSQFGFSDQPS | ||||||
Region | 1235-1257 | Disordered | ||||
Sequence: EPNQSPQVPPMETSQPYEEVSQP |
Domain
The C-terminal acid phosphatase-like domain binds PtdIns(3,4,5)P3 and InsP6. Despite its similarity with the phosphatase domain of histidine acid phosphatases, it has no phosphatase activity.
Sequence similarities
Belongs to the histidine acid phosphatase family. VIP1 subfamily.
Phylogenomic databases
Family and domain databases
Sequence & Isoforms
- Sequence statusComplete
This entry describes 7 isoforms produced by Alternative splicing.
Q6PFW1-1
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
- Length1,433
- Mass (Da)159,521
- Last updated2004-07-05 v1
- ChecksumBA0DEFB2A71B1467
Q6PFW1-2
- Name2
- Differences from canonical
- 818-821: Missing
- 1082-1082: N → NG
Q6PFW1-3
- Name3
- Differences from canonical
- 818-821: Missing
- 1062-1082: Missing
Q6PFW1-4
- Name4
- Differences from canonical
- 653-653: Missing
- 818-821: Missing
- 1062-1082: Missing
Q6PFW1-5
- Name5
- Differences from canonical
- 810-821: Missing
- 865-957: Missing
- 1107-1240: Missing
Q6PFW1-6
- Name6
- Differences from canonical
- 818-1433: Missing
Q6PFW1-7
- Name7
- Differences from canonical
- 818-821: Missing
- 1020-1082: Missing
- 1167-1167: Y → LETRFCHVGQAGLELLTSSDLPASASQSAGITGVSHRTQPD
Computationally mapped potential isoform sequences
There are 11 potential isoforms mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
C9J5E6 | C9J5E6_HUMAN | PPIP5K1 | 114 | ||
C9J490 | C9J490_HUMAN | PPIP5K1 | 71 | ||
A0A2R8YGT1 | A0A2R8YGT1_HUMAN | PPIP5K1 | 499 | ||
C9JZX6 | C9JZX6_HUMAN | PPIP5K1 | 133 | ||
F8W9A8 | F8W9A8_HUMAN | PPIP5K1 | 1409 | ||
H0Y3Y5 | H0Y3Y5_HUMAN | PPIP5K1 | 196 | ||
A0A9L9PYJ9 | A0A9L9PYJ9_HUMAN | PPIP5K1 | 1458 | ||
H7C436 | H7C436_HUMAN | PPIP5K1 | 118 | ||
H7C398 | H7C398_HUMAN | PPIP5K1 | 259 | ||
B7WPL9 | B7WPL9_HUMAN | PPIP5K1 | 1429 | ||
A0A8J8ZH50 | A0A8J8ZH50_HUMAN | PPIP5K1 | 1490 |
Sequence caution
Features
Showing features for sequence conflict, alternative sequence, compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 44 | in Ref. 4; CAD97968 | ||||
Sequence: D → G | ||||||
Sequence conflict | 304 | in Ref. 4; CAD97968 | ||||
Sequence: V → M | ||||||
Sequence conflict | 374 | in Ref. 4; CAD97968 | ||||
Sequence: E → V | ||||||
Sequence conflict | 423 | in Ref. 1; AAP30843/AAP30845/AAN40768 | ||||
Sequence: E → Q | ||||||
Sequence conflict | 473 | in Ref. 4; CAD97968 | ||||
Sequence: L → P | ||||||
Sequence conflict | 483 | in Ref. 1; AAP30845/AAN40768 | ||||
Sequence: F → S | ||||||
Sequence conflict | 490 | in Ref. 4; CAD97968 | ||||
Sequence: V → E | ||||||
Sequence conflict | 548 | in Ref. 4; CAD97968 | ||||
Sequence: G → V | ||||||
Alternative sequence | VSP_030615 | 653 | in isoform 4 | |||
Sequence: Missing | ||||||
Sequence conflict | 738 | in Ref. 1; AAP30845/AAN40768 | ||||
