O60331 (PI51C_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Phosphatidylinositol 4-phosphate 5-kinase type-1 gamma
Short name=PIP5K1-gamma
Short name=PtdIns(4)P-5-kinase 1 gamma
EC=2.7.1.68

Alternative name(s):
Phosphatidylinositol 4-phosphate 5-kinase type I gamma
Short name=PIP5KIgamma

Gene names

Name:	PIP5K1C
Synonyms:	KIAA0589

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	668 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Catalyzes the phosphorylation of phosphatidylinositol 4-phosphate (PtdIns4P) to form phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2). PtdIns(4,5)P2 is involved in a variety of cellular processes and is the substrate to form phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3), another second messenger. The majority of PtdIns(4,5)P2 is thought to occur via type I phosphatidylinositol 4-phosphate 5-kinases given the abundance of PtdIns4P. Participates in a variety of cellular processes such as vesicle mediated transport, cell adhesion, cell polarization and cell migration. Together with PIP5K1A is required for phagocytosis, but they regulate different types of actin remodeling at sequential steps. Promotes particle attachment by generating the pool of PtdIns(4,5)P2 that induces controlled actin depolymerization to facilitate Fc-gamma-R clustering. Mediates RAC1-dependent reorganization of actin filaments. Required for synaptic vesicle transport. Controls the plasma membrane pool of PtdIns(4,5)P2 implicated in synaptic vesicle endocytosis and exocytosis. Plays a role in endocytosis mediated by clathrin and AP-2 (adaptor protein complex 2). Required for clathrin-coated pits assembly at the synapse. Participates in cell junction assembly. Modulates adherens junctions formation by facilitating CDH1 trafficking. Required for focal adhesion dynamics. Modulates the targeting of talins (TLN1 and TLN2) to the plasma membrane and their efficient assembly into focal adhesions. Regulates the interaction between talins (TLN1 and TLN2) and beta-integrins. Required for uropodium formation and retraction of the cell rear during directed migration. Has a role in growth factor- stimulated directional cell migration and adhesion. Required for talin assembly into nascent adhesions forming at the leading edge toward the direction of the growth factor. Negative regulator of T-cell activation and adhesion. Negatively regulates integrin alpha-L/beta-2 (LFA-1) polarization and adhesion induced by T-cell receptor. Together with PIP5K1A have a role during embryogenesis and together with PIP5K1B may have a role immediately after birth. Ref.5 Ref.6 Ref.8 Ref.9
Catalytic activity	ATP + 1-phosphatidyl-1D-myo-inositol 4-phosphate = ADP + 1-phosphatidyl-1D-myo-inositol 4,5-bisphosphate.
Enzyme regulation	Activated by interaction with TLN2. Ref.5
Subunit structure	Interacts with TLN1 By similarity. Interacts with TLN2; interaction stimulates lipid kinase activity. May compete with beta-integrins for the same binding site on TLN1 and TLN2. Interacts with ARF6. Interacts with AP2B1. Interacts with AP2M1; phosphorylation of PIP5K1C by CSK disrupts the interaction; clathrin competes with PIP5K1C By similarity. Interacts with CDH1. Interacts with CSK By similarity. Interacts with PLCG1; interaction is abolished upon EGF stimulation By similarity. Ref.5 Ref.6 Ref.8
Subcellular location	Cell membrane; Peripheral membrane protein; Cytoplasmic side. Endomembrane system. Cytoplasm. Cell junction › focal adhesion. Cell junction › adherens junction. Cell projection › ruffle membrane. Cell projection › phagocytic cup. Cell projection › uropodium. Note: Detected in plasma membrane invaginations. Isoform 3 is detected in intracellular vesicle-like structures. Ref.1 Ref.5 Ref.6 Ref.8 Isoform 2: Cytoplasm. Nucleus Ref.1 Ref.5 Ref.6 Ref.8.
Tissue specificity	Isoform 1 is strongly expressed in brain and also detected in heart and lung. Isoform 2 is strongly expressed in pancreas and liver and in lesser quantities in brain, heart, lung and kidney. Isoform 3 is detected in large amounts in heart and large intestine, is also present in lung, pancreas and thyroid, and to a lesser extent in brain, stomach and kidney. Ref.1
Post-translational modification	Phosphorylation on Ser-650 negatively regulates binding to TLN2 and is strongly stimulated in mitosis. Phosphorylation on Tyr-649 is necessary for targeting to focal adhesions. Phosphorylation on Ser-650 and Tyr-649 are mutually exclusive. Phosphorylated by SYK and CSK By similarity. Tyrosine phosphorylation is enhanced by PTK2 signaling. Phosphorylated at Tyr-639 upon EGF stimulation. Some studies suggest that phosphorylation on Tyr-649 enhances binding to tailins (TLN1 and TLN2). According to Ref.7 phosphorylation at Tyr-649 does not directly enhance binding to tailins (TLN1 and TLN2) but may act indirectly by inhibiting phosphorylation at Ser-650. Ref.7 Acetylation at Lys-265 and Lys-268 seems to decrease lipid kinase activity. Deacetylation of these sites by SIRT1 positively regulates the exocytosis of TSH-containing granules from pituitary cells.
Involvement in disease	Lethal congenital contracture syndrome 3 (LCCS3) [MIM:611369]: A form of lethal congenital contracture syndrome, an autosomal recessive disorder characterized by degeneration of anterior horn neurons, extreme skeletal muscle atrophy, and congenital non-progressive joint contractures (arthrogryposis). The contractures can involve the upper or lower limbs and/or the vertebral column, leading to various degrees of flexion or extension limitations evident at birth. LCCS3 patients present at birth with severe multiple joint contractures and severe muscle wasting and atrophy, mainly in the legs. Death occurrs minutes to hours after birth due to respiratory insufficiency. The phenotype can be distinguished from that of LCCS1 by the absence of hydrops, fractures and multiple pterygia, and from LCCS2 by the absence of neurogenic bladder defect. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.12
Sequence similarities	Contains 1 PIPK domain.
Sequence caution	The sequence BAA25515.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

