Full text data of PITPNA
PITPNA
(PITPN)
[Confidence: low (only semi-automatic identification from reviews)]
Phosphatidylinositol transfer protein alpha isoform; PI-TP-alpha; PtdIns transfer protein alpha; PtdInsTP alpha
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Phosphatidylinositol transfer protein alpha isoform; PI-TP-alpha; PtdIns transfer protein alpha; PtdInsTP alpha
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
Q00169
ID PIPNA_HUMAN Reviewed; 270 AA.
AC Q00169;
DT 01-DEC-1992, integrated into UniProtKB/Swiss-Prot.
read moreDT 23-JAN-2007, sequence version 2.
DT 22-JAN-2014, entry version 129.
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;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; 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
RT protein and occurrence of a related sequence in widely divergent
RT 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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP PROTEIN SEQUENCE OF 135-146, AND MASS SPECTROMETRY.
RC TISSUE=Brain, and Cajal-Retzius cell;
RA Lubec G., Afjehi-Sadat L.;
RL Submitted (MAR-2007) to UniProtKB.
RN [5]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-215, AND MASS SPECTROMETRY.
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M.,
RA Walther T.C., 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 [6]
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.,
RA Buerckstuemmer T., 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 [7]
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.,
RA Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K.,
RA Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-
RT terminal acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [8]
RP X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS) IN COMPLEX WITH
RP PHOSPHATIDYLINOSITOL.
RX PubMed=14962392; DOI=10.1016/S0969-2126(04)00025-5;
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
RT protein alpha bound to phosphatidylinositol.";
RL Structure 12:317-326(2004).
CC -!- FUNCTION: Catalyzes the transfer of PtdIns and phosphatidylcholine
CC between membranes.
CC -!- SUBCELLULAR LOCATION: Cytoplasm.
CC -!- TISSUE SPECIFICITY: Expressed in a wide range of tissues.
CC -!- SIMILARITY: Belongs to the PtdIns transfer protein family. PI
CC transfer class I subfamily.
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
CC -----------------------------------------------------------------------
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 PIR; I53775; I53775.
DR RefSeq; NP_006215.1; NM_006224.3.
DR UniGene; Hs.429819; -.
DR PDB; 1UW5; X-ray; 2.90 A; A/B/C/D=1-270.
DR PDBsum; 1UW5; -.
DR ProteinModelPortal; Q00169; -.
DR SMR; Q00169; 1-269.
DR IntAct; Q00169; 3.
DR STRING; 9606.ENSP00000316809; -.
DR PhosphoSite; Q00169; -.
DR DMDM; 130770; -.
DR PaxDb; Q00169; -.
DR PRIDE; Q00169; -.
DR DNASU; 5306; -.
DR Ensembl; ENST00000313486; ENSP00000316809; ENSG00000174238.
DR GeneID; 5306; -.
DR KEGG; hsa:5306; -.
DR UCSC; uc010cjt.3; human.
DR CTD; 5306; -.
DR GeneCards; GC17M001421; -.
DR HGNC; HGNC:9001; PITPNA.
DR HPA; HPA000528; -.
DR MIM; 600174; gene.
DR neXtProt; NX_Q00169; -.
DR PharmGKB; PA33335; -.
DR eggNOG; NOG250489; -.
DR HOVERGEN; HBG058915; -.
DR InParanoid; Q00169; -.
DR OMA; MVLLKEY; -.
DR OrthoDB; EOG7PGDRB; -.
DR Reactome; REACT_111045; Developmental Biology.
DR ChiTaRS; PITPNA; human.
DR EvolutionaryTrace; Q00169; -.
DR GeneWiki; Phosphatidylinositol_transfer_protein,_alpha; -.
DR GenomeRNAi; 5306; -.
DR NextBio; 20510; -.
DR PRO; PR:Q00169; -.
DR ArrayExpress; Q00169; -.
DR Bgee; Q00169; -.
