Result Untitled Document Tissue-type plasminogen activatorSourceHomo sapiens (human) Taxonomy Homo sapiens Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.Keywords3D-structure; Alternative splicing; Cleavage on pair of basic residues; Complete proteome; Direct protein sequencing; Disulfide bond; EGF-like domain; Glycoprotein; Hydrolase; Kringle; Pharmaceutical; Plasminogen activation; Polymorphism; Protease; Repeat; Secreted; Serine protease; Signal; Zymogen.DetailsFunction: 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. Play a direct role in facilitating neuronal migration. Post-translational modification: 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 Xa. 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 fibrin. N-glycosylation of Asn-152; the bound oligomannosidic glycan is involved in the interaction with the mannose receptor. Characterization of O-linked glycan was studied in Bowes melanoma cell line. Similarity: Belongs to the peptidase S1 family. Contains 1 EGF-like domain. Contains 1 fibronectin type-I domain. Contains 2 kringle domains. Contains 1 peptidase S1 domain. Subcellular location: Secreted, extracellular space. Subunit structure: Heterodimer of chain A and chain B held by a disulfide bond. 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. 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. Disease: Increased activity of TPA is the cause of hyperfibrinolysis Alternative products: Event=Alternative splicing; Named isoforms=4; Name=1; Synonyms=Long; IsoId=P00750-1; Sequence=Displayed; Name=2; Synonyms=Short; IsoId=P00750-2; Sequence=VSP_005411, VSP_005412; Note=May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay; Name=3; IsoId=P00750-3; Sequence=VSP_015957; Note=No experimental confirmation available; Name=4; Synonyms=Neonatal; IsoId=P00750-4; Sequence=VSP_028029, VSP_028030; Note=No experimental confirmation available. Sequence length: 562 AA. SequenceMDAMKRGLCCVLLLCGAVFVSPSQEIHARFRRGARSYQVICRDEKTQMIYQQHQSWLRPVLRSNRVEYCWCNSGRAQCHSVPVKSCSEPRCFNGGTCQQALYFSDFVCQCPEGFAGKCCEIDTRATCYEDQGISYRGTWSTAESGAECTNWNSSALAQKPYSGRRPDAIRLGLGNHNYCRNPDRDSKPWCYVFKAGKYSSEFCSTPACSEGNSDCYFGNGSAYRGTHSLTESGASCLPWNSMILIGKVYTAQNPSAQALGLGKHNYCRNPDGDAKPWCHVLKNRRLTWEYCDVPSCSTCGLRQYSQPQFRIKGGLFADIASHPWQAAIFAKHRRSPGERFLCGGILISSCWILSAAHCFQERFPPHHLTVILGRTYRVVPGEEEQKFEVEKYIVHKEFDDDTYDNDIALLQLKSDSSRCAQESSVVRTVCLPPADLQLPDWTECELSGYGKHEALSPFYSERLKEAHVRLYPSSRCTSQHLLNRTVTDNMLCAGDTRSGGPQANLHDACQGDSGGPLVCLNDGRMTLVGIISWGLGCGQKDVPGVYTKVTNYLDWIRDNMRPAccession NumberP00750 PubMed ID6337343, 6089198, 3009482, 3090401, 2824147, 3133640, 2107528, 14702039, 15489334, 3161893, 1368681, 6682760, 6433976, 6572897, 2513186, 1900431, 1645336, 11384978, 14759258, 2558718, 1901789, 1762144, 1310033, 1602484, 7582899, 8613982, 9305622 CTD DB5327eggNOG DBprNOG16610Ensembl DBENST00000220809CATHG3DSA:2.10.70.10, G3DSA:2.40.20.10Genecard DBGC08M042151GeneID DB5327GermOnline DBENSG00000104368GO DB0005615, 0004252, 0007596, 0006464, 0006508HGNC DB9051HPA DBCAB009335, HPA003412InterPro DBIPR016060, IPR006209, IPR006210, IPR013032, IPR000742, IPR000083, IPR000001, IPR013806, IPR018056, IPR018059, IPR018114, IPR001254, IPR001314, IPR009003H-InvDBHIX0007476IPI