Ontologies

Keywords
Biological process	Cell adhesion Chemotaxis Endocytosis Exocytosis Phagocytosis
Cellular component	Cell junction Cell membrane Cell projection Cytoplasm Membrane Nucleus
Coding sequence diversity	Alternative splicing
Disease	Disease mutation
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Transferase
PTM	Acetylation Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	actin cytoskeleton organization Traceable author statement Ref.11. Source: UniProtKB adherens junction assembly Traceable author statement Ref.11. Source: UniProtKB axon guidance Traceable author statement. Source: Reactome cell-cell adhesion Traceable author statement Ref.11. Source: UniProtKB clathrin-mediated endocytosis Traceable author statement Ref.11. Source: UniProtKB neutrophil chemotaxis Traceable author statement Ref.11. Source: UniProtKB phagocytosis Traceable author statement Ref.11. Source: UniProtKB phosphatidylinositol biosynthetic process Traceable author statement. Source: Reactome phosphatidylinositol phosphorylation Inferred from electronic annotation. Source: GOC small molecule metabolic process Traceable author statement. Source: Reactome synaptic vesicle endocytosis Traceable author statement Ref.11. Source: UniProtKB synaptic vesicle exocytosis Traceable author statement Ref.11. Source: UniProtKB
Cellular_component	cytosol Traceable author statement. Source: Reactome endomembrane system Inferred from electronic annotation. Source: UniProtKB-SubCell focal adhesion Traceable author statement Ref.11. Source: UniProtKB nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell phagocytic cup Inferred from electronic annotation. Source: UniProtKB-SubCell ruffle membrane Inferred from electronic annotation. Source: UniProtKB-SubCell uropod Traceable author statement Ref.11. Source: UniProtKB
Molecular_function	1-phosphatidylinositol-4-phosphate 5-kinase activity Inferred from electronic annotation. Source: EC ATP binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Alternative products

