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Q7L5A8 (FA2H_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 103. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Fatty acid 2-hydroxylase

EC=1.-.-.-
Alternative name(s):
Fatty acid alpha-hydroxylase
Gene names
Name:FA2H
Synonyms:FAAH
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length372 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Required for alpha-hydroxylation of free fatty acids and the formation of alpha-hydroxylated sphingolipids. Ref.6 Ref.7

Cofactor

Iron By similarity.

Subcellular location

Endoplasmic reticulum membrane; Multi-pass membrane protein. Microsome membrane; Multi-pass membrane protein Ref.6.

Tissue specificity

Detected in differentiating cultured keratinocytes (at protein level). Detected in epidermis and cultured keratinocytes. Highly expressed in brain and colon. Detected at lower levels in testis, prostate, pancreas and kidney. Ref.6 Ref.7

Induction

Up-regulated during keratinocyte differentiation. Ref.7

Domain

The histidine box domains may contain the active site and/or be involved in metal ion binding.

Involvement in disease

Spastic paraplegia 35, autosomal recessive (SPG35) [MIM:612319]: A form of spastic paraplegia, a neurodegenerative disorder characterized by a slow, gradual, progressive weakness and spasticity of the lower limbs. Rate of progression and the severity of symptoms are quite variable. Initial symptoms may include difficulty with balance, weakness and stiffness in the legs, muscle spasms, and dragging the toes when walking. In some forms of the disorder, bladder symptoms (such as incontinence) may appear, or the weakness and stiffness may spread to other parts of the body. SPG35 is a complicated form characterized by childhood onset of gait difficulties. It has a rapid progression and many patients become wheelchair-bound as young adults. Patients manifest cognitive decline associated with leukodystrophy. Other variable neurologic features, such as dystonia, optic atrophy, and seizures may also occur.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.8 Ref.9 Ref.10

Sequence similarities

Belongs to the sterol desaturase family. SCS7 subfamily.

Contains 1 cytochrome b5 heme-binding domain.

Sequence caution

The sequence AAC23496.1 differs from that shown. Reason: Erroneous gene model prediction.

Ontologies

Keywords
   Biological processElectron transport
Fatty acid biosynthesis
Fatty acid metabolism
Lipid biosynthesis
Lipid metabolism
Transport
   Cellular componentEndoplasmic reticulum
Membrane
Microsome
   Coding sequence diversityPolymorphism
   DiseaseDisease mutation
Hereditary spastic paraplegia
Leukodystrophy
Neurodegeneration
   DomainTransmembrane
Transmembrane helix
   LigandHeme
Iron
Metal-binding
   Molecular functionOxidoreductase
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processcell death

Inferred from electronic annotation. Source: UniProtKB-KW

central nervous system myelin maintenance

Inferred from electronic annotation. Source: Ensembl

fatty acid biosynthetic process

Inferred from electronic annotation. Source: UniProtKB-KW

lipid modification

Inferred from electronic annotation. Source: Ensembl

peripheral nervous system myelin maintenance

Inferred from electronic annotation. Source: Ensembl

regulation of cell proliferation

Inferred from electronic annotation. Source: Ensembl

regulation of hair cycle

Inferred from electronic annotation. Source: Ensembl

sebaceous gland cell differentiation

Inferred from electronic annotation. Source: Ensembl

sphingolipid metabolic process

Inferred from electronic annotation. Source: InterPro

   Cellular_componentendoplasmic reticulum membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

integral component of membrane

Inferred from electronic annotation. Source: UniProtKB-KW

   Molecular_functionfatty acid alpha-hydroxylase activity

Inferred from electronic annotation. Source: Ensembl

heme binding

Inferred from electronic annotation. Source: InterPro

iron ion binding

Inferred from electronic annotation. Source: InterPro

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 372372Fatty acid 2-hydroxylase
PRO_0000312349

Regions

Transmembrane168 – 18821Helical; Potential
Transmembrane213 – 23321Helical; Potential
Transmembrane268 – 28821Helical; Potential
Transmembrane290 – 31021Helical; Potential
Domain8 – 8679Cytochrome b5 heme-binding

Sites

Metal binding431Iron (heme axial ligand) By similarity
Metal binding691Iron (heme axial ligand) By similarity

