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Protein

Cytochrome P450 2D6

Gene

CYP2D6

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic antidepressants.1 Publication

Catalytic activityi

RH + [reduced NADPH--hemoprotein reductase] + O2 = ROH + [oxidized NADPH--hemoprotein reductase] + H2O.1 Publication

Cofactori

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei301SubstrateCurated1
Metal bindingi443Iron (heme axial ligand)1

GO - Molecular functioni

GO - Biological processi

  • alkaloid catabolic process Source: BHF-UCL
  • alkaloid metabolic process Source: BHF-UCL
  • arachidonic acid metabolic process Source: GO_Central
  • coumarin metabolic process Source: BHF-UCL
  • drug catabolic process Source: BHF-UCL
  • drug metabolic process Source: BHF-UCL
  • heterocycle metabolic process Source: BHF-UCL
  • isoquinoline alkaloid metabolic process Source: BHF-UCL
  • monoterpenoid metabolic process Source: BHF-UCL
  • negative regulation of binding Source: BHF-UCL
  • negative regulation of cellular organofluorine metabolic process Source: BHF-UCL
  • oxidation-reduction process Source: BHF-UCL
  • oxidative demethylation Source: BHF-UCL
  • steroid metabolic process Source: BHF-UCL
  • xenobiotic metabolic process Source: BHF-UCL
Complete GO annotation...

Keywords - Molecular functioni

Monooxygenase, Oxidoreductase

Keywords - Biological processi

Lipid metabolism, Steroid metabolism, Sterol metabolism

Keywords - Ligandi

Heme, Iron, Metal-binding

Enzyme and pathway databases

BioCyciZFISH:HS01997-MONOMER.
BRENDAi1.14.14.1. 2681.
1.14.99.38. 2681.
ReactomeiR-HSA-211935. Fatty acids.
R-HSA-211958. Miscellaneous substrates.
R-HSA-211981. Xenobiotics.
R-HSA-211999. CYP2E1 reactions.
SABIO-RKP10635.

Chemistry databases

SwissLipidsiSLP:000001204.

Names & Taxonomyi

Protein namesi
Recommended name:
Cytochrome P450 2D6 (EC:1.14.14.11 Publication)
Alternative name(s):
CYPIID6
Cholesterol 25-hydroxylase1 Publication
Cytochrome P450-DB1
Debrisoquine 4-hydroxylase
Gene namesi
Name:CYP2D6
Synonyms:CYP2DL1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 22

Organism-specific databases

HGNCiHGNC:2625. CYP2D6.

Subcellular locationi

GO - Cellular componenti

  • endoplasmic reticulum Source: BHF-UCL
  • endoplasmic reticulum membrane Source: Reactome
  • mitochondrion Source: BHF-UCL
  • organelle membrane Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Endoplasmic reticulum, Membrane, Microsome

Pathology & Biotechi

Organism-specific databases

DisGeNETi1565.
MalaCardsiCYP2D6.
MIMi608902. phenotype.
OpenTargetsiENSG00000100197.
Orphaneti413667. Antidepressant or antipsychotics toxicity or dose selection.
240867. Codeine toxicity.
240947. Resistance to tamoxifene.
PharmGKBiPA128.

