UniProt functional annotation for P00738



	UniProt functional annotation for P00738

UniProt code: P00738.

Organism: Homo sapiens (Human).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.

Function: As a result of hemolysis, hemoglobin is found to accumulate in the kidney and is secreted in the urine. Haptoglobin captures, and combines with free plasma hemoglobin to allow hepatic recycling of heme iron and to prevent kidney damage. Haptoglobin also acts as an antioxidant, has antibacterial activity, and plays a role in modulating many aspects of the acute phase response. Hemoglobin/haptoglobin complexes are rapidly cleared by the macrophage CD163 scavenger receptor expressed on the surface of liver Kupfer cells through an endocytic lysosomal degradation pathway. {ECO:0000269|PubMed:21248165}.

Function: The uncleaved form of allele alpha-2 (2-2), known as zonulin, plays a role in intestinal permeability, allowing intercellular tight junction disassembly, and controlling the equilibrium between tolerance and immunity to non-self antigens. {ECO:0000269|PubMed:21248165}.

Subunit: Tetramer of two alpha and two beta chains; disulfide-linked. The hemoglobin/haptoglobin complex is composed of a haptoglobin dimer bound to two hemoglobin alpha-beta dimers. Interacts with CD163.

Subcellular location: Secreted.

Tissue specificity: Expressed by the liver and secreted in plasma.

Polymorphism: In human populations there are two major allelic forms, alpha-1 (1-1) with 83 residues and alpha-2 (2-2) with 142 residues. These alleles determine 3 possible genotypes, homozygous (1-1 or 2-2) and heterozygous (2-1), and 3 major phenotypes HP*1F/HP*1S and HP*2FS. The two main alleles of HP*1 are called HP*1F (fast) and HP*1S (slow). The alleles exhibit different oligomerization properties. In healthy males, but not in females, the Hp 2-2 phenotype is associated with higher serum iron, decreased antimicrobial and antioxidant capability, and less efficient clearance from the circulation, than Hp 1-1 and 2-1. The sequence displayed in this entry corresponds to allele alpha-2 (2- 2). {ECO:0000269|PubMed:4018023, ECO:0000269|PubMed:6330675, ECO:0000269|PubMed:6546723}.

Disease: Anhaptoglobinemia (AHP) [MIM:614081]: A condition characterized by the absence of the serum glycoprotein haptoglobin. Serum levels of haptoglobin vary among normal persons: levels are low in the neonatal period and in the elderly, differ by population, and can be influenced by environmental factors, such as infection. Secondary hypohaptoglobinemia can occur as a consequence of hemolysis, during which haptoglobin binds to free hemoglobin. Congenital haptoglobin deficiency is a risk factor for anaphylactic non-hemolytic transfusion reactions. {ECO:0000269|PubMed:14999562}. Note=The disease is caused by variants affecting the gene represented in this entry.

Similarity: Belongs to the peptidase S1 family. {ECO:0000255|PROSITE- ProRule:PRU00274}.

Annotations taken from UniProtKB at the EBI.


Organism:		Homo sapiens (Human).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.



Function:		As a result of hemolysis, hemoglobin is found to accumulate in the kidney and is secreted in the urine. Haptoglobin captures, and combines with free plasma hemoglobin to allow hepatic recycling of heme iron and to prevent kidney damage. Haptoglobin also acts as an antioxidant, has antibacterial activity, and plays a role in modulating many aspects of the acute phase response. Hemoglobin/haptoglobin complexes are rapidly cleared by the macrophage CD163 scavenger receptor expressed on the surface of liver Kupfer cells through an endocytic lysosomal degradation pathway. {ECO:0000269\|PubMed:21248165}.



Function:		The uncleaved form of allele alpha-2 (2-2), known as zonulin, plays a role in intestinal permeability, allowing intercellular tight junction disassembly, and controlling the equilibrium between tolerance and immunity to non-self antigens. {ECO:0000269\|PubMed:21248165}.


Subunit:		Tetramer of two alpha and two beta chains; disulfide-linked. The hemoglobin/haptoglobin complex is composed of a haptoglobin dimer bound to two hemoglobin alpha-beta dimers. Interacts with CD163.
Subcellular location:		Secreted.
Tissue specificity:		Expressed by the liver and secreted in plasma.
Polymorphism:		In human populations there are two major allelic forms, alpha-1 (1-1) with 83 residues and alpha-2 (2-2) with 142 residues. These alleles determine 3 possible genotypes, homozygous (1-1 or 2-2) and heterozygous (2-1), and 3 major phenotypes HP1F/HP1S and HP2FS. The two main alleles of HP1 are called HP1F (fast) and HP1S (slow). The alleles exhibit different oligomerization properties. In healthy males, but not in females, the Hp 2-2 phenotype is associated with higher serum iron, decreased antimicrobial and antioxidant capability, and less efficient clearance from the circulation, than Hp 1-1 and 2-1. The sequence displayed in this entry corresponds to allele alpha-2 (2- 2). {ECO:0000269\|PubMed:4018023, ECO:0000269\|PubMed:6330675, ECO:0000269\|PubMed:6546723}.
Disease:		Anhaptoglobinemia (AHP) [MIM:614081]: A condition characterized by the absence of the serum glycoprotein haptoglobin. Serum levels of haptoglobin vary among normal persons: levels are low in the neonatal period and in the elderly, differ by population, and can be influenced by environmental factors, such as infection. Secondary hypohaptoglobinemia can occur as a consequence of hemolysis, during which haptoglobin binds to free hemoglobin. Congenital haptoglobin deficiency is a risk factor for anaphylactic non-hemolytic transfusion reactions. {ECO:0000269\|PubMed:14999562}. Note=The disease is caused by variants affecting the gene represented in this entry.
Similarity:		Belongs to the peptidase S1 family. {ECO:0000255\|PROSITE- ProRule:PRU00274}.