Identification

Name
Protein S human
Accession Number
DB13149
Type
Biotech
Groups
Approved
Biologic Classification
Protein Based Therapies
Blood factors
Description

Protein S human is a vitamin K-dependent plasma glycoprotein which has antcoagulant properties [1]. It serves as a negative feedback mechanism in the coagulation cascade.

Protein structure
Db13149
Protein chemical formula
Not Available
Protein average weight
75123.0 Da
Sequences
>sp|P07225|PROS_HUMAN Vitamin K-dependent protein S OS=Homo sapiens GN=PROS1 PE=1 SV=1
MRVLGGRCGALLACLLLVLPVSEANFLSKQQASQVLVRKRRANSLLEETKQGNLERECIE
ELCNKEEAREVFENDPETDYFYPKYLVCLRSFQTGLFTAARQSTNAYPDLRSCVNAIPDQ
CSPLPCNEDGYMSCKDGKASFTCTCKPGWQGEKCEFDINECKDPSNINGGCSQICDNTPG
SYHCSCKNGFVMLSNKKDCKDVDECSLKPSICGTAVCKNIPGDFECECPEGYRYNLKSKS
CEDIDECSENMCAQLCVNYPGGYTCYCDGKKGFKLAQDQKSCEVVSVCLPLNLDTKYELL
YLAEQFAGVVLYLKFRLPEISRFSAEFDFRTYDSEGVILYAESIDHSAWLLIALRGGKIE
VQLKNEHTSKITTGGDVINNGLWNMVSVEELEHSISIKIAKEAVMDINKPGPLFKPENGL
LETKVYFAGFPRKVESELIKPINPRLDGCIRSWNLMKQGASGIKEIIQEKQNKHCLVTVE
KGSYYPGSGIAQFHIDYNNVSSAEGWHVNVTLNIRPSTGTGVMLALVSGNNTVPFAVSLV
DSTSEKSQDILLSVENTVIYRIQALSLCSDQQSHLEFRVNRNNLELSTPLKIETISHEDL
QRQLAVLDKAMKAKVATYLGGLPDVPFSATPVNAFYNGCMEVNINGVQLDLDEAISKHND
IRAHSCPSVWKKTKNS
Download FASTA Format
Synonyms
  • Protein S
  • Protein S (human)
  • Vitamin K-dependent protein S
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
Beriplex P/n 1000Protein S human (1360 unit) + Coagulation Factor IX Human (1240 unit) + Coagulation factor VII human (1000 unit) + Coagulation factor X human (2040 unit) + Protein C (1640 unit) + Prothrombin (1600 unit)Powder, for solutionIntravenousCsl Behring2013-11-21Not applicableCanada
Beriplex P/n 500Protein S human (680 unit) + Coagulation Factor IX Human (620 unit) + Coagulation factor VII human (500 unit) + Coagulation factor X human (1020 unit) + Protein C (820 unit) + Prothrombin (800 unit)Powder, for solutionIntravenousCsl Behring2011-07-28Not applicableCanada
KcentraProtein S human (920 U/40mL) + Coagulation Factor IX Human (1020 U/40mL) + Coagulation factor VII human (700 U/40mL) + Coagulation factor X human (1520 U/40mL) + Protein C (1240 U/40mL) + Prothrombin (1180 U/40mL)KitCSL Behring GmbH2013-12-13Not applicableUs
KcentraProtein S human (460 U/20mL) + Coagulation Factor IX Human (510 U/20mL) + Coagulation factor VII human (350 U/20mL) + Coagulation factor X human (760 U/20mL) + Protein C (620 U/20mL) + Prothrombin (590 U/20mL)KitCSL Behring GmbH2013-04-29Not applicableUs
OctaplexProtein S human (1280 unit) + Coagulation Factor IX Human (1000 unit) + Coagulation factor VII human (960 unit) + Coagulation factor X human (1200 unit) + Protein C (1240 unit) + Prothrombin (1520 unit)Kit; Powder, for solutionIntravenousOctapharma Pharmazeutika Produktionsges M B H2015-08-11Not applicableCanada
OctaplexProtein S human (640 unit) + Coagulation Factor IX Human (500 unit) + Coagulation factor VII human (480 unit) + Coagulation factor X human (600 unit) + Protein C (620 unit) + Prothrombin (760 unit)Kit; Powder, for solutionIntravenousOctapharma Pharmazeutika Produktionsges M B H2008-07-08Not applicableCanada
Categories
UNII
90J3F6N5FN
CAS number
Not Available

Pharmacology

Indication

For use in the emergency reversal of coagulation factor deficiency in patients recieving vitamin K antagonist therapy [Label]. Protein S is administered as part of a cocktail containing several other coagulation factors.

Associated Conditions
Pharmacodynamics

Protein S acts as an anticoagulant serves as a negative feedback mechanism in the coagulation cascade [1].

Mechanism of action

Thrombin converts protein C to activated protein C (APC) [1]. Protein S functions as a cofactor for APC and together they proteolytically cleave factor Va and VIIIa [1] [2]. This inhibits the activities of the prothrombinase and tenase complexes respectively and leads to a reduction in thrombin generation. The reduction in thrombin generation suppresses the coagulation cascade preventing additional clotting from occuring. Protein S is suggested to inhibit factors Va and Xa through protein-protein interactions [4] [1]. Protein S is also suggested to inhibit production of factor Xa by the tenase complex by competing for binding to phospholipids via its gamma-carboxyglutamic acid domain.

Protein S is thought to exert an anti-inflammatory effect in addition to its anticoagulant properties. The protein S-C4b-binding protein complex is believed to bind to phosphotidylserines on the cell membranes of apoptotic cells and interact with macrophages, signalling them to phagocytose the cell before it can rupture [3].

