DEGS2_HUMAN
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 03-AUG-2022, entry version 132.
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 as both 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; Q6QHC5; -.
DR PeptideAtlas; Q6QHC5; -.
DR PRIDE; Q6QHC5; -.
DR ProteomicsDB; 67288; -.
DR Antibodypedia; 54980; 85 antibodies from 14 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 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; FTYIHLL; -.
DR OrthoDB; 1255438at2759; -.
DR PhylomeDB; Q6QHC5; -.
DR TreeFam; TF313582; -.
DR BioCyc; MetaCyc:HS15665-MON; -.
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; 10 hits in 1066 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 148 other tissues.
DR ExpressionAtlas; Q6QHC5; baseline and differential.
DR Genevisible; Q6QHC5; HS.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; TAS:Reactome.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0042284; F:sphingolipid delta-4 desaturase activity; IBA:GO_Central.
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; 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 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; 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
