Disease relevance of Arg-Lys

• The amino acid sequence in this region (Gly-29 Lys Lys Arg Ser Lys Ala) is similar to the nuclear location signal in simian virus 40 large T antigen (Pro-126 Lys Lys Lys Arg Lys Val) (D. Kalderon, B.L. Roberts, W.D. Richardson, and A.E. Smith, Cell 39:499-509, 1984) [1].
• In this paper, we report a systematic comparison of the effects of positively (Arg, Lys, His) as well as negatively (Asp, Glu) charged residues on the membrane topology of a model Escherichia coli inner membrane protein [2].
• An Arg/Lys-rich core peptide mimics TRBP binding to the HIV-1 TAR RNA upper-stem/loop [3].
• The distinct Arg/Lys-rich and Met-rich region at positions 10-36 of the PLA2 homolog presumably are involved in its heparin-binding and the cell membrane-interference leading to edema and myotoxicity [4].
• An Arg-Lys insertion at the hemagglutinin cleavage site of an H5N2 avian influenza isolate [5].

High impact information on Arg-Lys

• The cDNA sequence reveals a long open reading frame (ORF) of 1773 nucleotides, with a putative nuclear targeting signal (Glu Arg Arg Lys Lys Lys Thr) at the extreme carboxyl terminus and an internal histidine (His)-rich region with a repeated conserved amino acid sequence between His pairs [6].
• It was previously shown that the mRNA for the cat-1 Arg/Lys transporter is translated from an internal ribosome entry site (IRES) that is regulated by cellular stress [7].
• Protein methylation plays a central role in both of these fields, as several different residues (Arg, Lys, Gln) are methylated in cells and methylation plays a central role in the "histone code" that regulates chromatin structure and impacts transcription [8].
• The Sld2 protein has a cluster of 11 cyclin-dependent kinase (CDK) phosphorylation motifs (Ser/Thr-Pro), six of which match the canonical sequences Ser/Thr-Pro-X-Lys/Arg, Lys/Arg-Ser/Thr-Pro and Ser/Thr-Pro-Lys/Arg [9].
• Sea urchin sperm-specific histones H1 and H2B have distinctive N-terminal, and in the case of H1 also C-terminal, domains containing repeats of a basic motif (-Ser-Pro-Lys/Arg-Lys/Arg- or a closely related sequence) [10].

Biological context of Arg-Lys

• The DNA sequence of the mutant predicts the alteration of Lys 128----Thr within the sequence 127 Lys Lys Lys Arg Lys 131 of large T [11].
• Semi-random cassette mutagenesis was used to generate mutants with replacements of residues 164-167 by Arg, Lys, Ser, or Asn [12].
• The Arg-Lys sequence at positions 25-31, which resembles the binding site of apolipoprotein E, may mediate the high affinity binding of lactoferrin and block the binding of beta-VLDL to the remnant receptor with high efficiency [13].
• The BD peptide also contains novel structural features such as a predicted Asx bend or "hook" at its amino-terminal end and laterally projecting cationic Arg/Lys side chains or "bristles" which may contribute to the binding properties of the HMG-I proteins [14].
• We mutated His(73) in yeast actin to Arg, Lys, Ala, Gln, and Glu and detected no altered phenotypes associated with the mutations in vivo [15].

Anatomical context of Arg-Lys

• An Arg-Lys esteropeptidase that converts somatostatin-28 in vitro into somatostatin-14 was previously characterized in extracts of rat cerebral cortex [16].
• A seven residue peptide containing residues 368-374, Val Tyr Tyr Val Gly Arg Lys, was demonstrated to be capable of inducing chemotactic migration of human peripheral blood neutrophils, monocytes, monocyte leukemia cell line THP-1, and infant foreskin fibroblasts [17].
• Recent experiments have shown that Arg, Lys, and Leu can be incorporated posttranslationally into proteins of regenerating sciatic nerves of rats [18].
• Basic charge motifs, such as the BBB, BXXBB, and BBXXB motifs in alpha-helical integral membrane proteins, are significantly more frequent near cytoplasmic membrane surface than expected from the Arg/Lys (B) frequency [19].
• Protein phosphorylation in neutrophils was monitored with two phosphospecific antibodies (pAbs) [termed pPKC(S1) Ab and pPKC(S2) Ab] that recognize products of protein kinase C (PKC) and other Arg/Lys-directed Ser/Thr protein kinases [20].

Associations of Arg-Lys with other chemical compounds

• Mutations of the invariant Tyr(10) with either hydrophobic (Ala), aromatic (Phe), or positively charged (Arg, Lys) residues yielded Ca(V)beta 3-responsive whole cell currents, whereas mutations with negatively charged residues (Asp, Glu) disrupted Ca(V)beta 3 binding and modulation [21].
• We demonstrated previously that two type II metacaspases of Arabidopsis thaliana, AtMC4 and AtMC9 are Arg/Lys-specific cysteine-dependent proteases [22].
• This architectural arrangement apparently couples directional A-form duplex binding, by a hydrogen-bonding Arg-Lys phosphate ruler motif, to substrate-discrimination, by a tyrosine finger motif, thereby providing substrate-specific catalytic activity [23].
• Setting the stage for new catalytic functions in designed proteins--exploring the imine pathway in the efficient decarboxylation of oxaloacetate by an Arg-Lys site in a four-helix bundle protein scaffold [24].
• Since then, seven PCs have so far been discovered that cleave at the carboxy-terminal of a basic amino acid characterized by the consensus sequence Arg/Lys/His-X-X/Lys/Arg-Arg downward arrow, where X denotes any amino acid other than Cys [25].

Gene context of Arg-Lys

• The primary translation product consists of 178 amino acid residues containing a putative signal sequence, a transmembrane domain, the mature BTC domain and a cytoplasmic domain containing a highly hydrophilic Arg-Lys-rich region similar to that of mouse BTC and human BTC [26].
• On the basis of microsomal enzyme activities from heterozygotes, CYP1A1*1/2A, CYP1A1*1/2B, CYP1A1*1/4, and AHR(554) Arg/Lys variants do not appear to significantly affect CYP1A1 activities in human lung, and we observed no association between CYP1A1 activity and the GSTM1-null polymorphism [27].
• A distinct, Arg/Lys-rich N-terminal region targets CKA1 to the cell periphery [28].
• These studies have revealed that the amino acid sequence of human cardiac alpha tropomyosin is identical to that of the rabbit skeletal alpha tropomyosin, but for a single conservative substitution of Arg/Lys at position 220 [29].
• Comparison of their N-terminal sequences showed 30% nonidentity over the first 35 amino acids, and comparison of their amino acid compositions demonstrated a marked difference in their Arg/Lys ratios, which was approximately 1 for chymase and 10 for cathepsin G [30].

Analytical, diagnostic and therapeutic context of Arg-Lys

• Peptide mapping provided additional proof that p17 is a fragment which comprises the entire FK506 binding domain I of chicken hsp56, terminating with an Arg-Lys which might represent a processing site [31].
• HPLC analysis of peptide fragments produced, followed by their amino acid analysis, revealed that the enzyme preferentially hydrolyzed the Arg-Arg or Arg-Lys bonds in dynorphins A 1-10, 1-9, and 1-8, beta-neoendorphin, adenorphin, and neurotensin [32].

References