Q7L5A8 (FA2H_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Fatty acid 2-hydroxylase
EC=1.-.-.-

Alternative name(s):
Fatty acid alpha-hydroxylase

Gene names

Name:	FA2H
Synonyms:	FAAH

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	372 AA.
Sequence status	Complete.
Protein existence	Evidence 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 autosomal recessive 35 (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 process	Electron transport Fatty acid biosynthesis Fatty acid metabolism Lipid biosynthesis Lipid metabolism Transport
Cellular component	Endoplasmic reticulum Membrane Microsome
Coding sequence diversity	Polymorphism
Disease	Disease mutation Hereditary spastic paraplegia Leukodystrophy Neurodegeneration
Domain	Transmembrane Transmembrane helix
Ligand	Heme Iron Metal-binding
Molecular function	Oxidoreductase
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cell death Inferred from electronic annotation. Source: UniProtKB-KW central nervous system myelin maintenance Inferred from electronic annotation. Source: Compara electron transport chain Inferred from electronic annotation. Source: UniProtKB-KW fatty acid biosynthetic process Inferred from electronic annotation. Source: UniProtKB-KW lipid modification Inferred from electronic annotation. Source: Compara peripheral nervous system myelin maintenance Inferred from electronic annotation. Source: Compara regulation of cell proliferation Inferred from electronic annotation. Source: Compara regulation of hair cycle Inferred from electronic annotation. Source: Compara sebaceous gland cell differentiation Inferred from electronic annotation. Source: Compara sphingolipid metabolic process Inferred from electronic annotation. Source: InterPro
Cellular_component	endoplasmic reticulum membrane Inferred from electronic annotation. Source: UniProtKB-SubCell integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW
Molecular_function	fatty acid alpha-hydroxylase activity Inferred from electronic annotation. Source: Compara heme binding Inferred from electronic annotation. Source: InterPro iron ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 372	372	Fatty acid 2-hydroxylase		PRO_0000312349
Regions
	Transmembrane	168 – 188	21	Helical; Potential
	Transmembrane	213 – 233	21	Helical; Potential
	Transmembrane	268 – 288	21	Helical; Potential
	Transmembrane	290 – 310	21	Helical; Potential
	Domain	8 – 86	79	Cytochrome b5 heme-binding
Sites
	Metal binding	43	1	Iron (heme axial ligand) By similarity
	Metal binding	69	1	Iron (heme axial ligand) By similarity
Natural variations
	Natural variant	35	1	D → Y in SPG35; patients present spastic paraparesis associated with leukodystrophy and dystonia. Ref.8		VAR_054893
	Natural variant	53 – 58	6	Missing in SPG35; significantly reduced enzymatic function.		VAR_064620
	Natural variant	97	1	P → A. Corresponds to variant rs35874850 [ dbSNP | Ensembl ].		VAR_037503
	Natural variant	154	1	R → C in SPG35. Ref.9		VAR_065245
	Natural variant	235	1	R → C in SPG35; significantly reduced enzymatic function. Ref.10		VAR_064621
Experimental info
	Sequence conflict	184	1	S → G in BAB71632. Ref.1
	Sequence conflict	356	1	D → G in BAB71632. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Q7L5A8 [UniParc]. Last modified November 23, 2004. Version 1. Checksum: 3F56B4C689B317BE	FASTA	372	42,791
	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

References

	« Hide 'large scale' referencesShow '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. , 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. , 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.
IPI	IPI00304492.
RefSeq	NP_077282.3. NM_024306.4.
UniGene	Hs.461329.
3D structure databases
HSSP	HSSP built from PDB template 1ICC based on UniProtKB P04166.
ProteinModelPortal	Q7L5A8.
ModBase	Search...
Protein-protein interaction databases
MINT	MINT-2876220.
STRING	9606.ENSP00000219368.
Polymorphism databases
DMDM	74749893.
Proteomic databases
PaxDb	Q7L5A8.
PRIDE	Q7L5A8.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000219368; ENSP00000219368; ENSG00000103089.
GeneID	79152.
KEGG	hsa:79152.
UCSC	uc002fde.2. human.
Organism-specific databases
CTD	79152.
GeneCards	GC16M074746.
HGNC	HGNC:21197. FA2H.
MIM	611026. gene. 612319. phenotype.
neXtProt	NX_Q7L5A8.
Orphanet	171629. Autosomal recessive spastic paraplegia type 35. 35069. Infantile neuroaxonal dystrophy. 171857. Leukodystrophy - spastic paraplegia - dystonia.
PharmGKB	PA145148065.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG3000.
HOGENOM	HOG000023981.
HOVERGEN	HBG054265.
InParanoid	Q7L5A8.
OMA	THYYLHF.
OrthoDB	EOG4PK28C.
PhylomeDB	Q7L5A8.
Gene expression databases
ArrayExpress	Q7L5A8.
Bgee	Q7L5A8.
CleanEx	HS_FA2H.
Genevestigator	Q7L5A8.
Family and domain databases
Gene3D	3.10.120.10. 1 hit.
InterPro	IPR001199. Cyt_B5-like_heme/steroid-bd. IPR018506. Cyt_B5_heme-BS. IPR006694. Fatty_acid_hydroxylase. IPR014430. Ino-phos-ceramide-B_Hydrxlase. [Graphical view]
Pfam	PF00173. Cyt-b5. 1 hit. PF04116. FA_hydroxylase. 1 hit. [Graphical view]
PIRSF	PIRSF005149. IPC-B_HD. 1 hit.
PRINTS	PR00363. CYTOCHROMEB5.
SUPFAM	SSF55856. Cyt_B5. 1 hit.
PROSITE	PS00191. CYTOCHROME_B5_1. 1 hit. PS50255. CYTOCHROME_B5_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	79152.
NextBio	68068.
SOURCE	Search...

Entry information

Entry name

FA2H_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 93 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.