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O43314 (VIP2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 99. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Inositol hexakisphosphate and diphosphoinositol-pentakisphosphate kinase 2

EC=2.7.4.21
EC=2.7.4.24
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 names
Name:PPIP5K2
Synonyms:HISPPD1, KIAA0433, VIP2
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length1243 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

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 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. Ref.6 Ref.7

Catalytic activity

ATP + 1D-myo-inositol hexakisphosphate = ADP + 1D-myo-inositol 5-diphosphate 1,2,3,4,6-pentakisphosphate. Ref.6 Ref.7 Ref.11

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. Ref.6 Ref.7 Ref.11

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. Ref.6 Ref.7 Ref.11

ATP + 1D-myo-inositol hexakisphosphate = ADP + 1D-myo-inositol 1-diphosphate 2,3,4,5,6-pentakisphosphate.

Subcellular location

Cytoplasmcytosol Ref.6.

Domain

The polyphosphoinositide-binding domain mediates binding of PtdIns(3,4,5)P3 and InsP6. Despite its similarity with the phosphatase domain of histidine acid phosphatases, it has no phosphatase activity. Ref.11

Sequence similarities

Belongs to the histidine acid phosphatase family. VIP1 subfamily.

Biophysicochemical properties

Kinetic parameters:

KM=0.13 µM for InsP6 Ref.6

KM=0.19 µM for InsP7

Vmax=0.39 nmol/min/mg enzyme with InsP6 as substrate

Vmax=1.38 nmol/min/mg enzyme with InsP7 as substrate

Sequence caution

The sequence BAA24863.2 differs from that shown. Reason: Erroneous initiation.

The sequence EAW49076.1 differs from that shown. Reason: Erroneous gene model prediction.

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: O43314-1)

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.
Isoform 2 (identifier: O43314-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1097-1117: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 12431243Inositol hexakisphosphate and diphosphoinositol-pentakisphosphate kinase 2
PRO_0000315692

Regions

Nucleotide binding237 – 2404ATP
Nucleotide binding246 – 2483ATP
Nucleotide binding321 – 3233ATP
Region53 – 542Substrate binding
Region213 – 2142Substrate binding
Region326 – 3294Substrate binding
Region371 – 44272Polyphosphoinositide-binding domain

Sites

Binding site1341ATP
Binding site1871ATP
Binding site1941ATP
Binding site2131ATP
Binding site2481Substrate
Binding site2621Substrate
Binding site2641ATP
Binding site3091ATP

Amino acid modifications

Modified residue381Phosphoserine Ref.9
Modified residue10061Phosphoserine Ref.8
Modified residue10161Phosphoserine Ref.8
Modified residue11721Phosphoserine Ref.8

Natural variations

Alternative sequence1097 – 111721Missing in isoform 2.
VSP_030636
Natural variant9441A → G.
Corresponds to variant rs17155115 [ dbSNP | Ensembl ].
VAR_038276
Natural variant9851E → K.
Corresponds to variant rs12519525 [ dbSNP | Ensembl ].
VAR_038277
Natural variant10031R → K.
Corresponds to variant rs12520040 [ dbSNP | Ensembl ].
VAR_038278
Natural variant12061P → Q.
Corresponds to variant rs17155138 [ dbSNP | Ensembl ].
VAR_038279
Natural variant12321T → M.
Corresponds to variant rs17155147 [ dbSNP | Ensembl ].
VAR_038280

Experimental info

Mutagenesis2131R → A or K: Reduces enzyme activity by about 99%. Ref.12
Mutagenesis2481K → A: Loss of enzyme activity. Ref.12
Mutagenesis2621R → A: Reduces enzyme activity by about 99%. Ref.12

Secondary structure

............................................................. 1243
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified January 15, 2008. Version 3.
Checksum: A8831DDDAB9B2E6E

FASTA1,243140,407
        10         20         30         40         50         60 
MSEAPRFFVG PEDTEINPGN YRHFFHHADE DDEEEDDSPP ERQIVVGICS MAKKSKSKPM 

        70         80         90        100        110        120 
KEILERISLF KYITVVVFEE EVILNEPVEN WPLCDCLISF HSKGFPLDKA VAYAKLRNPF 

       130        140        150        160        170        180 
VINDLNMQYL IQDRREVYSI LQAEGILLPR YAILNRDPNN PKECNLIEGE DHVEVNGEVF 

