PIPNA_HUMAN
ID PIPNA_HUMAN Reviewed; 270 AA.
AC Q00169;
DT 01-DEC-1992, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 2.
DT 03-AUG-2022, entry version 192.
DE RecName: Full=Phosphatidylinositol transfer protein alpha isoform;
DE Short=PI-TP-alpha;
DE Short=PtdIns transfer protein alpha;
DE Short=PtdInsTP alpha;
GN Name=PITPNA; Synonyms=PITPN;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Testis;
RX PubMed=8194769; DOI=10.1016/0378-1119(94)90279-8;
RA Dickeson S.K., Helmkamp G.M. Jr., Yarbrough L.R.;
RT "Sequence of a human cDNA encoding phosphatidylinositol transfer protein
RT and occurrence of a related sequence in widely divergent eukaryotes.";
RL Gene 142:301-305(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Brain;
RA Tanaka S., Yamashita S., Hosaka K.;
RL Submitted (NOV-1995) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain, and Ovary;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP PROTEIN SEQUENCE OF 135-146, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC TISSUE=Brain, and Cajal-Retzius cell;
RA Lubec G., Afjehi-Sadat L.;
RL Submitted (MAR-2007) to UniProtKB.
RN [5]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=10531358; DOI=10.1074/jbc.274.44.31553;
RA Fullwood Y., dos Santos M., Hsuan J.J.;
RT "Cloning and characterization of a novel human phosphatidylinositol
RT transfer protein, rdgBbeta.";
RL J. Biol. Chem. 274:31553-31558(1999).
RN [6]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=15522822; DOI=10.1016/j.bbalip.2004.08.003;
RA Hunt A.N., Skippen A.J., Koster G., Postle A.D., Cockcroft S.;
RT "Acyl chain-based molecular selectivity for HL60 cellular
RT phosphatidylinositol and of phosphatidylcholine by phosphatidylinositol
RT transfer protein alpha.";
RL Biochim. Biophys. Acta 1686:50-60(2004).
RN [7]
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, AND MUTAGENESIS OF
RP CYS-94; CYS-187 AND 202-TRP-TRP-203.
RX PubMed=18636990; DOI=10.1111/j.1600-0854.2008.00794.x;
RA Shadan S., Holic R., Carvou N., Ee P., Li M., Murray-Rust J., Cockcroft S.;
RT "Dynamics of lipid transfer by phosphatidylinositol transfer proteins in
RT cells.";
RL Traffic 9:1743-1756(2008).
RN [8]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-215, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C.,
RA Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [10]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=22822086; DOI=10.1074/jbc.m112.375840;
RA Garner K., Hunt A.N., Koster G., Somerharju P., Groves E., Li M., Raghu P.,
RA Holic R., Cockcroft S.;
RT "Phosphatidylinositol transfer protein, cytoplasmic 1 (PITPNC1) binds and
RT transfers phosphatidic acid.";
RL J. Biol. Chem. 287:32263-32276(2012).
RN [11]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [12]
RP X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS) IN COMPLEX WITH PHOSPHATIDYLINOSITOL,
RP FUNCTION, CATALYTIC ACTIVITY, PHOSPHATIDYLINOSITOL LIPID HEADGROUP BINDING,
RP AND MUTAGENESIS OF THR-58; LYS-60; GLU-85; ASN-89; TYR-102 AND
RP 202-TRP-TRP-203.
RX PubMed=14962392; DOI=10.1016/j.str.2004.01.013;
RA Tilley S.J., Skippen A., Murray-Rust J., Swigart P.M., Stewart A.,
RA Morgan C.P., Cockcroft S., McDonald N.Q.;
RT "Structure-function analysis of human phosphatidylinositol transfer protein
RT alpha bound to phosphatidylinositol.";
RL Structure 12:317-326(2004).
CC -!- FUNCTION: Catalyzes the transfer of phosphatidylinositol (PI) and
CC phosphatidylcholine (PC) between membranes (PubMed:10531358,
CC PubMed:22822086, PubMed:15522822, PubMed:18636990, PubMed:14962392).