DR CleanEx; HS_PITPNA; -.
DR Genevestigator; Q00169; -.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0000062; F:fatty-acyl-CoA binding; IEA:Ensembl.
DR GO; GO:0008525; F:phosphatidylcholine transporter activity; TAS:ProtInc.
DR GO; GO:0035091; F:phosphatidylinositol binding; IEA:Ensembl.
DR GO; GO:0008526; F:phosphatidylinositol transporter activity; TAS:ProtInc.
DR GO; GO:0070540; F:stearic acid binding; IEA:Ensembl.
DR GO; GO:0007411; P:axon guidance; TAS:Reactome.
DR GO; GO:0006629; P:lipid metabolic process; NAS:ProtInc.
DR GO; GO:0007601; P:visual perception; TAS:ProtInc.
DR Gene3D; 3.30.530.20; -; 1.
DR InterPro; IPR001666; PI_transfer.
DR InterPro; IPR023393; START-like_dom.
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; Complete proteome; Cytoplasm;
KW Direct protein sequencing; Lipid-binding; Reference proteome;
KW Transport.
FT INIT_MET 1 1 Removed (By similarity).
FT CHAIN 2 270 Phosphatidylinositol transfer protein
FT alpha isoform.
FT /FTId=PRO_0000191639.
FT BINDING 58 58 Phosphatidylinositol lipid headgroup.
FT BINDING 60 60 Phosphatidylinositol lipid headgroup.
FT BINDING 85 85 Phosphatidylinositol lipid headgroup.
FT BINDING 89 89 Phosphatidylinositol lipid headgroup.
FT BINDING 96 96 Phosphatidylinositol lipid headgroup.
FT BINDING 194 194 Phosphatidylinositol lipid headgroup.
FT MOD_RES 215 215 N6-acetyllysine.
FT CONFLICT 45 45 N -> P (in Ref. 2; BAA06276).
FT STRAND 3 13
FT HELIX 15 33
FT STRAND 38 49
FT STRAND 54 65
FT HELIX 70 73
FT STRAND 81 90
FT STRAND 93 99
FT HELIX 101 103
FT STRAND 106 120
FT TURN 123 126
FT HELIX 130 133
FT STRAND 137 141
FT HELIX 146 148
FT HELIX 151 153
FT HELIX 156 158
FT HELIX 160 162
FT TURN 166 168
FT HELIX 177 182
FT STRAND 190 200
FT TURN 203 205
FT HELIX 206 230
FT HELIX 232 235
FT HELIX 240 260
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
//
ID PIPNA_HUMAN Reviewed; 270 AA.
AC Q00169;
DT 01-DEC-1992, integrated into UniProtKB/Swiss-Prot.
read moreDT 23-JAN-2007, sequence version 2.
DT 22-JAN-2014, entry version 129.
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;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; 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
RT protein and occurrence of a related sequence in widely divergent
RT 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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP PROTEIN SEQUENCE OF 135-146, AND MASS SPECTROMETRY.
RC TISSUE=Brain, and Cajal-Retzius cell;
RA Lubec G., Afjehi-Sadat L.;
RL Submitted (MAR-2007) to UniProtKB.
RN [5]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-215, AND MASS SPECTROMETRY.
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M.,
RA Walther T.C., 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 [6]
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.,
RA Buerckstuemmer T., 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 [7]
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.,
RA Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K.,
RA Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-
RT terminal acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [8]
RP X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS) IN COMPLEX WITH
RP PHOSPHATIDYLINOSITOL.
RX PubMed=14962392; DOI=10.1016/S0969-2126(04)00025-5;
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
RT protein alpha bound to phosphatidylinositol.";
RL Structure 12:317-326(2004).
CC -!- FUNCTION: Catalyzes the transfer of PtdIns and phosphatidylcholine
CC between membranes.
CC -!- SUBCELLULAR LOCATION: Cytoplasm.
CC -!- TISSUE SPECIFICITY: Expressed in a wide range of tissues.
