FA2H_RAT
ID FA2H_RAT Reviewed; 372 AA.
AC Q2LAM0;
DT 04-DEC-2007, integrated into UniProtKB/Swiss-Prot.
DT 04-DEC-2007, sequence version 2.
DT 03-AUG-2022, entry version 103.
DE RecName: Full=Fatty acid 2-hydroxylase {ECO:0000303|PubMed:17901466};
DE EC=1.14.18.- {ECO:0000250|UniProtKB:Q7L5A8, ECO:0000305|PubMed:17901466};
DE AltName: Full=Fatty acid alpha-hydroxylase {ECO:0000303|PubMed:17901466};
GN Name=Fa2h {ECO:0000303|PubMed:17901466, ECO:0000312|RGD:1310347};
GN Synonyms=Faah;
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] OF 1-347.
RC STRAIN=Wistar;
RA Molto E., Bonzon-Kulichenko E., Gallardo N., Andres A.;
RL Submitted (DEC-2005) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 254-372.
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 [3]
RP TISSUE SPECIFICITY.
RX PubMed=16998236; DOI=10.1194/jlr.m600362-jlr200;
RA Alderson N.L., Maldonado E.N., Kern M.J., Bhat N.R., Hama H.;
RT "FA2H-dependent fatty acid 2-hydroxylation in postnatal mouse brain.";
RL J. Lipid Res. 47:2772-2780(2006).
RN [4]
RP FUNCTION, INDUCTION, DEVELOPMENTAL STAGE, TISSUE SPECIFICITY, PATHWAY, AND
RP CATALYTIC ACTIVITY.
RX PubMed=17901466; DOI=10.1194/jlr.m700400-jlr200;
RA Maldonado E.N., Alderson N.L., Monje P.V., Wood P.M., Hama H.;
RT "FA2H is responsible for the formation of 2-hydroxy galactolipids in
RT peripheral nervous system myelin.";
RL J. Lipid Res. 49:153-161(2008).
CC -!- FUNCTION: Catalyzes the hydroxylation of free fatty acids at the C-2
CC position to produce 2-hydroxy fatty acids, which are building blocks of
CC sphingolipids and glycosphingolipids common in neural tissue and
CC epidermis (Probable). FA2H is stereospecific for the production of (R)-
CC 2-hydroxy fatty acids (By similarity). Plays an essential role in the
CC synthesis of galactosphingolipids of the myelin sheath
CC (PubMed:17901466). Responsible for the synthesis of sphingolipids and
CC glycosphingolipids involved in the formation of epidermal lamellar
CC bodies critical for skin permeability barrier (By similarity).
CC Participates in the synthesis of glycosphingolipids and a fraction of
CC type II wax diesters in sebaceous gland, specifically regulating hair
CC follicle homeostasis. Involved in the synthesis of sphingolipids of
CC plasma membrane rafts, controlling lipid raft mobility and trafficking
CC of raft-associated proteins (By similarity).
CC {ECO:0000250|UniProtKB:Q5MPP0, ECO:0000250|UniProtKB:Q7L5A8,
CC ECO:0000269|PubMed:17901466, ECO:0000305|PubMed:17901466}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 1,2-saturated fatty acid + 2 Fe(II)-[cytochrome b5] + 2 H(+)
CC + O2 = a (R)-2-hydroxy fatty acid + 2 Fe(III)-[cytochrome b5] + H2O;
CC Xref=Rhea:RHEA:38855, 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:76177,
CC ChEBI:CHEBI:83955; Evidence={ECO:0000250|UniProtKB:Q7L5A8,
CC ECO:0000305|PubMed:17901466};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38856;
CC Evidence={ECO:0000250|UniProtKB:Q7L5A8};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2 Fe(II)-[cytochrome b5] + 2 H(+) + hexadecanoate + O2 = (R)-
CC 2-hydroxyhexadecanoate + 2 Fe(III)-[cytochrome b5] + H2O;
CC Xref=Rhea:RHEA:38551, Rhea:RHEA-COMP:10438, Rhea:RHEA-COMP:10439,
CC ChEBI:CHEBI:7896, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:29033, ChEBI:CHEBI:29034,
CC ChEBI:CHEBI:75927; Evidence={ECO:0000250|UniProtKB:Q7L5A8};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38552;
CC Evidence={ECO:0000250|UniProtKB:Q7L5A8};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2 Fe(II)-[cytochrome b5] + 2 H(+) + O2 + octadecanoate = (R)-
CC 2-hydroxyoctadecanoate + 2 Fe(III)-[cytochrome b5] + H2O;
CC Xref=Rhea:RHEA:39815, Rhea:RHEA-COMP:10438, Rhea:RHEA-COMP:10439,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:25629, ChEBI:CHEBI:29033, ChEBI:CHEBI:29034,
CC ChEBI:CHEBI:57562; Evidence={ECO:0000250|UniProtKB:Q7L5A8};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:39816;
CC Evidence={ECO:0000250|UniProtKB:Q7L5A8};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=docosanoate + 2 Fe(II)-[cytochrome b5] + 2 H(+) + O2 = 2-
CC hydroxydocosanoate + 2 Fe(III)-[cytochrome b5] + H2O;
CC Xref=Rhea:RHEA:39819, Rhea:RHEA-COMP:10438, Rhea:RHEA-COMP:10439,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:23858, ChEBI:CHEBI:29033, ChEBI:CHEBI:29034,
CC ChEBI:CHEBI:76722; Evidence={ECO:0000250|UniProtKB:Q7L5A8};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:39820;
CC Evidence={ECO:0000250|UniProtKB:Q7L5A8};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2 Fe(II)-[cytochrome b5] + 2 H(+) + O2 + tetracosanoate = (R)-
CC 2-hydroxytetracosanoate + 2 Fe(III)-[cytochrome b5] + H2O;
CC Xref=Rhea:RHEA:38559, 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:31014,
CC ChEBI:CHEBI:75935; Evidence={ECO:0000250|UniProtKB:Q7L5A8,
CC ECO:0000305|PubMed:17901466};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:38560;
CC Evidence={ECO:0000250|UniProtKB:Q7L5A8, ECO:0000305|PubMed:17901466};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000250|UniProtKB:Q03529};
CC Note=Binds 2 Zn(2+) ions per subunit that likely form a catalytic
CC dimetal center. {ECO:0000250|UniProtKB:Q03529};
CC -!- PATHWAY: Lipid metabolism; fatty acid metabolism.
