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Protein

Inositol hexakisphosphate and diphosphoinositol-pentakisphosphate kinase 1

Gene

Ppip5k1

Organism
Mus musculus (Mouse)
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. Activated when cells are exposed to hyperosmotic stress.By similarity

Catalytic activityi

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

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei145ATPBy similarity1
Binding sitei198ATPBy similarity1
Binding sitei205ATPBy similarity1
Binding sitei224ATPBy similarity1
Binding sitei259SubstrateBy similarity1
Binding sitei273SubstrateBy similarity1
Binding sitei275ATPBy similarity1
Binding sitei320ATPBy similarity1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi248 – 251ATPBy similarity4
Nucleotide bindingi257 – 259ATPBy similarity3
Nucleotide bindingi332 – 334ATPBy similarity3

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Kinase, Transferase

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

ReactomeiR-MMU-1855167. Synthesis of pyrophosphates in the cytosol.

Names & Taxonomyi

Protein namesi
Recommended name:
Inositol hexakisphosphate and diphosphoinositol-pentakisphosphate kinase 1 (EC:2.7.4.21, EC:2.7.4.24)
Alternative name(s):
Diphosphoinositol pentakisphosphate kinase 1
Histidine acid phosphatase domain-containing protein 2A
InsP6 and PP-IP5 kinase 1
VIP1 homolog
Gene namesi
Name:Ppip5k1
Synonyms:Hisppd2a, Kiaa0377, Vip1
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 2

Organism-specific databases

MGIiMGI:2443281. Ppip5k1.

Subcellular locationi

  • Cytoplasmcytosol By similarity
  • Cell membrane By similarity

  • Note: Relocalizes to the plasma membrane upon activation of the PtdIns 3-kinase pathway.By similarity

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00003156891 – 1436Inositol hexakisphosphate and diphosphoinositol-pentakisphosphate kinase 1Add BLAST1436

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei939PhosphoserineBy similarity1
Modified residuei982PhosphoserineBy similarity1
Modified residuei1032PhosphoserineBy similarity1
Modified residuei1068PhosphoserineBy similarity1
Modified residuei1140PhosphoserineCombined sources1
Modified residuei1147PhosphoserineCombined sources1

Keywords - PTMi

Phosphoprotein

Proteomic databases

MaxQBiA2ARP1.
PaxDbiA2ARP1.
PeptideAtlasiA2ARP1.
PRIDEiA2ARP1.

PTM databases

iPTMnetiA2ARP1.
PhosphoSitePlusiA2ARP1.

Expressioni

Gene expression databases

BgeeiENSMUSG00000033526.
CleanExiMM_HISPPD2A.
ExpressionAtlasiA2ARP1. baseline and differential.
GenevisibleiA2ARP1. MM.

Interactioni

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000057632.

Structurei

3D structure databases

ProteinModelPortaliA2ARP1.
SMRiA2ARP1.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni64 – 65Substrate bindingBy similarity2
Regioni224 – 225Substrate bindingBy similarity2
Regioni337 – 340Substrate bindingBy similarity4
Regioni382 – 453Polyphosphoinositide-binding domainBy similarityAdd 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.By similarity

Sequence similaritiesi

Phylogenomic databases

eggNOGiKOG1057. Eukaryota.
ENOG410XNSN. LUCA.
GeneTreeiENSGT00390000009048.
HOVERGENiHBG108657.
InParanoidiA2ARP1.
KOiK13024.
OMAiMHSNQAS.
OrthoDBiEOG091G00ZU.
PhylomeDBiA2ARP1.
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.
IPR030138. PPIP5K1.
[Graphical view]
PANTHERiPTHR12750:SF11. PTHR12750:SF11. 1 hit.
PfamiPF00328. His_Phos_2. 1 hit.
[Graphical view]
SUPFAMiSSF53254. SSF53254. 3 hits.
PROSITEiPS00616. HIS_ACID_PHOSPHAT_1. 1 hit.
[Graphical view]

Sequences (6)i

Sequence statusi: Complete.

