CERT_HUMAN
ID CERT_HUMAN Reviewed; 624 AA.
AC Q9Y5P4; A8K7S2; B3KUB7; Q53YV1; Q53YV2; Q96Q85; Q96Q88; Q9H2S7; Q9H2S8;
DT 15-MAY-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1999, sequence version 1.
DT 03-AUG-2022, entry version 192.
DE RecName: Full=Ceramide transfer protein {ECO:0000303|PubMed:14685229, ECO:0000305};
DE Short=hCERT {ECO:0000303|PubMed:14685229};
DE AltName: Full=Collagen type IV alpha-3-binding protein {ECO:0000305};
DE AltName: Full=Goodpasture antigen-binding protein {ECO:0000303|PubMed:10212244};
DE Short=GPBP;
DE AltName: Full=START domain-containing protein 11;
DE Short=StARD11;
DE AltName: Full=StAR-related lipid transfer protein 11;
GN Name=CERT1 {ECO:0000312|HGNC:HGNC:2205};
GN Synonyms=CERT, COL4A3BP {ECO:0000312|HGNC:HGNC:2205}, STARD11;
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] (ISOFORM 1), AND CHARACTERIZATION.
RX PubMed=10212244; DOI=10.1074/jbc.274.18.12642;
RA Raya A., Revert F., Navarro S., Saus J.;
RT "Characterization of a novel type of serine/threonine kinase that
RT specifically phosphorylates the human goodpasture antigen.";
RL J. Biol. Chem. 274:12642-12649(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORMS 1 AND 2).
RX PubMed=11007769; DOI=10.1074/jbc.m002769200;
RA Raya A., Revert-Ros F., Martinez-Martinez P., Navarro S., Rosello E.,
RA Vieites B., Granero F., Forteza J., Saus J.;
RT "Goodpasture antigen-binding protein, the kinase that phosphorylates the
RT Goodpasture antigen, is an alternatively spliced variant implicated in
RT autoimmune pathogenesis.";
RL J. Biol. Chem. 275:40392-40399(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), FUNCTION, AND DOMAIN START.
RX PubMed=14685229; DOI=10.1038/nature02188;
RA Hanada K., Kumagai K., Yasuda S., Miura Y., Kawano M., Fukasawa M.,
RA Nishijima M.;
RT "Molecular machinery for non-vesicular trafficking of ceramide.";
RL Nature 426:803-809(2003).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 3).
RC TISSUE=Lung, and Synovium;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15372022; DOI=10.1038/nature02919;
RA Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S.,
RA Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M.,
RA She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S.,
RA Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M.,
RA Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M.,
RA Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T.,
RA Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A.,
RA Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R.,
RA Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L.,
RA Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N.,
RA Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J.,
RA Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A.,
RA Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M.;
RT "The DNA sequence and comparative analysis of human chromosome 5.";
RL Nature 431:268-274(2004).
RN [6]
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 [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Placenta;
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 [8]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-77.
RA Ogi T., Yamamoto Y., Ohmori H.;
RT "Homo sapiens genomic sequence, containing DINB1 and GPBP gene.";
RL Submitted (JAN-2000) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-315, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling
RT networks.";
RL Cell 127:635-648(2006).
RN [10]
RP INTERACTION WITH VAPA AND VAPB, SUBCELLULAR LOCATION, MUTAGENESIS OF
RP ASP-324, DOMAIN FFAT MOTIF, AND DOMAIN PH.
RX PubMed=16895911; DOI=10.1074/jbc.m605032200;
RA Kawano M., Kumagai K., Nishijima M., Hanada K.;
RT "Efficient trafficking of ceramide from the endoplasmic reticulum to the
RT Golgi apparatus requires a VAMP-associated protein-interacting FFAT motif
RT of CERT.";
RL J. Biol. Chem. 281:30279-30288(2006).
RN [11]
RP PHOSPHORYLATION AT SER-132, FUNCTION, AND MUTAGENESIS OF SER-132.
RX PubMed=17591919; DOI=10.1083/jcb.200612017;
RA Fugmann T., Hausser A., Schoeffler P., Schmid S., Pfizenmaier K.,
RA Olayioye M.A.;
RT "Regulation of secretory transport by protein kinase D-mediated
RT phosphorylation of the ceramide transfer protein.";
RL J. Cell Biol. 178:15-22(2007).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-377, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [13]
RP PHOSPHORYLATION BY CSNK1G2/CK1.