DBIPI00019590, IPI00479511, IPI00910450, IPI00953228KEGGhsa:5327NCBIL00153, AAB59510, L00141, L00142, L00143, L00144, L00145, L00146, L00147, L00148, L00149, L00150, L00151, K03021, AAA98809, M15518, AAA60111, M18182, AAA36800, X07393, CAA30302, X13097, CAA31489, AF260825, AAK11956, AY221101, AAO34406, AK289387, BAF82076, AK290575, BAF83264, AK313342, BAG36145, BT007060, AAP35709, AY291060, AAP34246, CH471080.2, EAW63235, EAW63233, BC002795.2, AAH02795.3, BC007231, AAH07231, BC013968.2, AAH13968.3, BC018636.2, AAH18636.3, BC095403, AAH95403, M11890, AAA61213, M11889, D01096, BAA00881, V00570, CAA23833, NP_000921, NP_127509OMATCGLRQYOMIM105200, 134820, 202400, 134830, 202400, 134850, 202400, 176930, 601367, 134390, 188055, 227400, 600880, 601367, 612309, 227500, 134500, 306700, 300746, 306900, 227600, 176860, 188050, 612283, 612304, 176880, 612336, 264900, 612416, 234000, 610618, 610619, 229000, 612423, 107300, 188050, 134570, 134580, 193400, 277480, 228960, 612358, 176895, 173350, 188050, 217090, 173370OrthoDBEOG9TQPVKPDB1A5H_A, 1A5H_B, 1A5H_C, 1A5H_D, 1BDA_A, 1BDA_B, 1PK2_A, 1PML_A, 1PML_B, 1PML_C, 1RTF_B, 1TPG_A, 1TPK_A, 1TPK_B, 1TPK_C, 1TPM_A, 1TPN_APfamPF00008, PF00039, PF00051, PF00089PharmaGKBPA33381PROSITE DBPS00022, PS01186, PS50026, PS01253, PS51091, PS00021, PS50070, PS50240, PS00134, PS00135SMART DBSM00181, SM00058, SM00130, SM00020UCSCuc003xos.2, uc003xot.2, uc010lxf.1UniGeneHs.491582
Result
Tissue-type plasminogen activator
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. Play a direct role in facilitating neuronal migration. Post-translational modification: 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 Xa. 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 fibrin. N-glycosylation of Asn-152; the bound oligomannosidic glycan is involved in the interaction with the mannose receptor. Characterization of O-linked glycan was studied in Bowes melanoma cell line. Similarity: Belongs to the peptidase S1 family. Contains 1 EGF-like domain. Contains 1 fibronectin type-I domain. Contains 2 kringle domains. Contains 1 peptidase S1 domain. Subcellular location: Secreted, extracellular space. Subunit structure: Heterodimer of chain A and chain B held by a disulfide bond. 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. 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. Disease: Increased activity of TPA is the cause of hyperfibrinolysis Alternative products: Event=Alternative splicing; Named isoforms=4; Name=1; Synonyms=Long; IsoId=P00750-1; Sequence=Displayed; Name=2; Synonyms=Short; IsoId=P00750-2; Sequence=VSP_005411, VSP_005412; Note=May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay; Name=3; IsoId=P00750-3; Sequence=VSP_015957; Note=No experimental confirmation available; Name=4; Synonyms=Neonatal; IsoId=P00750-4; Sequence=VSP_028029, VSP_028030; Note=No experimental confirmation available. Sequence length: 562 AA.
MDAMKRGLCCVLLLCGAVFVSPSQEIHARFRRGARSYQVICRDEKTQMIYQQHQSWLRPVLRSNRVEYCWCNSGRAQCHSVPVKSCSEPRCFNGGTCQQALYFSDFVCQCPEGFAGKCCEIDTRATCYEDQGISYRGTWSTAESGAECTNWNSSALAQKPYSGRRPDAIRLGLGNHNYCRNPDRDSKPWCYVFKAGKYSSEFCSTPACSEGNSDCYFGNGSAYRGTHSLTESGASCLPWNSMILIGKVYTAQNPSAQALGLGKHNYCRNPDGDAKPWCHVLKNRRLTWEYCDVPSCSTCGLRQYSQPQFRIKGGLFADIASHPWQAAIFAKHRRSPGERFLCGGILISSCWILSAAHCFQERFPPHHLTVILGRTYRVVPGEEEQKFEVEKYIVHKEFDDDTYDNDIALLQLKSDSSRCAQESSVVRTVCLPPADLQLPDWTECELSGYGKHEALSPFYSERLKEAHVRLYPSSRCTSQHLLNRTVTDNMLCAGDTRSGGPQANLHDACQGDSGGPLVCLNDGRMTLVGIISWGLGCGQKDVPGVYTKVTNYLDWIRDNMRP
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