This entry describes 6 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: A2ARP1-1) [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
MWSLTANEDE STTAHFFLGA GDEGLGTCGI GMRTEESDSE LLEDEEDEVP
60 70 80 90 100
PEPQIIVGIC AMTKKSKSKP MTQILERLCR FDYLTVVILG EDVILNEPVE
110 120 130 140 150
NWPSCHCLIS FHSKGFPLDK AVAYSKLRNP FLINDLAMQY YIQDRREVYR
160 170 180 190 200
ILQEEGIDLP RYAVLNRDPA CPEECSLIEG EDQVEVNGAV FPKPFVEKPV
210 220 230 240 250
SAEDHNVYIY YPSSAGGGSQ RLFRKIGSRS SVYSPESSVR KTGSYIYEEF
260 270 280 290 300
MPTDGTDVKV YTVGPDYAHA EARKSPALDG KVERDSEGKE VRYPVMLTAM
310 320 330 340 350
EKLVARKVCV AFKQTVCGFD LLRANGHSFV CDVNGFSFVK NSMKYYDDCA
360 370 380 390 400
KILGNTIMRE LAPQFQIPWS IPTEAEDIPI VPTTSGTMME LRCVIAIIRH
410 420 430 440 450
GDRTPKQKMK MEVTHPRFFA LFEKHGGYKT GKLKLKRPEQ LQEVLDITRL
460 470 480 490 500
LLAELEKEPE AEIEEKTGKL EQLKSVLEMY GHFSGINRKV QLTYYPHGVK
510 520 530 540 550
ASNEGQDLQR EPLAPSLLLV LKWGGELTPD GRVQAEELGR AFRCMYPGGQ
560 570 580 590 600
GDYAGFPGCG LLRLHSTFRH DLKIYASDEG RVQMTAAAFA KGLLALEGEL
610 620 630 640 650
TPILVQMVKS ANMNGLLDSD SDSLSSCQHR VKARLHHILQ QDAPFGPEDY
660 670 680 690 700
DQLAPTGSTS LLNSMSVIQN PVKVCDQVFA LIENLTHQIR ERMQDPSSVD
710 720 730 740 750
LQLYHSETLE LMLQRWSKLE RDFRQKSGRY DISKIPDIYD CVKYDVQHNG
760 770 780 790 800
SLGLQGTAEL LRLSKALADV VIPQEYGISR EEKVEIAVGF CLPLLRKILL
810 820 830 840 850
DLQRTHEDES VNKLHPLYSR GVLSPGRHVR TRLYFTSESH VHSLLSVFRY
860 870 880 890 900
GGLLDETQDA QWQRALAYLS AISELNYMTQ IVIMLYEDNT RDPLSEERFH
910 920 930 940 950
VELHFSPGVK GVEEGSAPAG CGFRPASSEN EEMKTDPGSI ENLCPGKASD
960 970 980 990 1000
EPDRALQTSP QPVEGTGLPR RSPLIRNRKA GSMEVLSETS SSRPGGYRLF
1010 1020 1030 1040 1050
SSSRPPTEMK QSGLGSQCTG LFSTTVLGGS SSAPNLQDYA RTHGKKLPPA
1060 1070 1080 1090 1100
SLKHRDELLF VPAVKRFSVS FAKHPTNGFE GCSMVPTIYP LETLHNALSL
1110 1120 1130 1140 1150
RQVSEFLTKV CQRHTDAHAQ ASAALFDSMH NHQASDSPFS PPRTLHSPPL
1160 1170 1180 1190 1200
QLRHRSEKPP WYSSGPSSTV SSAGPSSPTT VDGNSHFGFS DQSSVNIHMT
1210 1220 1230 1240 1250
EEKQGFGLLQ ETPGDGTREL HIERQQELVE PAQSPQELPV EICPSGSQGV
1260 1270 1280 1290 1300
TKVSQTCQEV PDIVQPCHNI HEEIGQPQQE VPDISQLLLK DHDTTTNTCH
1310 1320 1330 1340 1350
LCQASQLSQK VCEEICQLCQ DNHEESNQLC QEVSVKLGRM VHGFPVNVDS
1360 1370 1380 1390 1400
TAQETLMEIG RPTQEIPEDP YQEFSVKVGV LAQKAPAISE LSQDIPEADK
1410 1420 1430
PSQELSEETE LQAQEVSEEI DQESEVVDEL PPEAIS
Length:1,436
Mass (Da):159,923
Last modified:February 20, 2007 - v1
Checksum:iD160DDDA7F34B4F2
GO
Isoform 2 (identifier: A2ARP1-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     818-837: Missing.

