O95864 (FADS2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Fatty acid desaturase 2
EC=1.14.19.-

Alternative name(s):
Delta(6) fatty acid desaturase
Short name=D6D
Short name=Delta(6) desaturase
Short name=Delta-6 desaturase

Gene names

Name:

FADS2

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	444 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Component of a lipid metabolic pathway that catalyzes biosynthesis of highly unsaturated fatty acids (HUFA) from precursor essential polyunsaturated fatty acids (PUFA) linoleic acid (LA) (18:2n-6) and alpha-linolenic acid (ALA) (18:3n-3). Catalyzes the first and rate limiting step in this pathway which is the desaturation of LA (18:2n-6) and ALA (18:3n-3) into gamma-linoleic acid (GLA) (18:3n-6) and stearidonic acid (18:4n-3) respectively and other desaturation steps. Highly unsaturated fatty acids (HUFA) play pivotal roles in many biological functions. It catalizes as well the introduction of a cis double bond in palmitate to produce the mono-unsaturated fatty acid sapienate, the most abundant fatty acid in sebum. Ref.1 Ref.10
Pathway	Lipid metabolism; polyunsaturated fatty acid biosynthesis.
Subcellular location	Endoplasmic reticulum membrane; Multi-pass membrane protein Potential.
Tissue specificity	Expressed in a wide array of tissues, highest expression is found in liver followed by brain, lung, heart, and retina. A lower level is found in breast tumor when compared with normal tissues; lowest levels were found in patients with poor prognostic index. Ref.1 Ref.2 Ref.13
Developmental stage	Found in fetal heart.
Induction	Repressed by dietary highly unsaturated fatty acids. Ref.9 Ref.12
Domain	The histidine box domains may contain the active site and/or be involved in metal ion binding.
Sequence similarities	Belongs to the fatty acid desaturase family. Contains 1 cytochrome b5 heme-binding domain.

Ontologies

Keywords
Biological process	Electron transport Fatty acid biosynthesis Fatty acid metabolism Lipid biosynthesis Lipid metabolism Transport
Cellular component	Endoplasmic reticulum Membrane
Coding sequence diversity	Alternative splicing
Domain	Transmembrane Transmembrane helix
Molecular function	Oxidoreductase
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	alpha-linolenic acid metabolic process Traceable author statement. Source: Reactome electron transport chain Inferred from electronic annotation. Source: UniProtKB-KW linoleic acid metabolic process Traceable author statement. Source: Reactome unsaturated fatty acid biosynthetic process Traceable author statement Ref.1. Source: ProtInc
Cellular_component	endoplasmic reticulum membrane Traceable author statement. Source: Reactome integral to plasma membrane Traceable author statement Ref.1. Source: ProtInc
Molecular_function	heme binding Inferred from electronic annotation. Source: InterPro iron ion binding Inferred from electronic annotation. Source: InterPro stearoyl-CoA 9-desaturase activity Inferred from electronic annotation. Source: Compara
Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: O95864-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: O95864-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-69: MGKGGNQGEG...IGHYAGEDAT → MHGREAGPFV...SAGHPITGQQ

Isoform 3 (identifier: O95864-3)

The sequence of this isoform differs from the canonical sequence as follows:
     386-444: HLFPTMPRHNLHKIAPLVKSLCAKHGIEYQEKPLLRALLDIIRSLKKSGKLWLDAYLHK → Q

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 444	444	Fatty acid desaturase 2		PRO_0000307101
Regions
	Topological domain	1 – 131	131	Cytoplasmic Potential
	Transmembrane	132 – 152	21	Helical; Potential
	Topological domain	153 – 157	5	Lumenal Potential
	Transmembrane	158 – 178	21	Helical; Potential
	Topological domain	179 – 264	86	Cytoplasmic Potential
	Transmembrane	265 – 285	21	Helical; Potential
	Topological domain	286 – 305	20	Lumenal Potential
	Transmembrane	306 – 326	21	Helical; Potential
	Topological domain	327 – 444	118	Cytoplasmic Potential
	Domain	18 – 95	78	Cytochrome b5 heme-binding
	Motif	180 – 184	5	Histidine box-1
	Motif	217 – 221	5	Histidine box-2
	Motif	382 – 386	5	Histidine box-3
Natural variations
	Alternative sequence	1 – 69	69	MGKGG…GEDAT → MHGREAGPFVCVCVLLASIP TPQTPLLQASLPPFHPASAG HPITGQQ in isoform 2.		VSP_028568
	Alternative sequence	386 – 444	59	HLFPT…AYLHK → Q in isoform 3.		VSP_028569
Experimental info
	Sequence conflict	134 – 137	4	LLLL → RTRG in CAB43280. Ref.8
	Sequence conflict	380 – 381	2	NF → SL in BAB55167. Ref.4
	Sequence conflict	429 – 431	3	SLK → DLM in CAB43280. Ref.8

