ID EPB41_HUMAN Reviewed; 864 AA. AC P11171; B1ALH8; B1ALH9; D3DPM9; D3DPN0; P11176; Q14245; Q5TB35; Q5VXN8; AC Q8IXV9; Q9Y578; Q9Y579; DT 01-JUL-1989, integrated into UniProtKB/Swiss-Prot. DT 07-MAR-2006, sequence version 4. DT 27-MAR-2024, entry version 245. DE RecName: Full=Protein 4.1; DE Short=P4.1; DE AltName: Full=4.1R; DE AltName: Full=Band 4.1; DE AltName: Full=EPB4.1; DE AltName: Full=Erythrocyte membrane protein band 4.1 {ECO:0000312|HGNC:HGNC:3377}; GN Name=EPB41 {ECO:0000312|HGNC:HGNC:3377}; Synonyms=E41P; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 4), INVOLVEMENT IN EL1, AND PROTEIN RP SEQUENCE OF 378-393. RC TISSUE=Reticulocyte; RX PubMed=3467321; DOI=10.1073/pnas.83.24.9512; RA Conboy J.G., Kan Y.W., Shohet S.B., Mohandas N.; RT "Molecular cloning of protein 4.1, a major structural element of the human RT erythrocyte membrane skeleton."; RL Proc. Natl. Acad. Sci. U.S.A. 83:9512-9516(1986). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 5 AND 6). RX PubMed=3223413; DOI=10.1007/978-1-4684-5571-7_12; RA Tang T.K., Leto T.L., Marchesi V.T., Benz E.J. Jr.; RT "Expression of specific isoforms of protein 4.1 in erythroid and non- RT erythroid tissues."; RL Adv. Exp. Med. Biol. 241:81-95(1988). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 5 AND 6). RX PubMed=3375238; DOI=10.1073/pnas.85.11.3713; RA Tang T.K., Leto T.L., Correas I., Alonso M.A., Marchesi V.T., RA Benz E.J. Jr.; RT "Selective expression of an erythroid-specific isoform of protein 4.1."; RL Proc. Natl. Acad. Sci. U.S.A. 85:3713-3717(1988). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3). RX PubMed=2022644; DOI=10.1016/s0021-9258(18)92973-x; RA Conboy J.G., Chan J.Y.C., Chasis J.A., Kan Y.W., Mohandas N.; RT "Tissue- and development-specific alternative RNA splicing regulates RT expression of multiple isoforms of erythroid membrane protein 4.1."; RL J. Biol. Chem. 266:8273-8280(1991). RN [5] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RA Huang S.C., Wang C., Lichtenauer U., Vortmeyer A., Zhuang Z.; RT "Sequence of protein 4.1 from a human neuroblastoma cell line: LAN5."; RL Submitted (JUN-1999) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16710414; DOI=10.1038/nature04727; RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K., RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.; RT "The DNA sequence and biological annotation of human chromosome 1."; RL Nature 441:315-321(2006). RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 7). RC TISSUE=Brain; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [9] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 157-227, AND VARIANT ILE-214. RA Lichtenauer U., Huang S.C., Vortmeyer A., Zhuang Z.; RT "Valine to isoleucine polymorphism in exon 4 of human protein 4.1."; RL Submitted (JUN-1999) to the EMBL/GenBank/DDBJ databases. RN [10] RP NUCLEOTIDE SEQUENCE OF 669-864 (ISOFORM 4), AND ALTERNATIVE SPLICING. RX PubMed=3194408; DOI=10.1073/pnas.85.23.9062; RA Conboy J.G., Chan J., Mohandas N., Kan Y.W.; RT "Multiple protein 4.1 isoforms produced by alternative splicing in human RT erythroid cells."; RL Proc. Natl. Acad. Sci. U.S.A. 85:9062-9065(1988). RN [11] RP PROTEIN SEQUENCE OF 534-541; 693-701 AND 793-794, AND PHOSPHORYLATION AT RP SER-540 AND SER-709. RX PubMed=2171679; DOI=10.1016/0167-4889(90)90095-u; RA Horne W.C., Prinz W.C., Tang E.K.; RT "Identification of two cAMP-dependent phosphorylation sites on erythrocyte RT protein 4.1."; RL Biochim. Biophys. Acta 1055:87-92(1990). RN [12] RP PROTEIN SEQUENCE OF 648-714. RX