Tclin Antithrombin-III

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Most important serine protease inhibitor in plasma that regulates the blood coagulation cascade. AT-III inhibits thrombin, matriptase-3/TMPRSS7, as well as factors IXa, Xa and XIa. Its inhibitory activity is greatly enhanced in the presence of heparin.

The protein encoded by this gene is a plasma protease inhibitor and a member of the serpin superfamily. This protein inhibits thrombin as well as other activated serine proteases of the coagulation system, and it regulates the blood coagulation cascade. The protein includes two functional domains: the heparin binding-domain at the N-terminus of the mature protein, and the reactive site domain at the C-terminus. The inhibitory activity is enhanced by the presence of heparin. More than 120 mutations have been identified for this gene, many of which are known to cause antithrombin-III deficiency. [provided by RefSeq, Jul 2009]

Comments

Property Summary

Ligand Count	11
NCBI Gene PubMed Count	221
PubMed Score	9678.88

PubTator Score	4170.72

Knowledge Summary

Patent

No data available

TINX Plot

Disease (6)

Disease	Target Count	Z-score	Confidence
Antithrombin III deficiency	14	7.467	3.7
Acute coronary syndrome	39	0.0	0.0
Blood Coagulation Disorders	42	0.0	0.0
Brain Injuries	65	0.0	0.0
Cerebral Hemorrhage	42	0.0	0.0
Craniocerebral Trauma	1	0.0	0.0
Intracranial Thrombosis	3	0.0	0.0
Liver Failure, Acute	29	0.0	0.0
Nephrotic Syndrome	78	0.0	0.0
Respiratory Distress Syndrome, Adult	40	0.0	0.0
Thrombosis	46	0.0	0.0
Venous Thromboembolism	8	0.0	0.0
Venous Thrombosis	47	0.0	0.0

Disease	Target Count
Pulmonary embolism	55
Autosomal recessive predisposition	1442
Deep Vein Thrombosis	8
Thrombosis of cerebral veins	6
Thrombosis, recurrent	2

Disease	Target Count
Deep Vein Thrombosis with Pulmonary Embolism	2
Deep venous thrombosis	2
Disseminated intravascular coagulation	38
Maintain Patency of Indwelling Vascular Catheter	1
Non-Q wave myocardial infarction	4
Peripheral Arterial Thromboembolism Prevention	2
Peripheral arterial embolism	1
Prevention of Cardiac Ischemia in Unstable Angina	1
Prevention of Ischemic Complications of Non-Q Wave MI	1
Prevention of Recurrent Venous Thrombosis Associated with Malignancy	1
Prevention of deep vein thrombosis	7
Pulmonary Thromboembolism Prevention	2
Pulmonary thromboembolism	2

Disease	Target Count	P-value
adult high grade glioma	3801	5.2e-04

Disease	Target Count	Z-score	Confidence
Carcinoma	11493	0.0	0.9

Disease	Target Count	Z-score	Confidence
Thrombophilia	38	7.985	4.0
Blood protein disease	11	6.749	3.4
Protein C deficiency	19	6.506	3.3
Coronary artery disease	268	5.624	2.8
Thrombocytopenia	197	5.507	2.8
Cerebrovascular disease	238	5.336	2.7
Antiphospholipid syndrome	19	5.185	2.6
Thrombophlebitis	19	5.137	2.6
Hyperhomocysteinemia	37	5.112	2.6
Portal vein thrombosis	12	4.951	2.5
Hypertension	396	4.93	2.5
Heart disease	306	4.847	2.4
Liver disease	237	4.83	2.4
Kidney disease	430	4.828	2.4
post-thrombotic syndrome	7	4.547	2.3
Placental abruption	18	4.454	2.2
Cancer	2499	4.392	2.2
Purpura	43	4.352	2.2
Budd-Chiari syndrome	12	4.194	2.1
Hepatic veno-occlusive disease	16	4.163	2.1
Peripheral vascular disease	87	4.16	2.1
Atherosclerosis	291	4.13	2.1
Lung disease	142	3.944	2.0
diabetes mellitus	1728	3.888	1.9
Lupus erythematosus	57	3.871	1.9
Thrombocytosis	38	3.857	1.9
Leech infestation	1	3.646	1.8
Anemia	365	3.577	1.8
Varicose veins	20	3.553	1.8
Pancreatitis	123	3.501	1.8
Connective tissue disease	62	3.469	1.7
Vasculitis	80	3.422	1.7
Homocystinuria	21	3.305	1.7
Aortic aneurysm	38	3.212	1.6
Congenital disorder of glycosylation	54	3.18	1.6
Inflammatory bowel disease	151	3.173	1.6
Intermittent claudication	20	3.13	1.6
Hemophilia B	11	3.118	1.6
Familial encephalopathy with neuroserpin inclusion bodies	10	3.104	1.6
Peritonitis	43	3.05	1.5

