UniProtKB - Q7Z449 (CP2U1_HUMAN)
Protein
Cytochrome P450 2U1
Gene
CYP2U1
Organism
Homo sapiens (Human)
Status
Functioni
A cytochrome P450 monooxygenase involved in the metabolism of arachidonic acid and its conjugates (PubMed:14660610, PubMed:24563460). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (CPR; NADPH-ferrihemoprotein reductase) (PubMed:14660610, PubMed:24563460). Acts as an omega and omega-1 hydroxylase for arachidonic acid and possibly for other long chain fatty acids. May modulate the arachidonic acid signaling pathway and play a role in other fatty acid signaling processes (PubMed:14660610, PubMed:24563460). May downregulate the biological activities of N-arachidonoyl-serotonin, an endocannabinoid that has anti-nociceptive effects through inhibition of fatty acid amide hydrolase FAAH, TRPV1 receptor and T-type calcium channels. Catalyzes C-2 oxidation of the indole ring of N-arachidonoyl-serotonin forming a less active product 2-oxo-N-arachidonoyl-serotonin (PubMed:24563460).2 Publications
Catalytic activityi
- an ω-methyl-long-chain fatty acid + O2 + reduced [NADPH—hemoprotein reductase] = an ω-hydroxy-long-chain fatty acid + H+ + H2O + oxidized [NADPH—hemoprotein reductase]2 PublicationsEC:1.14.14.802 PublicationsThis reaction proceeds in the forward2 Publications direction.
- (5Z,8Z,11Z,14Z)-eicosatetraenoate + O2 + reduced [NADPH—hemoprotein reductase] = 19-hydroxy-(5Z,8Z,11Z,14Z)-eicosatetraenoate + H+ + H2O + oxidized [NADPH—hemoprotein reductase]2 PublicationsThis reaction proceeds in the forward2 Publications direction.
- (5Z,8Z,11Z,14Z)-eicosatetraenoate + O2 + reduced [NADPH—hemoprotein reductase] = 20-hydroxy-(5Z,8Z,11Z,14Z)-eicosatetraenoate + H+ + H2O + oxidized [NADPH—hemoprotein reductase]2 PublicationsThis reaction proceeds in the forward2 Publications direction.
- N-[(5Z,8Z,11Z,14Z)-eicosatetraenoyl]-serotonin + O2 + reduced [NADPH—hemoprotein reductase] = 2-oxo-N-[(5Z,8Z,11Z,14Z)-eicosatetraenoyl]-serotonin + H+ + H2O + oxidized [NADPH—hemoprotein reductase]1 PublicationThis reaction proceeds in the forward1 Publication direction.
Cofactori
heme1 Publication
Kineticsi
- KM=2.7 µM for arachidonic acid
- KM=82 µM for N-arachidonoylserotonin1 Publication
: arachidonate metabolism Pathwayi
This protein is involved in the pathway arachidonate metabolism, which is part of Lipid metabolism.2 PublicationsView all proteins of this organism that are known to be involved in the pathway arachidonate metabolism and in Lipid metabolism.
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Metal bindingi | 490 | Iron (heme axial ligand)By similarity | 1 |
GO - Molecular functioni
- arachidonic acid omega-hydroxylase activity Source: UniProtKB
- heme binding Source: GO_Central
- iron ion binding Source: InterPro
- long-chain fatty acid omega-hydroxylase activity Source: UniProtKB-EC
- oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen Source: GO_Central
- steroid hydroxylase activity Source: GO_Central
GO - Biological processi
- exogenous drug catabolic process Source: GO_Central
- omega-hydroxylase P450 pathway Source: UniProtKB
- organic acid metabolic process Source: GO_Central
- xenobiotic metabolic process Source: GO_Central
Keywordsi
Molecular function | Monooxygenase, Oxidoreductase |
Ligand | Heme, Iron, Metal-binding |
Enzyme and pathway databases
PathwayCommonsi | Q7Z449 |
Reactomei | R-HSA-211958, Miscellaneous substrates R-HSA-2142816, Synthesis of (16-20)-hydroxyeicosatetraenoic acids (HETE) R-HSA-5579011, Defective CYP2U1 causes Spastic paraplegia 56, autosomal recessive (SPG56) |
SABIO-RKi | Q7Z449 |
UniPathwayi | UPA00383 |
Chemistry databases
SwissLipidsi | SLP:000001048 |
Names & Taxonomyi
Protein namesi | Recommended name: Cytochrome P450 2U11 PublicationAlternative name(s): Long-chain fatty acid omega-monooxygenase1 Publication (EC:1.14.14.802 Publications) |
Gene namesi | |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:20582, CYP2U1 |
MIMi | 610670, gene |
neXtProti | NX_Q7Z449 |
VEuPathDBi | HostDB:ENSG00000155016.17 |
Subcellular locationi
Endoplasmic reticulum
- Endoplasmic reticulum membrane 1 Publication; Multi-pass membrane protein Sequence analysis
- Microsome membrane 1 Publication; Multi-pass membrane protein Sequence analysis
Mitochondrion
- Mitochondrion inner membrane 1 Publication; Multi-pass membrane protein Sequence analysis