Natural variations

Natural variant351D → Y in SPG35; patients present spastic paraparesis associated with leukodystrophy and dystonia. Ref.8
VAR_054893
Natural variant53 – 586Missing in SPG35; significantly reduced enzymatic function.
VAR_064620
Natural variant971P → A.
Corresponds to variant rs35874850 [ dbSNP | Ensembl ].
VAR_037503
Natural variant1541R → C in SPG35. Ref.9
VAR_065245
Natural variant2351R → C in SPG35; significantly reduced enzymatic function. Ref.10
VAR_064621

Experimental info

Sequence conflict1841S → G in BAB71632. Ref.1
Sequence conflict3561D → G in BAB71632. Ref.1

Sequences

Sequence LengthMass (Da)Tools
Q7L5A8 [UniParc].

Last modified November 23, 2004. Version 1.
Checksum: 3F56B4C689B317BE

FASTA37242,791
        10         20         30         40         50         60 
MAPAPPPAAS FSPSEVQRRL AAGACWVRRG ARLYDLSSFV RHHPGGEQLL RARAGQDISA 

        70         80         90        100        110        120 
DLDGPPHRHS ANARRWLEQY YVGELRGEQQ GSMENEPVAL EETQKTDPAM EPRFKVVDWD 

       130        140        150        160        170        180 
KDLVDWRKPL LWQVGHLGEK YDEWVHQPVT RPIRLFHSDL IEGLSKTVWY SVPIIWVPLV 

       190        200        210        220        230        240 
LYLSWSYYRT FAQGNVRLFT SFTTEYTVAV PKSMFPGLFM LGTFLWSLIE YLIHRFLFHM 

       250        260        270        280        290        300 
KPPSDSYYLI MLHFVMHGQH HKAPFDGSRL VFPPVPASLV IGVFYLCMQL ILPEAVGGTV 

       310        320        330        340        350        360 
FAGGLLGYVL YDMTHYYLHF GSPHKGSYLY SLKAHHVKHH FAHQKSGFGI STKLWDYCFH 

       370 
TLTPEKPHLK TQ 

« Hide

References

« Hide 'large scale' references
[1]"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. expand/collapse author list , 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].
Tissue: Gastric mucosa.
[2]"Genome duplications and other features in 12 Mb of DNA sequence from human chromosome 16p and 16q."
Loftus B.J., Kim U.-J., Sneddon V.P., Kalush F., Brandon R., Fuhrmann J., Mason T., Crosby M.L., Barnstead M., Cronin L., Mays A.D., Cao Y., Xu R.X., Kang H.-L., Mitchell S., Eichler E.E., Harris P.C., Venter J.C., Adams M.D.
Genomics 60:295-308(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]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. expand/collapse author list , 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 (DEC-2006) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]"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].
Tissue: Colon and Pancreas.
[5]"Cloning of human fatty acid hydroxylase."
Van Veldhoven P.P.
Submitted (MAY-2000) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 93-372.
[6]"The human FA2H gene encodes a fatty acid 2-hydroxylase."
Alderson N.L., Rembiesa B.M., Walla M.D., Bielawska A., Bielawski J., Hama H.
J. Biol. Chem. 279:48562-48568(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[7]"Fatty acid 2-hydroxylase, encoded by FA2H, accounts for differentiation-associated increase in 2-OH ceramides during keratinocyte differentiation."
Uchida Y., Hama H., Alderson N.L., Douangpanya S., Wang Y., Crumrine D.A., Elias P.M., Holleran W.M.
J. Biol. Chem. 282:13211-13219(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INDUCTION, TISSUE SPECIFICITY.
[8]"Mutations in the fatty acid 2-hydroxylase gene are associated with leukodystrophy with spastic paraparesis and dystonia."
Edvardson S., Hama H., Shaag A., Gomori J.M., Berger I., Soffer D., Korman S.H., Taustein I., Saada A., Elpeleg O.
Am. J. Hum. Genet. 83:643-648(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT SPG35 TYR-35.
[9]"Defective FA2H leads to a novel form of neurodegeneration with brain iron accumulation (NBIA)."
Kruer M.C., Paisan-Ruiz C., Boddaert N., Yoon M.Y., Hama H., Gregory A., Malandrini A., Woltjer R.L., Munnich A., Gobin S., Polster B.J., Palmeri S., Edvardson S., Hardy J., Houlden H., Hayflick S.J.
Ann. Neurol. 68:611-618(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT SPG35 CYS-154.
[10]"Mutation of FA2H underlies a complicated form of hereditary spastic paraplegia (SPG35)."
Dick K.J., Eckhardt M., Paisan-Ruiz C., Alshehhi A.A., Proukakis C., Sibtain N.A., Maier H., Sharifi R., Patton M.A., Bashir W., Koul R., Raeburn S., Gieselmann V., Houlden H., Crosby A.H.
Hum. Mutat. 31:E1251-E1260(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS SPG35 53-ARG--ILE-58 DEL AND CYS-235, CHARACTERIZATION OF VARIANTS SPG35 53-ARG--ILE-58 DEL AND CYS-235.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AK058016 mRNA. Translation: BAB71632.1.
AC004685 Genomic DNA. Translation: AAC23496.1. Sequence problems.
CH471114 Genomic DNA. Translation: EAW95678.1.
BC002679 mRNA. Translation: AAH02679.2.
BC004263 mRNA. Translation: AAH04263.2.
BC017049 mRNA. Translation: AAH17049.2.
AJ278219 mRNA. Translation: CAC20436.1.
CCDSCCDS10911.1.
RefSeqNP_077282.3. NM_024306.4.
UniGeneHs.461329.

