IthaID: 1076

Context nucleotide sequence:
GCCTGGCTCACCTGGACAACCTCAA [G>C] GGCACCTTTGCCACACTGAGTGAGC (Strand: -)

Protein sequence:
MVHLTPEEKSAVTALWGKVNVDEVGGEALGRLLVVYPWTQRFFESFGDLSTPDAVMGNPKVKAHGKKVLGAFSDGLAHLDNLNGTFATLSELHCDKLHVDPENFRLLGNVLVCVLAHHFGKEFTPPVQAAYQKVVAGVANALAHKYH

Also known as:

Comments: Hb Providence occurs in the red cells in two forms; Hb Providence Asn (asparagine) and Hb Providence Asp (aspartic acid), the latter resulting from the post-translational deamidation of the substituted asparagine residue. The amino acid change occurs at the EF6 position of the β chains that is normally occupied by an invariant lysyl residue (β82 (EF6) Lys). This position normally serves as a binding site for 2,3-diphosphoglycerate (2,3-DPG) and chloride. The replacement of Lys by Asn or Asp reduces the net positive charge of this site, which causes a weakening in the interaction with 2,3-DPG and, in turn, stabilizes the T-state conformation and decreases hemoglobin affinity for oxygen. This occurs without a concomitant change in the degree of cooperativity. Hb Providence Asp is the faster abnormal Hb component as seen by electrophretic methods and column chromatography. The parial binding of 2,3-DPG to Hb Providence Asn limits the deamidation process, which results in the Asp form making about two thirds of the Hb Providence in the red cells of carriers. Reported as a β82 AAG>AAC change by bidirectional sequence analysis.

We follow the HGVS sequence variant nomenclature and IUPAC standards.

Heterozygous records (preview in IthaPhen)

1. Moo-Penn WF, Jue DL, Bechtel KC, Johnson MH, Schmidt RM, Hemoglobin Providence. A human hemoglobin variant occurring in two forms in vivo., The Journal of biological chemistry, 251(23), 7557-62, 1976 PubMed
2. Bonaventura J, Bonaventura C, Sullivan B, Ferruzzi G, McCurdy PR, Fox J, Moo-Penn WF, Hemoglobin providence. Functional consequences of two alterations of the 2,3-diphosphoglycerate binding site at position beta 82., J Biol Chem, 251(23), 7563-71, 1976 PubMed
3. Charache S, Fox J, McCurdy P, Kazazian H, Winslow R, Hathaway P, van Beneden R, Jessop M, Postsynthetic deamidation of hemoglobin Providence (beta 82 Lys replaced by Asn, Asp) and its effect on oxygen transport., J Clin Invest, 59(4), 652-8, 1977 PubMed
4. Bardakjian J, Leclerc L, Blouquit Y, Oules O, Rafaillat D, Arous N, Bohn B, Poyart C, Rosa J, Galacteros F, A new case of hemoglobin Providence (alpha 2 beta 2 82 (EF6) Lys----Asn or Asp) discovered in a French Caucasian family. Structural and functional studies., Hemoglobin, 9(4), 333-48, 1985 PubMed
5. Newman CN, Litwin CM, Bowlby DA, Lewis KA, Paulo RC, Hemoglobin Providence (β82 Lys > Asn, Asp) and lower-than-expected HbA1c in a nonadherent teenager with type 1 diabetes: a case report and literature review., Clin Case Rep, 5(12), 2000-2002, 2017 PubMed