Q6PFW1 (VIP1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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
IP6 kinase
Inositol pyrophosphate synthase 1
InsP6 and PP-IP5 kinase 1
VIP1 homolog
Short name=hsVIP1

Gene names

Name:	PPIP5K1
Synonyms:	HISPPD2A, IP6K, IPS1, KIAA0377, VIP1

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	1433 AA.
Sequence status	Complete.
Protein existence	Evidence 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. Activated when cells are exposed to hyperosmotic stress. Ref.7 Ref.8 Ref.9
Catalytic activity	ATP + 1D-myo-inositol hexakisphosphate = ADP + 1D-myo-inositol 5-diphosphate 1,2,3,4,6-pentakisphosphate. Ref.7 Ref.8 Ref.9 Ref.12 Ref.13 ATP + 1D-myo-inositol 1,3,4,5,6-pentakisphosphate = ADP + 1D-myo-inositol diphosphate tetrakisphosphate (isomeric configuration unknown). Ref.7 Ref.8 Ref.9 Ref.12 Ref.13 ATP + 1D-myo-inositol 5-diphosphate pentakisphosphate = ADP + 1D-myo-inositol bisdiphosphate tetrakisphosphate (isomeric configuration unknown). Ref.7 Ref.8 Ref.9 Ref.12 Ref.13
Subcellular location	Cytoplasm › cytosol. Cell membrane. Note: Relocalizes to the plasma membrane upon activation of the PtdIns 3-kinase pathway. Ref.7 Ref.8 Ref.13
Tissue specificity	Widely expressed, with a higher expression in skeletal muscle, heart and brain. Ref.7
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.13). Ref.13
Sequence similarities	Belongs to the histidine acid phosphatase family. VIP1 subfamily.
Biophysicochemical properties	Kinetic parameters: The catalytic efficiency is 80 folds higher for 5-PP-InsP5 (InsP7) compared to InsP6. KM=0.12 µM for InsP6 Ref.7 Ref.8 Ref.13 KM=0.10 µM for InsP7 Vmax=0.03 nmol/min/mg enzyme with InsP6 as substrate Vmax=0.13 nmol/min/mg enzyme with InsP7 as substrate
Sequence caution	The sequence BAA20831.2 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

Ontologies

Keywords
Cellular component	Cell membrane Cytoplasm Membrane
Coding sequence diversity	Alternative splicing
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Transferase
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	inositol metabolic process Inferred from direct assay Ref.9. Source: UniProtKB inositol phosphate metabolic process Traceable author statement. Source: Reactome
Cellular_component	cytosol Inferred from direct assay Ref.8. Source: UniProtKB nucleus Inferred from direct assay. Source: HPA plasma membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW acid phosphatase activity Inferred from electronic annotation. Source: InterPro diphosphoinositol-pentakisphosphate kinase activity Inferred from direct assay Ref.9. Source: UniProtKB inositol hexakisphosphate 1-kinase activity Inferred from electronic annotation. Source: EC inositol hexakisphosphate 3-kinase activity Inferred from electronic annotation. Source: EC inositol hexakisphosphate 5-kinase activity Inferred from direct assay Ref.9. Source: UniProtKB inositol-1,3,4,5,6-pentakisphosphate kinase activity Inferred from direct assay Ref.9. Source: UniProtKB kinase activity Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Alternative products

This entry describes 7 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: 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.

Isoform 2 (identifier: Q6PFW1-2)

The sequence of this isoform differs from the canonical sequence as follows:
     818-821: Missing.
     1082-1082: N → NG

Isoform 3 (identifier: Q6PFW1-3)

The sequence of this isoform differs from the canonical sequence as follows:
     818-821: Missing.
     1062-1082: Missing.

Isoform 4 (identifier: Q6PFW1-4)

The sequence of this isoform differs from the canonical sequence as follows:
     653-653: Missing.
     818-821: Missing.
     1062-1082: Missing.

Isoform 5 (identifier: Q6PFW1-5)

The sequence of this isoform differs from the canonical sequence as follows:
     810-821: Missing.
     865-957: Missing.
     1107-1240: Missing.

Isoform 6 (identifier: Q6PFW1-6)

The sequence of this isoform differs from the canonical sequence as follows:
     818-1433: Missing.

Note: No experimental confirmation available.

Isoform 7 (identifier: Q6PFW1-7)

The sequence of this isoform differs from the canonical sequence as follows:
     818-821: Missing.
     1020-1082: Missing.
     1167-1167: Y → LETRFCHVGQAGLELLTSSDLPASASQSAGITGVSHRTQPD