Chemistry databases

ChEMBLiCHEMBL289.
DrugBankiDB05812. Abiraterone.
DB01193. Acebutolol.
DB00316. Acetaminophen.
DB03128. Acetylcholine.
DB01426. Ajmaline.
DB00918. Almotriptan.
DB06203. Alogliptin.
DB00866. Alprenolol.
DB01424. Aminophenazone.
DB01118. Amiodarone.
DB00321. Amitriptyline.
DB00381. Amlodipine.
DB00613. Amodiaquine.
DB00543. Amoxapine.
DB00182. Amphetamine.
DB00701. Amprenavir.
DB00276. Amsacrine.
DB01435. Antipyrine.
DB01429. Aprindine.
DB01274. Arformoterol.
DB01238. Aripiprazole.
DB06697. Artemether.
DB06216. Asenapine.
DB00637. Astemizole.
DB00289. Atomoxetine.
DB01076. Atorvastatin.
DB00972. Azelastine.
DB00245. Benzatropine.
DB06770. Benzyl alcohol.
DB01244. Bepridil.
DB00195. Betaxolol.
DB01128. Bicalutamide.
DB00810. Biperiden.
DB00612. Bisoprolol.
DB00188. Bortezomib.
DB09128. Brexpiprazole.
DB00835. Brompheniramine.
DB00297. Bupivacaine.
DB00921. Buprenorphine.
DB01156. Bupropion.
DB00490. Buspirone.
DB00201. Caffeine.
DB01197. Captopril.
DB00748. Carbinoxamine.
DB06016. Cariprazine.
DB00521. Carteolol.
DB01136. Carvedilol.
DB00482. Celecoxib.
DB00567. Cephalexin.
DB00185. Cevimeline.
DB00475. Chlordiazepoxide.
DB00608. Chloroquine.
DB01114. Chlorphenamine.
DB00477. Chlorpromazine.
DB00356. Chlorzoxazone.
DB00169. Cholecalciferol.
DB01410. Ciclesonide.
DB01166. Cilostazol.
DB00501. Cimetidine.
DB01012. Cinacalcet.
DB00568. Cinnarizine.
DB00604. Cisapride.
DB00215. Citalopram.
DB00283. Clemastine.
DB04920. Clevidipine.
DB00349. Clobazam.
DB01242. Clomipramine.
DB00575. Clonidine.
DB00257. Clotrimazole.
DB00363. Clozapine.
DB09065. Cobicistat.
DB00907. Cocaine.
DB00318. Codeine.
DB00924. Cyclobenzaprine.
DB00531. Cyclophosphamide.
DB00091. Cyclosporine.
DB06292. Dapagliflozin.
DB00496. Darifenacin.
DB04840. Debrisoquin.
DB00705. Delavirdine.
DB01151. Desipramine.
DB00967. Desloratadine.
DB01234. Dexamethasone.
DB01191. Dexfenfluramine.
DB00633. Dexmedetomidine.
DB06701. Dexmethylphenidate.
DB01576. Dextroamphetamine.
DB00514. Dextromethorphan.
DB00647. Dextropropoxyphene.
DB01551. Dihydrocodeine.
DB00343. Diltiazem.
DB01093. Dimethyl sulfoxide.
DB01075. Diphenhydramine.
DB00757. Dolasetron.
DB01184. Domperidone.
DB00843. Donepezil.
DB00988. Dopamine.
DB00590. Doxazosin.
DB01142. Doxepin.
DB00997. Doxorubicin.
DB04855. Dronedarone.
DB00476. Duloxetine.
DB00625. Efavirenz.
DB00216. Eletriptan.
DB09039. Eliglustat.
DB01228. Encainide.
DB08899. Enzalutamide.
DB00751. Epinastine.
DB00530. Erlotinib.
DB01175. Escitalopram.
DB01466. Ethylmorphine.
DB01628. Etoricoxib.
DB01023. Felodipine.
DB06702. Fesoterodine.
DB00950. Fexofenadine.
DB08868. Fingolimod.
DB01195. Flecainide.
DB04841. Flunarizine.
DB00472. Fluoxetine.
DB00623. Fluphenazine.
DB01095. Fluvastatin.
DB00176. Fluvoxamine.
DB00983. Formoterol.
DB00674. Galantamine.
DB00317. Gefitinib.
DB01437. Glutethimide.
DB00889. Granisetron.
DB01218. Halofantrine.
DB00502. Haloperidol.
DB01159. Halothane.
DB00667. Histamine Phosphate.
DB00956. Hydrocodone.
DB00327. Hydromorphone.
DB01611. Hydroxychloroquine.
DB01005. Hydroxyurea.
DB00557. Hydroxyzine.
DB09053. Ibrutinib.
DB01177. Idarubicin.
DB04946. Iloperidone.
DB00619. Imatinib.
DB00458. Imipramine.
DB00224. Indinavir.
DB00332. Ipratropium bromide.
DB01029. Irbesartan.
DB00951. Isoniazid.
DB01167. Itraconazole.
DB09570. Ixazomib.
DB01026. Ketoconazole.
DB00598. Labetalol.
DB00448. Lansoprazole.
DB00528. Lercanidipine.
DB01235. Levodopa.
DB08918. Levomilnacipran.
DB00281. Lidocaine.
DB00589. Lisuride.
DB01206. Lomustine.
DB00836. Loperamide.
DB01601. Lopinavir.
DB00455. Loratadine.
DB04871. Lorcaserin.
DB00227. Lovastatin.
DB06708. Lumefantrine.
DB00934. Maprotiline.
DB00358. Mefloquine.
DB06691. Mepyramine.
DB01071. Mequitazine.
DB00933. Mesoridazine.
DB00333. Methadone.
DB01577. Methamphetamine.
DB00703. Methazolamide.
DB00763. Methimazole.
DB01403. Methotrimeprazine.
DB01028. Methoxyflurane.
DB06800. Methylnaltrexone.
DB00422. Methylphenidate.
DB01107. Methyprylon.
DB01233. Metoclopramide.
DB00264. Metoprolol.
DB00379. Mexiletine.
DB06148. Mianserin.
DB01110. Miconazole.
DB00211. Midodrine.
DB00834. Mifepristone.
DB00805. Minaprine.
DB08893. Mirabegron.
DB00370. Mirtazapine.
DB01171. Moclobemide.
DB00295. Morphine.
DB09049. Naloxegol.
DB00731. Nateglinide.
DB04861. Nebivolol.
DB01149. Nefazodone.
DB00220. Nelfinavir.
DB09048. Netupitant.
DB00238. Nevirapine.
DB00627. Niacin.
DB00622. Nicardipine.
DB00699. Nicergoline.
DB02701. Nicotinamide.
DB00184. Nicotine.
DB01115. Nifedipine.
DB04868. Nilotinib.
DB00336. Nitrofural.
DB00540. Nortriptyline.
DB00334. Olanzapine.
DB00338. Omeprazole.
DB00904. Ondansetron.
DB01096. Oxamniquine.
DB01580. Oxprenolol.
DB01062. Oxybutynin.
DB00497. Oxycodone.
DB06412. Oxymetholone.
DB01192. Oxymorphone.
DB01267. Paliperidone.
DB00377. Palonosetron.
DB06603. Panobinostat.
DB00715. Paroxetine.
DB06589. Pazopanib.
DB00738. Pentamidine.
DB01186. Pergolide.
DB01074. Perhexiline.
DB00850. Perphenazine.
DB00454. Pethidine.
DB00914. Phenformin.
DB00191. Phentermine.
DB01100. Pimozide.
DB00960. Pindolol.
DB01132. Pioglitazone.
DB00592. Piperazine.
DB01621. Pipotiazine.
DB08901. Ponatinib.
DB00175. Pravastatin.
DB01058. Praziquantel.
DB01087. Primaquine.
DB01035. Procainamide.
DB00433. Prochlorperazine.
DB00396. Progesterone.
DB01131. Proguanil.
DB01069. Promethazine.
DB01182. Propafenone.
DB00818. Propofol.
DB00571. Propranolol.
DB00344. Protriptyline.
DB00852. Pseudoephedrine.
DB00205. Pyrimethamine.
DB01224. Quetiapine.
DB00908. Quinidine.
DB00468. Quinine.
DB01129. Rabeprazole.
DB00863. Ranitidine.
DB00243. Ranolazine.
DB00234. Reboxetine.
DB00409. Remoxipride.
DB01201. Rifapentine.
DB00734. Risperidone.
DB00503. Ritonavir.
DB00989. Rivastigmine.
DB09291. Rolapitant.
DB00268. Ropinirole.
DB00296. Ropivacaine.
DB00412. Rosiglitazone.
DB05271. Rotigotine.
DB01232. Saquinavir.
DB01037. Selegiline.
DB06144. Sertindole.
DB01104. Sertraline.
DB00203. Sildenafil.
DB00641. Simvastatin.
DB00398. Sorafenib.
DB00259. Sulfanilamide.
DB06729. Sulfaphenazole.
DB00675. Tamoxifen.
DB00706. Tamsulosin.
DB06204. Tapentadol.
DB00976. Telithromycin.
DB06287. Temsirolimus.
DB00857. Terbinafine.
DB04844. Tetrabenazine.
DB00277. Theophylline.
DB00679. Thioridazine.
DB01623. Thiothixene.
DB00208. Ticlopidine.
DB00373. Timolol.
DB01409. Tiotropium.
DB00932. Tipranavir.
DB01036. Tolterodine.
DB05109. Trabectedin.
DB00193. Tramadol.
DB00752. Tranylcypromine.
DB00656. Trazodone.
DB00726. Trimipramine.
DB00792. Tripelennamine.
DB00427. Triprolidine.
DB00209. Trospium.
DB09076. Umeclidinium.
DB08881. Vemurafenib.
DB00285. Venlafaxine.
DB00661. Verapamil.
DB06684. Vilazodone.
DB00570. Vinblastine.
DB00361. Vinorelbine.
DB09068. Vortioxetine.
DB01392. Yohimbine.
DB00549. Zafirlukast.
DB00943. Zalcitabine.
DB00246. Ziprasidone.
DB00425. Zolpidem.
DB01624. Zuclopenthixol.
GuidetoPHARMACOLOGYi1329.

