Q94IN5 (PNO_EUGGR) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Pyruvate dehydrogenase [NADP+], mitochondrial
EC=1.16.1.5
EC=1.2.1.51

Alternative name(s):
Aquacobalamin reductase [NADPH]
EgPNOmt
Pyruvate:NADP+ oxidoreductase

Gene names

Name:

PNO

Organism

Euglena gracilis

Taxonomic identifier

3039 [NCBI]

Taxonomic lineage

Eukaryota › Euglenozoa › Euglenida › Euglenales › Euglena

Protein attributes

Sequence length	1803 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	Pyruvate dehydrogenase [NADP+] is one of three enzymes participating in respiratory metabolism. Ref.5 Aquacobalamin reductase is involved in the synthesis of cobalamin coenzymes. Ref.5
Catalytic activity	Pyruvate + CoA + NADP+ = acetyl-CoA + CO2 + NADPH. Ref.1 2 cob(II)alamin + NADP+ = 2 aquacob(III)alamin + NADPH.
Cofactor	Binds 1 FAD per subunit. Ref.5 Binds 1 FMN per subunit. Ref.5 Thiamine pyrophosphate. Ref.5
Subunit structure	Homodimer. Ref.5
Subcellular location	Mitochondrion Ref.2 Ref.5.
Induction	Expressed in both aerobic and anaerobic conditions.
Miscellaneous	Arose from gene fusion of pyruvate:ferredoxin oxidoreductase and cytochrome-P450 reductase. Gene fusion has only been found in Euglena and Cryptosporidium. Ref.1 Ref.2 Euglena cells absolutely require thiamine for growth due to the lack of a pyrimidine formation biosynthetic pathway. Thiamine is actively taken up into the cells and is used as a cofactor after being converted to TPP (thiamine pyrophosphate). Ref.5
Sequence similarities	Contains 2 4Fe-4S ferredoxin-type domains. Contains 1 FAD-binding FR-type domain. Contains 1 flavodoxin-like domain.

