CD177 NB1(neutrophil specific antigen B1), HNA-2A (human neutrophil antigen-2A), PRV1(polycythemia vera rubra 1)
Molecule TypeAntigen ExpressionMolecular Weight
Min / Max
Non-lineage Restricted Molecule
GPI anchor
Neutrophil
Basophil
NK Cell
T Cell
Monocyte
Endothelial Cell
Bone Marrow
Metamyelocyte
Promyelocyte
Myelocyte
Megakaryocyte
Leukemia cell
Erythroblast
49 / 49
64 / 64

Expression
In healthy individuals, CD177 is expressed by 56-64% on the surface of a subset of neutrophils, neutrophilic metamyelocytes, megakaryocytes, promyelocytes, myelocytes and in secondary granules.  Expression is greater on neutrophils from women than men although the CD177 expression decreases in women with age but remains constant in men.  CD177 is over expressed on neutrophils in patients with polycythemia vera and with essential thrombocythemia and is transiently increased in patients with severe burns or infections and in healthy subjects given G-CSF.  Exprsssion is reduced on neutrophils of patients with paroxysmal nocturnal hemaglobinuria and chronic myelogenous leukemia.  Expression is on basophils, NK cells, T cell subsets, monocytes and endothelials.  There is strong expression in bone marrow early erythroblasts and slight expression in fetal liver.

Structure
MOLECULAR FAMILY NAME:  Belongs to the Ly-6 gene superfamily.

CD177 is a single-chain GPI-anchored 437 aa glycoprotein.  It contains a 21 aa N-terminal signal sequence, 2 homologous 188 aa cytseine-rich domains that share homology with uPAR domains, 3 N-linked glycosylation sites but no O-linked carbohydrate side chains and a highly hydrophobic C-terminal sequence probably encoding a GPI link.  CD177 is located on secondary granules as well as plasma membranes.  While some GPI-anchored proteins are shed by f-met-leu-phe treated neutrophils, soluble CD177 was not present in the plasma.  Several single nuckeotide polymorphisms that result in amino acid substitutions have been described.

MOLECULAR MASS
CellType Unreduced Reduced
49 kDa-55 kDa 56 kDa-64 kDa

Purified glycoprotein has a Mr of 50.556 kDa.

POST-TRANSCRIPTIONAL MODIFICATION

Alternative splicing yields 3 different isoforms.

POST-TRANSLATIONAL MODIFICATION

CD177 has N-linked but no O-linked carbohydrate site chains.  Removal of the N-linked carbohydrates with endogycosidase-F from immunoprecipated CD177 glycoprotein decreased the apparent Mr of the protein to ~45 kDa. 

Ligands
LIGANDS AND MOLECULES ASSOCIATED WITH CD177: No information.

Function
The role of CD177 in neutrophil function is unknown.  In some studies CD177+ neutrophils were significantly less adherent to human umbilical vein endothelial cells than CD177- neutrophils.  The expression of CD177 is upregulated in response to the chemotactic peptide after f-met-leu-phe (fMLP) stimulation.  CD177 internalization upon antibody cross-linking and activation of the respiratory burst after binding of CD177 antibodies to CD177 bearing neutrophils suggests a possible role as a hematopoietic receptor molecule.

BIOCHEMICAL ACTIVITY: No information.

DISEASE RELEVANCE AND FUNCTION OF CD177 IN INTACT ANIMAL

CD177 is polymorphic and is expressed in 89%-97% of healthy individuals.  3% of people whose neutrophils lack CD177 are not at risk of infection or autoimmune disorders.  CD177 expression is reduced on neutrophils from people with paraxysmal nocturnal hemoglobinuria, PNH chronic myelogenous leukemia and CML, but it is not known if any clinical significance is due to lack of  expression.  NB antigens play a critical role in autoimmune neonatal neutropenia and autoimmune neutropenia.  CD177-negative mothers with CD177-positive neonates can elicit a CD177-specific antibody response that can reult in a child experiencing severe neutropenia for several weeks.  Transfusion of blood or blood products containing alloantibodies specific for CD177 can cause severe lung injury in the transfusion recipient.  Alloantibodies are sometime produced in patients receiving CD177-positive granulocyte concentrates and can result in febrile transfusion reactions and reduced survival of the transfused granulocytes.  CD177-positive neutrophils are less adherent to human umbilical vein endothelial cells that CD177-negative neutrophils.


Comments
MOLECULAR INTERACTIONS -
PROTEINS AND DNA ELEMENTS WHICH REGULATE TRANSCRIPTION OF CD177: No information.

SUBSTRATES: No information.

ENZYMES WHICH MODIFY CD177: No information.




Database accession numbers
AnimalPIRSWISSPROTEMGBL/GENBANK
 
HumanEntrezgene57126Q8N6Q3
Antibodies
MEM-166   View Reactivity

Revised June 25, 2008


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