RX PubMed=19005213; DOI=10.1091/mbc.e08-07-0669;
RA Tomishige N., Kumagai K., Kusuda J., Nishijima M., Hanada K.;
RT "Casein kinase I{gamma}2 down-regulates trafficking of ceramide in the
RT synthesis of sphingomyelin.";
RL Mol. Biol. Cell 20:348-357(2009).
RN [14]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [15]
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 [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-126; TYR-372; SER-373 AND
RP SER-380, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [17]
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 [18]
RP INVOLVEMENT IN MRD34, AND VARIANT MRD34 LEU-132.
RX PubMed=25533962; DOI=10.1038/nature14135;
RG Deciphering Developmental Disorders Study;
RT "Large-scale discovery of novel genetic causes of developmental
RT disorders.";
RL Nature 519:223-228(2015).
RN [19]
RP IDENTIFICATION BY MASS SPECTROMETRY, INTERACTION WITH MOSPD2, SUBCELLULAR
RP LOCATION, DOMAIN, FFAT MOTIF, AND MUTAGENESIS OF ASP-324.
RX PubMed=29858488; DOI=10.15252/embr.201745453;
RA Di Mattia T., Wilhelm L.P., Ikhlef S., Wendling C., Spehner D., Nomine Y.,
RA Giordano F., Mathelin C., Drin G., Tomasetto C., Alpy F.;
RT "Identification of MOSPD2, a novel scaffold for endoplasmic reticulum
RT membrane contact sites.";
RL EMBO Rep. 19:0-0(2018).
RN [20]
RP X-RAY CRYSTALLOGRAPHY (1.4 ANGSTROMS) OF 347-624 IN COMPLEXES WITH
RP CERAMIDES AND DIACYLGLYCEROL, MUTAGENESIS OF GLU-472; GLN-493 AND ASN-530,
RP FUNCTION, SUBCELLULAR LOCATION, AND CERAMIDE-BINDING.
RX PubMed=18184806; DOI=10.1073/pnas.0709191105;
RA Kudo N., Kumagai K., Tomishige N., Yamaji T., Wakatsuki S., Nishijima M.,
RA Hanada K., Kato R.;
RT "Structural basis for specific lipid recognition by CERT responsible for
RT nonvesicular trafficking of ceramide.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:488-493(2008).
RN [21]
RP X-RAY CRYSTALLOGRAPHY (1.66 ANGSTROMS) OF 347-624 IN COMPLEXES WITH
RP CERAMIDE AND INHIBITOR, MUTAGENESIS OF TRP-499, FUNCTION, AND
RP CERAMIDE-BINDING.
RX PubMed=20036255; DOI=10.1016/j.jmb.2009.12.029;
RA Kudo N., Kumagai K., Matsubara R., Kobayashi S., Hanada K., Wakatsuki S.,
RA Kato R.;
RT "Crystal structures of the CERT START domain with inhibitors provide
RT insights into the mechanism of ceramide transfer.";
RL J. Mol. Biol. 396:245-251(2010).
RN [22]
RP VARIANT CYS-138.
RX PubMed=23033978; DOI=10.1056/nejmoa1206524;
RA de Ligt J., Willemsen M.H., van Bon B.W., Kleefstra T., Yntema H.G.,
RA Kroes T., Vulto-van Silfhout A.T., Koolen D.A., de Vries P., Gilissen C.,
RA del Rosario M., Hoischen A., Scheffer H., de Vries B.B., Brunner H.G.,
RA Veltman J.A., Vissers L.E.;
RT "Diagnostic exome sequencing in persons with severe intellectual
RT disability.";
RL N. Engl. J. Med. 367:1921-1929(2012).
RN [23]
RP VARIANT MRD34 ARG-243.
RX PubMed=25356899; DOI=10.1371/journal.pgen.1004772;
RA Hamdan F.F., Srour M., Capo-Chichi J.M., Daoud H., Nassif C., Patry L.,
RA Massicotte C., Ambalavanan A., Spiegelman D., Diallo O., Henrion E.,
RA Dionne-Laporte A., Fougerat A., Pshezhetsky A.V., Venkateswaran S.,
RA Rouleau G.A., Michaud J.L.;
RT "De novo mutations in moderate or severe intellectual disability.";
RL PLoS Genet. 10:E1004772-E1004772(2014).
CC -!- FUNCTION: Shelters ceramides and diacylglycerol lipids inside its START
CC domain and mediates the intracellular trafficking of ceramides and
CC diacylglycerol lipids in a non-vesicular manner.