TargetActionsOrganism
ACoagulation factor V
antagonist
Human
ACoagulation factor X
antagonist
Human
AVitamin K-dependent protein C
cofactor
Human
Absorption
Not Available
Volume of distribution
Not Available
Protein binding

Approximately 60% of protein S is bound to C4b-binding protein in systemic circulation [1].

Metabolism
Not Available
Route of elimination
Not Available
Half life
Not Available
Clearance
Not Available
Toxicity
Not Available
Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
AcemetacinThe risk or severity of bleeding can be increased when Protein S human is combined with Acemetacin.
Acetylsalicylic acidThe risk or severity of bleeding can be increased when Protein S human is combined with Acetylsalicylic acid.
AnagrelideThe risk or severity of bleeding can be increased when Protein S human is combined with Anagrelide.
Antihemophilic factor, human recombinantThe therapeutic efficacy of Antihemophilic factor, human recombinant can be decreased when used in combination with Protein S human.
ApixabanApixaban may increase the anticoagulant activities of Protein S human.
ArgatrobanThe risk or severity of bleeding can be increased when Argatroban is combined with Protein S human.
Azficel-TThe risk or severity of adverse effects can be increased when Protein S human is combined with Azficel-T.
CitalopramThe risk or severity of hemorrhage can be increased when Citalopram is combined with Protein S human.
Coagulation Factor IX (Recombinant)The therapeutic efficacy of Coagulation Factor IX (Recombinant) can be decreased when used in combination with Protein S human.
Coagulation factor VIIa Recombinant HumanThe therapeutic efficacy of Coagulation factor VIIa Recombinant Human can be decreased when used in combination with Protein S human.
Food Interactions
Not Available

References

General References
  1. Rigby AC, Grant MA: Protein S: a conduit between anticoagulation and inflammation. Crit Care Med. 2004 May;32(5 Suppl):S336-41. [PubMed:15118541]
  2. Somajo S, Koshiar RL, Norstrom E, Dahlback B: Protein S and factor V in regulation of coagulation on platelet microparticles by activated protein C. Thromb Res. 2014 Jul;134(1):144-52. doi: 10.1016/j.thromres.2014.04.031. Epub 2014 May 2. [PubMed:24835672]
  3. Webb JH, Blom AM, Dahlback B: Vitamin K-dependent protein S localizing complement regulator C4b-binding protein to the surface of apoptotic cells. J Immunol. 2002 Sep 1;169(5):2580-6. [PubMed:12193728]
  4. Hackeng TM, van 't Veer C, Meijers JC, Bouma BN: Human protein S inhibits prothrombinase complex activity on endothelial cells and platelets via direct interactions with factors Va and Xa. J Biol Chem. 1994 Aug 19;269(33):21051-8. [PubMed:8063724]
External Links
PubChem Substance
347911433
FDA label
Download (638 KB)
MSDS
Download (744 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
3CompletedTreatmentReversal of Anticoagulant Treatment1
3RecruitingTreatmentSignificant Bleeding Risk1
4WithdrawnTreatmentPostpartum Haemorrhage (PPH)1

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
Powder, for solutionIntravenous
Kit
Kit; powder, for solutionIntravenous
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available

Taxonomy

Description
Not Available
Kingdom
Organic Compounds
Super Class
Organic Acids
Class
Carboxylic Acids and Derivatives
Sub Class
Amino Acids, Peptides, and Analogues
Direct Parent
Peptides
Alternative Parents
Not Available
Substituents
Not Available
Molecular Framework
Not Available
External Descriptors
Not Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
General Function
Copper ion binding
Specific Function
Central regulator of hemostasis. It serves as a critical cofactor for the prothrombinase activity of factor Xa that results in the activation of prothrombin to thrombin.
Gene Name
F5
Uniprot ID
P12259
Uniprot Name
Coagulation factor V
Molecular Weight
251701.245 Da
References
  1. Hackeng TM, van 't Veer C, Meijers JC, Bouma BN: Human protein S inhibits prothrombinase complex activity on endothelial cells and platelets via direct interactions with factors Va and Xa. J Biol Chem. 1994 Aug 19;269(33):21051-8. [PubMed:8063724]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
General Function
Serine-type endopeptidase activity
Specific Function
Factor Xa is a vitamin K-dependent glycoprotein that converts prothrombin to thrombin in the presence of factor Va, calcium and phospholipid during blood clotting.
Gene Name
F10
Uniprot ID
P00742
Uniprot Name
Coagulation factor X
Molecular Weight
54731.255 Da
References
  1. Hackeng TM, van 't Veer C, Meijers JC, Bouma BN: Human protein S inhibits prothrombinase complex activity on endothelial cells and platelets via direct interactions with factors Va and Xa. J Biol Chem. 1994 Aug 19;269(33):21051-8. [PubMed:8063724]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Cofactor
General Function
Serine-type endopeptidase activity
Specific Function
Protein C is a vitamin K-dependent serine protease that regulates blood coagulation by inactivating factors Va and VIIIa in the presence of calcium ions and phospholipids (PubMed:25618265). Exerts ...
Gene Name
PROC
Uniprot ID
P04070
Uniprot Name
Vitamin K-dependent protein C
Molecular Weight
52070.82 Da
References
  1. Somajo S, Koshiar RL, Norstrom E, Dahlback B: Protein S and factor V in regulation of coagulation on platelet microparticles by activated protein C. Thromb Res. 2014 Jul;134(1):144-52. doi: 10.1016/j.thromres.2014.04.031. Epub 2014 May 2. [PubMed:24835672]

Drug created on November 18, 2016 13:51 / Updated on October 01, 2018 15:26