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P01050 (HIRV1_HIRME) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 105. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Hirudin variant-1
Alternative name(s):
Hirudin-1
Hirudin-I
Lepirudin
OrganismHirudo medicinalis (Medicinal leech)
Taxonomic identifier6421 [NCBI]
Taxonomic lineageEukaryotaMetazoaLophotrochozoaAnnelidaClitellataHirudinidaHirudineaArhynchobdellidaHirudiniformesHirudinidaeHirudo

Protein attributes

Sequence length65 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Hirudin is a potent thrombin-specific protease inhibitor. It forms a stable non-covalent complex with alpha-thrombin, thereby abolishing its ability to cleave fibrinogen. Ref.13

Subcellular location

Secreted.

Pharmaceutical use

Available under the name Refludan (Hoechst Marion Roussel). Used to treat heparin-induced thrombocytopenia (HIT).

Sequence similarities

Belongs to the protease inhibitor I14 (hirudin) family. [View classification]

Ontologies

Keywords
   Cellular componentSecreted
   Molecular functionProtease inhibitor
Serine protease inhibitor
   PTMDisulfide bond
Glycoprotein
Sulfation
   Technical term3D-structure
Direct protein sequencing
Pharmaceutical
Gene Ontology (GO)
   Cellular_componentextracellular region

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular_functionserine-type endopeptidase inhibitor activity

Inferred from electronic annotation. Source: UniProtKB-KW

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 6565Hirudin variant-1
PRO_0000195639

Regions

Region1 – 33Interaction with thrombin active site
Region55 – 6511Interaction with fibrinogen-binding exosite of thrombin

Amino acid modifications

Modified residue631Sulfotyrosine Ref.12 Ref.14
Glycosylation451O-linked (GalNAc...) By similarity
Disulfide bond6 ↔ 14 Ref.7 Ref.13 Ref.14
Disulfide bond16 ↔ 28 Ref.7 Ref.13 Ref.14
Disulfide bond22 ↔ 39 Ref.7 Ref.13 Ref.14

Experimental info

Mutagenesis11V → E or K: Strongly decreased affinity for thrombin. Ref.5
Mutagenesis11V → G or S: Decreased affinity for thrombin. Ref.5
Mutagenesis11V → L or R: No effect. Ref.5
Mutagenesis21V → E or G: Strongly decreased affinity for thrombin. Ref.5
Mutagenesis21V → L: Decreased affinity for thrombin. Ref.5
Mutagenesis31Y → A: Strongly decreased affinity for thrombin. Ref.5
Mutagenesis41T → A: Decreased affinity for thrombin. Ref.5
Mutagenesis51D → A or E: Decreased affinity for thrombin. Ref.5
Mutagenesis151L → A: Strongly decreased affinity for thrombin. Ref.6
Mutagenesis171E → A: Slightly decreased affinity for thrombin.
Mutagenesis201N → A: Decreased affinity for thrombin. Ref.6
Mutagenesis211V → A: Slightly decreased affinity for thrombin. Ref.6
Mutagenesis561F → A or W: Slightly decreased affinity for thrombin. Ref.4
Mutagenesis561F → I, L, T or V: Strongly decreased affinity for thrombin. Ref.4
Mutagenesis561F → Y: No effect. Ref.4
Mutagenesis601P → A or G: Decreased affinity for thrombin. Ref.4
Mutagenesis631Y → A, E or L: Slightly decreased affinity for thrombin. Ref.4
Mutagenesis631Y → F: No effect. Ref.4
Mutagenesis631Y → V: Decreased affinity for thrombin. Ref.4

Secondary structure

.............. 65
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P01050 [UniParc].

