Protein Z: Difference between revisions

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{{protein
{{Other uses|Z-gene (disambiguation){{!}}Z-gene}}
{{infobox protein
| Name = protein Z
| Name = protein Z
| caption =  
| caption = Crystallographic structure protein Z.<ref name="pmid12604795">{{PDB|1LP1}}: {{cite journal |vauthors=Högbom M, Eklund M, Nygren PA, Nordlund P | title = Structural basis for recognition by an in vitro evolved affibody | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 100 | issue = 6 | pages = 3191–6 |date=March 2003 | pmid = 12604795 | pmc = 404300 | doi = 10.1073/pnas.0436100100 | url = | issn = }}</ref>
| image =  
| image = Protein Z.png
| width =  
| width =  
| HGNCid = 9460
| HGNCid = 9460
Line 11: Line 12:
| RefSeq = NM_003891
| RefSeq = NM_003891
| UniProt = P22891
| UniProt = P22891
| PDB =  
| PDB = 1LP1
| ECnumber =  
| ECnumber =  
| Chromosome = 13
| Chromosome = 13
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| LocusSupplementaryData =  
| LocusSupplementaryData =  
}}
}}
{{Protbox finish}}  
'''Protein Z''' ('''PZ''' or '''PROZ''') is a [[protein]] which in humans is encoded by the ''PROZ'' [[gene]].<ref name="pmid2244898">{{cite journal |vauthors=Ichinose A, Takeya H, Espling E, Iwanaga S, Kisiel W, Davie EW | title = Amino acid sequence of human protein Z, a vitamin K-dependent plasma glycoprotein | journal = Biochem. Biophys. Res. Commun. | volume = 172 | issue = 3 | pages = 1139–44 |date=November 1990 | pmid = 2244898 | doi = 10.1016/0006-291X(90)91566-B | url =  | issn = }}</ref><ref name="pmid2403355">{{cite journal |vauthors=Sejima H, Hayashi T, Deyashiki Y, Nishioka J, Suzuki K | title = Primary structure of vitamin K-dependent human protein Z | journal = Biochem. Biophys. Res. Commun. | volume = 171 | issue = 2 | pages = 661–8 |date=September 1990 | pmid = 2403355 | doi = 10.1016/0006-291X(90)91197-Z  | url = | issn = }}</ref>
{{SI}}
{{CMG}}


{{EH}}
Protein Z is a member of the [[coagulation|coagulation cascade]], the group of blood proteins that leads to the formation of [[blood clot]]s. It is a [[gla domain]] protein and thus [[vitamin K]]-dependent, and its functionality is therefore impaired in [[warfarin]] therapy. It is a [[glycoprotein]].


==Overview==
== Physiology ==
'''Protein Z''' is a member of the [[coagulation|coagulation cascade]], the group of blood proteins that leads to the formation of [[blood clot]]s. It is [[vitamin K]]-dependent, and its functionality is therefore impaired in [[warfarin]] therapy. It is a [[glycoprotein]].


==Physiology==
Although it is not enzymatically active, it is structurally related to several [[serine protease]]s of the coagulation cascade: [[factor VII|factors VII]], [[factor IX|IX]], [[factor X|X]] and [[protein C]]. The [[carboxyglutamate]] residues (which require vitamin K) bind protein Z to [[phospholipid]] surfaces.
Although it is not enzymatically active, it is structurally related to several [[serine protease]]s of the coagulation cascade: [[factor VII|factors VII]], [[factor IX|IX]], [[factor X|X]] and [[protein C]]. The carboxyglutamate residues (which require vitamin K) bind protein Z to [[phospholipid]] surfaces.


The main role of protein Z appears to be the degradation of [[factor X]]a. This is done by [[protein Z-related protease inhibitor]] (ZPI), but the reaction is accelerated 1000-fold by the presence of protein Z. Oddly, ZPI also degrades [[factor XI]], but this reaction does not require the presence of protein Z.
The main role of protein Z appears to be the degradation of [[factor Xa]]. This is done by [[protein Z-related protease inhibitor]] (ZPI), but the reaction is accelerated 1000-fold by the presence of protein Z. Oddly, ZPI also degrades [[factor XI]], but this reaction does not require the presence of protein Z.


In some studies, deficiency states have been associated with a propensity to [[thrombosis]]. Others, however, link it to [[hemorrhagic diathesis|bleeding tendency]]; there is no clear explanation for this, as it acts physiologically as an inhibitor, and deficiency would logically have led to a predisposition for [[thrombosis]].
In some studies, deficiency states have been associated with a propensity to [[thrombosis]]. Others, however, link it to [[hemorrhagic diathesis|bleeding tendency]]; there is no clear explanation for this, as it acts physiologically as an inhibitor, and deficiency would logically have led to a predisposition for [[thrombosis]].


==Genetics==
== Genetics ==
 
It is 62 [[kDa]] large and 396 [[amino acid]]s long. The ''PROZ'' [[gene]] has been linked to the thirteenth [[chromosome]] (13q34).
It is 62 [[kDa]] large and 396 [[amino acid]]s long. The ''PROZ'' [[gene]] has been linked to the thirteenth [[chromosome]] (13q34).


It has four domains: a [[carboxyglutamate|gla]]-rich region, two EGF-like domains and a trypsin-like domain. It lacks the [[serine]] residue that would make it catalytically active as a [[serine protease]].
It has four domains: a [[carboxyglutamate|gla]]-rich region, two EGF-like domains and a trypsin-like domain. It lacks the [[serine]] residue that would make it catalytically active as a [[serine protease]].


