CPTP_HUMAN
ID CPTP_HUMAN Reviewed; 214 AA.
AC Q5TA50; Q4G0E6; Q7L5A4;
DT 05-FEB-2008, integrated into UniProtKB/Swiss-Prot.
DT 21-DEC-2004, sequence version 1.
DT 03-AUG-2022, entry version 126.
DE RecName: Full=Ceramide-1-phosphate transfer protein {ECO:0000303|PubMed:23863933, ECO:0000305};
DE Short=CPTP {ECO:0000303|PubMed:23863933, ECO:0000305};
DE AltName: Full=Glycolipid transfer protein domain-containing protein 1 {ECO:0000305};
DE Short=GLTP domain-containing protein 1 {ECO:0000303|PubMed:23863933, ECO:0000305};
GN Name=CPTP {ECO:0000312|HGNC:HGNC:28116};
GN Synonyms=GLTPD1 {ECO:0000303|PubMed:23863933, ECO:0000312|HGNC:HGNC:28116};
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 [LARGE SCALE MRNA].
RC TISSUE=B-cell;
RA Li W.B., Gruber C., Jessee J., Polayes D.;
RT "Full-length cDNA libraries and normalization.";
RL Submitted (JUL-2004) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 55-214.
RC TISSUE=Neuroblastoma;
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 [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [6]
RP FUNCTION, AND MUTAGENESIS OF LYS-60 AND ARG-106.
RX PubMed=29164996; DOI=10.1080/15548627.2017.1393129;
RA Mishra S.K., Gao Y.G., Deng Y., Chalfant C.E., Hinchcliffe E.H.,
RA Brown R.E.;
RT "CPTP: A sphingolipid transfer protein that regulates autophagy and
RT inflammasome activation.";
RL Autophagy 14:862-879(2018).
RN [7]
RP FUNCTION, AND LIPID-BINDING.
RX PubMed=28011644; DOI=10.1074/jbc.m116.760256;
RA Zhai X., Gao Y.G., Mishra S.K., Simanshu D.K., Boldyrev I.A., Benson L.M.,
RA Bergen H.R. III, Malinina L., Mundy J., Molotkovsky J.G., Patel D.J.,
RA Brown R.E.;
RT "Phosphatidylserine Stimulates Ceramide 1-Phosphate (C1P) Intermembrane
RT Transfer by C1P Transfer Proteins.";
RL J. Biol. Chem. 292:2531-2541(2017).
RN [8]
RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) IN COMPLEXES WITH
RP CERAMIDE-1-PHOSPHATE, FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION,
RP LIPID-BINDING, MUTAGENESIS OF PHE-42; LEU-43; PHE-50; ILE-53; ASP-56;
RP LYS-60; ARG-97; ARG-106; ARG-110; ARG-113; TRP-117; LEU-118; TYR-149 AND
RP VAL-158, AND TISSUE SPECIFICITY.
RX PubMed=23863933; DOI=10.1038/nature12332;
RA Simanshu D.K., Kamlekar R.K., Wijesinghe D.S., Zou X., Zhai X.,
RA Mishra S.K., Molotkovsky J.G., Malinina L., Hinchcliffe E.H.,
RA Chalfant C.E., Brown R.E., Patel D.J.;
RT "Non-vesicular trafficking by a ceramide-1-phosphate transfer protein
RT regulates eicosanoids.";
RL Nature 500:463-467(2013).
CC -!- FUNCTION: Mediates the intracellular transfer of ceramide-1-phosphate
CC (C1P) between organelle membranes and the cell membrane. Required for
CC normal structure of the Golgi stacks. Can bind phosphoceramides with a
CC variety of aliphatic chains, but has a preference for lipids with
CC saturated C16:0 or monounsaturated C18:1 aliphatic chains, and is
CC inefficient with phosphoceramides containing lignoceryl (C24:0). Plays
CC a role in the regulation of the cellular levels of ceramide-1-
CC phosphate, and thereby contributes to the regulation of phospholipase
CC PLA2G4A activity and the release of arachidonic acid. Has no activity
CC with galactosylceramide, lactosylceramide, sphingomyelin,
CC phosphatidylcholine, phosphatidic acid and ceramide. C1P transfer is
CC stimulated by phosphatidylserine in C1P source vesicles
CC (PubMed:28011644). Regulates autophagy, inflammasome mediated IL1B and
CC IL18 processing, and pyroptosis, but not apoptosis (PubMed:29164996).
