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Category Symbol Source: HGNC EntrezGene Ensembl GeneCards RNA genes CroW21

GIFtS
-

PLAT Gene

protein-coding GIFtS: 76
GCID: GC08M042032

plasminogen activator, tissue

Explore 238 diseases affiliated with
PLAT via

MalaCards

our new
Human Malady Compendium

(According to ¹HGNC, ²Entrez Gene,
³UniProtKB/Swiss-Prot, ⁴UniProtKB/TrEMBL, ⁵OMIM, ⁶GeneLoc, ⁷Ensembl, ⁸DME, ⁹miRBase, and/or ¹⁰fRNAdb)
About This Section

Aliases
Plasminogen Activator, Tissue¹ ²		Tissue Plasminogen Activator (T-PA)²
T-Plasminogen Activator² ³		Tissue-Type Plasminogen Activator²
EC 3.4.21.68³ ⁸		Alteplase³
TPA² ⁵		Reteplase³
T-PA²		T-PA²
Alteplase³		TPA² ⁵
Plasminogen Activator, Tissue Type²		EC 3.4.21⁸
Reteplase³

External Ids:	HGNC: 9051¹	Entrez Gene: 5327²	Ensembl: ENSG00000104368⁷	OMIM: 173370⁵	UniProtKB: P00750³

Export aliases for PLAT gene to outside databases

Previous GC identifers: GC08M041417 GC08M042061 GC08M041773 GC08M042050 GC08M042151 GC08M040559

(According to Entrez Gene, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
About This Section

Entrez Gene summary for PLAT:

This gene encodes tissue-type plasminogen activator, a secreted serine protease which converts the proenzyme

plasminogen to plasmin, a fibrinolytic enzyme. Tissue-type plasminogen activator is synthesized as a single chain

which is cleaved by plasmin to a two chain disulfide linked protein. This enzyme plays a role in cell migration and

tissue remodeling. Increased enzymatic activity causes hyperfibrinolysis, which manifests as excessive bleeding;

decreased activity leads to hypofibrinolysis which can result in thrombosis or embolism. Alternative splicing of this

gene results in multiple transcript variants encoding different isoforms. (provided by RefSeq, Jul 2008)

UniProtKB/Swiss-Prot: TPA_HUMAN, P00750

Function: Converts the abundant, but inactive, zymogen plasminogen to plasmin by hydrolyzing a single Arg-Val bond in

plasminogen. By controlling plasmin-mediated proteolysis, it plays an important role in tissue remodeling and

degradation, in cell migration and many other physiopathological events. Plays a direct role in facilitating neuronal

migration

Gene Wiki entry for PLAT (Tissue plasminogen activator)

(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 69), Regulatory elements and Epigenetics data according to QIAGEN, SABiosciences, and/or SwitchGear Genomics)
About This Section

RefSeq DNA sequence:

NC_000008.10 NC_018919.1 NT_167187.1

Regulatory elements:

SABiosciences Regulatory transcription factor binding sites in the PLAT gene promoter:
CREB deltaCREB
Other transcription factors

SwitchGear Promoter luciferase reporter plasmid: PLAT promoter sequence

Search SABiosciences Chromatin IP Primers for PLAT

Epigenetics:

QIAGEN PyroMark CpG Assay predesigned Pyrosequencing DNA Methylation assays in human, mouse, rat PLAT

Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 8p12 Ensembl cytogenetic band: 8p11.21 HGNC cytogenetic band: 8p11.21

PLAT Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
PLAT gene location

GeneLoc information about chromosome 8 GeneLoc Exon Structure

GeneLoc location for GC08M042032: view genomic region (about GC identifiers)

Start:	42,032,236 bp from pter	End:	42,065,242 bp from pter
Size:	33,007 bases	Orientation:	minus strand

(According to ¹UniProtKB, HORDE, neXtProt, Ensembl, and/or Reactome, Modification sites according to ²PhosphoSitePlus, Specific Peptides from DME, Protein expression images according to data from SPIRE MOPED and PaxDb, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, and/or Uscn,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, and/or Uscn, Ontologies according to Gene Ontology Consortium 01 Mar 2013 and Entrez Gene, Antibodies by EMD Millipore, R&D Systems, GenScript, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, Abcam, and/or Uscn)
About This Section

UniProtKB/Swiss-Prot: TPA_HUMAN, P00750 (See protein sequence)

Recommended Name: Tissue-type plasminogen activator precursor

Size: 562 amino acids; 62917 Da

Subunit: Heterodimer of chain A and chain B held by a disulfide bond. Forms a heterodimer with SERPINA5. Binds to

fibrin with high affinity. This interaction leads to an increase in the catalytic efficiency of the enzyme between

100-fold and 1000-fold, due to an increase in affinity for plasminogen. Similarly, binding to heparin increases the

activation of plasminogen. Binds to annexin A2, cytokeratin-8, fibronectin and laminin. Binds to mannose receptor and

the low-density lipoprotein receptor-related protein (LRP1); these proteins are involved in TPA clearance. Yet

unidentified interactions on endothelial cells and vascular smooth muscle cells (VSMC) lead to a 100-fold stimulation

of plasminogen activation. In addition, binding to VSMC reduces TPA inhibition by PAI-1 by 30-fold. Binds LRP1B;

binding is followed by internalization and degradation

Subcellular location: Secreted, extracellular space

6/9 PDB 3D structures from and Proteopedia for PLAT (see all 9):

1A5H (3D)

1BDA (3D)

1PK2 (3D)

1PML (3D)

1RTF (3D)

1TPG (3D)

Secondary accessions: A8K022 B2R8E8 Q15103 Q503B0 Q6PJA5 Q7Z7N2 Q86YK8 Q9BU99 Q9BZW1