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 1433	1433	Inositol hexakisphosphate and diphosphoinositol-pentakisphosphate kinase 1		PRO_0000315688
Regions
	Nucleotide binding	248 – 251	4	ATP By similarity
	Nucleotide binding	257 – 259	3	ATP By similarity
	Nucleotide binding	332 – 334	3	ATP By similarity
	Region	64 – 65	2	Substrate binding By similarity
	Region	224 – 225	2	Substrate binding By similarity
	Region	337 – 340	4	Substrate binding By similarity
	Region	382 – 453	72	Polyphosphoinositide-binding domain
Sites
	Binding site	145	1	ATP By similarity
	Binding site	198	1	ATP By similarity
	Binding site	205	1	ATP By similarity
	Binding site	224	1	ATP By similarity
	Binding site	259	1	Substrate By similarity
	Binding site	273	1	Substrate By similarity
	Binding site	275	1	ATP By similarity
	Binding site	320	1	ATP By similarity
Amino acid modifications
	Modified residue	1152	1	Phosphoserine Ref.10
Natural variations
	Alternative sequence	653	1	Missing in isoform 4.		VSP_030615
	Alternative sequence	810 – 821	12	Missing in isoform 5.		VSP_030616
	Alternative sequence	818 – 1433	616	Missing in isoform 6.		VSP_030617
	Alternative sequence	818 – 821	4	Missing in isoform 2, isoform 3, isoform 4 and isoform 7.		VSP_030618
	Alternative sequence	865 – 957	93	Missing in isoform 5.		VSP_030619
	Alternative sequence	1020 – 1082	63	Missing in isoform 7.		VSP_030620
	Alternative sequence	1062 – 1082	21	Missing in isoform 3 and isoform 4.		VSP_030621
	Alternative sequence	1082	1	N → NG in isoform 2.		VSP_030622
	Alternative sequence	1107 – 1240	134	Missing in isoform 5.		VSP_030623
	Alternative sequence	1167	1	Y → LETRFCHVGQAGLELLTSSD LPASASQSAGITGVSHRTQP D in isoform 7.		VSP_030624
Experimental info
	Mutagenesis	399	1	R → A: Decreases 8-fold the affinity for PtdIns(3,4,5)P3. Ref.13
	Mutagenesis	417	1	R → A: Decreases 16-fold the affinity for PtdIns(3,4,5)P3. Ref.13
	Sequence conflict	44	1	D → G in CAD97968. Ref.4
	Sequence conflict	304	1	V → M in CAD97968. Ref.4
	Sequence conflict	374	1	E → V in CAD97968. Ref.4
	Sequence conflict	423	1	E → Q in AAP30843. Ref.1
	Sequence conflict	423	1	E → Q in AAP30845. Ref.1
	Sequence conflict	423	1	E → Q in AAN40768. Ref.1
	Sequence conflict	473	1	L → P in CAD97968. Ref.4
	Sequence conflict	483	1	F → S in AAP30845. Ref.1
	Sequence conflict	483	1	F → S in AAN40768. Ref.1
	Sequence conflict	490	1	V → E in CAD97968. Ref.4
	Sequence conflict	548	1	G → V in CAD97968. Ref.4
	Sequence conflict	738	1	I → L in AAP30845. Ref.1
	Sequence conflict	738	1	I → L in AAN40768. Ref.1
	Sequence conflict	788	1	V → A in AAP30845. Ref.1
	Sequence conflict	788	1	V → A in AAN40768. Ref.1
	Sequence conflict	936	1	E → G in CAI46011. Ref.4
	Sequence conflict	985	1	A → V in AAP30845. Ref.1
	Sequence conflict	985	1	A → V in AAN40768. Ref.1
	Sequence conflict	1020	1	G → A in AAP30843. Ref.1
	Sequence conflict	1041	1	L → P in AAP30845. Ref.1
	Sequence conflict	1041	1	L → P in AAN40768. Ref.1