CC Shows a preference for PI and PC containing shorter saturated or
CC monosaturated acyl chains at the sn-1 and sn-2 positions
CC (PubMed:15522822, PubMed:22822086). Preference order for PC is C16:1 >
CC C16:0 > C18:1 > C18:0 > C20:4 and for PI is C16:1 > C16:0 > C18:1 >
CC C18:0 > C20:4 > C20:3 (PubMed:22822086). {ECO:0000269|PubMed:10531358,
CC ECO:0000269|PubMed:14962392, ECO:0000269|PubMed:15522822,
CC ECO:0000269|PubMed:18636990, ECO:0000269|PubMed:22822086}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 1,2-diacyl-sn-glycero-3-phosphocholine(in) = a 1,2-diacyl-
CC sn-glycero-3-phosphocholine(out); Xref=Rhea:RHEA:38571,
CC ChEBI:CHEBI:57643; Evidence={ECO:0000269|PubMed:14962392,
CC ECO:0000269|PubMed:15522822, ECO:0000269|PubMed:22822086};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38572;
CC Evidence={ECO:0000305|PubMed:22822086};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol)(in) = a
CC 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-inositol)(out);
CC Xref=Rhea:RHEA:38691, ChEBI:CHEBI:57880;
CC Evidence={ECO:0000269|PubMed:10531358, ECO:0000269|PubMed:14962392,
CC ECO:0000269|PubMed:15522822, ECO:0000269|PubMed:18636990,
CC ECO:0000269|PubMed:22822086};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38692;
CC Evidence={ECO:0000305|PubMed:10531358};
CC -!- ACTIVITY REGULATION: Phosphatidylinositol transfer activity is
CC inhibited by N-ethylmaleimide. {ECO:0000269|PubMed:18636990}.
CC -!- INTERACTION:
CC Q00169; P55212: CASP6; NbExp=3; IntAct=EBI-1042490, EBI-718729;
CC Q00169; P13473-2: LAMP2; NbExp=3; IntAct=EBI-1042490, EBI-21591415;
CC Q00169; Q9Y371: SH3GLB1; NbExp=3; IntAct=EBI-1042490, EBI-2623095;
CC Q00169; P31930: UQCRC1; NbExp=3; IntAct=EBI-1042490, EBI-1052596;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:P53810}. Nucleus
CC {ECO:0000250|UniProtKB:P53810}.
CC -!- SIMILARITY: Belongs to the PtdIns transfer protein family. PI transfer
CC class I subfamily. {ECO:0000305}.
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DR EMBL; M73704; AAA36441.1; -; mRNA.
DR EMBL; D30036; BAA06276.1; -; mRNA.
DR EMBL; BC082976; AAH82976.1; -; mRNA.
DR EMBL; BC045108; AAH45108.1; -; mRNA.
DR CCDS; CCDS45563.1; -.
DR PIR; I53775; I53775.
DR RefSeq; NP_006215.1; NM_006224.3.
DR PDB; 1UW5; X-ray; 2.90 A; A/B/C/D=1-270.
DR PDBsum; 1UW5; -.
DR AlphaFoldDB; Q00169; -.
DR SMR; Q00169; -.
DR BioGRID; 111323; 32.
DR IntAct; Q00169; 13.
DR MINT; Q00169; -.
DR STRING; 9606.ENSP00000316809; -.
DR DrugBank; DB03690; (Z,Z)-4-Hydroxy-N,N,N-Trimethyl-10-Oxo-7-[(1-Oxo-9-Octadecenyl)Oxy]-3,5,9-Trioxa-4-Phosphaheptacos-18-En-1-Aminium-4-Oxide.
DR DrugBank; DB02144; 1,2-diacyl-sn-glycero-3-phosphoinositol.
DR SwissLipids; SLP:000000415; -.
DR GlyGen; Q00169; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q00169; -.
DR MetOSite; Q00169; -.
DR PhosphoSitePlus; Q00169; -.
DR BioMuta; PITPNA; -.
DR EPD; Q00169; -.
DR jPOST; Q00169; -.
DR MassIVE; Q00169; -.
DR PaxDb; Q00169; -.
DR PeptideAtlas; Q00169; -.
DR PRIDE; Q00169; -.
DR ProteomicsDB; 57841; -.
DR Antibodypedia; 5311; 193 antibodies from 33 providers.
DR DNASU; 5306; -.
DR Ensembl; ENST00000313486.12; ENSP00000316809.7; ENSG00000174238.16.
DR GeneID; 5306; -.
DR KEGG; hsa:5306; -.
DR MANE-Select; ENST00000313486.12; ENSP00000316809.7; NM_006224.4; NP_006215.1.
DR CTD; 5306; -.
DR DisGeNET; 5306; -.
DR GeneCards; PITPNA; -.
DR HGNC; HGNC:9001; PITPNA.
DR HPA; ENSG00000174238; Low tissue specificity.
DR MIM; 600174; gene.
DR neXtProt; NX_Q00169; -.
DR OpenTargets; ENSG00000174238; -.
DR PharmGKB; PA33335; -.
DR VEuPathDB; HostDB:ENSG00000174238; -.
DR eggNOG; KOG3668; Eukaryota.
DR GeneTree; ENSGT00940000157119; -.
DR HOGENOM; CLU_046509_0_0_1; -.
DR InParanoid; Q00169; -.
DR OMA; VQPVMTC; -.
DR OrthoDB; 951268at2759; -.
