DEFINITION
Haptoglobin (abbreviated as Hp) is a protein that in humans is encoded by the HP gene. In blood plasma, haptoglobin binds free hemoglobin (Hb) released from erythrocytes with high affinity and thereby inhibits its oxidative activity. The haptoglobin-hemoglobin complex will then be removed by the reticuloendothelial system (mostly the spleen and the liver).
THE GENE
CHEMICAL STRUCTURE AND IMAGES
Hp Polymorphism
Characterization of human haptoglobin cDNAs coding for alpha 2FS beta and alpha 1S beta variants. 1984
A human liver library, derived from a heterozygous (Hp2-1) donor, has been used to isolate cDNA clones coding for the haptoglobin (Hp) alpha 1S beta and alpha 2FS beta variants. DNA sequencing has shown that the two variants are identical except for the alpha F duplicated segment in Hp alpha 2FS beta. Four nucleotide changes have been found between the phenotypically different F and S regions of the Hp alpha 2 gene, resulting in an Asp,Lys/Asn,Glu substitution.
Prohaptoglobin is proteolytically cleaved in the endoplasmic reticulum by the complement C1r-like protein, 2004
Identification of human zonulin, a physiological modulator of tight junctions, as prehaptoglobin-2, 2008
pre-HP1
MSALGAVIAL LLWGQLFAVD SGNDVTDIAD DGCPKPPEIA HGYVEHSVRY QCKNYYKLRT
EGDGVYTLND KKQWINKAVG DKLPECEADD GCPKPPEIAH GYVEHSVRYQ CKNYYKLRTE
GDGVYTLNNE KQWINKAVGD KLPECEAVCG KPKNPANPVQ RILGGHLDAK GSFPWQAKMV
SHHNLTTGAT LINEQWLLTT AKNLFLNHSE NATAKDIAPT LTLYVGKKQL VEIEKVVLHP
NYSQVDIGLI KLKQKVSVNE RVMPICLPSK DYAEVGRVGY VSGWGRNANF KFTDHLKYVM
LPVADQDQCI RHYEGSTVPE KKTPKSPVGV QPILNEHTFC AGMSKYQEDT CYGDAGSAFA
VHDLEEDTWY ATGILSFDKS CAVAEYGVYV KVTSIQDWVQ KTIAEN
Duplicated trait
AD DGCPKPPEIA HGYVEHSVRY QCKNYYKLRT EGDGVYTLND KKQWINKAVG DKLPECE
pre-HP2
MSALGAVIAL LLWGQLFAVD SGNDVTDI AD DGCPKPPEIA HGYVEHSVRY QCKNYYKLRT EGDGVYTLND KKQWINKAVG DKLPECE AD DGCPKPPEIA HGYVEHSVRY QCKNYYKLRT EGDGVYTLND KKQWINKAVG DKLPECE ADD GCPKPPEIAH GYVEHSVRYQ CKNYYKLRTE
GDGVYTLNNE KQWINKAVGD KLPECEAVCG KPKNPANPVQ RILGGHLDAK GSFPWQAKMV
SHHNLTTGAT LINEQWLLTT AKNLFLNHSE NATAKDIAPT LTLYVGKKQL VEIEKVVLHP
NYSQVDIGLI KLKQKVSVNE RVMPICLPSK DYAEVGRVGY VSGWGRNANF KFTDHLKYVM
LPVADQDQCI RHYEGSTVPE KKTPKSPVGV QPILNEHTFC AGMSKYQEDT CYGDAGSAFA
VHDLEEDTWY ATGILSFDKS CAVAEYGVYV KVTSIQDWVQ KTIAEN
- Secondary structure
- Tertiary structure
- Quaternary structure
AA percentage
SYNTHESIS AND TURNOVER
mRNA synthesis
mRNA is found mostly in adult liver and fetal lung and liver.