PubMed=3531202; DOI=10.1016/s0021-9258(18)69313-5; RA Correas I., Speicher D.W., Marchesi V.T.; RT "Structure of the spectrin-actin binding site of erythrocyte protein 4.1."; RL J. Biol. Chem. 261:13362-13366(1986). RN [13] RP STRUCTURE OF CARBOHYDRATES. RX PubMed=2808371; DOI=10.1016/s0021-9258(19)84689-6; RA Inaba M., Maede Y.; RT "O-N-acetyl-D-glucosamine moiety on discrete peptide of multiple protein RT 4.1 isoforms regulated by alternative pathways."; RL J. Biol. Chem. 264:18149-18155(1989). RN [14] RP PHOSPHORYLATION AT TYR-660 BY EGFR. RX PubMed=1647028; DOI=10.1073/pnas.88.12.5222; RA Subrahmanyan G., Bertics P.J., Anderson R.A.; RT "Phosphorylation of protein 4.1 on tyrosine-418 modulates its function in RT vitro."; RL Proc. Natl. Acad. Sci. U.S.A. 88:5222-5226(1991). RN [15] RP INTERACTION WITH DLG1. RX PubMed=7937897; DOI=10.1073/pnas.91.21.9818; RA Lue R.A., Marfatia S.M., Branton D., Chishti A.H.; RT "Cloning and characterization of hdlg: the human homologue of the RT Drosophila discs large tumor suppressor binds to protein 4.1."; RL Proc. Natl. Acad. Sci. U.S.A. 91:9818-9822(1994). RN [16] RP INTERACTION WITH CALMODULIN. RX PubMed=10692436; DOI=10.1074/jbc.275.9.6360; RA Nunomura W., Takakuwa Y., Parra M., Conboy J.G., Mohandas N.; RT "Ca(2+)-dependent and Ca(2+)-independent calmodulin binding sites in RT erythrocyte protein 4.1. Implications for regulation of protein 4.1 RT interactions with transmembrane proteins."; RL J. Biol. Chem. 275:6360-6367(2000). RN [17] RP INTERACTION WITH CENPJ. RX PubMed=11003675; DOI=10.1128/mcb.20.20.7813-7825.2000; RA Hung L.-Y., Tang C.J., Tang T.K.; RT "Protein 4.1 R-135 interacts with a novel centrosomal protein (CPAP) which RT is associated with the gamma-tubulin complex."; RL Mol. Cell. Biol. 20:7813-7825(2000). RN [18] RP CHARACTERIZATION OF C-TERMINAL DOMAIN. RX PubMed=11432737; DOI=10.1046/j.1432-1327.2001.02276.x; RA Scott C., Phillips G.W., Baines A.J.; RT "Properties of the C-terminal domain of 4.1 proteins."; RL Eur. J. Biochem. 268:3709-3717(2001). RN [19] RP SUBCELLULAR LOCATION, AND ALTERNATIVE SPLICING. RX PubMed=12427749; DOI=10.1074/jbc.m201521200; RA Luque C.M., Perez-Ferreiro C.M., Perez-Gonzalez A., Englmeier L., RA Koffa M.D., Correas I.; RT "An alternative domain containing a leucine-rich sequence regulates nuclear RT cytoplasmic localization of protein 4.1R."; RL J. Biol. Chem. 278:2686-2691(2003). RN [20] RP MUTAGENESIS OF THR-60 AND SER-712, AND PHOSPHORYLATION AT THR-60 AND RP SER-712. RX PubMed=15525677; DOI=10.1091/mbc.e04-05-0426; RA Huang S.-C., Liu E.S., Chan S.-H., Munagala I.D., Cho H.T., RA Jagadeeswaran R., Benz E.J. Jr.; RT "Mitotic regulation of protein 4.1R involves phosphorylation by cdc2 RT kinase."; RL Mol. Biol. Cell 16:117-127(2005). RN [21] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-188; SER-191; SER-555 AND RP SER-712, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [22] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Leukemic T-cell; RX PubMed=19690332; DOI=10.1126/scisignal.2000007; RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., RA Rodionov V., Han D.K.; RT "Quantitative phosphoproteomic analysis of T cell receptor signaling RT reveals system-wide modulation of protein-protein interactions."; RL Sci. Signal. 2:RA46-RA46(2009). RN [23] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-84; SER-85; SER-188 AND RP SER-712, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=20068231; DOI=10.1126/scisignal.2000475; RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.; RT "Quantitative phosphoproteomics reveals widespread full phosphorylation RT site occupancy during mitosis."; RL Sci. Signal. 