Polymorphism and mutation databases

BioMutaiCYP2D6.
DMDMi84028191.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000517311 – 497Cytochrome P450 2D6Add BLAST497

Proteomic databases

PaxDbiP10635.
PeptideAtlasiP10635.
PRIDEiP10635.

PTM databases

iPTMnetiP10635.
PhosphoSitePlusiP10635.

Expressioni

Inductioni

By pregnancy.

Gene expression databases

BgeeiENSG00000100197.
CleanExiHS_CYP2D6.
ExpressionAtlasiP10635. baseline and differential.
GenevisibleiP10635. HS.

Organism-specific databases

HPAiHPA045223.

Interactioni

Protein-protein interaction databases

BioGridi107940. 4 interactors.
STRINGi9606.ENSP00000353820.

Chemistry databases

BindingDBiP10635.

Structurei

Secondary structure

1497
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Turni41 – 43Combined sources3
Helixi46 – 48Combined sources3
Helixi54 – 65Combined sources12
Beta strandi67 – 73Combined sources7
Beta strandi76 – 81Combined sources6
Helixi83 – 91Combined sources9
Turni92 – 94Combined sources3
Helixi95 – 97Combined sources3
Helixi105 – 110Combined sources6
Beta strandi119 – 121Combined sources3
Helixi126 – 141Combined sources16
Beta strandi145 – 147Combined sources3
Helixi148 – 165Combined sources18
Turni166 – 169Combined sources4
Helixi175 – 191Combined sources17
Helixi200 – 214Combined sources15
Helixi219 – 226Combined sources8
Helixi228 – 232Combined sources5
Helixi234 – 240Combined sources7
Helixi242 – 261Combined sources20
Helixi271 – 281Combined sources11
Turni282 – 284Combined sources3
Helixi292 – 323Combined sources32
Helixi325 – 338Combined sources14
Beta strandi341 – 343Combined sources3
Helixi347 – 350Combined sources4
Helixi354 – 367Combined sources14
Beta strandi370 – 372Combined sources3
Beta strandi382 – 384Combined sources3
Beta strandi387 – 389Combined sources3
Beta strandi394 – 397Combined sources4
Helixi399 – 403Combined sources5
Turni406 – 408Combined sources3
Beta strandi409 – 411Combined sources3
Helixi417 – 420Combined sources4
Helixi439 – 441Combined sources3
Helixi446 – 463Combined sources18
Beta strandi464 – 467Combined sources4
Beta strandi470 – 472Combined sources3
Beta strandi479 – 487Combined sources9
Beta strandi492 – 496Combined sources5

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2F9QX-ray3.00A/B/C/D34-497[»]
3QM4X-ray2.85A/B34-497[»]
3TBGX-ray2.10A/B/C/D34-497[»]
3TDAX-ray2.67A/B/C/D34-497[»]
4WNTX-ray2.60A/B34-497[»]
4WNUX-ray2.26A/B/C/D34-497[»]
4WNVX-ray2.35A/B/C/D48-497[»]
4WNWX-ray3.30A/B34-497[»]
4XRYX-ray2.50A/B/C/D34-497[»]
4XRZX-ray2.40A/B/C/D34-497[»]
ProteinModelPortaliP10635.
SMRiP10635.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP10635.

Family & Domainsi

Sequence similaritiesi

Belongs to the cytochrome P450 family.Curated

Phylogenomic databases

eggNOGiKOG0156. Eukaryota.
COG2124. LUCA.
GeneTreeiENSGT00760000118775.
HOVERGENiHBG015789.
InParanoidiP10635.
KOiK17712.
OMAiDEANWEK.
OrthoDBiEOG091G0BT8.
PhylomeDBiP10635.
TreeFamiTF352043.