	Sequence conflict	1066	1	V → L in AAP30842. Ref.1
	Sequence conflict	1126	1	A → T in CAI46011. Ref.4
	Sequence conflict	1134	1	M → V in CAI46011. Ref.4
	Sequence conflict	1198	1	P → R in CAI46011. Ref.4
	Sequence conflict	1293	1	H → M in AAP30845. Ref.1
	Sequence conflict	1293	1	H → M in AAN40768. Ref.1
	Sequence conflict	1294	1	D → T in AAP30845. Ref.1
	Sequence conflict	1294	1	D → T in AAN40768. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified July 5, 2004. Version 1. Checksum: BA0DEFB2A71B1467	FASTA	1,433	159,521
	10 20 30 40 50 60 MWSLTASEGE STTAHFFLGA GDEGLGTRGI GMRPEESDSE LLEDEEDEVP PEPQIIVGIC 70 80 90 100 110 120 AMTKKSKSKP MTQILERLCR FDYLTVVILG EDVILNEPVE NWPSCHCLIS FHSKGFPLDK 130 140 150 160 170 180 AVAYSKLRNP FLINDLAMQY YIQDRREVYR ILQEEGIDLP RYAVLNRDPA RPEECNLIEG 190 200 210 220 230 240 EDQVEVNGAV FPKPFVEKPV SAEDHNVYIY YPSSAGGGSQ RLFRKIGSRS SVYSPESSVR 250 260 270 280 290 300 KTGSYIYEEF MPTDGTDVKV YTVGPDYAHA EARKSPALDG KVERDSEGKE IRYPVMLTAM 310 320 330 340 350 360 EKLVARKVCV AFKQTVCGFD LLRANGHSFV CDVNGFSFVK NSMKYYDDCA KILGNTIMRE 370 380 390 400 410 420 LAPQFQIPWS IPTEAEDIPI VPTTSGTMME LRCVIAIIRH GDRTPKQKMK MEVKHPRFFA 430 440 450 460 470 480 LFEKHGGYKT GKLKLKRPEQ LQEVLDITRL LLAELEKEPG GEIEEKTGKL EQLKSVLEMY 490 500 510 520 530 540 GHFSGINRKV QLTYYPHGVK ASNEGQDPQR ETLAPSLLLV LKWGGELTPA GRVQAEELGR 550 560 570 580 590 600 AFRCMYPGGQ GDYAGFPGCG LLRLHSTFRH DLKIYASDEG RVQMTAAAFA KGLLALEGEL 610 620 630 640 650 660 TPILVQMVKS ANMNGLLDSD GDSLSSCQHR VKARLHHILQ QDAPFGPEDY DQLAPTRSTS 670 680 690 700 710 720 LLNSMTIIQN PVKVCDQVFA LIENLTHQIR ERMQDPRSVD LQLYHSETLE LMLQRWSKLE 730 740 750 760 770 780 RDFRQKSGRY DISKIPDIYD CVKYDVQHNG SLGLQGTAEL LRLSKALADV VIPQEYGISR 790 800 810 820 830 840 EEKLEIAVGF CLPLLRKILL DLQRTHEDES VNKLHPLCYL RYSRGVLSPG RHVRTRLYFT 850 860 870 880 890 900 SESHVHSLLS VFRYGGLLDE TQDAQWQRAL DYLSAISELN YMTQIVIMLY EDNTQDPLSE 910 920 930 940 950 960 ERFHVELHFS PGVKGVEEEG SAPAGCGFRP ASSENEEMKT NQGSMENLCP GKASDEPDRA 970 980 990 1000 1010 1020 LQTSPQPPEG PGLPRRSPLI RNRKAGSMEV LSETSSSRPG GYRLFSSSRP PTEMKQSGLG 1030 1040 1050 1060 1070 1080 SQCTGLFSTT VLGGSSSAPN LQDYARSHGK KLPPASLKHR DELLFVPAVK RFSVSFAKHP 1090 1100 1110 1120 1130 1140 TNGFEGCSMV PTIYPLETLH NALSLRQVSE FLSRVCQRHT DAQAQASAAL FDSMHSSQAS 1150 1160 1170 1180 1190 1200 DNPFSPPRTL HSPPLQLQQR SEKPPWYSSG PSSTVSSAGP SSPTTVDGNS QFGFSDQPSL 1210 1220 1230 1240 1250 1260 NSHVAEEHQG LGLLQETPGS GAQELSIEGE QELFEPNQSP QVPPMETSQP YEEVSQPCQE 1270 1280 1290 1300 1310 1320 VPDISQPCQD ISEALSQPCQ KVPDISQQCQ ENHDNGNHTC QEVPHISQPC QKSSQLCQKV 1330 1340 1350 1360 1370 1380 SEEVCQLCLE NSEEVSQPCQ GVSVEVGKLV HKFHVGVGSL VQETLVEVGS PAEEIPEEVI 1390 1400 1410 1420 1430 QPYQEFSVEV GRLAQETSAI NLLSQGIPEI DKPSQEFPEE IDLQAQEVPE EIN
	Isoform 2 [UniParc]. Checksum: 11E6EC888FB5703C	FASTA	1,430	159,042