This entry describes 4 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: O60331-1)

Also known as: PIPKIgamma-90; PIPKIgamma-668; PIPkinIgamma-a; PIPKIgamma_i2;

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: O60331-2)

Also known as: variant 700; PIPKIgamma-700; PIPKIgamma_i4;

The sequence of this isoform differs from the canonical sequence as follows:
     640-668: FPTDERSWVYSPLHYSAQAPPASDGESDT → FWRLWGPHAP...GAMSCCVSVS

Isoform 3 (identifier: O60331-3)

Also known as: variant 707; PIPKIgamma-707; PIPKIgamma_i5;

The sequence of this isoform differs from the canonical sequence as follows:
     641-668: PTDERSWVYSPLHYSAQAPPASDGESDT → FTDGRYWIYS...TSVVFQKGFG

Isoform 4 (identifier: O60331-4)

Also known as: PIPKIgamma-87; PIPKIgamma-640; PIPkinIgamma-b; PIPKIgamma_i1;

The sequence of this isoform differs from the canonical sequence as follows:
     641-668: Missing.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 668

668

Phosphatidylinositol 4-phosphate 5-kinase type-1 gamma

PRO_0000185462

Regions

Domain

75 – 443

369

PIPK

Region

641 – 668

28

Mediates interaction with TLN2

Amino acid modifications

Modified residue

265

1

N6-acetyllysine Ref.10

Modified residue

268

1

N6-acetyllysine Ref.10

Modified residue

639

1

Phosphotyrosine; by EGFR By similarity

Modified residue

649

1

Phosphotyrosine; by CSK Ref.7

Modified residue

650

1

Phosphoserine; by CDK5, MAPK1 and CDK1 Ref.7

Natural variations

Alternative sequence

640 – 668

29

FPTDE…GESDT → FWRLWGPHAPTWPWRREGRA ACLCPYPPHVVTPFPGTGLC ASWSPDGTGGLGAMSCCVSV S in isoform 2.

VSP_042078

Alternative sequence

641 – 668

28

PTDER…GESDT → FTDGRYWIYSPRHRRLRAVT LSASGTVSDRSRPPWGEGAV PLGQQGAAGPRPEAQCLTSV VFQKGFG in isoform 3.

VSP_042080

Alternative sequence

641 – 668

28

Missing in isoform 4.

VSP_042079

Natural variant

253

1

D → N in LCCS3; loss of activity. Ref.12

VAR_036996

Experimental info

Mutagenesis

650

1

S → D: Abolishes binding to TLN2. Affects localization to focal adhesions. Ref.7

Mutagenesis

650

1

S → N: Does not affect binding to TLN2 and localization to focal adhesions. Ref.7

Sequence conflict

236

1

V → M in BAH14283. Ref.3

Secondary structure

1

.

.

.

668

Helix Strand Turn

Details...