Endoplasmic reticulum
- endoplasmic reticulum membrane Source: Reactome
Mitochondrion
- mitochondrial inner membrane Source: UniProtKB-SubCell
Other locations
- cytoplasm Source: GO_Central
- integral component of membrane Source: UniProtKB-KW
- intracellular membrane-bounded organelle Source: GO_Central
Topology
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Transmembranei | 30 – 50 | HelicalSequence analysisAdd BLAST | 21 | |
Transmembranei | 113 – 133 | HelicalSequence analysisAdd BLAST | 21 | |
Transmembranei | 261 – 281 | HelicalSequence analysisAdd BLAST | 21 | |
Transmembranei | 342 – 362 | HelicalSequence analysisAdd BLAST | 21 | |
Transmembranei | 495 – 515 | HelicalSequence analysisAdd BLAST | 21 |
Keywords - Cellular componenti
Endoplasmic reticulum, Membrane, Microsome, Mitochondrion, Mitochondrion inner membranePathology & Biotechi
Involvement in diseasei
Spastic paraplegia 56, autosomal recessive (SPG56)1 Publication
The disease is caused by variants affecting the gene represented in this entry.
Disease descriptionA 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. Complicated forms are recognized by additional variable features including spastic quadriparesis, seizures, dementia, amyotrophy, extrapyramidal disturbance, cerebral or cerebellar atrophy, optic atrophy, and peripheral neuropathy, as well as by extra neurological manifestations. In SPG56, upper limbs are often also affected. Some SPG56 patients may have a subclinical axonal neuropathy.
Related information in OMIMFeature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_069575 | 262 | C → R in SPG56. 1 PublicationCorresponds to variant dbSNP:rs397514515EnsemblClinVar. | 1 | |
Natural variantiVAR_069576 | 316 | D → V in SPG56. 1 PublicationCorresponds to variant dbSNP:rs397514513EnsemblClinVar. | 1 | |
Natural variantiVAR_069577 | 380 | E → G in SPG56. 1 PublicationCorresponds to variant dbSNP:rs397514514EnsemblClinVar. | 1 | |
Natural variantiVAR_069578 | 488 | R → W in SPG56. 1 PublicationCorresponds to variant dbSNP:rs141431913EnsemblClinVar. | 1 |
Keywords - Diseasei
Disease variant, Hereditary spastic paraplegia, NeurodegenerationOrganism-specific databases
DisGeNETi | 113612 |
MalaCardsi | CYP2U1 |
MIMi | 615030, phenotype |
OpenTargetsi | ENSG00000155016 |
Orphaneti | 320411, Autosomal recessive spastic paraplegia type 56 |
PharmGKBi | PA134924269 |
Miscellaneous databases
Pharosi | Q7Z449, Tbio |
Genetic variation databases
BioMutai | CYP2U1 |
DMDMi | 74762432 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000291756 | 1 – 544 | Cytochrome P450 2U1Add BLAST | 544 |
Proteomic databases
EPDi | Q7Z449 |
jPOSTi | Q7Z449 |
MassIVEi | Q7Z449 |
MaxQBi | Q7Z449 |
PaxDbi | Q7Z449 |
PeptideAtlasi | Q7Z449 |
PRIDEi | Q7Z449 |
ProteomicsDBi | 69149 [Q7Z449-1] 69150 [Q7Z449-2] |
PTM databases
iPTMneti | Q7Z449 |
PhosphoSitePlusi | Q7Z449 |
Expressioni
Tissue specificityi
Widely expressed with stronger expression in thymus, heart and cerebellum.3 Publications
Developmental stagei
Expressed in fetal thymus.2 Publications
Gene expression databases
Bgeei | ENSG00000155016, Expressed in thymus and 204 other tissues |
ExpressionAtlasi | Q7Z449, baseline and differential |
Genevisiblei | Q7Z449, HS |
Organism-specific databases
HPAi | ENSG00000155016, Tissue enriched (lymphoid) |
Interactioni
Protein-protein interaction databases
BioGRIDi | 125252, 1 interactor |
IntActi | Q7Z449, 1 interactor |
STRINGi | 9606.ENSP00000333212 |
Miscellaneous databases
RNActi | Q7Z449, protein |
Family & Domainsi
Sequence similaritiesi
Belongs to the cytochrome P450 family.Curated
Keywords - Domaini
Transmembrane, Transmembrane helixPhylogenomic databases
eggNOGi | KOG0156, Eukaryota |
GeneTreei | ENSGT00940000157714 |
HOGENOMi | CLU_001570_22_3_1 |
InParanoidi | Q7Z449 |
OMAi | KQRKFCH |
OrthoDBi | 702827at2759 |
PhylomeDBi | Q7Z449 |
TreeFami | TF352043 |
Family and domain databases
Gene3Di | 1.10.630.10, 1 hit |
InterProi | View protein in InterPro IPR001128, Cyt_P450 IPR017972, Cyt_P450_CS IPR002401, Cyt_P450_E_grp-I IPR008069, Cyt_P450_E_grp-I_CYP2D-like IPR036396, Cyt_P450_sf |
Pfami | View protein in Pfam PF00067, p450, 1 hit |
PRINTSi | PR00463, EP450I PR01686, EP450ICYP2D PR00385, P450 |
SUPFAMi | SSF48264, SSF48264, 1 hit |
PROSITEi | View protein in PROSITE PS00086, CYTOCHROME_P450, 1 hit |
s (2+)i Sequence
Sequence statusi: Complete.