CC {ECO:0000269|PubMed:23863933, ECO:0000269|PubMed:28011644,
CC ECO:0000269|PubMed:29164996}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=N-(hexadecanoyl)-sphing-4-enine-1-phosphate(in) = N-
CC (hexadecanoyl)-sphing-4-enine-1-phosphate(out); Xref=Rhea:RHEA:45680,
CC ChEBI:CHEBI:72963; Evidence={ECO:0000269|PubMed:23863933};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45681;
CC Evidence={ECO:0000305|PubMed:23863933};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=N-(9Z-octadecenoyl)-sphing-4-enine-1-phosphate(in) = N-(9Z-
CC octadecenoyl)-sphing-4-enine-1-phosphate(out); Xref=Rhea:RHEA:45688,
CC ChEBI:CHEBI:85378; Evidence={ECO:0000269|PubMed:23863933};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45689;
CC Evidence={ECO:0000305|PubMed:23863933};
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000269|PubMed:23863933}.
CC Golgi apparatus, trans-Golgi network membrane
CC {ECO:0000269|PubMed:23863933}; Peripheral membrane protein
CC {ECO:0000269|PubMed:23863933}. Cell membrane
CC {ECO:0000269|PubMed:23863933}; Peripheral membrane protein
CC {ECO:0000269|PubMed:23863933}; Cytoplasmic side
CC {ECO:0000269|PubMed:23863933}. Endosome membrane
CC {ECO:0000269|PubMed:23863933}; Peripheral membrane protein
CC {ECO:0000269|PubMed:23863933}. Nucleus outer membrane
CC {ECO:0000269|PubMed:23863933}; Peripheral membrane protein
CC {ECO:0000269|PubMed:23863933}.
CC -!- TISSUE SPECIFICITY: Ubiquitous. Detected in heart, brain, placenta,
CC lung, liver, skeletal muscle, kidney, pancreas, spleen, thymus,
CC prostate, testis, ovary, small intestine, colon and peripheral blood
CC leukocytes. {ECO:0000269|PubMed:23863933}.
CC -!- SIMILARITY: Belongs to the GLTP family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=EAW56230.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; CR599582; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; AL139287; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471183; EAW56230.1; ALT_SEQ; Genomic_DNA.
DR EMBL; BC098429; AAH98429.1; -; mRNA.
DR CCDS; CCDS30555.1; -.
DR RefSeq; NP_001025056.1; NM_001029885.1.
DR RefSeq; XP_005244858.1; XM_005244801.3.
DR RefSeq; XP_011540502.1; XM_011542200.2.
DR PDB; 4K80; X-ray; 2.05 A; A=1-214.
DR PDB; 4K84; X-ray; 1.90 A; A/B=1-214.
DR PDB; 4K85; X-ray; 1.90 A; A/B/C/D=1-214.
DR PDB; 4K8N; X-ray; 3.10 A; A/B/C/D/E/F=1-214.
DR PDB; 4KBS; X-ray; 1.90 A; A/B=1-214.
DR PDB; 4KF6; X-ray; 3.20 A; A/B/C/D/E/F=1-214.
DR PDBsum; 4K80; -.
DR PDBsum; 4K84; -.
DR PDBsum; 4K85; -.
DR PDBsum; 4K8N; -.
DR PDBsum; 4KBS; -.
DR PDBsum; 4KF6; -.
DR AlphaFoldDB; Q5TA50; -.
DR SMR; Q5TA50; -.
DR BioGRID; 123305; 7.
DR IntAct; Q5TA50; 8.
DR STRING; 9606.ENSP00000343890; -.
DR SwissLipids; SLP:000000406; -.
DR GlyGen; Q5TA50; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q5TA50; -.
DR PhosphoSitePlus; Q5TA50; -.
DR BioMuta; CPTP; -.
DR DMDM; 74745771; -.
DR EPD; Q5TA50; -.
DR jPOST; Q5TA50; -.
DR MassIVE; Q5TA50; -.
DR PaxDb; Q5TA50; -.
DR PeptideAtlas; Q5TA50; -.
DR PRIDE; Q5TA50; -.
DR ProteomicsDB; 64828; -.
DR Antibodypedia; 66414; 19 antibodies from 8 providers.
DR DNASU; 80772; -.
DR Ensembl; ENST00000343938.9; ENSP00000343890.4; ENSG00000224051.7.
DR GeneID; 80772; -.
DR KEGG; hsa:80772; -.
