FACR2_HUMAN
ID FACR2_HUMAN Reviewed; 515 AA.
AC Q96K12; F8VV73; Q9H0D5; Q9NVW8;
DT 28-NOV-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2001, sequence version 1.
DT 03-AUG-2022, entry version 156.
DE RecName: Full=Fatty acyl-CoA reductase 2 {ECO:0000305|PubMed:15220348};
DE EC=1.2.1.84 {ECO:0000269|PubMed:15220348};
DE AltName: Full=Male sterility domain-containing protein 1 {ECO:0000312|HGNC:HGNC:25531};
GN Name=FAR2 {ECO:0000312|HGNC:HGNC:25531};
GN Synonyms=MLSTD1 {ECO:0000312|HGNC:HGNC:25531};
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 [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Testis;
RX PubMed=11230166; DOI=10.1101/gr.gr1547r;
RA Wiemann S., Weil B., Wellenreuther R., Gassenhuber J., Glassl S.,
RA Ansorge W., Boecher M., Bloecker H., Bauersachs S., Blum H., Lauber J.,
RA Duesterhoeft A., Beyer A., Koehrer K., Strack N., Mewes H.-W.,
RA Ottenwaelder B., Obermaier B., Tampe J., Heubner D., Wambutt R., Korn B.,
RA Klein M., Poustka A.;
RT "Towards a catalog of human genes and proteins: sequencing and analysis of
RT 500 novel complete protein coding human cDNAs.";
RL Genome Res. 11:422-435(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Heart, Placenta, and Teratocarcinoma;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16541075; DOI=10.1038/nature04569;
RA Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y.,
RA Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C.,
RA Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C.,
RA Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R.,
RA Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E.,
RA Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y.,
RA Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G.,
RA Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H.,
RA Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S.,
RA Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M.,
RA Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H.,
RA Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q.,
RA Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V.,
RA Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E.,
RA Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K.,
RA Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D.,
RA Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R.,
RA David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E.,
RA D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N.,
RA Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N.,
RA Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R.,
RA Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S.,
RA LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H.,
RA Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P.,
RA Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G.,
RA Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E.,
RA Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S.,
RA Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O.,
RA Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J.,
RA Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A.,
RA Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M.,
RA Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I.,
RA Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A.,
RA Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y.,
RA Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A.,
RA Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F.,
RA Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L.,
RA Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G.,
RA Gibbs R.A.;
RT "The finished DNA sequence of human chromosome 12.";
RL Nature 440:346-351(2006).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Placenta;
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 FUNCTION, CATALYTIC ACTIVITY, AND SUBCELLULAR LOCATION.
RX PubMed=15220348; DOI=10.1074/jbc.m406225200;
RA Cheng J.B., Russell D.W.;
RT "Mammalian wax biosynthesis: I. Identification of two fatty acyl-coenzyme A
RT reductases with different substrate specificities and tissue
RT distributions.";
RL J. Biol. Chem. 279:37789-37797(2004).
RN [6]
RP SUBCELLULAR LOCATION, AND TOPOLOGY.
RX PubMed=24108123; DOI=10.1074/jbc.m113.498345;
RA Honsho M., Asaoku S., Fukumoto K., Fujiki Y.;
RT "Topogenesis and homeostasis of fatty acyl-CoA reductase 1.";
RL J. Biol. Chem. 288:34588-34598(2013).