Family and domain databases

Gene3Di1.10.630.10. 1 hit.
InterProiIPR001128. Cyt_P450.
IPR017972. Cyt_P450_CS.
IPR002401. Cyt_P450_E_grp-I.
IPR008069. Cyt_P450_E_grp-I_CYP2D-like.
[Graphical view]
PfamiPF00067. p450. 1 hit.
[Graphical view]
PRINTSiPR00463. EP450I.
PR01686. EP450ICYP2D.
PR00385. P450.
SUPFAMiSSF48264. SSF48264. 1 hit.
PROSITEiPS00086. CYTOCHROME_P450. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P10635-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MGLEALVPLA VIVAIFLLLV DLMHRRQRWA ARYPPGPLPL PGLGNLLHVD
60 70 80 90 100
FQNTPYCFDQ LRRRFGDVFS LQLAWTPVVV LNGLAAVREA LVTHGEDTAD
110 120 130 140 150
RPPVPITQIL GFGPRSQGVF LARYGPAWRE QRRFSVSTLR NLGLGKKSLE
160 170 180 190 200
QWVTEEAACL CAAFANHSGR PFRPNGLLDK AVSNVIASLT CGRRFEYDDP
210 220 230 240 250
RFLRLLDLAQ EGLKEESGFL REVLNAVPVL LHIPALAGKV LRFQKAFLTQ
260 270 280 290 300
LDELLTEHRM TWDPAQPPRD LTEAFLAEME KAKGNPESSF NDENLRIVVA
310 320 330 340 350
DLFSAGMVTT STTLAWGLLL MILHPDVQRR VQQEIDDVIG QVRRPEMGDQ
360 370 380 390 400
AHMPYTTAVI HEVQRFGDIV PLGVTHMTSR DIEVQGFRIP KGTTLITNLS
410 420 430 440 450
SVLKDEAVWE KPFRFHPEHF LDAQGHFVKP EAFLPFSAGR RACLGEPLAR
460 470 480 490
MELFLFFTSL LQHFSFSVPT GQPRPSHHGV FAFLVSPSPY ELCAVPR
Length:497
Mass (Da):55,769
Last modified:December 20, 2005 - v2
Checksum:i542B1D505DF3CDAC
GO
Isoform 2 (identifier: P10635-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     118-168: Missing.

Note: No experimental confirmation available.
Show »
Length:446
Mass (Da):50,061
Checksum:iD1FB49C5A4B10965
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti374V → M in AAA52153 (PubMed:3410476).Curated1
Sequence conflicti374V → M in CAA30807 (PubMed:3123997).Curated1

Polymorphismi

Genetic variations in CYP2D6 are the cause of poor drug metabolism CYP2D6-related [MIMi:608902]. The CYP2D6 gene is highly polymorphic. CYP2D6 activity ranges widely within a population comprising ultrarapid (UM), extensive (EM), intermediate (IM) and poor (PM) metabolizer phenotypes. UM and PM are those most at risk for treatment failure or dose-dependent drug toxicity, respectively. Of the Caucasian populations of Europe and North America, 5%-10% are of the PM phenotype and are unable to metabolize the antihypersensitive drug debrisoquine and numerous other drugs. Different alleles are known, including CYP2D6*1 (PubMed:15768052), CYP2D6*2 (PubMed:25469868), CYP2D6*6B/6C (PubMed:7868129), CYP2D6*7 also known CYP2D6E (PubMed:7845481), CYP2D6*9 also known CYP2D6C (PubMed:1844820), CYP2D6*10 also known CYP2D6J (PubMed:8287064, PubMed:25469868), CYP2D6*12 (PubMed:8655150), CYP2D6*14 (PubMed:10064570), CYP2D6*17 also known CYP2D6Z (PubMed:8971426), CYP2D6*41B (PubMed:15768052), CYP2D6*45A (PubMed:15768052), CYP2D6*45B (PubMed:15768052), CYP2D6*46 (PubMed:15768052), CYP2D6*87 (PubMed:25469868), CYP2D6*88 (PubMed:25469868), CYP2D6*89 (PubMed:25469868), CYP2D6*90 (PubMed:25469868), CYP2D6*91 (PubMed:25469868), CYP2D6*93 (PubMed:25469868), C CYP2D6*94 (PubMed:25469868), CYP2D6*97 (PubMed:25469868) and CYP2D6*98 (PubMed:25469868). Isozymes CYP2D6.45 (Lys-155, Cys-296 and Thr-486) and CYP2D6.46 (His-26, Lys-155, Cys-296 and Thr-486) are functional (PubMed:15768052).9 Publications

