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Primary Information | |
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| BoMiProt ID | Bomi3887 |
| Protein Name | Angiotensinogen/Serpin A8 |
| Organism | Bos taurus |
| Uniprot ID | P01017 |
| Milk Fraction | Exosomes |
| Aminoacid Length | 476 |
| Molecular Weight | 51424 |
| FASTA Sequence | Download |
| Gene Name | AGT/SERPINA8 |
| Protein Existence Status | reviewed |
Secondary Information | |
| Presence in other biological fluids/tissue/cells | Angiotensinogen is synthesised in the liver and secreted in plasma |
| Protein Function | component of the renin-angiotensin system (RAS),regulates blood pressure and fluid balance.Angiotensinogen is catalytically cleaved by renin to produce angiotensin I in response to lowered blood pressure.Angiotensin converting enzyme (ACE), subsequently removes a dipeptide to produce angiotensin II, the physiologically active peptide, which functions in the regulation of volume and mineral balance of body fluids.Angiotensin I and angiotensin II can be further processed to generate angiotensin III, which stimulates aldosterone release.Resolution of the crystal structure of AGT protein found that the renin cleavage site of AGT was buried in the AGT N-terminal tail. |
| Biochemical Properties | AGT is a member of the non-inhibitory serpin (serine protease inhibitor) superfamily.Cysteines at positions 18 and 138 of human AGT (Cys18-Cys137 in mice) have the potential to form an intermolecular disulfide bond that is conserved across species.The AGT protein is secreted with the disulfide bond.The signature structural elements of serpins consist of three β sheets and 8 to 9 α helices. |
| PTMs | Glycosylation,Disulfide bond formation,Proteolytic cleavage |
| Site(s) of PTM(s) N-glycosylation, O-glycosylation, Phosphorylation | >sp|P01017|ANGT_BOVIN Angiotensinogen OS=Bos taurus OX=9913 GN=AGT PE=1 SV=2 MAPAGLSLGAAILCLLAWAGLAAGDRVYVHPFHLLVYSKSNCDQLEKPSVETPPDPTFTP VPIQTKSSAVDEEALWEQLVRATEKLEAEDRLRASEVGLLLNFMGFHMYKTLSETWSVAS GAVFSPVALFSTLTSFYVGALDPTASRLQAFLGVPGEGQGCTSRLDGHKVLSSLQTIQGL LVAQGGASSQARLLLSTVVGLFTAPGLHLKQPFVQSLSSFAPITLPRSLDLSTDPNLAAE KINRFMQSVTGWNMGRALTAVSPDSTLLFNAYVHFQGKMKGFSLLPGLKEFWVDN*295TTSVS VPMLSGTGIFHFWSDSQNN*319LSVTRVPLSANTYLLLIQPHHTPDLRKVEALTFQHNFLTRM KN*362LSPRAIHLTMPQLTLKASYDLQDLLAQAKLPTLLGAEAN*401LSKISDANLRVGKVLNSVL FELKADGEQAPESVPQPAGPEALEVTLNSPFLLAVLERSSGALHFLGRVSRPLSAE |
| CATH | Matched CATH superfamily n/a |
| Predicted Disorder Regions | 44-78, 429-439 |
| DisProt Annotation | |
| TM Helix Prediction | 2TMHs; (4-22) & (116-138) |
| Significance of PTMs | Proteolytic cleavage during synthesis of Angiotensin 1.Angiotensin-1 and angiotensin-2 can be further processed to generate angiotensin-3, angiotensin-4. Angiotensin 1-9 is cleaved from angiotensin-1 by ACE2 and can be further processed by ACE to produce angiotensin 1-7, angiotensin 1-5 and angiotensin 1-4. Angiotensin 1-7 has also been proposed to be cleaved from angiotensin-2 by ACE2 or from angiotensin-1 by MME. |
| PDB ID | 1GVU, 3ER5, |
| Additional Comments | Angiotensinogen appears to be associated with a predisposition to essential hypertension; it is also associated with pregnancy-induced hypertension (pih) (preeclampsia), a heterogeneous disorder that complicates 5-7% of all pregnancies and remains a leading cause of maternal, foetal and neonatal morbidity and mortality |
| Bibliography | 1.Lu H, Cassis LA, Kooi CW, Daugherty A. Structure and functions of angiotensinogen. Hypertens Res. 2016 Jul;39(7):492-500. doi: 10.1038/hr.2016.17. Epub 2016 Feb 18. Erratum in: Hypertens Res. 2016 Nov;39(11):827. PMID: 26888118; PMCID: PMC4935807. 2.Sparks, M. A., Crowley, S. D., Gurley, S. B., Mirotsou, M., & Coffman, T. M. (2014). Classical Renin-Angiotensin system in kidney physiology. Comprehensive Physiology, 4(3), 1201–1228. https://doi.org/10.1002/cphy.c130040 |