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3.A.1.205.4
Multidrug resistance protein, Cdr1 (Candida drug resistance 1) confers resistance to cycloheximide, xenobiotics and antifungal agents such as azoles and terbinafine (Holmes et al., 2006; Schuetzer-Muehlbauer et al., 2003); also, transports phospholipids (Shukla et al., 2007). It is the major fluconazole efflux system in fluconazole-resistant C. albicans (Holmes et al., 2008; Basso et al., 2010). Similar to Cdr2. For additional details of both systems, as well as other MDR pumps in various Candida species, see Cannon et al., 1998. Chimeras between Cdr1 and Cdr2 revealed regions determining substrate specificity (Tanabe et al., 2011).  The protein has a large polyspecific drug-binding pocket formed by many of the TMSs (Rawal et al. 2013).  The macrocyclic polyketide, FK520, an analologue of antifungal FK506, and a potent immunosuppressant that prevents T-cell proliferation, displays fungicidal synergism with azoles in Candida albicans and inhibits drug efflux mediated by ABC multidrug transporters including Cdr (Nim et al. 2014).  TMS 5 residues impart substrate specificity and selectively act as a communication link between ATP hydrolysis and drug transport (Puri et al. 2009).  The 4 domains (2Cs and 2 Ms) are connected by intracellular loops that allow coupling between ATP hydrolysis and transport  (Shah et al. 2015) and faciliitate membrane targetting (Shah et al. 2015). Multiple drug binding sites have been identified (Nim et al. 2016). The system also transports steroid hormones such as β-estradiol and corticosterone as well as rhodamine 6G using specific but overlapping binding sites (Baghel et al. 2017). The 23-membered-ring macrolide, tacrolimus, a commonly used immunosuppressant also known as FK506, is a broad-spectrum inhibitor and an efflux pump substrate, and mutations that minimize its export have been isolated (Tanabe et al. 2018). A structural motif, called the E-helix, plays a role in the maintenance of proper structural fold and/or inter-domain contacts (Vishwakarma et al. 2019).

Accession Number:P43071
Protein Name:Cdr1
Length:1501
Molecular Weight:169938.00
Species:Candida albicans (Yeast) [5476]
Number of TMSs:13
Location1 / Topology2 / Orientation3: Membrane1 / Multi-pass membrane protein2
Substrate steroid hormones, corticosterone, beta-estradiol, Rhodamine 6G, cycloheximide, Azoles, Terbinafine, Phosphoplipids, Fluconazole

Cross database links:

Pfam: PF01061    PF00005    PF06422   

Gene Ontology

GO:0016021 C:integral to membrane
GO:0005524 F:ATP binding
GO:0042626 F:ATPase activity, coupled to transmembrane m...
GO:0046677 P:response to antibiotic
GO:0046898 P:response to cycloheximide
GO:0006810 P:transport

References (1)

[1] “Molecular cloning and characterization of a novel gene of Candida albicans, CDR1, conferring multiple resistance to drugs and antifungals.”  Prasad R.et.al.   7614555

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Predict TMSs (Predict number of transmembrane segments)
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FASTA formatted sequence
1:	MSDSKMSSQD ESKLEKAISQ DSSSENHSIN EYHGFDAHTS ENIQNLARTF THDSFKDDSS 
61:	AGLLKYLTHM SEVPGVNPYE HEEINNDQLN PDSENFNAKF WVKNLRKLFE SDPEYYKPSK 
121:	LGIGYRNLRA YGVANDSDYQ PTVTNALWKL ATEGFRHFQK DDDSRYFDIL KSMDAIMRPG 
181:	ELTVVLGRPG AGCSTLLKTI AVNTYGFHIG KESQITYDGL SPHDIERHYR GDVIYSAETD 
241:	VHFPHLSVGD TLEFAARLRT PQNRGEGIDR ETYAKHMASV YMATYGLSHT RNTNVGNDFV 
301:	RGVSGGERKR VSIAEASLSG ANIQCWDNAT RGLDSATALE FIRALKTSAV ILDTTPLIAI 
361:	YQCSQDAYDL FDKVVVLYEG YQIFFGKATK AKEYFEKMGW KCPQRQTTAD FLTSLTNPAE 
421:	REPLPGYEDK VPRTAQEFET YWKNSPEYAE LTKEIDEYFV ECERSNTRET YRESHVAKQS 
481:	NNTRPASPYT VSFFMQVRYG VARNFLRMKG DPSIPIFSVF GQLVMGLILS SVFYNLSQTT 
541:	GSFYYRGAAM FFAVLFNAFS SLLEIMSLFE ARPIVEKHKK YALYRPSADA LASIISELPV 
601:	KLAMSMSFNF VFYFMVNFRR NPGRFFFYWL MCIWCTFVMS HLFRSIGAVS TSISGAMTPA 
661:	TVLLLAMVIY TGFVIPTPSM LGWSRWINYI NPVGYVFESL MVNEFHGREF QCAQYVPSGP 
721:	GYENISRSNQ VCTAVGSVPG NEMVSGTNYL AGAYQYYNSH KWRNLGITIG FAVFFLAIYI 
781:	ALTEFNKGAM QKGEIVLFLK GSLKKHKRKT AASNKGDIEA GPVAGKLDYQ DEAEAVNNEK 
841:	FTEKGSTGSV DFPENREIFF WRDLTYQVKI KKEDRVILDH VDGWVKPGQI TALMGASGAG 
901:	KTTLLNCLSE RVTTGIITDG ERLVNGHALD SSFQRSIGYV QQQDVHLPTS TVREALQFSA 
961:	YLRQSNKISK KEKDDYVDYV IDLLEMTDYA DALVGVAGEG LNVEQRKRLT IGVELVAKPK 
1021:	LLLFLDEPTS GLDSQTAWSI CKLMRKLADH GQAILCTIHQ PSALIMAEFD RLLFLQKGGR 
1081:	TAYFGELGEN CQTMINYFEK YGADPCPKEA NPAEWMLQVV GAAPGSHAKQ DYFEVWRNSS 
1141:	EYQAVREEIN RMEAELSKLP RDNDPEALLK YAAPLWKQYL LVSWRTIVQD WRSPGYIYSK 
1201:	IFLVVSAALF NGFSFFKAKN NMQGLQNQMF SVFMFFIPFN TLVQQMLPYF VKQRDVYEVR 
1261:	EAPSRTFSWF AFIAGQITSE IPYQVAVGTI AFFCWYYPLG LYNNATPTDS VNPRGVLMWM 
1321:	LVTAFYVYTA TMGQLCMSFS ELADNAANLA TLLFTMCLNF CGVLAGPDVL PGFWIFMYRC 
1381:	NPFTYLVQAM LSTGLANTFV KCAEREYVSV KPPNGESCST YLDPYIKFAG GYFETRNDGS 
1441:	CAFCQMSSTN TFLKSVNSLY SERWRNFGIF IAFIAINIIL TVIFYWLARV PKGNREKKNK 
1501:	K