PI4KA

Protein identityUniProt · HPA

UniProt accession

P42356

Gene

PI4KA

Ensembl

ENSG00000241973

Chromosome

22

Canonical length

2102 aa

Protein class

Disease related genes, Enzymes, Human disease related genes, Metabolic proteins, Plasma proteins, Potential drug targets, Predicted intracellular proteins, Predicted membrane proteins

Subcellular location

Nucleoplasm,Plasma membrane

OverviewNCBI Gene

This gene encodes a phosphatidylinositol (PI) 4-kinase which catalyzes the first committed step in the biosynthesis of phosphatidylinositol 4,5-bisphosphate. The mammalian PI 4-kinases have been classified into two types, II and III, based on their molecular mass, and modulation by detergent and adenosine. The protein encoded by this gene is a type III enzyme that is not inhibited by adenosine. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Apr 2018]

Canonical amino-acid sequenceUniProt

2102 residues, UniProt reviewed canonical sequence.

>P42356|PI4KA
     1  MAAAPARGGG GGGGGGGGCS GSGSSASRGF YFNTVLSLAR SLAVQRPASL EKVQKLLCMC
    61  PVDFHGIFQL DERRRDAVIA LGIFLIESDL QHKDCVVPYL LRLLKGLPKV YWVEESTARK
   121  GRGALPVAES FSFCLVTLLS DVAYRDPSLR DEILEVLLQV LHVLLGMCQA LEIQDKEYLC
   181  KYAIPCLIGI SRAFGRYSNM EESLLSKLFP KIPPHSLRVL EELEGVRRRS FNDFRSILPS
   241  NLLTVCQEGT LKRKTSSVSS ISQVSPERGM PPPSSPGGSA FHYFEASCLP DGTALEPEYY
   301  FSTISSSFSV SPLFNGVTYK EFNIPLEMLR ELLNLVKKIV EEAVLKSLDA IVASVMEANP
   361  SADLYYTSFS DPLYLTMFKM LRDTLYYMKD LPTSFVKEIH DFVLEQFNTS QGELQKILHD
   421  ADRIHNELSP LKLRCQANAA CVDLMVWAVK DEQGAENLCI KLSEKLQSKT SSKVIIAHLP
   481  LLICCLQGLG RLCERFPVVV HSVTPSLRDF LVIPSPVLVK LYKYHSQYHT VAGNDIKISV
   541  TNEHSESTLN VMSGKKSQPS MYEQLRDIAI DNICRCLKAG LTVDPVIVEA FLASLSNRLY
   601  ISQESDKDAH LIPDHTIRAL GHIAVALRDT PKVMEPILQI LQQKFCQPPS PLDVLIIDQL
   661  GCLVITGNQY IYQEVWNLFQ QISVKASSVV YSATKDYKDH GYRHCSLAVI NALANIAANI
   721  QDEHLVDELL MNLLELFVQL GLEGKRASER ASEKGPALKA SSSAGNLGVL IPVIAVLTRR
   781  LPPIKEAKPR LQKLFRDFWL YSVLMGFAVE GSGLWPEEWY EGVCEIATKS PLLTFPSKEP
   841  LRSVLQYNSA MKNDTVTPAE LSELRSTIIN LLDPPPEVSA LINKLDFAMS TYLLSVYRLE
   901  YMRVLRSTDP DRFQVMFCYF EDKAIQKDKS GMMQCVIAVA DKVFDAFLNM MADKAKTKEN
   961  EEELERHAQF LLVNFNHIHK RIRRVADKYL SGLVDKFPHL LWSGTVLKTM LDILQTLSLS
  1021  LSADIHKDQP YYDIPDAPYR ITVPDTYEAR ESIVKDFAAR CGMILQEAMK WAPTVTKSHL
  1081  QEYLNKHQNW VSGLSQHTGL AMATESILHF AGYNKQNTTL GATQLSERPA CVKKDYSNFM
  1141  ASLNLRNRYA GEVYGMIRFS GTTGQMSDLN KMMVQDLHSA LDRSHPQHYT QAMFKLTAML
  1201  ISSKDCDPQL LHHLCWGPLR MFNEHGMETA LACWEWLLAG KDGVEVPFMR EMAGAWHMTV
  1261  EQKFGLFSAE IKEADPLAAS EASQPKPCPP EVTPHYIWID FLVQRFEIAK YCSSDQVEIF
  1321  SSLLQRSMSL NIGGAKGSMN RHVAAIGPRF KLLTLGLSLL HADVVPNATI RNVLREKIYS
  1381  TAFDYFSCPP KFPTQGEKRL REDISIMIKF WTAMFSDKKY LTASQLVPPD NQDTRSNLDI
  1441  TVGSRQQATQ GWINTYPLSS GMSTISKKSG MSKKTNRGSQ LHKYYMKRRT LLLSLLATEI
  1501  ERLITWYNPL SAPELELDQA GENSVANWRS KYISLSEKQW KDNVNLAWSI SPYLAVQLPA
  1561  RFKNTEAIGN EVTRLVRLDP GAVSDVPEAI KFLVTWHTID ADAPELSHVL CWAPTDPPTG
  1621  LSYFSSMYPP HPLTAQYGVK VLRSFPPDAI LFYIPQIVQA LRYDKMGYVR EYILWAASKS
  1681  QLLAHQFIWN MKTNIYLDEE GHQKDPDIGD LLDQLVEEIT GSLSGPAKDF YQREFDFFNK
  1741  ITNVSAIIKP YPKGDERKKA CLSALSEVKV QPGCYLPSNP EAIVLDIDYK SGTPMQSAAK
  1801  APYLAKFKVK RCGVSELEKE GLRCRSDSED ECSTQEADGQ KISWQAAIFK VGDDCRQDML
  1861  ALQIIDLFKN IFQLVGLDLF VFPYRVVATA PGCGVIECIP DCTSRDQLGR QTDFGMYDYF
  1921  TRQYGDESTL AFQQARYNFI RSMAAYSLLL FLLQIKDRHN GNIMLDKKGH IIHIDFGFMF
  1981  ESSPGGNLGW EPDIKLTDEM VMIMGGKMEA TPFKWFMEMC VRGYLAVRPY MDAVVSLVTL
  2041  MLDTGLPCFR GQTIKLLKHR FSPNMTEREA ANFIMKVIQS CFLSNRSRTY DMIQYYQNDI
  2101  PY