Note: No experimental confirmation available.
Show »
Length:1,416
Mass (Da):157,588
Checksum:i39D0CF8B9C48BF98
GO
Isoform 3 (identifier: A2ARP1-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1057-1077: Missing.

Note: No experimental confirmation available.
Show »
Length:1,415
Mass (Da):157,553
Checksum:iF51E050A638DA33A
GO
Isoform 4 (identifier: A2ARP1-5) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     261-266: YTVGPD → MVDAEI
     267-1436: Missing.

Note: No experimental confirmation available.
Show »
Length:266
Mass (Da):29,888
Checksum:i3058794BBECC2253
GO
Isoform 5 (identifier: A2ARP1-6) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     403-439: RTPKQKMKMEVTHPRFFALFEKHGGYKTGKLKLKRPE → HPSFVIEKLVPWRCCLKLHLQDLVATVCFHLHGHQQR
     440-1436: Missing.

Note: No experimental confirmation available.
Show »
Length:439
Mass (Da):49,416
Checksum:i5886DD464B506F60
GO
Isoform 6 (identifier: A2ARP1-7) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     653-671: LAPTGSTSLLNSMSVIQNP → VTLFSSPCSNYIATQFLKF
     672-1436: Missing.

Note: No experimental confirmation available.
Show »
Length:671
Mass (Da):75,262
Checksum:iDDF3D544D053FE04
GO

Sequence cautioni

The sequence BAC32838 differs from that shown. Intron retention.Curated
The sequence BAC37198 differs from that shown. Reason: Frameshift at position 42.Curated
The sequence BAC65546 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti441L → I in BAC38780 (PubMed:16141072).Curated1
Sequence conflicti831T → A in BAC32838 (PubMed:16141072).Curated1
Sequence conflicti1049P → S in BAC65546 (PubMed:12693553).Curated1
Sequence conflicti1180T → A in AAP46293 (Ref. 1) Curated1
Sequence conflicti1180T → A in BAC65546 (PubMed:12693553).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_030625261 – 266YTVGPD → MVDAEI in isoform 4. 1 Publication6
Alternative sequenceiVSP_030626267 – 1436Missing in isoform 4. 1 PublicationAdd BLAST1170
Alternative sequenceiVSP_030627403 – 439RTPKQ…LKRPE → HPSFVIEKLVPWRCCLKLHL QDLVATVCFHLHGHQQR in isoform 5. 1 PublicationAdd BLAST37
Alternative sequenceiVSP_030628440 – 1436Missing in isoform 5. 1 PublicationAdd BLAST997
Alternative sequenceiVSP_030629653 – 671LAPTG…VIQNP → VTLFSSPCSNYIATQFLKF in isoform 6. 1 PublicationAdd BLAST19
Alternative sequenceiVSP_030630672 – 1436Missing in isoform 6. 1 PublicationAdd BLAST765
Alternative sequenceiVSP_030631818 – 837Missing in isoform 2. CuratedAdd BLAST20
Alternative sequenceiVSP_0306341057 – 1077Missing in isoform 3. CuratedAdd BLAST21

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF502585 mRNA. Translation: AAP46293.1.
AK122264 mRNA. Translation: BAC65546.1. Different initiation.
AK046696 mRNA. Translation: BAC32838.1. Sequence problems.
AK078268 mRNA. Translation: BAC37198.1. Frameshift.
AK083140 mRNA. Translation: BAC38780.1.
AL845466 Genomic DNA. Translation: CAM24220.1.
AL845466 Genomic DNA. Translation: CAM24221.1.
AL845466 Genomic DNA. Translation: CAM24222.1.
BC065138 mRNA. Translation: AAH65138.1.
CCDSiCCDS16639.1. [A2ARP1-1]
RefSeqiNP_848910.3. NM_178795.4. [A2ARP1-1]
XP_006499804.1. XM_006499741.3. [A2ARP1-1]
XP_011237919.1. XM_011239617.2. [A2ARP1-3]
UniGeneiMm.386076.