Alternative splicing: 4 isoforms: P00750-1 P00750-2 P00750-3 P00750-4 (No experimental confirmation available)

Explore the universe of human proteins at neXtProt for PLAT: NX_P00750

Post-translational modifications:

The single chain, almost fully active enzyme, can be further processed into a two-chain fully active form by a cleavage

after Arg-310 catalyzed by plasmin, tissue kallikrein or factor Xa¹

Differential cell-specific N-linked glycosylation gives rise to two glycoforms, type I (glycosylated at Asn-219) and

type II (not glycosylated at Asn-219). The single chain type I glycoform is less readily converted into the two-chain

form by plasmin, and the two-chain type I glycoform has a lower activity than the two-chain type II glycoform in the

presence of fibrin¹

N-glycosylation of Asn-152; the bound oligomannosidic glycan is involved in the interaction with the mannose receptor¹

Characterization of O-linked glycan was studied in Bowes melanoma cell line¹

View modification sites using PhosphoSitePlus²

View neXtProt modification sites for NX_P00750

4/22 DME Specific Peptides for PLAT (P00750) (see all 22)

CRNPDGD

DNDIALL

CFNGGTC

NYCRNPD

PLAT Protein expression data from MOPED and PaxDb: About this image

REFSEQ proteins (2 alternative transcripts):

NP_000921.1 NP_127509.1

ENSEMBL proteins:

ENSP00000392045 ENSP00000220809 ENSP00000270188 ENSP00000428886 ENSP00000407861

ENSP00000429401 ENSP00000429542 ENSP00000428797 ENSP00000429801 ENSP00000270189

Reactome Protein details: P00750
Human Recombinant Protein Products:

	Browse Purified and Recombinant Proteins at EMD Millipore
	R&D Systems Recombinant & Natural Proteins for PLAT (t-Plasminogen Activator/tPA)
	Browse recombinant and purified proteins available from Enzo Life Sciences
	Browse OriGene full length recombinant human proteins expressed in human HEK293 cells OriGene Protein Over-expression Lysate (see all 2): PLAT OriGene Custom Protein Services for PLAT
	GenScript Custom Purified and Recombinant Proteins Services for PLAT
	Novus Biologicals PLAT Protein Novus Biologicals PLAT Lysates
	Sino Biological Recombinant Protein for PLAT
	ProSpec Recombinant Protein for PLAT
	Uscn Proteins for PLAT

Gene Ontology (GO): 5/8 cellular component terms (GO ID links to tree view) (see all 8): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0005576	extracellular region	TAS	--
GO:0005615	extracellular space	IEA	--
GO:0005737	cytoplasm	IDA	1632457
GO:0009986	cell surface	IDA	1632457
GO:0030141	secretory granule	IEA	--

PLAT for ontologies About GeneDecksing

PLAT Antibody Products:

	EMD Millipore Mono- and Polyclonal Antibodies for the study of PLAT
	R&D Systems Antibodies for PLAT (t-Plasminogen Activator/tPA)
	Browse OriGene Antibodies OriGene Custom Antibody Services for PLAT
	GenScript Custom Superior Antibodies Services for PLAT
	Novus Biologicals PLAT Antibodies
	Abcam antibodies for PLAT
	Uscn Antibodies for PLAT
	ThermoFisher Antibodies for PLAT

Assay Products for PLAT:

	Browse Kits and Assays available from EMD Millipore
	OriGene Custom Immunoassay Development Browse OriGene Fluorogenic Cell Assay Kits
	Browse R&D Systems for biochemical assays
	GenScript Custom Assay Services for PLAT
	Browse Enzo Life Sciences for kits & assays
	Uscn ELISAs and CLIAs for PLAT

(According to InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
About This Section

PLAT for domains About GeneDecksing

5/11 InterPro domains/families (see all 11):

IPR000083 Fibronectin_type1

IPR001314 Peptidase_S1A

IPR000742 EG-like_dom

IPR026280 Tissue_plasm_act

IPR018056 Kringle_CS

Graphical View of Domain Structure for InterPro Entry P00750

ProtoNet protein and cluster: P00750

5 Blocks protein families:

IPB000001 Kringle

IPB000083 Fibronectin

IPB001254 Serine protease

IPB001314 Chymotrypsin serine protease family (S1) signature

IPB006210 Type I EGF

UniProtKB/Swiss-Prot: TPA_HUMAN, P00750

Domain: Both FN1 and one of the kringle domains are required for binding to fibrin

Domain: Both FN1 and EGF-like domains are important for binding to LRP1

Domain: The FN1 domain mediates binding to annexin A2

Domain: The second kringle domain is implicated in binding to cytokeratin-8 and to the endothelial cell surface binding

site

Similarity: Belongs to the peptidase S1 family

Similarity: Contains 1 EGF-like domain

Similarity: Contains 1 fibronectin type-I domain

Similarity: Contains 2 kringle domains

Similarity: Contains 1 peptidase S1 domain

(According to ¹UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or ²DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013,
bound targets from SABiosciences, miRNA Gene Targets from miRTarBase shRNA from OriGene, RNAi from EMD Millipore, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, Gene Editing from DNA2.0, Clones from EMD Millipore, OriGene, SwitchGear Genomics, GenScript, Sino Biological, DNA2.0, and Vector BioLabs, Cell Lines from GenScript, LifeMap BioReagents, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Mar 2013 via Entrez Gene.)
About This Section

Function Summary:

UniProtKB/Swiss-Prot: TPA_HUMAN, P00750

Function: Converts the abundant, but inactive, zymogen plasminogen to plasmin by hydrolyzing a single Arg-Val bond in

plasminogen. By controlling plasmin-mediated proteolysis, it plays an important role in tissue remodeling and

degradation, in cell migration and many other physiopathological events. Plays a direct role in facilitating neuronal

migration

Catalytic activity: Specific cleavage of Arg- -Val bond in plasminogen to form plasmin

