ACOD1_RAT
ID ACOD1_RAT Reviewed; 358 AA.
AC P07308; Q8JZL5;
DT 01-APR-1988, integrated into UniProtKB/Swiss-Prot.
DT 23-NOV-2004, sequence version 2.
DT 03-AUG-2022, entry version 172.
DE RecName: Full=Acyl-CoA desaturase 1;
DE EC=1.14.19.1 {ECO:0000269|PubMed:2892838, ECO:0000269|PubMed:7947684};
DE AltName: Full=Delta(9)-desaturase 1 {ECO:0000305};
DE Short=Delta-9 desaturase 1 {ECO:0000305};
DE AltName: Full=Fatty acid desaturase 1;
DE AltName: Full=Stearoyl-CoA desaturase 1 {ECO:0000303|PubMed:12419843};
GN Name=Scd1; Synonyms=Scd;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND PARTIAL PROTEIN SEQUENCE.
RX PubMed=2428815; DOI=10.1016/s0021-9258(18)69295-6;
RA Thiede M.A., Ozols J., Strittmatter P.;
RT "Construction and sequence of cDNA for rat liver stearyl coenzyme A
RT desaturase.";
RL J. Biol. Chem. 261:13230-13235(1986).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, AND INDUCTION BY FAT-FREE
RP DIET.
RX PubMed=1982442; DOI=10.1093/oxfordjournals.jbchem.a123301;
RA Mihara K.;
RT "Structure and regulation of rat liver microsomal stearoyl-CoA desaturase
RT gene.";
RL J. Biochem. 108:1022-1029(1990).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Brown Norway, and Fischer 344;
RX PubMed=12419843; DOI=10.1093/carcin/23.11.1933;
RA Falvella F.S., Pascale R.M., Gariboldi M., Manenti G., De Miglio M.R.,
RA Simile M.M., Dragani T.A., Feo F.;
RT "Stearoyl-CoA desaturase 1 (Scd1) gene overexpression is associated with
RT genetic predisposition to hepatocarcinogenesis in mice and rats.";
RL Carcinogenesis 23:1933-1936(2002).
RN [4]
RP FUNCTION, CATALYTIC ACTIVITY, COFACTOR, SUBCELLULAR LOCATION, AND TISSUE
RP SPECIFICITY.
RX PubMed=2892838; DOI=10.1016/s0021-9258(18)69239-7;
RA Strittmatter P., Thiede M.A., Hackett C.S., Ozols J.;
RT "Bacterial synthesis of active rat Stearoyl-CoA desaturase lacking the 26-
RT residue amino-terminal amino acid sequence.";
RL J. Biol. Chem. 263:2532-2535(1988).
RN [5]
RP CATALYTIC ACTIVITY, COFACTOR, AND MUTAGENESIS OF HIS-119; HIS-124; HIS-156;
RP ARG-157; HIS-159; HIS-160; HIS-166; HIS-170; ARG-173; HIS-297; HIS-300 AND
RP HIS-301.
RX PubMed=7947684; DOI=10.1021/bi00209a009;
RA Shanklin J., Whittle E., Fox B.G.;
RT "Eight histidine residues are catalytically essential in a membrane-
RT associated iron enzyme, stearoyl-CoA desaturase, and are conserved in
RT alkane hydroxylase and xylene monooxygenase.";
RL Biochemistry 33:12787-12794(1994).
CC -!- FUNCTION: Stearoyl-CoA desaturase that utilizes O(2) and electrons from
CC reduced cytochrome b5 to introduce the first double bond into saturated
CC fatty acyl-CoA substrates (PubMed:2892838, PubMed:7947684). Catalyzes
CC the insertion of a cis double bond at the Delta-9 position into fatty
CC acyl-CoA substrates including palmitoyl-CoA and stearoyl-CoA
CC (PubMed:2892838, PubMed:7947684). Gives rise to a mixture of 16:1 and
CC 18:1 unsaturated fatty acids. Plays an important role in lipid
CC biosynthesis. Plays an important role in regulating the expression of
CC genes that are involved in lipogenesis and in regulating mitochondrial
CC fatty acid oxidation (By similarity). Plays an important role in body
CC energy homeostasis (By similarity). Contributes to the biosynthesis of
CC membrane phospholipids, cholesterol esters and triglycerides
CC (PubMed:7947684). Required for normal development of sebaceous glands.