CC {ECO:0000269|PubMed:14685229, ECO:0000269|PubMed:17591919,
CC ECO:0000269|PubMed:18184806, ECO:0000269|PubMed:20036255}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=N-hexadecanoylsphing-4-enine(in) = N-hexadecanoylsphing-4-
CC enine(out); Xref=Rhea:RHEA:45720, ChEBI:CHEBI:72959;
CC Evidence={ECO:0000250|UniProtKB:Q6VVX2};
CC -!- SUBUNIT: Interacts with VAPA and VAPB. Interaction with VAPB is less
CC efficient than with VAPA (PubMed:16895911). Interacts (via FFAT motif)
CC with MOSPD2 (via MSP domain) (PubMed:29858488).
CC {ECO:0000269|PubMed:16895911, ECO:0000269|PubMed:29858488}.
CC -!- INTERACTION:
CC Q9Y5P4; Q9H568: ACTL8; NbExp=3; IntAct=EBI-739994, EBI-10306917;
CC Q9Y5P4; Q15041: ARL6IP1; NbExp=5; IntAct=EBI-739994, EBI-714543;
CC Q9Y5P4; P78368: CSNK1G2; NbExp=5; IntAct=EBI-739994, EBI-748380;
CC Q9Y5P4; Q13352: ITGB3BP; NbExp=4; IntAct=EBI-739994, EBI-712105;
CC Q9Y5P4; O95197: RTN3; NbExp=3; IntAct=EBI-739994, EBI-740467;
CC Q9Y5P4; Q9NQC3: RTN4; NbExp=3; IntAct=EBI-739994, EBI-715945;
CC Q9Y5P4-1; P02743: APCS; NbExp=6; IntAct=EBI-21199571, EBI-2115799;
CC Q9Y5P4-2; Q9H568: ACTL8; NbExp=3; IntAct=EBI-11156432, EBI-10306917;
CC Q9Y5P4-2; P02743: APCS; NbExp=4; IntAct=EBI-11156432, EBI-2115799;
CC Q9Y5P4-2; Q15041: ARL6IP1; NbExp=3; IntAct=EBI-11156432, EBI-714543;
CC Q9Y5P4-2; Q8WZ55: BSND; NbExp=3; IntAct=EBI-11156432, EBI-7996695;
CC Q9Y5P4-2; Q9Y5P4-2: CERT1; NbExp=3; IntAct=EBI-11156432, EBI-11156432;
CC Q9Y5P4-2; P78368: CSNK1G2; NbExp=4; IntAct=EBI-11156432, EBI-748380;
CC Q9Y5P4-2; Q9UET6: FTSJ1; NbExp=3; IntAct=EBI-11156432, EBI-1055987;
CC Q9Y5P4-2; Q9UPX6: MINAR1; NbExp=3; IntAct=EBI-11156432, EBI-11977115;
CC Q9Y5P4-2; Q8IYS1: PM20D2; NbExp=3; IntAct=EBI-11156432, EBI-11339910;
CC Q9Y5P4-2; Q96HR9-2: REEP6; NbExp=3; IntAct=EBI-11156432, EBI-14065960;
CC Q9Y5P4-2; Q2TAY7: SMU1; NbExp=3; IntAct=EBI-11156432, EBI-298027;
CC Q9Y5P4-2; P32856-2: STX2; NbExp=3; IntAct=EBI-11156432, EBI-11956649;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:16895911,
CC ECO:0000269|PubMed:18184806}. Golgi apparatus
CC {ECO:0000269|PubMed:16895911, ECO:0000269|PubMed:18184806,
CC ECO:0000269|PubMed:29858488}. Endoplasmic reticulum
CC {ECO:0000269|PubMed:16895911, ECO:0000269|PubMed:18184806}.
CC Note=Preferentially localized to the Golgi apparatus.
CC {ECO:0000305|PubMed:16895911}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1; Synonyms=CERTL {ECO:0000303|PubMed:14685229};
CC IsoId=Q9Y5P4-1; Sequence=Displayed;
CC Name=2; Synonyms=Delta26, GPBPD26, CERT {ECO:0000303|PubMed:14685229};
CC IsoId=Q9Y5P4-2; Sequence=VSP_006276;
CC Name=3;
CC IsoId=Q9Y5P4-3; Sequence=VSP_041022;
CC -!- TISSUE SPECIFICITY: Widely expressed.
CC -!- DOMAIN: The START domain recognizes ceramides and diacylglycerol
CC lipids, interacts with membranes, and mediates the intermembrane
CC transfer of ceramides and diacylglycerol lipids.
CC {ECO:0000269|PubMed:14685229}.
CC -!- DOMAIN: The PH domain targets the Golgi apparatus.
CC {ECO:0000269|PubMed:16895911}.