Differential Expression (1)

Disease	log2 FC	p
adult high grade glioma	1.100	5.2e-04

Liver 18,071

Testis 18,518

Kidney - Cortex 17,329

Whole Blood 17,439

Spleen 17,614

Lung 18,057

Artery - Coronary 17,949

Brain - Cerebellum 17,983

Adipose - Visceral (Omentum) 17,937

Nerve - Tibial 18,007

Artery - Aorta 17,896

Esophagus - Muscularis 18,017

Vagina 17,834

Pituitary 18,147

Esophagus - Gastroesophageal Junction 18,000

Thyroid 18,024

Esophagus - Mucosa 18,076

Brain - Cerebellar Hemisphere 18,015

Stomach 17,879

Ovary 17,971

Adipose - Subcutaneous 18,110

Skin - Sun Exposed (Lower leg) 17,968

Artery - Tibial 17,631

Uterus 17,618

Skin - Not Sun Exposed (Suprapubic) 18,081

Colon - Sigmoid 18,089

Breast - Mammary Tissue 18,103

Prostate 18,213

Adrenal Gland 18,071

Brain - Spinal cord (cervical c-1) 17,973

Brain - Nucleus accumbens (basal ganglia... 18,024

Minor Salivary Gland 18,005

Brain - Frontal Cortex (BA9) 18,069

Small Intestine - Terminal Ileum 17,954

Brain - Caudate (basal ganglia) 18,001

Brain - Cortex 18,039

Brain - Putamen (basal ganglia) 17,863

Brain - Substantia nigra 17,981

Cells - EBV-transformed lymphocytes 18,186

Heart - Atrial Appendage 17,896

Colon - Transverse 17,825

Brain - Hypothalamus 18,169

Brain - Hippocampus 18,011

Brain - Amygdala 18,006

Brain - Anterior cingulate cortex (BA24) 17,989

Cells - Transformed fibroblasts 17,577

Muscle - Skeletal 17,778

Heart - Left Ventricle 18,006

Pancreas 18,123

Adult Ovary 10,192

Monocytes 7,422

Adult Testis 10,836

Adult Gallbladder 7,612

Adult Prostate 8,952

Adult Colon 7,915

Adult Kidney 6,723

Adult Lung 6,663

Adult Esophagus 4,936

Adult Urinary Bladder 7,592

Adult Pancreas 9,168

Adult Adrenal 8,475

Adult Liver 9,113

Adult Rectum 8,022

Adult Heart 6,506

Adult Spinal Cord 7,594

Fetal Gut 8,640

Fetal Ovary 9,118

Adult Retina 10,115

Fetal Brain 7,866

Fetal Liver 8,402

Platelets 6,131

Fetal Heart 9,228

Fetal Testis 7,955

NK Cells 8,475

Adult Frontal Cortex 9,048

Adrenal gland

Blood platelet

Brain

Colon

Frontal lobe

Gall bladder

Gut

Heart

Kidney

Liver

Lung

Monocyte

Natural killer cell

Esophagus

Ovary

Pancreas

Placenta 6,083

Prostate gland

Rectum

Retina

Spinal cord

Testis

Urinary bladder

adipose tissue 15,837

adrenal gland 15,963

breast 16,063

cerebral cortex 16,630

endometrium 16,349

epididymis 15,863

kidney 15,917

liver 14,587

lymph node 15,833

placenta 15,937

prostate 16,460

spleen 15,972

stomach 16,099

testis 17,936

thyroid gland 15,959

Liver and Pancreas 16,750

Digestive Tract 17,369

Urinary Tract 16,678

Endocrine System 18,159

Blood and immune system 16,909

Respiratory system 16,393