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified May 1, 1999. Version 1. Checksum: F65CE58076961A7A	FASTA	444	52,259
	10 20 30 40 50 60 MGKGGNQGEG AAEREVSVPT FSWEEIQKHN LRTDRWLVID RKVYNITKWS IQHPGGQRVI 70 80 90 100 110 120 GHYAGEDATD AFRAFHPDLE FVGKFLKPLL IGELAPEEPS QDHGKNSKIT EDFRALRKTA 130 140 150 160 170 180 EDMNLFKTNH VFFLLLLAHI IALESIAWFT VFYFGNGWIP TLITAFVLAT SQAQAGWLQH 190 200 210 220 230 240 DYGHLSVYRK PKWNHLVHKF VIGHLKGASA NWWNHRHFQH HAKPNIFHKD PDVNMLHVFV 250 260 270 280 290 300 LGEWQPIEYG KKKLKYLPYN HQHEYFFLIG PPLLIPMYFQ YQIIMTMIVH KNWVDLAWAV 310 320 330 340 350 360 SYYIRFFITY IPFYGILGAL LFLNFIRFLE SHWFVWVTQM NHIVMEIDQE AYRDWFSSQL 370 380 390 400 410 420 TATCNVEQSF FNDWFSGHLN FQIEHHLFPT MPRHNLHKIA PLVKSLCAKH GIEYQEKPLL 430 440 RALLDIIRSL KKSGKLWLDA YLHK
	Isoform 2 [UniParc]. Checksum: A4A7EB76FBF1FFA4	FASTA	422	49,326
	10 20 30 40 50 60 MHGREAGPFV CVCVLLASIP TPQTPLLQAS LPPFHPASAG HPITGQQDAF RAFHPDLEFV 70 80 90 100 110 120 GKFLKPLLIG ELAPEEPSQD HGKNSKITED FRALRKTAED MNLFKTNHVF FLLLLAHIIA 130 140 150 160 170 180 LESIAWFTVF YFGNGWIPTL ITAFVLATSQ AQAGWLQHDY GHLSVYRKPK WNHLVHKFVI 190 200 210 220 230 240 GHLKGASANW WNHRHFQHHA KPNIFHKDPD VNMLHVFVLG EWQPIEYGKK KLKYLPYNHQ 250 260 270 280 290 300 HEYFFLIGPP LLIPMYFQYQ IIMTMIVHKN WVDLAWAVSY YIRFFITYIP FYGILGALLF 310 320 330 340 350 360 LNFIRFLESH WFVWVTQMNH IVMEIDQEAY RDWFSSQLTA TCNVEQSFFN DWFSGHLNFQ 370 380 390 400 410 420 IEHHLFPTMP RHNLHKIAPL VKSLCAKHGI EYQEKPLLRA LLDIIRSLKK SGKLWLDAYL HK
	Isoform 3 [UniParc]. Checksum: 2A18FA9CBFBFE432	FASTA	386	45,524
	10 20 30 40 50 60 MGKGGNQGEG AAEREVSVPT FSWEEIQKHN LRTDRWLVID RKVYNITKWS IQHPGGQRVI 70 80 90 100 110 120 GHYAGEDATD AFRAFHPDLE FVGKFLKPLL IGELAPEEPS QDHGKNSKIT EDFRALRKTA 130 140 150 160 170 180 EDMNLFKTNH VFFLLLLAHI IALESIAWFT VFYFGNGWIP TLITAFVLAT SQAQAGWLQH 190 200 210 220 230 240 DYGHLSVYRK PKWNHLVHKF VIGHLKGASA NWWNHRHFQH HAKPNIFHKD PDVNMLHVFV 250 260 270 280 290 300 LGEWQPIEYG KKKLKYLPYN HQHEYFFLIG PPLLIPMYFQ YQIIMTMIVH KNWVDLAWAV 310 320 330 340 350 360 SYYIRFFITY IPFYGILGAL LFLNFIRFLE SHWFVWVTQM NHIVMEIDQE AYRDWFSSQL 370 380 TATCNVEQSF FNDWFSGHLN FQIEHQ

