P30403 (VMRH_CALRH) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Zinc metalloproteinase/disintegrin

Cleaved into the following 2 chains:

1. Metalloproteinase rhodostoxin
   EC=3.4.24.-
   Alternative name(s):
   Hemorrhagic protein
2. Disintegrin rhodostomin
   Short name=RHO
   Alternative name(s):
   Disintegrin kistrin
   Platelet aggregation activation inhibitor

Gene names

Name:

RHOD

Organism

Calloselasma rhodostoma (Malayan pit viper) (Agkistrodon rhodostoma)

Taxonomic identifier

8717 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Lepidosauria › Squamata › Scleroglossa › Serpentes › Colubroidea › Viperidae › Crotalinae › Calloselasma

Protein attributes

Sequence length	478 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	The metalloprotease is a zinc protease from snake venom that acts in hemorrhage. The disintegrin inhibits fibrinogen interaction with platelet receptors expressed on glycoprotein IIb-IIIa complex. Acts by binding to the glycoprotein IIb-IIIa receptor on the platelet surface and inhibits aggregation induced by ADP, thrombin, platelet-activating factor and collagen.
Cofactor	Binds 1 zinc ion.
Subcellular location	Secreted.
Tissue specificity	Expressed by the venom gland.
Post-translational modification	Glycans are composed of 4 GlcNAc, 3 Man, 2 Gal, 2 NeuAC and 1 Fuc residue.
Sequence similarities	Belongs to the venom metalloproteinase family. P-II subfamily. Contains 1 disintegrin domain. Contains 1 peptidase M12B domain.

Ontologies

Keywords
Biological process	Blood coagulation Cell adhesion
Cellular component	Secreted
Domain	Signal
Ligand	Metal-binding Zinc
Molecular function	Hydrolase Metalloprotease Protease Toxin
PTM	Disulfide bond Glycoprotein Zymogen
Technical term	3D-structure Direct protein sequencing
Gene Ontology (GO)
Biological process	blood coagulation Inferred from electronic annotation. Source: UniProtKB-KW cell adhesion Inferred from electronic annotation. Source: UniProtKB-KW proteolysis Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	extracellular region Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	metalloendopeptidase activity Inferred from electronic annotation. Source: InterPro zinc ion 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

Signal peptide

1 – 20

20

Potential

Propeptide

21 – 188

168

PRO_0000028956

Chain

189 – 391

203

Metalloproteinase rhodostoxin

PRO_0000028957

Propeptide

392 – 407

16

PRO_0000028958

Chain

408 – 475

68

Disintegrin rhodostomin

PRO_0000028959

Propeptide

476 – 478

3

PRO_0000028960

Regions

Domain

194 – 391

198

Peptidase M12B

Domain

397 – 478

82

Disintegrin

Motif

456 – 458

3

Cell attachment site

Sites

Active site

331

1

By similarity

Metal binding

330

1

Zinc; catalytic Probable

Metal binding

334

1

Zinc; catalytic Probable

Metal binding

340

1

Zinc; catalytic Probable

Amino acid modifications

Glycosylation

279

1

N-linked (GlcNAc...) (complex) Ref.4

Glycosylation

369

1

N-linked (GlcNAc...) (complex) Ref.4

Disulfide bond

207 ↔ 248

Ref.4 Ref.7

Disulfide bond

305 ↔ 386

Ref.4 Ref.7

Disulfide bond

345 ↔ 370

Probable

Disulfide bond

347 ↔ 353

Probable

Disulfide bond

411 ↔ 426

Ref.4 Ref.7

Disulfide bond

413 ↔ 421

Ref.4 Ref.7

Disulfide bond

420 ↔ 443

Ref.4 Ref.7

Disulfide bond

434 ↔ 440

Ref.4 Ref.7

Disulfide bond

439 ↔ 464

Ref.4 Ref.7

Disulfide bond

452 ↔ 471

Ref.4 Ref.7

Experimental info

Sequence conflict

287

1

M → T AA sequence Ref.4

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

478

Helix Strand Turn

Details...