Enzyme regulation: Inhibited by SERPINA5

Genatlas biochemistry entry for PLAT:

plasminogen activator,tissue-type

Enzyme Numbers (IUBMB): EC 3.4.21.68¹ ² EC 3.4.21²

miRNA Products:		miRTarBase miRNAs that target PLAT: hsa-mir-21 (MIRT005953), hsa-mir-204 (MIRT005838)

		OriGene 3'-UTR Clone (see all 2): PLAT Browse MicroRNA Expression Plasmids
		QIAGEN Custom miScript Target Protector blocks miRNA-binding site of human, mouse, rat PLAT
		8/23 QIAGEN miScript miRNA Assays for microRNAs that regulate PLAT (see all 23):
		hsa-miR-548j hsa-miR-3194-5p hsa-miR-642a hsa-miR-548i hsa-miR-3660 hsa-miR-138-2* hsa-miR-340 hsa-miR-144

		SwitchGear 3'UTR luciferase reporter plasmid: PLAT 3' UTR sequence

Inhib. RNA Products:		Browse for Gene Knock-down Tools from EMD Millipore
		OriGene 29mer shRNA kits in GFP-retroviral vector in human, mouse, rat for PLAT (see all 7) OriGene shRNA RFP: PLAT OriGene siRNA: PLAT
		QIAGEN FlexiTube/FlexiPlate siRNA for gene silencing in human, mouse, rat PLAT

Gene Editing
Products:

DNA2.0 Custom Protein Engineering Service for PLAT

Clone Products:		Browse Clones for the Expression of Recombinant Proteins Available from EMD Millipore
		OriGene Myc/DDK tagged cDNA clones in CMV expression vector in human, mouse, rat for PLAT (see all 4) OriGene untagged cDNA clones in CMV expression vector in human, mouse, rat for PLAT (see all 3) OriGene custom cloning services � gene synthesis, subcloning, mutagenesis, variant library, vector shuttling
		GenScript: all cDNA clones in your preferred vector (see all 2): PLAT (NM_033011)
		Sino Biological Human cDNA Clone for PLAT
		DNA2.0 Custom Codon Optimized Gene Synthesis Service for PLAT
		Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat PLAT

Cell Line Products:		GenScript Custom overexpressing Cell Line Services for PLAT
		Search LifeMap BioReagents cell lines for PLAT

In Situ Assay
Products:

Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for PLAT

Gene Ontology (GO): 2 molecular function terms (GO ID links to tree view): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0004252	serine-type endopeptidase activity	TAS	--
GO:0005515	protein binding	IPI	2503541

PLAT for ontologies About GeneDecksing

1 GenomeRNAi human phenotype for PLAT:

Increased G1 DNA content

Animal Models:
Mouse knock-out Plat^tm1Mlg for PLAT
15/17 MGI mutant phenotypes (inferred from 1 allele) (MGI details for Plat) (see all 17):

behavior/neurological	cardiovascular system	cellular	craniofacial	digestive/alimentary
growth/size	hearing/vestibular/ear	hematopoietic system	homeostasis/metabolism	immune system
mortality/aging	muscle	nervous system	reproductive system	respiratory system

PLAT for phenotypes About GeneDecksing

(Pathways according to EMD Millipore, R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to SABiosciences, and/or STRING, Interactions according to ¹UniProtKB, ²MINT, ³I2D, and/or ⁴STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Mar 2013 via Entrez Gene).
About This Section

Unified GeneCards pathways - 5/12 super-pathways (see all 12) About this table

See pathways by source

Super-pathway

contained gene-specific pathways

Development_CNTF receptor signaling

	Cell adhesion_PLAU signaling	0.35			Cell adhesion Plasmin signaling	0.07
	Cell adhesion PLAU signaling	0.35			Cell adhesion_Plasmin signaling	0.07

Cell adhesion_ECM remodeling

Cell adhesion ECM remodeling

1.00

Cell adhesion_ECM remodeling

1.00

Complement and coagulation cascades

Complement and coagulation cascades

1.00

Complement and Coagulation Cascades

0.72

Formation of Fibrin Clot (Clotting Cascade)

Blood Coagulation Signaling Pathways

0.51

Blood Clotting Cascade

0.36

Selenium Pathway

Selenium Pathway

1.00

Pathway sources
See GeneCards unified pathways
Show all pathways

3 EMD Millipore Pathways for PLAT

	Cell adhesion PLAU signaling
	Cell adhesion ECM remodeling
	Cell adhesion Plasmin signaling

1 R&D Systems Pathway for PLAT

Blood Coagulation Signaling Pathways

3 GeneGo (Thomson Reuters) Pathways for PLAT

	Cell adhesion PLAU signaling
	Cell adhesion ECM remodeling
	Cell adhesion Plasmin signaling

5/6 BioSystems Pathways for PLAT (see all 6)

	Senescence and Autophagy
	Blood Clotting Cascade
	Complement and Coagulation Cascades
	Endochondral Ossification
	Selenium Pathway

4 Reactome Pathways for PLAT

	Hemostasis
	Signal Transduction
	Dissolution of Fibrin Clot
	Signaling by PDGF

1 Kegg Pathway (Kegg details for PLAT):

Complement and coagulation cascades

PLAT for pathways About GeneDecksing

Interactions:

SABiosciences Gene Network Central^TM Interacting Genes and Proteins Network for PLAT

STRING Interaction Network Preview (showing 5 interactants - click image to see 25)

5/34 Interacting proteins for PLAT (P00750^{2, 3} ENSP00000220809⁴) via UniProtKB, MINT, STRING, and/or I2D (see all 34)