3:RA3-RA3(2010). RN [24] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [25] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-14; SER-149; SER-151 AND RP SER-152, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21406692; DOI=10.1126/scisignal.2001570; RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.; RT "System-wide temporal characterization of the proteome and phosphoproteome RT of human embryonic stem cell differentiation."; RL Sci. Signal. 4:RS3-RS3(2011). RN [26] RP FUNCTION, INTERACTION WITH NUMA1, AND SUBCELLULAR LOCATION. RX PubMed=23870127; DOI=10.1016/j.cell.2013.06.010; RA Kiyomitsu T., Cheeseman I.M.; RT "Cortical dynein and asymmetric membrane elongation coordinately position RT the spindle in anaphase."; RL Cell 154:391-402(2013). RN [27] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-60; SER-95; SER-104; SER-188; RP SER-191; THR-378; SER-521; SER-540; SER-542; TYR-660; SER-674; SER-684; RP SER-709; SER-712; THR-736 AND THR-859, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma, and Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [28] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-542 AND SER-555, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [29] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25944712; DOI=10.1002/pmic.201400617; RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D., RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.; RT "N-terminome analysis of the human mitochondrial proteome."; RL Proteomics 15:2519-2524(2015). RN [30] RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 210-488. RX PubMed=11017195; DOI=10.1038/82819; RA Han B.-G., Nunomura W., Takakuwa Y., Mohandas N., Jap B.K.; RT "Protein 4.1R core domain structure and insights into regulation of RT cytoskeletal organization."; RL Nat. Struct. Biol. 7:871-875(2000). CC -!- FUNCTION: Protein 4.1 is a major structural element of the erythrocyte CC membrane skeleton. It plays a key role in regulating membrane physical CC properties of mechanical stability and deformability by stabilizing CC spectrin-actin interaction. Recruits DLG1 to membranes. Required for CC dynein-dynactin complex and NUMA1 recruitment at the mitotic cell CC cortex during anaphase (PubMed:23870127). CC {ECO:0000269|PubMed:23870127}. CC -!- SUBUNIT: Binds with a high affinity to glycophorin and with lower CC affinity to band III protein. Associates with the nuclear mitotic CC apparatus. Interacts with calmodulin (PubMed:10692436). Interacts with CC CENPJ (PubMed:11003675). Interacts with DLG1 (PubMed:7937897). Also CC found to associate with contractile apparatus and tight junctions. CC Interacts with NUMA1; this interaction is negatively regulated by CDK1 CC during metaphase and promotes anaphase-specific localization of NUMA1 CC in symmetrically dividing cells (PubMed:23870127). Interacts with CC ATP2B1; regulates small intestinal calcium absorption through CC regulation of membrane expression of ATP2B1 (By similarity). CC {ECO:0000250|UniProtKB:P48193, ECO:0000269|PubMed:10692436, CC ECO:0000269|PubMed:11003675, ECO:0000269|PubMed:23870127, CC ECO:0000269|PubMed:7937897}. CC -!