Ontologies

Keywords
Biological process	Electron transport Transport
Cellular component	Mitochondrion
Domain	Repeat Transit peptide
Ligand	4Fe-4S FAD FMN Flavoprotein Iron Iron-sulfur Metal-binding NADP Thiamine pyrophosphate
Molecular function	Oxidoreductase
Technical term	Direct protein sequencing
Gene Ontology (GO)
Biological process	cellular respiration Inferred from direct assay Ref.5. Source: UniProtKB electron transport chain Inferred from electronic annotation. Source: UniProtKB-KW pyruvate metabolic process Inferred from direct assay Ref.2Ref.5. Source: UniProtKB transport Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	mitochondrion Inferred from direct assay Ref.2Ref.5. Source: UniProtKB
Molecular function	4 iron, 4 sulfur cluster binding Inferred from electronic annotation. Source: UniProtKB-KW FMN binding Inferred from electronic annotation. Source: InterPro aquacobalamin reductase (NADPH) activity Inferred from electronic annotation. Source: EC electron carrier activity Inferred from electronic annotation. Source: InterPro iron ion binding Inferred from electronic annotation. Source: InterPro pyruvate dehydrogenase (NADP+) activity Inferred from electronic annotation. Source: EC thiamine pyrophosphate binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Transit peptide	1 – 37	37	Mitochondrion Ref.3 Ref.5
	Chain	38 – 1803	1766	Pyruvate dehydrogenase [NADP+], mitochondrial Ref.5		PRO_0000023867
Regions
	Domain	747 – 776	30	4Fe-4S ferredoxin-type 1
	Domain	802 – 831	30	4Fe-4S ferredoxin-type 2
	Domain	1248 – 1391	144	Flavodoxin-like
	Domain	1425 – 1650	226	FAD-binding FR-type
	Nucleotide binding	1458 – 1469	12	FAD By similarity UniProtKB Q09878
	Nucleotide binding	1585 – 1595	11	FAD By similarity UniProtKB Q09878
Sites
	Metal binding	756	1	Iron-sulfur 1 (4Fe-4S) Potential UniProtKB Q06879
	Metal binding	759	1	Iron-sulfur 1 (4Fe-4S) Potential UniProtKB Q06879
	Metal binding	762	1	Iron-sulfur 1 (4Fe-4S) Potential UniProtKB Q06879
	Metal binding	766	1	Iron-sulfur 1 (4Fe-4S) Potential UniProtKB Q06879
	Metal binding	811	1	Iron-sulfur 2 (4Fe-4S) Potential UniProtKB Q06879
	Metal binding	814	1	Iron-sulfur 2 (4Fe-4S) Potential UniProtKB Q06879
	Metal binding	817	1	Iron-sulfur 2 (4Fe-4S) Potential UniProtKB Q06879
	Metal binding	821	1	Iron-sulfur 2 (4Fe-4S) Potential UniProtKB Q06879
Experimental info
	Sequence conflict	50	1	P → S AA sequence Ref.3
	Sequence conflict	52	1	H → A AA sequence Ref.3
	Sequence conflict	53	1	V → K AA sequence Ref.3
	Sequence conflict	598 – 599	2	NV → KL in BAB12024. Ref.1
	Sequence conflict	1256	1	T → E AA sequence Ref.3
	Sequence conflict	1558	1	M → T in BAB12024. Ref.1
	Sequence conflict	1673 – 1674	2	ER → DG in BAB12024. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Q94IN5 [UniParc]. Last modified December 1, 2001. Version 1. Checksum: 5AFB6E3869CADCC6	FASTA	1,803	199,821
