P02879 (RICI_RICCO) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names	Recommended name: Ricin Cleaved into the following 3 chains: Ricin A chain EC=3.2.2.22 Alternative name(s): rRNA N-glycosidase Linker peptide Ricin B chain
Organism	Ricinus communis (Castor bean) [Complete proteome]
Taxonomic identifier	3988 [NCBI]
Taxonomic lineage	cellular organisms › Eukaryota › Viridiplantae › Streptophyta › Streptophytina › Embryophyta › Tracheophyta › Euphyllophyta › Spermatophyta › Magnoliophyta › eudicotyledons › core eudicotyledons › rosids › fabids › Malpighiales › Euphorbiaceae › Acalyphoideae › Acalypheae › Ricinus

Protein attributes

Sequence length	576 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	Ricin is highly toxic to animal cells and to a lesser extent to plant cells. The A chain acts as a glycosidase that removes a specific adenine residue from an exposed loop of the 28S rRNA (A4324 in mammals), leading to rRNA breakage. As this loop is involved in elongation factor binding, modified ribosomes are catalytically inactive and unable to support protein synthesis. The A chain can inactivate a few thousand ribosomes per minute, faster than the cell can make new ones. Therefore a single A chain molecule can kill an animal cell. The B chain binds to beta-D-galactopyranoside moieties on cell surface glycoproteins and glycolipids and facilitates the entry into the cell of the A chain; B chains are also responsible for cell agglutination (Lectin activity).
Catalytic activity	Endohydrolysis of the N-glycosidic bond at one specific adenosine on the 28S rRNA.
Subunit structure	Disulfide-linked dimer of A and B chains.
Domain	The B chain is composed of two domains, each domain consists of 3 homologous subdomains (alpha, beta, gamma).
Biotechnological use	A deglycosylated A chain may be linked to monoclonal antibodies to produce immunotoxins exploited in cancer treatment. However, a point mutation should be introduced to eliminate vascular leak syndrome, a side effect resulting from endothelial damage.
Sequence similarities	In the N-terminal section; belongs to the ribosome-inactivating protein family. Type 2 RIP subfamily. Contains 2 ricin B-type lectin domains.
Sequence caution	The sequence described in Ref.4 differs from that shown. Reason: High number of conflicts with the sequence translated from DNA. The sequence described in Ref.5 differs from that shown. Reason: High number of conflicts with the sequence translated from DNA.

Ontologies

Keywords
Biological process	Plant defense
Domain	Repeat Signal
Ligand	Lectin Nucleotide-binding
Molecular function	Hydrolase Protein synthesis inhibitor Toxin
PTM	Disulfide bond Glycoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing
Gene Ontology (GO)
Biological_process	defense response Inferred from electronic annotation. Source: UniProtKB-KW negative regulation of translation Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	endoplasmic reticulum Inferred from direct assay PubMed 11870775. Source: UniProtKB
Molecular_function	nucleotide binding Inferred from electronic annotation. Source: UniProtKB-KW rRNA N-glycosylase 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

Signal peptide

1 – 35

35

Ref.4

Chain

36 – 302

267

Ricin A chain

PRO_0000030741

Peptide

303 – 314

12

Linker peptide

PRO_0000030742

Chain

315 – 576

262

Ricin B chain

PRO_0000030743

Regions

Domain

321 – 448

128

Ricin B-type lectin 1

Repeat

331 – 373

43

1-alpha

Repeat

374 – 414

41

1-beta

Repeat

417 – 449

33

1-gamma

Domain

451 – 575

125

Ricin B-type lectin 2

Repeat

462 – 497

36

2-alpha

Repeat

501 – 540

40

2-beta

Repeat

543 – 570

28

2-gamma

Nucleotide binding

115 – 116

2

AMP

Nucleotide binding

156 – 158

3

AMP

Region

43 – 45

3

Carbohydrate binding By similarity

Region

176 – 181

6

Carbohydrate binding

Region

230 – 232

3

Carbohydrate binding

Region

336 – 340

5

Carbohydrate binding

Region

548 – 551

4

Carbohydrate binding

Region

565 – 569

5

Carbohydrate binding

Sites

Active site

212

1

Binding site

50

1

Carbohydrate; via amide nitrogen

Binding site

85

1

Carbohydrate; via amide nitrogen

Binding site

324

1

Carbohydrate; via carbonyl oxygen By similarity

Binding site

349

1

Carbohydrate

Binding site

354

1

Carbohydrate

Binding site

360

1

Carbohydrate

Binding site

409

1

Carbohydrate By similarity

Binding site

449

1

Carbohydrate By similarity

Amino acid modifications

Glycosylation

45

1

N-linked (GlcNAc...) Ref.6

CAR_000080

Glycosylation

271

1

N-linked (GlcNAc...); partial Ref.6

CAR_000081

Glycosylation

409

1

N-linked (GlcNAc...)

