Reviewed, UniProtKB/Swiss-Prot O60331 (PI51C_HUMAN)

Names and origin

Protein names

Recommended name:
    Phosphatidylinositol-4-phosphate 5-kinase type-1 gamma
    EC=2.7.1.68
Alternative name(s):
    Phosphatidylinositol-4-phosphate 5-kinase type I gamma
      Short name=PtdIns(4)P-5-kinase gamma
      Short name=PtdInsPKIgamma
      Short name=PIP5KIgamma

Gene names

Name:	PIP5K1C
Synonyms:	KIAA0589

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	668 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Plays a role in membrane ruffling and assembly of clathrin-coated pits at the synapse. Mediates RAC1-dependent reorganization of actin filaments By similarity. Participates in the biosynthesis of phosphatidylinositol-4,5-bisphosphate.
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.
Subunit structure	Interacts with TLN1 and CSK By similarity. Interacts with TLN2 and ARF6.
Subcellular location	Cell membrane; Peripheral membrane protein; Cytoplasmic side. Note= Cytoplasmic, associated with the plasma membrane. Detected in focal adhesion plaques, membrane ruffles and plasma membrane invaginations.
Involvement in disease	Defects in PIP5K1C are the cause of lethal congenital contractural syndrome type 3 (LCCS3) [MIM:611369]; also known as multiple contractural syndrome Israeli Bedouin type B. LCCS is an autosomal recessive disorder characterized by early fetal hydrops and akinesia, the Pena-Shokeir phenotype, specific neuropathology with degeneration of anterior horn neurons and extreme skeletal muscle atrophy. LCCS3 patients present at birth with severe multiple joint contractures with severe muscle wasting and atrophy, mainly in the legs. LCCS3 can be distinguished from the original LCCS by the absence of hydrops, fractures, and multiple pterygia.
Sequence similarities	Contains 1 PI5K domain.

Ontologies

Keywords
Cellular component	Cell membrane Membrane
Disease	Disease mutation
Molecular function	Kinase Transferase
PTM	Phosphoprotein
Gene Ontology (GO)
Biological process	phosphatidylinositol metabolic process Inferred from electronic annotation. Source: InterPro
Cellular component	plasma membrane Inferred from electronic annotation. Source: UniProtKB-KW
Molecular function	1-phosphatidylinositol-4-phosphate 5-kinase activity Inferred from electronic annotation. Source: EC
Complete GO annotation...

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	157 – 443	287	PI5K
	Region	641 – 668	28	Mediates interaction with TLN2
Amino acid modifications
	Modified residue	649	1	Phosphotyrosine; by CSK By similarity
Natural variations
	Natural variant	253	1	D → N in LCCS3; loss of activity.		VAR_036996

Sequences

	Sequence		Length	Mass (Da)
	O60331-1 [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

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"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: 9628581] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain.
[2]	"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: 15057824] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]	"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: 12422219] [Abstract] Cited for: INTERACTION WITH TLN2, PHOSPHORYLATION, SUBCELLULAR LOCATION.
[4]	"Membrane ruffling requires coordination between type Ialpha phosphatidylinositol phosphate kinase and Rac signaling." Doughman R.L., Firestone A.J., Wojtasiak M.L., Bunce M.W., Anderson R.A. J. Biol. Chem. 278:23036-23045(2003) [PubMed: 12682053] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION.
[5]	"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: 12847086] [Abstract] Cited for: INTERACTION WITH ARF6, SUBCELLULAR LOCATION, FUNCTION.
[6]	"Lethal contractural syndrome type 3 (LCCS3) is caused by a mutation in PIP5K1C, which encodes PIPKI gamma of the phophatidylinsitol 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: 17701898] [Abstract] Cited for: VARIANT LCCS3 ASN-253, CHARACTERIZATION OF VARIANT LCCS3 ASN-253.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	AB011161 mRNA. Translation: BAA25515.1. Different initiation. AC005542 Genomic DNA. Translation: AAC32904.1. AC093071 Genomic DNA. No translation available. AC004637 Genomic DNA. No translation available.
RefSeq	NP_036530.1.
UniGene	Hs.282177
3D structure databases
HSSP	HSSP built from PDB template 1BO1 based on UniProtKB P78356.
ModBase	Search...
PTM databases
PhosphoSite	O60331.
Genome annotation databases
Ensembl	ENSG00000186111. Homo sapiens. [Contig view]
GeneID	23396.
KEGG	hsa:23396.
Organism-specific databases
H-InvDB	HIX0014644.
HGNC	HGNC:8996. PIP5K1C.
HPA	HPA017168.
MIM	606102. gene. 611369. phenotype.
Orphanet	137783. Lethal congenital contracture syndrome type 3.
PharmGKB	PA33329.
HUGE	Search...
GenAtlas	Search...
GeneCards	Search...
Phylogenomic databases
HOGENOM	O60331.
HOVERGEN	O60331.
Gene expression databases
ArrayExpress	O60331.
CleanEx	HS_PIP5K1C.
GermOnline	ENSG00000186111. Homo sapiens.
Family and domain databases
InterPro	IPR002498. PIP5K_core. IPR016034. PIP5K_core_sub. [Graphical view]
PANTHER	PTHR23086. PIP5K. 1 hit.
Pfam	PF01504. PIP5K. 1 hit. [Graphical view]
SMART	SM00330. PIPKc. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
LinkHub	O60331.
NextBio	45537.
SOURCE	Search...

Entry information

Entry name

PI51C_HUMAN

Accession

Primary (citable) accession number: O60331
Secondary accession number(s): Q7LE07

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 25, 2005
Last sequence update:	October 25, 2005
Last modified:	November 25, 2008
This is version 53 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)