- INTERACTION: CC P11171-2; P05067: APP; NbExp=3; IntAct=EBI-10197451, EBI-77613; CC P11171-2; P54105: CLNS1A; NbExp=3; IntAct=EBI-10197451, EBI-724693; CC P11171-2; P57060: RWDD2B; NbExp=3; IntAct=EBI-10197451, EBI-724442; CC P11171-2; Q8TBK6: ZCCHC10; NbExp=3; IntAct=EBI-10197451, EBI-597063; CC P11171-7; P05067: APP; NbExp=3; IntAct=EBI-25852354, EBI-77613; CC P11171-7; Q494V2-2: CFAP100; NbExp=3; IntAct=EBI-25852354, EBI-11953200; CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton CC {ECO:0000269|PubMed:12427749}. Cytoplasm, cell cortex CC {ECO:0000269|PubMed:12427749, ECO:0000269|PubMed:23870127}. Nucleus CC {ECO:0000269|PubMed:12427749}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=7; CC Name=1; CC IsoId=P11171-1; Sequence=Displayed; CC Name=2; CC IsoId=P11171-2; Sequence=VSP_000470; CC Name=3; CC IsoId=P11171-3; Sequence=VSP_000468, VSP_000471; CC Name=4; Synonyms=Erythroid; CC IsoId=P11171-4; Sequence=VSP_000468, VSP_000470, VSP_000473; CC Name=5; Synonyms=Non-erythroid A; CC IsoId=P11171-5; Sequence=VSP_000469, VSP_000470, VSP_000472; CC Name=6; Synonyms=Non-erythroid B; CC IsoId=P11171-6; Sequence=VSP_000468, VSP_000469, VSP_000470, CC VSP_000472; CC Name=7; CC IsoId=P11171-7; Sequence=VSP_000471, VSP_012872, VSP_012873; CC -!- PTM: Phosphorylated at multiple sites by different protein kinases and CC each phosphorylation event selectively modulates the protein's CC functions. CC -!- PTM: Phosphorylation on Tyr-660 reduces the ability of 4.1 to promote CC the assembly of the spectrin/actin/4.1 ternary complex. CC {ECO:0000269|PubMed:1647028}. CC -!- PTM: O-glycosylated; contains N-acetylglucosamine side chains in the C- CC terminal domain. CC -!- DISEASE: Elliptocytosis 1 (EL1) [MIM:611804]: A Rhesus-linked form of CC hereditary elliptocytosis, a genetically heterogeneous, autosomal CC dominant hematologic disorder. It is characterized by variable CC hemolytic anemia and elliptical or oval red cell shape. CC {ECO:0000269|PubMed:3467321}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; M14993; AAA35795.1; -; mRNA. DR EMBL; J03796; AAA35793.1; -; mRNA. DR EMBL; J03796; AAA35794.1; -; mRNA. DR EMBL; M61733; AAA35797.1; -; mRNA. DR EMBL; AF156225; AAD42222.1; -; mRNA. DR EMBL; AL138785; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL357500; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471059; EAX07663.1; -; Genomic_DNA. DR EMBL; CH471059; EAX07665.1; -; Genomic_DNA. DR EMBL; CH471059; EAX07667.1; -; Genomic_DNA. DR EMBL; CH471059; EAX07668.1; -; Genomic_DNA. DR EMBL; BC039079; AAH39079.1; -; mRNA. DR EMBL; AF156226; AAD42223.1; -; Genomic_DNA. DR CCDS; CCDS330.1; -. [P11171-5] DR CCDS; CCDS331.1; -. [P11171-4] DR CCDS; CCDS53288.1; -. [P11171-1] DR CCDS; CCDS53289.1; -. [P11171-7] DR PIR; A39810; MMHUE4. DR RefSeq; NP_001159477.1; NM_001166005.1. [P11171-1] DR RefSeq; NP_001159478.1; NM_001166006.1. [P11171-7] DR RefSeq; NP_004428.1; NM_004437.3. [P11171-4] DR RefSeq; NP_976217.1; NM_203342.2. [P11171-3] DR RefSeq; XP_005245818.1; XM_005245761.1. DR RefSeq; XP_005245821.1; XM_005245764.1. [P11171-2] DR RefSeq; XP_016856078.1; XM_017000589.1. DR PDB; 1GG3; X-ray; 2.80 A; A/B/C=210-488. DR PDB; 2RQ1; NMR; -; A=292-396. DR PDB; 3QIJ; X-ray; 1.80 A; A/B=211-488. DR PDBsum; 1GG3; -. DR PDBsum; 2RQ1; -. DR PDBsum; 3QIJ; -. DR AlphaFoldDB; P11171; -. DR BMRB; P11171; -. DR SMR; P11171; -. DR BioGRID; 108349; 113. DR CORUM; P11171; -. DR DIP; DIP-17032N; -. DR IntAct; P11171; 31. DR MINT; P11171; -. DR STRING; 9606.ENSP00000345259; -. DR TCDB; 8.A.25.1.2; the ezrin/radixin/moesin (ezrin) family. DR GlyConnect; 515; 1 O-GlcNAc glycan (2 sites). DR GlyCosmos; P11171; 3 sites, 1 glycan. DR GlyGen; P11171; 4 sites, 2 O-linked glycans (4 sites). DR iPTMnet; P11171; -. DR MetOSite; P11171; -. DR PhosphoSitePlus; P11171; -. DR