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against PI4KA can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Cell surface

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.26

Highest tissue expression

103 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about PI4KA.

Disease | AllUniProt

Conditions PI4KA is implicated in, by any mechanism.

• Neurodevelopmental disorder with spasticity, hypomyelinating leukodystrophy, and brain abnormalities (NEDSPLB) MIM:616531
• Gastrointestinal defects and immunodeficiency syndrome 2 (GIDID2) MIM:619708
• Spastic paraplegia 84, autosomal recessive (SPG84) MIM:619621

Disease | GeneticClinVar

43 pathogenic / likely-pathogenic of 440 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Polymicrogyria, perisylvian, with cerebellar hypoplasia and arthrogryposis
• Spastic paraplegia 84, autosomal recessive
• PI4KA-related disorder
• Gastrointestinal defects and immunodeficiency syndrome 2
• Phenylketonuria

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.46

gnomAD pLI

0

gnomAD missense Z

3.53

DepMap mean gene effect

-0.63

DepMap dependency class

common

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 5% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• host-mediated perturbation of viral process
• phosphatidylinositol biosynthetic process
• phosphatidylinositol phosphate biosynthetic process
• phosphatidylinositol-mediated signaling
• signal transduction
• reorganization of cellular membranes to establish viral sites of replication

Molecular functions

• 1-phosphatidylinositol 4-kinase activity
• ATP binding
• cadherin binding

Cellular components

• cytoplasm
• cytosol
• extracellular exosome
• focal adhesion
• Golgi-associated vesicle membrane
• membrane
• plasma membrane

Protein domainsUniProt · Pfam · InterPro

• Phosphatidylinositol 3-/4-kinase, catalytic domain
• Phosphoinositide 3-kinase, accessory (PIK) domain
• Protein kinase-like domain superfamily
• Phosphatidylinositol 3-/4-kinase
• Armadillo-type fold
• Phosphatidylinositol 3-/4-kinase, conserved site
• Phosphatidylinositol 3-/4-kinase, catalytic domain superfamily
• Phosphoinositide 3-kinase, accessory (PIK) domain superfamily
• PI4-kinase, N-terminal
• Phosphatidylinositol 3- and 4-kinase
• Phosphoinositide 3-kinase family, accessory domain (PIK domain)
• PI4-kinase N-terminal region

KeywordsUniProt

• ATP-binding
• Cell membrane
• Cytoplasm
• Hereditary spastic paraplegia
• Kinase
• Lipid metabolism
• Membrane
• Neurodegeneration
• Nucleotide-binding
• Phosphoprotein
• Transferase

InteractionsUniProt · HPA

Protein binding partners of PI4KA in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• TMEM150A
• TTC7A
• TTC7B
• HYCC1