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UniProtKB - O43314 (VIP2_HUMAN)

Protein

Inositol hexakisphosphate and diphosphoinositol-pentakisphosphate kinase 2

Gene

PPIP5K2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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

View the complete GO annotation on QuickGO ...

GO - Biological processi

View the complete GO annotation on QuickGO ...

Keywordsi

Molecular functionKinase, Transferase
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.4.21 2681
2.7.4.24 2681
ReactomeiR-HSA-1855167 Synthesis of pyrophosphates in the cytosol
SABIO-RKiO43314

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 lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
Proteomesi
  • UP000005640 Componenti: Chromosome 5

Organism-specific databases

EuPathDBiHostDB:ENSG00000145725.19
HGNCiHGNC:29035 PPIP5K2
MIMi611648 gene
neXtProtiNX_O43314

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

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
ProteomicsDBi48892
48893 [O43314-2]

PTM databases

iPTMnetiO43314
PhosphoSitePlusiO43314

Expressioni

Gene expression databases

BgeeiENSG00000145725 Expressed in 225 organ(s), highest expression level in intestine
CleanExiHS_HISPPD1
ExpressionAtlasiO43314 baseline and differential
GenevisibleiO43314 HS

Organism-specific databases

HPAiHPA037895
HPA038442

Interactioni

Protein-protein interaction databases

BioGridi116864, 23 interactors
IntActiO43314, 5 interactors
STRINGi9606.ENSP00000313070

Structurei

Secondary structure

11243
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

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

Belongs to the histidine acid phosphatase family. VIP1 subfamily.Curated

Phylogenomic databases

eggNOGiKOG1057 Eukaryota
ENOG410XNSN LUCA
GeneTreeiENSGT00390000009048
HOGENOMiHOG000177917
HOVERGENiHBG108657
InParanoidiO43314
KOiK13024
PhylomeDBiO43314
TreeFamiTF313594

Family and domain databases

CDDicd07061 HP_HAP_like, 1 hit
InterProiView protein in InterPro
IPR033379 Acid_Pase_AS
IPR000560 His_Pase_clade-2
IPR037446 His_Pase_VIP1
IPR029033 His_PPase_superfam
PANTHERiPTHR12750 PTHR12750, 1 hit
PfamiView protein in Pfam
PF00328 His_Phos_2, 1 hit
SUPFAMiSSF53254 SSF53254, 1 hit
PROSITEiView protein in PROSITE
PS00616 HIS_ACID_PHOSPHAT_1, 1 hit

Sequences (2+)i

Sequence statusi: Complete.

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

This entry has 2 described isoforms and 9 potential isoforms that are computationally mapped.Show allAlign All

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

Computationally mapped potential isoform sequencesi

There are 9 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
A0A087WZV0A0A087WZV0_HUMAN
Inositol hexakisphosphate and dipho...
PPIP5K2
1,278Annotation score:
D6RBU4D6RBU4_HUMAN
Inositol hexakisphosphate and dipho...
PPIP5K2
452Annotation score:
H0Y9S9H0Y9S9_HUMAN
Inositol hexakisphosphate and dipho...
PPIP5K2
398Annotation score:
H0Y9M0H0Y9M0_HUMAN
Inositol hexakisphosphate and dipho...
PPIP5K2
209Annotation score:
D6RFG4D6RFG4_HUMAN
Inositol hexakisphosphate and dipho...
PPIP5K2
58Annotation score:
K7EPT7K7EPT7_HUMAN
Inositol hexakisphosphate and dipho...
PPIP5K2
58Annotation score:
A0A087WWN8A0A087WWN8_HUMAN
Inositol hexakisphosphate and dipho...
PPIP5K2
357Annotation score:
K7ENU7K7ENU7_HUMAN
Inositol hexakisphosphate and dipho...
PPIP5K2
255Annotation score:
K7EJG8K7EJG8_HUMAN
Inositol hexakisphosphate and dipho...
PPIP5K2
51Annotation score:

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 dbSNP:rs17155115Ensembl.1
Natural variantiVAR_038277985E → K. Corresponds to variant dbSNP:rs12519525Ensembl.1
Natural variantiVAR_0382781003R → K. Corresponds to variant dbSNP:rs12520040Ensembl.1
Natural variantiVAR_0382791206P → Q. Corresponds to variant dbSNP:rs17155138Ensembl.1
Natural variantiVAR_0382801232T → M. Corresponds to variant dbSNP:rs17155147Ensembl.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_001268400.1, NM_001281471.2
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

Similar proteinsi

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_001268400.1, NM_001281471.2
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, 23 interactors
IntActiO43314, 5 interactors
STRINGi9606.ENSP00000313070

PTM databases

iPTMnetiO43314
PhosphoSitePlusiO43314

Proteomic databases

EPDiO43314
MaxQBiO43314
PaxDbiO43314
PeptideAtlasiO43314
PRIDEiO43314
ProteomicsDBi48892
48893 [O43314-2]

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
EuPathDBiHostDB:ENSG00000145725.19
GeneCardsiPPIP5K2
H-InvDBiHIX0005068
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

BRENDAi2.7.4.21 2681
2.7.4.24 2681
ReactomeiR-HSA-1855167 Synthesis of pyrophosphates in the cytosol
SABIO-RKiO43314

Miscellaneous databases

ChiTaRSiPPIP5K2 human
GenomeRNAii23262
PROiPR:O43314
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000145725 Expressed in 225 organ(s), highest expression level in intestine
CleanExiHS_HISPPD1
ExpressionAtlasiO43314 baseline and differential
GenevisibleiO43314 HS

Family and domain databases

CDDicd07061 HP_HAP_like, 1 hit
InterProiView protein in InterPro
IPR033379 Acid_Pase_AS
IPR000560 His_Pase_clade-2
IPR037446 His_Pase_VIP1
IPR029033 His_PPase_superfam
PANTHERiPTHR12750 PTHR12750, 1 hit
PfamiView protein in Pfam
PF00328 His_Phos_2, 1 hit
SUPFAMiSSF53254 SSF53254, 1 hit
PROSITEiView protein in PROSITE
PS00616 HIS_ACID_PHOSPHAT_1, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiVIP2_HUMAN
AccessioniPrimary (citable) accession number: O43314
Secondary accession number(s): A1NI53, A6NGS8, Q8TB50
Entry historyiIntegrated into UniProtKB/Swiss-Prot: January 15, 2008
Last sequence update: January 15, 2008
Last modified: November 7, 2018
This is version 142 of the entry and version 3 of the sequence. See 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. SIMILARITY comments
    Index of protein domains and families
  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. Human chromosome 5
    Human chromosome 5: entries, gene names and cross-references to MIM
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