	10 20 30 40 50 60 MWSLTASEGE STTAHFFLGA GDEGLGTRGI GMRPEESDSE LLEDEEDEVP PEPQIIVGIC 70 80 90 100 110 120 AMTKKSKSKP MTQILERLCR FDYLTVVILG EDVILNEPVE NWPSCHCLIS FHSKGFPLDK 130 140 150 160 170 180 AVAYSKLRNP FLINDLAMQY YIQDRREVYR ILQEEGIDLP RYAVLNRDPA RPEECNLIEG 190 200 210 220 230 240 EDQVEVNGAV FPKPFVEKPV SAEDHNVYIY YPSSAGGGSQ RLFRKIGSRS SVYSPESSVR 250 260 270 280 290 300 KTGSYIYEEF MPTDGTDVKV YTVGPDYAHA EARKSPALDG KVERDSEGKE IRYPVMLTAM 310 320 330 340 350 360 EKLVARKVCV AFKQTVCGFD LLRANGHSFV CDVNGFSFVK NSMKYYDDCA KILGNTIMRE 370 380 390 400 410 420 LAPQFQIPWS IPTEAEDIPI VPTTSGTMME LRCVIAIIRH GDRTPKQKMK MEVKHPRFFA 430 440 450 460 470 480 LFEKHGGYKT GKLKLKRPEQ LQEVLDITRL LLAELEKEPG GEIEEKTGKL EQLKSVLEMY 490 500 510 520 530 540 GHFSGINRKV QLTYYPHGVK ASNEGQDPQR ETLAPSLLLV LKWGGELTPA GRVQAEELGR 550 560 570 580 590 600 AFRCMYPGGQ GDYAGFPGCG LLRLHSTFRH DLKIYASDEG RVQMTAAAFA KGLLALEGEL 610 620 630 640 650 660 TPILVQMVKS ANMNGLLDSD GDSLSSCQHR VKARLHHILQ QDAPFGPEDY DQLAPTRSTS 670 680 690 700 710 720 LLNSMTIIQN PVKVCDQVFA LIENLTHQIR ERMQDPRSVD LQLYHSETLE LMLQRWSKLE 730 740 750 760 770 780 RDFRQKSGRY DISKIPDIYD CVKYDVQHNG SLGLQGTAEL LRLSKALADV VIPQEYGISR 790 800 810 820 830 840 EEKLEIAVGF CLPLLRKILL DLQRTHEDES VNKLHPLYSR GVLSPGRHVR TRLYFTSESH 850 860 870 880 890 900 VHSLLSVFRY GGLLDETQDA QWQRALDYLS AISELNYMTQ IVIMLYEDNT QDPLSEERFH 910 920 930 940 950 960 VELHFSPGVK GVEEEGSAPA GCGFRPASSE NEEMKTNQGS MENLCPGKAS DEPDRALQTS 970 980 990 1000 1010 1020 PQPPEGPGLP RRSPLIRNRK AGSMEVLSET SSSRPGGYRL FSSSRPPTEM KQSGLGSQCT 1030 1040 1050 1060 1070 1080 GLFSTTVLGG SSSAPNLQDY ARSHGKKLPP ASLKHRDELL FVPAVKRFSV SFAKHPTNGG 1090 1100 1110 1120 1130 1140 FEGCSMVPTI YPLETLHNAL SLRQVSEFLS RVCQRHTDAQ AQASAALFDS MHSSQASDNP 1150 1160 1170 1180 1190 1200 FSPPRTLHSP PLQLQQRSEK PPWYSSGPSS TVSSAGPSSP TTVDGNSQFG FSDQPSLNSH 1210 1220 1230 1240 1250 1260 VAEEHQGLGL LQETPGSGAQ ELSIEGEQEL FEPNQSPQVP PMETSQPYEE VSQPCQEVPD 1270 1280 1290 1300 1310 1320 ISQPCQDISE ALSQPCQKVP DISQQCQENH DNGNHTCQEV PHISQPCQKS SQLCQKVSEE 1330 1340 1350 1360 1370 1380 VCQLCLENSE EVSQPCQGVS VEVGKLVHKF HVGVGSLVQE TLVEVGSPAE EIPEEVIQPY 1390 1400 1410 1420 1430 QEFSVEVGRL AQETSAINLL SQGIPEIDKP SQEFPEEIDL QAQEVPEEIN
	Isoform 3 [UniParc]. Checksum: E88E96597599F5BA	FASTA	1,408	156,616
	10 20 30 40 50 60 MWSLTASEGE STTAHFFLGA GDEGLGTRGI GMRPEESDSE LLEDEEDEVP PEPQIIVGIC 70 80 90 100 110 120 AMTKKSKSKP MTQILERLCR FDYLTVVILG EDVILNEPVE NWPSCHCLIS FHSKGFPLDK 130 140 150 160 170 180 AVAYSKLRNP FLINDLAMQY YIQDRREVYR ILQEEGIDLP RYAVLNRDPA RPEECNLIEG 190 200 210 220 230 240 EDQVEVNGAV FPKPFVEKPV SAEDHNVYIY YPSSAGGGSQ RLFRKIGSRS SVYSPESSVR 250 260 270 280 290 300 KTGSYIYEEF MPTDGTDVKV YTVGPDYAHA EARKSPALDG KVERDSEGKE IRYPVMLTAM 310 320 330 340 350 360 EKLVARKVCV AFKQTVCGFD LLRANGHSFV CDVNGFSFVK NSMKYYDDCA KILGNTIMRE 370 380 390 400 410 420 LAPQFQIPWS IPTEAEDIPI VPTTSGTMME LRCVIAIIRH GDRTPKQKMK MEVKHPRFFA 430 440 450 460 470 480 LFEKHGGYKT GKLKLKRPEQ LQEVLDITRL LLAELEKEPG GEIEEKTGKL EQLKSVLEMY 490 500 510 520 530 540 GHFSGINRKV QLTYYPHGVK ASNEGQDPQR ETLAPSLLLV LKWGGELTPA GRVQAEELGR 550 560 570 580 590 600 AFRCMYPGGQ GDYAGFPGCG LLRLHSTFRH DLKIYASDEG