       190        200        210        220        230        240 
QKPFVEKPVS AEDHNVYIYY PTSAGGGSQR LFRKIGSRSS VYSPESNVRK TGSYIYEEFM 

       250        260        270        280        290        300 
PTDGTDVKVY TVGPDYAHAE ARKSPALDGK VERDSEGKEV RYPVILNARE KLIAWKVCLA 

       310        320        330        340        350        360 
FKQTVCGFDL LRANGQSYVC DVNGFSFVKN SMKYYDDCAK ILGNIVMREL APQFHIPWSI 

       370        380        390        400        410        420 
PLEAEDIPIV PTTSGTMMEL RCVIAVIRHG DRTPKQKMKM EVRHQKFFDL FEKCDGYKSG 

       430        440        450        460        470        480 
KLKLKKPKQL QEVLDIARQL LMELGQNNDS EIEENKPKLE QLKTVLEMYG HFSGINRKVQ 

       490        500        510        520        530        540 
LTYLPHGCPK TSSEEEDSRR EEPSLLLVLK WGGELTPAGR VQAEELGRAF RCMYPGGQGD 

       550        560        570        580        590        600 
YAGFPGCGLL RLHSTYRHDL KIYASDEGRV QMTAAAFAKG LLALEGELTP ILVQMVKSAN 

       610        620        630        640        650        660 
MNGLLDSDSD SLSSCQQRVK ARLHEILQKD RDFTAEDYEK LTPSGSISLI KSMHLIKNPV 

       670        680        690        700        710        720 
KTCDKVYSLI QSLTSQIRHR MEDPKSSDIQ LYHSETLELM LRRWSKLEKD FKTKNGRYDI 

       730        740        750        760        770        780 
SKIPDIYDCI KYDVQHNGSL KLENTMELYR LSKALADIVI PQEYGITKAE KLEIAKGYCT 

       790        800        810        820        830        840 
PLVRKIRSDL QRTQDDDTVN KLHPVYSRGV LSPERHVRTR LYFTSESHVH SLLSILRYGA 

       850        860        870        880        890        900 
LCNESKDEQW KRAMDYLNVV NELNYMTQIV IMLYEDPNKD LSSEERFHVE LHFSPGAKGC 

       910        920        930        940        950        960 
EEDKNLPSGY GYRPASRENE GRRPFKIDND DEPHTSKRDE VDRAVILFKP MVSEPIHIHR 

       970        980        990       1000       1010       1020 
KSPLPRSRKT ATNDEESPLS VSSPEGTGTW LHYTSGVGTG RRRRRSGEQI TSSPVSPKSL 

      1030       1040       1050       1060       1070       1080 
AFTSSIFGSW QQVVSENANY LRTPRTLVEQ KQNPTVGSHC AGLFSTSVLG GSSSAPNLQD 

      1090       1100       1110       1120       1130       1140 
YARTHRKKLT SSGCIDDATR GSAVKRFSIS FARHPTNGFE LYSMVPSICP LETLHNALSL 

      1150       1160       1170       1180       1190       1200 
KQVDEFLASI ASPSSDVPRK TAEISSTALR SSPIMRKKVS LNTYTPAKIL PTPPATLKST 

      1210       1220       1230       1240 
KASSKPATSG PSSAVVPNTS SRKKNITSKT ETHEHKKNTG KKK 

« Hide

Isoform 2 [UniParc].

Checksum: C61F832FE77F87F3
Show »