CC -!- SIMILARITY: Belongs to the PtdIns transfer protein family. PI
CC transfer class I subfamily.
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
CC -----------------------------------------------------------------------
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 PIR; I53775; I53775.
DR RefSeq; NP_006215.1; NM_006224.3.
DR UniGene; Hs.429819; -.
DR PDB; 1UW5; X-ray; 2.90 A; A/B/C/D=1-270.
DR PDBsum; 1UW5; -.
DR ProteinModelPortal; Q00169; -.
DR SMR; Q00169; 1-269.
DR IntAct; Q00169; 3.
DR STRING; 9606.ENSP00000316809; -.
DR PhosphoSite; Q00169; -.
DR DMDM; 130770; -.
DR PaxDb; Q00169; -.
DR PRIDE; Q00169; -.
DR DNASU; 5306; -.
DR Ensembl; ENST00000313486; ENSP00000316809; ENSG00000174238.
DR GeneID; 5306; -.
DR KEGG; hsa:5306; -.
DR UCSC; uc010cjt.3; human.
DR CTD; 5306; -.
DR GeneCards; GC17M001421; -.
DR HGNC; HGNC:9001; PITPNA.
DR HPA; HPA000528; -.
DR MIM; 600174; gene.
DR neXtProt; NX_Q00169; -.
DR PharmGKB; PA33335; -.
DR eggNOG; NOG250489; -.
DR HOVERGEN; HBG058915; -.
DR InParanoid; Q00169; -.
DR OMA; MVLLKEY; -.
DR OrthoDB; EOG7PGDRB; -.
DR Reactome; REACT_111045; Developmental Biology.
DR ChiTaRS; PITPNA; human.
DR EvolutionaryTrace; Q00169; -.
DR GeneWiki; Phosphatidylinositol_transfer_protein,_alpha; -.
DR GenomeRNAi; 5306; -.
DR NextBio; 20510; -.
DR PRO; PR:Q00169; -.
DR ArrayExpress; Q00169; -.
DR Bgee; Q00169; -.
DR CleanEx; HS_PITPNA; -.
DR Genevestigator; Q00169; -.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0000062; F:fatty-acyl-CoA binding; IEA:Ensembl.
DR GO; GO:0008525; F:phosphatidylcholine transporter activity; TAS:ProtInc.
DR GO; GO:0035091; F:phosphatidylinositol binding; IEA:Ensembl.
DR GO; GO:0008526; F:phosphatidylinositol transporter activity; TAS:ProtInc.
DR GO; GO:0070540; F:stearic acid binding; IEA:Ensembl.
DR GO; GO:0007411; P:axon guidance; TAS:Reactome.
DR GO; GO:0006629; P:lipid metabolic process; NAS:ProtInc.
DR GO; GO:0007601; P:visual perception; TAS:ProtInc.
DR Gene3D; 3.30.530.20; -; 1.
DR InterPro; IPR001666; PI_transfer.
DR InterPro; IPR023393; START-like_dom.
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; Complete proteome; Cytoplasm;
KW Direct protein sequencing; Lipid-binding; Reference proteome;
KW Transport.
FT INIT_MET 1 1 Removed (By similarity).
FT CHAIN 2 270 Phosphatidylinositol transfer protein
FT alpha isoform.
FT /FTId=PRO_0000191639.
FT BINDING 58 58 Phosphatidylinositol lipid headgroup.
FT BINDING 60 60 Phosphatidylinositol lipid headgroup.
FT BINDING 85 85 Phosphatidylinositol lipid headgroup.
FT BINDING 89 89 Phosphatidylinositol lipid headgroup.
FT BINDING 96 96 Phosphatidylinositol lipid headgroup.
FT BINDING 194 194 Phosphatidylinositol lipid headgroup.
FT MOD_RES 215 215 N6-acetyllysine.
FT CONFLICT 45 45 N -> P (in Ref. 2; BAA06276).