RVQMTAAAFA KGLLALEGEL 610 620 630 640 650 660 TPILVQMVKS ANMNGLLDSD GDSLSSCQHR VKARLHHILQ QDAPFGPEDY DQLAPTRSTS 670 680 690 700 710 720 LLNSMTIIQN PVKVCDQVFA LIENLTHQIR ERMQDPRSVD LQLYHSETLE LMLQRWSKLE 730 740 750 760 770 780 RDFRQKSGRY DISKIPDIYD CVKYDVQHNG SLGLQGTAEL LRLSKALADV VIPQEYGISR 790 800 810 820 830 840 EEKLEIAVGF CLPLLRKILL DLQRTHEDES VNKLHPLYSR GVLSPGRHVR TRLYFTSESH 850 860 870 880 890 900 VHSLLSVFRY GGLLDETQDA QWQRALDYLS AISELNYMTQ IVIMLYEDNT QDPLSEERFH 910 920 930 940 950 960 VELHFSPGVK GVEEEGSAPA GCGFRPASSE NEEMKTNQGS MENLCPGKAS DEPDRALQTS 970 980 990 1000 1010 1020 PQPPEGPGLP RRSPLIRNRK AGSMEVLSET SSSRPGGYRL FSSSRPPTEM KQSGLGSQCT 1030 1040 1050 1060 1070 1080 GLFSTTVLGG SSSAPNLQDY ARSHGKKLPP ASLKHRDGFE GCSMVPTIYP LETLHNALSL 1090 1100 1110 1120 1130 1140 RQVSEFLSRV CQRHTDAQAQ ASAALFDSMH SSQASDNPFS PPRTLHSPPL QLQQRSEKPP 1150 1160 1170 1180 1190 1200 WYSSGPSSTV SSAGPSSPTT VDGNSQFGFS DQPSLNSHVA EEHQGLGLLQ ETPGSGAQEL 1210 1220 1230 1240 1250 1260 SIEGEQELFE PNQSPQVPPM ETSQPYEEVS QPCQEVPDIS QPCQDISEAL SQPCQKVPDI 1270 1280 1290 1300 1310 1320 SQQCQENHDN GNHTCQEVPH ISQPCQKSSQ LCQKVSEEVC QLCLENSEEV SQPCQGVSVE 1330 1340 1350 1360 1370 1380 VGKLVHKFHV GVGSLVQETL VEVGSPAEEI PEEVIQPYQE FSVEVGRLAQ ETSAINLLSQ 1390 1400 GIPEIDKPSQ EFPEEIDLQA QEVPEEIN
	Isoform 4 [UniParc]. Checksum: 1DC5FCBF5A726F14	FASTA	1,407	156,502
	10 20 30 40 50 60 MWSLTASEGE STTAHFFLGA GDEGLGTRGI GMRPEESDSE LLEDEEDEVP PEPQIIVGIC 70 80 90 100 110 120 AMTKKSKSKP MTQILERLCR FDYLTVVILG EDVILNEPVE NWPSCHCLIS FHSKGFPLDK 130 140 150 160 170 180 AVAYSKLRNP FLINDLAMQY YIQDRREVYR ILQEEGIDLP RYAVLNRDPA RPEECNLIEG 190 200 210 220 230 240 EDQVEVNGAV FPKPFVEKPV SAEDHNVYIY YPSSAGGGSQ RLFRKIGSRS SVYSPESSVR 250 260 270 280 290 300 KTGSYIYEEF MPTDGTDVKV YTVGPDYAHA EARKSPALDG KVERDSEGKE IRYPVMLTAM 310 320 330 340 350 360 EKLVARKVCV AFKQTVCGFD LLRANGHSFV CDVNGFSFVK NSMKYYDDCA KILGNTIMRE 370 380 390 400 410 420 LAPQFQIPWS IPTEAEDIPI VPTTSGTMME LRCVIAIIRH GDRTPKQKMK MEVKHPRFFA 430 440 450 460 470 480 LFEKHGGYKT GKLKLKRPEQ LQEVLDITRL LLAELEKEPG GEIEEKTGKL EQLKSVLEMY 490 500 510 520 530 540 GHFSGINRKV QLTYYPHGVK ASNEGQDPQR ETLAPSLLLV LKWGGELTPA GRVQAEELGR 550 560 570 580 590 600 AFRCMYPGGQ GDYAGFPGCG LLRLHSTFRH DLKIYASDEG RVQMTAAAFA KGLLALEGEL 610 620 630 640 650 660 TPILVQMVKS ANMNGLLDSD GDSLSSCQHR VKARLHHILQ QDAPFGPEDY DQAPTRSTSL 670 680 690 700 710 720 LNSMTIIQNP VKVCDQVFAL IENLTHQIRE RMQDPRSVDL QLYHSETLEL MLQRWSKLER 730 740 750 760 770 780 DFRQKSGRYD ISKIPDIYDC VKYDVQHNGS LGLQGTAELL RLSKALADVV IPQEYGISRE 790 800 810 820 830 840 EKLEIAVGFC LPLLRKILLD LQRTHEDESV NKLHPLYSRG VLSPGRHVRT RLYFTSESHV 850 860 870 880 890 900 HSLLSVFRYG GLLDETQDAQ WQRALDYLSA ISELNYMTQI VIMLYEDNTQ DPLSEERFHV 910 920 930 940 950 960 ELHFSPGVKG VEEEGSAPAG CGFRPASSEN EEMKTNQGSM ENLCPGKASD EPDRALQTSP 970 980 990 1000 1010 1020 QPPEGPGLPR RSPLIRNRKA GSMEVLSETS SSRPGGYRLF SSSRPPTEMK QSGLGSQCTG 1030 1040 1050 1060 1070 1080 LFSTTVLGGS SSAPNLQDYA RSHGKKLPPA SLKHRDGFEG CSMVPTIYPL