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Protein

Inositol hexakisphosphate and diphosphoinositol-pentakisphosphate kinase 2

Gene

PPIP5K2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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 positions 1 or 3 to produce PP-InsP5 which is in turn phosphorylated by IP6Ks to produce (PP)2-InsP4. Alternatively, phosphorylates at position 1 or 3 PP-InsP5, produced by IP6Ks from InsP6, to produce (PP)2-InsP4.2 Publications

Catalytic activityi

ATP + 1D-myo-inositol hexakisphosphate = ADP + 1D-myo-inositol 5-diphosphate 1,2,3,4,6-pentakisphosphate.1 Publication
ATP + 1D-myo-inositol 1-diphosphate 2,3,4,5,6-pentakisphosphate = ADP + 1D-myo-inositol 1,5-bis(diphosphate) 2,3,4,6-tetrakisphosphate.1 Publication
ATP + 1D-myo-inositol 5-diphosphate 1,2,3,4,6-pentakisphosphate = ADP + 1D-myo-inositol 1,5-bis(diphosphate) 2,3,4,6-tetrakisphosphate.1 Publication
ATP + 1D-myo-inositol hexakisphosphate = ADP + 1D-myo-inositol 1-diphosphate 2,3,4,5,6-pentakisphosphate.1 Publication

Kineticsi

  1. KM=0.13 µM for InsP61 Publication
  2. KM=0.19 µM for InsP71 Publication
  1. Vmax=0.39 nmol/min/mg enzyme with InsP6 as substrate1 Publication
  2. Vmax=1.38 nmol/min/mg enzyme with InsP7 as substrate1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei134ATPCombined sources1 Publication1
Binding sitei187ATPCombined sources1 Publication1
Binding sitei194ATPCombined sources1 Publication1
Binding sitei213ATPCombined sources1 Publication1
Binding sitei248SubstrateCombined sources1 Publication1
Binding sitei262SubstrateCombined sources1 Publication1
Binding sitei264ATPCombined sources1 Publication1
Binding sitei309ATPCombined sources1 Publication1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi237 – 240ATPCombined sources1 Publication4
Nucleotide bindingi246 – 248ATPCombined sources1 Publication3
Nucleotide bindingi321 – 323ATPCombined sources1 Publication3

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Kinase, Transferase

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

BioCyciZFISH:HS07278-MONOMER.
BRENDAi2.7.4.21. 2681.
2.7.4.24. 2681.
ReactomeiR-HSA-1855167. Synthesis of pyrophosphates in the cytosol.

Names & Taxonomyi

Protein namesi
Recommended name:
Inositol hexakisphosphate and diphosphoinositol-pentakisphosphate kinase 2 (EC:2.7.4.211 Publication, EC:2.7.4.241 Publication)
Alternative name(s):
Diphosphoinositol pentakisphosphate kinase 2
Histidine acid phosphatase domain-containing protein 1
InsP6 and PP-IP5 kinase 2
VIP1 homolog 2
Short name:
hsVIP2
Gene namesi
Name:PPIP5K2
Synonyms:HISPPD1, KIAA0433, VIP2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 5

Organism-specific databases

HGNCiHGNC:29035. PPIP5K2.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi213R → A or K: Reduces enzyme activity by about 99%. 1 Publication1
Mutagenesisi248K → A: Loss of enzyme activity. 1 Publication1
Mutagenesisi262R → A: Reduces enzyme activity by about 99%. 1 Publication1

Organism-specific databases

DisGeNETi23262.
OpenTargetsiENSG00000145725.
PharmGKBiPA165660454.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00003156921 – 1243Inositol hexakisphosphate and diphosphoinositol-pentakisphosphate kinase 2Add BLAST1243

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei38PhosphoserineCombined sources1
Modified residuei223PhosphoserineCombined sources1
Modified residuei1006PhosphoserineCombined sources1
Modified residuei1016PhosphoserineCombined sources1
Modified residuei1074PhosphoserineCombined sources1
Modified residuei1091PhosphoserineCombined sources1
Modified residuei1165PhosphoserineCombined sources1
Modified residuei1172PhosphoserineCombined sources1
Modified residuei1180PhosphoserineCombined sources1
Modified residuei1220PhosphoserineCombined sources1
Modified residuei1221PhosphoserineCombined sources1

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiO43314.
MaxQBiO43314.
PaxDbiO43314.
PeptideAtlasiO43314.
PRIDEiO43314.

PTM databases

iPTMnetiO43314.
PhosphoSitePlusiO43314.

Expressioni

Gene expression databases

BgeeiENSG00000145725.
CleanExiHS_HISPPD1.
ExpressionAtlasiO43314. baseline and differential.
GenevisibleiO43314. HS.

