Protein 4.1

EPB41
Available structures PDB Ortholog search:PDBeRCSB List of PDB id codes 1GG3,2RQ1,3QIJ
Identifiers
Aliases	EPB41,erythrocyte membrane protein band 4.1, 4.1R, EL1, HE
External IDs	OMIM:130500;MGI:95401;HomoloGene:44324;GeneCards:EPB41;OMA:EPB41 - orthologs
Gene location (Human) Chr. Chromosome 1 (human) Band 1p35.3 Start 28,887,091bp End 29,120,046bp
Gene location (Mouse) Chr. Chromosome 4 (mouse) Band 4 D2.3|4 64.54 cM Start 131,923,413bp End 132,075,321bp
RNA expressionpattern Bgee Human Mouse(ortholog) Top expressed in trabecular bone cerebellar hemisphere right hemisphere of cerebellum epithelium of colon tonsil blood amniotic fluid epithelium of nasopharynx monocyte bone marrow Top expressed in blood neural layer of retina genital tubercle tail of embryo tibiofemoral joint fetal liver hematopoietic progenitor cell zygote ventricular zone cerebellar cortex lens More reference expression data BioGPS More reference expression data
Gene ontology Molecular function spectrin binding structural molecule activity calmodulin binding cytoskeletal protein binding 1-phosphatidylinositol binding structural constituent of cytoskeleton protein binding actin binding protein C-terminus binding protein N-terminus binding phosphoprotein binding Cellular component membrane cortical cytoskeleton cell junction cell cortex spectrin-associated cytoskeleton cytoskeleton nucleus cytoplasm cytosol cytoplasmic side of plasma membrane postsynaptic density plasma membrane cell cortex region protein-containing complex basolateral plasma membrane Biological process positive regulation of protein binding cortical actin cytoskeleton organization actin cytoskeleton organization actomyosin structure organization regulation of cell shape positive regulation of protein localization to cell cortex cell cycle cell division protein-containing complex assembly regulation of calcium ion transport regulation of intestinal absorption Sources:Amigo/QuickGO
Orthologs Species Human Mouse Entrez 2035 269587 Ensembl ENSG00000159023 ENSMUSG00000028906 UniProt P11171 P48193 RefSeq (mRNA) NM_001166005 NM_001166006 NM_001166007 NM_004437 NM_203342 NM_203343 NM_001376013 NM_001376014 NM_001376015 NM_001376016 NM_001376017 NM_001376018 NM_001376019 NM_001376020 NM_001376021 NM_001376022 NM_001376023 NM_001376024 NM_001376025 NM_001376026 NM_001376027 NM_001376028 NM_001128606 NM_001128607 NM_183428 RefSeq (protein) NP_001159477 NP_001159478 NP_001159479 NP_004428 NP_976217 NP_976218 NP_001362942 NP_001362943 NP_001362944 NP_001362945 NP_001362946 NP_001362947 NP_001362948 NP_001362949 NP_001362950 NP_001362951 NP_001362952 NP_001362953 NP_001362954 NP_001362955 NP_001362956 NP_001362957 NP_001122078 NP_001122079 NP_906273 Location (UCSC) Chr 1: 28.89 – 29.12 Mb Chr 4: 131.92 – 132.08 Mb PubMedsearch
Wikidata
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Protein 4.1,(Erythrocyte membrane protein band 4.1), is aproteinassociated with thecytoskeletonthat in humans is encoded by theEPB41gene.Protein 4.1 is a major structural element of theerythrocytemembraneskeleton. It plays a key role in regulating membrane physical properties of mechanical stability and deformability by stabilizingspectrin-actininteraction. Protein 4.1 (80 kD) interacts with spectrin and shortactin filamentsto form the erythrocyte membrane skeleton. Mutations of spectrin and protein 4.1 are associated withelliptocytosisorspherocytosisandanemiaof varying severity.

Clinical significance

A schematic diagram representing the relationships between cytoskeletal molecules as relevant to hereditary elliptocytosis.

Elliptocytosis is a hematologic disorder characterized by elliptically shaped erythrocytes and a variable degree of hemolytic anemia. Inherited as an autosomal dominant, elliptocytosis results from mutation in any one of several genes encoding proteins of the red cell membrane skeleton. The form discussed here is the one found in the 1950s to be linked to Rh blood group and more recently shown to be caused by a defect in protein 4.1. 'Rh-unlinked' forms of elliptocytosis are caused by mutation in the alpha-spectringene (MIM 182860), the beta-spectringene (MIM 182870), or theband 3gene (MIM 109270) [supplied by OMIM].

Interactions

Protein 4.1 has been shown tointeractwith:

• CENPJ,
• EIF3G
• NUMA1,and
• TJP2.