ETLHNALSLR 1090 1100 1110 1120 1130 1140 QVSEFLSRVC QRHTDAQAQA SAALFDSMHS SQASDNPFSP PRTLHSPPLQ LQQRSEKPPW 1150 1160 1170 1180 1190 1200 YSSGPSSTVS SAGPSSPTTV DGNSQFGFSD QPSLNSHVAE EHQGLGLLQE TPGSGAQELS 1210 1220 1230 1240 1250 1260 IEGEQELFEP NQSPQVPPME TSQPYEEVSQ PCQEVPDISQ PCQDISEALS QPCQKVPDIS 1270 1280 1290 1300 1310 1320 QQCQENHDNG NHTCQEVPHI SQPCQKSSQL CQKVSEEVCQ LCLENSEEVS QPCQGVSVEV 1330 1340 1350 1360 1370 1380 GKLVHKFHVG VGSLVQETLV EVGSPAEEIP EEVIQPYQEF SVEVGRLAQE TSAINLLSQG 1390 1400 IPEIDKPSQE FPEEIDLQAQ EVPEEIN
	Isoform 5 [UniParc]. Checksum: F29D866BFAD98841	FASTA	1,194	133,447
	10 20 30 40 50 60 MWSLTASEGE STTAHFFLGA GDEGLGTRGI GMRPEESDSE LLEDEEDEVP PEPQIIVGIC 70 80 90 100 110 120 AMTKKSKSKP MTQILERLCR FDYLTVVILG EDVILNEPVE NWPSCHCLIS FHSKGFPLDK 130 140 150 160 170 180 AVAYSKLRNP FLINDLAMQY YIQDRREVYR ILQEEGIDLP RYAVLNRDPA RPEECNLIEG 190 200 210 220 230 240 EDQVEVNGAV FPKPFVEKPV SAEDHNVYIY YPSSAGGGSQ RLFRKIGSRS SVYSPESSVR 250 260 270 280 290 300 KTGSYIYEEF MPTDGTDVKV YTVGPDYAHA EARKSPALDG KVERDSEGKE IRYPVMLTAM 310 320 330 340 350 360 EKLVARKVCV AFKQTVCGFD LLRANGHSFV CDVNGFSFVK NSMKYYDDCA KILGNTIMRE 370 380 390 400 410 420 LAPQFQIPWS IPTEAEDIPI VPTTSGTMME LRCVIAIIRH GDRTPKQKMK MEVKHPRFFA 430 440 450 460 470 480 LFEKHGGYKT GKLKLKRPEQ LQEVLDITRL LLAELEKEPG GEIEEKTGKL EQLKSVLEMY 490 500 510 520 530 540 GHFSGINRKV QLTYYPHGVK ASNEGQDPQR ETLAPSLLLV LKWGGELTPA GRVQAEELGR 550 560 570 580 590 600 AFRCMYPGGQ GDYAGFPGCG LLRLHSTFRH DLKIYASDEG RVQMTAAAFA KGLLALEGEL 610 620 630 640 650 660 TPILVQMVKS ANMNGLLDSD GDSLSSCQHR VKARLHHILQ QDAPFGPEDY DQLAPTRSTS 670 680 690 700 710 720 LLNSMTIIQN PVKVCDQVFA LIENLTHQIR ERMQDPRSVD LQLYHSETLE LMLQRWSKLE 730 740 750 760 770 780 RDFRQKSGRY DISKIPDIYD CVKYDVQHNG SLGLQGTAEL LRLSKALADV VIPQEYGISR 790 800 810 820 830 840 EEKLEIAVGF CLPLLRKILL DLQRTHEDEY SRGVLSPGRH VRTRLYFTSE SHVHSLLSVF 850 860 870 880 890 900 RYGGLLDETQ DADRALQTSP QPPEGPGLPR RSPLIRNRKA GSMEVLSETS SSRPGGYRLF 910 920 930 940 950 960 SSSRPPTEMK QSGLGSQCTG LFSTTVLGGS SSAPNLQDYA RSHGKKLPPA SLKHRDELLF 970 980 990 1000 1010 1020 VPAVKRFSVS FAKHPTNGFE GCSMVPTIYP LETLHNALSL RQVPPMETSQ PYEEVSQPCQ 1030 1040 1050 1060 1070 1080 EVPDISQPCQ DISEALSQPC QKVPDISQQC QENHDNGNHT CQEVPHISQP CQKSSQLCQK 1090 1100 1110 1120 1130 1140 VSEEVCQLCL ENSEEVSQPC QGVSVEVGKL VHKFHVGVGS LVQETLVEVG SPAEEIPEEV 1150 1160 1170 1180 1190 IQPYQEFSVE VGRLAQETSA INLLSQGIPE IDKPSQEFPE EIDLQAQEVP EEIN
	Isoform 6 [UniParc]. Checksum: 4DBCE9B366905530	FASTA	817	92,061
	10 20 30 40 50 60 MWSLTASEGE STTAHFFLGA GDEGLGTRGI GMRPEESDSE LLEDEEDEVP PEPQIIVGIC 70 80 90 100 110 120 AMTKKSKSKP MTQILERLCR FDYLTVVILG EDVILNEPVE NWPSCHCLIS FHSKGFPLDK 130 140 150 160 170 180 AVAYSKLRNP FLINDLAMQY YIQDRREVYR ILQEEGIDLP RYAVLNRDPA RPEECNLIEG 190 200 210 220 230 240 EDQVEVNGAV FPKPFVEKPV SAEDHNVYIY YPSSAGGGSQ RLFRKIGSRS SVYSPESSVR 250 260 270 280 290 300 KTGSYIYEEF MPTDGTDVKV YTVGPDYAHA EARKSPALDG KVERDSEGKE IRYPVMLTAM 310 320 330 340 350 360 EKLVARKVCV