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P01050

- HIRV1_HIRME

UniProt

P01050 - HIRV1_HIRME

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Protein

Hirudin variant-1

Gene
N/A
Organism
Hirudo medicinalis (Medicinal leech)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli

Functioni

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.1 Publication

GO - Molecular functioni

  1. serine-type endopeptidase inhibitor activity Source: UniProtKB-KW
Complete GO annotation...

Keywords - Molecular functioni

Protease inhibitor, Serine protease inhibitor

Protein family/group databases

MEROPSiI14.001.

Names & Taxonomyi

Protein namesi
Recommended name:
Hirudin variant-1
Alternative name(s):
Hirudin-1
Hirudin-I
Lepirudin
OrganismiHirudo medicinalis (Medicinal leech)
Taxonomic identifieri6421 [NCBI]
Taxonomic lineageiEukaryotaMetazoaLophotrochozoaAnnelidaClitellataHirudinidaHirudineaArhynchobdellidaHirudiniformesHirudinidaeHirudo

Subcellular locationi

GO - Cellular componenti

  1. extracellular region Source: UniProtKB-KW
Complete GO annotation...

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Pharmaceutical usei

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

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi1 – 11V → E or K: Strongly decreased affinity for thrombin. 1 Publication
Mutagenesisi1 – 11V → G or S: Decreased affinity for thrombin. 1 Publication
Mutagenesisi1 – 11V → L or R: No effect. 1 Publication
Mutagenesisi2 – 21V → E or G: Strongly decreased affinity for thrombin. 1 Publication
Mutagenesisi2 – 21V → L: Decreased affinity for thrombin. 1 Publication
Mutagenesisi3 – 31Y → A: Strongly decreased affinity for thrombin. 1 Publication
Mutagenesisi4 – 41T → A: Decreased affinity for thrombin. 1 Publication
Mutagenesisi5 – 51D → A or E: Decreased affinity for thrombin. 1 Publication
Mutagenesisi15 – 151L → A: Strongly decreased affinity for thrombin. 1 Publication
Mutagenesisi17 – 171E → A: Slightly decreased affinity for thrombin.
Mutagenesisi20 – 201N → A: Decreased affinity for thrombin. 1 Publication
Mutagenesisi21 – 211V → A: Slightly decreased affinity for thrombin. 1 Publication
Mutagenesisi56 – 561F → A or W: Slightly decreased affinity for thrombin. 1 Publication
Mutagenesisi56 – 561F → I, L, T or V: Strongly decreased affinity for thrombin. 1 Publication
Mutagenesisi56 – 561F → Y: No effect. 1 Publication
Mutagenesisi60 – 601P → A or G: Decreased affinity for thrombin. 1 Publication
Mutagenesisi63 – 631Y → A, E or L: Slightly decreased affinity for thrombin. 1 Publication
Mutagenesisi63 – 631Y → F: No effect. 1 Publication
Mutagenesisi63 – 631Y → V: Decreased affinity for thrombin. 1 Publication

Protein family/group databases

Allergomei9843. Hir me Hirudin.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 6565Hirudin variant-1PRO_0000195639Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi6 ↔ 14
Disulfide bondi16 ↔ 28
Disulfide bondi22 ↔ 39
Glycosylationi45 – 451O-linked (GalNAc...)By similarity
Modified residuei63 – 631Sulfotyrosine2 Publications

Keywords - PTMi

Disulfide bond, Glycoprotein, Sulfation

Structurei

Secondary structure

1
65
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi11 – 155
Beta strandi17 – 193
Beta strandi20 – 223
Beta strandi26 – 294
Beta strandi32 – 343
Beta strandi38 – 425
Helixi61 – 633

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
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[»]
1BA8X-ray1.80C53-64[»]
1BB0X-ray2.10C53-64[»]
1BCUX-ray2.00I54-65[»]
1CA8X-ray2.10C53-64[»]
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-A1-65[»]
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[»]
4LXBX-ray1.61I53-65[»]
4MLFX-ray2.20D1-65[»]
5HIRNMR-A1-65[»]
6HIRNMR-A1-65[»]
DisProtiDP00137.
ProteinModelPortaliP01050.
SMRiP01050. Positions 1-65.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP01050.

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni1 – 33Interaction with thrombin active site
Regioni55 – 6511Interaction with fibrinogen-binding exosite of thrombinAdd
BLAST

Sequence similaritiesi

Family and domain databases

Gene3Di2.70.10.10. 1 hit.
InterProiIPR024793. Hirudin.
IPR011061. Hirudin/antistatin.
IPR000429. Prot_inh_hirudin.
[Graphical view]
PfamiPF00713. Hirudin. 1 hit.
[Graphical view]
PIRSFiPIRSF001640. Hirudin. 1 hit.
PRINTSiPR00777. HIRUDIN.
ProDomiPD004216. Prot_inh_hirudin. 1 hit.
[Graphical view] [Entries sharing at least one domain]
SUPFAMiSSF57262. SSF57262. 1 hit.

Sequencei

Sequence statusi: Complete.

P01050-1 [UniParc]FASTAAdd to Basket

« Hide

        10         20         30         40         50
VVYTDCTESG QNLCLCEGSN VCGQGNKCIL GSDGEKNQCV TGEGTPKPQS
60
HNDGDFEEIP EEYLQ
Length:65
Mass (Da):6,970
Last modified:July 21, 1986 - v1
Checksum:i9085A5876E3DE9FF
GO

Sequence databases

PIRiA91318. HULXH.
S05672.

Cross-referencesi

Web resourcesi

Refludan

Clinical information on Refludan

Sequence databases

PIRi A91318. HULXH.
S05672.

