P16237 (HMDH_SCHMA) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names	Recommended name: 3-hydroxy-3-methylglutaryl-coenzyme A reductase Short name=HMG-CoA reductase EC=1.1.1.34
Organism	Schistosoma mansoni (Blood fluke)
Taxonomic identifier	6183 [NCBI]
Taxonomic lineage	Eukaryota › Metazoa › Platyhelminthes › Trematoda › Digenea › Strigeidida › Schistosomatoidea › Schistosomatidae › Schistosoma

Protein attributes

Sequence length	948 AA.
Sequence status	Complete.
Protein existence	Evidence at transcript level

General annotation (Comments)

Function	This transmembrane glycoprotein is involved in the control of cholesterol and nonsterol isoprenoid compounds biosynthesis. It is the rate-limiting enzyme of sterol biosynthesis.
Catalytic activity	(R)-mevalonate + CoA + 2 NADP+ = (S)-3-hydroxy-3-methylglutaryl-CoA + 2 NADPH.
Pathway	Metabolic intermediate biosynthesis; (R)-mevalonate biosynthesis; (R)-mevalonate from acetyl-CoA: step 3/3.
Subcellular location	Endoplasmic reticulum membrane; Multi-pass membrane protein. Peroxisome membrane; Multi-pass membrane protein.
Sequence similarities	Belongs to the HMG-CoA reductase family.

Ontologies

Keywords
Biological process	Cholesterol biosynthesis Lipid synthesis Steroid biosynthesis Sterol biosynthesis
Cellular component	Endoplasmic reticulum Membrane Peroxisome
Domain	Transmembrane Transmembrane helix
Ligand	NADP
Molecular function	Oxidoreductase
PTM	Glycoprotein
Gene Ontology (GO)
Biological process	cholesterol biosynthetic process Inferred from electronic annotation. Source: UniProtKB-KW coenzyme A metabolic process Inferred from electronic annotation. Source: InterPro isoprenoid biosynthetic process Inferred from electronic annotation. Source: InterPro
Cellular component	endoplasmic reticulum membrane Inferred from electronic annotation. Source: UniProtKB-SubCell integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW peroxisomal membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	NADP binding Inferred from electronic annotation. Source: InterPro hydroxymethylglutaryl-CoA reductase (NADPH) activity Inferred from electronic annotation. Source: EC
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 948	948	3-hydroxy-3-methylglutaryl-coenzyme A reductase		PRO_0000114432
Regions
	Transmembrane	9 – 25	17	Helical; Potential
	Transmembrane	55 – 71	17	Helical; Potential
	Transmembrane	96 – 112	17	Helical; Potential
	Transmembrane	124 – 140	17	Helical; Potential
	Transmembrane	207 – 223	17	Helical; Potential
	Transmembrane	286 – 302	17	Helical; Potential
	Transmembrane	347 – 363	17	Helical; Potential
	Region	364 – 466	103	Linker
	Region	467 – 948	482	Catalytic
Sites
	Active site	567	1	Charge relay system By similarity
	Active site	699	1	Charge relay system By similarity
	Active site	777	1	Charge relay system By similarity
	Active site	869	1	Proton donor By similarity
Amino acid modifications
	Glycosylation	316	1	N-linked (GlcNAc...) Potential
	Glycosylation	430	1	N-linked (GlcNAc...) Potential
	Glycosylation	895	1	N-linked (GlcNAc...) Potential