DR PhylomeDB; Q00169; -.
DR TreeFam; TF313279; -.
DR PathwayCommons; Q00169; -.
DR Reactome; R-HSA-418890; Role of second messengers in netrin-1 signaling.
DR Reactome; R-HSA-8950505; Gene and protein expression by JAK-STAT signaling after Interleukin-12 stimulation.
DR SignaLink; Q00169; -.
DR BioGRID-ORCS; 5306; 11 hits in 1081 CRISPR screens.
DR ChiTaRS; PITPNA; human.
DR EvolutionaryTrace; Q00169; -.
DR GeneWiki; Phosphatidylinositol_transfer_protein,_alpha; -.
DR GenomeRNAi; 5306; -.
DR Pharos; Q00169; Tbio.
DR PRO; PR:Q00169; -.
DR Proteomes; UP000005640; Chromosome 17.
DR RNAct; Q00169; protein.
DR Bgee; ENSG00000174238; Expressed in pigmented layer of retina and 212 other tissues.
DR ExpressionAtlas; Q00169; baseline and differential.
DR Genevisible; Q00169; HS.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0000062; F:fatty-acyl-CoA binding; IEA:Ensembl.
DR GO; GO:0031210; F:phosphatidylcholine binding; IDA:UniProtKB.
DR GO; GO:0120019; F:phosphatidylcholine transfer activity; IDA:UniProtKB.
DR GO; GO:0008525; F:phosphatidylcholine transporter activity; IDA:BHF-UCL.
DR GO; GO:1901611; F:phosphatidylglycerol binding; TAS:BHF-UCL.
DR GO; GO:0035091; F:phosphatidylinositol binding; IDA:UniProtKB.
DR GO; GO:0008526; F:phosphatidylinositol transfer activity; IDA:UniProtKB.
DR GO; GO:0070540; F:stearic acid binding; IEA:Ensembl.
DR GO; GO:0006629; P:lipid metabolic process; NAS:ProtInc.
DR GO; GO:0015914; P:phospholipid transport; IDA:BHF-UCL.
DR GO; GO:0007601; P:visual perception; TAS:ProtInc.
DR DisProt; DP02327; -.
DR Gene3D; 3.30.530.20; -; 1.
DR InterPro; IPR001666; PI_transfer.
DR InterPro; IPR023393; START-like_dom_sf.
DR PANTHER; PTHR10658; PTHR10658; 1.
DR Pfam; PF02121; IP_trans; 1.
DR PRINTS; PR00391; PITRANSFER.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Cytoplasm; Direct protein sequencing;
KW Lipid transport; Lipid-binding; Nucleus; Reference proteome; Transport.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:Q2HJ54"
FT CHAIN 2..270
FT /note="Phosphatidylinositol transfer protein alpha isoform"
FT /id="PRO_0000191639"
FT REGION 250..270
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 58
FT /ligand="a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-
FT inositol)"
FT /ligand_id="ChEBI:CHEBI:57880"
FT /evidence="ECO:0000269|PubMed:14962392"
FT BINDING 60
FT /ligand="a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-
FT inositol)"
FT /ligand_id="ChEBI:CHEBI:57880"
FT /evidence="ECO:0000269|PubMed:14962392"
FT BINDING 85
FT /ligand="a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-
FT inositol)"
FT /ligand_id="ChEBI:CHEBI:57880"
FT /evidence="ECO:0000269|PubMed:14962392"
FT BINDING 89
FT /ligand="a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-
FT inositol)"
FT /ligand_id="ChEBI:CHEBI:57880"
FT /evidence="ECO:0000269|PubMed:14962392"
FT BINDING 96
FT /ligand="a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-
FT inositol)"
FT /ligand_id="ChEBI:CHEBI:57880"
FT /evidence="ECO:0000269|PubMed:14962392"
FT BINDING 194
FT /ligand="a 1,2-diacyl-sn-glycero-3-phospho-(1D-myo-
FT inositol)"
FT /ligand_id="ChEBI:CHEBI:57880"
FT /evidence="ECO:0000269|PubMed:14962392"
FT MOD_RES 215
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MUTAGEN 58
FT /note="T->A: Reduced phosphatidylinositol and
FT phosphatidylcholine transfer activity."
FT /evidence="ECO:0000269|PubMed:14962392"
FT MUTAGEN 58
FT /note="T->E: Complete loss of phosphatidylinositol transfer
FT activity but no effect on phosphatidylcholine transfer
FT activity."
FT /evidence="ECO:0000269|PubMed:14962392"
FT MUTAGEN 58
FT /note="T->S: Reduced phosphatidylinositol transfer activity
FT but no effect on phosphatidylcholine transfer activity."