SwissPalm; P11171; -. DR BioMuta; EPB41; -. DR DMDM; 90101808; -. DR EPD; P11171; -. DR jPOST; P11171; -. DR MassIVE; P11171; -. DR MaxQB; P11171; -. DR PaxDb; 9606-ENSP00000345259; -. DR PeptideAtlas; P11171; -. DR ProteomicsDB; 52706; -. [P11171-1] DR ProteomicsDB; 52707; -. [P11171-2] DR ProteomicsDB; 52708; -. [P11171-3] DR ProteomicsDB; 52709; -. [P11171-4] DR ProteomicsDB; 52710; -. [P11171-5] DR ProteomicsDB; 52711; -. [P11171-6] DR ProteomicsDB; 52712; -. [P11171-7] DR Pumba; P11171; -. DR Antibodypedia; 30998; 399 antibodies from 30 providers. DR DNASU; 2035; -. DR Ensembl; ENST00000343067.9; ENSP00000345259.4; ENSG00000159023.23. [P11171-1] DR Ensembl; ENST00000347529.7; ENSP00000290100.6; ENSG00000159023.23. [P11171-5] DR Ensembl; ENST00000373797.2; ENSP00000362903.1; ENSG00000159023.23. [P11171-7] DR Ensembl; ENST00000373798.5; ENSP00000362904.1; ENSG00000159023.23. [P11171-1] DR Ensembl; ENST00000373800.7; ENSP00000362906.3; ENSG00000159023.23. [P11171-4] DR GeneID; 2035; -. DR KEGG; hsa:2035; -. DR MANE-Select; ENST00000343067.9; ENSP00000345259.4; NM_001376013.1; NP_001362942.1. DR UCSC; uc001brg.3; human. [P11171-1] DR AGR; HGNC:3377; -. DR CTD; 2035; -. DR DisGeNET; 2035; -. DR GeneCards; EPB41; -. DR HGNC; HGNC:3377; EPB41. DR HPA; ENSG00000159023; Tissue enhanced (retina). DR MalaCards; EPB41; -. DR MIM; 130500; gene. DR MIM; 611804; phenotype. DR neXtProt; NX_P11171; -. DR OpenTargets; ENSG00000159023; -. DR Orphanet; 288; Hereditary elliptocytosis. DR PharmGKB; PA27810; -. DR VEuPathDB; HostDB:ENSG00000159023; -. DR eggNOG; KOG3527; Eukaryota. DR GeneTree; ENSGT00940000157833; -. DR HOGENOM; CLU_003623_0_1_1; -. DR InParanoid; P11171; -. DR OMA; TYEAAQX; -. DR OrthoDB; 5391231at2759; -. DR PhylomeDB; P11171; -. DR TreeFam; TF351626; -. DR PathwayCommons; P11171; -. DR Reactome; R-HSA-6794361; Neurexins and neuroligins. DR SignaLink; P11171; -. DR SIGNOR; P11171; -. DR BioGRID-ORCS; 2035; 19 hits in 1176 CRISPR screens. DR ChiTaRS; EPB41; human. DR EvolutionaryTrace; P11171; -. DR GeneWiki; EPB41; -. DR GenomeRNAi; 2035; -. DR Pharos; P11171; Tbio. DR PRO; PR:P11171; -. DR Proteomes; UP000005640; Chromosome 1. DR RNAct; P11171; Protein. DR Bgee; ENSG00000159023; Expressed in trabecular bone tissue and 177 other cell types or tissues. DR ExpressionAtlas; P11171; baseline and differential. DR GO; GO:0016323; C:basolateral plasma membrane; ISS:UniProtKB. DR GO; GO:0005938; C:cell cortex; IDA:UniProtKB. DR GO; GO:0030054; C:cell junction; IDA:HPA. DR GO; GO:0030863; C:cortical cytoskeleton; IDA:UniProtKB. DR GO; GO:0009898; C:cytoplasmic side of plasma membrane; IEA:Ensembl. DR GO; GO:0005856; C:cytoskeleton; IBA:GO_Central. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:0045171; C:intercellular bridge; IDA:HPA. DR GO; GO:0072686; C:mitotic spindle; IDA:HPA. DR GO; GO:0016604; C:nuclear body; IDA:HPA. DR GO; GO:0005886; C:plasma membrane; IDA:HPA. DR GO; GO:0032991; C:protein-containing complex; IDA:UniProtKB. DR GO; GO:0014731; C:spectrin-associated cytoskeleton; TAS:BHF-UCL. DR GO; GO:0005545; F:1-phosphatidylinositol binding; IDA:UniProtKB. DR GO; GO:0003779; F:actin binding; IEA:UniProtKB-KW. DR GO; GO:0005516; F:calmodulin binding; IEA:UniProtKB-KW. DR GO; GO:0051219; F:phosphoprotein binding; IMP:CAFA. DR GO; GO:0030507; F:spectrin binding; TAS:BHF-UCL. DR GO; GO:0005200; F:structural constituent of cytoskeleton; IMP:UniProtKB. DR GO; GO:0030036; P:actin cytoskeleton organization; NAS:UniProtKB. DR GO; GO:0031032; P:actomyosin structure organization; IBA:GO_Central. DR GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW. DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW. DR GO; GO:0030866; P:cortical actin cytoskeleton organization; IEA:InterPro. DR GO; GO:0032092; P:positive regulation of protein binding; IDA:BHF-UCL. DR GO; GO:1904778; P:positive regulation of protein localization to cell cortex; IMP:UniProtKB. DR GO; GO:0065003; P:protein-containing complex assembly; IEA:Ensembl. DR GO; GO:0051924; P:regulation of calcium ion transport; ISS:UniProtKB. DR GO; GO:1904478; P:regulation of intestinal absorption; ISS:UniProtKB. DR CDD; cd14473; FERM_B-lobe; 1. DR CDD; cd13184; FERM_C_4_1_family; 1. DR CDD; cd17105; FERM_F1_EPB41; 1. DR DisProt; DP00678; -. DR Gene3D; 1.20.80.10; -; 1. DR Gene3D; 2.30.29.30; Pleckstrin-homology domain (PH domain)/Phosphotyrosine-binding domain (PTB); 1. DR InterPro; IPR008379; Band_4.1_C. DR InterPro; IPR019749; Band_41_domain. DR InterPro; IPR021187; EPB4.1_FERM_F1. DR InterPro; IPR000798; Ez/rad/moesin-like. DR InterPro; IPR014847; FA. DR InterPro; IPR014352; FERM/acyl-CoA-bd_prot_sf. DR InterPro; IPR035963; FERM_2. DR InterPro; IPR019748; FERM_central. DR InterPro; IPR019747; FERM_CS. DR InterPro; IPR000299; FERM_domain. DR InterPro; IPR018979; FERM_N. DR InterPro; IPR018980; FERM_PH-like_C. DR InterPro; IPR011993; PH-like_dom_sf. DR InterPro; IPR007477; SAB_dom. DR InterPro; IPR029071; Ubiquitin-like_domsf. DR PANTHER; PTHR23280; 4.1 G PROTEIN; 1. DR PANTHER; PTHR23280:SF12; PROTEIN 4.1; 1. DR Pfam; PF05902; 4_1_CTD; 1. DR Pfam; PF08736; FA; 1. DR Pfam; PF09380; FERM_C; 1. DR Pfam; PF00373; FERM_M; 1. DR Pfam; PF09379; FERM_N; 1. DR Pfam; PF04382; SAB; 1. DR PIRSF; PIRSF002304; Membrane_skeletal_4_1; 1. DR PRINTS; PR00935; BAND41. DR PRINTS; PR00661; ERMFAMILY. DR SMART; SM00295; B41; 1. DR SMART; SM01195; FA; 1. DR SMART; SM01196; FERM_C; 1. DR SUPFAM; SSF50729; PH domain-like; 1. DR SUPFAM; SSF47031; Second domain of FERM; 1. DR SUPFAM; SSF54236; Ubiquitin-like; 1. DR PROSITE; PS00660; FERM_1; 1. DR PROSITE; PS00661; FERM_2; 1. DR PROSITE; PS50057; FERM_3; 1. DR Genevisible; P11171; HS. PE 1: Evidence at protein level; KW 3D-structure; Actin-binding; Alternative splicing; Calmodulin-binding; KW Cell cycle; Cell division; Cytoplasm; Cytoskeleton; KW Direct protein sequencing; Elliptocytosis; Glycoprotein; KW Hereditary hemolytic anemia; Mitosis; Nucleus; Phosphoprotein; KW Pyropoikilocytosis; Reference proteome; Transport. FT CHAIN 1..864 FT /note="Protein 4.1" FT /id="PRO_0000219390" FT DOMAIN 210..491 FT /note="FERM" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00084" FT REGION 1..122 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 136..170 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 182..202 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 494..614 FT /note="Hydrophilic" FT REGION 518..572 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 586..611 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 615..713 FT /note="Spectrin--actin-binding" FT REGION 714..864 FT /note="C-terminal (CTD)" FT COMPBIAS 27..45 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 57..77 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 91..122 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 14 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:21406692" FT MOD_RES 60 FT /note="Phosphothreonine; by CDK1" FT /evidence="ECO:0000269|PubMed:15525677, FT ECO:0007744|PubMed:23186163" FT MOD_RES 84 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:20068231" FT MOD_RES 85 