CERT_CRIGR
ID CERT_CRIGR Reviewed; 598 AA.
AC Q6VVX2;
DT 23-OCT-2007, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 03-AUG-2022, entry version 85.
DE RecName: Full=Ceramide transfer protein {ECO:0000305};
DE Short=CERT;
DE AltName: Full=Collagen type IV alpha-3-binding protein;
GN Name=CERT1; Synonyms=CERT, COL4A3BP;
OS Cricetulus griseus (Chinese hamster) (Cricetulus barabensis griseus).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea;
OC Cricetidae; Cricetinae; Cricetulus.
OX NCBI_TaxID=10029;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], VARIANT GLU-67, FUNCTION, SUBCELLULAR LOCATION,
RP AND CATALYTIC ACTIVITY.
RC TISSUE=Ovary;
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 [2]
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).
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 (PubMed:19005213).
CC {ECO:0000269|PubMed:19005213}.
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:0000269|PubMed:14685229};
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:0000269|PubMed:14685229}. Golgi
CC apparatus {ECO:0000269|PubMed:14685229}. Endoplasmic reticulum
CC {ECO:0000250|UniProtKB:Q9Y5P4}. Note=Preferentially localized to the
CC Golgi apparatus. {ECO:0000250|UniProtKB:Q9Y5P4}.
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 PH domain targets the Golgi apparatus.
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 -!- PTM: Phosphorylation on Ser-132 decreases the affinity toward
CC phosphatidylinositol 4-phosphate at Golgi membranes and reduces
CC ceramide transfer activity (By similarity). Inactivated by
CC hyperphosphorylation of serine residues by CSNK1G2/CK1 that triggers
CC dissociation from the Golgi complex, thus down-regulating ER-to-Golgi
CC transport of ceramide and sphingomyelin synthesis (PubMed:19005213).
CC {ECO:0000250|UniProtKB:Q9Y5P4, ECO:0000269|PubMed:19005213}.
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DR EMBL; AY323813; AAQ89690.1; -; mRNA.
DR RefSeq; XP_007646800.1; XM_007648610.1.
DR AlphaFoldDB; Q6VVX2; -.
DR BMRB; Q6VVX2; -.
DR SMR; Q6VVX2; -.
DR STRING; 10029.NP_001230955.1; -.
DR SwissLipids; SLP:000001549; -.
DR Ensembl; ENSCGRT00001025947; ENSCGRP00001021703; ENSCGRG00001020451.
DR GeneID; 100689038; -.
DR KEGG; cge:100689038; -.
DR CTD; 10087; -.
DR eggNOG; KOG1739; Eukaryota.
DR GeneTree; ENSGT00940000155123; -.
DR PRO; PR:Q6VVX2; -.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0005783; C:endoplasmic reticulum; IEA:UniProtKB-SubCell.
DR GO; GO:0005794; C:Golgi apparatus; IDA:UniProtKB.
DR GO; GO:0120017; F:ceramide transfer activity; IMP:GO_Central.
DR GO; GO:0070273; F:phosphatidylinositol-4-phosphate binding; IDA:UniProtKB.
DR GO; GO:0035621; P:ER to Golgi ceramide transport; IMP:UniProtKB.
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 Coiled coil; Cytoplasm; Endoplasmic reticulum; Golgi apparatus;
KW Lipid transport; Phosphoprotein; Transport.
FT CHAIN 1..598
FT /note="Ceramide transfer protein"
FT /id="PRO_0000307355"
FT DOMAIN 23..117
FT /note="PH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00145"
FT DOMAIN 363..592
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 REGION 202..221
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 268..301
FT /evidence="ECO:0000255"
FT MOTIF 321..327
FT /note="FFAT"
FT /evidence="ECO:0000250|UniProtKB:Q9Y5P4"
FT COMPBIAS 1..16
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 446
FT /ligand="an N-acylsphing-4-enine"
FT /ligand_id="ChEBI:CHEBI:52639"
FT /evidence="ECO:0000250|UniProtKB:Q9Y5P4"
FT BINDING 467
FT /ligand="an N-acylsphing-4-enine"
FT /ligand_id="ChEBI:CHEBI:52639"
FT /evidence="ECO:0000250|UniProtKB:Q9Y5P4"
FT BINDING 504
FT /ligand="an N-acylsphing-4-enine"
FT /ligand_id="ChEBI:CHEBI:52639"
FT /evidence="ECO:0000250|UniProtKB:Q9Y5P4"
FT BINDING 553
FT /ligand="an N-acylsphing-4-enine"
FT /ligand_id="ChEBI:CHEBI:52639"
FT /evidence="ECO:0000250|UniProtKB:Q9Y5P4"
FT MOD_RES 126
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9Y5P4"
FT MOD_RES 132
FT /note="Phosphoserine; by PKD"
FT /evidence="ECO:0000250|UniProtKB:Q9Y5P4"
FT MOD_RES 135
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9EQG9"
FT MOD_RES 315
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9Y5P4"
FT VARIANT 67
FT /note="G -> E (in LY-A cell line; destroys the
FT phosphatidylinositol 4-phosphate-binding activity,
FT abolishes localization to the Golgi apparatus)"
FT /evidence="ECO:0000269|PubMed:14685229"
SQ SEQUENCE 598 AA; 68154 MW; FAA281C113AA0ACA CRC64;
MSDNQSWNSS GSEEDPETES GPPVERCGVL SKWTNYIHGW QDRWVVLKNN TLSYYKSEDE
TEYGCRGSIC LSKAVITPHD FDECRFDISV NDSVWYLRAQ DPDHRQQWID AIEQHKTESG
YGSESSLRRH GSMVSLVSGA SGYSATSTSS FKKGHSLREK LAEMETFRDI LCRQVDTLQK
YFDVCADAVS KDELQRDKVV EDDEDDFPTT RSDGDFLHNT NGNKEKLFPH VTPKGINGID
FKGEAITFKA TTAGILATLS HCIELMVKRE ESWQKRHDKE MEKRRRLEEA YKNAMAELKK
KPRFGGPDYE EGPNSLINEE EFFDAVEAAL DRQDKIEEQS QSEKVRLHWP TPLPSGDAFS
SVGTHRFVQK VEEMVQNHMT YSLQDVGGDA NWQLVVEEGE MKVYRREVEE NGIVLDPLKA
THAVKGVTGH EVCNYFWSVD VRNDWETTIE NFHVVETLAD NAIIIYQTHK RVWPASQRDV
LYLSAIRKIP ALTENDPETW IVCNFSVDHD SAPLNNRCVR AKINVAMICQ TLVSPPEGNQ
EISRDNILCK ITYVANVNPG GWAPASVLRA VAKREYPKFL KRFTSYVQEK TAGKPILF