CC {ECO:0000269|PubMed:17901466}.
CC -!- PATHWAY: Sphingolipid metabolism; galactosylceramide biosynthesis.
CC {ECO:0000269|PubMed:17901466}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:Q7L5A8}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:Q7L5A8}. Microsome membrane
CC {ECO:0000250|UniProtKB:Q7L5A8}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:Q7L5A8}.
CC -!- TISSUE SPECIFICITY: Detected in oligodendrocytes (at protein level).
CC Detected in sciatic nerve. {ECO:0000269|PubMed:16998236,
CC ECO:0000269|PubMed:17901466}.
CC -!- DEVELOPMENTAL STAGE: Detected at low levels in sciatic nerve from
CC newborns. Levels increase strongly during the first 3 weeks, and
CC decrease thereafter to reach a low, constitutive level in 4 week olds.
CC Expressed at a low, constitutive level in adults.
CC {ECO:0000269|PubMed:17901466}.
CC -!- INDUCTION: Up-regulated in sciatic nerve during myelination. Up-
CC regulated in differentiating cultured Schwann cells.
CC {ECO:0000269|PubMed:17901466}.
CC -!- DOMAIN: The histidine box domains may contain the active site and/or be
CC involved in metal ion binding.
CC -!- DOMAIN: The N-terminal cytochrome b5 heme-binding domain is essential
CC for catalytic activity. {ECO:0000250|UniProtKB:Q7L5A8}.
CC -!- SIMILARITY: Belongs to the sterol desaturase family. SCS7 subfamily.
CC {ECO:0000305}.
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DR EMBL; DQ339484; ABC71132.1; -; mRNA.
DR EMBL; CO396956; -; NOT_ANNOTATED_CDS; mRNA.
DR RefSeq; NP_001129055.1; NM_001135583.1.
DR AlphaFoldDB; Q2LAM0; -.
DR SMR; Q2LAM0; -.
DR STRING; 10116.ENSRNOP00000025625; -.
DR SwissLipids; SLP:000001975; -.
DR PaxDb; Q2LAM0; -.
DR Ensembl; ENSRNOT00000025625; ENSRNOP00000025625; ENSRNOG00000018950.
DR GeneID; 307855; -.
DR KEGG; rno:307855; -.
DR UCSC; RGD:1310347; rat.
DR CTD; 79152; -.
DR RGD; 1310347; Fa2h.
DR eggNOG; KOG0537; Eukaryota.
DR eggNOG; KOG0539; Eukaryota.
DR GeneTree; ENSGT00390000002142; -.
DR HOGENOM; CLU_034756_2_0_1; -.
DR InParanoid; Q2LAM0; -.
DR OMA; HFADYEN; -.
DR OrthoDB; 1049908at2759; -.
DR PhylomeDB; Q2LAM0; -.
DR TreeFam; TF314955; -.
DR Reactome; R-RNO-1660661; Sphingolipid de novo biosynthesis.
DR UniPathway; UPA00199; -.
DR UniPathway; UPA00787; -.
DR PRO; PR:Q2LAM0; -.
DR Proteomes; UP000002494; Chromosome 19.
DR Bgee; ENSRNOG00000018950; Expressed in stomach and 9 other tissues.
DR Genevisible; Q2LAM0; RN.
DR GO; GO:0005783; C:endoplasmic reticulum; ISO:RGD.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0016020; C:membrane; ISS:UniProtKB.
DR GO; GO:0080132; F:fatty acid alpha-hydroxylase activity; IMP:UniProtKB.
DR GO; GO:0020037; F:heme binding; IEA:InterPro.
DR GO; GO:0005506; F:iron ion binding; IEA:InterPro.
DR GO; GO:0032286; P:central nervous system myelin maintenance; ISO:RGD.