CC -!- FUNCTION: Catalyzes the reduction of saturated but not unsaturated C16
CC or C18 fatty acyl-CoA to fatty alcohols. A lower activity can be
CC observed with shorter fatty acyl-CoA substrates (PubMed:15220348). It
CC may play a role in the production of ether lipids/plasmalogens and wax
CC monoesters which synthesis requires fatty alcohols as substrates (By
CC similarity). {ECO:0000250|UniProtKB:Q8WVX9,
CC ECO:0000269|PubMed:15220348}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a long-chain fatty acyl-CoA + 2 H(+) + 2 NADPH = a long-chain
CC primary fatty alcohol + CoA + 2 NADP(+); Xref=Rhea:RHEA:52716,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57287, ChEBI:CHEBI:57783,
CC ChEBI:CHEBI:58349, ChEBI:CHEBI:77396, ChEBI:CHEBI:83139; EC=1.2.1.84;
CC Evidence={ECO:0000269|PubMed:15220348};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:52717;
CC Evidence={ECO:0000305|PubMed:15220348};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2 H(+) + hexadecanoyl-CoA + 2 NADPH = CoA + hexadecan-1-ol + 2
CC NADP(+); Xref=Rhea:RHEA:36315, ChEBI:CHEBI:15378, ChEBI:CHEBI:16125,
CC ChEBI:CHEBI:57287, ChEBI:CHEBI:57379, ChEBI:CHEBI:57783,
CC ChEBI:CHEBI:58349; EC=1.2.1.84;
CC Evidence={ECO:0000269|PubMed:15220348};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:36316;
CC Evidence={ECO:0000305|PubMed:15220348};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2 H(+) + 2 NADPH + octadecanoyl-CoA = CoA + 2 NADP(+) +
CC octadecan-1-ol; Xref=Rhea:RHEA:36319, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:32154, ChEBI:CHEBI:57287, ChEBI:CHEBI:57394,
CC ChEBI:CHEBI:57783, ChEBI:CHEBI:58349; EC=1.2.1.84;
CC Evidence={ECO:0000250|UniProtKB:Q7TNT2};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:36320;
CC Evidence={ECO:0000250|UniProtKB:Q7TNT2};
CC -!- SUBCELLULAR LOCATION: Peroxisome membrane {ECO:0000269|PubMed:15220348,
CC ECO:0000269|PubMed:24108123}; Single-pass membrane protein
CC {ECO:0000305|PubMed:24108123}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q96K12-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q96K12-2; Sequence=VSP_055648;
CC -!- SIMILARITY: Belongs to the fatty acyl-CoA reductase family.
CC {ECO:0000305}.
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DR EMBL; AL136843; CAB66777.1; -; mRNA.
DR EMBL; AK001324; BAA91625.1; -; mRNA.
DR EMBL; AK027756; BAB55347.1; -; mRNA.
DR EMBL; AK129857; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; AC009318; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC012150; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC022267; AAH22267.1; -; mRNA.
DR CCDS; CCDS61084.1; -. [Q96K12-2]
DR CCDS; CCDS8717.1; -. [Q96K12-1]
DR RefSeq; NP_001258712.1; NM_001271783.1. [Q96K12-1]
DR RefSeq; NP_060569.3; NM_018099.4. [Q96K12-1]
DR AlphaFoldDB; Q96K12; -.
DR BioGRID; 120834; 44.
DR IntAct; Q96K12; 12.
DR STRING; 9606.ENSP00000443291; -.
DR SwissLipids; SLP:000000209; -.
DR iPTMnet; Q96K12; -.
DR PhosphoSitePlus; Q96K12; -.
DR BioMuta; FAR2; -.
DR DMDM; 74732166; -.
DR EPD; Q96K12; -.
DR jPOST; Q96K12; -.
DR MassIVE; Q96K12; -.
DR MaxQB; Q96K12; -.
DR PaxDb; Q96K12; -.
DR PeptideAtlas; Q96K12; -.
DR PRIDE; Q96K12; -.
DR ProteomicsDB; 28799; -.
DR ProteomicsDB; 77023; -. [Q96K12-1]
DR Antibodypedia; 2982; 91 antibodies from 18 providers.
DR DNASU; 55711; -.
DR Ensembl; ENST00000182377.8; ENSP00000182377.4; ENSG00000064763.12. [Q96K12-1]
DR Ensembl; ENST00000536681.8; ENSP00000443291.2; ENSG00000064763.12. [Q96K12-1]
DR Ensembl; ENST00000547116.5; ENSP00000449349.1; ENSG00000064763.12. [Q96K12-2]
DR Ensembl; ENST00000690162.1; ENSP00000510233.1; ENSG00000064763.12. [Q96K12-2]
DR GeneID; 55711; -.
DR KEGG; hsa:55711; -.
DR MANE-Select; ENST00000536681.8; ENSP00000443291.2; NM_001271783.2; NP_001258712.1.
DR UCSC; uc001ris.6; human. [Q96K12-1]
DR CTD; 55711; -.
DR DisGeNET; 55711; -.
DR GeneCards; FAR2; -.
DR HGNC; HGNC:25531; FAR2.
DR HPA; ENSG00000064763; Tissue enhanced (epididymis, intestine).
DR MIM; 616156; gene.
DR neXtProt; NX_Q96K12; -.
DR OpenTargets; ENSG00000064763; -.
DR PharmGKB; PA162388036; -.
DR VEuPathDB; HostDB:ENSG00000064763; -.
DR eggNOG; KOG1221; Eukaryota.
DR GeneTree; ENSGT00390000006367; -.
DR HOGENOM; CLU_024661_0_0_1; -.