Interactant		Interaction Details
GeneCard	External ID(s)	Interaction Details
SERPINE1	P05121²^,³, ENSP00000223095⁴	MINT-8309311 I2D: score=3 STRING: ENSP00000223095
ANXA2	P07355³, ENSP00000346032⁴	I2D: score=3 STRING: ENSP00000346032
CALR	P27797³, ENSP00000320866⁴	I2D: score=3 STRING: ENSP00000320866
LRP1	Q07954³, ENSP00000243077⁴	I2D: score=3 STRING: ENSP00000243077
SERPINI1	Q99574³, ENSP00000295777⁴	I2D: score=3 STRING: ENSP00000295777

About this table

Gene Ontology (GO): 5/16 biological process terms (GO ID links to tree view) (see all 16): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0001666	response to hypoxia	IEA	--
GO:0006464	cellular protein modification process	TAS	3087818
GO:0006508	proteolysis	IEA	--
GO:0007596	blood coagulation	TAS	--
GO:0014909	smooth muscle cell migration	IEA	--

PLAT for ontologies About GeneDecksing

(Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience HMDB, BitterDB, and/or Novoseek, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB, with drugs/clinical trials/news search links to CenterWatch)
About This Section

PLAT for compounds About GeneDecksing

EMD Millipore small molecules for PLAT:
Small Molecule - inhibitor

Browse drugs & compounds from Enzo Life Sciences

Browse Tocris compounds for PLAT
UniProtKB/Swiss-Prot: TPA_HUMAN, P00750

Pharmaceutical: Available under the names Activase (Genentech) and Retavase (Centocor and Roche) [Retavase is a

fragment of TPA that contains kringle 2 and the protease domain; it was also known as BM 06.022]. Used in Acute

Myocardial Infarction (AMI), in Acute Ischemic Stroke (AIS) and Pulmonary Embolism (PE) to initiate fibrinolysis

5 DrugBank Compounds for PLAT About this table

Compound	Synonyms	CAS #	Type	Actions	PubMed Ids
Iloprost	--	78919-13-8	target	other/unknown	1726988 1689620 1370924 1717784 17510465
Urokinase	U-plasminogen activator (see all 3)	9039-53-6	target	--	12893898 14507109 12826021 12745435 12787697
Aminocaproic Acid	6-aminohexanoic acid (see all 7)	60-32-2	target	antagonist	3146348 8073394 7962113 2502209
6-Amino Hexanoic Acid	--	--	target	--	17139284 17016423
5-(DIMETHYLAMINO)-2-NAPHTHALENESULFONIC ACID	--	--	target	--	10592235

10/138 Novoseek chemical compound relationships for PLAT gene (see all 138) About this table

Compound	-log (P-Val)	Hits	PubMed IDs for Articles with Shared Sentences (# sentences)
fibrinogen	87.7	732	1708387 (6), 7774110 (5), 14592559 (4), 9159836 (4) (see all 99)
heparin	79	684	1512328 (7), 1708387 (6), 8874867 (6), 17068072 (6) (see all 99)
abciximab	77.8	337	14982910 (9), 15353917 (8), 15028807 (7), 11071800 (7) (see all 78)
epsilon aminocaproic acid	73.4	47	14743974 (5), 1525179 (4), 8533120 (3), 8112348 (2) (see all 18)
aspirin	61.4	85	9054741 (3), 11680515 (3), 16480745 (3), 8277097 (2) (see all 61)
serine	61.2	182	2110366 (2), 1901356 (2), 15268626 (2), 7495809 (2) (see all 99)
aprotinin	61.1	18	9308747 (2), 15668193 (2), 8641034 (1), 1720262 (1) (see all 13)
nplg	60.1	2	2148848 (1), 2107598 (1)
desmopressin	59.1	90	9427706 (6), 1606286 (5), 10959689 (4), 8854651 (3) (see all 38)
eaca	58.9	7	2123871 (2), 8073394 (2), 7804168 (1), 7759476 (1)

Search CenterWatch for drugs/clinical trials and news about PLAT / TPA

(Secondary structures according to fRNAdb,
GenBank/EMBL/DDBJ Accessions according to
Unigene (Build 235 Homo sapiens; Mar 10 2013) or GenBank,
RefSeq according to Entrez Gene,
DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
RNAi Products from EMD Millipore,
siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN,
Tagged/untagged cDNA clones from OriGene, SwitchGear Genomics, GenScript, DNA2.0, Vector BioLabs, Primers from OriGene, SABiosciences, and/or QIAGEN )
About This Section

REFSEQ mRNAs for PLAT gene (3 alternative transcripts):

NM_000930.3 NM_033011.2 NM_000931.2

Unigene Cluster for PLAT:

Plasminogen activator, tissue

Hs.491582 [show with all ESTs]

Unigene Representative Sequence: BX641021

13 Ensembl transcripts including schematic representations, and UCSC links where relevant:

ENST00000429089 ENST00000220809 ENST00000352041 ENST00000519510 ENST00000429710

ENST00000524009 ENST00000522812 ENST00000521042 ENST00000524261 ENST00000521647

ENST00000520523 ENST00000521694 ENST00000270189(uc010lxf.1 uc010lxg.1 uc003xos.2 uc003xot.2 uc011lcm.1 uc011lcn.1)

miRNA Products:		OriGene 3'-UTR Clone (see all 2): PLAT Browse OriGene MicroRNA Expression Plasmids
		QIAGEN Custom miScript Target Protector blocks miRNA-binding site of human, mouse, rat PLAT
		8/23 QIAGEN miScript miRNA Assays for microRNAs that regulate PLAT (see all 23):
		hsa-miR-548j hsa-miR-3194-5p hsa-miR-642a hsa-miR-548i hsa-miR-3660 hsa-miR-138-2* hsa-miR-340 hsa-miR-144

