Reviewed, UniProtKB/Swiss-Prot Q02928 (CP4AB_HUMAN)

Names and origin

Protein names

Recommended name:
    Cytochrome P450 4A11
Alternative name(s):
    CYPIVA11
    Lauric acid omega-hydroxylase
    EC=1.14.15.3
    Fatty acid omega-hydroxylase
    P-450 HK omega
    CYP4AII
    P450-HL-omega
    20-hydroxyeicosatetraenoic acid synthase
      Short name=20-HETE synthase

Gene names

Name:	CYP4A11
Synonyms:	CYP4A2

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	519 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Catalyzes the omega- and (omega-1)-hydroxylation of various fatty acids such as laurate, myristate and palmitate. Has little activity toward prostaglandins A1 and E1. Oxidizes arachidonic acid to 20-hydroxyeicosatetraenoic acid (20-HETE). Ref.12
Catalytic activity	Octane + reduced rubredoxin + O2 = 1-octanol + oxidized rubredoxin + H2O.
Cofactor	Heme group By similarity.
Subcellular location	Endoplasmic reticulum membrane; Peripheral membrane protein. Microsome membrane; Peripheral membrane protein.
Tissue specificity	Kidney and liver.
Polymorphism	CYP4A11v seems to be a rare allelic variant of CYP4A11, it seems to be unstable and not to metabolize lauric acid.
Sequence similarities	Belongs to the cytochrome P450 family.

Ontologies

Keywords
Cellular component	Endoplasmic reticulum Membrane Microsome
Coding sequence diversity	Alternative splicing Polymorphism
Ligand	Heme Iron Metal-binding
Molecular function	Monooxygenase Oxidoreductase
Technical term	Complete proteome Direct protein sequencing
Gene Ontology (GO)
Biological process	fatty acid metabolic process Ref.1 Traceable author statement. Source: ProtInc oxidation reduction Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	endoplasmic reticulum membrane Inferred from Experiment. Source: Reactome microsome Ref.3 Traceable author statement. Source: ProtInc
Molecular function	alkane 1-monooxygenase activity Inferred from electronic annotation. Source: EC electron carrier activity Inferred from electronic annotation. Source: InterPro fatty acid (omega-1)-hydroxylase activity Ref.1 Traceable author statement. Source: ProtInc heme binding Inferred from electronic annotation. Source: InterPro oxygen binding Inferred from Experiment. Source: Reactome
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q02928-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: Q02928-2)

The sequence of this isoform differs from the canonical sequence as follows:
     356-519: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Propeptide	1 – 4	4	Ref.2 Ref.8		PRO_0000003579
	Chain	5 – 519	515	Cytochrome P450 4A11		PRO_0000003580
Regions
	Compositional bias	24 – 31	8	Poly-Leu
	Compositional bias	131 – 134	4	Poly-Leu
Sites
	Metal binding	457	1	Iron (heme axial ligand)
	Binding site	321	1	Heme (covalent; via 1 link)
Natural variations
	Alternative sequence	356 – 519	164	Missing in isoform 2.		VSP_034595
	Natural variant	226	1	N → S: dbSNP rs12759923.		VAR_048452
	Natural variant	353	1	S → G Ref.9 Ref.13		VAR_044377
	Natural variant	434	1	F → S Associated with hypertension; significantly reduced arachidonic acid and lauric acid metabolizing activity. dbSNP rs1126742. Ref.12 Ref.9 Ref.13 Ref.3 Ref.5		VAR_019160
	Natural variant	500 – 519	20	NGIHL…DKDQL → MESTCVSGGSLTLVKTRTSF EGLHLPSCLPDPRFCPLPVC PYPVFCLPTFPSSHLPAVPQ SACPSLSHLSPGLPTCLSTC LLPTCISCWEKS in CYP4A11V.		VAR_001257
Experimental info
	Mutagenesis	130	1	G → S: Loss of activity. Ref.12
	Mutagenesis	321	1	E → A: Loss of covalent heme binding. Ref.11
	Sequence conflict	5	1	V → A AA sequence Ref.8
	Sequence conflict	383	1	Y → F in AAO16078. Ref.4
	Sequence conflict	390	1	G → S in CAA50586. Ref.9
	Sequence conflict	410 – 412	3	MVL → TVM in CAA50586. Ref.9