DR InParanoid; Q96K12; -.
DR OMA; WLEYTEN; -.
DR OrthoDB; 815047at2759; -.
DR PhylomeDB; Q96K12; -.
DR TreeFam; TF313011; -.
DR PathwayCommons; Q96K12; -.
DR Reactome; R-HSA-9640463; Wax biosynthesis.
DR SignaLink; Q96K12; -.
DR BioGRID-ORCS; 55711; 164 hits in 1085 CRISPR screens.
DR ChiTaRS; FAR2; human.
DR GenomeRNAi; 55711; -.
DR Pharos; Q96K12; Tbio.
DR PRO; PR:Q96K12; -.
DR Proteomes; UP000005640; Chromosome 12.
DR RNAct; Q96K12; protein.
DR Bgee; ENSG00000064763; Expressed in upper leg skin and 147 other tissues.
DR ExpressionAtlas; Q96K12; baseline and differential.
DR Genevisible; Q96K12; HS.
DR GO; GO:0005779; C:integral component of peroxisomal membrane; IDA:UniProtKB.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IBA:GO_Central.
DR GO; GO:0005778; C:peroxisomal membrane; TAS:Reactome.
DR GO; GO:0005777; C:peroxisome; ISS:UniProtKB.
DR GO; GO:0102965; F:alcohol-forming fatty acyl-CoA reductase activity; IEA:UniProtKB-EC.
DR GO; GO:0080019; F:fatty-acyl-CoA reductase (alcohol-forming) activity; IDA:UniProtKB.
DR GO; GO:0016491; F:oxidoreductase activity; TAS:Reactome.
DR GO; GO:0006629; P:lipid metabolic process; IEA:UniProtKB-KW.
DR GO; GO:0035336; P:long-chain fatty-acyl-CoA metabolic process; IDA:UniProtKB.
DR GO; GO:0010025; P:wax biosynthetic process; TAS:Reactome.
DR CDD; cd09071; FAR_C; 1.
DR InterPro; IPR026055; FAR.
DR InterPro; IPR033640; FAR_C.
DR InterPro; IPR013120; Far_NAD-bd.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR PANTHER; PTHR11011; PTHR11011; 1.
DR Pfam; PF07993; NAD_binding_4; 1.
DR Pfam; PF03015; Sterile; 1.
DR SUPFAM; SSF51735; SSF51735; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Lipid biosynthesis; Lipid metabolism; Membrane; NADP;
KW Oxidoreductase; Peroxisome; Reference proteome; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..515
FT /note="Fatty acyl-CoA reductase 2"
FT /id="PRO_0000261401"
FT TOPO_DOM 1..464
FT /note="Cytoplasmic"
FT /evidence="ECO:0000269|PubMed:24108123"
FT TRANSMEM 465..484
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 485..515
FT /note="Peroxisomal"
FT /evidence="ECO:0000269|PubMed:24108123"
FT VAR_SEQ 1..97
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_055648"
FT CONFLICT 51
FT /note="T -> A (in Ref. 1; CAB66777)"
FT /evidence="ECO:0000305"
FT CONFLICT 167
FT /note="I -> T (in Ref. 2; BAA91625)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 515 AA; 59438 MW; 6EFC67ED29796094 CRC64;
MSTIAAFYGG KSILITGATG FLGKVLMEKL FRTSPDLKVI YILVRPKAGQ TLQQRVFQIL
DSKLFEKVKE VCPNVHEKIR AIYADLNQND FAISKEDMQE LLSCTNIIFH CAATVRFDDT
LRHAVQLNVT ATRQLLLMAS QMPKLEAFIH ISTAYSNCNL KHIDEVIYPC PVEPKKIIDS
LEWLDDAIID EITPKLIRDW PNIYTYTKAL GEMVVQQESR NLNIAIIRPS IVGATWQEPF
PGWVDNINGP NGIIIATGKG FLRAIKATPM AVADVIPVDT VVNLMLAVGW YTAVHRPKST
LVYHITSGNM NPCNWHKMGV QVLATFEKIP FERPFRRPNA NFTSNSFTSQ YWNAVSHRAP
AIIYDCYLRL TGRKPRMTKL MNRLLRTVSM LEYFINRSWE WSTYNTEMLM SELSPEDQRV
FNFDVRQLNW LEYIENYVLG VKKYLLKEDM AGIPKAKQRL KRLRNIHYLF NTALFLIAWR
LLIARSQMAR NVWFFIVSFC YKFLSYFRAS STLKV