CC -!- DOMAIN: The FFAT motif is required for interaction with VAPA, VAPB and
CC MOSPD2. {ECO:0000269|PubMed:16895911, ECO:0000269|PubMed:29858488}.
CC -!- PTM: Phosphorylation on Ser-132 decreases the affinity toward
CC phosphatidylinositol 4-phosphate at Golgi membranes and reduces
CC ceramide transfer activity. Inactivated by hyperphosphorylation of
CC serine residues by CSNK1G2/CK1 that triggers dissociation from the
CC Golgi complex, thus down-regulating ER-to-Golgi transport of ceramide
CC and sphingomyelin synthesis. {ECO:0000269|PubMed:17591919,
CC ECO:0000269|PubMed:19005213}.
CC -!- DISEASE: Intellectual developmental disorder, autosomal dominant 34
CC (MRD34) [MIM:616351]: A disorder characterized by significantly below
CC average general intellectual functioning associated with impairments in
CC adaptive behavior and manifested during the developmental period.
CC {ECO:0000269|PubMed:25356899, ECO:0000269|PubMed:25533962}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- CAUTION: Was originally reported to have a protein kinase activity and
CC to phosphorylate on Ser and Thr residues the Goodpasture autoantigen
CC (in vitro). {ECO:0000305|PubMed:10212244}.
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DR EMBL; AF136450; AAD30288.1; -; mRNA.
DR EMBL; AF232930; AAG42046.1; -; mRNA.
DR EMBL; AF232935; AAG42051.1; -; Genomic_DNA.
DR EMBL; AY453385; AAR26717.1; -; mRNA.
DR EMBL; AY453386; AAR26718.1; -; mRNA.
DR EMBL; AK091851; BAC03762.1; -; mRNA.
DR EMBL; AK096854; BAG53379.1; -; mRNA.
DR EMBL; AK292087; BAF84776.1; -; mRNA.
DR EMBL; AC008897; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC112183; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC116341; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471084; EAW95757.1; -; Genomic_DNA.
DR EMBL; CH471084; EAW95760.1; -; Genomic_DNA.
DR EMBL; BC000102; AAH00102.1; -; mRNA.
DR EMBL; AB036934; BAB58974.1; -; Genomic_DNA.
DR EMBL; AB036936; BAB58977.1; -; Genomic_DNA.
DR CCDS; CCDS4028.1; -. [Q9Y5P4-1]
DR CCDS; CCDS4029.1; -. [Q9Y5P4-2]
DR CCDS; CCDS47235.1; -. [Q9Y5P4-3]
DR RefSeq; NP_001123577.1; NM_001130105.1. [Q9Y5P4-3]
DR RefSeq; NP_005704.1; NM_005713.2. [Q9Y5P4-1]
DR RefSeq; NP_112729.1; NM_031361.2. [Q9Y5P4-2]
DR RefSeq; XP_006714576.1; XM_006714513.2.
DR RefSeq; XP_016864408.1; XM_017008919.1.
DR PDB; 2E3M; X-ray; 2.20 A; A=347-624.
DR PDB; 2E3N; X-ray; 1.40 A; A=347-624.
DR PDB; 2E3O; X-ray; 1.55 A; A=347-624.
DR PDB; 2E3P; X-ray; 1.40 A; A/B=347-624.
DR PDB; 2E3Q; X-ray; 2.08 A; A=347-624.
DR PDB; 2E3R; X-ray; 1.65 A; A/B=347-624.
DR PDB; 2E3S; X-ray; 1.94 A; A=347-624.
DR PDB; 2RSG; NMR; -; A=24-117.
DR PDB; 2Z9Y; X-ray; 1.80 A; A=347-624.
DR PDB; 2Z9Z; X-ray; 1.74 A; A=347-624.
DR PDB; 3H3Q; X-ray; 2.00 A; A/B=347-624.
DR PDB; 3H3R; X-ray; 1.85 A; A/B=347-624.
DR PDB; 3H3S; X-ray; 1.66 A; A/B=347-624.
DR PDB; 3H3T; X-ray; 2.40 A; A/B=347-624.
DR PDB; 4HHV; X-ray; 1.75 A; A/B=20-121.
DR PDB; 5JJD; X-ray; 2.40 A; A=20-122, B=385-624.
DR PDB; 5ZYG; X-ray; 1.80 A; A=390-624.
DR PDB; 5ZYH; X-ray; 1.95 A; A=390-624.
DR PDB; 5ZYI; X-ray; 1.90 A; A=390-624.
DR PDB; 5ZYJ; X-ray; 1.90 A; A=390-624.