FT STRAND 3 13
FT HELIX 15 33
FT STRAND 38 49
FT STRAND 54 65
FT HELIX 70 73
FT STRAND 81 90
FT STRAND 93 99
FT HELIX 101 103
FT STRAND 106 120
FT TURN 123 126
FT HELIX 130 133
FT STRAND 137 141
FT HELIX 146 148
FT HELIX 151 153
FT HELIX 156 158
FT HELIX 160 162
FT TURN 166 168
FT HELIX 177 182
FT STRAND 190 200
FT TURN 203 205
FT HELIX 206 230
FT HELIX 232 235
FT HELIX 240 260
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
//
MIM
600174
*RECORD*
*FIELD* NO
600174
*FIELD* TI
*600174 PHOSPHATIDYLINOSITOL TRANSFER PROTEIN, ALPHA; PITPNA
;;PITPN
*FIELD* TX
DESCRIPTION
read more
Phosphatidylinositol transfer protein is a member of a diverse set of
cytosolic phospholipid transfer proteins that are distinguished by their
ability to transfer phospholipids between membranes in vitro (Wirtz,
1991).
CLONING
The rat Pitpna gene encodes a polypeptide of 271 amino acids and is
expressed in a wide range of tissues (Dickeson et al., 1989). The
protein predicted by the human PITPNA gene cloned and sequenced by
Dickeson et al. (1994) showed only 3 amino acid sequence differences
from the rat protein, 2 of which represented conservative substitutions.
Hay and Martin (1993) reported studies suggesting that PITPNA is
identical to priming-specific factor-3, one of the 3 priming factors
involved in the ATP-dependent priming of Ca(2+)-activated secretion. Rat
Pitpna shares 40% amino acid homology over its entire length with the
Drosophila retinal degeneration B (rdgB) protein (Vihtelic et al.,
1993). Flies carrying the rdgB mutation undergo light-enhanced retinal
degeneration.
MAPPING
As a first step toward investigations of possible involvement of the
PITPNA locus in retinal degeneration, Fitzgibbon et al. (1994) mapped
the PITPNA gene to human chromosome 17p13.3 by PCR analysis of a somatic
cell hybrid panel followed by fluorescence in situ hybridization. They
mapped the homologous gene to mouse chromosome 11 by interspecific mouse
backcross mapping.
ANIMAL MODEL
The mouse 'vibrator' (vb) mutation causes an early-onset progressive
action tremor, degeneration of brainstem and spinal cord neurons, and
juvenile death. Hamilton et al. (1997) cloned the vb mutation using an
in vivo positional complementation approach followed by complete
resequencing of the resulting 76-kb critical region in vb and its
progenitor strain. The authors showed that the vb mutation is an
intracisternal A particle retroposon insertion in intron 4 of the Pitpn
gene, causing a 5-fold reduction in Pitpn RNA and protein levels.
Expression of neurofilament light chain (NEFL; 162280) was also reduced
in vb mice, suggesting 1 signaling pathway that may underlie vb
pathology. The vb phenotype was suppressed in 1 intercross. By a
complete genome scan, they mapped a major suppressor locus (Mvb1) to
proximal mouse chromosome 19.
The modifier-of-vibrator-1 locus (Mvb1) controls levels of correctly
processed mRNA from genes mutated by endogenous retrovirus insertions
into introns, including the Pitpn(vb) tremor mutation. By positional
complementation cloning, Floyd et al. (2003) identified Mvb1 as the
nuclear export factor Nxf1 (602647), providing an unexpected link
between the mRNA export receptor and pre-mRNA processing.