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:20068231" FT MOD_RES 95 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 104 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 121 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P48193" FT MOD_RES 149 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:21406692" FT MOD_RES 151 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:21406692" FT MOD_RES 152 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:21406692" FT MOD_RES 188 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163" FT MOD_RES 191 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:23186163" FT MOD_RES 222 FT /note="Phosphotyrosine" FT /evidence="ECO:0000250|UniProtKB:P48193" FT MOD_RES 378 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 521 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 540 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:2171679, FT ECO:0007744|PubMed:23186163" FT MOD_RES 542 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163, FT ECO:0007744|PubMed:24275569" FT MOD_RES 555 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:24275569" FT MOD_RES 660 FT /note="Phosphotyrosine; by EGFR" FT /evidence="ECO:0000269|PubMed:1647028, FT ECO:0007744|PubMed:23186163" FT MOD_RES 664 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P48193" FT MOD_RES 674 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 684 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 709 FT /note="Phosphoserine" FT /evidence="ECO:0000269|PubMed:2171679, FT ECO:0007744|PubMed:23186163" FT MOD_RES 712 FT /note="Phosphoserine; by CDK1" FT /evidence="ECO:0000269|PubMed:15525677, FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:20068231, FT ECO:0007744|PubMed:23186163" FT MOD_RES 736 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 859 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:23186163" FT VAR_SEQ 1..209 FT /note="Missing (in isoform 3, isoform 4 and isoform 6)" FT /evidence="ECO:0000303|PubMed:2022644, FT ECO:0000303|PubMed:3223413, ECO:0000303|PubMed:3375238, FT ECO:0000303|PubMed:3467321" FT /id="VSP_000468" FT VAR_SEQ 228..262 FT /note="Missing (in isoform 5 and isoform 6)" FT /evidence="ECO:0000303|PubMed:3223413, FT ECO:0000303|PubMed:3375238" FT /id="VSP_000469" FT VAR_SEQ 616..648 FT /note="Missing (in isoform 2, isoform 4, isoform 5 and FT isoform 6)" FT /evidence="ECO:0000303|PubMed:3223413, FT ECO:0000303|PubMed:3375238, ECO:0000303|PubMed:3467321" FT /id="VSP_000470" FT VAR_SEQ 635..648 FT /note="Missing (in isoform 3 and isoform 7)" FT /evidence="ECO:0000303|PubMed:15489334, FT ECO:0000303|PubMed:2022644" FT /id="VSP_000471" FT VAR_SEQ 649..669 FT /note="Missing (in isoform 5 and isoform 6)" FT /evidence="ECO:0000303|PubMed:3223413, FT ECO:0000303|PubMed:3375238" FT /id="VSP_000472" FT VAR_SEQ 729..734 FT /note="PPLVKT -> VSTLST (in isoform 7)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_012872" FT VAR_SEQ 735..864 FT /note="Missing (in isoform 7)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_012873" FT VAR_SEQ 772..805 FT /note="Missing (in isoform 4)" FT /evidence="ECO:0000303|PubMed:3467321" FT /id="VSP_000473" FT VARIANT 214 FT /note="V -> I (in dbSNP:rs111642750)" FT /evidence="ECO:0000269|Ref.9" FT /id="VAR_009122" FT MUTAGEN 60 FT /note="T->A: Loss of CDK1-mediated phosphorylation. FT Abolishes targeting onto the mitotic spindle; when FT associated with A-712." FT /evidence="ECO:0000269|PubMed:15525677" FT MUTAGEN 712 FT /note="S->A: Loss of CDK1-mediated phosphorylation. FT