See also

• Elliptocytosis

Further reading

• Conboy JG (1993). "Structure, function, and molecular genetics of erythroid membrane skeletal protein 4.1 in normal and abnormal red blood cells".Semin. Hematol.30(1): 58–73.PMID8434260.
• Calinisan V, Gravem D, Chen RP, Brittin S, Mohandas N, Lecomte MC, Gascard P (2006)."New insights into potential functions for the protein 4.1 superfamily of proteins in kidney epithelium".Front. Biosci.11:1646–66.doi:10.2741/1911.PMID16368544.S2CID26325962.
• Dalla Venezia N, Gilsanz F, Alloisio N, Ducluzeau MT, Benz EJ, Delaunay J (1992)."Homozygous 4.1(-) hereditary elliptocytosis associated with a point mutation in the downstream initiation codon of protein 4.1 gene".J. Clin. Invest.90(5): 1713–7.doi:10.1172/JCI116044.PMC443228.PMID1430200.
• Jöns T, Drenckhahn D (1992)."Identification of the binding interface involved in linkage of cytoskeletal protein 4.1 to the erythrocyte anion exchanger".EMBO J.11(8): 2863–7.doi:10.1002/j.1460-2075.1992.tb05354.x.PMC556766.PMID1639060.
• Subrahmanyam G, Bertics PJ, Anderson RA (1991)."Phosphorylation of protein 4.1 on tyrosine-418 modulates its function in vitro".Proc. Natl. Acad. Sci. U.S.A.88(12): 5222–6.Bibcode:1991PNAS...88.5222S.doi:10.1073/pnas.88.12.5222.PMC51844.PMID1647028.
• Conboy JG, Chan JY, Chasis JA, Kan YW, Mohandas N (1991)."Tissue- and development-specific alternative RNA splicing regulates expression of multiple isoforms of erythroid membrane protein 4.1".J. Biol. Chem.266(13): 8273–80.doi:10.1016/S0021-9258(18)92973-X.PMID2022644.
• Horne WC, Prinz WC, Tang EK (1990). "Identification of two cAMP-dependent phosphorylation sites on erythrocyte protein 4.1".Biochim. Biophys. Acta.1055(1): 87–92.doi:10.1016/0167-4889(90)90095-U.PMID2171679.
• Conboy J, Marchesi S, Kim R, Agre P, Kan YW, Mohandas N (1990)."Molecular analysis of insertion/deletion mutations in protein 4.1 in elliptocytosis. II. Determination of molecular genetic origins of rearrangements".J. Clin. Invest.86(2): 524–30.doi:10.1172/JCI114739.PMC296755.PMID2384598.
• Inaba M, Maede Y (1989)."O-N-acetyl-D-glucosamine moiety on discrete peptide of multiple protein 4.1 isoforms regulated by alternative pathways".J. Biol. Chem.264(30): 18149–55.doi:10.1016/S0021-9258(19)84689-6.PMID2808371.
• Korsgren C, Cohen CM (1988)."Associations of human erythrocyte band 4.2. Binding to ankyrin and to the cytoplasmic domain of band 3".J. Biol. Chem.263(21): 10212–8.doi:10.1016/S0021-9258(19)81500-4.PMID2968981.
• Conboy JG, Chan J, Mohandas N, Kan YW (1988)."Multiple protein 4.1 isoforms produced by alternative splicing in human erythroid cells".Proc. Natl. Acad. Sci. U.S.A.85(23): 9062–5.Bibcode:1988PNAS...85.9062C.doi:10.1073/pnas.85.23.9062.PMC282663.PMID3194408.
• Tang TK, Leto TL, Marchesi VT, Benz EJ (1988). "Expression of Specific Isoforms of Protein 4.1 in Erythroid and Non-Erythroid Tissues".Molecular Biology of Hemopoiesis.Advances in Experimental Medicine and Biology. Vol. 241. pp. 81–95.doi:10.1007/978-1-4684-5571-7_12.ISBN978-1-4684-5573-1.PMID3223413.
• Tang TK, Leto TL, Correas I, Alonso MA, Marchesi VT, Benz EJ (1988)."Selective expression of an erythroid-specific isoform of protein 4.1".Proc. Natl. Acad. Sci. U.S.A.85(11): 3713–7.Bibcode:1988PNAS...85.3713T.doi:10.1073/pnas.85.11.3713.PMC280288.PMID3375238.
• Conboy J, Kan YW, Shohet SB, Mohandas N (1987)."Molecular cloning of protein 4.1, a major structural element of the human erythrocyte membrane skeleton".Proc. Natl. Acad. Sci. U.S.A.83(24): 9512–6.doi:10.1073/pnas.83.24.9512.PMC387170.PMID3467321.
• Correas I, Speicher DW, Marchesi VT (1986)."Structure of the spectrin-actin binding site of erythrocyte protein 4.1".J. Biol. Chem.261(28): 13362–6.doi:10.1016/S0021-9258(18)69313-5.PMID3531202.
• Tchernia G, Mohandas N, Shohet SB (1981)."Deficiency of skeletal membrane protein band 4.1 in homozygous hereditary elliptocytosis. Implications for erythrocyte membrane stability".J. Clin. Invest.68(2): 454–60.doi:10.1172/JCI110275.PMC370818.PMID6894932.
• Schischmanoff PO, Winardi R, Discher DE, Parra MK, Bicknese SE, Witkowska HE, Conboy JG, Mohandas N (1995)."Defining of the minimal domain of protein 4.1 involved in spectrin-actin binding".J. Biol. Chem.270(36): 21243–50.doi:10.1074/jbc.270.36.21243.PMID7673158.
• Lue RA, Marfatia SM, Branton D, Chishti AH (1994)."Cloning and characterization of hdlg: the human homologue of the Drosophila discs large tumor suppressor binds to protein 4.1".Proc. Natl. Acad. Sci. U.S.A.91(21): 9818–22.Bibcode:1994PNAS...91.9818L.doi:10.1073/pnas.91.21.9818.PMC44908.PMID7937897.
• Conboy JG, Chasis JA, Winardi R, Tchernia G, Kan YW, Mohandas N (1993)."An isoform-specific mutation in the protein 4.1 gene results in hereditary elliptocytosis and complete deficiency of protein 4.1 in erythrocytes but not in nonerythroid cells".J. Clin. Invest.91(1): 77–82.doi:10.1172/JCI116203.PMC329997.PMID8423235.

External links

• erythrocyte+membrane+band+4.1+proteinat the U.S. National Library of MedicineMedical Subject Headings(MeSH)