Female tissues 17,400

Male tissues 17,142

Skin and soft tissues 17,230

Nervous System 16,725

Cardiovascular System 15,192

Bile 19

Blood platelet 538

Cerebrospinal fluid 45

Plasma cell 284

Liver 5,008

CL-48 cell 200

See source...

Blood plasma 163

Blood clot 64

Artery 356

Heart 914

Blood vessel endothelium 133

Liver 1,045

Leukocyte 26

Adult 1,013

Neonate 92

Erythrocyte 70

Inferior vena cava 21

Mesenteric vein 9

Hip 108

Lung 663

Phagocyte 24

Capillary 104

Kidney 888

Blood vessel wall 31

Venous system 12

Jugular vein 20

Renal vein 8

Portal vein 24

Marrow cell 18

Urine 298

Mononuclear cell 51

Muscle 1,170

Knee 120

Immune system 1,205

Intestine 665

Skin 763

Bronchoalveolar lavage 108

Brain 1,516

See source...

Synonym

Accession	P01008 B2R6P0 P78439 P78447 Q13815 Q5TC78 Q7KZ43 Q7KZ97 Q9UC78 ATIII
Symbols	AT3 AT3D ATIII THPH7

Gene

SERPINC1

PANTHER Protein Class (3)

enzyme modulator 645

protease inhibitor 256

serine protease inhibitor 94

Ortholog (13)

Species	Source	Disease
Zebrafish 9,726	Inparanoid OMA EggNOG
Chimp 14,140	OMA EggNOG
Macaque 12,761	Inparanoid OMA EggNOG
Mouse 16,570	Inparanoid OMA EggNOG
Dog 15,073	Inparanoid OMA EggNOG
Horse 14,252	Inparanoid OMA EggNOG
Cow 15,320	Inparanoid OMA EggNOG
Pig 10,168	Inparanoid OMA EggNOG
Opossum 12,230	Inparanoid OMA EggNOG
Platypus 5,703	OMA EggNOG
Chicken 7,827	OMA EggNOG
Anole lizard 10,588	Inparanoid OMA EggNOG
Xenopus 10,468	Inparanoid OMA EggNOG

UniProt Keyword (17)

Complete proteome 20,231

Polymorphism 12,194

Reference proteome 20,231

Disease mutation 2,804

Phosphoprotein 8,216

Disulfide bond 3,599

Glycoprotein 4,623

3D-structure 6,226

Secreted 2,041

Signal 3,561

See all...

GO Function (4)

identical protein binding 1,084

heparin binding 161

serine-type endopeptidase inhibitor acti... 96

protease binding 108

GO Component (6)

plasma membrane 4,414

extracellular region 1,833

extracellular space 1,380

extracellular exosome 2,767

endoplasmic reticulum lumen 291

blood microparticle 175

GO Process (7)

post-translational protein modification 356

response to nutrient 71

cellular protein metabolic process 192

blood coagulation 170

lactation 42

acute inflammatory response to antigenic... 7

regulation of blood coagulation, intrins... 1

Compartment GO Term (40)

Cell 16,178

Cell part 16,177

Cell periphery 5,382

Cell surface 842

Cytoplasm 10,983

Cytoplasmic part 9,247

Cytosol 6,686

Cytosolic part 407

Endomembrane system 4,237

Endoplasmic reticulum 2,001

Endoplasmic reticulum lumen 303

Endoplasmic reticulum part 1,359

Extracellular region 2,732

Extracellular region part 1,628

Extracellular space 1,124

See all...