Last modified July 21, 1986. Version 1.
Checksum: 9085A5876E3DE9FF

FASTA656,970
        10         20         30         40         50         60 
VVYTDCTESG QNLCLCEGSN VCGQGNKCIL GSDGEKNQCV TGEGTPKPQS HNDGDFEEIP 


EEYLQ 

« Hide

References

[1]"The complete amino acid sequence of hirudin, a thrombin specific inhibitor. Application of colour carboxymethylation."
Dodt J., Mueller H.-P., Seemueller U., Chang J.-Y.
FEBS Lett. 165:180-183(1984)
Cited for: PROTEIN SEQUENCE.
[2]Petersen T.E., Roberts H.R., Sottrup-Jensen L., Magnusson S., Bagdy D.
(In) Peeters H. (eds.); Protides of the biological fluids, Proc. 23th colloquium, pp.145-149, Pergamon Press, New York (1976)
Cited for: PROTEIN SEQUENCE.
[3]"Primary structures of new 'iso-hirudins'."
Scharf M., Engels J., Tripier D.
FEBS Lett. 255:105-110(1989) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 1-17 AND 28-65.
[4]"Role of interactions involving C-terminal nonpolar residues of hirudin in the formation of the thrombin-hirudin complex."
Betz A., Hofsteenge J., Stone S.R.
Biochemistry 30:9848-9853(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: MUTAGENESIS OF PHE-56; PRO-60 AND TYR-63.
[5]"Interaction of the N-terminal region of hirudin with the active-site cleft of thrombin."
Betz A., Hofsteenge J., Stone S.R.
Biochemistry 31:4557-4562(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: MUTAGENESIS OF VAL-1; VAL-2; TYR-3; THR-4 AND ASP-5.
[6]"Contribution of interactions with the core domain of hirudin to the stability of its complex with thrombin."
Betz A., Hopkins P.C.R., Le Bonniec B.F., Stone S.R.
Biochem. J. 298:507-510(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: MUTAGENESIS OF LEU-15; ASN-20 AND VAL-21.
[7]"Solution structure of recombinant hirudin and the Lys-47-->Glu mutant: a nuclear magnetic resonance and hybrid distance geometry-dynamical simulated annealing study."
Folkers P.J.M., Clore G.M., Driscoll P.C., Dodt J., Koehler S., Gronenborn A.M.
Biochemistry 28:2601-2617(1989) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR, DISULFIDE BONDS.
[8]"Conformation of recombinant desulfatohirudin in aqueous solution determined by nuclear magnetic resonance."
Haruyama H., Wuethrich K.
Biochemistry 28:4301-4312(1989) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR.
[9]"Crystal structure of the thrombin-hirudin complex: a novel mode of serine protease inhibition."
Gruetter M.G., Priestle J.P., Rahuel J., Grossenbacher H., Bode W., Hofsteenge J., Stone S.R.
EMBO J. 9:2361-2365(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.95 ANGSTROMS) IN COMPLEX WITH THROMBIN.
[10]"The structure of a complex of bovine alpha-thrombin and recombinant hirudin at 2.8-A resolution."
Vitali J., Martin P.D., Malkowski M.G., Robertson W.D., Lazar J.B., Winant R.C., Johnson P.H., Edwards B.F.P.
J. Biol. Chem. 267:17670-17678(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 51-65 IN COMPLEX WITH THROMBIN.
[11]"Nuclear magnetic resonance solution structure of hirudin(1-51) and comparison with corresponding three-dimensional structures determined using the complete 65-residue hirudin polypeptide chain."
Szyperski T., Guentert P., Stone S.R., Wuethrich K.
J. Mol. Biol. 228:1193-1205(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR OF 1-51.
[12]"Changes in interactions in complexes of hirudin derivatives and human alpha-thrombin due to different crystal forms."
Priestle J.P., Rahuel J., Rink H., Tones M., Gruetter M.G.
Protein Sci. 2:1630-1642(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 54-65 IN COMPLEX WITH THROMBIN, SULFATION AT TYR-63.
[13]"The NMR solution structure of recombinant RGD-hirudin."
Song X., Mo W., Liu X., Zhu L., Yan X., Song H., Dai L.
Biochem. Biophys. Res. Commun. 360:103-108(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR OF 1-57 OF MUTANT 32-R--D-34, FUNCTION, DISULFIDE BONDS.
[14]"Crystal structure of a biosynthetic sulfo-hirudin complexed to thrombin."
Liu C.C., Brustad E., Liu W., Schultz P.G.
J. Am. Chem. Soc. 129:10648-10649(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.84 ANGSTROMS), DISULFIDE BONDS, SULFATION AT TYR-63.
+Additional computationally mapped references.

