Q6ZWL3 (CP4V2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Cytochrome P450 4V2
EC=1.14.13.-

Gene names

Name:

CYP4V2

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	525 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Catalyzes the omega-hydroxylation of medium-chain saturated fatty acids such as laurate, myristate and palmitate in an NADPH-dependent pathway. The substrate specificity is higher for myristate > laurate > palmitate (C14>C16>C12). May have a role in fatty acid and steroid metabolism in the eye. Ref.6
Cofactor	Heme group By similarity.
Enzyme regulation	Inhibited by N-hydroxy-N'-(4-n-butyl-2-methylphenyl formamidine)(HET0016) with an IC50 of 38 nM. Ref.6
Subcellular location	Endoplasmic reticulum membrane; Single-pass membrane protein Potential.
Tissue specificity	Broadly expressed. Detected in heart, brain, placenta, lung, liver, skeletal muscle, kidney, pancreas, retina, retinal pigment epithelium (RPE) and lymphocytes. Ref.1
Involvement in disease	Bietti crystalline corneoretinal dystrophy (BCD) [MIM:210370]: An autosomal recessive ocular disease characterized by retinal degeneration and marginal corneal dystrophy. Typical features include multiple glistening intraretinal crystals scattered over the fundus, a characteristic degeneration of the retina, and sclerosis of the choroidal vessels, ultimately resulting in progressive night blindness and constriction of the visual field. Most patients have similar crystals at the corneoscleral limbus. Patients develop decreased vision, nyctalopia, and paracentral scotomata between the 2nd and 4th decade of life. Later, they develop peripheral visual field loss and marked visual impairment, usually progressing to legal blindness by the 5th or 6th decade of life. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.1
Sequence similarities	Belongs to the cytochrome P450 family.
Biophysicochemical properties	Kinetic parameters: Vmax is the nearly the same for myristic acid and for lauric acid and reduced about 30% for palmitic acid. KM=65 µM for myristic acid Ref.6 KM=140 µM for lauric acid KM=430 µM for palmitic acid

Ontologies

Keywords
Biological process	Sensory transduction Vision
Cellular component	Endoplasmic reticulum Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Corneal dystrophy Disease mutation
Domain	Transmembrane Transmembrane helix
Ligand	Heme Iron Metal-binding
Molecular function	Monooxygenase Oxidoreductase
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	fatty acid omega-oxidation Inferred from direct assay Ref.6. Source: UniProtKB response to stimulus Inferred from electronic annotation. Source: UniProtKB-KW visual perception Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	endoplasmic reticulum membrane Inferred from electronic annotation. Source: UniProtKB-SubCell integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW
Molecular_function	electron carrier activity Inferred from electronic annotation. Source: InterPro heme binding Inferred from electronic annotation. Source: InterPro iron ion binding Inferred from electronic annotation. Source: InterPro monooxygenase activity Inferred from electronic annotation. Source: UniProtKB-KW oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen 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: Q6ZWL3-1)

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: Q6ZWL3-2)

The sequence of this isoform differs from the canonical sequence as follows:
     42-63: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 525	525	Cytochrome P450 4V2		PRO_0000051859
Regions
	Transmembrane	13 – 33	21	Helical; Potential
Sites
	Metal binding	467	1	Iron (heme axial ligand) By similarity
	Binding site	329	1	Heme (covalent; via 1 link) By similarity
Amino acid modifications
	Modified residue	403	1	Phosphoserine By similarity
Natural variations
	Alternative sequence	42 – 63	22	Missing in isoform 2.		VSP_014918
	Natural variant	22	1	L → V. Ref.3 Corresponds to variant rs1055138 [ dbSNP | Ensembl ].		VAR_038606
	Natural variant	44	1	W → R in BCD. Ref.1		VAR_023084
	Natural variant	61	1	G → S in BCD. Ref.1		VAR_023085
	Natural variant	79	1	E → D in BCD. Ref.1		VAR_023086
	Natural variant	111	1	I → T in BCD. Ref.1		VAR_023087
	Natural variant	123	1	M → V in BCD. Ref.1		VAR_023088
	Natural variant	213	1	S → N. Ref.3 Corresponds to variant rs34331648 [ dbSNP | Ensembl ].		VAR_038607
	Natural variant	259	1	Q → K. Ref.1 Ref.2 Ref.5 Corresponds to variant rs13146272 [ dbSNP | Ensembl ].		VAR_033821
	Natural variant	275	1	E → K. Ref.3 Corresponds to variant rs34745240 [ dbSNP | Ensembl ].		VAR_055379
	Natural variant	331	1	H → P in BCD. Ref.1		VAR_023089
	Natural variant	341	1	S → P in BCD. Ref.1		VAR_023090
	Natural variant	372	1	V → I. Ref.3		VAR_055380
	Natural variant	443	1	R → Q. Ref.3		VAR_055381
	Natural variant	508	1	R → H in BCD. Ref.1		VAR_023091

