4NUU , 4NUV
41-603: MPZ or mpz may refer to: Myelin protein zero , a single membrane glycoprotein which in humans is encoded by the MPZ gene MPZ, the DS100 code for Penzberg station , Bavaria, Germany MPZ, the IATA and FAA LID code for Mount Pleasant Municipal Airport (Iowa) , Iowa, United States mpz, the ISO 639-3 code for Mpi language , Thailand Topics referred to by
82-752: A Duffy antigen negative individual in Mauritania has also been reported. Similar infections have been reported in Brazil and Kenya . Additional cases of infection in Duffy antigen negative individuals have been reported from the Congo and Uganda. A study in Brazil of the protection against P. vivax offered by the lack of the Duffy antigen found no differential resistance to malaria vivax between Duffy antigen positive and negative individuals. Nancy Ma's night monkey ( A. nancymaae )
123-578: A multiply-transfused hemophiliac named Richard Duffy, whose serum contained the first example of anti-Fya antibody . In 1951, the antibody to a second antigen, Fyb, was discovered in serum . Using these two antibodies, three common phenotypes were defined: Fy(a+b+), Fy(a+b-), and Fy(a-b+). Several other types were later discovered bringing the current total up to 6: Fya, Fyb, Fy3, Fy4, Fy5 and Fy6. Only Fya, Fyb and Fy3 are considered clinically important. Reactions to Fy5 have also rarely been reported. The Fy4 antigen, originally described on Fy (a–b–) RBCs,
164-624: A multispecific receptor for chemokines of both the C-C and C-X-C families, including: and the angiogenic CXC chemokines: Consequently, the Fy protein is also known as DARC (Duffy Antigen Receptor for Chemokines). The chemokine binding site on the receptor appears to be localised to the amino terminus . The antigen is predicted to have 7 transmembrane domains, an exocellular N-terminal domain and an endocellular C-terminal domain. Alignment with other seven transmembrane G-protein-coupled receptors shows that DARC lacks
205-399: A myelinating cell wraps its membrane around an axon multiple times, generating multiple layers of myelin, myelin protein zero helps keep these sheets compact by serving as a "glue" that keeps the layers of myelin together. It does so by holding its characteristic coil structure together by the electrostatic interactions of its positively charged intracellular domain with acidic lipids in
246-641: A role in erythrocyte invasion in the rodent malarial parasite P. yoelii . The epitope Fy6 is required for P. vivax invasion. The protection to P. vivax malaria conferred by the absence of the Duffy antigen appears to be very limited at best in Madagascar . Although 72% of the population are Duffy antigen negative, 8.8% of the Duffy antigen negative individuals were asymptomatic carriers of P. vivax . Malaria has also been found in Angola and Equatorial Guinea in Duffy negative individuals. P. vivax malaria in
287-943: A role in neutrophil migration from the blood into the tissues and in modulating the inflammatory response. The protein is also known to interact with the protein KAI1 ( CD82 ) a surface glycoprotein of leukocytes and may have a role in the control of cancer. The Duffy antigen has been shown to exist as a constitutive homo-oligomer and that it hetero-oligomerizes with the CC chemokine receptor CCR5 ( CD195 ). The formation of this heterodimer impairs chemotaxis and calcium flux through CCR5, whereas internalization of CCR5 in response to ligand binding remains unchanged. DARC has been shown to internalise chemokines but does not scavenge them. It mediates chemokine transcytosis, which leads to apical retention of intact chemokines and more leukocyte migration. Binding melanoma growth-stimulating activity inhibits
328-517: A smaller positively charged intracellular region (151–219). Its cytoplasmic domain is highly positively charged but presumably does not fold into a globular structure. The extracellular domain is structurally similar to the immunoglobulin domain and therefore the protein is considered as belonging to immunoglobulin superfamily . Besides existing as a monomer, myelin protein zero is also known to form dimers and tetramers with other myelin protein zero molecules in vertebrates. The myelin sheath
369-426: A sponge and provide a mechanism by which inflammatory chemokines may be removed from circulation as well as their concentration modified in the local environment. This hypothesis has also been questioned after knock out mice were created. These animals appeared healthy and had normal responses to infection. While the function of the Duffy antigen remains presently (2006) unknown, evidence is accumulating that suggests
410-467: Is 100% Whites, 99.9% Asians and 32% Blacks. Phenotype frequencies are: While a possible role in the protection of humans from malaria had been previously suggested, this was only confirmed clinically in 1976. Since then many surveys have been carried out to elucidate the prevalence of Duffy antigen alleles in different populations including: There appears to have been a selective sweep in Africa which reduced