Web resources

Refludan

Clinical information on Refludan

Cross-references

Sequence databases

PIRHULXH. A91318.
S05672.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1AD8X-ray2.00I55-64[»]
1AE8X-ray2.00I55-64[»]
1AFEX-ray2.00I55-64[»]
1AHTX-ray1.60I55-64[»]
1AI8X-ray1.85I55-64[»]
1AWFX-ray2.20I55-64[»]
1AY6X-ray1.80I55-64[»]
1BCUX-ray2.00I54-65[»]
1D3DX-ray2.04H54-65[»]
1D3PX-ray2.10H54-65[»]
1D3QX-ray2.90H54-65[»]
1D3TX-ray3.00H54-65[»]
1D4PX-ray2.07H54-65[»]
1H8DX-ray1.40I55-64[»]
1H8IX-ray1.75I55-64[»]
1HICNMR-A1-51[»]
1HRTX-ray2.80I1-65[»]
1HXEX-ray2.10I55-64[»]
1HXFX-ray2.10I55-64[»]
1NO9X-ray1.90I55-65[»]
1QHRX-ray2.20I55-64[»]
1QJ1X-ray2.00I55-64[»]
1QJ6X-ray2.20I55-64[»]
1QJ7X-ray2.20I55-64[»]
1TMTX-ray2.20I53-65[»]
1TMUX-ray2.50I55-65[»]
1UMAX-ray2.00I55-64[»]
1WBGX-ray2.20I55-64[»]
2HIRNMR-A1-65[»]
2JOONMR-A1-61[»]
2PW8X-ray1.84I3-65[»]
2UUFX-ray1.26H55-64[»]
2UUJX-ray1.32H55-64[»]
2UUKX-ray1.39H55-64[»]
2V3OX-ray1.79I56-65[»]
2ZC9X-ray1.58I54-64[»]
2ZDAX-ray1.73I54-64[»]
2ZDVX-ray1.72I54-64[»]
2ZF0X-ray2.20I54-64[»]
2ZFFX-ray1.47I54-64[»]
2ZFPX-ray2.25I54-64[»]
2ZGBX-ray1.60I54-64[»]
2ZGXX-ray1.80I54-64[»]
2ZHQX-ray1.96I54-64[»]
2ZI2X-ray1.65I54-64[»]
2ZIQX-ray1.65I54-64[»]
2ZNKX-ray1.80I54-64[»]
2ZO3X-ray1.70I54-64[»]
3D49X-ray1.50I54-64[»]
3DHKX-ray1.73I54-64[»]
3DT0X-ray2.40I54-64[»]
3DUXX-ray1.60I54-64[»]
3EGKX-ray2.20I54-64[»]
3EQ0X-ray1.53I54-64[»]
3LDXX-ray2.25I55-65[»]
3UTUX-ray1.55I54-64[»]
4AX9X-ray1.90I55-65[»]
4BAHX-ray1.94D53-64[»]
4BAKX-ray1.94D53-64[»]
4BAMX-ray1.88D53-64[»]
4BANX-ray1.87D53-64[»]
4BAQX-ray1.89D53-64[»]
4HIRNMR-A1-65[»]
4MLFX-ray2.20D1-65[»]
5HIRNMR-A1-65[»]
6HIRNMR-A1-65[»]
DisProtDP00137.
ProteinModelPortalP01050.
SMRP01050. Positions 1-65.
ModBaseSearch...
MobiDBSearch...

Chemistry

DrugBankDB00001. Lepirudin.

Protein family/group databases

Allergome9843. Hir me Hirudin.
MEROPSI14.001.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Family and domain databases

Gene3D2.70.10.10. 1 hit.
InterProIPR024793. Hirudin.
IPR011061. Hirudin/antistatin.
IPR000429. Prot_inh_hirudin.
[Graphical view]
PfamPF00713. Hirudin. 1 hit.
[Graphical view]
PIRSFPIRSF001640. Hirudin. 1 hit.
PRINTSPR00777. HIRUDIN.
ProDomPD004216. Prot_inh_hirudin. 1 hit.
[Graphical view] [Entries sharing at least one domain]
SUPFAMSSF57262. SSF57262. 1 hit.
ProtoNetSearch...

Other

EvolutionaryTraceP01050.

Entry information

Entry nameHIRV1_HIRME
AccessionPrimary (citable) accession number: P01050
Secondary accession number(s): P28501
Entry history
Integrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: July 21, 1986
Last modified: April 16, 2014
This is version 105 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references