DR PDB; 5ZYK; X-ray; 1.55 A; A=390-624.
DR PDB; 5ZYL; X-ray; 1.80 A; A=390-624.
DR PDB; 5ZYM; X-ray; 1.90 A; A=390-624.
DR PDB; 6IEZ; X-ray; 1.90 A; A=390-624.
DR PDB; 6IF0; X-ray; 1.80 A; A=390-624.
DR PDB; 6J0O; X-ray; 1.80 A; A=390-624.
DR PDB; 6J81; X-ray; 1.80 A; A=390-624.
DR PDBsum; 2E3M; -.
DR PDBsum; 2E3N; -.
DR PDBsum; 2E3O; -.
DR PDBsum; 2E3P; -.
DR PDBsum; 2E3Q; -.
DR PDBsum; 2E3R; -.
DR PDBsum; 2E3S; -.
DR PDBsum; 2RSG; -.
DR PDBsum; 2Z9Y; -.
DR PDBsum; 2Z9Z; -.
DR PDBsum; 3H3Q; -.
DR PDBsum; 3H3R; -.
DR PDBsum; 3H3S; -.
DR PDBsum; 3H3T; -.
DR PDBsum; 4HHV; -.
DR PDBsum; 5JJD; -.
DR PDBsum; 5ZYG; -.
DR PDBsum; 5ZYH; -.
DR PDBsum; 5ZYI; -.
DR PDBsum; 5ZYJ; -.
DR PDBsum; 5ZYK; -.
DR PDBsum; 5ZYL; -.
DR PDBsum; 5ZYM; -.
DR PDBsum; 6IEZ; -.
DR PDBsum; 6IF0; -.
DR PDBsum; 6J0O; -.
DR PDBsum; 6J81; -.
DR AlphaFoldDB; Q9Y5P4; -.
DR BMRB; Q9Y5P4; -.
DR SMR; Q9Y5P4; -.
DR BioGRID; 115396; 46.
DR ELM; Q9Y5P4; -.
DR IntAct; Q9Y5P4; 35.
DR MINT; Q9Y5P4; -.
DR STRING; 9606.ENSP00000369862; -.
DR BindingDB; Q9Y5P4; -.
DR ChEMBL; CHEMBL3399913; -.
DR SwissLipids; SLP:000000407; -.
DR iPTMnet; Q9Y5P4; -.
DR PhosphoSitePlus; Q9Y5P4; -.
DR BioMuta; COL4A3BP; -.
DR DMDM; 20978413; -.
DR EPD; Q9Y5P4; -.
DR jPOST; Q9Y5P4; -.
DR MassIVE; Q9Y5P4; -.
DR MaxQB; Q9Y5P4; -.
DR PaxDb; Q9Y5P4; -.
DR PeptideAtlas; Q9Y5P4; -.
DR PRIDE; Q9Y5P4; -.
DR ProteomicsDB; 86463; -. [Q9Y5P4-1]
DR ProteomicsDB; 86464; -. [Q9Y5P4-2]
DR ProteomicsDB; 86465; -. [Q9Y5P4-3]
DR Antibodypedia; 24390; 373 antibodies from 35 providers.
DR DNASU; 10087; -.
DR Ensembl; ENST00000261415.12; ENSP00000261415.8; ENSG00000113163.19. [Q9Y5P4-1]
DR Ensembl; ENST00000405807.10; ENSP00000383996.4; ENSG00000113163.19. [Q9Y5P4-3]
DR Ensembl; ENST00000643780.2; ENSP00000495760.1; ENSG00000113163.19. [Q9Y5P4-1]
DR Ensembl; ENST00000644072.2; ENSP00000494110.2; ENSG00000113163.19. [Q9Y5P4-1]
DR Ensembl; ENST00000644445.1; ENSP00000496243.1; ENSG00000113163.19. [Q9Y5P4-2]
DR Ensembl; ENST00000645483.1; ENSP00000493563.1; ENSG00000113163.19. [Q9Y5P4-2]
DR Ensembl; ENST00000646511.1; ENSP00000495446.1; ENSG00000113163.19. [Q9Y5P4-2]
DR GeneID; 10087; -.
DR KEGG; hsa:10087; -.
DR MANE-Select; ENST00000643780.2; ENSP00000495760.1; NM_001379029.1; NP_001365958.1.
DR UCSC; uc003kds.4; human. [Q9Y5P4-1]
DR CTD; 10087; -.
DR DisGeNET; 10087; -.
DR GeneCards; CERT1; -.
DR HGNC; HGNC:2205; CERT1.
DR HPA; ENSG00000113163; Low tissue specificity.