451-697: Is a point mutation in the erythroid specific promoter (a T -> C mutation at position -33 in the GATA box ). This mutation occurs in the Fy-b allele and has been designated Fy-b (erythroid silent). Two isotypes have been identified. The Fy-x allele is characterized by a weak anti-Fy-b reaction and appears to be the result of two separate transitions : Cytosine 265 Threonine ( Arginine 89 Cysteine ) and Guanine 298 Adenosine ( Alanine 100 Threonine ). A third mutation (a transversion ) in this gene has also been described - G145T ( Alanine 49 Serine ) - that has been associated with
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#1733085667271492-568: Is a protein that in humans is encoded by the ACKR1 gene . The Duffy antigen is located on the surface of red blood cells , and is named after the patient in whom it was discovered. The protein encoded by this gene is a glycosylated membrane protein and a non-specific receptor for several chemokines . The protein is also the receptor for the human malarial parasites Plasmodium vivax , Plasmodium knowlesi and simian malarial parasite Plasmodium cynomolgi . Polymorphisms in this gene are
533-416: Is a multi-layered membrane, unique to the nervous system, that functions as an insulator to greatly increase the velocity of axonal impulse conduction. Myelin protein zero, absent in the central nervous system, is a major component of the myelin sheath in peripheral nerves . Mutations that disrupt the function of myelin protein zero can lead to less expression of myelin and degeneration of myelin sheath in
574-640: Is a single membrane glycoprotein which in humans is encoded by the MPZ gene. P0 is a major structural component of the myelin sheath in the peripheral nervous system (PNS) . Myelin protein zero is expressed by Schwann cells and accounts for over 50% of all proteins in the peripheral nervous system, making it the most common protein expressed in the PNS. Mutations in myelin protein zero can cause myelin deficiency and are associated with neuropathies like Charcot–Marie–Tooth disease and Dejerine–Sottas disease . In humans,
615-510: Is also known as Fy-b or Fy-b . This gene has been redesignated ACKR1 . Fy-a and Fy-b differ by in a single amino acid at position 42: glycine in Fy-a and aspartic acid in Fy-b ( guanine in Fy-a and adenosine in Fy-b at position 125). A second mutation causing a Duffy negative phenotype is known: the responsible mutation is G -> A at position 298. The genetic basis for the Fy(a-b-) phenotype
656-428: Is different from Wikidata All article disambiguation pages All disambiguation pages Myelin protein zero 3OAI 4359 17528 ENSG00000158887 ENSMUSG00000056569 P25189 P27573 NM_000530 NM_001315491 NM_008623 NM_001315499 NM_001315500 NP_000521 NP_001302420 NP_001302428 NP_001302429 NP_032649 Myelin protein zero ( P0 , MPZ )
697-1003: Is due to a third mutation that results in an unstable protein (Arg89Cys: cytosine -> thymidine at position 265). The silent allele has evolved at least twice in the black population of Africa and evidence for selection for this allele has been found. The selection pressure involved here appears to be more complex than many text books might suggest. An independent evolution of this phenotype occurred in Papua New Guinea has also been documented. A comparative study of this gene in seven mammalian species revealed significant differences between species. The species examined included Pan troglodytes (chimpanzee), Macaca mulatta (rhesus monkey), Pongo pygmaeus (orangutan), Rattus norvegicus (brown rat), Mus musculus (mouse), Monodelphis domestica (opossum), Bos taurus (cow) and Canis familiaris (dog). Three exons are present in humans and chimpanzees, whereas only two exons occur in
738-410: Is in two exons . The gene encodes a 336 amino acid acidic glycoprotein . It carries the antigenic determinants of the Duffy blood group system which consist of four codominant alleles —FY*A and FY*B—coding for the Fy-a and Fy-b antigens respectively, FY*X and FY*Fy, five phenotypes (Fy-a, Fy-b, Fy-o, Fy-x and Fy-y) and five antigens. Fy-x is a form of Fy-b where the Fy-b gene is poorly expressed. Fy-x
779-535: Is not known. The mouse ortholog has been cloned and exhibits 63% homology to the human gene at the amino acid level. The mouse gene is located on chromosome 1 between the genetic markers Xmv41 and D1Mit166. The mouse gene has two exons (100 and 1064 nucleotides in length), separated by a 461 base pair intron. In the mouse DARC is expressed during embryonic development between days 9.5 and 12. In yellow baboons ( Papio cynocephalus ) mutations in this gene have been associated with protection from infection with species of
