DEGS2_MOUSE
ID DEGS2_MOUSE Reviewed; 323 AA.
AC Q8R2F2; Q3TR85; Q78JJ1;
DT 04-DEC-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2002, sequence version 1.
DT 03-AUG-2022, entry version 136.
DE RecName: Full=Sphingolipid delta(4)-desaturase/C4-monooxygenase DES2;
DE EC=1.14.18.5 {ECO:0000269|PubMed:11937514, ECO:0000269|PubMed:14731113, ECO:0000269|PubMed:16571104};
DE EC=1.14.19.17 {ECO:0000269|PubMed:14731113, ECO:0000269|PubMed:16571104};
DE AltName: Full=Degenerative spermatocyte homolog 2;
DE AltName: Full=Sphingolipid 4-desaturase;
DE AltName: Full=Sphingolipid C4-monooxygenase;
GN Name=Degs2 {ECO:0000312|MGI:MGI:1917309};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, PATHWAY, AND CATALYTIC
RP ACTIVITY.
RC STRAIN=FVB/N {ECO:0000312|EMBL:AAM12533.1};
RX PubMed=11937514; DOI=10.1074/jbc.m202947200;
RA Ternes P., Franke S., Zaehringer U., Sperling P., Heinz E.;
RT "Identification and characterization of a sphingolipid delta 4-desaturase
RT family.";
RL J. Biol. Chem. 277:25512-25518(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC STRAIN=C57BL/6J {ECO:0000312|EMBL:BAE37145.1};
RC TISSUE=Thymus {ECO:0000312|EMBL:BAE37145.1};
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=FVB/N {ECO:0000312|EMBL:AAH16427.2};
RC TISSUE=Colon {ECO:0000312|EMBL:AAH16427.2};
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 [4]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND TISSUE
RP SPECIFICITY.
RX PubMed=14731113; DOI=10.1042/bj20031425;
RA Omae F., Miyazaki M., Enomoto A., Suzuki M., Suzuki Y., Suzuki A.;
RT "DES2 protein is responsible for phytoceramide biosynthesis in the mouse
RT small intestine.";
RL Biochem. J. 379:687-695(2004).
RN [5]
RP REGION REQUIRED FOR HYDROLASE ACTIVITY.
RX PubMed=15474011; DOI=10.1016/j.febslet.2004.08.060;
RA Omae F., Miyazaki M., Enomoto A., Suzuki A.;
RT "Identification of an essential sequence for dihydroceramide C-4
RT hydroxylase activity of mouse DES2.";
RL FEBS Lett. 576:63-67(2004).
RN [6]
RP FUNCTION, CATALYTIC ACTIVITY, AND SUBCELLULAR LOCATION.
RX PubMed=16571104; DOI=10.1042/bj20051938;
RA Enomoto A., Omae F., Miyazaki M., Kozutsumi Y., Yubisui T., Suzuki A.;
RT "Dihydroceramide:sphinganine C-4-hydroxylation requires Des2 hydroxylase
RT and the membrane form of cytochrome b5.";
RL Biochem. J. 397:289-295(2006).
CC -!- FUNCTION: Bifunctional enzyme which acts as both a sphingolipid
CC delta(4)-desaturase and a sphingolipid C4-monooxygenase.
