Reviewed, UniProtKB/Swiss-Prot Q5TCH4 (CP4AM_HUMAN)

Names and origin

Protein names

Recommended name:
    Cytochrome P450 4A22
Alternative name(s):
    CYPIVA22
    Lauric acid omega-hydroxylase
    EC=1.14.15.3
    Fatty acid omega-hydroxylase

Gene names

Name:

CYP4A22

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 and palmitate. Shows no activity towards arachidonic acid and prostaglandin A1. Lacks functional activity in the kidney and does not contribute to renal 20-hydroxyeicosatetraenoic acid (20-HETE) biosynthesis. Ref.1 Ref.2
Catalytic activity	Octane + reduced rubredoxin + O2 = 1-octanol + oxidized rubredoxin + H2O.
Subcellular location	Endoplasmic reticulum membrane; Peripheral membrane protein By similarity. Microsome membrane; Peripheral membrane protein By similarity.
Sequence similarities	Belongs to the cytochrome P450 family.
Caution	Was originally (Ref.1) termed CYP4A11.
Biophysicochemical properties	Kinetic parameters: Vmax:15.2 µmol/min/µmol enzyme. KM=56.7 µM for laurate

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
Gene Ontology (GO)
Biological process	oxidation reduction Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	endoplasmic reticulum Inferred from electronic annotation. Source: UniProtKB-KW extrinsic to membrane Inferred from electronic annotation. Source: UniProtKB-SubCell microsome Inferred from electronic annotation. Source: UniProtKB-KW
Molecular function	alkane 1-monooxygenase activity Inferred from electronic annotation. Source: EC electron carrier activity Inferred from electronic annotation. Source: InterPro heme binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Alternative products

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

Isoform 1 (identifier: Q5TCH4-1)

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: Q5TCH4-2)

