CERT_DANRE
ID CERT_DANRE Reviewed; 620 AA.
AC Q5M7Y0; A2BGX3; A2BGX4; B4XAM8; B4XAM9;
DT 23-OCT-2007, integrated into UniProtKB/Swiss-Prot.
DT 22-SEP-2009, sequence version 2.
DT 03-AUG-2022, entry version 113.
DE RecName: Full=Ceramide transfer protein {ECO:0000305};
DE Short=CERT;
DE AltName: Full=Collagen type IV alpha-3-binding protein;
DE AltName: Full=Goodpasture antigen-binding protein;
DE Short=GPBP;
GN Name=cert1; Synonyms=cert, col4a3bp, gpbp; ORFNames=si:ch211-129a6.6;
OS Danio rerio (Zebrafish) (Brachydanio rerio).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes;
OC Danionidae; Danioninae; Danio.
OX NCBI_TaxID=7955;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), FUNCTION, TISSUE
RP SPECIFICITY, DEVELOPMENTAL STAGE, AND MUTAGENESIS OF GLY-64.
RC TISSUE=Embryo;
RX PubMed=18424781; DOI=10.1074/jbc.m801806200;
RA Granero-Molto F., Sarmah S., O'Rear L., Spagnoli A., Abrahamson D.,
RA Saus J., Hudson B.G., Knapik E.W.;
RT "Goodpasture antigen-binding protein and its spliced variant, ceramide
RT transfer protein, have different functions in the modulation of apoptosis
RT during zebrafish development.";
RL J. Biol. Chem. 283:20495-20504(2008).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Tuebingen;
RX PubMed=23594743; DOI=10.1038/nature12111;
RA Howe K., Clark M.D., Torroja C.F., Torrance J., Berthelot C., Muffato M.,
RA Collins J.E., Humphray S., McLaren K., Matthews L., McLaren S., Sealy I.,
RA Caccamo M., Churcher C., Scott C., Barrett J.C., Koch R., Rauch G.J.,
RA White S., Chow W., Kilian B., Quintais L.T., Guerra-Assuncao J.A., Zhou Y.,
RA Gu Y., Yen J., Vogel J.H., Eyre T., Redmond S., Banerjee R., Chi J., Fu B.,
RA Langley E., Maguire S.F., Laird G.K., Lloyd D., Kenyon E., Donaldson S.,
RA Sehra H., Almeida-King J., Loveland J., Trevanion S., Jones M., Quail M.,
RA Willey D., Hunt A., Burton J., Sims S., McLay K., Plumb B., Davis J.,
RA Clee C., Oliver K., Clark R., Riddle C., Elliot D., Threadgold G.,
RA Harden G., Ware D., Begum S., Mortimore B., Kerry G., Heath P.,
RA Phillimore B., Tracey A., Corby N., Dunn M., Johnson C., Wood J., Clark S.,
RA Pelan S., Griffiths G., Smith M., Glithero R., Howden P., Barker N.,
RA Lloyd C., Stevens C., Harley J., Holt K., Panagiotidis G., Lovell J.,
RA Beasley H., Henderson C., Gordon D., Auger K., Wright D., Collins J.,
RA Raisen C., Dyer L., Leung K., Robertson L., Ambridge K., Leongamornlert D.,
RA McGuire S., Gilderthorp R., Griffiths C., Manthravadi D., Nichol S.,
RA Barker G., Whitehead S., Kay M., Brown J., Murnane C., Gray E.,
RA Humphries M., Sycamore N., Barker D., Saunders D., Wallis J., Babbage A.,
RA Hammond S., Mashreghi-Mohammadi M., Barr L., Martin S., Wray P.,
RA Ellington A., Matthews N., Ellwood M., Woodmansey R., Clark G., Cooper J.,
RA Tromans A., Grafham D., Skuce C., Pandian R., Andrews R., Harrison E.,
RA Kimberley A., Garnett J., Fosker N., Hall R., Garner P., Kelly D., Bird C.,
RA Palmer S., Gehring I., Berger A., Dooley C.M., Ersan-Urun Z., Eser C.,
RA Geiger H., Geisler M., Karotki L., Kirn A., Konantz J., Konantz M.,
RA Oberlander M., Rudolph-Geiger S., Teucke M., Lanz C., Raddatz G.,
RA Osoegawa K., Zhu B., Rapp A., Widaa S., Langford C., Yang F.,
RA Schuster S.C., Carter N.P., Harrow J., Ning Z., Herrero J., Searle S.M.,
RA Enright A., Geisler R., Plasterk R.H., Lee C., Westerfield M.,
RA de Jong P.J., Zon L.I., Postlethwait J.H., Nusslein-Volhard C.,
RA Hubbard T.J., Roest Crollius H., Rogers J., Stemple D.L.;
RT "The zebrafish reference genome sequence and its relationship to the human
RT genome.";
RL Nature 496:498-503(2013).