Abolishes targeting onto the mitotic spindle; when FT associated with A-60." FT /evidence="ECO:0000269|PubMed:15525677" FT CONFLICT 51 FT /note="Q -> H (in Ref. 5; AAD42222)" FT /evidence="ECO:0000305" FT CONFLICT 76 FT /note="S -> N (in Ref. 5; AAD42222)" FT /evidence="ECO:0000305" FT CONFLICT 168 FT /note="F -> S (in Ref. 9; AAD42223)" FT /evidence="ECO:0000305" FT CONFLICT 259 FT /note="A -> T (in Ref. 5; AAD42222)" FT /evidence="ECO:0000305" FT CONFLICT 665 FT /note="N -> S (in Ref. 5; AAD42222)" FT /evidence="ECO:0000305" FT CONFLICT 669 FT /note="E -> K (in Ref. 10; no nucleotide entry)" FT /evidence="ECO:0000305" FT CONFLICT 679 FT /note="K -> E (in Ref. 5; AAD42222)" FT /evidence="ECO:0000305" FT CONFLICT 802 FT /note="Q -> K (in Ref. 2; no nucleotide entry and 3; FT AAA35793/AAA35794)" FT /evidence="ECO:0000305" FT CONFLICT 852 FT /note="K -> L (in Ref. 10; no nucleotide entry)" FT /evidence="ECO:0000305" FT CONFLICT 863 FT /note="D -> E (in Ref. 10; no nucleotide entry)" FT /evidence="ECO:0000305" FT STRAND 211..215 FT /evidence="ECO:0007829|PDB:3QIJ" FT STRAND 221..225 FT /evidence="ECO:0007829|PDB:3QIJ" FT HELIX 232..243 FT /evidence="ECO:0007829|PDB:3QIJ" FT HELIX 248..250 FT /evidence="ECO:0007829|PDB:3QIJ" FT STRAND 251..258 FT /evidence="ECO:0007829|PDB:3QIJ" FT STRAND 261..264 FT /evidence="ECO:0007829|PDB:3QIJ" FT HELIX 271..274 FT /evidence="ECO:0007829|PDB:3QIJ" FT TURN 275..277 FT /evidence="ECO:0007829|PDB:1GG3" FT STRAND 281..288 FT /evidence="ECO:0007829|PDB:3QIJ" FT HELIX 293..295 FT /evidence="ECO:0007829|PDB:3QIJ" FT HELIX 299..314 FT /evidence="ECO:0007829|PDB:3QIJ" FT HELIX 322..337 FT /evidence="ECO:0007829|PDB:3QIJ" FT HELIX 342..345 FT /evidence="ECO:0007829|PDB:3QIJ" FT HELIX 350..352 FT /evidence="ECO:0007829|PDB:1GG3" FT STRAND 356..358 FT /evidence="ECO:0007829|PDB:3QIJ" FT HELIX 361..372 FT /evidence="ECO:0007829|PDB:3QIJ" FT HELIX 379..390 FT /evidence="ECO:0007829|PDB:3QIJ" FT TURN 394..397 FT /evidence="ECO:0007829|PDB:3QIJ" FT STRAND 399..404 FT /evidence="ECO:0007829|PDB:3QIJ" FT STRAND 410..415 FT /evidence="ECO:0007829|PDB:3QIJ" FT STRAND 417..424 FT /evidence="ECO:0007829|PDB:3QIJ" FT STRAND 427..433 FT /evidence="ECO:0007829|PDB:3QIJ" FT HELIX 434..436 FT /evidence="ECO:0007829|PDB:3QIJ" FT STRAND 437..443 FT /evidence="ECO:0007829|PDB:3QIJ" FT STRAND 446..451 FT /evidence="ECO:0007829|PDB:3QIJ" FT STRAND 454..458 FT /evidence="ECO:0007829|PDB:1GG3" FT STRAND 461..466 FT /evidence="ECO:0007829|PDB:3QIJ" FT HELIX 470..486 FT /evidence="ECO:0007829|PDB:3QIJ" SQ SEQUENCE 864 AA; 97017 MW; B466E7A9D7FBF12B CRC64; MTTEKSLVTE AENSQHQQKE EGEEAINSGQ QEPQQEESCQ TAAEGDNWCE QKLKASNGDT PTHEDLTKNK ERTSESRGLS RLFSSFLKRP KSQVSEEEGK EVESDKEKGE GGQKEIEFGT SLDEEIILKA PIAAPEPELK TDPSLDLHSL SSAETQPAQE ELREDPDFEI KEGEGLEECS KIEVKEESPQ SKAETELKAS QKPIRKHRNM HCKVSLLDDT VYECVVEKHA KGQDLLKRVC EHLNLLEEDY FGLAIWDNAT SKTWLDSAKE IKKQVRGVPW NFTFNVKFYP PDPAQLTEDI TRYYLCLQLR QDIVAGRLPC SFATLALLGS YTIQSELGDY DPELHGVDYV SDFKLAPNQT KELEEKVMEL HKSYRSMTPA QADLEFLENA KKLSMYGVDL HKAKDLEGVD IILGVCSSGL LVYKDKLRIN RFPWPKVLKI SYKRSSFFIK IRPGEQEQYE STIGFKLPSY RAAKKLWKVC VEHHTFFRLT STDTIPKSKF LALGSKFRYS GRTQAQTRQA SALIDRPAPH FERTASKRAS RSLDGAAAVD SADRSPRPTS APAITQGQVA EGGVLDASAK KTVVPKAQKE TVKAEVKKED EPPEQAEPEP TEAWKVEKTH IEVTVPTSNG DQTQKLAEKT EDLIRMRKKK RERLDGENIY IRHSNLMLED LDKSQEEIKK HHASISELKK NFMESVPEPR PSEWDKRLST HSPFRTLNIN GQIPTGEGPP LVKTQTVTIS DNANAVKSEI PTKDVPIVHT ETKTITYEAA QTDDNSGDLD PGVLLTAQTI TSETPSSTTT TQITKTVKGG ISETRIEKRI VITGDADIDH DQVLVQAIKE AKEQHPDMSV TKVVVHQETE IADE //