CC {ECO:0000269|PubMed:11937514, ECO:0000269|PubMed:14731113,
CC ECO:0000269|PubMed:16571104}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a dihydroceramide + 2 Fe(II)-[cytochrome b5] + 2 H(+) + O2 = a
CC phytoceramide + 2 Fe(III)-[cytochrome b5] + H2O;
CC Xref=Rhea:RHEA:55808, Rhea:RHEA-COMP:10438, Rhea:RHEA-COMP:10439,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:29033, ChEBI:CHEBI:29034, ChEBI:CHEBI:139048,
CC ChEBI:CHEBI:139051; EC=1.14.18.5;
CC Evidence={ECO:0000269|PubMed:14731113, ECO:0000269|PubMed:16571104};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=an N-acylsphinganine + 2 Fe(II)-[cytochrome b5] + 2 H(+) + O2
CC = an N-acylsphing-4-enine + 2 Fe(III)-[cytochrome b5] + 2 H2O;
CC Xref=Rhea:RHEA:46544, Rhea:RHEA-COMP:10438, Rhea:RHEA-COMP:10439,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:29033, ChEBI:CHEBI:29034, ChEBI:CHEBI:31488,
CC ChEBI:CHEBI:52639; EC=1.14.19.17;
CC Evidence={ECO:0000269|PubMed:11937514, ECO:0000269|PubMed:14731113,
CC ECO:0000269|PubMed:16571104};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46545;
CC Evidence={ECO:0000305|PubMed:11937514};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=an N-acylsphinganine + 2 Fe(II)-[cytochrome b5] + 2 H(+) + O2
CC = an N-acyl-(4R)-4-hydroxysphinganine + 2 Fe(III)-[cytochrome b5] +
CC H2O; Xref=Rhea:RHEA:46364, Rhea:RHEA-COMP:10438, Rhea:RHEA-
CC COMP:10439, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:29033, ChEBI:CHEBI:29034, ChEBI:CHEBI:31488,
CC ChEBI:CHEBI:31998; EC=1.14.18.5;
CC Evidence={ECO:0000269|PubMed:11937514};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46365;
CC Evidence={ECO:0000305|PubMed:11937514};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2 Fe(II)-[cytochrome b5] + 2 H(+) + N-octanoylsphinganine + O2
CC = 2 Fe(III)-[cytochrome b5] + H2O + N-octanoyl-4-hydroxysphinganine;
CC Xref=Rhea:RHEA:43116, Rhea:RHEA-COMP:10438, Rhea:RHEA-COMP:10439,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:29033, ChEBI:CHEBI:29034, ChEBI:CHEBI:82841,
CC ChEBI:CHEBI:82842; Evidence={ECO:0000250|UniProtKB:Q6QHC5};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43117;
CC Evidence={ECO:0000250|UniProtKB:Q6QHC5};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC pH dependence:
CC Optimum pH is 7.0-8.0. {ECO:0000269|PubMed:14731113};
CC -!- PATHWAY: Membrane lipid metabolism; sphingolipid biosynthesis.
CC {ECO:0000269|PubMed:11937514}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:16571104, ECO:0000305}; Multi-pass membrane protein
CC {ECO:0000269|PubMed:16571104, ECO:0000305}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1 {ECO:0000269|PubMed:11937514};
CC IsoId=Q8R2F2-1; Sequence=Displayed;
CC Name=2 {ECO:0000269|PubMed:16141072};
CC IsoId=Q8R2F2-2; Sequence=VSP_052629;
CC -!- TISSUE SPECIFICITY: Highly expressed in intestinal crypt cells and
CC adjacent epithelial cells (at protein level).
CC {ECO:0000269|PubMed:14731113}.
CC -!- SIMILARITY: Belongs to the fatty acid desaturase type 1 family. DEGS
CC subfamily. {ECO:0000305}.
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DR EMBL; AF466377; AAM12533.1; -; mRNA.
DR EMBL; AK162979; BAE37145.1; -; mRNA.
DR EMBL; BC016427; AAH16427.2; -; mRNA.
DR CCDS; CCDS26162.1; -. [Q8R2F2-1]
DR CCDS; CCDS49170.1; -. [Q8R2F2-2]
DR RefSeq; NP_001164473.1; NM_001171002.1. [Q8R2F2-2]
DR RefSeq; NP_081575.2; NM_027299.5. [Q8R2F2-1]
DR AlphaFoldDB; Q8R2F2; -.
DR STRING; 10090.ENSMUSP00000021691; -.
DR SwissLipids; SLP:000000168; -.
DR PhosphoSitePlus; Q8R2F2; -.
DR PaxDb; Q8R2F2; -.
DR PRIDE; Q8R2F2; -.
DR ProteomicsDB; 279400; -. [Q8R2F2-1]
DR ProteomicsDB; 279401; -. [Q8R2F2-2]
DR Antibodypedia; 54980; 85 antibodies from 14 providers.
DR DNASU; 70059; -.
DR Ensembl; ENSMUST00000021691; ENSMUSP00000021691; ENSMUSG00000021263. [Q8R2F2-1]
DR Ensembl; ENSMUST00000167978; ENSMUSP00000125891; ENSMUSG00000021263. [Q8R2F2-2]
DR GeneID; 70059; -.
DR KEGG; mmu:70059; -.
DR UCSC; uc007pab.2; mouse. [Q8R2F2-1]
DR UCSC; uc011yrv.1; mouse. [Q8R2F2-2]
DR CTD; 123099; -.
DR MGI; MGI:1917309; Degs2.
DR VEuPathDB; HostDB:ENSMUSG00000021263; -.
DR eggNOG; KOG2987; Eukaryota.