		SwitchGear 3'UTR luciferase reporter plasmid: PLAT 3' UTR sequence

Inhib. RNA Products:		Browse for Gene Knock-down Tools from EMD Millipore
		OriGene 29mer shRNA kits in GFP-retroviral vector in human, mouse, rat for PLAT (see all 7) OriGene shRNA RFP: PLAT OriGene siRNA: PLAT
		QIAGEN FlexiTube/FlexiPlate siRNA for gene silencing in human, mouse, rat PLAT

Clone Products:		OriGene Myc/DDK tagged cDNA clones in CMV expression vector in human, mouse, rat for PLAT (see all 4) OriGene untagged cDNA clones in CMV expression vector in human, mouse, rat for PLAT (see all 3) OriGene custom cloning services � gene synthesis, subcloning, mutagenesis, variant library, vector shuttling
		GenScript: all cDNA clones in your preferred vector (see all 2): PLAT (NM_033011)
		DNA2.0 Custom Codon Optimized Gene Synthesis Service for PLAT
		Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat PLAT

Primer Products:		OriGene genome-wide validated SYBR primer pairs in human, mouse, rat for PLAT Browse OriGene validated miRNA SYBR primer pairs
		SABiosciences RT² qPCR Primer Assay in human, mouse, rat PLAT
		QIAGEN QuantiTect SYBR Green Assays in human, mouse, rat PLAT
		QIAGEN QuantiFast Probe-based Assays in human, mouse, rat PLAT

Additional cDNA sequence:

AF260825.1 AF282882.1 AK289387.1 AK290575.1 AK297738.1 AK297937.1 AK299205.1 AK300984.1

AK313342.1 AY221101.1 BC002795.2 BC007231.1 BC013968.2 BC018636.2 BC095403.1 BT007060.1

BX641021.1 D01096.1 FM956488.1 M15518.1 M18182.1 V00570.1 X02901.1 X07393.1

X13097.1

20 DOTS entries:

DT.97768693 DT.118738 DT.95257885 DT.100817321 DT.100817313 DT.95257876 DT.95261443 DT.101963746

DT.92447062 DT.95257877 DT.99933134 DT.100817320 DT.95257857 DT.102828184 DT.120645473 DT.120645543

DT.95257856 DT.95257863 DT.95296556 DT.97845240

24/486 AceView cDNA sequences (see all 486):

BU845014 BM503846 BQ436922 NM_000931 BQ685814 AA111972 BX329047 AA370689

BC018636 AU134370 V00570 BQ890669 AI986392 T29900 BU157241 BU157686

AI139272 BQ072488 BQ877849 AU131208 BM986813 CF125651 AA338993 AI394152

GeneLoc Exon Structure

5/8 Alternative Splicing Database (ASD) splice patterns (SP) for PLAT (see all 8) About this scheme

ExUns:	1a	·	1b	·	1c	·	1d	^	2	^	3	^	4a	·	4b	^	5a	·	5b	·	5c	·	5d	^	6	^	7a	·	7b	^	8a	·	8b	^	9a	·	9b	^	10a	·	10b	^	11a	·	11b	·	11c	^	12a	·	12b	^
SP1:																																							-								-
SP2:													-		-																								-								-
SP3:																																			-		-		-		-		-		-		-		-
SP4:													-		-								-		-		-		-		-								-
SP5:																					-		-		-		-		-		-		-		-				-

ExUns:	13	^	14
SP1:
SP2:
SP3:
SP4:
SP5:

ECgene alternative splicing isoforms for PLAT

(RNA expression data according to H-InvDB, NONCODE, miRBase, and RNAdb, Expression images according to data from BioGPS, Illumina Human BodyMap, and CGAP SAGE, Sets of similar genes according to GeneDecks, in vivo and in vitro expression data from LifeMap Discovery™, plus additional links to Genevestigator, and/or SOURCE, and/or BioGPS, and/or UniProtKB,
PCR Arrays from SABiosciences, Primers from OriGene, SABiosciences, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
About This Section

PLAT expression in normal human tissues (normalized intensities)
See probesets specificity/sensitivity at GeneAnnot
About this imageBioGPS
CGAP TAG: TTAGTTTTTA

About this image

PLAT expression in embryonic tissues and stem cells

Expression by the Database of Embryonic development, Stem cell research, and Regenerative medicine About this table

4 LifeMap In Vivo Development Anatomical Compartments/Cells

Tissue

Anatomical Compartment

Cell

Category (developmental path)

Hypoblast

Parietal Endoderm Cells

Extraembryonic Tissues

Kidney

Kidney

Kidney

Expression:

Positive

Negative

Selective marker

Experimental details:

Curated

Microarrays

In-situ hybridization

Stem Cell Differentiation: 5 LifeMap Cells

Name

Category

Extra-embryonic endoderm cells (Fetal Stem / Progenitor Cell)

Extraembryonic Tissues

PureStem™ progenitor RASMO12 (Embryonic Progenitor Cell)

PureStem™ progenitor W10 (Embryonic Progenitor Cell)

Adult human kidney epithelial cells (Primary Cell)

Kidney

Extraembryonic endoderm-like cells (Generation of extrae...)