Helix

644 – 646

3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (PIPKIgamma-90) (PIPKIgamma-668) (PIPkinIgamma-a) (PIPKIgamma_i2) [UniParc]. Last modified October 25, 2005. Version 2. Checksum: 45A9FB32B4E43083	FASTA	668	73,260
	10 20 30 40 50 60 MELEVPDEAE SAEAGAVPSE AAWAAESGAA AGLAQKKAAP TEVLSMTAQP GPGHGKKLGH 70 80 90 100 110 120 RGVDASGETT YKKTTSSTLK GAIQLGIGYT VGHLSSKPER DVLMQDFYVV ESIFFPSEGS 130 140 150 160 170 180 NLTPAHHFQD FRFKTYAPVA FRYFRELFGI RPDDYLYSLC NEPLIELSNP GASGSLFYVT 190 200 210 220 230 240 SDDEFIIKTV MHKEAEFLQK LLPGYYMNLN QNPRTLLPKF YGLYCVQSGG KNIRVVVMNN 250 260 270 280 290 300 ILPRVVKMHL KFDLKGSTYK RRASKKEKEK SFPTYKDLDF MQDMPEGLLL DADTFSALVK 310 320 330 340 350 360 TLQRDCLVLE SFKIMDYSLL LGVHNIDQHE RERQAQGAQS TSDEKRPVGQ KALYSTAMES 370 380 390 400 410 420 IQGGAARGEA IESDDTMGGI PAVNGRGERL LLHIGIIDIL QSYRFIKKLE HTWKALVHDG 430 440 450 460 470 480 DTVSVHRPSF YAERFFKFMS NTVFRKNSSL KSSPSKKGRG GALLAVKPLG PTAAFSASQI 490 500 510 520 530 540 PSEREEAQYD LRGARSYPTL EDEGRPDLLP CTPPSFEEAT TASIATTLSS TSLSIPERSP 550 560 570 580 590 600 SETSEQPRYR RRTQSSGQDG RPQEEPPAEE DLQQITVQVE PACSVEIVVP KEEDAGVEAS 610 620 630 640 650 660 PAGASAAVEV ETASQASDEE GAPASQASDE EDAPATDIYF PTDERSWVYS PLHYSAQAPP ASDGESDT
	Isoform 2 (variant 700) (PIPKIgamma-700) (PIPKIgamma_i4) [UniParc]. Checksum: D3E3DC89BDF2E868	FASTA	700	76,620
	10 20 30 40 50 60 MELEVPDEAE SAEAGAVPSE AAWAAESGAA AGLAQKKAAP TEVLSMTAQP GPGHGKKLGH 70 80 90 100 110 120 RGVDASGETT YKKTTSSTLK GAIQLGIGYT VGHLSSKPER DVLMQDFYVV ESIFFPSEGS 130 140 150 160 170 180 NLTPAHHFQD FRFKTYAPVA FRYFRELFGI RPDDYLYSLC NEPLIELSNP GASGSLFYVT 190 200 210 220 230 240 SDDEFIIKTV MHKEAEFLQK LLPGYYMNLN QNPRTLLPKF YGLYCVQSGG KNIRVVVMNN 250 260 270 280 290 300 ILPRVVKMHL KFDLKGSTYK RRASKKEKEK SFPTYKDLDF MQDMPEGLLL DADTFSALVK 310 320 330 340 350 360 TLQRDCLVLE SFKIMDYSLL LGVHNIDQHE RERQAQGAQS TSDEKRPVGQ KALYSTAMES 370 380 390 400 410 420 IQGGAARGEA IESDDTMGGI PAVNGRGERL LLHIGIIDIL QSYRFIKKLE HTWKALVHDG 430 440 450 460 470 480 DTVSVHRPSF YAERFFKFMS NTVFRKNSSL KSSPSKKGRG GALLAVKPLG PTAAFSASQI 490 500 510 520 530 540 PSEREEAQYD LRGARSYPTL EDEGRPDLLP CTPPSFEEAT TASIATTLSS TSLSIPERSP 550 560 570 580 590 600 SETSEQPRYR RRTQSSGQDG RPQEEPPAEE DLQQITVQVE PACSVEIVVP KEEDAGVEAS 610 620 630 640 650 660 PAGASAAVEV ETASQASDEE GAPASQASDE EDAPATDIYF WRLWGPHAPT WPWRREGRAA 670 680 690 700 CLCPYPPHVV TPFPGTGLCA SWSPDGTGGL GAMSCCVSVS