Sequence: I → L | ||||||
Sequence conflict | 788 | in Ref. 1; AAP30845/AAN40768 | ||||
Sequence: V → A | ||||||
Alternative sequence | VSP_030616 | 810-821 | in isoform 5 | |||
Sequence: Missing | ||||||
Alternative sequence | VSP_030618 | 818-821 | in isoform 2, isoform 3, isoform 4 and isoform 7 | |||
Sequence: Missing | ||||||
Alternative sequence | VSP_030617 | 818-1433 | in isoform 6 | |||
Sequence: Missing | ||||||
Alternative sequence | VSP_030619 | 865-957 | in isoform 5 | |||
Sequence: Missing | ||||||
Compositional bias | 934-948 | Polar residues | ||||
Sequence: ENEEMKTNQGSMENL | ||||||
Sequence conflict | 936 | in Ref. 4; CAI46011 | ||||
Sequence: E → G | ||||||
Sequence conflict | 985 | in Ref. 1; AAP30845/AAN40768 | ||||
Sequence: A → V | ||||||
Compositional bias | 988-1020 | Polar residues | ||||
Sequence: MEVLSETSSSRPGGYRLFSSSRPPTEMKQSGLG | ||||||
Sequence conflict | 1020 | in Ref. 1; AAP30843 | ||||
Sequence: G → A | ||||||
Alternative sequence | VSP_030620 | 1020-1082 | in isoform 7 | |||
Sequence: Missing | ||||||
Sequence conflict | 1041 | in Ref. 1; AAP30845/AAN40768 | ||||
Sequence: L → P | ||||||
Alternative sequence | VSP_030621 | 1062-1082 | in isoform 3 and isoform 4 | |||
Sequence: Missing | ||||||
Sequence conflict | 1066 | in Ref. 1; AAP30842 | ||||
Sequence: V → L | ||||||
Alternative sequence | VSP_030622 | 1082 | in isoform 2 | |||
Sequence: N → NG | ||||||
Alternative sequence | VSP_030623 | 1107-1240 | in isoform 5 | |||
Sequence: Missing | ||||||
Sequence conflict | 1126 | in Ref. 4; CAI46011 | ||||
Sequence: A → T | ||||||
Sequence conflict | 1134 | in Ref. 4; CAI46011 | ||||
Sequence: M → V | ||||||
Alternative sequence | VSP_030624 | 1167 | in isoform 7 | |||
Sequence: Y → LETRFCHVGQAGLELLTSSDLPASASQSAGITGVSHRTQPD | ||||||
Sequence conflict | 1198 | in Ref. 4; CAI46011 | ||||
Sequence: P → R | ||||||
Sequence conflict | 1293 | in Ref. 1; AAP30845/AAN40768 | ||||
Sequence: H → M | ||||||
Sequence conflict | 1294 | in Ref. 1; AAP30845/AAN40768 | ||||
Sequence: D → T |
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AF502586 EMBL· GenBank· DDBJ | AAP30842.1 EMBL· GenBank· DDBJ | mRNA | ||
AF502587 EMBL· GenBank· DDBJ | AAP30843.1 EMBL· GenBank· DDBJ | mRNA | ||
AF502588 EMBL· GenBank· DDBJ | AAP30844.1 EMBL· GenBank· DDBJ | mRNA | ||
AF502589 EMBL· GenBank· DDBJ | AAP30845.1 EMBL· GenBank· DDBJ | mRNA | ||
AF543190 EMBL· GenBank· DDBJ | AAN40768.1 EMBL· GenBank· DDBJ | mRNA | ||
AB002375 EMBL· GenBank· DDBJ | BAA20831.2 EMBL· GenBank· DDBJ | mRNA | Different initiation | |
BX538022 EMBL· GenBank· DDBJ | CAD97968.1 EMBL· GenBank· DDBJ | mRNA | ||
BX647814 EMBL· GenBank· DDBJ | CAI46011.1 EMBL· GenBank· DDBJ | mRNA | ||
BC050263 EMBL· GenBank· DDBJ | AAH50263.1 EMBL· GenBank· DDBJ | mRNA | ||
BC057395 EMBL· GenBank· DDBJ | AAH57395.1 EMBL· GenBank· DDBJ | mRNA |