DEGS1_MOUSE
ID DEGS1_MOUSE Reviewed; 323 AA.
AC O09005; Q8R4H3;
DT 04-DEC-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-1997, sequence version 1.
DT 03-AUG-2022, entry version 152.
DE RecName: Full=Sphingolipid delta(4)-desaturase DES1 {ECO:0000305};
DE EC=1.14.19.17 {ECO:0000269|PubMed:11937514};
DE AltName: Full=Degenerative spermatocyte homolog 1;
DE AltName: Full=Dihydroceramide desaturase-1;
DE AltName: Full=Retinol isomerase;
DE EC=5.2.1.- {ECO:0000250|UniProtKB:Q5F3C1};
GN Name=Degs1 {ECO:0000312|MGI:MGI:1097711}; Synonyms=Degs, Des1, Mdes;
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], AND TISSUE SPECIFICITY.
RC STRAIN=ddY; TISSUE=Testis;
RX PubMed=9227906; DOI=10.1046/j.1440-169x.1997.00015.x;
RA Endo K., Matsuda Y., Kobayashi S.;
RT "Mdes, a mouse homolog of the Drosophila degenerative spermatocyte gene is
RT expressed during mouse spermatogenesis.";
RL Dev. Growth Differ. 39:399-403(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND CATALYTIC ACTIVITY.
RC STRAIN=C57BL/6J; TISSUE=Kidney;
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J;
RC TISSUE=Bone marrow macrophage, Egg, Kidney, Ovary, and Uterus;
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Mammary tumor;
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=Kidney, Lung, Pancreas, Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [6]
RP TISSUE SPECIFICITY, AND CATALYTIC ACTIVITY.
RX PubMed=23143414; DOI=10.1038/nchembio.1114;
RA Kaylor J.J., Yuan Q., Cook J., Sarfare S., Makshanoff J., Miu A., Kim A.,
RA Kim P., Habib S., Roybal C.N., Xu T., Nusinowitz S., Travis G.H.;
RT "Identification of DES1 as a vitamin A isomerase in Mueller glial cells of
RT the retina.";
RL Nat. Chem. Biol. 9:30-36(2013).
CC -!- FUNCTION: Has sphingolipid-delta-4-desaturase activity. Converts D-
CC erythro-sphinganine to D-erythro-sphingosine (E-sphing-4-enine).
CC Catalyzes the equilibrium isomerization of retinols (By similarity).
CC {ECO:0000250|UniProtKB:Q5F3C1, ECO:0000269|PubMed:11937514}.
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};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46545;
CC Evidence={ECO:0000305|PubMed:11937514};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=all-trans-retinol = 11-cis-retinol; Xref=Rhea:RHEA:19141,
CC ChEBI:CHEBI:16302, ChEBI:CHEBI:17336;
CC Evidence={ECO:0000269|PubMed:23143414};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:19142;
CC Evidence={ECO:0000305|PubMed:23143414};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:19143;
CC Evidence={ECO:0000250|UniProtKB:Q5F3C1};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=all-trans-retinol = 9-cis-retinol; Xref=Rhea:RHEA:55348,
CC ChEBI:CHEBI:17336, ChEBI:CHEBI:78272;
CC Evidence={ECO:0000250|UniProtKB:Q5F3C1};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:55349;
CC Evidence={ECO:0000250|UniProtKB:Q5F3C1};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=all-trans-retinol = 13-cis-retinol; Xref=Rhea:RHEA:55352,
CC ChEBI:CHEBI:17336, ChEBI:CHEBI:45479;
CC Evidence={ECO:0000250|UniProtKB:Q5F3C1};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:55353;
CC Evidence={ECO:0000250|UniProtKB:Q5F3C1};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=11-cis-retinol = 13-cis-retinol; Xref=Rhea:RHEA:55356,
CC ChEBI:CHEBI:16302, ChEBI:CHEBI:45479;
CC Evidence={ECO:0000250|UniProtKB:Q5F3C1};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:55357;
CC Evidence={ECO:0000250|UniProtKB:Q5F3C1};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=11-cis-retinol = 9-cis-retinol; Xref=Rhea:RHEA:55360,
CC ChEBI:CHEBI:16302, ChEBI:CHEBI:78272;
CC Evidence={ECO:0000250|UniProtKB:Q5F3C1};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:55361;
CC Evidence={ECO:0000250|UniProtKB:Q5F3C1};
CC -!- SUBUNIT: Interacts with RLBP1; the interaction increases synthesis of
CC chromophore-precursors by DEGS1. {ECO:0000250|UniProtKB:Q5F3C1}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion membrane
CC {ECO:0000250|UniProtKB:O15121}. Endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:O15121}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:O15121}.
CC -!- TISSUE SPECIFICITY: Detected in testis. Detected in pachytene
CC spermatocytes and round spermatids. Expressed in retina and retinal
CC pigment epithelium by Mueller cells (at protein level)
CC (PubMed:23143414). {ECO:0000269|PubMed:23143414,
CC ECO:0000269|PubMed:9227906}.
CC -!- PTM: Myristoylation can target the enzyme to the mitochondria leading
CC to an increase in ceramide levels. {ECO:0000250|UniProtKB:O15121}.
CC -!- SIMILARITY: Belongs to the fatty acid desaturase type 1 family. DEGS
CC subfamily. {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; Y08460; CAA69714.1; -; mRNA.
DR EMBL; AF466376; AAM12532.1; -; mRNA.