820-449: Is now thought to be a distinct, unrelated antigen and is no longer included in the FY system. The Duffy antigen/chemokine receptor gene (gp-Fy; CD234) is located on the long arm of chromosome 1 (1.q22-1.q23) and was cloned in 1993. The gene was first localised to chromosome 1 in 1968, and was the first blood system antigen to be localised. It is a single copy gene spanning over 1500 bases and
861-485: Is used as an animal model of P. vivax infection. This species' erythrocytes possess the Duffy antigen and this antigen is used as the receptor for P. vivax on the erythrocytes in this species. Examination of this gene in 497 patients in the Amazonas State , Brazil, made by the doctor Sérgio Albuquerque, suggests that the genotypes FY*A/FY*B-33 and FY*B/FY*B-33 (where -33 refers to the null mutation at position -33 in
SECTION 20
#1733085667271902-474: The cytoplasmic face of the opposite bilayer. and by interaction between hydrophobic globular 'heads' of adjacent extracellular domains . Myelin protein zero's function is similar to the function of other proteins with immunoglobin domains like polyimmunoglobin and T4 protein. These proteins function as binding and adhesion molecules and participate in homotypic interactions, or interactions that involve two similar proteins. Myelin protein zero holds together
943-493: The Duffy antigen acts as a receptor for invasion by the human malarial parasites P. vivax and P. knowlesi . This was first shown in 1980. Duffy negative individuals whose erythrocytes do not express the receptor are believed to be resistant to merozoite invasion although P. vivax infection has been reported in Duffy negative children in Kenya, suggesting a role in resistance to disease, not infection. This antigen may also play
984-622: The Duffy antigen is uncommon in those of Black African descent, the presence of this antigen has been used to detect genetic admixture . In a sample of unrelated African Americans (n = 235), Afro-Caribbeans (n = 90) and Colombians (n = 93), the frequency of the -46T (Duffy positive) allele was 21.7%, 12.2% and 74.7% respectively. Overall the frequencies of Fya and Fyb antigens in Whites are 66% and 83% respectively, in Asians 99% and 18.5% respectively and in blacks 10% and 23% respectively. The frequency of Fy3
1025-432: The Duffy antigen with dissociation constants (KD) binding values of 24 ± 4.9, 20 ± 4.7, 41.9 ± 12.8, and 33.9 ± 7 nanoMoles for MGSA, interleukin-8, RANTES and monocyte chemotactic peptide-1 respectively. In DARC-transfected cells, DARC is internalized following ligand binding and this led to the hypothesis that expression of DARC on the surface of erythrocytes, endothelial , neuronal cells and epithelial cells may act as
1066-535: The Fy-x phenotype. Most Duffy negative black people carry a silent Fy-b allele with a single T to C substitution at nucleotide -33, impairing the promoter activity in erythroid cells by disrupting a binding site for the GATA1 erythroid transcription factor . The gene is still transcribed in non erythroid cells in the presence of this mutation . The Duffy negative phenotype occurs at low frequency among whites (~3.5%) and
1107-408: The basis of the Duffy blood group system. It was noted in the 1920s that black Africans had some intrinsic resistance to malaria, but the basis for this remained unknown. The Duffy antigen gene was the fourth gene associated with the resistance after the genes responsible for sickle cell anaemia , thalassemia and glucose-6-phosphate dehydrogenase . In 1950, the Duffy antigen was discovered in
1148-520: The binding of P. knowlesi to DARC. Differences in the racial distribution of the Duffy antigens were discovered in 1954, when it was found that the overwhelming majority of people of African descent had the erythrocyte phenotype Fy(a-b-): 68% in African Americans and 88-100% in African people (including more than 90% of West African people). This phenotype is exceedingly rare in Whites. Because
1189-556: The cytoplasmic domain or changing the tertiary structure of myelin protein zero can also result in neuropathy because the cytoplasmic domain has been demonstrated to be necessary for homotypic interactions. Duffy antigen system 2532 13349 ENSG00000213088 ENSMUSG00000037872 Q16570 Q9QUI6 NM_002036 NM_001122951 NM_010045 NP_001116423 NP_002027 NP_034175 Duffy antigen/chemokine receptor ( DARC ), also known as Fy glycoprotein ( FY ) or CD234 ( Cluster of Differentiation 234 ),
1230-431: The development of myelin early on in life or myelin degeneration on the axon later on in life. Some mutations can cause neuropathy in infancy like Derjerine-Sottas disease while other mutations can cause neuropathy within the first two decades of life like Charcot-Marie-Tooth disease . Adding a charged amino acid or changing a cysteine residue in the extracellular membrane can lead to neuropathy onset early on. Truncating