Beta strand

412 – 414

3

Beta strand

419 – 421

3

Turn

423 – 425

3

Beta strand

426 – 428

3

Beta strand

435 – 437

3

Beta strand

451 – 453

3

Sequences

	Sequence		Length	Mass (Da)
	P30403 [UniParc]. Last modified February 1, 1994. Version 2. Checksum: 6490A2B171D3A830	FASTA	478	54,006
	10 20 30 40 50 60 MIQVLLVTIC LAAFPYQGSS IILESGNVND YEVVYPRKVI ALSEGAAQQK YEDTMQYEFK 70 80 90 100 110 120 VNGEPVVLHL EKNKGLFAKD YSETHYSPDG TRITTYPSVE DHCYYQGRIH NDADSTASIS 130 140 150 160 170 180 ACNGLKGHFK LQGETYFIEP MKLPDSEAHA VFKYENIEKE DESPKMCGVT ETNWESDEPI 190 200 210 220 230 240 KKVSQLNLNH EIKRHVDIVV VVDSRFCTKH SNDLEVIRKF VHEVVNAIIE SYKYMHFGIS 250 260 270 280 290 300 LVNLETWCNG DLINVQEDSY ETLKAFGKWR ESDLIKHVNH SNAQFLMDMK FIKNIIGKAY 310 320 330 340 350 360 LDSICDPERS VGIVQNYHGI TLNVAAIMAH EMGHNLGVRH DGEYCTCYGS SECIMSSHIS 370 380 390 400 410 420 DPPSKYFSNC SYYQFWKYIE NQNPQCILNK PLRTVSIPVS GNEHLEAGKE CDCSSPENPC 430 440 450 460 470 CDAATCKLRP GAQCGEGLCC EQCKFSRAGK ICRIPRGDMP DDRCTGQSAD CPRYHSHA

References

[1]	"Nucleotide sequence of a full-length cDNA encoding a common precursor of platelet aggregation inhibitor and hemorrhagic protein from Calloselasma rhodostoma venom." Au L.-C. Biochim. Biophys. Acta 1173:243-245(1993) [PubMed: 7916635] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Venom gland.
[2]	"A common precursor for a putative hemorrhagic protein and rhodostomin, a platelet aggregation inhibitor of the venom of Calloselasma rhodostoma: molecular cloning and sequence analysis." Au L.-C., Huang Y.-B., Huang T.-F., Teh G.-W., Lin H.-H., Choo K.-B. Biochem. Biophys. Res. Commun. 181:585-593(1991) [PubMed: 1755841] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 77-478. Tissue: Venom gland.
[3]	"Rhodostomin, an RGD-containing peptide expressed from a synthetic gene in Escherichia coli, facilitates the attachment of human hepatoma cells." Chang H.H., Hu S.T., Huang T.-F., Chen S.H., Lee Y.H., Lo S.J. Biochem. Biophys. Res. Commun. 190:242-249(1993) [PubMed: 7916592] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 408-475. Tissue: Venom gland.
[4]	"Structural studies of a major hemorrhagin (rhodostoxin) from the venom of Calloselasma rhodostoma (Malayan pit viper)." Chung M.C., Ponnudurai G., Kataoka M., Shimizu S., Tan N.H. Arch. Biochem. Biophys. 325:199-208(1996) [PubMed: 8561498] [Abstract] Cited for: PROTEIN SEQUENCE OF 189-391, DISULFIDE BONDS, GLYCOSYLATION AT ASN-279 AND ASN-369, GLYCAN STRUCTURE, MASS SPECTROMETRY. Tissue: Venom.
[5]	"Disintegrins: a family of integrin inhibitory proteins from viper venoms." Gould R.J., Polokoff M.A., Friedman P.A., Huang T.-F., Holt J.C., Cook J.J., Niecviarowski S. Proc. Soc. Exp. Biol. Med. 195:168-171(1990) [PubMed: 2236100] [Abstract] Cited for: PROTEIN SEQUENCE OF 408-475. Tissue: Venom.
[6]	"Platelet glycoprotein IIb-IIIa protein antagonists from snake venoms: evidence for a family of platelet-aggregation inhibitors." Dennis M.S., Henzel W.J., Pitti R.M., Lipari M.T., Napier M.A., Deisher T.A., Bunting S., Lazarus R.A. Proc. Natl. Acad. Sci. U.S.A. 87:2471-2475(1990) [PubMed: 2320569] [Abstract] Cited for: PROTEIN SEQUENCE OF 408-475. Tissue: Venom.
[7]	"Cysteine pairing in the glycoprotein IIbIIIa antagonist kistrin using NMR, chemical analysis, and structure calculations." Adler M., Carter P., Lazarus R.A., Wagner G. Biochemistry 32:282-289(1993) [PubMed: 8418848] [Abstract] Cited for: STRUCTURE BY NMR OF 408-475, DISULFIDE BONDS.
[8]	"Solution structure of kistrin, a potent platelet aggregation inhibitor and GP IIb-IIIa antagonist." Adler M., Lazarus R.A., Dennis M.S., Wagner G. Science 253:445-448(1991) [PubMed: 1862345] [Abstract] Cited for: STRUCTURE BY NMR OF 408-475.
[9]	"Sequential 1H NMR assignments of kistrin, a potent platelet aggregation inhibitor and glycoprotein IIb-IIIa antagonist." Adler M., Wagner G. Biochemistry 31:1031-1039(1992) [PubMed: 1734953] [Abstract] Cited for: STRUCTURE BY NMR OF 408-475.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