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning, expression, and nutritional regulation of the mammalian Delta-6 desaturase." Cho H.P., Nakamura M.T., Clarke S.D. J. Biol. Chem. 274:471-477(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, TISSUE SPECIFICITY.
[2]	"cDNA cloning, genomic structure, and chromosomal localization of three members of the human fatty acid desaturase family." Marquardt A., Stoehr H., White K., Weber B.H. Genomics 66:175-183(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY.
[3]	Zhang J.S.S., Reddel R.R. Submitted (NOV-1998) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). Tissue: Mesothelium.
[4]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 277-444 (ISOFORMS 1/2). Tissue: Tongue.
[5]	"Signal sequence and keyword trap in silico for selection of full-length human cDNAs encoding secretion or membrane proteins from oligo-capped cDNA libraries." Otsuki T., Ota T., Nishikawa T., Hayashi K., Suzuki Y., Yamamoto J., Wakamatsu A., Kimura K., Sakamoto K., Hatano N., Kawai Y., Ishii S., Saito K., Kojima S., Sugiyama T., Ono T., Okano K., Yoshikawa Y. , Aotsuka S., Sasaki N., Hattori A., Okumura K., Nagai K., Sugano S., Isogai T. DNA Res. 12:117-126(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[6]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3). Tissue: Brain.
[8]	"The full-ORF clone resource of the German cDNA consortium." Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I. BMC Genomics 8:399-399(2007) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 134-444 (ISOFORMS 1/2). Tissue: Uterus.
[9]	"The E-box like sterol regulatory element mediates the suppression of human Delta-6 desaturase gene by highly unsaturated fatty acids." Nara T.Y., He W.S., Tang C., Clarke S.D., Nakamura M.T. Biochem. Biophys. Res. Commun. 296:111-117(2002) [PubMed] [Europe PMC] [Abstract] Cited for: INDUCTION.
[10]	"Identification of the delta-6 desaturase of human sebaceous glands: expression and enzyme activity." Ge L., Gordon J.S., Hsuan C., Stenn K., Prouty S.M. J. Invest. Dermatol. 120:707-714(2003) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[11]	Erratum Ge L., Gordon J.S., Hsuan C., Stenn K., Prouty S.M. J. Invest. Dermatol. 121:434-434(2003)
[12]	"Regulation of human delta-6 desaturase gene transcription: identification of a functional direct repeat-1 element." Tang C., Cho H.P., Nakamura M.T., Clarke S.D. J. Lipid Res. 44:686-695(2003) [PubMed] [Europe PMC] [Abstract] Cited for: INDUCTION.
[13]	"Expression of human delta-6-desaturase is associated with aggressiveness of human breast cancer." Lane J., Mansel R.E., Jiang W.G. Int. J. Mol. Med. 12:253-257(2003) [PubMed] [Europe PMC] [Abstract] Cited for: TISSUE SPECIFICITY.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF126799 mRNA. Translation: AAD20018.1. AF084559 mRNA. Translation: AAG23121.1. AF108658 mRNA. Translation: AAG43192.1. AK027513 mRNA. Translation: BAB55167.1. AK290291 mRNA. Translation: BAF82980.1. AK074939 mRNA. Translation: BAC11305.1. CH471076 Genomic DNA. Translation: EAW73975.1. BC009011 mRNA. Translation: AAH09011.1. AL050118 mRNA. Translation: CAB43280.1. BX640945 mRNA. Translation: CAE45971.1.
IPI	IPI00023484. IPI00183786. IPI00867558.
PIR	T13155.
RefSeq	NP_004256.1. NM_004265.2.
UniGene	Hs.502745.
3D structure databases
HSSP	HSSP built from PDB template 1SH4 based on UniProtKB P00171.
ProteinModelPortal	O95864.
ModBase	Search...
Protein-protein interaction databases
MINT	MINT-2866355.
STRING	9606.ENSP00000278840.
PTM databases
PhosphoSite	O95864.
Proteomic databases
PaxDb	O95864.
PeptideAtlas	O95864.
PRIDE	O95864.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000257261; ENSP00000257261; ENSG00000134824. ENST00000278840; ENSP00000278840; ENSG00000134824. ENST00000521849; ENSP00000431091; ENSG00000134824.
GeneID	9415.
KEGG	hsa:9415.
UCSC	uc001nsj.2. human. uc001nsk.3. human. uc001nsl.1. human.
Organism-specific databases
CTD	9415.
GeneCards	GC11P061583.
HGNC	HGNC:3575. FADS2.
HPA	HPA006741.
MIM	606149. gene.
neXtProt	NX_O95864.
PharmGKB	PA27974.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG5274.
HOVERGEN	HBG002839.
InParanoid	O95864.
KO	K10226.
OMA	VMESIAW.
PhylomeDB	O95864.
Enzyme and pathway databases
BioCyc	MetaCyc:HS05918-MONOMER.
Reactome	REACT_111217. Metabolism.
UniPathway	UPA00658.
Gene expression databases
ArrayExpress	O95864.
Bgee	O95864.
CleanEx	HS_FADS2.
Genevestigator	O95864.
Family and domain databases
Gene3D	3.10.120.10. 1 hit.
InterPro	IPR001199. Cyt_B5-like_heme/steroid-bd. IPR012171. Fatty_acid/sphinglp_desaturase. IPR005804. Fatty_acid_desaturase-1. [Graphical view]
Pfam	PF00173. Cyt-b5. 1 hit. PF00487. FA_desaturase. 1 hit. [Graphical view]
PIRSF	PIRSF015921. FA_sphinglp_des. 1 hit.
SUPFAM	SSF55856. Cyt_B5. 1 hit.
PROSITE	PS00191. CYTOCHROME_B5_1. False negative. PS50255. CYTOCHROME_B5_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
BindingDB	O95864.
ChEMBL	CHEMBL6097.
ChiTaRS	FADS2. human.
DrugBank	DB00132. Alpha-Linolenic Acid.
GenomeRNAi	9415.
NextBio	35274.
SOURCE	Search...

Entry information

Entry name

FADS2_HUMAN

Accession

Primary (citable) accession number: O95864
Secondary accession number(s): A8K2M6 , Q6MZQ7, Q96H07, Q96SV8, Q9H3G3, Q9Y3X4

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 2, 2007
Last sequence update:	May 1, 1999
Last modified:	May 1, 2013
This is version 101 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.