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified May 18, 2010. Version 2. Checksum: A26F0A517C9569AD	FASTA	525	60,724
	10 20 30 40 50 60 MAGLWLGLVW QKLLLWGAAS ALSLAGASLV LSLLQRVASY ARKWQQMRPI PTVARAYPLV 70 80 90 100 110 120 GHALLMKPDG REFFQQIIEY TEEYRHMPLL KLWVGPVPMV ALYNAENVEV ILTSSKQIDK 130 140 150 160 170 180 SSMYKFLEPW LGLGLLTSTG NKWRSRRKML TPTFHFTILE DFLDIMNEQA NILVKKLEKH 190 200 210 220 230 240 INQEAFNCFF YITLCALDII CETAMGKNIG AQSNDDSEYV RAVYRMSEMI FRRIKMPWLW 250 260 270 280 290 300 LDLWYLMFKE GWEHKKSLQI LHTFTNSVIA ERANEMNANE DCRGDGRGSA PSKNKRRAFL 310 320 330 340 350 360 DLLLSVTDDE GNRLSHEDIR EEVDTFMFEG HDTTAAAINW SLYLLGSNPE VQKKVDHELD 370 380 390 400 410 420 DVFGKSDRPA TVEDLKKLRY LECVIKETLR LFPSVPLFAR SVSEDCEVAG YRVLKGTEAV 430 440 450 460 470 480 IIPYALHRDP RYFPNPEEFQ PERFFPENAQ GRHPYAYVPF SAGPRNCIGQ KFAVMEEKTI 490 500 510 520 LSCILRHFWI ESNQKREELG LEGQLILRPS NGIWIKLKRR NADER
	Isoform 2 [UniParc]. Checksum: 117B6B2EC969AF96	FASTA	503	58,166
	10 20 30 40 50 60 MAGLWLGLVW QKLLLWGAAS ALSLAGASLV LSLLQRVASY ALLMKPDGRE FFQQIIEYTE 70 80 90 100 110 120 EYRHMPLLKL WVGPVPMVAL YNAENVEVIL TSSKQIDKSS MYKFLEPWLG LGLLTSTGNK 130 140 150 160 170 180 WRSRRKMLTP TFHFTILEDF LDIMNEQANI LVKKLEKHIN QEAFNCFFYI TLCALDIICE 190 200 210 220 230 240 TAMGKNIGAQ SNDDSEYVRA VYRMSEMIFR RIKMPWLWLD LWYLMFKEGW EHKKSLQILH 250 260 270 280 290 300 TFTNSVIAER ANEMNANEDC RGDGRGSAPS KNKRRAFLDL LLSVTDDEGN RLSHEDIREE 310 320 330 340 350 360 VDTFMFEGHD TTAAAINWSL YLLGSNPEVQ KKVDHELDDV FGKSDRPATV EDLKKLRYLE 370 380 390 400 410 420 CVIKETLRLF PSVPLFARSV SEDCEVAGYR VLKGTEAVII PYALHRDPRY FPNPEEFQPE 430 440 450 460 470 480 RFFPENAQGR HPYAYVPFSA GPRNCIGQKF AVMEEKTILS CILRHFWIES NQKREELGLE 490 500 GQLILRPSNG IWIKLKRRNA DER