By examining lipid profiles, Monaco et al. (2004) observed increased
neutral lipids, including cholesterol esters, triglycerides, and free
fatty acids, in vb/vb liver compared with wildtype. No changes were
detected in vb/vb liver phospholipid content or in the vb/vb brain lipid
profile. Mammary glands of vb/vb mice were significantly underdeveloped
compared with wildtype, and vb/vb mammary fat pads contained brown
rather than white adipose tissue. No defect in phospholipid-mediated
signaling was observed in isolated vb/vb fibroblasts. In Ptpa-null mice,
Monaco et al. (2004) found reduced circulating triglycerides, overall
reduction in body fat, low ATP/ADP ratio, and histologic evidence of
steatosis in liver and duodenal tissue. Monaco et al. (2004) suggested
that reduced Ptpa activity may result in biochemical uncoupling of
mitochondrial fuel metabolism from energy production.
*FIELD* RF
1. Dickeson, S. K.; Helmkamp, G. M., Jr.; Yarbrough, L. R.: Sequence
of a human cDNA encoding phosphatidylinositol transfer protein and
occurrence of a related sequence in widely divergent eukaryotes. Gene 142:
301-305, 1994.
2. Dickeson, S. K.; Lim, C. N.; Schuyler, G. T.; Dalton, T. P.; Helmkamp,
G. M., Jr.; Yarbrough, L. R.: Isolation and sequence of cDNA clones
encoding rat phosphatidylinositol transfer protein. J. Biol. Chem. 264:
16557-16564, 1989.
3. Fitzgibbon, J.; Pilz, A.; Gayther, S.; Appukuttan, B.; Dulai, K.
S.; Delhanty, J. D. A.; Helmkamp, G. M., Jr.; Yarbrough, L. R.; Hunt,
D. M.: Localization of the gene encoding human phosphatidylinositol
transfer protein (PITPN) to 17p13.3: a gene showing homology to the
Drosophila retinal degeneration B gene (rdgB). Cytogenet. Cell Genet. 67:
205-207, 1994.
4. Floyd, J. A.; Gold, D. A.; Concepcion, D.; Poon, T. H.; Wang, X.;
Keithley, E.; Chen, D.; Ward, E. J.; Chinn, S. B.; Friedman, R. A.;
Yu, H.-T.; Moriwaki, K.; Shiroishi, T.; Hamilton, B. A.: A natural
allele of Nxf1 suppresses retrovirus insertional mutations. Nature
Genet. 35: 221-228, 2003.
5. Hamilton, B. A.; Smith, D. J.; Mueller, K. L.; Kerrebrock, A. W.;
Bronson, R. T.; van Berkel, V.; Daly, M. J.; Kruglyak, L.; Reeve,
M. P.; Nemhauser, J. L.; Hawkins, T. L.; Rubin, E. M.; Lander, E.
S.: The vibrator mutation causes neurodegeneration via reduced expression
of PITP-alpha: positional complementation cloning and extragenic suppression. Neuron 18:
711-722, 1997.
6. Hay, J. C.; Martin, T. F. J.: Phosphatidylinositol transfer protein
required for ATP-dependent priming of Ca(2+)-activated secretion. Nature 366:
572-575, 1993.
7. Monaco, M. E.; Kim, J.; Ruan, W.; Wieczorek, R.; Kleinberg, D.
L.; Walden, P. D.: Lipid metabolism in phosphatidylinositol transfer
protein alpha-deficient vibrator mice. Biochem. Biophys. Res. Commun. 317:
444-450, 2004.
8. Vihtelic, T. S.; Goebl, M.; Milligan, S.; O'Tousa, J. E.; Hyde,
D. R.: Localization of Drosophila retinal degeneration B, a membrane-associated
phosphatidylinositol transfer protein. J. Cell Biol. 122: 1013-1022,
1993.
9. Wirtz, K. W. A.: Phospholipid transfer proteins. Annu. Rev. Biochem. 60:
73-99, 1991.