This entry describes 2 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 2 described isoforms and 1 potential isoform that is computationally mapped.Show allAlign All
Isoform 1 (identifier: Q7Z449-1) [UniParc]FASTAAdd to basket
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
10 20 30 40 50
MSSPGPSQPP AEDPPWPARL LRAPLGLLRL DPSGGALLLC GLVALLGWSW
60 70 80 90 100
LRRRRARGIP PGPTPWPLVG NFGHVLLPPF LRRRSWLSSR TRAAGIDPSV
110 120 130 140 150
IGPQVLLAHL ARVYGSIFSF FIGHYLVVVL SDFHSVREAL VQQAEVFSDR
160 170 180 190 200
PRVPLISIVT KEKGVVFAHY GPVWRQQRKF SHSTLRHFGL GKLSLEPKII
210 220 230 240 250
EEFKYVKAEM QKHGEDPFCP FSIISNAVSN IICSLCFGQR FDYTNSEFKK
260 270 280 290 300
MLGFMSRGLE ICLNSQVLLV NICPWLYYLP FGPFKELRQI EKDITSFLKK
310 320 330 340 350
IIKDHQESLD RENPQDFIDM YLLHMEEERK NNSNSSFDEE YLFYIIGDLF
360 370 380 390 400
IAGTDTTTNS LLWCLLYMSL NPDVQEKVHE EIERVIGANR APSLTDKAQM
410 420 430 440 450
PYTEATIMEV QRLTVVVPLA IPHMTSENTV LQGYTIPKGT LILPNLWSVH
460 470 480 490 500
RDPAIWEKPE DFYPNRFLDD QGQLIKKETF IPFGIGKRVC MGEQLAKMEL
510 520 530 540
FLMFVSLMQS FAFALPEDSK KPLLTGRFGL TLAPHPFNIT ISRR
Computationally mapped potential isoform sequencesi
There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basketE9PGH5 | E9PGH5_HUMAN | Cytochrome P450 2U1 | CYP2U1 | 335 | Annotation score: |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_069575 | 262 | C → R in SPG56. 1 PublicationCorresponds to variant dbSNP:rs397514515EnsemblClinVar. | 1 | |
Natural variantiVAR_069576 | 316 | D → V in SPG56. 1 PublicationCorresponds to variant dbSNP:rs397514513EnsemblClinVar. | 1 | |
Natural variantiVAR_069577 | 380 | E → G in SPG56. 1 PublicationCorresponds to variant dbSNP:rs397514514EnsemblClinVar. | 1 | |
Natural variantiVAR_069578 | 488 | R → W in SPG56. 1 PublicationCorresponds to variant dbSNP:rs141431913EnsemblClinVar. | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_026222 | 164 – 168 | GVVFA → ELFQE in isoform 2. 1 Publication | 5 | |
Alternative sequenceiVSP_026223 | 169 – 544 | Missing in isoform 2. 1 PublicationAdd BLAST | 376 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AY343323 mRNA Translation: AAQ21380.1 CH471057 Genomic DNA Translation: EAX06216.1 BC012027 mRNA Translation: AAH12027.1 BC132767 mRNA Translation: AAI32768.1 BC136483 mRNA Translation: AAI36484.1 |
CCDSi | CCDS34047.1 [Q7Z449-1] |
RefSeqi | NP_898898.1, NM_183075.2 [Q7Z449-1] |
Genome annotation databases
Ensembli | ENST00000332884; ENSP00000333212; ENSG00000155016 [Q7Z449-1] |
GeneIDi | 113612 |
KEGGi | hsa:113612 |
UCSCi | uc003hyp.4, human [Q7Z449-1] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AY343323 mRNA Translation: AAQ21380.1 CH471057 Genomic DNA Translation: EAX06216.1 BC012027 mRNA Translation: AAH12027.1 BC132767 mRNA Translation: AAI32768.1 BC136483 mRNA Translation: AAI36484.1 |
CCDSi | CCDS34047.1 [Q7Z449-1] |
RefSeqi | NP_898898.1, NM_183075.2 [Q7Z449-1] |
3D structure databases
SMRi | Q7Z449 |
ModBasei | Search... |
Protein-protein interaction databases
BioGRIDi | 125252, 1 interactor |
IntActi | Q7Z449, 1 interactor |
STRINGi | 9606.ENSP00000333212 |
Chemistry databases
SwissLipidsi | SLP:000001048 |
PTM databases
iPTMneti | Q7Z449 |