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 (By similarity).
CC Isoform 1 plays a role in neural development and skeletal muscle
CC development. Negatively regulates apoptosis during development.
CC {ECO:0000250|UniProtKB:Q9Y5P4, ECO:0000269|PubMed:18424781}.
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. Interacts (via FFAT motif) with the MOSPD2
CC (via MSP domain). {ECO:0000250|UniProtKB:Q9Y5P4}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q9Y5P4}. Golgi
CC apparatus {ECO:0000250|UniProtKB:Q9Y5P4}. Endoplasmic reticulum
CC {ECO:0000250|UniProtKB:Q9Y5P4}. Note=Preferentially localized to the
CC Golgi apparatus. {ECO:0000250|UniProtKB:Q9Y5P4}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1; Synonyms=Gpbp;
CC IsoId=Q5M7Y0-1; Sequence=Displayed;
CC Name=2; Synonyms=GpbpD26, GpbpDelta26, GpbpDelta26/CERT;
CC IsoId=Q5M7Y0-2; Sequence=VSP_038156;
CC Name=3;
CC IsoId=Q5M7Y0-3; Sequence=VSP_038154, VSP_038155;
CC -!- TISSUE SPECIFICITY: Widely expressed during embryogenesis.
CC {ECO:0000269|PubMed:18424781}.
CC -!- DEVELOPMENTAL STAGE: The isoforms are differentially expressed during
CC development. Isoform 1 is expressed maternally with expression
CC gradually decreasing as development progresses, whereas expression of
CC isoform 2 is barely detectable during the first 12 hours post-
CC fertilization (hpf) but increases by the second day of development.
CC {ECO:0000269|PubMed:18424781}.
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:0000250|UniProtKB:Q9Y5P4}.
CC -!- DOMAIN: The FFAT motif is required for interaction with VAPA, VAPB and
CC MOSPD2. {ECO:0000250|UniProtKB:Q9Y5P4}.
CC -!- DOMAIN: The PH domain targets the Golgi apparatus.
CC {ECO:0000250|UniProtKB:Q9Y5P4}.
CC -!- SEQUENCE CAUTION:
CC Sequence=CAM13175.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
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DR EMBL; EU000165; ABV60275.1; -; mRNA.
DR EMBL; EU000166; ABV60276.1; -; mRNA.
DR EMBL; BX511209; CAM13175.1; ALT_SEQ; Genomic_DNA.
DR EMBL; BX511209; CAM13176.1; -; Genomic_DNA.
DR AlphaFoldDB; Q5M7Y0; -.
DR SMR; Q5M7Y0; -.
DR STRING; 7955.ENSDARP00000124594; -.
DR PaxDb; Q5M7Y0; -.
DR PRIDE; Q5M7Y0; -.
DR Ensembl; ENSDART00000191393; ENSDARP00000157335; ENSDARG00000110459. [Q5M7Y0-3]
DR ZFIN; ZDB-GENE-080724-10; cert1a.
DR eggNOG; KOG1739; Eukaryota.
DR InParanoid; Q5M7Y0; -.
DR PhylomeDB; Q5M7Y0; -.
DR BRENDA; 2.7.11.9; 928.
DR PRO; PR:Q5M7Y0; -.
DR Proteomes; UP000000437; Genome assembly.
DR Proteomes; UP000814640; Unplaced.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0005783; C:endoplasmic reticulum; IEA:UniProtKB-SubCell.
DR GO; GO:0005794; C:Golgi apparatus; ISS:UniProtKB.
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; ISS:UniProtKB.
DR GO; GO:0120017; F:ceramide transfer activity; ISS:UniProtKB.
DR GO; GO:0070273; F:phosphatidylinositol-4-phosphate binding; IBA:GO_Central.
