Post translational modifications (PTM)

Main chain modification
* Proteolytic cleavage
** Signal peptidase (preprotein): "molecular postal code", N(basic, +ve charged region), H(hydrophobic region), C(specificity region, has Ala-X-Ala consensus sequence in positions -3,-2,-1), eg secretion systems, in eukarytotes (co-translational translocation in ER) vs Post-Translational translocation in prokaryotes http://en.wikipedia.org/wiki/Secretory_pathway
** Zymogen (proprotein) eg trypsin digestive enzyme, from trypsinogen (inactive) to trypsin (active form)
** pre-pro peptide hormone: eg insulin, forms hexamer with Zn, signal is cleaved by signal peptidase and delivered to ER, then an intermediate (proprotein) form where it's needed to position the two chains in the correct place to form disulfide bonds, the intermediate peptide is cleaved by PC1 and PC2 endoprotease then digested by exoprotease to produce active form
** viral RNA - is used to make polyprotein (for viral coats) - protein that, after synthesis, is cleaved to produce several functionally distinct polypeptides.
** Inteins - intron-exon like at a protein level (has exteins too)
* N-terminal modifications
** Acetylation - added by Acetyl-Coa at N-term, blocks sequencing (for side-chains, it's Lys and Arg, because methyls CH3 are electron donating groups, so want to donate electrons to + charge groups)
** Myristylation - 14 carbon myristol(fatty acid) group, associate protein with membranes

Side chain modification
* glycosylation - proteins covalently linked with carbohydrate (for proteins bound to membrane)
** n-linked - N-linked (ND2 from Asn, N is single letter code for Asn) to sugar GlcNAc, occurs cotranslationally in ER, consensus Ans-X-Ser/Thr
** o-linked - O-linked (OG from Ser/Thr) to sugar GalNAc (both vowels, o, a, OH pointing same direction as CH2OH) and occurs post-translationally in Golgi (another vowel o)
* methylation - add methyl Lys or Arg
* phosphorylation - regulate activity, kinase phosphorylate proteins, groups with hydroxyl are phosphorylated: ser (happens 1000times)/thr(100times)/tyr(1time)
* sulfation - happens in Tyr, happens permanently, for stabilizing, NOT for regulatory modification, eg fibrinogen, donor is PAPS,
* prenylation/lipidation - adds 15 carbon farnesyl or 20 carbon geranylgeranyl group to Cys at carboxy terminus, consensus is CAAX (A is any aliphatic residue except Ala)
* hydroxylation - vitamin c-dependent modification - Pro and Lys hydroxylation (add OH), eg collagen
* carboxylation - vitamin k-dependent modification - Carboxylation of Glu (so two carbonyls), for blood clotting, chelating Ca2+ ions
* disulfide bond formation - oxidized 2 Cys residues in ER (oxidizing environment), in vivo, glutathione (glutamine+cysteine+glycine) (GSH) -> GSSG (glutatione disulfide) (oxidized form) -> these are the oxidizers
* citrullination (deimination) - neutralize arginine+ charge
* deamidation - replace amide of asparagine with carbonyl, changing it to aspartic acid

Summary:
http://en.wikipedia.org/wiki/Prenylation
Cysteine - Disulfide bond formation, Prenylation
N-termini - Acetylation, Myristorylation, Methylation
Aginine - Methylation, Citrullination (deamination) (NH to O)
C-term - Amidation
Asparagine - N-Glycosylation, deamiDation (Asparagine to Aspartic Acid and IsoAspartic Acid)
Ubiquitination - E1 activating, E2 conjugating, E3 ubiquitin protean ligase
Glutamate - Carboxylation (Vit K dependent)
Hydroxyl Groups (S/T) - Phosphorylation, O-linked Glycosylation
Tyrosine - Sulfation
Proline - Hydroxylation (Vit C dependent)
Lysine - Hydroxylation (Vit C dependent), Methylation