Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0026764 (multiple myeloma)
 36,148 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A complete amino acid sequence has been determined for the UP1 single-stranded DNA binding protein from calf thymus that was first described by G. Herrick and B. M. Alberts [(1976) J. Biol. Chem. 251, 2124-2132]. Peptides required to establish the UP1 sequence were isolated by reversed-phase HPLC of digests produced by endoproteinase Lys-C, trypsin, chymotrypsin, Staphylococcus aureus V8 protease, and cyanogen bromide cleavage of UP1. The purified peptides were coupled to aminopolystyrene prior to solid-phase sequencing. UP1 contains 195 amino acids and has a molecular weight of 22,162. UP1 has a blocked NH2 terminus and contains a single NG,NG-dimethylarginine residue near its COOH terminus. Gas-phase sequencing of tryptic peptides derived from an analogous protein from mouse myeloma cells [Planck, S. R. & Wilson, S. H. (1980) J. Biol. Chem. 255, 11547-11556] revealed that this mouse helix-destabilizing protein shares a high degree of sequence homology with UP1. Of the 59 amino acids in the mouse protein that have so far been found to be homologous with UP1, 48 correspond exactly to sequences found in UP1. Most of the 11 differences that have been found between the sequences of these two proteins are conservative in nature, involving primarily the interchange of chemically similar amino acids. One 9-residue mouse sequence that is not obviously homologous to UP1 may be a result of the larger size of the mouse myeloma protein as compared to UP1. Since none of the UP1 or mouse myeloma helix-destabilizing protein sequence appears to be homologous to that of any previously sequenced protein, we presume that these two proteins represent a distinct class of single-stranded nucleic acid binding proteins that probably play a role in metabolism of single-stranded RNA or DNA in vivo.
 ...
PMID:Amino acid sequence of the UP1 calf thymus helix-destabilizing protein and its homology to an analogous protein from mouse myeloma. 299 41

A 36,000-Mr protein purified from mouse myeloma on the basis of selective binding to a single-stranded DNA (ssDNA)-cellulose column has been identified as the lactate dehydrogenase A (LDH-A) subunit. A homogeneous preparation of this mouse myeloma ssDNA-binding protein, termed the 'low-salt-eluting protein', was found to possess LDH activity, and rabbit antiserum prepared against this protein was shown to cross-react with purified 36,000-Mr LDH-A subunits from mouse and bovine sources. In addition, bovine and human LHD-A4 isoenzymes were shown to be capable of binding ssDNA. These enzymic and immunological identities with LDH-A were not observed with purified helix-destabilizing protein 1 from mouse myeloma. A model for ssDNA-LDH binding is discussed.
 ...
PMID:Identification of the mouse low-salt-eluting single-stranded DNA-binding protein as a mammalian lactate dehydrogenase-A isoenzyme. 370 35

A mouse helix-destabilizing protein (HD protein-1) has been purified and characterized, and controlled tryptic digestion has been used to generate two large fragments of this protein and to study structural changes accompanying DNA binding. HD protein-1, a DNA-binding protein that has higher affinity for single-stranded DNA (ssDNA)-cellulose than for double-stranded DNA (dsDNA)-cellulose and is resistant to a dextran sulfate elution from ssDNA-cellulose, was purified from mouse myeloma by the method described by Herrick and Alberts (Herrick, G., and Alberts, B. M. (1976) J. Biol. Chem. 251, 2124-2132). HD protein-1 was heterogeneous with regard to apparent molecular weight (range of Mr = 24,000 to 33,000), but individual Mr species shared extensive primary structure homology as revealed by tryptic peptide mapping. The predominant species of this protein, Mr = 27,000, was resolved from other species and obtained in nearly homogeneous form by preparative isoelectric focusing. Mouse HD protein-1 was capable of lowering the Tm of poly[d(A-T)] by 25 degrees C, indicating that it is a helix-destabilizing protein. Sedimentation boundary analysis revealed that binding to ssDNA was noncooperative and that the binding site covered about 6 nucleotide residues. There was a 35% increase in the intrinsic tryptophan fluorescence of the protein in the presence of ssDNA, suggesting that structural change accompanies binding. Subcellular localization studies indicated that 75% of mouse HD protein-1 is nuclear, but not chromatin-associated, and primary structure analysis indicated that HD protein-1 is distinct from high mobility group proteins 1 and 2, histones, and P8 protein. Tryptic hydrolysis of HD protein-1 produced discrete, large fragments whose apparent molecular weights ranged from 19,000 to 24,000, and whose relative abundance was changed by the presence of ssDNA during the digestion. Thus, a Mr = 22,000 fragment (22 HDP*) predominated in the absence of ssDNA, and a Mr = 19,000, fragment (19 HDP*) predominated in the presence of ssDNA. Poly(dT) and denatured calf thymus DNA were more effective than were other polynucleotides tested in promoting accumulation of 19 HDP*; (dT)8 was as effective as were longer molecules of (dT)n, but (dT)4 and (dT)6 were much less effective, indicating that the binding site involved in 19 HDP* accumulation covered between 6 and 8 residues of (dT)n. Both 19 HDP* and 22 HDP* have the same COOH-terminal end and the same affinity for ssDNA-cellulose as does the native HD protein-1, indicating that a Mr = 8,000 sequence at the NH2-terminal end of HD protein-1 is not required for binding to ssDNA. Even though 22 HDP* retained the ability to bind to ssDNA, it could not be converted to 19 HDP* by further trypsin digestion.
 ...
PMID:Studies on the structure of mouse helix-destabilizing protein-1. DNA binding and controlled proteolysis with trypsin. 625 73

Highly purified, but not homogeneous, samples of helix-destabilizing protein 1 from mouse myeloma contain a novel oligonucleotide-releasing DNA exonuclease. This enzyme was separated from helix-destabilizing protein 1 and obtained in highly purified form. A polypeptide of Mr 41 000 is a main constituent of the purified enzyme, and this polypeptide comigrated with the exonuclease activity during the final step of the purification, Sephacryl S-200 gel filtration where the enzyme had a native Mr of 40 000. Overall purification of enzyme activity was greater than 20 000-fold. This exonuclease releases 5'-oligonucleotides in a limited processive manner in both the 5'----3' and 3'----5' directions. Activity of the enzyme is resistant to 1 mM N-ethylmaleimide, requires a divalent cation, has an alkaline pH optimum, and degrades single-stranded DNA much faster than double-stranded DNA or RNA. The predominant oligonucleotide product with uniformly labeled substrates is (pdN)2. With 3' end labeled substrates, greater than 95% of the labeled products are (pdN)4 and (pdN)5; with 5' end labeled substrates, the main labeled product is (pdA)2. The rate of product release from 3' and 5' end labeled substrates is nearly identical at 37 degrees C. A model of the action of this enzyme and a comparison with a human placenta exonuclease [Doniger, J., & Grossman, L. (1976) J. Biol. Chem. 251, 4579-4587] are discussed.
 ...
PMID:Properties of a novel oligonucleotide-releasing bidirectional DNA exonuclease from mouse myeloma. 653 98