	10 20 30 40 50 60 MKQSVRPIIS NVLRKEVALY STIIGQDKGK EPTGRTYTSG PKPASHIEVP HHVTVPATDR 70 80 90 100 110 120 TPNPDAQFFQ SVDGSQATSH VAYALSDTAF IYPITPSSVM GELADVWMAQ GRKNAFGQVV 130 140 150 160 170 180 DVREMQSEAG AAGALHGALA AGAIATTFTA SQGLLLMIPN MYKIAGELMP SVIHVAAREL 190 200 210 220 230 240 AGHALSIFGG HADVMAVRQT GWAMLCSHTV QQSHDMALIS HVATLKSSIP FVHFFDGFRT 250 260 270 280 290 300 SHEVNKIKML PYAELKKLVP PGTMEQHWAR SLNPMHPTIR GTNQSADIYF QNMESANQYY 310 320 330 340 350 360 TDLAEVVQET MDEVAPYIGR HYKIFEYVGA PDAEEVTVLM GSGATTVNEA VDLLVKRGKK 370 380 390 400 410 420 VGAVLVHLYR PWSTKAFEKV LPKTVKRIAA LDRCKEVTAL GEPLYLDVSA TLNLFPERQN 430 440 450 460 470 480 VKVIGGRYGL GSKDFIPEHA LAIYANLASE NPIQRFTVGI TDDVTGTSVP FVNERVDTLP 490 500 510 520 530 540 EGTRQCVFWG IGSDGTVGAN RSAVRIIGDN SDLMVQAYFQ FDAFKSGGVT SSHLRFGPKP 550 560 570 580 590 600 ITAQYLVTNA DYIACHFQEY VKRFDMLDAI REGGTFVLNS RWTTEDMEKE IPADFRRNVA 610 620 630 640 650 660 QKKVRFYNVD ARKICDSFGL GKRINMLMQA CFFKLSGVLP LAEAQRLLNE SIVHEYGKKG 670 680 690 700 710 720 GKVVEMNQAV VNAVFAGDLP QEVQVPAAWA NAVDTSTRTP TGIEFVDKIM RPLMDFKGDQ 730 740 750 760 770 780 LPVSVMTPGG TFPVGTTQYA KRAIAAFIPQ WIPANCTQCN YCSYVCPHAT IRPFVLTDQE 790 800 810 820 830 840 VQLAPESFVT RKAKGDYQGM NFRIQVAPED CTGCQVCVET CPDDALEMTD AFTATPVQRT 850 860 870 880 890 900 NWEFAIKVPN RGTMTDRYSL KGSQFQQPLL EFSGACEGCG ETPYVKLLTQ LFGERTVIAN 910 920 930 940 950 960 ATGCSSIWGG TAGLAPYTTN AKGQGPAWGN SLFEDNAEFG FGIAVANAQK RSRVRDCILQ 970 980 990 1000 1010 1020 AVEKKVADEG LTTLLAQWLQ DWNTGDKTLK YQDQIIAGLA QQRSKDPLLE QIYGMKDMLP 1030 1040 1050 1060 1070 1080 NISQWIIGGD GWANDIGFGG LDHVLASGQN LNVLVLDTEM YSNTGGQASK STHMASVAKF 1090 1100 1110 1120 1130 1140 ALGGKRTNKK NLTEMAMSYG NVYVATVSHG NMAQCVKAFV EAESYDGPSL IVGYAPCIEH 1150 1160 1170 1180 1190 1200 GLRAGMARMV QESEAAIATG YWPLYRFDPR LATEGKNPFQ LDSKRIKGNL QEYLDRQNRY 1210 1220 1230 1240 1250 1260 VNLKKNNPKG ADLLKSQMAD NITARFNRYR RMLEGPNTKA AAPSGNHVTI LYGSETGNSE 1270 1280 1290 1300 1310 1320 GLAKELATDF ERREYSVAVQ ALDDIDVADL ENMGFVVIAV STCGQGQFPR NSQLFWRELQ 1330 1340 1350 1360 1370 1380 RDKPEGWLKN LKYTVFGLGD STYYFYCHTA KQIDARLAAL GAQRVVPIGF GDDGDEDMFH 1390 1400 1410 1420 1430 1440 TGFNNWIPSV WNELKTKTPE EALFTPSIAV QLTPNATPQD FHFAKSTPVL SITGAERITP 1450 1460 1470 1480 1490 1500 ADHTRNFVTI RWKTDLSYQV GDSLGVFPEN TRSVVEEFLQ YYGLNPKDVI TIENKGSREL 1510 1520 1530 1540 1550 1560 PHCMAVGDLF TKVLDILGKP NNRFYKTLSY FAVDKAEKER LLKIAEMGPE YSNILSEMYH 1570 1580 1590 1600 1610 1620 YADIFHMFPS ARPTLQYLIE MIPNIKPRYY SISSAPIHTP GEVHSLVLID TWITLSGKHR 1630 1640 1650 1660 1670 1680 TGLTCTMLEH LQAGQVVDGC IHPTAMEFPD HEKPVVMCAM GSGLAPFVAF LRERSTLRKQ 1690 1700 1710 1720 1730 1740 GKKTGNMALY FGNRYEKTEF LMKEELKGHI NDGLLTLRCA FSRDDPKKKV YVQDLIKMDE 1750 1760 1770 1780 1790 1800 KMMYDYLVVQ KGSMYCCGSR SFIKPVQESL KHCFMKAGGL TAEQAENEVI DMFTTGRYNI EAW