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
1AD8 X-ray 2.00 I 55-64 [» ]
1AE8 X-ray 2.00 I 55-64 [» ]
1AFE X-ray 2.00 I 55-64 [» ]
1AHT X-ray 1.60 I 55-64 [» ]
1AI8 X-ray 1.85 I 55-64 [» ]
1AWF X-ray 2.20 I 55-64 [» ]
1AY6 X-ray 1.80 I 55-64 [» ]
1BA8 X-ray 1.80 C 53-64 [» ]
1BB0 X-ray 2.10 C 53-64 [» ]
1BCU X-ray 2.00 I 54-65 [» ]
1CA8 X-ray 2.10 C 53-64 [» ]
1D3D X-ray 2.04 H 54-65 [» ]
1D3P X-ray 2.10 H 54-65 [» ]
1D3Q X-ray 2.90 H 54-65 [» ]
1D3T X-ray 3.00 H 54-65 [» ]
1D4P X-ray 2.07 H 54-65 [» ]
1H8D X-ray 1.40 I 55-64 [» ]
1H8I X-ray 1.75 I 55-64 [» ]
1HIC NMR - A 1-51 [» ]
1HRT X-ray 2.80 I 1-65 [» ]
1HXE X-ray 2.10 I 55-64 [» ]
1HXF X-ray 2.10 I 55-64 [» ]
1NO9 X-ray 1.90 I 55-65 [» ]
1QHR X-ray 2.20 I 55-64 [» ]
1QJ1 X-ray 2.00 I 55-64 [» ]
1QJ6 X-ray 2.20 I 55-64 [» ]
1QJ7 X-ray 2.20 I 55-64 [» ]
1TMT X-ray 2.20 I 53-65 [» ]
1TMU X-ray 2.50 I 55-65 [» ]
1UMA X-ray 2.00 I 55-64 [» ]
1WBG X-ray 2.20 I 55-64 [» ]
2HIR NMR - A 1-65 [» ]
2JOO NMR - A 1-65 [» ]
2PW8 X-ray 1.84 I 3-65 [» ]
2UUF X-ray 1.26 H 55-64 [» ]
2UUJ X-ray 1.32 H 55-64 [» ]
2UUK X-ray 1.39 H 55-64 [» ]
2V3O X-ray 1.79 I 56-65 [» ]
2ZC9 X-ray 1.58 I 54-64 [» ]
2ZDA X-ray 1.73 I 54-64 [» ]
2ZDV X-ray 1.72 I 54-64 [» ]
2ZF0 X-ray 2.20 I 54-64 [» ]
2ZFF X-ray 1.47 I 54-64 [» ]
2ZFP X-ray 2.25 I 54-64 [» ]
2ZGB X-ray 1.60 I 54-64 [» ]
2ZGX X-ray 1.80 I 54-64 [» ]
2ZHQ X-ray 1.96 I 54-64 [» ]
2ZI2 X-ray 1.65 I 54-64 [» ]
2ZIQ X-ray 1.65 I 54-64 [» ]
2ZNK X-ray 1.80 I 54-64 [» ]
2ZO3 X-ray 1.70 I 54-64 [» ]
3D49 X-ray 1.50 I 54-64 [» ]
3DHK X-ray 1.73 I 54-64 [» ]
3DT0 X-ray 2.40 I 54-64 [» ]
3DUX X-ray 1.60 I 54-64 [» ]
3EGK X-ray 2.20 I 54-64 [» ]
3EQ0 X-ray 1.53 I 54-64 [» ]
3LDX X-ray 2.25 I 55-65 [» ]
3UTU X-ray 1.55 I 54-64 [» ]
4AX9 X-ray 1.90 I 55-65 [» ]
4BAH X-ray 1.94 D 53-64 [» ]
4BAK X-ray 1.94 D 53-64 [» ]
4BAM X-ray 1.88 D 53-64 [» ]
4BAN X-ray 1.87 D 53-64 [» ]
4BAQ X-ray 1.89 D 53-64 [» ]
4HIR NMR - A 1-65 [» ]
4LXB X-ray 1.61 I 53-65 [» ]
4MLF X-ray 2.20 D 1-65 [» ]
5HIR NMR - A 1-65 [» ]
6HIR NMR - A 1-65 [» ]
DisProti DP00137.
ProteinModelPortali P01050.
SMRi P01050. Positions 1-65.
ModBasei Search...
MobiDBi Search...

Protein family/group databases

Allergomei 9843. Hir me Hirudin.
MEROPSi I14.001.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Miscellaneous databases

EvolutionaryTracei P01050.

Family and domain databases

Gene3Di 2.70.10.10. 1 hit.
InterProi IPR024793. Hirudin.
IPR011061. Hirudin/antistatin.
IPR000429. Prot_inh_hirudin.
[Graphical view ]
Pfami PF00713. Hirudin. 1 hit.
[Graphical view ]
PIRSFi PIRSF001640. Hirudin. 1 hit.
PRINTSi PR00777. HIRUDIN.
ProDomi PD004216. Prot_inh_hirudin. 1 hit.
[Graphical view ] [Entries sharing at least one domain ]
SUPFAMi SSF57262. SSF57262. 1 hit.
ProtoNeti Search...

Publicationsi

  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.

Entry informationi

Entry nameiHIRV1_HIRME
AccessioniPrimary (citable) accession number: P01050
Secondary accession number(s): P28501
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 21, 1986
Last sequence update: July 21, 1986
Last modified: October 29, 2014
This is version 110 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)

Miscellaneousi

Keywords - Technical termi

3D-structure, Direct protein sequencing, Pharmaceutical

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3