Sequences

	Sequence		Length	Mass (Da)
	P16237 [UniParc]. Last modified April 1, 1990. Version 1. Checksum: CD5B9B84776371BF	FASTA	948	107,045
	10 20 30 40 50 60 MLKILNTVLL FFDCFSTGTF FVLLIYLFTR LRTHLLHFSS SNCHLDVIIY QSRAVIIFLV 70 80 90 100 110 120 VFVYFIGVLT CKINDKILVH TMLRNKRQLN TLFYTLILFT FALCSLSSVL FVPYTSFAIF 130 140 150 160 170 180 LLSTSVFLLF SDLSVFFIVL EYYLLEIELV NYEHAKRHCL LSHLFSNQLF VDHMLGMFLK 190 200 210 220 230 240 TSLFSISTTS KYAYLESIFK CTLMEQIIYI MIVFVFLPSF MRIFASYAKR MYGEQKKCLV 250 260 270 280 290 300 SNKGVSSSTR KRRHSYSSGH SYVEYRRMSV HNLIGYVVNP NCHYKCWSTT FVIFVSLIIL 310 320 330 340 350 360 HLNNRYSERI SSFKHNSSEN EVFPVLYHIT AYEVTSIFHF IYNIFHVINA NLVVYLFLGL 370 380 390 400 410 420 FLFKRIRLNK PINSQLRNLN IPKIKETLIS DQVKQSPVLP KFSKKLNDIP LQSRKRIYCL 430 440 450 460 470 480 HKDDDYIDRN DSSSVSTFSN TCKNSNERPS NVLDLDMLTE KIKQGLGHEL SDTEILQLLS 490 500 510 520 530 540 HGRLKTRELE SVVRNPFRAV ELRRLDLSTF LNNPHIIERI PYKDYDYRLV YGQCCEEVIG 550 560 570 580 590 600 YMPIPVGKIG PLLLDGRSHY IPLATTEGCL VASTNRGCRA IFLAGGIKSV VYRDQMTRAP 610 620 630 640 650 660 VVWFPSIIDS VKCIAWIDSE EGFQTLKSAF DKTSAHVNLL SVFACPAGRY IHIRFAARTG 670 680 690 700 710 720 DAMGMNMVSK ATDSALHCLK KYFSNMQVIS LSGNMCTDKK PATINTILGR GKSVIAEAHL 730 740 750 760 770 780 SADVLAQVLH TNAQRLARLT HSKNWIGSAM AGCPGMMGCN AHAANIIAGM FAATGQDLAQ 790 800 810 820 830 840 VVDSSSCLTQ LEVDLSDDSL VASVTMPCLE VGTVGGGTRL SGQRACLDLL DLSVDRPTEH 850 860 870 880 890 900 LSRIIAGTVL AAELSLMAAL DTDDLVKAHM HFNRAKQSTN SHSCSHSTTT DNNDNISNIY 910 920 930 940 DNHNVALSSK IPVTDNSDIR ESVHSLHVKP FPVKSDLSVN PEISHYTM

References

[1]	"Molecular cloning and sequence analysis of 3-hydroxy-3-methylglutaryl-coenzyme A reductase from the human parasite Schistosoma mansoni." Rajkovic A., Simonsen J.N., Davis R.E., Rottman F.M. Proc. Natl. Acad. Sci. U.S.A. 86:8217-8221(1989) [PubMed: 2813388] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"RNA trans-splicing in flatworms. Analysis of trans-spliced mRNAs and genes in the human parasite, Schistosoma mansoni." Davis R.E., Hardwick C., Tavernier P., Hodgson S., Singh H. J. Biol. Chem. 270:21813-21819(1995) [PubMed: 7665603] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-236. Strain: Puerto Rican.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	M27294 mRNA. Translation: AAA29896.1. U33178 Genomic DNA. Translation: AAC46885.1.
PIR	A34416.
3D structure databases
ProteinModelPortal	P16237.
SMR	P16237. Positions 468-866.
ModBase	Search...
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Family and domain databases
InterPro	IPR002202. HMG_CoA_Rdtase. IPR023074. HMG_CoA_Rdtase_cat. IPR023076. HMG_CoA_Rdtase_CS. IPR004554. HMG_CoA_Rdtase_eu_arc. IPR023282. HMG_CoA_Rdtase_N. IPR009023. HMG_CoA_Rdtase_NAD(P)-bd. IPR009029. HMG_CoA_Rdtase_sub-bd. [Graphical view]
Gene3D	G3DSA:3.30.70.420. G3DSA:3.30.70.420. 1 hit. G3DSA:3.90.770.10. HMG-CoA_red. 2 hits. G3DSA:1.10.3270.10. HMG_CoA_Rdtase_N. 1 hit.
PANTHER	PTHR10572. HMG-CoA_red. 1 hit.
Pfam	PF00368. HMG-CoA_red. 1 hit. [Graphical view]
PRINTS	PR00071. HMGCOARDTASE.
SUPFAM	SSF55035. HMG_CoA_NAD_bind. 1 hit. SSF56542. HMG_CoA_sub_bind. 1 hit.
TIGRFAMs	TIGR00533. HMG_CoA_R_NADP. 1 hit.
PROSITE	PS00066. HMG_COA_REDUCTASE_1. 1 hit. PS00318. HMG_COA_REDUCTASE_2. 1 hit. PS01192. HMG_COA_REDUCTASE_3. 1 hit. PS50065. HMG_COA_REDUCTASE_4. 1 hit. [Graphical view]
ProtoNet	Search...

Entry information

Entry name

HMDH_SCHMA

Accession

Primary (citable) accession number: P16237

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 1, 1990
Last sequence update:	April 1, 1990
Last modified:	June 28, 2011
This is version 92 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)