3D structure databases

ProteinModelPortalQ7L5A8.
SMRQ7L5A8. Positions 12-115.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid122570. 1 interaction.
MINTMINT-2876220.
STRING9606.ENSP00000219368.

Polymorphism databases

DMDM74749893.

Proteomic databases

MaxQBQ7L5A8.
PaxDbQ7L5A8.
PRIDEQ7L5A8.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000219368; ENSP00000219368; ENSG00000103089.
GeneID79152.
KEGGhsa:79152.
UCSCuc002fde.2. human.

Organism-specific databases

CTD79152.
GeneCardsGC16M074746.
GeneReviewsFA2H.
HGNCHGNC:21197. FA2H.
MIM611026. gene.
612319. phenotype.
neXtProtNX_Q7L5A8.
Orphanet171629. Autosomal recessive spastic paraplegia type 35.
329308. Fatty acid hydroxylase-associated neurodegeneration.
PharmGKBPA145148065.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG3000.
HOGENOMHOG000023981.
HOVERGENHBG054265.
InParanoidQ7L5A8.
OMAMKAHHVK.
OrthoDBEOG71P2BJ.
PhylomeDBQ7L5A8.
TreeFamTF314955.

Enzyme and pathway databases

BioCycMetaCyc:ENSG00000103089-MONOMER.

Gene expression databases

ArrayExpressQ7L5A8.
BgeeQ7L5A8.
CleanExHS_FA2H.
GenevestigatorQ7L5A8.

Family and domain databases

Gene3D3.10.120.10. 1 hit.
InterProIPR001199. Cyt_B5-like_heme/steroid-bd.
IPR018506. Cyt_B5_heme-BS.
IPR006694. Fatty_acid_hydroxylase.
IPR014430. Ino-phos-ceramide-B_Hydrxlase.
[Graphical view]
PfamPF00173. Cyt-b5. 1 hit.
PF04116. FA_hydroxylase. 1 hit.
[Graphical view]
PIRSFPIRSF005149. IPC-B_HD. 1 hit.
PRINTSPR00363. CYTOCHROMEB5.
SUPFAMSSF55856. SSF55856. 1 hit.
PROSITEPS00191. CYTOCHROME_B5_1. 1 hit.
PS50255. CYTOCHROME_B5_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiFA2H.
GenomeRNAi79152.
NextBio68068.
PROQ7L5A8.
SOURCESearch...

Entry information

Entry nameFA2H_HUMAN
AccessionPrimary (citable) accession number: Q7L5A8
Secondary accession number(s): O75213, Q96DK1, Q9H1A5
Entry history
Integrated into UniProtKB/Swiss-Prot: December 4, 2007
Last sequence update: November 23, 2004
Last modified: July 9, 2014
This is version 103 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 16

Human chromosome 16: entries, gene names and cross-references to MIM