See PLAT Protein Expression from SPIRE MOPED and PaxDB
Genevestigator expression for PLAT

SOURCE GeneReport for Unigene cluster: Hs.491582

UniProtKB/Swiss-Prot: TPA_HUMAN, P00750

Tissue specificity: Synthesized in numerous tissues (including tumors) and secreted into most extracellular body

fluids, such as plasma, uterine fluid, saliva, gingival crevicular fluid, tears, seminal fluid, and milk

SABiosciences Expression via Pathway-Focused PCR Arrays including PLAT (see all 9):

Fibrosis in human mouse rat

TGFB/BMP Signaling Pathway in human mouse rat

Wound Healing in human mouse rat

cAMP / Ca2+ Signaling PathwayFinder in human mouse rat

Endothelial Cell Biology in human mouse rat

Primer Products:		OriGene genome-wide validated SYBR primer pairs in human, mouse, rat for PLAT Browse OriGene validated miRNA SYBR primer pairs
		SABiosciences RT² qPCR Primer Assay in human, mouse, rat PLAT
		QIAGEN QuantiTect SYBR Green Assays in human, mouse, rat PLAT
		QIAGEN QuantiFast Probe-based Assays in human, mouse, rat PLAT

In Situ
Assay Products:

Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for PLAT

(Orthologs according to ^1,2HomoloGene (²older version, for species not in ¹newer version), ³euGenes, ⁴SGD , ⁵MGI Mar 06 2013, with possible further links to Flybase and/or WormBase, and/or ⁶Ensembl pan taxonomic compara , Gene Trees according to Ensembl and TreeFam)
About This Section

This gene was present in the common ancestor of animals.

Orthologs for PLAT gene from 5/15 species (see all 15) About this table

Organism	Taxonomic classification	Gene	Description	Human Similarity	Orthology Type	Details
chicken (Gallus gallus)	Aves	PLAT¹	plasminogen activator, tissue	64.61(n) 62.36(a)		426791 XM_424404.3 XP_424404.1
lizard (Anolis carolinensis)	Reptilia	PLAT⁶	--	59(a)	1 ↔ 1	GL343545.1(301208-313980)
African clawed frog (Xenopus laevis)	Amphibia	Xl.9397²	Xenopus laevis transcribed sequence with moderate similarity more	79.35(n)		BG347744.1
zebrafish (Danio rerio)	Actinopterygii	plat¹	plasminogen activator, tissue	56.89(n) 55.9(a)		100320028 XM_002663051.1 XP_002663097.1
honey bee (Apis mellifera)	Insecta	--	--	7(a)	possible ortholog	GroupUn.841(30640-42833)

ENSEMBL Gene Tree for PLAT (if available)
TreeFam Gene Tree for PLAT (if available)

(Paralogs according to ¹HomoloGene,
²Ensembl, and ³SIMAP, Pseudogenes according to ⁴Pseudogene.org Build 68)
About This Section

Paralogs for PLAT gene

KREMEN1² KREMEN2² PLG² HGFAC² LPA² PLAU² HABP2² MST1²

F12² MST1L² HGF²

18/55 SIMAP similar genes for PLAT using alignment to 9 protein entries: TPA_HUMAN (see all proteins) (see all similar genes):

tPA DKFZp686I03148 HGF PLG DKFZp586F0824 APOA

F12 TMPRSS5 ATF TMPRSS11D KLK13 HABP2

PRSS2 TRY6 TRY8 PLAU KLK9 PRSS1

PLAT for paralogs About GeneDecksing

(SNPs/Variants according to the ¹NCBI SNP Database, ²Ensembl, ³PupaSUITE, UniProtKB, and DNA2.0, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Mutations from the Human Gene Mutation Database (HGMD) and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers from QIAGEN, Cancer Mutation PCR Arrays and Assays and Copy Number PCR Arrays from SABiosciences)
About This Section

SNP ID	Valid	Clinical significance	Chr 8 pos	Sequence	#	AA Chg	Type	More	#	Pop	Total sample
Genomic Data					Transcription Related Data				Allele Frequencies
				--	--	--		--	--
rs8178811^1,2	C,F,H,	--	40559469(-)	`GAAATT/CGAACC`	2	--	ds500¹		18	NS EA NA CSA WA	1732
rs8178810^1,2	C,H,	--	40559816(-)	`AAATGA/C/GGTTGA`	4	--	ut3¹		6	NS EA	514
rs8178809^1,2	C,F,	--	40560094(-)	`GGCTAG/AGTGCT`	2	--	ut3¹		6	NS NA WA	352
rs8178808^1,2	C,F,	--	40560443(-)	`CTCCCT/CGGCTC`	2	--	ut3¹ ese³		7	NS NA CSA WA	356
rs8178807^1,2	C,F,H,	--	40560506(-)	`CTGGCT/CGGCCC`	2	--	ut3¹		12	NS NA CSA	1031
rs8178806^1,2	C,F,H,	--	40560566(-)	`AGAAAT/CAGACA`	2	--	ut3¹		6	NS EA	514
rs1804184^1,2	C,F,	--	40560916(-)	`AGGCGC/GAGTGC`	2	--	ut3¹ ese³		16	NS NA CSA WA	1020
rs8178804^1,2	C,F,H,	--	40561312(-)	`AGGAAT/CTGATT`	2	--	int¹		9	NS EA CSA WA	636
rs8178803^1,2	C,F,H,	--	40561488(-)	`CAGGCG/AGGACC`	2	--	int¹		6	NS EA	502
rs8178802^1,2	C,F,H,	--	40561556(-)	`CCAACG/CTGCTT`	2	--	int¹		8	NS EA CSA WA	634

HapMap Linkage Disequilibrium report for PLAT (42032236 - 42065242 bp)
Structural Variations (Copy Number Variations, Insertions/Deletions, Inversions)
Database of Genomic Variants (DGV): 1 variation for PLAT
1 CNV: 6613
Human Gene Mutation Database (HGMD): PLAT

SABiosciences Cancer Mutation PCR Assays

QIAGEN SeqTarget long-range PCR primers in human, mouse, rat for resequencing PLAT