Glycosylation

449

1

N-linked (GlcNAc...)

Disulfide bond

294 ↔ 318

Interchain (between A and B chains)

Disulfide bond

334 ↔ 353

Disulfide bond

377 ↔ 394

Disulfide bond

465 ↔ 478

Disulfide bond

504 ↔ 521

Experimental info

Mutagenesis

83

1

R → A: No effect on the toxic activity but suppresses the vascular leak syndrome. Ref.15

Mutagenesis

109

1

L → A or M: No effect on the toxic activity or the vascular leak syndrome. Ref.15

Mutagenesis

110

1

D → A, E or N: Suppresses the toxic activity. Ref.15

Mutagenesis

111

1

V → A or M: No effect on the toxic activity or the vascular leak syndrome. Ref.15

Mutagenesis

132

1

N → A: No effect on the toxic activity but Suppresses the vascular leak syndrome. Ref.15

Sequence conflict

76

1

E → D in CAA26230. Ref.3

Sequence conflict

551

1

A → R in CAA26230. Ref.3

Secondary structure

1

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576

Helix Strand Turn

Details...

Beta strand

43 – 48

6

Helix

53 – 67

15

Beta strand

72 – 74

3

Beta strand

77 – 79

3

Turn

83 – 85

3

Helix

88 – 90

3

Beta strand

91 – 98

8

Beta strand

104 – 110

7

Turn

111 – 113

3

Beta strand

116 – 121

6

Beta strand

124 – 127

4

Helix

133 – 139

7

Turn

140 – 145

6

Beta strand

147 – 151

5

Helix

158 – 165

8

Turn

166 – 168

3

Helix

169 – 171

3

Helix

176 – 188

13

Helix

189 – 191

3

Helix

196 – 215

20

Helix

217 – 228

12

Helix

237 – 254

18

Beta strand

260 – 268

9

Beta strand

274 – 279

6

Helix

280 – 283

4

Turn

284 – 286

3

Beta strand

298 – 300

3

Sequences

	Sequence		Length	Mass (Da)
	P02879 [UniParc]. Last modified August 13, 1987. Version 1. Checksum: C14C4B77A8B5470D	FASTA	576	64,091
	10 20 30 40 50 60 MKPGGNTIVI WMYAVATWLC FGSTSGWSFT LEDNNIFPKQ YPIINFTTAG ATVQSYTNFI 70 80 90 100 110 120 RAVRGRLTTG ADVRHEIPVL PNRVGLPINQ RFILVELSNH AELSVTLALD VTNAYVVGYR 130 140 150 160 170 180 AGNSAYFFHP DNQEDAEAIT HLFTDVQNRY TFAFGGNYDR LEQLAGNLRE NIELGNGPLE 190 200 210 220 230 240 EAISALYYYS TGGTQLPTLA RSFIICIQMI SEAARFQYIE GEMRTRIRYN RRSAPDPSVI 250 260 270 280 290 300 TLENSWGRLS TAIQESNQGA FASPIQLQRR NGSKFSVYDV SILIPIIALM VYRCAPPPSS 310 320 330 340 350 360 QFSLLIRPVV PNFNADVCMD PEPIVRIVGR NGLCVDVRDG RFHNGNAIQL WPCKSNTDAN 370 380 390 400 410 420 QLWTLKRDNT IRSNGKCLTT YGYSPGVYVM IYDCNTAATD ATRWQIWDNG TIINPRSSLV 430 440 450 460 470 480 LAATSGNSGT TLTVQTNIYA VSQGWLPTNN TQPFVTTIVG LYGLCLQANS GQVWIEDCSS 490 500 510 520 530 540 EKAEQQWALY ADGSIRPQQN RDNCLTSDSN IRETVVKILS CGPASSGQRW MFKNDGTILN 550 560 570 LYSGLVLDVR ASDPSLKQII LYPLHGDPNQ IWLPLF