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_0727645A → V in allele CYP2D6*87. 1 PublicationCorresponds to variant rs773790593dbSNPEnsembl.1
Natural variantiVAR_00836611V → M in allele CYP2D6*35. 1 PublicationCorresponds to variant rs769258dbSNPEnsembl.1
Natural variantiVAR_07276525R → Q.1 PublicationCorresponds to variant rs138417770dbSNPEnsembl.1
Natural variantiVAR_00836726R → H in allele CYP2D6*21 and allele CYP2D6*46. 3 PublicationsCorresponds to variant rs28371696dbSNPEnsembl.1
Natural variantiVAR_00836828R → C in allele CYP2D6*22. Corresponds to variant rs138100349dbSNPEnsembl.1
Natural variantiVAR_00833634P → S in allele CYP2D6*10 and allele CYP2D6*14; poor debrisquone metabolism. 3 PublicationsCorresponds to variant rs1065852dbSNPEnsembl.1
Natural variantiVAR_00125642G → R in allele CYP2D6*12; impaired metabolism of sparteine. 1 PublicationCorresponds to variant rs5030862dbSNPEnsembl.1
Natural variantiVAR_00836985A → V in allele CYP2D6*23. Corresponds to variant rs267608310dbSNPEnsembl.1
Natural variantiVAR_02472091L → M.1 PublicationCorresponds to variant rs28371703dbSNPEnsembl.1
Natural variantiVAR_02472194H → R.1 PublicationCorresponds to variant rs28371704dbSNPEnsembl.1
Natural variantiVAR_072766104V → A in allele CYP2D6*88. 1 PublicationCorresponds to variant rs76187628dbSNPEnsembl.1
Natural variantiVAR_008337107T → I in allele CYP2D6*17; poor debrisquone metabolism. 2 PublicationsCorresponds to variant rs28371706dbSNPEnsembl.1
Natural variantiVAR_024722120F → I.1 PublicationCorresponds to variant rs1135822dbSNPEnsembl.1
Natural variantiVAR_072767142L → S in allele CYP2D6*89; >90% decrease of monooxygenase activity towards dextromethorphan and bufuralol. 1 PublicationCorresponds to variant rs375135093dbSNPEnsembl.1
Natural variantiVAR_072768147K → R in allele CYP2D6*90. 1 PublicationCorresponds to variant rs569229126dbSNPEnsembl.1
Natural variantiVAR_024723155E → K in allele CYP2D6*45A, allele CYP2D6*45B and allele CYP2D6*46. 2 PublicationsCorresponds to variant rs28371710dbSNPEnsembl.1
Natural variantiVAR_072769161C → S in allele CYP2D6*91. 1 Publication1
Natural variantiVAR_072770164F → L.1 Publication1
Natural variantiVAR_008338169G → R in allele CYP2D6*14; poor debrisquone metabolism. 1 PublicationCorresponds to variant rs5030865dbSNPEnsembl.1
Natural variantiVAR_008339212G → E in allele CYP2D6*6B and allele CYP2D6*6C. 1 PublicationCorresponds to variant rs5030866dbSNPEnsembl.1
Natural variantiVAR_072771215E → K >90% decrease of monooxygenase activity towards dextromethorphan and bufuralol. 1 PublicationCorresponds to variant rs567606867dbSNPEnsembl.1
Natural variantiVAR_072772219F → S.1 PublicationCorresponds to variant rs371793722dbSNPEnsembl.1
Natural variantiVAR_045679231L → P.Corresponds to variant rs17002853dbSNPEnsembl.1
Natural variantiVAR_008370237A → S in allele CYP2D6*33. 1 PublicationCorresponds to variant rs28371717dbSNPEnsembl.1
Natural variantiVAR_072773249T → P in allele CYP2D6*93; >90% decrease of monooxygenase activity towards dextromethorphan and bufuralol. 1 Publication1
Natural variantiVAR_008347281Missing in allele CYP2D6*9. 1 Publication1
Natural variantiVAR_008340296R → C in allele CYP2D6*2, allele CYP2D6*12, allele CYP2D6*14, allele CYP2D6*17, allele CYP2D6*45A, allele CYP2D6*45B and allele CYP2D6*46; slightly decrease of monooxygenase activity towards bufuralol. 5 PublicationsCorresponds to variant rs16947dbSNPEnsembl.1
Natural variantiVAR_008371297I → L in allele CYP2D6*24. 1
Natural variantiVAR_045680300A → G.Corresponds to variant rs1058170dbSNPEnsembl.1
Natural variantiVAR_014633311S → L.Corresponds to variant rs1800754dbSNPEnsembl.1
Natural variantiVAR_008348324H → P in allele CYP2D6*7; loss of activity. 1 PublicationCorresponds to variant rs5030867dbSNPEnsembl.1
Natural variantiVAR_072774327V → M.1 Publication1
Natural variantiVAR_059150329R → L.Corresponds to variant rs3915951dbSNPEnsembl.1
Natural variantiVAR_072775336D → N.1 PublicationCorresponds to variant rs745746329dbSNPEnsembl.1
Natural variantiVAR_072776337D → G in allele CYP2D6*94. 1 PublicationCorresponds to variant rs748712690dbSNPEnsembl.1
Natural variantiVAR_072777342V → M.1 PublicationCorresponds to variant rs750996195dbSNPEnsembl.1
Natural variantiVAR_008372343R → G in allele CYP2D6*25. Corresponds to variant rs267608295dbSNPEnsembl.1
Natural variantiVAR_072778344R → Q.1 PublicationCorresponds to variant rs76088846dbSNPEnsembl.1
Natural variantiVAR_045681365R → H.Corresponds to variant rs1058172dbSNPEnsembl.1
Natural variantiVAR_008373369I → T in allele CYP2D6*26. 1
Natural variantiVAR_059151373G → S.Corresponds to variant rs2856959dbSNPEnsembl.1
Natural variantiVAR_008374410E → K in allele CYP2D6*27. Corresponds to variant rs769157652dbSNPEnsembl.1
Natural variantiVAR_024724418E → K.1 PublicationCorresponds to variant rs149157808dbSNPEnsembl.1
Natural variantiVAR_072779440R → C >90% decrease of monooxygenase activity towards dextromethorphan and bufuralol. 1 PublicationCorresponds to variant rs777560972dbSNPEnsembl.1
Natural variantiVAR_072780457F → L in allele CYP2D6*97. 1 Publication1
Natural variantiVAR_072781463H → D in allele CYP2D6*98. 1 Publication1
Natural variantiVAR_024725469P → A.1 PublicationCorresponds to variant rs1135833dbSNPEnsembl.1
Natural variantiVAR_024726478H → Y.1 PublicationCorresponds to variant rs28371735dbSNPEnsembl.1
Natural variantiVAR_008341486S → T in allele CYP2D6*2, allele CYP2D6*10, allele CYP2D6*12, allele CYP2D6*14, allele CYP2D6*17, allele CYP2D6*45A, allele CYP2D6*45B and allele CYP2D6*46; impaired metabolism of sparteine. 6 PublicationsCorresponds to variant rs1135840dbSNPEnsembl.1
Natural variantiVAR_072782497R → C.1 PublicationCorresponds to variant rs370580423dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_044486118 – 168Missing in isoform 2. 1 PublicationAdd BLAST51