DR GeneTree; ENSGT00390000013448; -.
DR HOGENOM; CLU_032156_0_0_1; -.
DR InParanoid; Q8R2F2; -.
DR OMA; FTYIHLL; -.
DR OrthoDB; 1255438at2759; -.
DR PhylomeDB; Q8R2F2; -.
DR TreeFam; TF313582; -.
DR BRENDA; 1.14.18.5; 3474.
DR Reactome; R-MMU-1660661; Sphingolipid de novo biosynthesis.
DR UniPathway; UPA00786; -.
DR BioGRID-ORCS; 70059; 3 hits in 75 CRISPR screens.
DR ChiTaRS; Degs2; mouse.
DR PRO; PR:Q8R2F2; -.
DR Proteomes; UP000000589; Chromosome 12.
DR RNAct; Q8R2F2; protein.
DR Bgee; ENSMUSG00000021263; Expressed in crypt of Lieberkuhn of small intestine and 84 other tissues.
DR ExpressionAtlas; Q8R2F2; baseline and differential.
DR Genevisible; Q8R2F2; MM.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0042284; F:sphingolipid delta-4 desaturase activity; IGI:MGI.
DR GO; GO:0000170; F:sphingosine hydroxylase activity; IBA:GO_Central.
DR GO; GO:0046513; P:ceramide biosynthetic process; IBA:GO_Central.
DR GO; GO:0006667; P:sphinganine metabolic process; IGI:MGI.
DR GO; GO:0030148; P:sphingolipid biosynthetic process; IGI:MGI.
DR CDD; cd03508; Delta4-sphingolipid-FADS-like; 1.
DR InterPro; IPR011388; DES1/DES2.
DR InterPro; IPR005804; FA_desaturase_dom.
DR InterPro; IPR013866; Sphingolipid_d4-desaturase_N.
DR Pfam; PF00487; FA_desaturase; 1.
DR Pfam; PF08557; Lipid_DES; 1.
DR PIRSF; PIRSF017228; Sphnglp_dlt4_des; 1.
DR SMART; SM01269; Lipid_DES; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Endoplasmic reticulum; Lipid biosynthesis;
KW Lipid metabolism; Lipoprotein; Membrane; Myristate; Oxidoreductase;
KW Reference proteome; Transmembrane; Transmembrane helix.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:Q564G3"
FT CHAIN 2..323
FT /note="Sphingolipid delta(4)-desaturase/C4-monooxygenase
FT DES2"
FT /evidence="ECO:0000250|UniProtKB:Q564G3"
FT /id="PRO_0000312817"
FT TRANSMEM 41..61
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 68..88
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 210..231
FT /note="Helical"
FT /evidence="ECO:0000255"
FT REGION 95..99
FT /note="Required for C4-hydroxylase activity"
FT /evidence="ECO:0000269|PubMed:15474011"
FT MOTIF 89..93
FT /note="Histidine box-1"
FT /evidence="ECO:0000305"
FT MOTIF 128..132
FT /note="Histidine box-2"
FT /evidence="ECO:0000305"
FT MOTIF 259..263
FT /note="Histidine box-3"
FT /evidence="ECO:0000305"
FT LIPID 2
FT /note="N-myristoyl glycine"
FT /evidence="ECO:0000250|UniProtKB:Q564G3"
FT VAR_SEQ 276..323
FT /note="VRKIAPEYYDHLPQHHSWVKVLWDFVFEDSMGPYSRVKRKCKLAKDHL ->
FT DDWNPVRRDVL (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_052629"
FT CONFLICT 88
FT /note="I -> T (in Ref. 2; BAE37145)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 323 AA; 37491 MW; E5B63884E45B5E16 CRC64;
MGNSAARSDF EWVYSDQPHT QRRKEMLAKY PAIKALMRPD PHIKWTVSGM VLVQVLACWL
VRGLSWRWLL FWAYAFGGCI NHSLTLAIHD ISHNTAFGTS CVSRNRWFAI FANLPIGLPY
ATSFKKYHVD HHRYLGGDGL DVDIPTNFEG WFFCTPARKL LWLVLQPFFY SLRPLCVNPK
VVTRMEILNA LVQLAFDVTI FALWGIKPIV YLLGSSLLGL GLHPISGHFV AEHYMFLKGH
ETYSYYGPLN WITFNVGYHM EHHDFPSIPG YYLPLVRKIA PEYYDHLPQH HSWVKVLWDF
VFEDSMGPYS RVKRKCKLAK DHL