==History==
== History ==
Protein Z was first isolated in cattle blood by Prowse and Esnouf in 1977,<ref>Prowse CV, Esnouf MP. ''The isolation of a new warfarin-sensitive protein from bovine plasma.'' Biochem Soc Trans 1977;5:255-256. PMID 892175.</ref> and Broze & Miletich determined it in human plasma in 1984.<ref>Broze GJ Jr, Miletich JP. ''Human Protein Z.'' J Clin Invest 1984;73:933-8. PMID 6707212.</ref>


==References==
Protein Z was first isolated in [[cattle]] blood by Prowse and Esnouf in 1977,<ref name="pmid892175">{{cite journal |vauthors=Prowse CV, Esnouf MP | title = The isolation of a new warfarin-sensitive protein from bovine plasma | journal = Biochem. Soc. Trans. | volume = 5 | issue = 1 | pages = 255–6 | year = 1977 | pmid = 892175 | doi = | url = | issn = }}</ref> and Broze & Miletich determined it in human plasma in 1984.<ref name="pmid6707212">{{cite journal |vauthors=Broze GJ, Miletich JP | title = Human Protein Z | journal = J. Clin. Invest. | volume = 73 | issue = 4 | pages = 933–8 |date=April 1984 | pmid = 6707212 | pmc = 425104 | doi = 10.1172/JCI111317 | url = | issn = }}</ref>
<references/>


==External links==
== Structure ==
 
Structural analysis of protein Z will allow better understanding of its function. The [[Ramachandran plot]] for protein Z indicates it will form alpha helices. The final structure, all alpha domain, was determined by x-ray diffraction. It consists of chain A and B, which are both helix-loop-helix motifs.<ref name="pmid12604795"/>
 
== References ==
{{Reflist|2}}
 
== External links ==
* [http://www.hprd.org/protein/07182 Human Protein Reference Database]
* [http://www.hprd.org/protein/07182 Human Protein Reference Database]


{{Coagulation}}
{{Coagulation}}
{{SIB}}


[[Category:Coagulation system]]
[[Category:Coagulation system]]
[[Category:Hematology]]
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Latest revision as of 03:11, 8 February 2017

For other uses, see Z-gene.
protein Z
File:Protein Z.png
Crystallographic structure protein Z.[1]
Identifiers
SymbolPROZ
Entrez8858
HUGO9460
OMIM176895
PDB1LP1
RefSeqNM_003891
UniProtP22891
Other data
LocusChr. 13 q34

Protein Z (PZ or PROZ) is a protein which in humans is encoded by the PROZ gene.[2][3]

Protein Z is a member of the coagulation cascade, the group of blood proteins that leads to the formation of blood clots. It is a gla domain protein and thus vitamin K-dependent, and its functionality is therefore impaired in warfarin therapy. It is a glycoprotein.

Physiology

Although it is not enzymatically active, it is structurally related to several serine proteases of the coagulation cascade: factors VII, IX, X and protein C. The carboxyglutamate residues (which require vitamin K) bind protein Z to phospholipid surfaces.

The main role of protein Z appears to be the degradation of factor Xa. This is done by protein Z-related protease inhibitor (ZPI), but the reaction is accelerated 1000-fold by the presence of protein Z. Oddly, ZPI also degrades factor XI, but this reaction does not require the presence of protein Z.

In some studies, deficiency states have been associated with a propensity to thrombosis. Others, however, link it to bleeding tendency; there is no clear explanation for this, as it acts physiologically as an inhibitor, and deficiency would logically have led to a predisposition for thrombosis.

Genetics

It is 62 kDa large and 396 amino acids long. The PROZ gene has been linked to the thirteenth chromosome (13q34).

It has four domains: a gla-rich region, two EGF-like domains and a trypsin-like domain. It lacks the serine residue that would make it catalytically active as a serine protease.

History

Protein Z was first isolated in cattle blood by Prowse and Esnouf in 1977,[4] and Broze & Miletich determined it in human plasma in 1984.[5]

Structure

Structural analysis of protein Z will allow better understanding of its function. The Ramachandran plot for protein Z indicates it will form alpha helices. The final structure, all alpha domain, was determined by x-ray diffraction. It consists of chain A and B, which are both helix-loop-helix motifs.[1]

References

  1. ↑ 1.0 1.1 PDB: 1LP1​: Högbom M, Eklund M, Nygren PA, Nordlund P (March 2003). "Structural basis for recognition by an in vitro evolved affibody". Proc. Natl. Acad. Sci. U.S.A. 100 (6): 3191–6. doi:10.1073/pnas.0436100100. PMC 404300. PMID 12604795.
  2. ↑ Ichinose A, Takeya H, Espling E, Iwanaga S, Kisiel W, Davie EW (November 1990). "Amino acid sequence of human protein Z, a vitamin K-dependent plasma glycoprotein". Biochem. Biophys. Res. Commun. 172 (3): 1139–44. doi:10.1016/0006-291X(90)91566-B. PMID 2244898.
  3. ↑ Sejima H, Hayashi T, Deyashiki Y, Nishioka J, Suzuki K (September 1990). "Primary structure of vitamin K-dependent human protein Z". Biochem. Biophys. Res. Commun. 171 (2): 661–8. doi:10.1016/0006-291X(90)91197-Z. PMID 2403355.
  4. ↑ Prowse CV, Esnouf MP (1977). "The isolation of a new warfarin-sensitive protein from bovine plasma". Biochem. Soc. Trans. 5 (1): 255–6. PMID 892175.
  5. ↑ Broze GJ, Miletich JP (April 1984). "Human Protein Z". J. Clin. Invest. 73 (4): 933–8. doi:10.1172/JCI111317. PMC 425104. PMID 6707212.

External links

Retrieved from "https://www.wikidoc.org/index.php?title=Protein_Z&oldid=1416180"