DR MANE-Select; ENST00000343938.9; ENSP00000343890.4; NM_001029885.2; NP_001025056.1.
DR CTD; 80772; -.
DR DisGeNET; 80772; -.
DR GeneCards; CPTP; -.
DR HGNC; HGNC:28116; CPTP.
DR HPA; ENSG00000224051; Low tissue specificity.
DR MIM; 615467; gene.
DR neXtProt; NX_Q5TA50; -.
DR OpenTargets; ENSG00000224051; -.
DR PharmGKB; PA162389853; -.
DR VEuPathDB; HostDB:ENSG00000224051; -.
DR eggNOG; KOG4189; Eukaryota.
DR GeneTree; ENSGT00940000161763; -.
DR HOGENOM; CLU_079649_1_0_1; -.
DR InParanoid; Q5TA50; -.
DR OMA; YKFFQLM; -.
DR OrthoDB; 1423493at2759; -.
DR PhylomeDB; Q5TA50; -.
DR TreeFam; TF316097; -.
DR PathwayCommons; Q5TA50; -.
DR Reactome; R-HSA-1660662; Glycosphingolipid metabolism.
DR SignaLink; Q5TA50; -.
DR BioGRID-ORCS; 80772; 12 hits in 1079 CRISPR screens.
DR GenomeRNAi; 80772; -.
DR Pharos; Q5TA50; Tbio.
DR PRO; PR:Q5TA50; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; Q5TA50; protein.
DR Bgee; ENSG00000224051; Expressed in apex of heart and 187 other tissues.
DR ExpressionAtlas; Q5TA50; baseline and differential.
DR Genevisible; Q5TA50; HS.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0010008; C:endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005794; C:Golgi apparatus; IEA:UniProtKB-SubCell.
DR GO; GO:0005640; C:nuclear outer membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:1902387; F:ceramide 1-phosphate binding; IDA:UniProtKB.
DR GO; GO:1902388; F:ceramide 1-phosphate transfer activity; IDA:UniProtKB.
DR GO; GO:0005543; F:phospholipid binding; IDA:UniProtKB.
DR GO; GO:1902389; P:ceramide 1-phosphate transport; IDA:UniProtKB.
DR GO; GO:0035627; P:ceramide transport; IBA:GO_Central.
DR GO; GO:0006687; P:glycosphingolipid metabolic process; TAS:Reactome.
DR GO; GO:0120009; P:intermembrane lipid transfer; IBA:GO_Central.
DR GO; GO:0010507; P:negative regulation of autophagy; IMP:UniProtKB.
DR GO; GO:0032691; P:negative regulation of interleukin-1 beta production; IMP:UniProtKB.
DR GO; GO:1900226; P:negative regulation of NLRP3 inflammasome complex assembly; IMP:UniProtKB.
DR Gene3D; 1.10.3520.10; -; 1.
DR InterPro; IPR036497; GLTP_sf.
DR InterPro; IPR014830; Glycolipid_transfer_prot_dom.
DR Pfam; PF08718; GLTP; 1.
DR SUPFAM; SSF110004; SSF110004; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cell membrane; Cytoplasm; Endosome; Golgi apparatus;
KW Lipid transport; Lipid-binding; Membrane; Nucleus; Reference proteome;
KW Transport.
FT CHAIN 1..214
FT /note="Ceramide-1-phosphate transfer protein"
FT /id="PRO_0000317156"
FT BINDING 56
FT /ligand="an N-acylsphingoid base 1-phosphate"
FT /ligand_id="ChEBI:CHEBI:84404"
FT /evidence="ECO:0000269|PubMed:23863933"
FT BINDING 60
FT /ligand="an N-acylsphingoid base 1-phosphate"
FT /ligand_id="ChEBI:CHEBI:84404"
FT /evidence="ECO:0000269|PubMed:23863933"
FT BINDING 106
FT /ligand="an N-acylsphingoid base 1-phosphate"
FT /ligand_id="ChEBI:CHEBI:84404"
FT /evidence="ECO:0000269|PubMed:23863933"
FT BINDING 110
FT /ligand="an N-acylsphingoid base 1-phosphate"
FT /ligand_id="ChEBI:CHEBI:84404"
FT /evidence="ECO:0000269|PubMed:23863933"
FT BINDING 150
FT /ligand="an N-acylsphingoid base 1-phosphate"
FT /ligand_id="ChEBI:CHEBI:84404"
FT /evidence="ECO:0000269|PubMed:23863933"
FT MUTAGEN 42
FT /note="F->A: Increases phosphoceramide transfer."
