Editing Hydroxyproline (section)

=== Animals ===

==== Collagen ====
Hydroxyproline is a major component of the [[protein]] [[collagen]],<ref name="SzpakJAS">{{Cite journal |last=Szpak |first=Paul |title=Fish bone chemistry and ultrastructure: implications for taphonomy and stable isotope analysis | url=https://www.academia.edu/801925 |journal=[[Journal of Archaeological Science]] |year=2011 |volume=38 |issue=12 |pages=3358–3372 |doi=10.1016/j.jas.2011.07.022 }}</ref> comprising roughly 13.5% of mammalian collagen. Hydroxyproline and proline play key roles for collagen stability.<ref name="Nelson">Nelson, D. L. and Cox, M. M. (2005) Lehninger's Principles of Biochemistry, 4th Edition, W. H. Freeman and Company, New York.</ref> They permit the sharp twisting of the collagen helix.<ref name="Brinckmann">Brinckmann, J., Notbohm, H. and Müller, P.K. (2005) Collagen, Topics in Current Chemistry 247, Springer, Berlin.</ref> In the canonical collagen Xaa-Yaa-Gly triad (where Xaa and Yaa are any amino acid), a proline occupying the Yaa position is hydroxylated to give a Xaa-Hyp-Gly sequence.  This modification of the proline residue increases the stability of the collagen [[triple helix]]. It was initially proposed that the stabilization was due to water molecules forming a hydrogen bonding network linking the prolyl hydroxyl groups and the main-chain carbonyl groups.<ref name="Bella1994">{{cite journal | last1 = Bella | first1 = J | last2 = Eaton | first2 = M | last3 = Brodsky | first3 = B | last4 = Berman | first4 = HM | title = Crystal and molecular structure of a collagen-like peptide at 1.9 A resolution | journal = Science | volume = 266 | issue = 5182 | pages = 75–81 | year = 1994 | pmid = 7695699 | doi=10.1126/science.7695699}}</ref> It was subsequently shown that the increase in stability is primarily through [[stereoelectronic effect]]s and that hydration of the hydroxyproline residues provides little or no additional stability.<ref name="Kotch2008">{{cite journal | doi = 10.1021/ja800225k | last1 = Kotch | first1 = F.W. | last2 = Guzei | first2 = I.A. | last3 = Raines | first3 = R.T. | year = 2008 | title = Stabilization of the Collagen Triple Helix by O-Methylation of Hydroxyproline Residues | journal = Journal of the American Chemical Society | volume = 130 | issue = 10| pages = 2952–2953 | pmid = 18271593 | pmc = 2802593 }}</ref>

==== Non-collagen ====
Hydroxyproline is  found in few proteins other than collagen. For this reason, hydroxyproline content has been used as an indicator to determine [[collagen]] and/or [[gelatin]] amount. However, the mammalian proteins [[elastin]] and [[Argonaute|argonaute 2]] have collagen-like domains in which hydroxyproline is formed. Some snail poisons, [[conotoxin]]s, contain hydroxyproline, but lack collagen-like sequences.<ref name="gorres" />

Hydroxylation of proline has been shown to be involved in targeting [[Hypoxia-inducible factor]] (HIF) alpha subunit ([[HIF-1 alpha]]) for degradation by [[proteolysis]]. Under [[normoxia]] (normal oxygen conditions) [[EGLN1]][https://www.ncbi.nlm.nih.gov/gene/54583] protein hydroxylates the proline at the 564 position of HIF-1 alpha, which allows [[ubiquitylation]] by the [[von Hippel-Lindau tumor suppressor]] (pVHL) and subsequent targeting for [[proteasome]] degradation.<ref name="Jaakkola">{{cite journal | doi = 10.1126/science.1059796 | last1 = Jaakkola | first1 = P. | last2 = Mole | first2 = D.R. | last3 = Tian | first3 = Y.M. | last4 = Wilson | first4 = M.I. | last5 = Gielbert | first5 = J. | last6 = Gaskell | first6 = S.J. | last7 = Kriegsheim | first7 = A.V. | last8 = Hebestreit | first8 = H.F. | last9 = Mukherji | first9 = M. | last10 = Schofield | first10 = C. J. | last11 = Maxwell | first11 = P. H. | last12 = Pugh | first12 = C. W. | last13 = Ratcliffe | first13 = P. J. | year = 2001 | title = Targeting of HIF-alpha to the von Hippel-Lindau ubiquitylation complex by O2-regulated prolyl hydroxylation | journal = Science | volume = 292 | issue = 5516| pages = 468–72 | pmid = 11292861 | bibcode = 2001Sci...292..468J | s2cid = 20914281 | display-authors = 8 | doi-access = free }}</ref>