DNA2.0 Custom Variant and Variant Library Synthesis for PLAT

(in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Novoseek, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
About This Section

PLAT for disorders           About GeneDecksing

OMIM gene information: 173370
OMIM disorders: 612348
UniProtKB/Swiss-Prot: TPA_HUMAN, P00750

Note=Increased activity of TPA results in increased fibrinolysis of fibrin blood clots that is associated with

excessive bleeding. Defective release of TPA results in hypofibrinolysis that can lead to thrombosis or embolism

20/238 diseases for PLAT (see all 238): About MalaCards

hyperfibrinolysis, familial, due to increased release of plat thrombophilia, familial, due to decreased release of plat thrombosis plasminogen activator inhibitor type 1 deficiency

superior vena cava syndrome central retinal vein occlusion disseminated intravascular coagulation retinal vein occlusion

deep vein thrombosis patent foramen ovale vitreous detachment spinal cord injury

central serous chorioretinopathy type 3 von willebrand disease von willebrand's disease plasminogen activator deficiency

basilar artery occlusion arterial occlusive disease hypersensitivity reaction type ii disease candida glabrata

20/22 diseases from the University of Copenhagen DISEASES database for PLAT (see all 22):

Cerebrovascular accident Myocardial infarction Pulmonary embolism Basilar artery occlusion

Coronary heart disease Atherosclerosis Hypertension Brain ischemia

Intermediate coronary syndrome Disseminated intravascular coagulation Central retinal vein occlusion Diabetes mellitus

Intracranial embolism Central retinal artery occlusion Cancer Intracranial thrombosis

Hemiplegia Aphasia Age related macular degeneration Venous insufficiency

10/97 Novoseek disease relationships for PLAT gene (see all 97) About this table

Disease	-log (P-Val)	Hits	PubMed IDs for Articles with Shared Sentences (# sentences)
acute myocardial infarction	85.1	514	7623530 (4), 7588083 (4), 7942523 (3), 9786806 (3) (see all 99)
stroke acute	84	166	19407229 (4), 18062448 (4), 16728683 (3), 11244203 (3) (see all 99)
stroke	81.4	1460	15699369 (6), 19804685 (6), 18208365 (6), 19423401 (6) (see all 99)
intracranial hemorrhages	80.5	82	9786806 (3), 10024933 (3), 18815396 (2), 17596135 (2) (see all 53)
venous occlusion	79.6	135	1631786 (4), 2128974 (3), 9893018 (3), 8706061 (3) (see all 83)
thrombosis	75.9	149	8657763 (3), 7692999 (2), 11387618 (2), 11719681 (2) (see all 99)
bleeding	75	391	17975562 (4), 11698625 (4), 11195747 (4), 16515019 (3) (see all 99)
myocardial infarction	74.5	231	8763515 (3), 10172669 (3), 10079776 (2), 10342921 (2) (see all 99)
intracerebral hemorrhage	72.7	68	1901466 (4), 9368550 (3), 11239197 (2), 16728683 (2) (see all 46)
fibrinolytic defect	67.9	4	1452521 (1), 14630788 (1), 1909902 (1)

Genatlas disease: PLAT

thrombosis,recurrent

Genetic Association Database (GAD): PLAT
Human Genome Epidemiology (HuGE) Navigator: PLAT (102 documents)
Tumor Gene Database (TGDB): PLAT

Export disorders for PLAT gene to outside databases

(in PubMed. Associations of this gene to articles via ¹Entrez Gene, ²UniProtKB/Swiss-Prot, ³HGNC, ⁴GAD, ⁵PharmGKB, ⁶HMDB, ⁷DrugBank, ⁸UniProtKB/TrEMBL, ⁹ Novoseek, and/or ¹⁰fRNAdb)
About This Section

PubMed articles for PLAT gene, integrated from 9 sources (see all 2834):
(articles sorted by number of sources associating them with PLAT)

Utopia: connect your pdf to the dynamic
world of online information

Genetic variation at the human tissue-type plasminogen activator (tPA) locus: haplotypes and analysis of association to plasma levels of tPA. (PubMed id 12891381)^{1, 4, 9} Ladenvall P....Jern C. (2003)
Is tissue-plasminogen activator gene polymorphism a risk factor for venous thromboembolism in every population? (PubMed id 15976969)^{1, 4, 9} Oguzulgen I.K....Akar N. (2005)
Influence of the Alu-repeat I/D polymorphism in t-PA gene intron 8 on the stimulated t-PA release after venous occlusion. (PubMed id 12643326)^{1, 4, 9} Sartori M.T....Girolami A. (2003)
Tissue plasminogen activator and plasminogen activator inhibitor type 1 gene polymorphism in patients with gastric ulcer complicated with bleeding. (PubMed id 12589088)^{1, 4, 9} Kim H.S....Hong S.Y. (2003)
Functionally inactive protein C inhibitor in seminal plasma may be associated with infertility. (PubMed id 10340997)^{1, 2, 9} He S....Liu Y.X. (1999)
Alu-repeat polymorphism in the gene coding for tissue-type plasminogen activator and the risk of hypertension in a Chinese Han population. (PubMed id 12484521)^{1, 4, 9} Wang B....He R. (2002)
Lysine 156 promotes the anomalous proenzyme activity of tPA: X-ray crystal structure of single-chain human tPA. (PubMed id 9305622)^{1, 2, 9} Renatus M....Bode W. (1997)
Linkage disequilibrium and haplotype analysis among eight novel single-nucleotide polymorphisms in the human tissue-type plasminogen activator (t-PA) gene. (PubMed id 11450845)^{1, 4, 9} Nakazawa I....Emi M. (2001)
The solution structure and backbone dynamics of the fibronectin type I and epidermal growth factor-like pair of modules of tissue-type plasminogen activator. (PubMed id 7582899)^{1, 2, 9} Smith B.O.... Campbell I.D. (1995)
Regulatory polymorphisms in extracellular matrix protease genes and susceptibility to rheumatoid arthritis: a case-control study. (PubMed id 16356191)^{1, 4} Rodriguez-Lopez J....Gonzalez A. (2006)