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Bietti crystalline corneoretinal dystrophy is caused by mutations in the novel gene CYP4V2." Li A., Jiao X., Munier F.L., Schorderet D.F., Yao W., Iwata F., Hayakawa M., Kanai A., Shy Chen M., Alan Lewis R., Heckenlively J., Weleber R.G., Traboulsi E.I., Zhang Q., Xiao X., Kaiser-Kupfer M., Sergeev Y.V., Hejtmancik J.F. Am. J. Hum. Genet. 74:817-826(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, VARIANTS BCD ARG-44; SER-61; ASP-79; THR-111; VAL-123; LYS-259; PRO-331; PRO-341 AND HIS-508. Tissue: Retina.
[2]	"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] (ISOFORMS 1 AND 2), VARIANT LYS-259. Tissue: Kidney and Uterus.
[3]	NIEHS SNPs program Submitted (NOV-2008) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS VAL-22; ASN-213; LYS-275; ILE-372 AND GLN-443.
[4]	"Generation and annotation of the DNA sequences of human chromosomes 2 and 4." Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K. Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"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] (ISOFORM 1), VARIANT LYS-259. Tissue: Placenta.
[6]	"Expression and characterization of CYP4V2 as a fatty acid omega-hydroxylase." Nakano M., Kelly E.J., Rettie A.E. Drug Metab. Dispos. 37:2119-2122(2009) [PubMed] [Europe PMC] [Abstract] Cited for: CATALYTIC ACTIVITY, FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, SUBSTRATE SPECIFICITY, ENZYME REGULATION.
+	Additional computationally mapped references.

Web resources

GeneReviews

NIEHS-SNPs

Cross-references

Sequence databases
EMBL GenBank DDBJ	AY422002 mRNA. Translation: AAR31180.1. AK122600 mRNA. Translation: BAC85487.1. AK126473 mRNA. Translation: BAC86562.1. FJ440682 Genomic DNA. Translation: ACK44069.1. AC110771 Genomic DNA. No translation available. BC060857 mRNA. Translation: AAH60857.1.
IPI	IPI00419217. IPI00619963.
RefSeq	NP_997235.3. NM_207352.3.
UniGene	Hs.587231.
3D structure databases
ProteinModelPortal	Q6ZWL3.
SMR	Q6ZWL3. Positions 48-520.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q6ZWL3. 1 interaction.
STRING	9606.ENSP00000368079.
PTM databases
PhosphoSite	Q6ZWL3.
Polymorphism databases
DMDM	296434466.
Proteomic databases
PaxDb	Q6ZWL3.
PRIDE	Q6ZWL3.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000378802; ENSP00000368079; ENSG00000145476.
GeneID	285440.
KEGG	hsa:285440.
UCSC	uc003iyw.4. human.
Organism-specific databases
CTD	285440.
GeneCards	GC04P187112.
H-InvDB	HIX0004688.
HGNC	HGNC:23198. CYP4V2.
HPA	HPA029122.
MIM	210370. phenotype. 608614. gene.
neXtProt	NX_Q6ZWL3.
Orphanet	41751. Bietti crystalline dystrophy.
PharmGKB	PA134912942.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG2124.
HOGENOM	HOG000233834.
HOVERGEN	HBG000182.
InParanoid	Q6ZWL3.
KO	K07427.
OMA	LKLWVGP.
OrthoDB	EOG4VMFFC.
Gene expression databases
ArrayExpress	Q6ZWL3.
Bgee	Q6ZWL3.
Genevestigator	Q6ZWL3.
GermOnline	ENSG00000145476. Homo sapiens.
Family and domain databases
Gene3D	1.10.630.10. 1 hit.
InterPro	IPR001128. Cyt_P450. IPR017972. Cyt_P450_CS. IPR002401. Cyt_P450_E_grp-I. [Graphical view]
Pfam	PF00067. p450. 1 hit. [Graphical view]
PRINTS	PR00463. EP450I. PR00385. P450.
SUPFAM	SSF48264. Cytochrome_P450. 1 hit.
PROSITE	PS00086. CYTOCHROME_P450. 1 hit. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	285440.
NextBio	95523.
SOURCE	Search...

Entry information

Entry name

CP4V2_HUMAN

Accession

Primary (citable) accession number: Q6ZWL3
Secondary accession number(s): B7U6W2, Q6ZTM4

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 2, 2005
Last sequence update:	May 18, 2010
Last modified:	May 1, 2013
This is version 99 of the entry and version 2 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.