References

[1]	"Genomic cloning and characterization of a ricin gene from Ricinus communis." Halling K.C., Halling A.C., Murray E.E., Ladin B.F., Houston L.L., Weaver R.F. Nucleic Acids Res. 13:8019-8033(1985) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[2]	"The lectin gene family of Ricinus communis: cloning of a functional ricin gene and three lectin pseudogenes." Tregear J.W., Roberts L.M. Plant Mol. Biol. 18:515-525(1992) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]	"Nucleotide sequence of cloned cDNA coding for preproricin." Lamb A., Roberts L.M., Lord J.M. Eur. J. Biochem. 148:265-270(1985) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 12-576.
[4]	"Isolation and sequences of peptic peptides, and the complete sequence of Ile chain of ricin-D." Yoshitake S., Funatsu G., Funatsu M. Agric. Biol. Chem. 42:1267-1274(1978) Cited for: PROTEIN SEQUENCE OF 36-302.
[5]	"Primary structure of Ala chain of ricin D." Funatsu G., Kimura M., Funatsu M. Agric. Biol. Chem. 43:2221-2224(1979) [AGRICOLA] [Europe PMC] Cited for: PROTEIN SEQUENCE OF 315-576.
[6]	"Structural analyses of sugar chains from ricin A-chain variant." Kimura Y., Kusuoku H., Tada M., Takagi S., Funatsu G. Agric. Biol. Chem. 54:157-162(1990) [PubMed] [Europe PMC] [Abstract] Cited for: GLYCOSYLATION AT ASN-45 AND ASN-271, PARTIAL PROTEIN SEQUENCE.
[7]	"Ricin." Olsnes S., Kozlov J.V. Toxicon 39:1723-1728(2001) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW.
[8]	"The three-dimensional structure of ricin at 2.8 A." Monfort W., Villafranca J.E., Monzingo A.F., Ernst S.R., Katzin B., Rutenber E., Xuong N.H., Hamlin R., Robertus J.D. J. Biol. Chem. 262:5398-5403(1987) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS).
[9]	"Structure of ricin A-chain at 2.5 A." Katzin B.J., Collins E.J., Robertus J.D. Proteins 10:251-259(1991) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF A-CHAIN.
[10]	"Structure of ricin B-chain at 2.5-A resolution." Rutenber E., Robertus J.D. Proteins 10:260-269(1991) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF B-CHAIN.
[11]	"X-ray structure of recombinant ricin A-chain at 1.8-A resolution." Weston S.A., Tucker A.D., Thatcher D.R., Derbyshire D.J., Pauptit R.A. J. Mol. Biol. 244:410-422(1994) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF A-CHAIN.
[12]	"Structure and activity of an active site substitution of ricin A chain." Day P.J., Ernst S.R., Frankel A.E., Monzingo A.F., Pascal J.M., Molina-Svinth M.C., Robertus J.D. Biochemistry 35:11098-11103(1996) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF MUTANT HIS-215.
[13]	"Structure-based identification of a ricin inhibitor." Yan X., Hollis T., Svinth M., Day P., Monzingo A.F., Milne G.W., Robertus J.D. J. Mol. Biol. 266:1043-1049(1997) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF A-CHAIN.
[14]	"Analysis of several key active site residues of ricin A chain by mutagenesis and X-ray crystallography." Kin Y., Robertus J.D. Protein Eng. 5:775-779(1992) [PubMed] [Europe PMC] [Abstract] Cited for: MUTAGENESIS.
[15]	"Genetic engineering of an immunotoxin to eliminate pulmonary vascular leak in mice." Smallshaw J.E., Ghetie V., Rizo J., Fulmer J.R., Trahan L.L., Ghetie M.-A., Vitetta E.S. Nat. Biotechnol. 21:387-391(2003) [PubMed] [Europe PMC] [Abstract] Cited for: MUTAGENESIS OF ARG-83; LEU-109; ASP-110; VAL-111 AND ASN-132.
+	Additional computationally mapped references.

Web resources

Protein Spotlight

Baneful beans - Issue 31 of February 2003

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

X03179 Genomic DNA. Translation: CAA26939.1.
X52908 Genomic DNA. Translation: CAA37095.1.
X02388 mRNA. Translation: CAA26230.1.

PIR

RLCSD. A24041.