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified November 1, 1997. Version 1. Checksum: A8D3073EEFF48AE9	FASTA	519	59,348
	10 20 30 40 50 60 MSVSVLSPSR LLGDVSGILQ AASLLILLLL LIKAVQLYLH RQWLLKALQQ FPCPPSHWLF 70 80 90 100 110 120 GHIQELQQDQ ELQRIQKWVE TFPSACPHWL WGGKVRVQLY DPDYMKVILG RSDPKSHGSY 130 140 150 160 170 180 RFLAPWIGYG LLLLNGQTWF QHRRMLTPAF HYDILKPYVG LMADSVRVML DKWEELLGQD 190 200 210 220 230 240 SPLEVFQHVS LMTLDTIMKC AFSHQGSIQV DRNSQSYIQA ISDLNNLVFS RVRNAFHQND 250 260 270 280 290 300 TIYSLTSAGR WTHRACQLAH QHTDQVIQLR KAQLQKEGEL EKIKRKRHLD FLDILLLAKM 310 320 330 340 350 360 ENGSILSDKD LRAEVDTFMF EGHDTTASGI SWILYALATH PKHQERCREE IHSLLGDGAS 370 380 390 400 410 420 ITWNHLDQMP YTTMCIKEAL RLYPPVPGIG RELSTPVTFP DGRSLPKGIM VLLSIYGLHH 430 440 450 460 470 480 NPKVWPNPEV FDPFRFAPGS AQHSHAFLPF SGGSRNCIGK QFAMNELKVA TALTLLRFEL 490 500 510 LPDPTRIPIP IARLVLKSKN GIHLRLRRLP NPCEDKDQL
	Isoform 2. Checksum: A108E4661ACF9824	FASTA	355	41,052
	10 20 30 40 50 60 MSVSVLSPSR LLGDVSGILQ AASLLILLLL LIKAVQLYLH RQWLLKALQQ FPCPPSHWLF 70 80 90 100 110 120 GHIQELQQDQ ELQRIQKWVE TFPSACPHWL WGGKVRVQLY DPDYMKVILG RSDPKSHGSY 130 140 150 160 170 180 RFLAPWIGYG LLLLNGQTWF QHRRMLTPAF HYDILKPYVG LMADSVRVML DKWEELLGQD 190 200 210 220 230 240 SPLEVFQHVS LMTLDTIMKC AFSHQGSIQV DRNSQSYIQA ISDLNNLVFS RVRNAFHQND 250 260 270 280 290 300 TIYSLTSAGR WTHRACQLAH QHTDQVIQLR KAQLQKEGEL EKIKRKRHLD FLDILLLAKM 310 320 330 340 350 ENGSILSDKD LRAEVDTFMF EGHDTTASGI SWILYALATH PKHQERCREE IHSLL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Characterization of a cDNA encoding a human kidney, cytochrome P-450 4A fatty acid omega-hydroxylase and the cognate enzyme expressed in Escherichia coli." Palmer C.N.A., Richardson T.H., Griffin K.J., Hsu M.-H., Muerhoff A.S., Clark J.E., Johnson E.F. Biochim. Biophys. Acta 1172:161-166(1993) [PubMed: 7679927] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), CHARACTERIZATION. Tissue: Kidney.
[2]	"Purification and cDNA cloning of human liver CYP4A fatty acid omega-hydroxylase." Kawashima H., Kusunose E., Kikuta Y., Kinoshita H., Tanaka S., Yamamoto S., Kishimoto T., Kusunose M. J. Biochem. 116:74-80(1994) [PubMed: 7798189] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PROTEIN SEQUENCE OF 5-24, CHARACTERIZATION. Tissue: Liver.
[3]	"Complete cDNA sequence and cDNA-directed expression of CYP4A11, a fatty acid omega-hydroxylase expressed in human kidney." Imaoka S., Ogawa H., Kimura S., Gonzalez F.J. DNA Cell Biol. 12:893-899(1993) [PubMed: 8274222] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT SER-434, CHARACTERIZATION. Tissue: Kidney.
[4]	"Characterization of the CYP4A11 gene, a second CYP4A gene in humans." Bellamine A., Wang Y., Waterman M.R., Gainer J.V. III, Dawson E.P., Brown N.J., Capdevila J.H. Arch. Biochem. Biophys. 409:221-227(2003) [PubMed: 12464262] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[5]	SeattleSNPs variation discovery resource Submitted (AUG-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1), VARIANT SER-434.
[6]	"The DNA sequence and biological annotation of human chromosome 1." Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R. Nature 441:315-321(2006) [PubMed: 16710414] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Tissue: Colon.
[8]	"Purification and NH2-terminal amino acid sequences of human and rat kidney fatty acid omega-hydroxylases." Kawashima H., Kusunose E., Kubota I., Maekawa M., Kusunose M. Biochim. Biophys. Acta 1123:156-162(1992) [PubMed: 1739747] [Abstract] Cited for: PARTIAL PROTEIN SEQUENCE OF 5-39, CHARACTERIZATION. Tissue: Kidney.
[9]	"Species-specific induction of cytochrome P-450 4A RNAs: PCR cloning of partial guinea-pig, human and mouse CYP4A cDNAs." Bell D.R., Plant N.J., Rider C.G., Na L., Brown S., Ateitalla I., Acharya S.K., Davies M.H., Elias E.E., Jenkins N.A., Gilbert D.J., Copeland N.G., Elcombe C.R. Biochem. J. 294:173-180(1993) [PubMed: 8363569] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 317-457, VARIANTS GLY-353 AND SER-434. Tissue: Liver.
[10]	"Covalently linked heme in cytochrome P4504A fatty acid hydroxylases." Hoch U., Ortiz de Montellano P.R. J. Biol. Chem. 276:11339-11346(2001) [PubMed: 11139583] [Abstract] Cited for: COVALENT HEME ATTACHMENT.
[11]	"Autocatalytic mechanism and consequences of covalent heme attachment in the cytochrome P4504A family." LeBrun L.A., Hoch U., Ortiz de Montellano P.R. J. Biol. Chem. 277:12755-12761(2002) [PubMed: 11821421] [Abstract] Cited for: COVALENT HEME ATTACHMENT, MUTAGENESIS OF GLU-321.
[12]	"Functional variant of CYP4A11 20-hydroxyeicosatetraenoic acid synthase is associated with essential hypertension." Gainer J.V., Bellamine A., Dawson E.P., Womble K.E., Grant S.W., Wang Y., Cupples L.A., Guo C.-Y., Demissie S., O'Donnell C.J., Brown N.J., Waterman M.R., Capdevila J.H. Circulation 111:63-69(2005) [PubMed: 15611369] [Abstract] Cited for: FUNCTION, MUTAGENESIS OF GYL-130, VARIANT SER-434.
[13]	"Highly polymorphic human CYP4A11 gene." Cho B.H., Park B.L., Kim L.H., Chung H.S., Shin H.D. J. Hum. Genet. 50:259-263(2005) [PubMed: 15895287] [Abstract] Cited for: VARIANTS GLY-353 AND SER-434.
+	Additional computationally mapped references.