PhosphoSitePlusi | Q7Z449 |
Genetic variation databases
BioMutai | CYP2U1 |
DMDMi | 74762432 |
Proteomic databases
EPDi | Q7Z449 |
jPOSTi | Q7Z449 |
MassIVEi | Q7Z449 |
MaxQBi | Q7Z449 |
PaxDbi | Q7Z449 |
PeptideAtlasi | Q7Z449 |
PRIDEi | Q7Z449 |
ProteomicsDBi | 69149 [Q7Z449-1] 69150 [Q7Z449-2] |
Protocols and materials databases
Antibodypediai | 26251, 140 antibodies |
DNASUi | 113612 |
Genome annotation databases
Ensembli | ENST00000332884; ENSP00000333212; ENSG00000155016 [Q7Z449-1] |
GeneIDi | 113612 |
KEGGi | hsa:113612 |
UCSCi | uc003hyp.4, human [Q7Z449-1] |
Organism-specific databases
CTDi | 113612 |
DisGeNETi | 113612 |
GeneCardsi | CYP2U1 |
HGNCi | HGNC:20582, CYP2U1 |
HPAi | ENSG00000155016, Tissue enriched (lymphoid) |
MalaCardsi | CYP2U1 |
MIMi | 610670, gene 615030, phenotype |
neXtProti | NX_Q7Z449 |
OpenTargetsi | ENSG00000155016 |
Orphaneti | 320411, Autosomal recessive spastic paraplegia type 56 |
PharmGKBi | PA134924269 |
VEuPathDBi | HostDB:ENSG00000155016.17 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG0156, Eukaryota |
GeneTreei | ENSGT00940000157714 |
HOGENOMi | CLU_001570_22_3_1 |
InParanoidi | Q7Z449 |
OMAi | KQRKFCH |
OrthoDBi | 702827at2759 |
PhylomeDBi | Q7Z449 |
TreeFami | TF352043 |
Enzyme and pathway databases
UniPathwayi | UPA00383 |
PathwayCommonsi | Q7Z449 |
Reactomei | R-HSA-211958, Miscellaneous substrates R-HSA-2142816, Synthesis of (16-20)-hydroxyeicosatetraenoic acids (HETE) R-HSA-5579011, Defective CYP2U1 causes Spastic paraplegia 56, autosomal recessive (SPG56) |
SABIO-RKi | Q7Z449 |
Miscellaneous databases
BioGRID-ORCSi | 113612, 3 hits in 990 CRISPR screens |
ChiTaRSi | CYP2U1, human |
GeneWikii | CYP2U1 |
GenomeRNAii | 113612 |
Pharosi | Q7Z449, Tbio |
PROi | PR:Q7Z449 |
RNActi | Q7Z449, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000155016, Expressed in thymus and 204 other tissues |
ExpressionAtlasi | Q7Z449, baseline and differential |
Genevisiblei | Q7Z449, HS |
Family and domain databases
Gene3Di | 1.10.630.10, 1 hit |
InterProi | View protein in InterPro IPR001128, Cyt_P450 IPR017972, Cyt_P450_CS IPR002401, Cyt_P450_E_grp-I IPR008069, Cyt_P450_E_grp-I_CYP2D-like IPR036396, Cyt_P450_sf |
Pfami | View protein in Pfam PF00067, p450, 1 hit |
PRINTSi | PR00463, EP450I PR01686, EP450ICYP2D PR00385, P450 |
SUPFAMi | SSF48264, SSF48264, 1 hit |
PROSITEi | View protein in PROSITE PS00086, CYTOCHROME_P450, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | CP2U1_HUMAN | |
Accessioni | Q7Z449Primary (citable) accession number: Q7Z449 Secondary accession number(s): B2RMV7, Q96EQ6 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | June 26, 2007 |
Last sequence update: | October 1, 2003 | |
Last modified: | April 7, 2021 | |
This is version 162 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | 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. |
Miscellaneousi
Keywords - Technical termi
Direct protein sequencing, Reference proteomeDocuments
- Human chromosome 4
Human chromosome 4: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PATHWAY comments
Index of metabolic and biosynthesis pathways - SIMILARITY comments
Index of protein domains and families