FT /evidence="ECO:0000269|PubMed:23863933"
FT MUTAGEN 43
FT /note="L->R: Nearly abolishes phosphoceramide transfer."
FT /evidence="ECO:0000269|PubMed:23863933"
FT MUTAGEN 50
FT /note="F->R: Slightly reduces phosphoceramide transfer."
FT /evidence="ECO:0000269|PubMed:23863933"
FT MUTAGEN 53
FT /note="I->N: Slightly decreases phosphoceramide transfer."
FT /evidence="ECO:0000269|PubMed:23863933"
FT MUTAGEN 56
FT /note="D->V: Slightly decreases phosphoceramide transfer."
FT /evidence="ECO:0000269|PubMed:23863933"
FT MUTAGEN 60
FT /note="K->A: Nearly abolishes phosphoceramide transfer.
FT Induces autophagy in a dominant negative manner."
FT /evidence="ECO:0000269|PubMed:23863933,
FT ECO:0000269|PubMed:29164996"
FT MUTAGEN 97
FT /note="R->L: No effect."
FT /evidence="ECO:0000269|PubMed:23863933"
FT MUTAGEN 106
FT /note="R->L: Nearly abolishes phosphoceramide transfer.
FT Induces autophagy in a dominant negative manner."
FT /evidence="ECO:0000269|PubMed:23863933,
FT ECO:0000269|PubMed:29164996"
FT MUTAGEN 110
FT /note="R->L: Reduces phosphoceramide transfer."
FT /evidence="ECO:0000269|PubMed:23863933"
FT MUTAGEN 113
FT /note="R->E,L: Strongly reduces phosphoceramide transfer."
FT /evidence="ECO:0000269|PubMed:23863933"
FT MUTAGEN 117
FT /note="W->A: Slightly reduces phosphoceramide transfer."
FT /evidence="ECO:0000269|PubMed:23863933"
FT MUTAGEN 118
FT /note="L->R: Abolishes phosphoceramide transfer."
FT /evidence="ECO:0000269|PubMed:23863933"
FT MUTAGEN 149
FT /note="Y->A: Reduces phosphoceramide transfer."
FT /evidence="ECO:0000269|PubMed:23863933"
FT MUTAGEN 158
FT /note="V->N: Abolishes phosphoceramide transfer."
FT /evidence="ECO:0000269|PubMed:23863933"
FT HELIX 10..15
FT /evidence="ECO:0007829|PDB:4K84"
FT HELIX 16..20
FT /evidence="ECO:0007829|PDB:4K84"
FT HELIX 29..46
FT /evidence="ECO:0007829|PDB:4K84"
FT HELIX 48..50
FT /evidence="ECO:0007829|PDB:4K84"
FT HELIX 51..69
FT /evidence="ECO:0007829|PDB:4K84"
FT HELIX 73..76
FT /evidence="ECO:0007829|PDB:4K84"
FT HELIX 79..88
FT /evidence="ECO:0007829|PDB:4K84"
FT STRAND 94..96
FT /evidence="ECO:0007829|PDB:4K84"
FT HELIX 104..127
FT /evidence="ECO:0007829|PDB:4K84"
FT HELIX 134..144
FT /evidence="ECO:0007829|PDB:4K84"
FT HELIX 146..149
FT /evidence="ECO:0007829|PDB:4K84"
FT HELIX 152..162
FT /evidence="ECO:0007829|PDB:4K84"
FT HELIX 168..174
FT /evidence="ECO:0007829|PDB:4K84"
FT STRAND 177..179
FT /evidence="ECO:0007829|PDB:4K84"
FT HELIX 180..207
FT /evidence="ECO:0007829|PDB:4K84"
SQ SEQUENCE 214 AA; 24365 MW; B66F4581FD9C60A0 CRC64;
MDDSETGFNL KVVLVSFKQC LDEKEEVLLD PYIASWKGLV RFLNSLGTIF SFISKDVVSK
LRIMERLRGG PQSEHYRSLQ AMVAHELSNR LVDLERRSHH PESGCRTVLR LHRALHWLQL
FLEGLRTSPE DARTSALCAD SYNASLAAYH PWVVRRAVTV AFCTLPTREV FLEAMNVGPP
EQAVQMLGEA LPFIQRVYNV SQKLYAEHSL LDLP