OMIM Phenotype (1)

Phenotype: Thrombophilia due to antithro... 1

MGI Phenotype (12)

homeostasis-metabolism phenotype 4,747

vision-eye phenotype 1,622

nervous system phenotype 3,447

hematopoietic system phenotype 3,383

cardiovascular system phenotype 2,660

reproductive system phenotype 1,999

mortality-aging 5,018

liver-biliary system phenotype 1,300

embryo phenotype 1,827

renal-urinary system phenotype 1,269

See all...

HCA RNA Cell Line (49)

A-431 16,131

A549 15,174

AF22 16,160

AN3-CA 15,648

BEWO 16,726

BJ 15,448

BJ hTERT+ 15,353

BJ hTERT+ SV40 Large T+ RasG12V 15,493

CACO-2 15,436

CAPAN-2 16,102

See all...

Pathway (16)

Complement and coagulation cascades 79

http://identifiers.org/panther.pathway/P... 38

http://pathwaycommons.org/pc2/Pathway_c8... 26

http://identifiers.org/smpdb/SMP00272 21

http://identifiers.org/smpdb/SMP00273 21

http://identifiers.org/smpdb/SMP00274 21

http://identifiers.org/smpdb/SMP00275 21

Metabolism of proteins 2,091

Post-translational protein modification 1,398

Hemostasis 666

See all...

Protein-protein Interaction (6)

TUBB1 TEX15 OS9 SUCLG1 CBWD1 BTD

PDB (27)

...
More...

Drug (3)

heparin
pKd 7.85

enoxaparin sodium

fondaparinux
pKd 7.49

Ligand (8)

CHEMBL51173
pIC50 6.24

CHEMBL609990
pKd 7.24

CHEMBL1909451
pKd 8.16

CHEMBL2303814
pKd 8.55

CHEMBL2303815
pKd 8.72

CHEMBL1908371
pKd 9.00

fondaparinux
pKd 7.49

heparin
pKd 7.85

Gene RIF (123)

AA Sequence

MYSNVIGTVTSGKRKVYLLSLLLIGFWDCVTCHGSPVDICTAKPRDIPMNPMCIYRSPEKKATEDEGSEQ      1 - 70
KIPEATNRRVWELSKANSRFATTFYQHLADSKNDNDNIFLSPLSISTAFAMTKLGACNDTLQQLMEVFKF     71 - 140
DTISEKTSDQIHFFFAKLNCRLYRKANKSSKLVSANRLFGDKSLTFNETYQDISELVYGAKLQPLDFKEN    141 - 210
AEQSRAAINKWVSNKTEGRITDVIPSEAINELTVLVLVNTIYFKGLWKSKFSPENTRKELFYKADGESCS    211 - 280
ASMMYQEGKFRYRRVAEGTQVLELPFKGDDITMVLILPKPEKSLAKVEKELTPEVLQEWLDELEEMMLVV    281 - 350
HMPRFRIEDGFSLKEQLQDMGLVDLFSPEKSKLPGIVAEGRDDLYVSDAFHKAFLEVNEEGSEAAASTAV    351 - 420
VIAGRSLNPNRVTFKANRPFLVFIREVPLNTIIFMGRVANPCVK                              421 - 464
//

Text Mined References (230)

Summary
Details

	PMID	Year	Title

Tclin Antithrombin-III Add to cart View Collections Empty Collection

Property Summary

Knowledge Summary

Patent

No data available

TINX Plot

Disease (6)

Expression

Differential Expression (1)

Synonym

Gene

PANTHER Protein Class (3)

Ortholog (13)

UniProt Keyword (17)

GO Function (4)

GO Component (6)

GO Process (7)

Compartment GO Term (40)

OMIM Phenotype (1)

MGI Phenotype (12)

HCA RNA Cell Line (49)

Pathway (16)

Protein-protein Interaction (6)

PDB (27)

Drug (3)

Ligand (8)

Gene RIF (123)

AA Sequence

Text Mined References (230)

Tclin Antithrombin-III

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