Web resources

Cytochrome P450 Allele Nomenclature Committee

CYP4A11 alleles

SeattleSNPs

Cross-references

Sequence databases
EMBLGenBankDDBJ	L04751 mRNA. Translation: AAA58436.1. D26481 mRNA. Translation: BAA05491.1. S67580 mRNA. Translation: AAB29502.1. S67581 mRNA. Translation: AAB29503.1. AF525488 Genomic DNA. Translation: AAO16078.1. AY369778 Genomic DNA. Translation: AAQ56847.1. AL731892 Genomic DNA. Translation: CAH72778.1. AL731892 Genomic DNA. Translation: CAH72779.1. BC041158 mRNA. Translation: AAH41158.1. X71480 mRNA. Translation: CAA50586.1.
IPI	IPI00646318. IPI00872799.
PIR	A56859. I53015. I65981. JX0331.
RefSeq	NP_000769.2.
UniGene	Hs.1645 Hs.567807
3D structure databases
HSSP	HSSP built from PDB template 1JPZ based on UniProtKB P14779.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q02928. 1 interaction.
Proteomic databases
PRIDE	Q02928.
Genome annotation databases
Ensembl	ENSG00000187048. Homo sapiens. [Contig view]
GeneID	1579.
KEGG	hsa:1579.
UCSC	uc001cqp.2. human. uc001cqq.2. human.
Organism-specific databases
GeneCards	GC01M047106.
H-InvDB	HIX0023641. HIX0028676.
HGNC	HGNC:2642. CYP4A11.
MIM	601310. gene.
PharmGKB	PA27118.
GenAtlas	Search...
Phylogenomic databases
HOVERGEN	Q02928.
Enzyme and pathway databases
BRENDA	1.14.15.3. 247.
Reactome	REACT_13433. Biological oxidations. REACT_649. Phase 1 functionalization.
Gene expression databases
Bgee	Q02928.
CleanEx	HS_CYP4A11.
GermOnline	ENSG00000187048. Homo sapiens.
Family and domain databases
InterPro	IPR001128. Cyt_P450. IPR017973. Cyt_P450_C. IPR017972. Cyt_P450_CS. IPR002401. Cyt_P450_E_grp-I. [Graphical view]
Gene3D	G3DSA:1.10.630.10. Cyt_P450. 1 hit.
PANTHER	PTHR19383. Cyt_P450. 1 hit.
Pfam	PF00067. p450. 1 hit. [Graphical view]
PRINTS	PR00463. EP450I. PR00385. P450.
PROSITE	PS00086. CYTOCHROME_P450. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
DrugBank	DB00157. NADH.
NextBio	6485.
SOURCE	Search...

Entry information

Entry name

CP4AB_HUMAN

Accession

Primary (citable) accession number: Q02928
Secondary accession number(s): Q06766 , Q16865, Q16866, Q5VSP8, Q86SU6, Q8IWY5

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	November 1, 1997
Last modified:	July 7, 2009
This is version 87 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)