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	By similarity		PRO_0000343408
	Chain	5 – 519	515	Cytochrome P450 4A22		PRO_0000343409
Regions
	Compositional bias	24 – 31	8	Poly-Leu
	Compositional bias	131 – 134	4	Poly-Leu
Sites
	Metal binding	457	1	Iron (heme axial ligand) By similarity
	Binding site	321	1	Heme (covalent; via 1 link) By similarity
Natural variations
	Alternative sequence	356 – 519	164	Missing in isoform 2.		VSP_034584
	Natural variant	11	1	R → C in allele CYP4A22*2 and CYP4A22*3. Ref.5		VAR_044349
	Natural variant	104	1	Y → F: dbSNP rs61507155.		VAR_061045
	Natural variant	121	1	K → R: dbSNP rs2758717. Ref.1		VAR_044350
	Natural variant	126	1	R → W in allele CYP4A22*8, allele CYP4A22*9, allele CYP4A22*11, allele CYP4A22*12, allele CYP4A22*13, allele CYP4A22*14 and allele CYP4A22*15. dbSNP rs12564525. Ref.2 Ref.5		VAR_044351
	Natural variant	130	1	G → S in allele CYP4A22*4, allele CYP4A22*10, allele CYP4A22*12, allele CYP4A22*13, allele CYP4A22*14 and allele CYP4A22*15. dbSNP rs2056900. Ref.2 Ref.5		VAR_044352
	Natural variant	152	1	N → Y in allele CYP4A22*2, allele CYP4A22*3, allele CYP4A22*4, allele CYP4A22*5, allele CYP4A22*6, allele CYP4A22*7, allele CYP4A22*8, allele CYP4A22*9, allele CYP4A22*10, allele CYP4A22*11, allele CYP4A22*12, allele CYP4A22*13, allele CYP4A22*14 and allele CYP4A22*15. dbSNP rs2056899. Ref.2 Ref.5		VAR_044353
	Natural variant	185	1	V → F in allele CYP4A22*10, allele CYP4A22*11, allele CYP4A22*12, allele CYP4A22*13, allele CYP4A22*14 and allele CYP4A22*15. Ref.5		VAR_044354
	Natural variant	226	1	S → N: dbSNP rs35202523. Ref.2		VAR_044355
	Natural variant	230	1	C → S: dbSNP rs35156123. Ref.2		VAR_044356
	Natural variant	231	1	C → R Allele CYP4A22*2, allele CYP4A22*3, allele CYP4A22*4, allele CYP4A22*5, allele CYP4A22*6, allele CYP4A22*7, allele CYP4A22*8, allele CYP4A22*9, allele CYP4A22*10, allele CYP4A22*11, allele CYP4A22*12, allele CYP4A22*13, allele CYP4A22*14 and allele CYP4A22*15. dbSNP rs10789501. Ref.2 Ref.5		VAR_044357
	Natural variant	276	1	K → T in allele CYP4A22*8, allele CYP4A22*11, allele CYP4A22*14 and allele CYP4A22*15. Ref.5		VAR_044358
	Natural variant	428	1	L → P in allele CYP4A22*6, allele CYP4A22*9, allele CYP4A22*10, allele CYP4A22*12, allele CYP4A22*13 and allele CYP4A22*15. dbSNP rs2405599. Ref.2 Ref.5		VAR_044359
	Natural variant	491	1	M → I: dbSNP rs2758714. Ref.1		VAR_044360
	Natural variant	509	1	L → F in allele CYP4A22*7, allele CYP4A22*10, allele CYP4A22*11, allele CYP4A22*13, allele CYP4A22*14 and allele CYP4A22*15. dbSNP rs4926600. Ref.2 Ref.5		VAR_044361
Experimental info
	Sequence conflict	2	1	S → A in AAQ21368. Ref.2
	Sequence conflict	114	1	P → S in AAQ21368. Ref.2
	Sequence conflict	225	1	N → S in AAQ21368. Ref.2
	Sequence conflict	232	1	M → V in AAQ21367. Ref.2
	Sequence conflict	238	1	E → Q in AAQ21367. Ref.2
	Sequence conflict	241	1	T → A in AAQ21368. Ref.2
	Sequence conflict	353	1	G → S in AAQ21367. Ref.2
	Sequence conflict	434	1	S → F in AAQ21367. Ref.2
	Sequence conflict	487	1	I → T in AAQ21367. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified December 21, 2004. Version 1. Checksum: AA96444A38EE79BC	FASTA	519	59,246
	10 20 30 40 50 60 MSVSVLSPSR RLGGVSGILQ VTSLLILLLL LIKAAQLYLH RQWLLKALQQ FPCPPSHWLF 70 80 90 100 110 120 GHIQEFQHDQ ELQRIQERVK TFPSACPYWI WGGKVRVQLY DPDYMKVILG RSDPKSHGSY 130 140 150 160 170 180 KFLAPRIGYG LLLLNGQTWF QHRRMLTPAF HNDILKPYVG LMADSVRVML DKWEELLGQD 190 200 210 220 230 240 SPLEVFQHVS LMTLDTIMKS AFSHQGSIQV DRNSQSYIQA ISDLNSLVFC CMRNAFHEND 250 260 270 280 290 300 TIYSLTSAGR WTHRACQLAH QHTDQVIQLR KAQLQKEGEL EKIKRKRHLD FLDILLLAKM 310 320 330 340 350 360 ENGSILSDKD LRAEVDTFMF EGHDTTASGI SWILYALATH PKHQERCREE IHGLLGDGAS 370 380 390 400 410 420 ITWNHLDQMP YTTMCIKEAL RLYPPVPGIG RELSTPVTFP DGRSLPKGIM VLLSIYGLHH 430 440 450 460 470 480 NPKVWPNLEV FDPSRFAPGS AQHSHAFLPF SGGSRNCIGK QFAMNQLKVA RALTLLRFEL 490 500 510 LPDPTRIPIP MARLVLKSKN GIHLRLRRLP NPCEDKDQL
	Isoform 2. Checksum: 392C812A7C120920	FASTA	355	40,922
	10 20 30 40 50 60 MSVSVLSPSR RLGGVSGILQ VTSLLILLLL LIKAAQLYLH RQWLLKALQQ FPCPPSHWLF 70 80 90 100 110 120 GHIQEFQHDQ ELQRIQERVK TFPSACPYWI WGGKVRVQLY DPDYMKVILG RSDPKSHGSY 130 140 150 160 170 180 KFLAPRIGYG LLLLNGQTWF QHRRMLTPAF HNDILKPYVG LMADSVRVML DKWEELLGQD 190 200 210 220 230 240 SPLEVFQHVS LMTLDTIMKS AFSHQGSIQV DRNSQSYIQA ISDLNSLVFC CMRNAFHEND 250 260 270 280 290 300 TIYSLTSAGR WTHRACQLAH QHTDQVIQLR KAQLQKEGEL EKIKRKRHLD FLDILLLAKM 310 320 330 340 350 ENGSILSDKD LRAEVDTFMF EGHDTTASGI SWILYALATH PKHQERCREE IHGLL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Human fatty acid omega-hydroxylase, CYP4A11: determination of complete genomic sequence and characterization of purified recombinant protein." Kawashima H., Naganuma T., Kusunose E., Kono T., Yasumoto R., Sugimura K., Kishimoto T. Arch. Biochem. Biophys. 378:333-339(2000) [PubMed: 10860550] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1), FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, VARIANTS ARG-121 AND ILE-491.
[2]	"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: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, VARIANTS TRP-126; SER-130; TYR-152; ASN-226; SER-230; ARG-231; PRO-428 AND PHE-509. Tissue: Kidney and Liver.
[3]	"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].
[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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[5]	"Genetic polymorphisms and haplotype structures of the CYP4A22 gene in a Japanese population." Hiratsuka M., Nozawa H., Katsumoto Y., Moteki T., Sasaki T., Konno Y., Mizugaki M. Mutat. Res. 599:98-104(2006) [PubMed: 16806293] [Abstract] Cited for: VARIANTS CYS-11; TRP-126; SER-130; TYR-152; PHE-185; ARG-231; THR-276; PRO-428 AND PHE-509.
+	Additional computationally mapped references.