(in PubMed, OMIM, and NCBI Bookshelf)
About This Section

		AND	OR
Aliases
Disorders
Free Text

Query String		PubMed OMIM NCBI Bookshelf
	(Note: In FireFox, select the above section and copy using Ctrl-C)

(According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
About This Section

Entrez Gene: 5327	HGNC: 9051	AceView: PLAT	Ensembl:ENSG00000104368	euGenes: HUgn5327
ECgene: PLAT	Kegg: 5327	H-InvDB: PLAT

(According to HUGE)
About This Section

(According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL,
Wikipedia and/or GeneReviews via UniProtKB/Swiss-Prot)
About This Section

Name	Description
PharmGKB entry for PLAT	Pharmacogenomics, SNPs, Pathways
ATLAS Chromosomes in Cancer entry for PLAT	Genetics and Cytogenetics in Oncology and Haematology
Wikipedia	http://en.wikipedia.org/wiki/Tissue_plasminogen_Activator
SeattleSNPs	http://pga.gs.washington.edu/data/plat/
SHMPD	http://shmpd.bii.a-star.edu.sg/gene.php?genestart=A&genename=PLAT
Activase	http://www.gene.com/gene/products/information/cardiovascular/activase/insert.jsp#pharmacology
Retavase	http://www.retavase.com/pdf/Retavase_PI.pdf

Intellectual Property for PLAT gene
(Patent information from GeneIP, Licensable technologies from WIS Yeda, Salk, Tufts, IP news from LifeMap Sciences, Inc.)

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Patent Information for PLAT gene:
Search GeneIP for patents involving PLAT

GeneCards and IP:
Japan Patent Office Licenses GeneCards European Patent Office Licenses GeneCards Improving the IP Search

(Antibodies, recombinant proteins, and assays from EMD Millipore, R&D Systems, OriGene, QIAGEN, GenScript, Cell Signaling Technology, SABiosciences, Novus Biologicals, Sino Biological, Enzo Life Sciences, Abcam, ProSpec, Uscn, Thermo Fisher Scientific, Gene Editing from DNA2.0, Clones from EMD Millipore, OriGene, GenScript, Sino Biological, DNA2.0, SwitchGear Genomics, Vector BioLabs, Cell lines from GenScript and LifeMap BioReagents, PCR Arrays from SABiosciences, Drugs and/or compounds from EMD Millipore, Tocris Bioscience, and/or Enzo Life Sciences),
In Situ Hybridization Assays from
Advanced Cell Diagnostics
About This Section

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PLAT Gene

plasminogen activator, tissue

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Hepatic Veno-Occlusive Disease
THROMBOTIC STROKE
CAROTID ARTERY INTERNAL OCCLUSION
artery occlusion
veno-occlusive disease
essential hypertension
Raynauds Phenomenon
coagulopathy
Acute myocardial infarction
INTRACEREBRAL HEMATOMA
Angioedema
Brain Hemorrhage
Myocardial Ischemia
Acute cerebrovascular disease
Ischemia
Atherosclerosis
vascular obstruction
PLATELET AGGREGATION, SPONTANEOUS
Anterior myocardial infarction
Ventricular Dysfunction Right
Deep vein thrombosis
Antiphospholipid Syndrome
Brain Ischemia
Hypofibrinogenemia
cell damage
Hypotension
FEMORAL ARTERY THROMBOSIS
Coronary Atherosclerosis
Chronic gingivitis
PULMONARY EMBOLISM ACUTE MASSIVE
Pathological Processes
Cerebral Infarction
ARTERIAL THROMBOSIS
FIBRINOLYTIC DEFECT
MACULAR DEGENERATION, SENILE
Inflammation
Vitreous Hemorrhage
Embolism
Coronary Thrombosis
Hyperhomocysteinemia
Intracerebral Hemorrhage
Cerebral Edema
Cardiovascular Diseases
Thrombosis
Necrosis
Sinus Thrombosis
HEMORRHAGIC STROKE
Disseminated Intravascular Coagulation
Preeclampsia
Coronary Heart Disease
Venous Ulcer
APC Resistance
Coronary Occlusion
Infarction Middle Cerebral Artery
Neurological Disorders
Shock Cardiogenic
Infarction inferior
Venous Thrombosis
atherosclerotic plaque
Cardiac Rupture
Occlusion Middle Cerebral Artery
Atrial Fibrillation
INTRAVENTRICULAR HEMORRHAGE
Hemorrhage subretinal
INFARCT
POADS
Arterial Occlusive Diseases
Stroke Acute
VENOUS OCCLUSION
BLEEDING TENDENCY
Dysfibrinogenemia
Intracranial Hemorrhages
Myocardial Infarction
Posterior Vitreous Detachment
Coronary Artery Disease
BUNDLE BRANCH BLOCK
Insulin Resistance
stasis
Complication hemorrhage
Bleeding
Subarachnoid Hemorrhage Aneurysmal
Hypertriglyceridemia
Thromboembolism Pulmonary
ANAPHYLACTOID REACTION
Hyphema
Hematoma
Thrombophilia
STROKE
Vascular Diseases
Cerebral Ischemia
Central retinal vein occlusion
Pulmonary Embolism
NIDDM
reactive hyperemia
Peritoneal Adhesions
EMBOLIC STROKE
Thromboembolism

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PLAT Gene

plasminogen activator, tissue

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