	Isoform 3 (variant 707) (PIPKIgamma-707) (PIPKIgamma_i5) [UniParc]. Checksum: 42BC87A1C20A5037	FASTA	707	77,484
	10 20 30 40 50 60 MELEVPDEAE SAEAGAVPSE AAWAAESGAA AGLAQKKAAP TEVLSMTAQP GPGHGKKLGH 70 80 90 100 110 120 RGVDASGETT YKKTTSSTLK GAIQLGIGYT VGHLSSKPER DVLMQDFYVV ESIFFPSEGS 130 140 150 160 170 180 NLTPAHHFQD FRFKTYAPVA FRYFRELFGI RPDDYLYSLC NEPLIELSNP GASGSLFYVT 190 200 210 220 230 240 SDDEFIIKTV MHKEAEFLQK LLPGYYMNLN QNPRTLLPKF YGLYCVQSGG KNIRVVVMNN 250 260 270 280 290 300 ILPRVVKMHL KFDLKGSTYK RRASKKEKEK SFPTYKDLDF MQDMPEGLLL DADTFSALVK 310 320 330 340 350 360 TLQRDCLVLE SFKIMDYSLL LGVHNIDQHE RERQAQGAQS TSDEKRPVGQ KALYSTAMES 370 380 390 400 410 420 IQGGAARGEA IESDDTMGGI PAVNGRGERL LLHIGIIDIL QSYRFIKKLE HTWKALVHDG 430 440 450 460 470 480 DTVSVHRPSF YAERFFKFMS NTVFRKNSSL KSSPSKKGRG GALLAVKPLG PTAAFSASQI 490 500 510 520 530 540 PSEREEAQYD LRGARSYPTL EDEGRPDLLP CTPPSFEEAT TASIATTLSS TSLSIPERSP 550 560 570 580 590 600 SETSEQPRYR RRTQSSGQDG RPQEEPPAEE DLQQITVQVE PACSVEIVVP KEEDAGVEAS 610 620 630 640 650 660 PAGASAAVEV ETASQASDEE GAPASQASDE EDAPATDIYF FTDGRYWIYS PRHRRLRAVT 670 680 690 700 LSASGTVSDR SRPPWGEGAV PLGQQGAAGP RPEAQCLTSV VFQKGFG
	Isoform 4 (PIPKIgamma-87) (PIPKIgamma-640) (PIPkinIgamma-b) (PIPKIgamma_i1) [UniParc]. Checksum: 197B427BF16392C8	FASTA	640	70,214
	10 20 30 40 50 60 MELEVPDEAE SAEAGAVPSE AAWAAESGAA AGLAQKKAAP TEVLSMTAQP GPGHGKKLGH 70 80 90 100 110 120 RGVDASGETT YKKTTSSTLK GAIQLGIGYT VGHLSSKPER DVLMQDFYVV ESIFFPSEGS 130 140 150 160 170 180 NLTPAHHFQD FRFKTYAPVA FRYFRELFGI RPDDYLYSLC NEPLIELSNP GASGSLFYVT 190 200 210 220 230 240 SDDEFIIKTV MHKEAEFLQK LLPGYYMNLN QNPRTLLPKF YGLYCVQSGG KNIRVVVMNN 250 260 270 280 290 300 ILPRVVKMHL KFDLKGSTYK RRASKKEKEK SFPTYKDLDF MQDMPEGLLL DADTFSALVK 310 320 330 340 350 360 TLQRDCLVLE SFKIMDYSLL LGVHNIDQHE RERQAQGAQS TSDEKRPVGQ KALYSTAMES 370 380 390 400 410 420 IQGGAARGEA IESDDTMGGI PAVNGRGERL LLHIGIIDIL QSYRFIKKLE HTWKALVHDG 430 440 450 460 470 480 DTVSVHRPSF YAERFFKFMS NTVFRKNSSL KSSPSKKGRG GALLAVKPLG PTAAFSASQI 490 500 510 520 530 540 PSEREEAQYD LRGARSYPTL EDEGRPDLLP CTPPSFEEAT TASIATTLSS TSLSIPERSP 550 560 570 580 590 600 SETSEQPRYR RRTQSSGQDG RPQEEPPAEE DLQQITVQVE PACSVEIVVP KEEDAGVEAS 610 620 630 640 PAGASAAVEV ETASQASDEE GAPASQASDE EDAPATDIYF