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M20403 mRNA. Translation: AAA52153.1.
X08006 mRNA. Translation: CAA30807.1.
M33388 Genomic DNA. Translation: AAA53500.1.
AY545216 Genomic DNA. Translation: AAS55001.1.
DQ282144 Genomic DNA. Translation: ABB77895.1.
DQ282145 Genomic DNA. Translation: ABB77896.1.
DQ282146 Genomic DNA. Translation: ABB77897.1.
DQ282151 Genomic DNA. Translation: ABB77899.1.
DQ282154 Genomic DNA. Translation: ABB77902.1.
DQ282155 Genomic DNA. Translation: ABB77903.1.
BX247885 Genomic DNA. Translation: CAP58857.1.
BC066877 mRNA. Translation: AAH66877.1.
BC075023 mRNA. Translation: AAH75023.1.
BC075024 mRNA. Translation: AAH75024.1.
CCDSiCCDS33657.1. [P10635-2]
CCDS46721.1. [P10635-1]
PIRiS01199. O4HUD1.
RefSeqiNP_000097.3. NM_000106.5. [P10635-1]
NP_001020332.2. NM_001025161.2. [P10635-2]
UniGeneiHs.648256.

Genome annotation databases

EnsembliENST00000359033; ENSP00000351927; ENSG00000100197. [P10635-2]
ENST00000360608; ENSP00000353820; ENSG00000100197. [P10635-1]
ENST00000612990; ENSP00000483677; ENSG00000275211.
GeneIDi1565.
KEGGihsa:1565.
UCSCiuc003bce.4. human. [P10635-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Web resourcesi

Cytochrome P450 Allele Nomenclature Committee

CYP2D6 alleles

Wikipedia

CYP2D6 entry

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M20403 mRNA. Translation: AAA52153.1.
X08006 mRNA. Translation: CAA30807.1.
M33388 Genomic DNA. Translation: AAA53500.1.
AY545216 Genomic DNA. Translation: AAS55001.1.
DQ282144 Genomic DNA. Translation: ABB77895.1.
DQ282145 Genomic DNA. Translation: ABB77896.1.
DQ282146 Genomic DNA. Translation: ABB77897.1.
DQ282151 Genomic DNA. Translation: ABB77899.1.
DQ282154 Genomic DNA. Translation: ABB77902.1.
DQ282155 Genomic DNA. Translation: ABB77903.1.
BX247885 Genomic DNA. Translation: CAP58857.1.
BC066877 mRNA. Translation: AAH66877.1.
BC075023 mRNA. Translation: AAH75023.1.
BC075024 mRNA. Translation: AAH75024.1.
CCDSiCCDS33657.1. [P10635-2]
CCDS46721.1. [P10635-1]
PIRiS01199. O4HUD1.
RefSeqiNP_000097.3. NM_000106.5. [P10635-1]
NP_001020332.2. NM_001025161.2. [P10635-2]
UniGeneiHs.648256.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2F9QX-ray3.00A/B/C/D34-497[»]
3QM4X-ray2.85A/B34-497[»]
3TBGX-ray2.10A/B/C/D34-497[»]
3TDAX-ray2.67A/B/C/D34-497[»]
4WNTX-ray2.60A/B34-497[»]
4WNUX-ray2.26A/B/C/D34-497[»]
4WNVX-ray2.35A/B/C/D48-497[»]
4WNWX-ray3.30A/B34-497[»]
4XRYX-ray2.50A/B/C/D34-497[»]
4XRZX-ray2.40A/B/C/D34-497[»]
ProteinModelPortaliP10635.
SMRiP10635.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi107940. 4 interactors.
STRINGi9606.ENSP00000353820.