CC Required for the biosynthesis of normal levels of Delta-9 unsaturated
CC fatty acids and 1-alkyl-2,3-diacylglycerol in the Harderian gland.
CC Required for normal production of meibum, an oily material that
CC prevents drying of the cornea (By similarity).
CC {ECO:0000250|UniProtKB:P13516, ECO:0000269|PubMed:2892838,
CC ECO:0000269|PubMed:7947684}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2 Fe(II)-[cytochrome b5] + 2 H(+) + O2 + octadecanoyl-CoA =
CC (9Z)-octadecenoyl-CoA + 2 Fe(III)-[cytochrome b5] + 2 H2O;
CC Xref=Rhea:RHEA:19721, 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:57387,
CC ChEBI:CHEBI:57394; EC=1.14.19.1;
CC Evidence={ECO:0000269|PubMed:2892838, ECO:0000269|PubMed:7947684};
CC -!- COFACTOR:
CC Name=Fe(2+); Xref=ChEBI:CHEBI:29033;
CC Evidence={ECO:0000305|PubMed:2892838, ECO:0000305|PubMed:7947684};
CC Note=Expected to bind 2 Fe(2+) ions per subunit.
CC {ECO:0000250|UniProtKB:P13516};
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:O00767}; Multi-pass membrane protein
CC {ECO:0000305}. Membrane {ECO:0000269|PubMed:2892838}; Multi-pass
CC membrane protein {ECO:0000269|PubMed:2892838}.
CC -!- TISSUE SPECIFICITY: Detected in liver (at protein level)
CC (PubMed:2892838). Detected in adipose tissue. Detected in liver when
CC rats are kept on a fat-free diet, but not when their food contains
CC unsaturated fatty acids. {ECO:0000269|PubMed:1982442}.
CC -!- INDUCTION: Up-regulated in liver in the absence of dietary unsaturated
CC fatty acids(PubMed:1982442). Expression in adipose tissue seems to be
CC constitutive (PubMed:1982442). {ECO:0000269|PubMed:1982442}.
CC -!- DOMAIN: The histidine box domains are involved in binding the catalytic
CC metal ions. {ECO:0000305|PubMed:7947684}.
CC -!- MISCELLANEOUS: Desaturase has a half-life of only 4 hours.
CC -!- SIMILARITY: Belongs to the fatty acid desaturase type 1 family.
CC {ECO:0000305}.
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DR EMBL; J02585; AAA42116.1; -; mRNA.
DR EMBL; AF509568; AAM34745.1; -; mRNA.
DR EMBL; AF509569; AAM34746.1; -; mRNA.
DR PIR; A24699; A24699.
DR RefSeq; NP_631931.2; NM_139192.2.
DR RefSeq; XP_006231495.1; XM_006231433.2.
DR AlphaFoldDB; P07308; -.
DR SMR; P07308; -.
DR BioGRID; 251497; 1.
DR STRING; 10116.ENSRNOP00000018447; -.
DR BindingDB; P07308; -.
DR ChEMBL; CHEMBL5424; -.
DR iPTMnet; P07308; -.
DR PhosphoSitePlus; P07308; -.
DR jPOST; P07308; -.
DR PaxDb; P07308; -.
DR PeptideAtlas; P07308; -.
DR PRIDE; P07308; -.
DR Ensembl; ENSRNOT00000018447; ENSRNOP00000018447; ENSRNOG00000013552.
DR GeneID; 246074; -.
DR KEGG; rno:246074; -.
DR CTD; 6319; -.
DR RGD; 621176; Scd1.
DR eggNOG; KOG1600; Eukaryota.
DR GeneTree; ENSGT00940000162971; -.
DR HOGENOM; CLU_027359_0_0_1; -.
DR InParanoid; P07308; -.
DR OMA; IGYHRLY; -.