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Two novel phosphatidylinositol-4-phosphate 5-kinase type Igamma splice variants expressed in human cells display distinctive cellular targeting." Schill N.J., Anderson R.A. Biochem. J. 422:473-482(2009) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2 AND 3), SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[2]	"Prediction of the coding sequences of unidentified human genes. IX. The complete sequences of 100 new cDNA clones from brain which can code for large proteins in vitro." Nagase T., Ishikawa K., Miyajima N., Tanaka A., Kotani H., Nomura N., Ohara O. DNA Res. 5:31-39(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Brain.
[3]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4).
[4]	"The DNA sequence and biology of human chromosome 19." Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E., Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A., Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S., Carrano A.V. , Caoile C., Chan Y.M., Christensen M., Cleland C.A., Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M., Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V., Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D., McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I., Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L., Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E., Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M., Rubin E.M., Lucas S.M. Nature 428:529-535(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"Recruitment and regulation of phosphatidylinositol phosphate kinase type 1 gamma by the FERM domain of talin." Di Paolo G., Pellegrini L., Letinic K., Cestra G., Zoncu R., Voronov S., Chang S., Guo J., Wenk M.R., De Camilli P. Nature 420:85-89(2002) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH TLN2, SUBCELLULAR LOCATION, ENZYME REGULATION.
[6]	"ARF6 stimulates clathrin/AP-2 recruitment to synaptic membranes by activating phosphatidylinositol phosphate kinase type Igamma." Krauss M., Kinuta M., Wenk M.R., De Camilli P., Takei K., Haucke V. J. Cell Biol. 162:113-124(2003) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH ARF6, SUBCELLULAR LOCATION.
[7]	"Regulation of the interaction between PIPKI gamma and talin by proline-directed protein kinases." Lee S.Y., Voronov S., Letinic K., Nairn A.C., Di Paolo G., De Camilli P. J. Cell Biol. 168:789-799(2005) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION AT TYR-649 AND SER-650, MUTAGENESIS OF SER-650.
[8]	"Type I gamma phosphatidylinositol phosphate kinase modulates adherens junction and E-cadherin trafficking via a direct interaction with mu 1B adaptin." Ling K., Bairstow S.F., Carbonara C., Turbin D.A., Huntsman D.G., Anderson R.A. J. Cell Biol. 176:343-353(2007) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH CDH1.
[9]	"Type I gamma phosphatidylinositol phosphate kinase is required for EGF-stimulated directional cell migration." Sun Y., Ling K., Wagoner M.P., Anderson R.A. J. Cell Biol. 178:297-308(2007) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN CELL MIGRATION AND ADHESION.
[10]	"SIRT1 regulates thyroid-stimulating hormone release by enhancing PIP5Kgamma activity through deacetylation of specific lysine residues in mammals." Akieda-Asai S., Zaima N., Ikegami K., Kahyo T., Yao I., Hatanaka T., Iemura S., Sugiyama R., Yokozeki T., Eishi Y., Koike M., Ikeda K., Chiba T., Yamaza H., Shimokawa I., Song S.Y., Matsuno A., Mizutani A. , Sawabe M., Chao M.V., Tanaka M., Kanaho Y., Natsume T., Sugimura H., Date Y., McBurney M.W., Guarente L., Setou M. PLoS ONE 5:E11755-E11755(2010) [PubMed] [Europe PMC] [Abstract] Cited for: ACETYLATION AT LYS-265 AND LYS-268, DEACETYLATION BY SIRT1.
[11]	"PIP5K-driven PtdIns(4,5)P2 synthesis: regulation and cellular functions." van den Bout I., Divecha N. J. Cell Sci. 122:3837-3850(2009) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW ON FUNCTION.
[12]	"Lethal contractural syndrome type 3 (LCCS3) is caused by a mutation in PIP5K1C, which encodes PIPKI gamma of the phophatidylinositol pathway." Narkis G., Ofir R., Landau D., Manor E., Volokita M., Hershkowitz R., Elbedour K., Birk O.S. Am. J. Hum. Genet. 81:530-539(2007) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT LCCS3 ASN-253, CHARACTERIZATION OF VARIANT LCCS3 ASN-253.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