*FIELD* CN
Patricia A. Hartz - updated: 4/28/2011
Victor A. McKusick - updated: 10/1/2003
Victor A. McKusick - updated: 3/26/1998
*FIELD* CD
Victor A. McKusick: 11/1/1994
*FIELD* ED
mgross: 05/19/2011
terry: 4/28/2011
wwang: 6/9/2010
terry: 3/3/2005
alopez: 10/31/2003
alopez: 10/1/2003
terry: 10/1/2003
carol: 4/24/2002
psherman: 3/27/1998
terry: 3/26/1998
joanna: 5/7/1997
terry: 11/1/1994
*RECORD*
*FIELD* NO
600174
*FIELD* TI
*600174 PHOSPHATIDYLINOSITOL TRANSFER PROTEIN, ALPHA; PITPNA
;;PITPN
*FIELD* TX
DESCRIPTION
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Phosphatidylinositol transfer protein is a member of a diverse set of
cytosolic phospholipid transfer proteins that are distinguished by their
ability to transfer phospholipids between membranes in vitro (Wirtz,
1991).
CLONING
The rat Pitpna gene encodes a polypeptide of 271 amino acids and is
expressed in a wide range of tissues (Dickeson et al., 1989). The
protein predicted by the human PITPNA gene cloned and sequenced by
Dickeson et al. (1994) showed only 3 amino acid sequence differences
from the rat protein, 2 of which represented conservative substitutions.
Hay and Martin (1993) reported studies suggesting that PITPNA is
identical to priming-specific factor-3, one of the 3 priming factors
involved in the ATP-dependent priming of Ca(2+)-activated secretion. Rat
Pitpna shares 40% amino acid homology over its entire length with the
Drosophila retinal degeneration B (rdgB) protein (Vihtelic et al.,
1993). Flies carrying the rdgB mutation undergo light-enhanced retinal
degeneration.
MAPPING
As a first step toward investigations of possible involvement of the
PITPNA locus in retinal degeneration, Fitzgibbon et al. (1994) mapped
the PITPNA gene to human chromosome 17p13.3 by PCR analysis of a somatic
cell hybrid panel followed by fluorescence in situ hybridization. They
mapped the homologous gene to mouse chromosome 11 by interspecific mouse
backcross mapping.
ANIMAL MODEL
The mouse 'vibrator' (vb) mutation causes an early-onset progressive
action tremor, degeneration of brainstem and spinal cord neurons, and
juvenile death. Hamilton et al. (1997) cloned the vb mutation using an
in vivo positional complementation approach followed by complete
resequencing of the resulting 76-kb critical region in vb and its
progenitor strain. The authors showed that the vb mutation is an
intracisternal A particle retroposon insertion in intron 4 of the Pitpn
gene, causing a 5-fold reduction in Pitpn RNA and protein levels.
Expression of neurofilament light chain (NEFL; 162280) was also reduced
in vb mice, suggesting 1 signaling pathway that may underlie vb
pathology. The vb phenotype was suppressed in 1 intercross. By a
complete genome scan, they mapped a major suppressor locus (Mvb1) to
proximal mouse chromosome 19.
The modifier-of-vibrator-1 locus (Mvb1) controls levels of correctly
processed mRNA from genes mutated by endogenous retrovirus insertions
into introns, including the Pitpn(vb) tremor mutation. By positional
complementation cloning, Floyd et al. (2003) identified Mvb1 as the
nuclear export factor Nxf1 (602647), providing an unexpected link
between the mRNA export receptor and pre-mRNA processing.
By examining lipid profiles, Monaco et al. (2004) observed increased
neutral lipids, including cholesterol esters, triglycerides, and free
fatty acids, in vb/vb liver compared with wildtype. No changes were
detected in vb/vb liver phospholipid content or in the vb/vb brain lipid
profile. Mammary glands of vb/vb mice were significantly underdeveloped
compared with wildtype, and vb/vb mammary fat pads contained brown
rather than white adipose tissue. No defect in phospholipid-mediated
signaling was observed in isolated vb/vb fibroblasts. In Ptpa-null mice,
Monaco et al. (2004) found reduced circulating triglycerides, overall
reduction in body fat, low ATP/ADP ratio, and histologic evidence of
steatosis in liver and duodenal tissue. Monaco et al. (2004) suggested
that reduced Ptpa activity may result in biochemical uncoupling of
mitochondrial fuel metabolism from energy production.