DR MalaCards; CERT1; -.
DR MIM; 604677; gene.
DR MIM; 616351; phenotype.
DR neXtProt; NX_Q9Y5P4; -.
DR OpenTargets; ENSG00000113163; -.
DR PharmGKB; PA26720; -.
DR VEuPathDB; HostDB:ENSG00000113163; -.
DR eggNOG; KOG1739; Eukaryota.
DR GeneTree; ENSGT00940000155123; -.
DR HOGENOM; CLU_017289_0_0_1; -.
DR InParanoid; Q9Y5P4; -.
DR OMA; EDQSKKF; -.
DR OrthoDB; 959972at2759; -.
DR PhylomeDB; Q9Y5P4; -.
DR TreeFam; TF106160; -.
DR BRENDA; 2.7.11.9; 2681.
DR PathwayCommons; Q9Y5P4; -.
DR Reactome; R-HSA-1660661; Sphingolipid de novo biosynthesis. [Q9Y5P4-2]
DR SignaLink; Q9Y5P4; -.
DR SIGNOR; Q9Y5P4; -.
DR BioGRID-ORCS; 10087; 31 hits in 1078 CRISPR screens.
DR ChiTaRS; COL4A3BP; human.
DR EvolutionaryTrace; Q9Y5P4; -.
DR GeneWiki; COL4A3BP; -.
DR GenomeRNAi; 10087; -.
DR Pharos; Q9Y5P4; Tbio.
DR PRO; PR:Q9Y5P4; -.
DR Proteomes; UP000005640; Chromosome 5.
DR RNAct; Q9Y5P4; protein.
DR Bgee; ENSG00000113163; Expressed in sperm and 212 other tissues.
DR ExpressionAtlas; Q9Y5P4; baseline and differential.
DR Genevisible; Q9Y5P4; HS.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; TAS:Reactome.
DR GO; GO:0005794; C:Golgi apparatus; IDA:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; IEA:Ensembl.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:1902387; F:ceramide 1-phosphate binding; IBA:GO_Central.
DR GO; GO:1902388; F:ceramide 1-phosphate transfer activity; IBA:GO_Central.
DR GO; GO:0097001; F:ceramide binding; IDA:UniProtKB.
DR GO; GO:0120017; F:ceramide transfer activity; IDA:GO_Central.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0016301; F:kinase activity; IEA:Ensembl.
DR GO; GO:0070273; F:phosphatidylinositol-4-phosphate binding; IDA:UniProtKB.
DR GO; GO:0000902; P:cell morphogenesis; IEA:Ensembl.
DR GO; GO:0008283; P:cell population proliferation; IEA:Ensembl.
DR GO; GO:0006672; P:ceramide metabolic process; IEA:Ensembl.
DR GO; GO:0035627; P:ceramide transport; IBA:GO_Central.
DR GO; GO:0007029; P:endoplasmic reticulum organization; IEA:Ensembl.
DR GO; GO:0035621; P:ER to Golgi ceramide transport; IMP:UniProtKB.
DR GO; GO:0003007; P:heart morphogenesis; IEA:Ensembl.
DR GO; GO:0006955; P:immune response; NAS:UniProtKB.
DR GO; GO:0001701; P:in utero embryonic development; IEA:Ensembl.
DR GO; GO:0120009; P:intermembrane lipid transfer; IBA:GO_Central.
DR GO; GO:0120012; P:intermembrane sphingolipid transfer; IDA:UniProtKB.
DR GO; GO:0055088; P:lipid homeostasis; IEA:Ensembl.
DR GO; GO:0070584; P:mitochondrion morphogenesis; IEA:Ensembl.
DR GO; GO:0006936; P:muscle contraction; IEA:Ensembl.
DR GO; GO:0034976; P:response to endoplasmic reticulum stress; IEA:Ensembl.
DR GO; GO:0007165; P:signal transduction; IEA:Ensembl.
DR CDD; cd08872; START_STARD11-like; 1.
DR Gene3D; 2.30.29.30; -; 1.
DR Gene3D; 3.30.530.20; -; 1.
DR InterPro; IPR011993; PH-like_dom_sf.
DR InterPro; IPR001849; PH_domain.
DR InterPro; IPR041952; STARD11_START.
DR InterPro; IPR023393; START-like_dom_sf.
DR InterPro; IPR002913; START_lipid-bd_dom.
DR Pfam; PF00169; PH; 1.
DR Pfam; PF01852; START; 1.
DR SMART; SM00233; PH; 1.
DR SMART; SM00234; START; 1.
DR PROSITE; PS50003; PH_DOMAIN; 1.