L08780 mRNA. Translation: AAA49196.1.

PIR

JQ1301. S33792.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1N4Y	NMR	-	A	408-475	[»]
1Q7I	NMR	-	A	408-475	[»]
1Q7J	NMR	-	A	408-475	[»]
2PJF	NMR	-	A	408-475	[»]
2PJG	NMR	-	A	408-475	[»]
2PJI	NMR	-	A	408-475	[»]

ProteinModelPortal

P30403.

SMR

P30403. Positions 193-475.

ModBase

Search...

Protein family/group databases

MEROPS

M12.161.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Phylogenomic databases

HOVERGEN

HBG006978.

Family and domain databases

InterPro

IPR001762. Blood-coag_inhib_Disintegrin.
IPR018358. Disintegrin_CS.
IPR024079. MetalloPept_cat_dom.
IPR001590. Peptidase_M12B.
IPR002870. Peptidase_M12B_N.
[Graphical view]

Gene3D

G3DSA:4.10.70.10. Blood-coag_inhib_Disintegrin. 1 hit.
G3DSA:3.40.390.10. G3DSA:3.40.390.10. 1 hit.

Pfam

PF00200. Disintegrin. 1 hit.
PF01562. Pep_M12B_propep. 1 hit.
PF01421. Reprolysin. 1 hit.
[Graphical view]

PRINTS

PR00289. DISINTEGRIN.

SMART

SM00050. DISIN. 1 hit.
[Graphical view]

SUPFAM

SSF57552. Disintegrin. 1 hit.

PROSITE

PS50215. ADAM_MEPRO. 1 hit.
PS00427. DISINTEGRIN_1. 1 hit.
PS50214. DISINTEGRIN_2. 1 hit.
PS00142. ZINC_PROTEASE. 1 hit.
[Graphical view]

ProtoNet

Search...

Entry information

Entry name

VMRH_CALRH

Accession

Primary (citable) accession number: P30403
Secondary accession number(s): P17494

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 1, 1993
Last sequence update:	February 1, 1994
Last modified:	January 25, 2012
This is version 95 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Animal Toxin Annotation Program

Annotation program

Chordata Protein Annotation Program