DR OrthoDB; 971318at2759; -.
DR BioCyc; MetaCyc:MON-14123; -.
DR BRENDA; 1.14.19.1; 5301.
DR PRO; PR:P07308; -.
DR Proteomes; UP000002494; Chromosome 1.
DR Bgee; ENSRNOG00000013552; Expressed in liver and 20 other tissues.
DR Genevisible; P07308; RN.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; ISS:UniProtKB.
DR GO; GO:0030176; C:integral component of endoplasmic reticulum membrane; ISO:RGD.
DR GO; GO:0016021; C:integral component of membrane; IDA:UniProtKB.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:RGD.
DR GO; GO:0005506; F:iron ion binding; IDA:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; ISO:RGD.
DR GO; GO:0016491; F:oxidoreductase activity; IMP:UniProtKB.
DR GO; GO:0032896; F:palmitoyl-CoA 9-desaturase activity; ISO:RGD.
DR GO; GO:0004768; F:stearoyl-CoA 9-desaturase activity; IDA:UniProtKB.
DR GO; GO:0050873; P:brown fat cell differentiation; ISO:RGD.
DR GO; GO:0034435; P:cholesterol esterification; ISO:RGD.
DR GO; GO:0050830; P:defense response to Gram-positive bacterium; ISO:RGD.
DR GO; GO:0006633; P:fatty acid biosynthetic process; ISO:RGD.
DR GO; GO:0008610; P:lipid biosynthetic process; IEP:RGD.
DR GO; GO:0055088; P:lipid homeostasis; ISO:RGD.
DR GO; GO:1903966; P:monounsaturated fatty acid biosynthetic process; ISO:RGD.
DR GO; GO:0120162; P:positive regulation of cold-induced thermogenesis; ISS:YuBioLab.
DR GO; GO:0033561; P:regulation of water loss via skin; ISO:RGD.
DR GO; GO:0009617; P:response to bacterium; ISO:RGD.
DR GO; GO:0070542; P:response to fatty acid; IDA:UniProtKB.
DR GO; GO:0048733; P:sebaceous gland development; ISO:RGD.
DR GO; GO:0034434; P:sterol esterification; ISO:RGD.
DR GO; GO:1903699; P:tarsal gland development; ISO:RGD.
DR GO; GO:0006641; P:triglyceride metabolic process; ISO:RGD.
DR GO; GO:0006636; P:unsaturated fatty acid biosynthetic process; IDA:UniProtKB.
DR GO; GO:0050872; P:white fat cell differentiation; ISO:RGD.
DR CDD; cd03505; Delta9-FADS-like; 1.
DR InterPro; IPR015876; Acyl-CoA_DS.
DR InterPro; IPR005804; FA_desaturase_dom.
DR InterPro; IPR001522; FADS-1_CS.
DR PANTHER; PTHR11351; PTHR11351; 1.
DR Pfam; PF00487; FA_desaturase; 1.
DR PRINTS; PR00075; FACDDSATRASE.
DR PROSITE; PS00476; FATTY_ACID_DESATUR_1; 1.