*FIELD* RF
1. Dickeson, S. K.; Helmkamp, G. M., Jr.; Yarbrough, L. R.: Sequence
of a human cDNA encoding phosphatidylinositol transfer protein and
occurrence of a related sequence in widely divergent eukaryotes. Gene 142:
301-305, 1994.
2. Dickeson, S. K.; Lim, C. N.; Schuyler, G. T.; Dalton, T. P.; Helmkamp,
G. M., Jr.; Yarbrough, L. R.: Isolation and sequence of cDNA clones
encoding rat phosphatidylinositol transfer protein. J. Biol. Chem. 264:
16557-16564, 1989.
3. Fitzgibbon, J.; Pilz, A.; Gayther, S.; Appukuttan, B.; Dulai, K.
S.; Delhanty, J. D. A.; Helmkamp, G. M., Jr.; Yarbrough, L. R.; Hunt,
D. M.: Localization of the gene encoding human phosphatidylinositol
transfer protein (PITPN) to 17p13.3: a gene showing homology to the
Drosophila retinal degeneration B gene (rdgB). Cytogenet. Cell Genet. 67:
205-207, 1994.
4. Floyd, J. A.; Gold, D. A.; Concepcion, D.; Poon, T. H.; Wang, X.;
Keithley, E.; Chen, D.; Ward, E. J.; Chinn, S. B.; Friedman, R. A.;
Yu, H.-T.; Moriwaki, K.; Shiroishi, T.; Hamilton, B. A.: A natural
allele of Nxf1 suppresses retrovirus insertional mutations. Nature
Genet. 35: 221-228, 2003.
5. Hamilton, B. A.; Smith, D. J.; Mueller, K. L.; Kerrebrock, A. W.;
Bronson, R. T.; van Berkel, V.; Daly, M. J.; Kruglyak, L.; Reeve,
M. P.; Nemhauser, J. L.; Hawkins, T. L.; Rubin, E. M.; Lander, E.
S.: The vibrator mutation causes neurodegeneration via reduced expression
of PITP-alpha: positional complementation cloning and extragenic suppression. Neuron 18:
711-722, 1997.
6. Hay, J. C.; Martin, T. F. J.: Phosphatidylinositol transfer protein
required for ATP-dependent priming of Ca(2+)-activated secretion. Nature 366:
572-575, 1993.
7. Monaco, M. E.; Kim, J.; Ruan, W.; Wieczorek, R.; Kleinberg, D.
L.; Walden, P. D.: Lipid metabolism in phosphatidylinositol transfer
protein alpha-deficient vibrator mice. Biochem. Biophys. Res. Commun. 317:
444-450, 2004.
8. Vihtelic, T. S.; Goebl, M.; Milligan, S.; O'Tousa, J. E.; Hyde,
D. R.: Localization of Drosophila retinal degeneration B, a membrane-associated
phosphatidylinositol transfer protein. J. Cell Biol. 122: 1013-1022,
1993.
9. Wirtz, K. W. A.: Phospholipid transfer proteins. Annu. Rev. Biochem. 60:
73-99, 1991.
*FIELD* CN
Patricia A. Hartz - updated: 4/28/2011
Victor A. McKusick - updated: 10/1/2003
Victor A. McKusick - updated: 3/26/1998
*FIELD* CD
Victor A. McKusick: 11/1/1994
*FIELD* ED
mgross: 05/19/2011
terry: 4/28/2011
wwang: 6/9/2010
terry: 3/3/2005
alopez: 10/31/2003
alopez: 10/1/2003
terry: 10/1/2003
carol: 4/24/2002
psherman: 3/27/1998
terry: 3/26/1998
joanna: 5/7/1997
terry: 11/1/1994