DR EMBL; AK002617; BAB22233.1; -; mRNA.
DR EMBL; AK077257; BAC36713.1; -; mRNA.
DR EMBL; AK149811; BAE29098.1; -; mRNA.
DR EMBL; AK163404; BAE37337.1; -; mRNA.
DR EMBL; BC003751; AAH03751.1; -; mRNA.
DR CCDS; CCDS15587.1; -.
DR RefSeq; NP_031879.1; NM_007853.4.
DR AlphaFoldDB; O09005; -.
DR BioGRID; 199114; 4.
DR IntAct; O09005; 1.
DR STRING; 10090.ENSMUSP00000048519; -.
DR SwissLipids; SLP:000000167; -.
DR iPTMnet; O09005; -.
DR PhosphoSitePlus; O09005; -.
DR SwissPalm; O09005; -.
DR EPD; O09005; -.
DR MaxQB; O09005; -.
DR PaxDb; O09005; -.
DR PeptideAtlas; O09005; -.
DR PRIDE; O09005; -.
DR ProteomicsDB; 279399; -.
DR DNASU; 13244; -.
DR Ensembl; ENSMUST00000035295; ENSMUSP00000048519; ENSMUSG00000038633.
DR GeneID; 13244; -.
DR KEGG; mmu:13244; -.
DR UCSC; uc007dxw.1; mouse.
DR CTD; 8560; -.
DR MGI; MGI:1097711; Degs1.
DR VEuPathDB; HostDB:ENSMUSG00000038633; -.
DR eggNOG; KOG2987; Eukaryota.
DR GeneTree; ENSGT00390000013448; -.
DR InParanoid; O09005; -.
DR OMA; VYYVFGI; -.
DR OrthoDB; 1255438at2759; -.
DR PhylomeDB; O09005; -.
DR TreeFam; TF313582; -.
DR BRENDA; 1.14.19.17; 3474.
DR Reactome; R-MMU-1660661; Sphingolipid de novo biosynthesis.
DR Reactome; R-MMU-6798695; Neutrophil degranulation.
DR BioGRID-ORCS; 13244; 5 hits in 74 CRISPR screens.
DR ChiTaRS; Degs1; mouse.
DR PRO; PR:O09005; -.
DR Proteomes; UP000000589; Chromosome 1.
DR RNAct; O09005; protein.
DR Bgee; ENSMUSG00000038633; Expressed in tail skin and 260 other tissues.
DR ExpressionAtlas; O09005; baseline and differential.
DR Genevisible; O09005; 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:0031966; C:mitochondrial membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005739; C:mitochondrion; ISO:MGI.
DR GO; GO:0050251; F:retinol isomerase activity; IDA:UniProtKB.
DR GO; GO:0042284; F:sphingolipid delta-4 desaturase activity; IMP:MGI.
DR GO; GO:0046513; P:ceramide biosynthetic process; IMP:MGI.
DR GO; GO:0006633; P:fatty acid biosynthetic process; IEA:UniProtKB-KW.
DR GO; GO:0043217; P:myelin maintenance; ISS:UniProtKB.
DR GO; GO:0043065; P:positive regulation of apoptotic process; IMP:MGI.
DR CDD; cd03508; Delta4-sphingolipid-FADS-like; 1.
DR InterPro; IPR031196; DES1.
DR InterPro; IPR011388; DES1/DES2.
DR InterPro; IPR005804; FA_desaturase_dom.
DR InterPro; IPR013866; Sphingolipid_d4-desaturase_N.
DR PANTHER; PTHR12879:SF2; PTHR12879:SF2; 1.
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 Endoplasmic reticulum; Fatty acid biosynthesis; Fatty acid metabolism;
KW Isomerase; Lipid biosynthesis; Lipid metabolism; Lipoprotein; Membrane;
KW Mitochondrion; Myristate; Oxidoreductase; Phosphoprotein;
KW Reference proteome; Transmembrane; Transmembrane helix.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:O15121"
FT CHAIN 2..323
FT /note="Sphingolipid delta(4)-desaturase DES1"
FT /id="PRO_0000312729"
FT TRANSMEM 41..61
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 68..88
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 104..124
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 152..172
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 184..204
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 209..229
FT /note="Helical"
FT /evidence="ECO:0000255"
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 MOD_RES 307
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O15121"
FT LIPID 2
FT /note="N-myristoyl glycine"
FT /evidence="ECO:0000250|UniProtKB:O15121"
FT CONFLICT 203
FT /note="V -> A (in Ref. 2; AAM12532)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 323 AA; 38241 MW; C1840C24E6FF29E0 CRC64;
MGSRVSREEF EWVYTDQPHA ARRKEILAKY PEIKSLMKPD HNLIWIVAMM LLVQLASFYL
VKDLDWKWVI FWSYVFGSCL NHSMTLAIHE ISHNFPFGHH KALWNRWFGM FANLSLGVPY
SISFKRYHMD HHRYLGADKI DVDIPTDFEG WFFCTTFRKF VWVILQPLFY AFRPLFINPK
PITYLEIINT VIQITFDIII YYVFGVKSLV YMLAATLLGL GLHPISGHFI AEHYMFLKGH
ETYSYYGPLN LLTFNVGYHN EHHDFPNVPG KNLPMVRKIA SEYYDDLPHY NSWIKVLYDF
VTDDTISPYS RMKRPPKGNE ILE