1271-480: The gene that encodes myelin protein zero is located on chromosome 1 near the Duffy locus or the Duffy antigen/chemokine receptor. The gene is about 7,000 bases long and is divided into 6 exons. In total, myelin protein zero is 219 amino acids long and has many basic amino acid residues. Myelin protein zero consists of an extracellular N-terminal domain (amino acids 1–124), a single transmembrane region (125–150), and
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1312-464: The genus Hepatocystis . The ancestral form of extant DARC alleles in humans appears to be the FY*B allele. The gene appears to be under strong purifying selection. The cause of this selective pressure has not yet been identified. Biochemical analysis of the Duffy antigen has shown that it has a high content of α-helical secondary structure - typical of chemokine receptors. Its N-glycans are mostly of
1353-494: The highly conserved DRY motif in the second intracellular loop of the protein that is known to be associated with G-protein signaling. Consistent with this finding ligand binding by DARC does not induce G-protein coupled signal transduction nor a Ca2+ flux unlike other chemokine receptors. Based on these alignments the Duffy antigen is considered to be most similar to the interleukin-8B receptors . Scatchard analysis of competition binding studies has shown high affinity binding to
1394-473: The incidence of this antigen there. This sweep appears to have occurred between 6,500 and 97,200 years ago (95% confidence interval) The distribution within India has been studied in some detail. Historically the role of this antigen other than its importance as a receptor for Plasmodium protozoa has not been appreciated. Recent work has identified a number of additional roles for this protein. On erythrocytes,
1435-524: The myelin sheath by participating in homotypic interactions with other myelin protein zero proteins. Myelin protein zero's extracellular domain binds to the myelin sphingolipid membrane and holds together myelin layers using homotypic interactions with other myelin protein zero extracellular domains, and with extracellular tryptophan residues interacting with the membrane. Myelin protein zero has also been demonstrated to interact with other proteins like peripheral myelin protein 22 . However, at this point
1476-415: The other species. This additional exon is located at the 5' end and is entirely non coding. Both intron and exon size vary considerably between the species examined. Between the chimpanzee and the human, 24 differences in the nucleotide sequence were noted. Of these 18 occurred in non coding regions. Of the remaining 6, 3 were synonymous and 3 non synonymous mutations. The significance of these mutations if any
1517-471: The peripheral nervous system. Currently, myelin protein zero expression is postulated to be produced by signals from the axon. However, more details about the regulation of myelin protein zero are unknown. It is postulated that myelin protein zero is a structural element in the formation and stabilization of peripheral nerve myelin. Myelin protein zero is also hypothesized to serve as a cell adhesion molecule, holding multiple layers of myelin together. When
1558-493: The post-capillary venules of some organs including the spleen, liver and kidney and the large pulmonary venules. Duffy antigen has then a very unique cell expression profile in cerebellar neurons, venular endothelial cells and erythroid cells. In some people who lack the Duffy antigen on their erythrocytes it is still expressed in the other cell types. It has two potential N-linked glycosylation sites at asparagine (Asn) 16 and Asn27. The Duffy antigen has been found to act as
1599-406: The purpose of these interactions has not yet been determined. Mutations in myelin protein zero are known to cause myelin degeneration and neuropathy . Mutations that reduce myelin protein zero's adhesion function or its ability to participate in homeotypic interactions with other myelin protein zero proteins are thought to cause neuropathy. Mutations to myelin protein zero can lead to issues with
1640-403: The same term [REDACTED] This disambiguation page lists articles associated with the title MPZ . If an internal link led you here, you may wish to change the link to point directly to the intended article. Retrieved from " https://en.wikipedia.org/w/index.php?title=MPZ&oldid=1167592375 " Category : Disambiguation pages Hidden categories: Short description
1681-455: The triantennary complex type terminated with α2-3- and α2-6-linked sialic acid residues with bisecting GlcNAc and α1-6-linked fucose at the core. The Duffy antigen is expressed in greater quantities on reticulocytes than on mature erythrocytes. While the Duffy antigen is expressed on bone marrow erythroblasts and circulating erythrocytes it is also found on Purkinje cells of the cerebellum , endothelial cells of thyroid capillaries ,