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   27-MAR-2024, entry version 165.
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   SMR; Q96K12; -.
DR   BioGRID; 120834; 47.
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; 9606-ENSP00000443291; -.
DR   PeptideAtlas; Q96K12; -.
DR   ProteomicsDB; 28799; -.
DR   ProteomicsDB; 77023; -. [Q96K12-1]
DR   Pumba; Q96K12; -.
DR   Antibodypedia; 2982; 106 antibodies from 19 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   AGR; HGNC:25531; -.
DR   CTD; 55711; -.
DR   DisGeNET; 55711; -.
DR   GeneCards; FAR2; -.
DR   HGNC; HGNC:25531; FAR2.
DR   HPA; ENSG00000064763; Tissue enhanced (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; NCILKHF; -.
DR   OrthoDB; 1434498at2759; -.
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 1163 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 149 other cell types or tissues.
DR   ExpressionAtlas; Q96K12; baseline and differential.
DR   GO; GO:0005778; C:peroxisomal membrane; IDA:UniProtKB.
DR   GO; GO:0005777; C:peroxisome; ISS:UniProtKB.
DR   GO; GO:0102965; F:alcohol-forming long-chain fatty acyl-CoA reductase activity; IEA:UniProtKB-EC.
DR   GO; GO:0080019; F:alcohol-forming very long-chain fatty acyl-CoA reductase activity; IDA:UniProtKB.
DR   GO; GO:0016491; F:oxidoreductase activity; TAS:Reactome.
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; cd05236; FAR-N_SDR_e; 1.
DR   CDD; cd09071; FAR_C; 1.
DR   Gene3D; 3.40.50.720; NAD(P)-binding Rossmann-like Domain; 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:SF117; FATTY ACYL-COA REDUCTASE 2; 1.
DR   PANTHER; PTHR11011; MALE STERILITY PROTEIN 2-RELATED; 1.
DR   Pfam; PF07993; NAD_binding_4; 1.
DR   Pfam; PF03015; Sterile; 1.
DR   SUPFAM; SSF51735; NAD(P)-binding Rossmann-fold domains; 1.
DR   Genevisible; Q96K12; HS.
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
//