Organism-specific databases

HPAiHPA037895.
HPA038442.

Interactioni

Protein-protein interaction databases

BioGridi116864. 11 interactors.
IntActiO43314. 1 interactor.
STRINGi9606.ENSP00000313070.

Structurei

Secondary structure

11243
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi44 – 50Combined sources7
Helixi52 – 55Combined sources4
Helixi58 – 67Combined sources10
Beta strandi73 – 77Combined sources5
Helixi80 – 85Combined sources6
Helixi88 – 90Combined sources3
Beta strandi95 – 99Combined sources5
Helixi107 – 117Combined sources11
Beta strandi120 – 123Combined sources4
Helixi127 – 131Combined sources5
Helixi134 – 143Combined sources10
Beta strandi151 – 154Combined sources4
Beta strandi158 – 160Combined sources3
Helixi161 – 163Combined sources3
Beta strandi164 – 168Combined sources5
Beta strandi170 – 175Combined sources6
Beta strandi178 – 190Combined sources13
Beta strandi197 – 199Combined sources3
Helixi202 – 204Combined sources3
Beta strandi208 – 215Combined sources8
Beta strandi218 – 224Combined sources7
Beta strandi230 – 232Combined sources3
Beta strandi234 – 238Combined sources5
Beta strandi243 – 253Combined sources11
Beta strandi257 – 263Combined sources7
Beta strandi265 – 267Combined sources3
Beta strandi275 – 279Combined sources5
Helixi288 – 300Combined sources13
Beta strandi303 – 313Combined sources11
Beta strandi316 – 325Combined sources10
Helixi332 – 354Combined sources23

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3T54X-ray1.90A37-366[»]
3T7AX-ray1.70A41-366[»]
3T99X-ray2.10A37-366[»]
3T9AX-ray1.80A41-366[»]
3T9BX-ray1.85A41-366[»]
3T9CX-ray1.90A41-366[»]
3T9DX-ray1.85A41-366[»]
3T9EX-ray1.90A41-366[»]
3T9FX-ray2.00A41-366[»]
4HN2X-ray1.90A41-366[»]
4NZMX-ray2.00A41-366[»]
4NZNX-ray1.75A41-366[»]
4NZOX-ray1.90A41-366[»]
4Q4CX-ray1.90A41-366[»]
4Q4DX-ray1.85A41-366[»]
5BYAX-ray1.90A41-366[»]
5BYBX-ray2.30A41-366[»]
5DGHX-ray2.10A41-366[»]
5DGIX-ray1.85A41-366[»]
ProteinModelPortaliO43314.
SMRiO43314.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni53 – 54Substrate bindingCombined sources1 Publication2
Regioni213 – 214Substrate bindingCombined sources1 Publication2
Regioni326 – 329Substrate bindingCombined sources1 Publication4
Regioni371 – 442Polyphosphoinositide-binding domain1 PublicationAdd BLAST72

Domaini

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.1 Publication

Sequence similaritiesi

Phylogenomic databases

eggNOGiKOG1057. Eukaryota.
ENOG410XNSN. LUCA.
GeneTreeiENSGT00390000009048.
HOGENOMiHOG000177917.
HOVERGENiHBG108657.
InParanoidiO43314.
KOiK13024.
PhylomeDBiO43314.
TreeFamiTF313594.