FT /evidence="ECO:0000269|PubMed:14962392"
FT MUTAGEN 60
FT /note="K->A: Complete loss of phosphatidylinositol transfer
FT activity but no effect on phosphatidylcholine transfer
FT activity."
FT /evidence="ECO:0000269|PubMed:14962392"
FT MUTAGEN 85
FT /note="E->A: Reduced phosphatidylinositol transfer activity
FT but no effect on phosphatidylcholine transfer activity."
FT /evidence="ECO:0000269|PubMed:14962392"
FT MUTAGEN 85
FT /note="E->Q: Reduced phosphatidylinositol and
FT phosphatidylcholine transfer activity."
FT /evidence="ECO:0000269|PubMed:14962392"
FT MUTAGEN 89
FT /note="N->F,L: Significant loss of phosphatidylinositol
FT transfer activity but no effect on phosphatidylcholine
FT transfer activity."
FT /evidence="ECO:0000269|PubMed:14962392"
FT MUTAGEN 94
FT /note="C->A,T: No effect on phosphatidylinositol transfer
FT activity. Resistant to inhibition by N-ethylmaleimide."
FT /evidence="ECO:0000269|PubMed:18636990"
FT MUTAGEN 102
FT /note="Y->A: Reduced phosphatidylinositol and
FT phosphatidylcholine transfer activity."
FT /evidence="ECO:0000269|PubMed:14962392"
FT MUTAGEN 187
FT /note="C->A: No effect on phosphatidylinositol transfer
FT activity."
FT /evidence="ECO:0000269|PubMed:18636990"
FT MUTAGEN 202..203
FT /note="WW->AA: Significant loss of phosphatidylinositol and
FT phosphatidylcholine transfer activity."
FT /evidence="ECO:0000269|PubMed:14962392,
FT ECO:0000269|PubMed:18636990"
FT CONFLICT 45
FT /note="N -> P (in Ref. 2; BAA06276)"
FT /evidence="ECO:0000305"
FT STRAND 3..13
FT /evidence="ECO:0007829|PDB:1UW5"
FT HELIX 15..33
FT /evidence="ECO:0007829|PDB:1UW5"
FT STRAND 38..49
FT /evidence="ECO:0007829|PDB:1UW5"
FT STRAND 54..65
FT /evidence="ECO:0007829|PDB:1UW5"
FT HELIX 70..73
FT /evidence="ECO:0007829|PDB:1UW5"
FT STRAND 81..90
FT /evidence="ECO:0007829|PDB:1UW5"
FT STRAND 93..99
FT /evidence="ECO:0007829|PDB:1UW5"
FT HELIX 101..103
FT /evidence="ECO:0007829|PDB:1UW5"
FT STRAND 106..120
FT /evidence="ECO:0007829|PDB:1UW5"
FT TURN 123..126
FT /evidence="ECO:0007829|PDB:1UW5"
FT HELIX 130..133
FT /evidence="ECO:0007829|PDB:1UW5"
FT STRAND 137..141
FT /evidence="ECO:0007829|PDB:1UW5"
FT HELIX 146..148
FT /evidence="ECO:0007829|PDB:1UW5"
FT HELIX 151..153
FT /evidence="ECO:0007829|PDB:1UW5"
FT HELIX 156..158
FT /evidence="ECO:0007829|PDB:1UW5"
FT HELIX 160..162
FT /evidence="ECO:0007829|PDB:1UW5"
FT TURN 166..168
FT /evidence="ECO:0007829|PDB:1UW5"
FT HELIX 177..182
FT /evidence="ECO:0007829|PDB:1UW5"
FT STRAND 190..200
FT /evidence="ECO:0007829|PDB:1UW5"
FT TURN 203..205
FT /evidence="ECO:0007829|PDB:1UW5"
FT HELIX 206..230
FT /evidence="ECO:0007829|PDB:1UW5"
FT HELIX 232..235
FT /evidence="ECO:0007829|PDB:1UW5"
FT HELIX 240..260
FT /evidence="ECO:0007829|PDB:1UW5"
SQ SEQUENCE 270 AA; 31806 MW; 4531E6E38697C93B CRC64;
MVLLKEYRVI LPVSVDEYQV GQLYSVAEAS KNETGGGEGV EVLVNEPYEK DGEKGQYTHK
IYHLQSKVPT FVRMLAPEGA LNIHEKAWNA YPYCRTVITN EYMKEDFLIK IETWHKPDLG
TQENVHKLEP EAWKHVEAVY IDIADRSQVL SKDYKAEEDP AKFKSIKTGR GPLGPNWKQE
LVNQKDCPYM CAYKLVTVKF KWWGLQNKVE NFIHKQERRL FTNFHRQLFC WLDKWVDLTM
DDIRRMEEET KRQLDEMRQK DPVKGMTADD