FJ965536 mRNA. Translation: ACS73483.1.
FJ965537 mRNA. Translation: ACS73484.1.
AB011161 mRNA. Translation: BAA25515.1. Different initiation.
AK315912 mRNA. Translation: BAH14283.1.
AC005542 Genomic DNA. Translation: AAC32904.1.
AC093071 Genomic DNA. No translation available.
AC004637 Genomic DNA. No translation available.

IPI

IPI01009827.

RefSeq

NP_001182662.1. NM_001195733.1.
NP_036530.1. NM_012398.2.

UniGene

Hs.282177.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3H1Z	X-ray	1.83	P	639-653	[»]
3H85	X-ray	2.60	P	646-653	[»]

ProteinModelPortal

O60331.

ModBase

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Protein-protein interaction databases

STRING

9606.ENSP00000335333.

PTM databases

PhosphoSite

O60331.

Proteomic databases

PaxDb

O60331.

PRIDE

O60331.

Protocols and materials databases

DNASU

23396.

StructuralBiologyKnowledgebase

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Genome annotation databases

Ensembl

ENST00000335312; ENSP00000335333; ENSG00000186111.
ENST00000537021; ENSP00000444779; ENSG00000186111.
ENST00000539785; ENSP00000445992; ENSG00000186111.
ENST00000589578; ENSP00000466363; ENSG00000186111.

GeneID

23396.

KEGG

hsa:23396.

UCSC

uc002lyj.2. human.

Organism-specific databases

CTD

23396.

GeneCards

GC19M003631.

HGNC

HGNC:8996. PIP5K1C.

HPA

HPA017168.

MIM

606102. gene.
611369. phenotype.

neXtProt

NX_O60331.

Orphanet

137783. Lethal congenital contracture syndrome type 3.

PharmGKB

PA33329.

HUGE

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GenAtlas

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Phylogenomic databases

eggNOG

COG5253.

HOGENOM

HOG000193876.

HOVERGEN

HBG052818.

InParanoid

O60331.

KO

K00889.

OMA

PTDERSW.

OrthoDB

EOG4JQ3Z0.

Enzyme and pathway databases

BioCyc

MetaCyc:HS02710-MONOMER.

Pathway_Interaction_DB

arf6_traffickingpathway. Arf6 trafficking events.

Reactome

REACT_111045. Developmental Biology.
REACT_111217. Metabolism.

Gene expression databases

ArrayExpress

O60331.

Bgee

O60331.

CleanEx

HS_PIP5K1C.

Genevestigator

O60331.

GermOnline

ENSG00000186111. Homo sapiens.

Family and domain databases

InterPro

IPR023610. PInositol-4-P-5-kinase.
IPR002498. PInositol-4-P-5-kinase_core.
IPR016034. PInositol-4P-5-kinase_core_sub.
[Graphical view]

PANTHER

PTHR23086. PTHR23086. 1 hit.

Pfam

PF01504. PIP5K. 1 hit.
[Graphical view]

SMART

SM00330. PIPKc. 1 hit.
[Graphical view]

PROSITE

PS51455. PIPK. 1 hit.
[Graphical view]

ProtoNet

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Other

BindingDB

O60331.

ChEMBL

CHEMBL1908383.

ChiTaRS

PIP5K1C. human.

EvolutionaryTrace

O60331.

GenomeRNAi

23396.

NextBio

45537.

SOURCE

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Entry information

Entry name

PI51C_HUMAN

Accession

Primary (citable) accession number: O60331
Secondary accession number(s): B7Z9E7 , C6GIJ7, C6GIJ8, Q7LE07

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 25, 2005
Last sequence update:	October 25, 2005
Last modified:	May 1, 2013
This is version 102 of the entry and version 2 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.