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P01050

- HIRV1_HIRME

UniProt

P01050 - HIRV1_HIRME

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
  1. 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

    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-SubCell

    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

    VVYTDCTESG QNLCLCEGSN VCGQGNKCIL GSDGEKNQCV TGEGTPKPQS   50
    HNDGDFEEIP EEYLQ 65
    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...

    Chemistry

    DrugBanki DB00001. Lepirudin.

    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 1, 2014
    This is version 109 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