DR GO; GO:0046513; P:ceramide biosynthetic process; ISS:UniProtKB.
DR GO; GO:0061436; P:establishment of skin barrier; ISS:UniProtKB.
DR GO; GO:0006633; P:fatty acid biosynthetic process; IEA:UniProtKB-KW.
DR GO; GO:0006631; P:fatty acid metabolic process; ISO:RGD.
DR GO; GO:0006682; P:galactosylceramide biosynthetic process; IMP:UniProtKB.
DR GO; GO:0006679; P:glucosylceramide biosynthetic process; ISS:UniProtKB.
DR GO; GO:0030258; P:lipid modification; ISO:RGD.
DR GO; GO:0032287; P:peripheral nervous system myelin maintenance; ISO:RGD.
DR GO; GO:0044857; P:plasma membrane raft organization; ISS:UniProtKB.
DR GO; GO:1904697; P:regulation of acinar cell proliferation; IEA:Ensembl.
DR GO; GO:0042127; P:regulation of cell population proliferation; ISO:RGD.
DR GO; GO:0042634; P:regulation of hair cycle; ISO:RGD.
DR GO; GO:1904002; P:regulation of sebum secreting cell proliferation; IEA:Ensembl.
DR GO; GO:0001949; P:sebaceous gland cell differentiation; ISO:RGD.
DR Gene3D; 3.10.120.10; -; 1.
DR InterPro; IPR001199; Cyt_B5-like_heme/steroid-bd.
DR InterPro; IPR036400; Cyt_B5-like_heme/steroid_sf.
DR InterPro; IPR018506; Cyt_B5_heme-BS.
DR InterPro; IPR006694; Fatty_acid_hydroxylase.
DR InterPro; IPR014430; Scs7.
DR PANTHER; PTHR12863; PTHR12863; 1.
DR Pfam; PF00173; Cyt-b5; 1.
DR Pfam; PF04116; FA_hydroxylase; 1.
DR PIRSF; PIRSF005149; IPC-B_HD; 1.
DR PRINTS; PR00363; CYTOCHROMEB5.
DR SMART; SM01117; Cyt-b5; 1.
DR SUPFAM; SSF55856; SSF55856; 1.
DR PROSITE; PS00191; CYTOCHROME_B5_1; 1.
DR PROSITE; PS50255; CYTOCHROME_B5_2; 1.
PE 1: Evidence at protein level;
KW Endoplasmic reticulum; Fatty acid biosynthesis; Fatty acid metabolism;
KW Heme; Iron; Lipid biosynthesis; Lipid metabolism; Membrane; Metal-binding;
KW Microsome; Oxidoreductase; Reference proteome; Sphingolipid metabolism;
KW Transmembrane; Transmembrane helix; Zinc.
FT CHAIN 1..372
FT /note="Fatty acid 2-hydroxylase"
FT /id="PRO_0000312352"
FT TRANSMEM 168..188
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 213..233
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 268..288
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 290..310
FT /note="Helical"
FT /evidence="ECO:0000255"
FT DOMAIN 8..86
FT /note="Cytochrome b5 heme-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00279"
FT DOMAIN 219..361
FT /note="Fatty acid hydroxylase"
FT /evidence="ECO:0000255"
FT BINDING 43
FT /ligand="heme"
FT /ligand_id="ChEBI:CHEBI:30413"
FT /ligand_part="Fe"
FT /ligand_part_id="ChEBI:CHEBI:18248"
FT /note="axial binding residue"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00279"
FT BINDING 69
FT /ligand="heme"
FT /ligand_id="ChEBI:CHEBI:30413"
FT /ligand_part="Fe"
FT /ligand_part_id="ChEBI:CHEBI:18248"
FT /note="axial binding residue"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00279"
FT BINDING 234
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q03529"
FT BINDING 239
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q03529"
FT BINDING 257
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q03529"
FT BINDING 260
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q03529"
FT BINDING 261
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q03529"
FT BINDING 315
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q03529"
FT BINDING 319
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q03529"
FT BINDING 336
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q03529"
FT BINDING 339
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q03529"
FT BINDING 340
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q03529"
SQ SEQUENCE 372 AA; 42673 MW; AC02C568DF1BF7A6 CRC64;
MAPAPPPAAS FTSAEVQRRL AAGACWVRRG ASLYDLTGFV RHHPGGEQLL LARAGQDISA
DLDGPPHKHS DNARRWLEQY YVGELRADPQ DPTENGAGAP AETQKTDAAI EPQFKVVDWD
KDLVDWQKPL LWQVGHLGEK YDEWVHQPVA RPIRLFHSDL IEAFSKTVWY SVPIIWVPLV
LYLSWSYYRT LTQDNIRLFA SFTRDYSLVV PESVFIGLFV LGMLIWTLVE YLIHRFLFHM
KPPSNSHYLI MLHFVMHGQH HKAPFDGSRL VFPPVPASVV VAFFYVFLRL ILPEAVAGIL
FAGGLLGYVL YDMTHYYLHF GSPHKGSYLY NMKAHHVKHH FEYQKSGFGI STKLWDYFFH
TLIPEEADPK MQ