DR GO; GO:0035627; P:ceramide transport; IBA:GO_Central.
DR GO; GO:0035621; P:ER to Golgi ceramide transport; ISS:UniProtKB.
DR GO; GO:0120009; P:intermembrane lipid transfer; IBA:GO_Central.
DR GO; GO:0007517; P:muscle organ development; IEA:UniProtKB-KW.
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 Alternative splicing; Coiled coil; Cytoplasm; Developmental protein;
KW Endoplasmic reticulum; Golgi apparatus; Lipid transport; Lipid-binding;
KW Myogenesis; Reference proteome; Transport.
FT CHAIN 1..620
FT /note="Ceramide transfer protein"
FT /id="PRO_0000307356"
FT DOMAIN 20..114
FT /note="PH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00145"
FT DOMAIN 385..614
FT /note="START"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00197"
FT COILED 265..298
FT /evidence="ECO:0000255"
FT MOTIF 318..324
FT /note="FFAT"
FT /evidence="ECO:0000250|UniProtKB:Q9Y5P4"
FT BINDING 468
FT /ligand="an N-acylsphing-4-enine"
FT /ligand_id="ChEBI:CHEBI:52639"
FT /evidence="ECO:0000250|UniProtKB:Q9Y5P4"
FT BINDING 489
FT /ligand="an N-acylsphing-4-enine"
FT /ligand_id="ChEBI:CHEBI:52639"
FT /evidence="ECO:0000250|UniProtKB:Q9Y5P4"
FT BINDING 526
FT /ligand="an N-acylsphing-4-enine"
FT /ligand_id="ChEBI:CHEBI:52639"
FT /evidence="ECO:0000250|UniProtKB:Q9Y5P4"
FT BINDING 575
FT /ligand="an N-acylsphing-4-enine"
FT /ligand_id="ChEBI:CHEBI:52639"
FT /evidence="ECO:0000250|UniProtKB:Q9Y5P4"
FT VAR_SEQ 1..241
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000305"
FT /id="VSP_038154"
FT VAR_SEQ 242..276
FT /note="AITFKATTAGILSTLSHCIDILVKREESWQKRLDK -> MTTVCSASVVNWV
FT SGSLRSANENWIPLCTQSSFFT (in isoform 3)"
FT /evidence="ECO:0000305"
FT /id="VSP_038155"
FT VAR_SEQ 367..392
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:18424781"
FT /id="VSP_038156"
FT MUTAGEN 64
FT /note="G->E: Fails to rescue the increased-apoptosis
FT phenotype, probably by abolishing ceramide transfer between
FT the endoplasmic reticulum and Golgi complex by disrupting
FT phosphatidylinositol 4-phosphate-binding activity."
FT /evidence="ECO:0000269|PubMed:18424781"
FT CONFLICT 385
FT /note="D -> E (in Ref. 1; ABV60275)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 620 AA; 70374 MW; D2485F872847F354 CRC64;
MSDCSSSGSD EDLDPESELL DELGGKLSKW TNYIHGWQDR WIALKGNILS YYRSADEKEY
GCRGSICLSK AVITPHEFDE CRFDISVNDS IWYLRAEHPL LRQQWIDTIE LHKAESGYGS
ESSLRRHGSL LSLTSAASGL STASASSFKK AYSLQEKLAE METFRDILCR QVDTLQKYFD
NCADNESKDE LHRDKVSDEE EDFPTLRPDA DYLLNNNNSS KEKLFSVNTL KDPAGIDFKG
EAITFKATTA GILSTLSHCI DILVKREESW QKRLDKEIER RRRAEDAYKA ALTELKKKPH
YGGPDYEEGP NSLINEEEFF DAVEAALDKH DQIEEQSQVE RSRASRQISL TPDTFSSIST
QKYLTKPHSH TSSLSSVDLI SASDDVHRFS AQVEEMVHSH MTYSLQDVGG DANWQLVVEE
GDMKVYRREV EENGIVLDPL KATHAVKGVT GHEVCHYFWD TAYRNDWETT VESFQVVETL
SDQACIIHQT LKRVWPASQR DVLYVSVMRK ILSTNENDPD TWLVCNFSVD HDGYPPSTRC
IRAKINVAMI CQTLISPPEG DKEISRDNII CKITYVANVN PGGWAPASVL RAVAKREYPK
FLKRFTSYVE VKTSSEAILF