References

[1]	"The origin of pyruvate:NADP+ oxidoreductase in mitochondria of Euglena gracilis." Nakazawa M., Inui H., Yamaji R., Yamamoto T., Takenaka S., Ueda M., Nakano Y., Miyatake K. FEBS Lett. 479:155-156(2000) [PubMed: 11023353] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Pyruvate: NADP oxidoreductase from the mitochondrion of Euglena gracilis and from the apicomplexan Cryptosporidium parvum: a biochemical relic linking pyruvate metabolism in mitochondriate and amitochondriate protists." Rotte C., Stejskal F., Zhu G., Keithly J.S., Martin W. Mol. Biol. Evol. 18:710-720(2001) [PubMed: 11319255] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], SUBCELLULAR LOCATION, TISSUE SPECIFICITY. Strain: SAG1224-5/25.
[3]	"Pyruvate:NADP+ oxidoreductase from Euglena gracilis: limited proteolysis of the enzyme with trypsin." Inui H., Yamaji R., Saidoh H., Miyatake K., Nakano Y., Kitaoka S. Arch. Biochem. Biophys. 286:270-276(1991) [PubMed: 1910287] [Abstract] Cited for: PROTEIN SEQUENCE OF 38-53 AND 1240-1259.
[4]	"Characterization of aquacobalamin reductase (NADPH) from Euglena gracilis." Watanabe F., Yamaji R., Isegawa Y., Yamamoto T., Tamura Y., Nakano Y. Arch. Biochem. Biophys. 305:421-427(1993) [PubMed: 8373179] [Abstract] Cited for: PROTEIN SEQUENCE OF 1240-1255, CHARACTERIZATION.
[5]	"Pyruvate:NADP(+) oxidoreductase is stabilized by its cofactor, thiamin pyrophosphate, in mitochondria of Euglena gracilis." Nakazawa M., Takenaka S., Ueda M., Inui H., Nakano Y., Miyatake K. Arch. Biochem. Biophys. 411:183-188(2003) [PubMed: 12623066] [Abstract] Cited for: FUNCTION, COFACTOR, SUBUNIT, SUBCELLULAR LOCATION.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AB021127 mRNA. Translation: BAB12024.1. AJ278425 mRNA. Translation: CAC37628.1.
PIR	S36876.
3D structure databases
ProteinModelPortal	Q94IN5.
ModBase	Search...
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Family and domain databases
InterPro	IPR001450. 4Fe4S-bd_dom. IPR017896. 4Fe4S_Fe-S-bd. IPR017900. 4Fe4S_Fe_S_CS. IPR003097. FAD-binding_1. IPR017927. Fd_Rdtase_FAD-bd. IPR001094. Flavdoxin. IPR008254. Flavodoxin/NO_synth. IPR001709. Flavoprot_Pyr_Nucl_cyt_Rdtase. IPR012285. Fum_reductase_C. IPR023173. NADPH_Cyt_P450_Rdtase_dom3. IPR001433. OxRdtase_FAD/NAD-bd. IPR019456. Pyrv-flavodox_OxRtase_EKR. IPR019752. Pyrv/ketoisovalerate_OxRed_cat. IPR002880. Pyrv_Fd/Flavodoxin_OxRdtase_N. IPR011895. Pyrv_flavodox_OxRed. IPR002869. Pyrv_flavodox_OxRed_cen. IPR017938. Riboflavin_synthase-like_b-brl. IPR011766. TPP_enzyme-bd_C. IPR009014. Transketo_C/Pyr-ferredox_oxred. IPR015941. Transketolase-like_C. [Graphical view]
Gene3D	G3DSA:1.10.1060.10. Fum_reductase_C. 1 hit. G3DSA:1.20.990.10. NADPH_Cyt_P450_Rdtase_dom3. 1 hit. G3DSA:4.10.780.10. Pyrv-flavodox_OxRtase_EKR. 1 hit. G3DSA:3.40.920.10. Pyrv_Fd/Flavodoxin_OxRdtase. 1 hit. G3DSA:3.40.50.920. Transketo_C_like. 1 hit.
Pfam	PF10371. EKR. 1 hit. PF00667. FAD_binding_1. 1 hit. PF12838. Fer4_7. 1 hit. PF00258. Flavodoxin_1. 1 hit. PF00175. NAD_binding_1. 1 hit. PF01558. POR. 1 hit. PF01855. POR_N. 1 hit. PF02775. TPP_enzyme_C. 1 hit. [Graphical view]
PRINTS	PR00369. FLAVODOXIN. PR00371. FPNCR.
SMART	SM00890. EKR. 1 hit. [Graphical view]
SUPFAM	SSF53323. Pyrv_Fd/Flavodoxin_OxRdtase. 1 hit. SSF63380. Riboflavin_synthase_like_b-brl. 1 hit. SSF52922. Transketo_C_like. 1 hit.
TIGRFAMs	TIGR02176. Pyruv_ox_red. 1 hit.
PROSITE	PS00198. 4FE4S_FER_1. 2 hits. PS51379. 4FE4S_FER_2. 2 hits. PS51384. FAD_FR. 1 hit. PS00201. FLAVODOXIN. False negative. PS50902. FLAVODOXIN_LIKE. 1 hit. [Graphical view]
ProtoNet	Search...

Entry information

Entry name

PNO_EUGGR

Accession

Primary (citable) accession number: Q94IN5
Secondary accession number(s): Q9FZP8

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 19, 2003
Last sequence update:	December 1, 2001
Last modified:	October 19, 2011
This is version 74 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)