AFKQTVCGFD LLRANGHSFV CDVNGFSFVK NSMKYYDDCA KILGNTIMRE 370 380 390 400 410 420 LAPQFQIPWS IPTEAEDIPI VPTTSGTMME LRCVIAIIRH GDRTPKQKMK MEVKHPRFFA 430 440 450 460 470 480 LFEKHGGYKT GKLKLKRPEQ LQEVLDITRL LLAELEKEPG GEIEEKTGKL EQLKSVLEMY 490 500 510 520 530 540 GHFSGINRKV QLTYYPHGVK ASNEGQDPQR ETLAPSLLLV LKWGGELTPA GRVQAEELGR 550 560 570 580 590 600 AFRCMYPGGQ GDYAGFPGCG LLRLHSTFRH DLKIYASDEG RVQMTAAAFA KGLLALEGEL 610 620 630 640 650 660 TPILVQMVKS ANMNGLLDSD GDSLSSCQHR VKARLHHILQ QDAPFGPEDY DQLAPTRSTS 670 680 690 700 710 720 LLNSMTIIQN PVKVCDQVFA LIENLTHQIR ERMQDPRSVD LQLYHSETLE LMLQRWSKLE 730 740 750 760 770 780 RDFRQKSGRY DISKIPDIYD CVKYDVQHNG SLGLQGTAEL LRLSKALADV VIPQEYGISR 790 800 810 EEKLEIAVGF CLPLLRKILL DLQRTHEDES VNKLHPL
	Isoform 7 [UniParc]. Checksum: 77C01F2E2AC7446D	FASTA	1,406	156,320
	10 20 30 40 50 60 MWSLTASEGE STTAHFFLGA GDEGLGTRGI GMRPEESDSE LLEDEEDEVP PEPQIIVGIC 70 80 90 100 110 120 AMTKKSKSKP MTQILERLCR FDYLTVVILG EDVILNEPVE NWPSCHCLIS FHSKGFPLDK 130 140 150 160 170 180 AVAYSKLRNP FLINDLAMQY YIQDRREVYR ILQEEGIDLP RYAVLNRDPA RPEECNLIEG 190 200 210 220 230 240 EDQVEVNGAV FPKPFVEKPV SAEDHNVYIY YPSSAGGGSQ RLFRKIGSRS SVYSPESSVR 250 260 270 280 290 300 KTGSYIYEEF MPTDGTDVKV YTVGPDYAHA EARKSPALDG KVERDSEGKE IRYPVMLTAM 310 320 330 340 350 360 EKLVARKVCV AFKQTVCGFD LLRANGHSFV CDVNGFSFVK NSMKYYDDCA KILGNTIMRE 370 380 390 400 410 420 LAPQFQIPWS IPTEAEDIPI VPTTSGTMME LRCVIAIIRH GDRTPKQKMK MEVKHPRFFA 430 440 450 460 470 480 LFEKHGGYKT GKLKLKRPEQ LQEVLDITRL LLAELEKEPG GEIEEKTGKL EQLKSVLEMY 490 500 510 520 530 540 GHFSGINRKV QLTYYPHGVK ASNEGQDPQR ETLAPSLLLV LKWGGELTPA GRVQAEELGR 550 560 570 580 590 600 AFRCMYPGGQ GDYAGFPGCG LLRLHSTFRH DLKIYASDEG RVQMTAAAFA KGLLALEGEL 610 620 630 640 650 660 TPILVQMVKS ANMNGLLDSD GDSLSSCQHR VKARLHHILQ QDAPFGPEDY DQLAPTRSTS 670 680 690 700 710 720 LLNSMTIIQN PVKVCDQVFA LIENLTHQIR ERMQDPRSVD LQLYHSETLE LMLQRWSKLE 730 740 750 760 770 780 RDFRQKSGRY DISKIPDIYD CVKYDVQHNG SLGLQGTAEL LRLSKALADV VIPQEYGISR 790 800 810 820 830 840 EEKLEIAVGF CLPLLRKILL DLQRTHEDES VNKLHPLYSR GVLSPGRHVR TRLYFTSESH 850 860 870 880 890 900 VHSLLSVFRY GGLLDETQDA QWQRALDYLS AISELNYMTQ IVIMLYEDNT QDPLSEERFH 910 920 930 940 950 960 VELHFSPGVK GVEEEGSAPA GCGFRPASSE NEEMKTNQGS MENLCPGKAS DEPDRALQTS 970 980 990 1000 1010 1020 PQPPEGPGLP RRSPLIRNRK AGSMEVLSET SSSRPGGYRL FSSSRPPTEM KQSGLGFEGC 1030 1040 1050 1060 1070 1080 SMVPTIYPLE TLHNALSLRQ VSEFLSRVCQ RHTDAQAQAS AALFDSMHSS QASDNPFSPP 1090 1100 1110 1120 1130 1140 RTLHSPPLQL QQRSEKPPWL ETRFCHVGQA GLELLTSSDL PASASQSAGI TGVSHRTQPD 1150 1160 1170 1180 1190 1200 SSGPSSTVSS AGPSSPTTVD GNSQFGFSDQ PSLNSHVAEE HQGLGLLQET PGSGAQELSI 1210 1220 1230 1240 1250 1260 EGEQELFEPN QSPQVPPMET SQPYEEVSQP CQEVPDISQP CQDISEALSQ PCQKVPDISQ 1270 1280 1290 1300 1310 1320 QCQENHDNGN HTCQEVPHIS QPCQKSSQLC QKVSEEVCQL CLENSEEVSQ PCQGVSVEVG 1330 1340 1350 1360 1370 1380 KLVHKFHVGV GSLVQETLVE VGSPAEEIPE EVIQPYQEFS VEVGRLAQET SAINLLSQGI 1390 1400 PEIDKPSQEF PEEIDLQAQE VPEEIN