RefSeq

XP_002534649.1. XM_002534603.1.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1BR5	X-ray	2.50	A	36-302	[»]
1BR6	X-ray	2.30	A	36-302	[»]
1IFS	X-ray	2.00	A	38-298	[»]
1IFT	X-ray	1.80	A	38-298	[»]
1IFU	X-ray	2.40	A	38-298	[»]
1IL3	X-ray	2.80	A	36-302	[»]
1IL4	X-ray	2.60	A	36-302	[»]
1IL5	X-ray	2.80	A/B	36-302	[»]
1IL9	X-ray	3.10	A	36-302	[»]
1J1M	X-ray	1.50	A	36-302	[»]
1OBS	X-ray	2.20	A	36-302	[»]
1OBT	X-ray	2.80	A	36-302	[»]
1RTC	X-ray	2.30	A	36-302	[»]
1UQ4	X-ray	1.90	A	40-302	[»]
1UQ5	X-ray	1.40	A	40-302	[»]
2AAI	X-ray	2.50	A	36-302	[»]
			B	315-576	[»]
2P8N	X-ray	1.94	A	36-302	[»]
2PJO	X-ray	1.80	A	36-302	[»]
2R2X	X-ray	2.40	A	36-302	[»]
2R3D	X-ray	2.09	A	36-302	[»]
2VC3	X-ray	1.60	A	36-302	[»]
2VC4	X-ray	1.39	A	36-302	[»]
3BJG	X-ray	2.14	A	36-302	[»]
3EJ5	X-ray	2.50	X	40-296	[»]
3HIO	X-ray	2.00	A	36-302	[»]
3LC9	X-ray	2.28	A	36-233	[»]
3MK9	X-ray	2.08	A	36-233	[»]
3PX8	X-ray	1.29	X	39-296	[»]
3PX9	X-ray	1.89	X	39-296	[»]
3RTI	X-ray	2.80	A	36-302	[»]
			B	315-576	[»]
3RTJ	X-ray	3.00	A	36-302	[»]
			B	315-576	[»]
3SRP	X-ray	2.14	A	36-302	[»]
4ESI	X-ray	1.87	A	36-302	[»]
4HUO	X-ray	1.52	X	36-302	[»]
4HUP	X-ray	1.70	X	36-302	[»]
4HV3	X-ray	1.54	A	36-302	[»]
4HV7	X-ray	1.87	X	36-302	[»]
4IMV	X-ray	2.25	A	36-233	[»]

ProteinModelPortal

P02879.

SMR

P02879. Positions 36-302, 315-576.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-46421N.

MINT

MINT-8391414.

Protein family/group databases

Allergome

2803. Ric c RIP.

CAZy

CBM13. Carbohydrate-Binding Module Family 13.

PTM databases

GlycoSuiteDB

P02879.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

GeneID

8287993.

KEGG

rcu:RCOM_2159910.

Phylogenomic databases

ProtClustDB

CLSN2726328.

Enzyme and pathway databases

BRENDA

3.2.2.22. 1204.

Family and domain databases

Gene3D

3.40.420.10. 1 hit.
4.10.470.10. 1 hit.

InterPro

IPR001574. Ribosome_inactivat_prot.
IPR017988. Ribosome_inactivat_prot_CS.
IPR016138. Ribosome_inactivat_prot_sub1.
IPR016139. Ribosome_inactivat_prot_sub2.
IPR017989. Ribosome_inactivat_prot_subgr.
IPR000772. Ricin_B_lectin.
[Graphical view]

Pfam

PF00652. Ricin_B_lectin. 2 hits.
PF00161. RIP. 1 hit.
[Graphical view]

PRINTS

PR00396. SHIGARICIN.

SMART

SM00458. RICIN. 2 hits.
[Graphical view]

SUPFAM

SSF56371. Ribosome_inactivat_prot. 1 hit.
SSF50370. RicinB_like. 2 hits.

PROSITE

PS50231. RICIN_B_LECTIN. 2 hits.
PS00275. SHIGA_RICIN. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

P02879.

ChEMBL

CHEMBL4756.

DrugBank

DB00173. Adenine.
DB00131. Adenosine monophosphate.

EvolutionaryTrace

P02879.

Entry information

Entry name

RICI_RICCO

Accession

Primary (citable) accession number: P02879
Secondary accession number(s): P02880

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 21, 1986
Last sequence update:	August 13, 1987
Last modified:	May 29, 2013
This is version 139 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Plant Protein Annotation Program