FASTA1,222138,106

References

« Hide 'large scale' references
[1]"Prediction of the coding sequences of unidentified human genes. VIII. 78 new cDNA clones from brain which code for large proteins in vitro."
Ishikawa K., Nagase T., Nakajima D., Seki N., Ohira M., Miyajima N., Tanaka A., Kotani H., Nomura N., Ohara O.
DNA Res. 4:307-313(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Brain.
[2]"Construction of expression-ready cDNA clones for KIAA genes: manual curation of 330 KIAA cDNA clones."
Nakajima D., Okazaki N., Yamakawa H., Kikuno R., Ohara O., Nagase T.
DNA Res. 9:99-106(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: SEQUENCE REVISION.
[3]"The DNA sequence and comparative analysis of human chromosome 5."
Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S., Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M., She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S. expand/collapse author list , Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M., Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R., Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J., Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A., Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M.
Nature 431:268-274(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
Tissue: Uterus.
[6]"Cloning and characterization of two human VIP1-like inositol hexakisphosphate and diphosphoinositol pentakisphosphate kinases."
Fridy P.C., Otto J.C., Dollins D.E., York J.D.
J. Biol. Chem. 282:30754-30762(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, ENZYME ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, SUBCELLULAR LOCATION.
[7]"Purification, sequencing, and molecular identification of a mammalian PP-InsP5 kinase that is activated when cells are exposed to hyperosmotic stress."
Choi J.H., Williams J., Cho J., Falck J.R., Shears S.B.
J. Biol. Chem. 282:30763-30775(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, ENZYME ACTIVITY.
[8]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1006; SER-1016 AND SER-1172, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[9]"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions."
Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K.
Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-38, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Leukemic T-cell.
[10]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[11]"Receptor-dependent compartmentalization of PPIP5K1, a kinase with a cryptic polyphosphoinositide binding domain."
Gokhale N.A., Zaremba A., Shears S.B.
Biochem. J. 434:415-426(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: CATALYTIC ACTIVITY, POLYPHOSPHOINOSITIDE-BINDING DOMAIN.
[12]"Structural basis for an inositol pyrophosphate kinase surmounting phosphate crowding."
Wang H., Falck J.R., Hall T.M., Shears S.B.
Nat. Chem. Biol. 8:111-116(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.70 ANGSTROMS) OF 41-366 IN COMPLEXES WITH ATP; SUBSTRATE AND TRANSITION STATE ANALOG, MUTAGENESIS OF ARG-213; LYS-248 AND ARG-262.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
RefSeqNP_001263206.1. NM_001276277.1.
NP_001268400.1. NM_001281471.1.
NP_056031.2. NM_015216.3.
XP_005271992.1. XM_005271935.1.
UniGeneHs.212046.

3D structure databases

PDBe
RCSB PDB
PDBj
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[»]
ProteinModelPortalO43314.
SMRO43314. Positions 42-360, 513-586.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid116864. 8 interactions.
IntActO43314. 1 interaction.

PTM databases

PhosphoSiteO43314.

Proteomic databases

PaxDbO43314.
PRIDEO43314.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000321521; ENSP00000313070; ENSG00000145725. [O43314-2]
ENST00000358359; ENSP00000351126; ENSG00000145725. [O43314-1]
ENST00000414217; ENSP00000416016; ENSG00000145725. [O43314-2]
ENST00000570566; ENSP00000459756; ENSG00000262234. [O43314-1]
ENST00000576175; ENSP00000458792; ENSG00000262234. [O43314-2]
GeneID23262.
KEGGhsa:23262.
UCSCuc003kod.5. human. [O43314-1]
uc003koe.4. human. [O43314-2]

Organism-specific databases

CTD23262.
GeneCardsGC05P102455.
H-InvDBHIX0005068.
HIX0029534.
HGNCHGNC:29035. PPIP5K2.
HPAHPA038442.
MIM611648. gene.
neXtProtNX_O43314.
PharmGKBPA165660454.
HUGESearch...
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG245915.
HOGENOMHOG000177917.
HOVERGENHBG108657.
InParanoidO43314.
KOK13024.
OMADGTDVKX.
PhylomeDBO43314.
TreeFamTF313594.

Enzyme and pathway databases

ReactomeREACT_111217. Metabolism.

Gene expression databases

ArrayExpressO43314.
BgeeO43314.
CleanExHS_HISPPD1.
GenevestigatorO43314.

Family and domain databases

InterProIPR000560. His_Pase_superF_clade-2.
[Graphical view]
PfamPF00328. His_Phos_2. 1 hit.
[Graphical view]
PROSITEPS00616. HIS_ACID_PHOSPHAT_1. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GenomeRNAi23262.
NextBio45000.
PROO43314.
SOURCESearch...

Entry information

Entry nameVIP2_HUMAN
AccessionPrimary (citable) accession number: O43314
Secondary accession number(s): A1NI53, A6NGS8, Q8TB50
Entry history
Integrated into UniProtKB/Swiss-Prot: January 15, 2008
Last sequence update: January 15, 2008
Last modified: April 16, 2014
This is version 99 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 5

Human chromosome 5: entries, gene names and cross-references to MIM