PE 1: Evidence at protein level;
KW Direct protein sequencing; Endoplasmic reticulum; Fatty acid biosynthesis;
KW Fatty acid metabolism; Iron; Lipid biosynthesis; Lipid metabolism;
KW Membrane; Metal-binding; Oxidoreductase; Reference proteome; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..358
FT /note="Acyl-CoA desaturase 1"
FT /id="PRO_0000185400"
FT TOPO_DOM 1..71
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P13516"
FT TRANSMEM 72..92
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P13516"
FT TOPO_DOM 93..96
FT /note="Lumenal"
FT /evidence="ECO:0000250|UniProtKB:P13516"
FT TRANSMEM 97..117
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P13516"
FT TOPO_DOM 118..216
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P13516"
FT TRANSMEM 217..236
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P13516"
FT TOPO_DOM 237..240
FT /note="Lumenal"
FT /evidence="ECO:0000250|UniProtKB:P13516"
FT TRANSMEM 241..262
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P13516"
FT TOPO_DOM 263..358
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P13516"
FT REGION 8..33
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 119..124
FT /note="Histidine box-1"
FT /evidence="ECO:0000305"
FT MOTIF 156..160
FT /note="Histidine box-2"
FT /evidence="ECO:0000305"
FT MOTIF 297..301
FT /note="Histidine box-3"
FT /evidence="ECO:0000305"
FT COMPBIAS 8..27
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 74
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:O00767"
FT BINDING 119
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P13516"
FT BINDING 124
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P13516"
FT BINDING 147
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:O00767"
FT BINDING 154
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:O00767"
FT BINDING 155
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:O00767"
FT BINDING 156
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P13516"
FT BINDING 159
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P13516"
FT BINDING 160
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P13516"
FT BINDING 187
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:O00767"
FT BINDING 188
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:O00767"
FT BINDING 261
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:O00767"
FT BINDING 268
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P13516"
FT BINDING 297
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P13516"
FT BINDING 300
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P13516"
FT BINDING 301
FT /ligand="Fe cation"
FT /ligand_id="ChEBI:CHEBI:24875"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P13516"
FT MUTAGEN 119
FT /note="H->A: Abolishes enzyme activity."
FT /evidence="ECO:0000269|PubMed:7947684"
FT MUTAGEN 124
FT /note="H->A: Abolishes enzyme activity."
FT /evidence="ECO:0000269|PubMed:7947684"
FT MUTAGEN 156
FT /note="H->A: Abolishes enzyme activity."
FT /evidence="ECO:0000269|PubMed:7947684"
FT MUTAGEN 157
FT /note="R->N: No effect on enzyme activity."
FT /evidence="ECO:0000269|PubMed:7947684"
FT MUTAGEN 159
FT /note="H->A: Abolishes enzyme activity."
FT /evidence="ECO:0000269|PubMed:7947684"
FT MUTAGEN 160
FT /note="H->A: Abolishes enzyme activity."
FT /evidence="ECO:0000269|PubMed:7947684"
FT MUTAGEN 166
FT /note="H->A: No effect on enzyme activity."
FT /evidence="ECO:0000269|PubMed:7947684"
FT MUTAGEN 170
FT /note="H->A: No effect on enzyme activity; when associated
FT with H-173."
FT /evidence="ECO:0000269|PubMed:7947684"
FT MUTAGEN 173
FT /note="R->H: No effect on enzyme activity; when associated
FT with A-170."
FT /evidence="ECO:0000269|PubMed:7947684"
FT MUTAGEN 297
FT /note="H->A: Abolishes enzyme activity."
FT /evidence="ECO:0000269|PubMed:7947684"
FT MUTAGEN 300
FT /note="H->A: Abolishes enzyme activity."
FT /evidence="ECO:0000269|PubMed:7947684"
FT MUTAGEN 301
FT /note="H->A: Abolishes enzyme activity."
FT /evidence="ECO:0000269|PubMed:7947684"
FT MUTAGEN 315
FT /note="H->A: No effect on enzyme activity."
FT /evidence="ECO:0000269|PubMed:7947684"
FT CONFLICT 291
FT /note="A -> S (in Ref. 1; AAA42116)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 358 AA; 41467 MW; B4C960A969B63774 CRC64;
MPAHMLQEIS SSYTTTTTIT EPPSGNLQNG REKMKKVPLY LEEDIRPEMR EDIHDPSYQD
EEGPPPKLEY VWRNIILMAL LHVGALYGIT LIPSSKVYTL LWGIFYYLIS ALGITAGAHR
LWSHRTYKAR LPLRIFLIIA NTMAFQNDVY EWARDHRAHH KFSETHADPH NSRRGFFFSH
VGWLLVRKHP AVKEKGGKLD MSDLKAEKLV MFQRRYYKPG LLLMCFILPT LVPWYCWGET
FLHSLFVSTF LRYTLVLNAT WLVNSAAHLY GYRPYDKNIQ SRENILVSLG AVGEGFHNYH
HAFPYDYSAS EYRWHINFTT FFIDCMAALG LAYDRKKVSK AAVLARIKRT GDGSHKSS