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"CATSPER2, a human autosomal nonsyndromic male infertility gene." Avidan N., Tamary H., Dgany O., Cattan D., Pariente A., Thulliez M., Borot N., Moati L., Barthelme A., Shalmon L., Krasnov T., Ben-Asher E., Olender T., Khen M., Yaniv I., Zaizov R., Shalev H., Delaunay J. , Fellous M., Lancet D., Beckmann J.S. Eur. J. Hum. Genet. 11:497-502(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2; 3 AND 5). Tissue: Bone marrow, Testis and Trachea.
[2]	"Prediction of the coding sequences of unidentified human genes. VII. The complete sequences of 100 new cDNA clones from brain which can code for large proteins in vitro." Nagase T., Ishikawa K., Nakajima D., Ohira M., Seki N., Miyajima N., Tanaka A., Kotani H., Nomura N., Ohara O. DNA Res. 4:141-150(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 7). Tissue: Brain.
[3]	Ohara O., Nagase T., Kikuno R., Nomura N. Submitted (JUL-1997) to the EMBL/GenBank/DDBJ databases Cited for: SEQUENCE REVISION.
[4]	"The full-ORF clone resource of the German cDNA consortium." Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I. BMC Genomics 8:399-399(2007) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 3 AND 4). Tissue: Endometrial adenocarcinoma.
[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] (ISOFORMS 1 AND 6). Tissue: Eye and Uterus.
[6]	"A probability-based approach for high-throughput protein phosphorylation analysis and site localization." Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P. Nat. Biotechnol. 24:1285-1292(2006) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: Cervix carcinoma.
[7]	"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, TISSUE SPECIFICITY.
[8]	"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, BIOPHYSICOCHEMICAL PROPERTIES, SUBCELLULAR LOCATION.
[9]	"A conserved family of enzymes that phosphorylate inositol hexakisphosphate." Mulugu S., Bai W., Fridy P.C., Bastidas R.J., Otto J.C., Dollins D.E., Haystead T.A., Ribeiro A.A., York J.D. Science 316:106-109(2007) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, ENZYME ACTIVITY.
[10]	"Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient phosphoproteomic analysis." Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III J. Proteome Res. 7:1346-1351(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1152, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[11]	"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: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: Cervix carcinoma.
[12]	"Structural analysis and detection of biological inositol pyrophosphates reveal that the family of VIP/diphosphoinositol pentakisphosphate kinases are 1/3-kinases." Lin H., Fridy P.C., Ribeiro A.A., Choi J.H., Barma D.K., Vogel G., Falck J.R., Shears S.B., York J.D., Mayr G.W. J. Biol. Chem. 284:1863-1872(2009) [PubMed] [Europe PMC] [Abstract] Cited for: CATALYTIC ACTIVITY.
[13]	"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: BIOPHYSICOCHEMICAL PROPERTIES, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, POLYPHOSPHOINOSITIDE-BINDING DOMAIN, MUTAGENESIS OF ARG-399 AND ARG-417.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF502586 mRNA. Translation: AAP30842.1. AF502587 mRNA. Translation: AAP30843.1. AF502588 mRNA. Translation: AAP30844.1. AF502589 mRNA. Translation: AAP30845.1. AF543190 mRNA. Translation: AAN40768.1. AB002375 mRNA. Translation: BAA20831.2. Different initiation. BX538022 mRNA. Translation: CAD97968.1. BX647814 mRNA. Translation: CAI46011.1. BC050263 mRNA. Translation: AAH50263.1. BC057395 mRNA. Translation: AAH57395.1.
IPI	IPI00005663. IPI00218030. IPI00384259. IPI00398511. IPI00657657. IPI00738361. IPI00877721.
RefSeq	NP_001124330.1. NM_001130858.2. NP_001124331.1. NM_001130859.2. NP_001177143.1. NM_001190214.1. NP_055474.3. NM_014659.5.
UniGene	Hs.156814. Hs.679911.
3D structure databases
ProteinModelPortal	Q6PFW1.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000380129.
PTM databases
PhosphoSite	Q6PFW1.
Polymorphism databases
DMDM	74758334.
Proteomic databases
PaxDb	Q6PFW1.
PRIDE	Q6PFW1.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000334933; ENSP00000334779; ENSG00000168781. ENST00000348806; ENSP00000308773; ENSG00000168781. ENST00000360135; ENSP00000353253; ENSG00000168781. ENST00000360301; ENSP00000353446; ENSG00000168781. ENST00000396923; ENSP00000380129; ENSG00000168781. ENST00000420765; ENSP00000400887; ENSG00000168781.
GeneID	9677.
KEGG	hsa:9677.
UCSC	uc001zrw.3. human. uc001zrx.2. human. uc001zry.4. human. uc021sjz.1. human.
Organism-specific databases
CTD	9677.
GeneCards	GC15M043826.
H-InvDB	HIX0012186.
HGNC	HGNC:29023. PPIP5K1.
HPA	HPA039380.
MIM	610979. gene.
neXtProt	NX_Q6PFW1.
PharmGKB	PA165479401.
HUGE	Search...
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG245915.
HOVERGEN	HBG108657.
InParanoid	Q6PFW1.
KO	K13024.
OrthoDB	EOG41VK25.
PhylomeDB	Q6PFW1.
Enzyme and pathway databases
BioCyc	MetaCyc:HS09822-MONOMER.
Reactome	REACT_111217. Metabolism.
Gene expression databases
ArrayExpress	Q6PFW1.
Bgee	Q6PFW1.
Genevestigator	Q6PFW1.
Family and domain databases
InterPro	IPR000560. His_Pase_superF_clade-2. [Graphical view]
Pfam	PF00328. His_Phos_2. 1 hit. [Graphical view]
PROSITE	PS00616. HIS_ACID_PHOSPHAT_1. 1 hit. PS00778. HIS_ACID_PHOSPHAT_2. False negative. [Graphical view]
ProtoNet	Search...
Other
ChEMBL	CHEMBL5046.
ChiTaRS	PPIP5K1. human.
GenomeRNAi	9677.
NextBio	36337.
SOURCE	Search...

Entry information

Entry name

VIP1_HUMAN

Accession

Primary (citable) accession number: Q6PFW1
Secondary accession number(s): O15082 , Q5HYF8, Q7Z3A7, Q86TE7, Q86UV3, Q86UV4, Q86XW8, Q8IZN0

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 15, 2008
Last sequence update:	July 5, 2004
Last modified:	May 29, 2013
This is version 84 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.