DR PROSITE; PS50848; START; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Coiled coil; Cytoplasm;
KW Disease variant; Endoplasmic reticulum; Golgi apparatus;
KW Intellectual disability; Lipid transport; Lipid-binding; Phosphoprotein;
KW Reference proteome; Transport.
FT CHAIN 1..624
FT /note="Ceramide transfer protein"
FT /id="PRO_0000220665"
FT DOMAIN 23..117
FT /note="PH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00145"
FT DOMAIN 389..618
FT /note="START"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00197"
FT REGION 1..24
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 263..303
FT /evidence="ECO:0000255"
FT MOTIF 321..327
FT /note="FFAT"
FT /evidence="ECO:0000269|PubMed:16895911,
FT ECO:0000269|PubMed:29858488"
FT COMPBIAS 1..16
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 472
FT /ligand="an N-acylsphing-4-enine"
FT /ligand_id="ChEBI:CHEBI:52639"
FT /evidence="ECO:0000269|PubMed:18184806,
FT ECO:0000269|PubMed:20036255"
FT BINDING 493
FT /ligand="an N-acylsphing-4-enine"
FT /ligand_id="ChEBI:CHEBI:52639"
FT /evidence="ECO:0000269|PubMed:18184806,
FT ECO:0000269|PubMed:20036255"
FT BINDING 530
FT /ligand="an N-acylsphing-4-enine"
FT /ligand_id="ChEBI:CHEBI:52639"
FT /evidence="ECO:0000269|PubMed:18184806,
FT ECO:0000269|PubMed:20036255"
FT BINDING 579
FT /ligand="an N-acylsphing-4-enine"
FT /ligand_id="ChEBI:CHEBI:52639"
FT /evidence="ECO:0000269|PubMed:18184806,
FT ECO:0000269|PubMed:20036255"
FT MOD_RES 126
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 132
FT /note="Phosphoserine; by PKD"
FT /evidence="ECO:0000269|PubMed:17591919"
FT MOD_RES 135
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9EQG9"
FT MOD_RES 315
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17081983"
FT MOD_RES 372
FT /note="Phosphotyrosine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 373
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 377
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 380
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT VAR_SEQ 1
FT /note="M -> MQHSCIPTPPSPFSAPPAFLPVVTRESRRGLSSGGSAGRNAGVTATA
FT AAADGWKGRLPSPLVLLPRSARCQARRRRGGRTSSLLLLPPTPERALFASPSPDPSPRG
FT LGASSGAAEGAGAGLLLGCRASM (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_041022"
FT VAR_SEQ 371..396
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:11007769,
FT ECO:0000303|PubMed:14685229, ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_006276"
FT VARIANT 132
FT /note="S -> L (in MRD34; dbSNP:rs1064794019)"
FT /evidence="ECO:0000269|PubMed:25533962"
FT /id="VAR_073721"
FT VARIANT 138
FT /note="S -> C (found in a patient with intellectual
FT disability)"
FT /evidence="ECO:0000269|PubMed:23033978"
FT /id="VAR_069403"
FT VARIANT 243
FT /note="G -> R (in MRD34; associated with authism and
FT epilepsy)"
FT /evidence="ECO:0000269|PubMed:25356899"
FT /id="VAR_078652"
FT VARIANT 599
FT /note="K -> R (in dbSNP:rs55882089)"
FT /id="VAR_061815"
FT MUTAGEN 132
FT /note="S->A: Abolishes the phosphorylation. Strongly
FT reduces the interaction with phosphatidylinositol 4-
FT phosphate. Increases the ceramide transfer activity."
FT /evidence="ECO:0000269|PubMed:17591919"
FT MUTAGEN 324
FT /note="D->A: Impairs the endoplasmic reticulum-to-Golgi
FT ceramide trafficking and abolishes the interaction with
FT VAPA and MOSPD2."
FT /evidence="ECO:0000269|PubMed:16895911,
FT ECO:0000269|PubMed:29858488"
FT MUTAGEN 472
FT /note="E->A: Reduces ceramide transfer."
FT /evidence="ECO:0000269|PubMed:18184806"
FT MUTAGEN 493
FT /note="Q->A: No effect on ceramide transfer activity."
FT /evidence="ECO:0000269|PubMed:18184806"
FT MUTAGEN 499
FT /note="W->A: Reduces affinity for membranes. Abolishes
FT ceramide transfer; when associated with A-588."
FT /evidence="ECO:0000269|PubMed:20036255"
FT MUTAGEN 530
FT /note="N->A: Reduces ceramide transfer."
