ID   DEGS2_HUMAN             Reviewed;         323 AA.
AC   Q6QHC5; Q6P492;
DT   04-DEC-2007, integrated into UniProtKB/Swiss-Prot.
DT   24-NOV-2009, sequence version 2.
DT   27-MAR-2024, entry version 140.
DE   RecName: Full=Sphingolipid delta(4)-desaturase/C4-monooxygenase DES2;
DE            EC=1.14.18.5 {ECO:0000269|PubMed:15063729};
DE            EC=1.14.19.17 {ECO:0000269|PubMed:15063729};
DE   AltName: Full=Degenerative spermatocyte homolog 2;
DE   AltName: Full=Sphingolipid 4-desaturase;
DE   AltName: Full=Sphingolipid C4-monooxygenase;
GN   Name=DEGS2 {ECO:0000312|HGNC:HGNC:20113}; Synonyms=C14orf66;
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], CATALYTIC ACTIVITY, TISSUE SPECIFICITY,
RP   INDUCTION, AND VARIANT ASN-8.
RC   TISSUE=Skin {ECO:0000312|EMBL:AAS68362.1};
RX   PubMed=15063729; DOI=10.1016/s0014-5793(04)00274-1;
RA   Mizutani Y., Kihara A., Igarashi Y.;
RT   "Identification of the human sphingolipid C4-hydroxylase, hDES2, and its
RT   up-regulation during keratinocyte differentiation.";
RL   FEBS Lett. 563:93-97(2004).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=12508121; DOI=10.1038/nature01348;
RA   Heilig R., Eckenberg R., Petit J.-L., Fonknechten N., Da Silva C.,
RA   Cattolico L., Levy M., Barbe V., De Berardinis V., Ureta-Vidal A.,
RA   Pelletier E., Vico V., Anthouard V., Rowen L., Madan A., Qin S., Sun H.,
RA   Du H., Pepin K., Artiguenave F., Robert C., Cruaud C., Bruels T.,
RA   Jaillon O., Friedlander L., Samson G., Brottier P., Cure S., Segurens B.,
RA   Aniere F., Samain S., Crespeau H., Abbasi N., Aiach N., Boscus D.,
RA   Dickhoff R., Dors M., Dubois I., Friedman C., Gouyvenoux M., James R.,
RA   Madan A., Mairey-Estrada B., Mangenot S., Martins N., Menard M., Oztas S.,
RA   Ratcliffe A., Shaffer T., Trask B., Vacherie B., Bellemere C., Belser C.,
RA   Besnard-Gonnet M., Bartol-Mavel D., Boutard M., Briez-Silla S.,
RA   Combette S., Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C.,
RA   Muselet D., Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P.,
RA   Trybou A., Vega-Czarny N., Bataille E., Bluet E., Bordelais I., Dubois M.,
RA   Dumont C., Guerin T., Haffray S., Hammadi R., Muanga J., Pellouin V.,
RA   Robert D., Wunderle E., Gauguet G., Roy A., Sainte-Marthe L., Verdier J.,
RA   Verdier-Discala C., Hillier L.W., Fulton L., McPherson J., Matsuda F.,
RA   Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W., Quetier F.,
RA   Waterston R., Hood L., Weissenbach J.;
RT   "The DNA sequence and analysis of human chromosome 14.";
RL   Nature 421:601-607(2003).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT ASN-8.
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   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT THR-57.
RC   TISSUE=Skin {ECO:0000312|EMBL:AAH63598.1};
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).
CC   -!- FUNCTION: Bifunctional enzyme which acts both as a sphingolipid
CC       delta(4)-desaturase and a sphingolipid C4-monooxygenase.
CC       {ECO:0000269|PubMed:15063729}.
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:15063729};
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:15063729};
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:0000269|PubMed:15063729};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43117;
CC         Evidence={ECO:0000305|PubMed:15063729};
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:15063729};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46365;
CC         Evidence={ECO:0000305|PubMed:15063729};
CC   -!- PATHWAY: Membrane lipid metabolism; sphingolipid biosynthesis.
CC   -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC       {ECO:0000250|UniProtKB:Q8R2F2}; Multi-pass membrane protein
CC       {ECO:0000250|UniProtKB:Q8R2F2}.
CC   -!- TISSUE SPECIFICITY: Highly expressed in skin, intestine and kidney.
CC       {ECO:0000269|PubMed:15063729}.
CC   -!- INDUCTION: Up-regulated during keratinocyte differentiation. Not
CC       expressed at the beginning or day 3 after differentiation, detected on
CC       day 6 and increases by day 9. {ECO:0000269|PubMed:15063729}.
CC   -!- SIMILARITY: Belongs to the fatty acid desaturase type 1 family. DEGS
CC       subfamily. {ECO:0000305}.
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DR   EMBL; AY541700; AAS68362.1; -; mRNA.
DR   EMBL; AL133523; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; CH471061; EAW81688.1; -; Genomic_DNA.
DR   EMBL; BC063598; AAH63598.1; -; mRNA.
DR   CCDS; CCDS9956.1; -.
DR   RefSeq; NP_996801.2; NM_206918.2.
DR   AlphaFoldDB; Q6QHC5; -.
DR   BioGRID; 125815; 1.
DR   STRING; 9606.ENSP00000307126; -.
DR   SwissLipids; SLP:000000170; -.
DR   iPTMnet; Q6QHC5; -.
DR   PhosphoSitePlus; Q6QHC5; -.
DR   BioMuta; DEGS2; -.