Family and domain databases

CDDicd07061. HP_HAP_like. 1 hit.
Gene3Di3.40.50.1240. 3 hits.
InterProiIPR033379. Acid_Pase_AS.
IPR000560. His_Pase_clade-2.
IPR029033. His_PPase_superfam.
[Graphical view]
PfamiPF00328. His_Phos_2. 1 hit.
[Graphical view]
SUPFAMiSSF53254. SSF53254. 3 hits.
PROSITEiPS00616. HIS_ACID_PHOSPHAT_1. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: O43314-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MSEAPRFFVG PEDTEINPGN YRHFFHHADE DDEEEDDSPP ERQIVVGICS
60 70 80 90 100
MAKKSKSKPM KEILERISLF KYITVVVFEE EVILNEPVEN WPLCDCLISF
110 120 130 140 150
HSKGFPLDKA VAYAKLRNPF VINDLNMQYL IQDRREVYSI LQAEGILLPR
160 170 180 190 200
YAILNRDPNN PKECNLIEGE DHVEVNGEVF QKPFVEKPVS AEDHNVYIYY
210 220 230 240 250
PTSAGGGSQR LFRKIGSRSS VYSPESNVRK TGSYIYEEFM PTDGTDVKVY
260 270 280 290 300
TVGPDYAHAE ARKSPALDGK VERDSEGKEV RYPVILNARE KLIAWKVCLA
310 320 330 340 350
FKQTVCGFDL LRANGQSYVC DVNGFSFVKN SMKYYDDCAK ILGNIVMREL
360 370 380 390 400
APQFHIPWSI PLEAEDIPIV PTTSGTMMEL RCVIAVIRHG DRTPKQKMKM
410 420 430 440 450
EVRHQKFFDL FEKCDGYKSG KLKLKKPKQL QEVLDIARQL LMELGQNNDS
460 470 480 490 500
EIEENKPKLE QLKTVLEMYG HFSGINRKVQ LTYLPHGCPK TSSEEEDSRR
510 520 530 540 550
EEPSLLLVLK WGGELTPAGR VQAEELGRAF RCMYPGGQGD YAGFPGCGLL
560 570 580 590 600
RLHSTYRHDL KIYASDEGRV QMTAAAFAKG LLALEGELTP ILVQMVKSAN
610 620 630 640 650
MNGLLDSDSD SLSSCQQRVK ARLHEILQKD RDFTAEDYEK LTPSGSISLI
660 670 680 690 700
KSMHLIKNPV KTCDKVYSLI QSLTSQIRHR MEDPKSSDIQ LYHSETLELM
710 720 730 740 750
LRRWSKLEKD FKTKNGRYDI SKIPDIYDCI KYDVQHNGSL KLENTMELYR
760 770 780 790 800
LSKALADIVI PQEYGITKAE KLEIAKGYCT PLVRKIRSDL QRTQDDDTVN
810 820 830 840 850
KLHPVYSRGV LSPERHVRTR LYFTSESHVH SLLSILRYGA LCNESKDEQW
860 870 880 890 900
KRAMDYLNVV NELNYMTQIV IMLYEDPNKD LSSEERFHVE LHFSPGAKGC
910 920 930 940 950
EEDKNLPSGY GYRPASRENE GRRPFKIDND DEPHTSKRDE VDRAVILFKP
960 970 980 990 1000
MVSEPIHIHR KSPLPRSRKT ATNDEESPLS VSSPEGTGTW LHYTSGVGTG
1010 1020 1030 1040 1050
RRRRRSGEQI TSSPVSPKSL AFTSSIFGSW QQVVSENANY LRTPRTLVEQ
1060 1070 1080 1090 1100
KQNPTVGSHC AGLFSTSVLG GSSSAPNLQD YARTHRKKLT SSGCIDDATR
1110 1120 1130 1140 1150
GSAVKRFSIS FARHPTNGFE LYSMVPSICP LETLHNALSL KQVDEFLASI
1160 1170 1180 1190 1200
ASPSSDVPRK TAEISSTALR SSPIMRKKVS LNTYTPAKIL PTPPATLKST
1210 1220 1230 1240
KASSKPATSG PSSAVVPNTS SRKKNITSKT ETHEHKKNTG KKK
Length:1,243
Mass (Da):140,407
Last modified:January 15, 2008 - v3
Checksum:iA8831DDDAB9B2E6E
GO
Isoform 2 (identifier: O43314-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1097-1117: Missing.

Note: No experimental confirmation available.
Show »
Length:1,222
Mass (Da):138,106
Checksum:iC61F832FE77F87F3
GO

Sequence cautioni

The sequence BAA24863 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated
The sequence EAW49076 differs from that shown. Reason: Erroneous gene model prediction.Curated

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_038276944A → G.Corresponds to variant rs17155115dbSNPEnsembl.1
Natural variantiVAR_038277985E → K.Corresponds to variant rs12519525dbSNPEnsembl.1
Natural variantiVAR_0382781003R → K.Corresponds to variant rs12520040dbSNPEnsembl.1
Natural variantiVAR_0382791206P → Q.Corresponds to variant rs17155138dbSNPEnsembl.1
Natural variantiVAR_0382801232T → M.Corresponds to variant rs17155147dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0306361097 – 1117Missing in isoform 2. 1 PublicationAdd BLAST21

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB007893 mRNA. Translation: BAA24863.2. Different initiation.
AC011362 Genomic DNA. No translation available.
CH471086 Genomic DNA. Translation: EAW49076.1. Sequence problems.
BC024591 mRNA. Translation: AAH24591.1.
CCDSiCCDS34207.1. [O43314-2]
CCDS64212.1. [O43314-1]
RefSeqiNP_001263206.1. NM_001276277.2. [O43314-1]
NP_056031.2. NM_015216.4. [O43314-2]
UniGeneiHs.212046.