Chemistry databases

BindingDBiP10635.
ChEMBLiCHEMBL289.
DrugBankiDB05812. Abiraterone.
DB01193. Acebutolol.
DB00316. Acetaminophen.
DB03128. Acetylcholine.
DB01426. Ajmaline.
DB00918. Almotriptan.
DB06203. Alogliptin.
DB00866. Alprenolol.
DB01424. Aminophenazone.
DB01118. Amiodarone.
DB00321. Amitriptyline.
DB00381. Amlodipine.
DB00613. Amodiaquine.
DB00543. Amoxapine.
DB00182. Amphetamine.
DB00701. Amprenavir.
DB00276. Amsacrine.
DB01435. Antipyrine.
DB01429. Aprindine.
DB01274. Arformoterol.
DB01238. Aripiprazole.
DB06697. Artemether.
DB06216. Asenapine.
DB00637. Astemizole.
DB00289. Atomoxetine.
DB01076. Atorvastatin.
DB00972. Azelastine.
DB00245. Benzatropine.
DB06770. Benzyl alcohol.
DB01244. Bepridil.
DB00195. Betaxolol.
DB01128. Bicalutamide.
DB00810. Biperiden.
DB00612. Bisoprolol.
DB00188. Bortezomib.
DB09128. Brexpiprazole.
DB00835. Brompheniramine.
DB00297. Bupivacaine.
DB00921. Buprenorphine.
DB01156. Bupropion.
DB00490. Buspirone.
DB00201. Caffeine.
DB01197. Captopril.
DB00748. Carbinoxamine.
DB06016. Cariprazine.
DB00521. Carteolol.
DB01136. Carvedilol.
DB00482. Celecoxib.
DB00567. Cephalexin.
DB00185. Cevimeline.
DB00475. Chlordiazepoxide.
DB00608. Chloroquine.
DB01114. Chlorphenamine.
DB00477. Chlorpromazine.
DB00356. Chlorzoxazone.
DB00169. Cholecalciferol.
DB01410. Ciclesonide.
DB01166. Cilostazol.
DB00501. Cimetidine.
DB01012. Cinacalcet.
DB00568. Cinnarizine.
DB00604. Cisapride.
DB00215. Citalopram.
DB00283. Clemastine.
DB04920. Clevidipine.
DB00349. Clobazam.
DB01242. Clomipramine.
DB00575. Clonidine.
DB00257. Clotrimazole.
DB00363. Clozapine.
DB09065. Cobicistat.
DB00907. Cocaine.
DB00318. Codeine.
DB00924. Cyclobenzaprine.
DB00531. Cyclophosphamide.
DB00091. Cyclosporine.
DB06292. Dapagliflozin.
DB00496. Darifenacin.
DB04840. Debrisoquin.
DB00705. Delavirdine.
DB01151. Desipramine.
DB00967. Desloratadine.
DB01234. Dexamethasone.
DB01191. Dexfenfluramine.
DB00633. Dexmedetomidine.
DB06701. Dexmethylphenidate.
DB01576. Dextroamphetamine.
DB00514. Dextromethorphan.
DB00647. Dextropropoxyphene.
DB01551. Dihydrocodeine.
DB00343. Diltiazem.
DB01093. Dimethyl sulfoxide.
DB01075. Diphenhydramine.
DB00757. Dolasetron.
DB01184. Domperidone.
DB00843. Donepezil.
DB00988. Dopamine.
DB00590. Doxazosin.
DB01142. Doxepin.
DB00997. Doxorubicin.
DB04855. Dronedarone.
DB00476. Duloxetine.
DB00625. Efavirenz.
DB00216. Eletriptan.
DB09039. Eliglustat.
DB01228. Encainide.
DB08899. Enzalutamide.
DB00751. Epinastine.
DB00530. Erlotinib.
DB01175. Escitalopram.
DB01466. Ethylmorphine.
DB01628. Etoricoxib.
DB01023. Felodipine.
DB06702. Fesoterodine.
DB00950. Fexofenadine.
DB08868. Fingolimod.
DB01195. Flecainide.
DB04841. Flunarizine.
DB00472. Fluoxetine.
DB00623. Fluphenazine.
DB01095. Fluvastatin.
DB00176. Fluvoxamine.
DB00983. Formoterol.
DB00674. Galantamine.
DB00317. Gefitinib.
DB01437. Glutethimide.
DB00889. Granisetron.
DB01218. Halofantrine.
DB00502. Haloperidol.
DB01159. Halothane.
DB00667. Histamine Phosphate.
DB00956. Hydrocodone.
DB00327. Hydromorphone.
DB01611. Hydroxychloroquine.
DB01005. Hydroxyurea.
DB00557. Hydroxyzine.
DB09053. Ibrutinib.
DB01177. Idarubicin.
DB04946. Iloperidone.
DB00619. Imatinib.
DB00458. Imipramine.
DB00224. Indinavir.
DB00332. Ipratropium bromide.
DB01029. Irbesartan.
DB00951. Isoniazid.
DB01167. Itraconazole.
DB09570. Ixazomib.
DB01026. Ketoconazole.
DB00598. Labetalol.
DB00448. Lansoprazole.
DB00528. Lercanidipine.
DB01235. Levodopa.
DB08918. Levomilnacipran.
DB00281. Lidocaine.
DB00589. Lisuride.
DB01206. Lomustine.
DB00836. Loperamide.
DB01601. Lopinavir.
DB00455. Loratadine.
DB04871. Lorcaserin.
DB00227. Lovastatin.
DB06708. Lumefantrine.
DB00934. Maprotiline.
DB00358. Mefloquine.
DB06691. Mepyramine.
DB01071. Mequitazine.
DB00933. Mesoridazine.
DB00333. Methadone.
DB01577. Methamphetamine.
DB00703. Methazolamide.
DB00763. Methimazole.
DB01403. Methotrimeprazine.
DB01028. Methoxyflurane.
DB06800. Methylnaltrexone.
DB00422. Methylphenidate.
DB01107. Methyprylon.
DB01233. Metoclopramide.
DB00264. Metoprolol.
DB00379. Mexiletine.
DB06148. Mianserin.
DB01110. Miconazole.
DB00211. Midodrine.
DB00834. Mifepristone.
DB00805. Minaprine.
DB08893. Mirabegron.
DB00370. Mirtazapine.
DB01171. Moclobemide.
DB00295. Morphine.
DB09049. Naloxegol.
DB00731. Nateglinide.
DB04861. Nebivolol.
DB01149. Nefazodone.
DB00220. Nelfinavir.
DB09048. Netupitant.
DB00238. Nevirapine.
DB00627. Niacin.
DB00622. Nicardipine.
DB00699. Nicergoline.
DB02701. Nicotinamide.
DB00184. Nicotine.
DB01115. Nifedipine.
DB04868. Nilotinib.
DB00336. Nitrofural.
DB00540. Nortriptyline.
DB00334. Olanzapine.
DB00338. Omeprazole.
DB00904. Ondansetron.
DB01096. Oxamniquine.
DB01580. Oxprenolol.
DB01062. Oxybutynin.
DB00497. Oxycodone.
DB06412. Oxymetholone.
DB01192. Oxymorphone.
DB01267. Paliperidone.
DB00377. Palonosetron.
DB06603. Panobinostat.
DB00715. Paroxetine.
DB06589. Pazopanib.
DB00738. Pentamidine.
DB01186. Pergolide.
DB01074. Perhexiline.
DB00850. Perphenazine.
DB00454. Pethidine.
DB00914. Phenformin.
DB00191. Phentermine.
DB01100. Pimozide.
DB00960. Pindolol.
DB01132. Pioglitazone.
DB00592. Piperazine.
DB01621. Pipotiazine.
DB08901. Ponatinib.
DB00175. Pravastatin.
DB01058. Praziquantel.
DB01087. Primaquine.
DB01035. Procainamide.
DB00433. Prochlorperazine.
DB00396. Progesterone.
DB01131. Proguanil.
DB01069. Promethazine.
DB01182. Propafenone.
DB00818. Propofol.
DB00571. Propranolol.
DB00344. Protriptyline.
DB00852. Pseudoephedrine.
DB00205. Pyrimethamine.
DB01224. Quetiapine.
DB00908. Quinidine.
DB00468. Quinine.
DB01129. Rabeprazole.
DB00863. Ranitidine.
DB00243. Ranolazine.
DB00234. Reboxetine.
DB00409. Remoxipride.
DB01201. Rifapentine.
DB00734. Risperidone.
DB00503. Ritonavir.
DB00989. Rivastigmine.
DB09291. Rolapitant.
DB00268. Ropinirole.
DB00296. Ropivacaine.
DB00412. Rosiglitazone.
DB05271. Rotigotine.
DB01232. Saquinavir.
DB01037. Selegiline.
DB06144. Sertindole.
DB01104. Sertraline.
DB00203. Sildenafil.
DB00641. Simvastatin.
DB00398. Sorafenib.
DB00259. Sulfanilamide.
DB06729. Sulfaphenazole.
DB00675. Tamoxifen.
DB00706. Tamsulosin.
DB06204. Tapentadol.
DB00976. Telithromycin.
DB06287. Temsirolimus.
DB00857. Terbinafine.
DB04844. Tetrabenazine.
DB00277. Theophylline.
DB00679. Thioridazine.
DB01623. Thiothixene.
DB00208. Ticlopidine.
DB00373. Timolol.
DB01409. Tiotropium.
DB00932. Tipranavir.
DB01036. Tolterodine.
DB05109. Trabectedin.
DB00193. Tramadol.
DB00752. Tranylcypromine.
DB00656. Trazodone.
DB00726. Trimipramine.
DB00792. Tripelennamine.
DB00427. Triprolidine.
DB00209. Trospium.
DB09076. Umeclidinium.
DB08881. Vemurafenib.
DB00285. Venlafaxine.
DB00661. Verapamil.
DB06684. Vilazodone.
DB00570. Vinblastine.
DB00361. Vinorelbine.
DB09068. Vortioxetine.
DB01392. Yohimbine.
DB00549. Zafirlukast.
DB00943. Zalcitabine.
DB00246. Ziprasidone.
DB00425. Zolpidem.
DB01624. Zuclopenthixol.
GuidetoPHARMACOLOGYi1329.
SwissLipidsiSLP:000001204.