FT /evidence="ECO:0000269|PubMed:18184806"
FT MUTAGEN 588
FT /note="W->A: Abolishes ceramide transfer; when associated
FT with A-499."
FT STRAND 26..33
FT /evidence="ECO:0007829|PDB:4HHV"
FT TURN 36..38
FT /evidence="ECO:0007829|PDB:4HHV"
FT STRAND 40..48
FT /evidence="ECO:0007829|PDB:4HHV"
FT STRAND 51..56
FT /evidence="ECO:0007829|PDB:4HHV"
FT STRAND 58..62
FT /evidence="ECO:0007829|PDB:4HHV"
FT STRAND 64..71
FT /evidence="ECO:0007829|PDB:4HHV"
FT STRAND 75..78
FT /evidence="ECO:0007829|PDB:4HHV"
FT STRAND 85..90
FT /evidence="ECO:0007829|PDB:4HHV"
FT STRAND 93..98
FT /evidence="ECO:0007829|PDB:4HHV"
FT HELIX 102..119
FT /evidence="ECO:0007829|PDB:4HHV"
FT HELIX 397..407
FT /evidence="ECO:0007829|PDB:2E3N"
FT STRAND 413..415
FT /evidence="ECO:0007829|PDB:2E3M"
FT STRAND 418..424
FT /evidence="ECO:0007829|PDB:2E3N"
FT STRAND 427..432
FT /evidence="ECO:0007829|PDB:2E3N"
FT STRAND 444..451
FT /evidence="ECO:0007829|PDB:2E3N"
FT HELIX 455..463
FT /evidence="ECO:0007829|PDB:2E3N"
FT HELIX 465..467
FT /evidence="ECO:0007829|PDB:2E3N"
FT HELIX 468..471
FT /evidence="ECO:0007829|PDB:2E3N"
FT STRAND 474..485
FT /evidence="ECO:0007829|PDB:2E3N"
FT STRAND 488..495
FT /evidence="ECO:0007829|PDB:2E3N"
FT STRAND 499..502
FT /evidence="ECO:0007829|PDB:3H3S"
FT STRAND 504..515
FT /evidence="ECO:0007829|PDB:2E3N"
FT STRAND 518..522
FT /evidence="ECO:0007829|PDB:2E3O"
FT STRAND 525..532
FT /evidence="ECO:0007829|PDB:2E3N"
FT STRAND 542..546
FT /evidence="ECO:0007829|PDB:2E3N"
FT STRAND 548..559
FT /evidence="ECO:0007829|PDB:2E3N"
FT STRAND 563..565
FT /evidence="ECO:0007829|PDB:3H3S"
FT HELIX 570..572
FT /evidence="ECO:0007829|PDB:2E3N"
FT STRAND 573..584
FT /evidence="ECO:0007829|PDB:2E3N"
FT HELIX 591..617
FT /evidence="ECO:0007829|PDB:2E3N"
FT STRAND 618..620
FT /evidence="ECO:0007829|PDB:2E3Q"
SQ SEQUENCE 624 AA; 70835 MW; A125162492AC5A0E CRC64;
MSDNQSWNSS GSEEDPETES GPPVERCGVL SKWTNYIHGW QDRWVVLKNN ALSYYKSEDE
TEYGCRGSIC LSKAVITPHD FDECRFDISV NDSVWYLRAQ DPDHRQQWID AIEQHKTESG
YGSESSLRRH GSMVSLVSGA SGYSATSTSS FKKGHSLREK LAEMETFRDI LCRQVDTLQK
YFDACADAVS KDELQRDKVV EDDEDDFPTT RSDGDFLHST NGNKEKLFPH VTPKGINGID
FKGEAITFKA TTAGILATLS HCIELMVKRE DSWQKRLDKE TEKKRRTEEA YKNAMTELKK
KSHFGGPDYE EGPNSLINEE EFFDAVEAAL DRQDKIEEQS QSEKVRLHWP TSLPSGDAFS
SVGTHRFVQK PYSRSSSMSS IDLVSASDDV HRFSSQVEEM VQNHMTYSLQ DVGGDANWQL
VVEEGEMKVY RREVEENGIV LDPLKATHAV KGVTGHEVCN YFWNVDVRND WETTIENFHV
VETLADNAII IYQTHKRVWP ASQRDVLYLS VIRKIPALTE NDPETWIVCN FSVDHDSAPL
NNRCVRAKIN VAMICQTLVS PPEGNQEISR DNILCKITYV ANVNPGGWAP ASVLRAVAKR
EYPKFLKRFT SYVQEKTAGK PILF