Genome annotation databases

EnsembliENST00000321521; ENSP00000313070; ENSG00000145725. [O43314-2]
ENST00000358359; ENSP00000351126; ENSG00000145725. [O43314-1]
ENST00000414217; ENSP00000416016; ENSG00000145725. [O43314-2]
GeneIDi23262.
KEGGihsa:23262.
UCSCiuc003kod.6. human. [O43314-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB007893 mRNA. Translation: BAA24863.2. Different initiation.
AC011362 Genomic DNA. No translation available.
CH471086 Genomic DNA. Translation: EAW49076.1. Sequence problems.
BC024591 mRNA. Translation: AAH24591.1.
CCDSiCCDS34207.1. [O43314-2]
CCDS64212.1. [O43314-1]
RefSeqiNP_001263206.1. NM_001276277.2. [O43314-1]
NP_056031.2. NM_015216.4. [O43314-2]
UniGeneiHs.212046.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3T54X-ray1.90A37-366[»]
3T7AX-ray1.70A41-366[»]
3T99X-ray2.10A37-366[»]
3T9AX-ray1.80A41-366[»]
3T9BX-ray1.85A41-366[»]
3T9CX-ray1.90A41-366[»]
3T9DX-ray1.85A41-366[»]
3T9EX-ray1.90A41-366[»]
3T9FX-ray2.00A41-366[»]
4HN2X-ray1.90A41-366[»]
4NZMX-ray2.00A41-366[»]
4NZNX-ray1.75A41-366[»]
4NZOX-ray1.90A41-366[»]
4Q4CX-ray1.90A41-366[»]
4Q4DX-ray1.85A41-366[»]
5BYAX-ray1.90A41-366[»]
5BYBX-ray2.30A41-366[»]
5DGHX-ray2.10A41-366[»]
5DGIX-ray1.85A41-366[»]
ProteinModelPortaliO43314.
SMRiO43314.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi116864. 11 interactors.
IntActiO43314. 1 interactor.
STRINGi9606.ENSP00000313070.

PTM databases

iPTMnetiO43314.
PhosphoSitePlusiO43314.

Proteomic databases

EPDiO43314.
MaxQBiO43314.
PaxDbiO43314.
PeptideAtlasiO43314.
PRIDEiO43314.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000321521; ENSP00000313070; ENSG00000145725. [O43314-2]
ENST00000358359; ENSP00000351126; ENSG00000145725. [O43314-1]
ENST00000414217; ENSP00000416016; ENSG00000145725. [O43314-2]
GeneIDi23262.
KEGGihsa:23262.
UCSCiuc003kod.6. human. [O43314-1]

Organism-specific databases

CTDi23262.
DisGeNETi23262.
GeneCardsiPPIP5K2.
H-InvDBHIX0005068.
HIX0029534.
HGNCiHGNC:29035. PPIP5K2.
HPAiHPA037895.
HPA038442.
MIMi611648. gene.
neXtProtiNX_O43314.
OpenTargetsiENSG00000145725.
PharmGKBiPA165660454.
HUGEiSearch...
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1057. Eukaryota.
ENOG410XNSN. LUCA.
GeneTreeiENSGT00390000009048.
HOGENOMiHOG000177917.
HOVERGENiHBG108657.
InParanoidiO43314.
KOiK13024.
PhylomeDBiO43314.
TreeFamiTF313594.

Enzyme and pathway databases

BioCyciZFISH:HS07278-MONOMER.
BRENDAi2.7.4.21. 2681.
2.7.4.24. 2681.
ReactomeiR-HSA-1855167. Synthesis of pyrophosphates in the cytosol.

Miscellaneous databases

ChiTaRSiPPIP5K2. human.
GenomeRNAii23262.
PROiO43314.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000145725.
CleanExiHS_HISPPD1.
ExpressionAtlasiO43314. baseline and differential.
GenevisibleiO43314. HS.

Family and domain databases

CDDicd07061. HP_HAP_like. 1 hit.
Gene3Di3.40.50.1240. 3 hits.
InterProiIPR033379. Acid_Pase_AS.
IPR000560. His_Pase_clade-2.
IPR029033. His_PPase_superfam.
[Graphical view]
PfamiPF00328. His_Phos_2. 1 hit.
[Graphical view]
SUPFAMiSSF53254. SSF53254. 3 hits.
PROSITEiPS00616. HIS_ACID_PHOSPHAT_1. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiVIP2_HUMAN
AccessioniPrimary (citable) accession number: O43314
Secondary accession number(s): A1NI53, A6NGS8, Q8TB50
Entry historyi
Integrated into UniProtKB/Swiss-Prot: January 15, 2008
Last sequence update: January 15, 2008
Last modified: November 30, 2016
This is version 125 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 5
    Human chromosome 5: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.