PTM databases

iPTMnetiP10635.
PhosphoSitePlusiP10635.

Polymorphism and mutation databases

BioMutaiCYP2D6.
DMDMi84028191.

Proteomic databases

PaxDbiP10635.
PeptideAtlasiP10635.
PRIDEiP10635.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000359033; ENSP00000351927; ENSG00000100197. [P10635-2]
ENST00000360608; ENSP00000353820; ENSG00000100197. [P10635-1]
ENST00000612990; ENSP00000483677; ENSG00000275211.
GeneIDi1565.
KEGGihsa:1565.
UCSCiuc003bce.4. human. [P10635-1]

Organism-specific databases

CTDi1565.
DisGeNETi1565.
GeneCardsiCYP2D6.
HGNCiHGNC:2625. CYP2D6.
HPAiHPA045223.
MalaCardsiCYP2D6.
MIMi124030. gene.
608902. phenotype.
neXtProtiNX_P10635.
OpenTargetsiENSG00000100197.
Orphaneti413667. Antidepressant or antipsychotics toxicity or dose selection.
240867. Codeine toxicity.
240947. Resistance to tamoxifene.
PharmGKBiPA128.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0156. Eukaryota.
COG2124. LUCA.
GeneTreeiENSGT00760000118775.
HOVERGENiHBG015789.
InParanoidiP10635.
KOiK17712.
OMAiDEANWEK.
OrthoDBiEOG091G0BT8.
PhylomeDBiP10635.
TreeFamiTF352043.

Enzyme and pathway databases

BioCyciZFISH:HS01997-MONOMER.
BRENDAi1.14.14.1. 2681.
1.14.99.38. 2681.
ReactomeiR-HSA-211935. Fatty acids.
R-HSA-211958. Miscellaneous substrates.
R-HSA-211981. Xenobiotics.
R-HSA-211999. CYP2E1 reactions.
SABIO-RKP10635.

Miscellaneous databases

EvolutionaryTraceiP10635.
GeneWikiiCYP2D6.
GenomeRNAii1565.
PROiP10635.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000100197.
CleanExiHS_CYP2D6.
ExpressionAtlasiP10635. baseline and differential.
GenevisibleiP10635. HS.

Family and domain databases

Gene3Di1.10.630.10. 1 hit.
InterProiIPR001128. Cyt_P450.
IPR017972. Cyt_P450_CS.
IPR002401. Cyt_P450_E_grp-I.
IPR008069. Cyt_P450_E_grp-I_CYP2D-like.
[Graphical view]
PfamiPF00067. p450. 1 hit.
[Graphical view]
PRINTSiPR00463. EP450I.
PR01686. EP450ICYP2D.
PR00385. P450.
SUPFAMiSSF48264. SSF48264. 1 hit.
PROSITEiPS00086. CYTOCHROME_P450. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiCP2D6_HUMAN
AccessioniPrimary (citable) accession number: P10635
Secondary accession number(s): Q16752
, Q2XND6, Q2XND7, Q2XNE0, Q6B012, Q6NXU8
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 1, 1989
Last sequence update: December 20, 2005
Last modified: November 2, 2016
This is version 186 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 22
    Human chromosome 22: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.