protein synthesis
post-translational modifications
degradation
Zonulin and Its Regulation of Intestinal Barrier Function: The Biological Door to Inflammation, Autoimmunity, and Cancer 2011
CELLULAR FUNCTIONS
cellular localization,
biological function
Haptoglobin plays a major role in Iron competition
- Enzymes
- Cell signaling and Ligand transport
- Structural proteins
REGULATION
DIAGNOSTIC USE
Polymorphism of human haptoglobin and its clinical importance, 2008
Polymorphism genotyping
Genotyping of the Common Haptoglobin Hp 1/2 Polymorphism Based on PCR 2002
Novel haptoglobin insertion/deletion polymorphism is associated with the lipid profile and C-reactive protein (CRP) concentration. 2002
Haptoglobin type neither influences iron accumulation in normal subjects nor predicts clinical presentation in HFE C282Y haemochromatosis: phenotype and genotype analysis. 2003 Fulltext
Association between Haptoglobin Gene Variants and Diabetic Nephropathy: Haptoglobin Polymorphism in Nephropathy Susceptibility 2007
Iron metabolism markers and haptoglobin phenotypes in susceptibility to HSV-1 or/and HSV-2 lesion relapses. 2010
Different haptoglobin (Hp) phenotypes play a role in several pathologic processes including infectious diseases. In order to evaluate the role of iron storage and metabolism in susceptibility to herpetic manifestations, we studied the frequency of the Hp phenotypes and iron metabolism in patients affected by H. Simplex virus 1 or 2 (HSV-1 or HSV-2), compared with controls. Hp phenotype and iron metabolism were determined in 100 patients with recurrent HSV-1 or HSV-2 manifestations during the relapses, and in 110 healthy subjects. The frequencies of the three Hp phenotypes in the patient group compared to the control group were 18% versus 14.5% p = NS for Hp 1.1, 25% versus 40% p = 0.03 for Hp 2.2 and 57% versus 45.5% p = NS for Hp 2.1. All iron metabolism parameters tested showed significant differences between patients and controls; haemoglobin (Hb), ferritin, and serum iron were lower, while transferrin was higher in the patients than in controls. Reductions in iron availability may be a risk factor for relapsing lesions of HSV-1 or HSV-2. Hp 2.2 phenotype may offer some protection against the recurrence of Herpes labialis or genitalis manifestations.
a deeper insight
Associated Diseases
Haptoglobin phenotype and risk of cervical neoplasia: a case-control study. 2007
1-1 is a risk factor in HPV positive patients
Haptoglobin phenotype 2-2 as a potentially new risk factor for spontaneous venous thromboembolism. 2005
Haptoglobin 2-2 phenotype is a risk factor for type 2 diabetes in Ghana 2002
Hypertensive and overweight individuals with the Hp2-2 phenotype in Ghana are at a high risk of developing type 2 diabetes
Haptoglobin phenotype and gestational diabetes. 2004
Body iron stores in relation to the metabolic syndrome, glycemic control and complications in female patients with type 2 diabetes. 2007
Haptoglobin polymorphism and diabetic retinopathy in Brazilian patients
Vânia P.A. Wobetoa, Endrigo T. Rosima, Mônica B. Melob, Luís Eduardo P Calliaric and Maria de Fátima Sonatia
Microarray and Large-Scale In Silico–Based Identification of Genes Functionally Related to Haptoglobin and/or Hemopexin, Altruda F: 2006
Clin Chem. 2000 Oct;46(10):1619-25.
The haptoglobin 2-2 phenotype affects serum markers of iron status in healthy males.
Langlois MR, Martin ME, Boelaert JR, Beaumont C, Taes YE, De Buyzere ML, Bernard DR, Neels HM, Delanghe JR.
Department of Clinical Chemistry, Immunology and Microbiology, University Hospital Gent, De Pintelaan 185, B-9000 Gent, Belgium. michel.langlois@rug.ac.be
BACKGROUND: Human iron status is influenced by environmental and genetic factors. We hypothesized that the genetic polymorphism of haptoglobin (Hp), a hemoglobin-binding plasma protein, could affect iron status. METHODS: Reference values of serum iron status markers were compared according to Hp phenotypes (Hp 1-1, Hp 2-1, Hp 2-2; determined by starch gel electrophoresis) in 717 healthy adults. Iron storage was investigated in peripheral blood monocyte-macrophages by measuring cytosolic L- and H-ferritins and by in vitro uptake of radiolabeled ((125)I) hemoglobin-haptoglobin complexes. RESULTS: In males but not in females, the Hp 2-2 phenotype was associated with higher serum iron (P <0.05), transferrin saturation (P <0.05), and ferritin (P <0.01) concentrations than Hp 1-1 and 2-1, whereas soluble transferrin receptor concentrations were lower (P <0.05). Moreover, serum ferritin correlated with monocyte L-ferritin content (r = 0.699), which was also highest in the male Hp 2-2 subgroup (P <0.01). In vitro, monocyte-macrophages took up a small fraction of (125)I-labeled hemoglobin complexed to Hp 2-2 but not to Hp 1-1 or 2-1. CONCLUSIONS: The Hp 2-2 phenotype affects serum iron status markers in healthy males and is associated with higher L-ferritin concentrations in monocyte-macrophages because of a yet undescribed iron delocalization pathway, selectively occurring in Hp 2-2 subjects.