Web resources

Cytochrome P450 Allele Nomenclature Committee

CYP4A22 alleles

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF208532 Genomic DNA. Translation: AAF76722.1. AY280371 mRNA. Translation: AAQ21367.1. AY280372 mRNA. Translation: AAQ21368.1. AL135960 Genomic DNA. Translation: CAI19737.1. AL135960 Genomic DNA. Translation: CAI19738.1. BC148248 mRNA. Translation: AAI48249.1.
IPI	IPI00429358. IPI00647932.
RefSeq	NP_001010969.2.
UniGene	Hs.1645 Hs.714775
3D structure databases
HSSP	HSSP built from PDB template 1W0F based on UniProtKB P08684.
ModBase	Search...
Protein-protein interaction databases
STRING	Q5TCH4.
Proteomic databases
PRIDE	Q5TCH4.
Genome annotation databases
Ensembl	ENST00000371891; ENSP00000360958; ENSG00000162365; Homo sapiens. [Genome view]
GeneID	284541.
KEGG	hsa:284541.
UCSC	uc001cqv.1. human. uc009vyo.1. human.
Organism-specific databases
CTD	284541.
GeneCards	GC01P047314. GC01P047375.
HGNC	HGNC:20575. CYP4A22.
PharmGKB	PA134979692.
GenAtlas	Search...
Phylogenomic databases
HOGENOM	HBG505954.
HOVERGEN	Q5TCH4.
InParanoid	Q5TCH4.
OMA	RNAFHEN.
OrthoDB	EOG9XWJH2.
PhylomeDB	Q5TCH4.
Enzyme and pathway databases
Reactome	REACT_602. Metabolism of lipids and lipoproteins.
Gene expression databases
ArrayExpress	Q5TCH4.
Bgee	Q5TCH4.
Genevestigator	Q5TCH4.
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
NextBio	94950.

Entry information

Entry name

CP4AM_HUMAN

Accession

Primary (citable) accession number: Q5TCH4
Secondary accession number(s): Q5TCH3 , Q6JXK7, Q6JXK8, Q9NRM4

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 1, 2008
Last sequence update:	December 21, 2004
Last modified:	January 19, 2010
This is version 51 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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.