DR   DMDM; 269849561; -.
DR   jPOST; Q6QHC5; -.
DR   MassIVE; Q6QHC5; -.
DR   PaxDb; 9606-ENSP00000307126; -.
DR   PeptideAtlas; Q6QHC5; -.
DR   ProteomicsDB; 67288; -.
DR   Antibodypedia; 54980; 100 antibodies from 15 providers.
DR   DNASU; 123099; -.
DR   Ensembl; ENST00000305631.7; ENSP00000307126.5; ENSG00000168350.8.
DR   GeneID; 123099; -.
DR   KEGG; hsa:123099; -.
DR   MANE-Select; ENST00000305631.7; ENSP00000307126.5; NM_206918.3; NP_996801.2.
DR   UCSC; uc001ygx.3; human.
DR   AGR; HGNC:20113; -.
DR   CTD; 123099; -.
DR   DisGeNET; 123099; -.
DR   GeneCards; DEGS2; -.
DR   HGNC; HGNC:20113; DEGS2.
DR   HPA; ENSG00000168350; Tissue enhanced (esophagus, intestine, skin).
DR   MIM; 610862; gene.
DR   neXtProt; NX_Q6QHC5; -.
DR   OpenTargets; ENSG00000168350; -.
DR   PharmGKB; PA134973300; -.
DR   VEuPathDB; HostDB:ENSG00000168350; -.
DR   eggNOG; KOG2987; Eukaryota.
DR   GeneTree; ENSGT00390000013448; -.
DR   HOGENOM; CLU_032156_0_0_1; -.
DR   InParanoid; Q6QHC5; -.
DR   OMA; FEWVYND; -.
DR   OrthoDB; 5485164at2759; -.
DR   PhylomeDB; Q6QHC5; -.
DR   TreeFam; TF313582; -.
DR   BioCyc; MetaCyc:HS15665-MONOMER; -.
DR   BRENDA; 1.14.18.5; 2681.
DR   PathwayCommons; Q6QHC5; -.
DR   Reactome; R-HSA-1660661; Sphingolipid de novo biosynthesis.
DR   UniPathway; UPA00786; -.
DR   BioGRID-ORCS; 123099; 11 hits in 1151 CRISPR screens.
DR   GenomeRNAi; 123099; -.
DR   Pharos; Q6QHC5; Tbio.
DR   PRO; PR:Q6QHC5; -.
DR   Proteomes; UP000005640; Chromosome 14.
DR   RNAct; Q6QHC5; Protein.
DR   Bgee; ENSG00000168350; Expressed in upper arm skin and 150 other cell types or tissues.
DR   ExpressionAtlas; Q6QHC5; baseline and differential.
DR   GO; GO:0005789; C:endoplasmic reticulum membrane; TAS:Reactome.
DR   GO; GO:0102772; F:sphingolipid C4-monooxygenase activity; IEA:UniProtKB-EC.
DR   GO; GO:0042284; F:sphingolipid delta-4 desaturase activity; IBA:GO_Central.
DR   GO; GO:0000170; F:sphingosine hydroxylase activity; TAS:Reactome.
DR   GO; GO:0046513; P:ceramide biosynthetic process; IBA:GO_Central.
DR   GO; GO:0006667; P:sphinganine metabolic process; IBA:GO_Central.
DR   GO; GO:0030148; P:sphingolipid biosynthetic process; TAS:Reactome.
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   PANTHER; PTHR12879; SPHINGOLIPID DELTA 4 DESATURASE/C-4 HYDROXYLASE PROTEIN DES2; 1.
DR   PANTHER; PTHR12879:SF21; SPHINGOLIPID DELTA(4)-DESATURASE_C4-MONOOXYGENASE DES2; 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.
DR   Genevisible; Q6QHC5; HS.
PE   1: Evidence at protein level;
KW   Endoplasmic reticulum; Lipid biosynthesis; Lipid metabolism; Lipoprotein;
KW   Membrane; Myristate; Oxidoreductase; Reference proteome; Transmembrane;
KW   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_0000312816"
FT   TRANSMEM        45..65
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:0000250|UniProtKB:Q8R2F2"
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   VARIANT         8
FT                   /note="S -> N (in dbSNP:rs7157599)"
FT                   /evidence="ECO:0000269|PubMed:15063729, ECO:0000269|Ref.3"
FT                   /id="VAR_060347"
FT   VARIANT         57
FT                   /note="A -> T (in dbSNP:rs4905937)"
FT                   /evidence="ECO:0000269|PubMed:15489334"
FT                   /id="VAR_055698"
SQ   SEQUENCE   323 AA;  37197 MW;  4726A4EBD357EB0F CRC64;
     MGNSASRSDF EWVYTDQPHT QRRKEILAKY PAIKALMRPD PRLKWAVLVL VLVQMLACWL
     VRGLAWRWLL FWAYAFGGCV NHSLTLAIHD ISHNAAFGTG RAARNRWLAV FANLPVGVPY
     AASFKKYHVD HHRYLGGDGL DVDVPTRLEG WFFCTPARKL LWLVLQPFFY SLRPLCVHPK
     AVTRMEVLNT LVQLAADLAI FALWGLKPVV YLLASSFLGL GLHPISGHFV AEHYMFLKGH
     ETYSYYGPLN WITFNVGYHV EHHDFPSIPG YNLPLVRKIA PEYYDHLPQH HSWVKVLWDF
     VFEDSLGPYA RVKRVYRLAK DGL
//