Genome annotation databases

EnsembliENSMUST00000052029; ENSMUSP00000057632; ENSMUSG00000033526. [A2ARP1-1]
ENSMUST00000110625; ENSMUSP00000106255; ENSMUSG00000033526. [A2ARP1-3]
ENSMUST00000110626; ENSMUSP00000106256; ENSMUSG00000033526. [A2ARP1-1]
ENSMUST00000110627; ENSMUSP00000106257; ENSMUSG00000033526. [A2ARP1-3]
ENSMUST00000110628; ENSMUSP00000106258; ENSMUSG00000033526. [A2ARP1-2]
GeneIDi327655.
KEGGimmu:327655.
UCSCiuc008lyl.1. mouse. [A2ARP1-1]
uc008lyq.1. mouse. [A2ARP1-7]
uc008lyr.1. mouse. [A2ARP1-5]
uc008lys.1. mouse. [A2ARP1-6]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF502585 mRNA. Translation: AAP46293.1.
AK122264 mRNA. Translation: BAC65546.1. Different initiation.
AK046696 mRNA. Translation: BAC32838.1. Sequence problems.
AK078268 mRNA. Translation: BAC37198.1. Frameshift.
AK083140 mRNA. Translation: BAC38780.1.
AL845466 Genomic DNA. Translation: CAM24220.1.
AL845466 Genomic DNA. Translation: CAM24221.1.
AL845466 Genomic DNA. Translation: CAM24222.1.
BC065138 mRNA. Translation: AAH65138.1.
CCDSiCCDS16639.1. [A2ARP1-1]
RefSeqiNP_848910.3. NM_178795.4. [A2ARP1-1]
XP_006499804.1. XM_006499741.3. [A2ARP1-1]
XP_011237919.1. XM_011239617.2. [A2ARP1-3]
UniGeneiMm.386076.

3D structure databases

ProteinModelPortaliA2ARP1.
SMRiA2ARP1.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000057632.

PTM databases

iPTMnetiA2ARP1.
PhosphoSitePlusiA2ARP1.

Proteomic databases

MaxQBiA2ARP1.
PaxDbiA2ARP1.
PeptideAtlasiA2ARP1.
PRIDEiA2ARP1.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000052029; ENSMUSP00000057632; ENSMUSG00000033526. [A2ARP1-1]
ENSMUST00000110625; ENSMUSP00000106255; ENSMUSG00000033526. [A2ARP1-3]
ENSMUST00000110626; ENSMUSP00000106256; ENSMUSG00000033526. [A2ARP1-1]
ENSMUST00000110627; ENSMUSP00000106257; ENSMUSG00000033526. [A2ARP1-3]
ENSMUST00000110628; ENSMUSP00000106258; ENSMUSG00000033526. [A2ARP1-2]
GeneIDi327655.
KEGGimmu:327655.
UCSCiuc008lyl.1. mouse. [A2ARP1-1]
uc008lyq.1. mouse. [A2ARP1-7]
uc008lyr.1. mouse. [A2ARP1-5]
uc008lys.1. mouse. [A2ARP1-6]

Organism-specific databases

CTDi9677.
MGIiMGI:2443281. Ppip5k1.
RougeiSearch...

Phylogenomic databases

eggNOGiKOG1057. Eukaryota.
ENOG410XNSN. LUCA.
GeneTreeiENSGT00390000009048.
HOVERGENiHBG108657.
InParanoidiA2ARP1.
KOiK13024.
OMAiMHSNQAS.
OrthoDBiEOG091G00ZU.
PhylomeDBiA2ARP1.
TreeFamiTF313594.

Enzyme and pathway databases

ReactomeiR-MMU-1855167. Synthesis of pyrophosphates in the cytosol.

Miscellaneous databases

PROiA2ARP1.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000033526.
CleanExiMM_HISPPD2A.
ExpressionAtlasiA2ARP1. baseline and differential.
GenevisibleiA2ARP1. MM.

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.
IPR030138. PPIP5K1.
[Graphical view]
PANTHERiPTHR12750:SF11. PTHR12750:SF11. 1 hit.
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 nameiVIP1_MOUSE
AccessioniPrimary (citable) accession number: A2ARP1
Secondary accession number(s): A2ARP2
, A2ARP3, A2ARP4, Q6P1C8, Q7TSP1, Q80U21, Q8BL16, Q8BUN6, Q8BVG9
Entry historyi
Integrated into UniProtKB/Swiss-Prot: January 15, 2008
Last sequence update: February 20, 2007
Last modified: November 2, 2016
This is version 91 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. 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.