EPB41_HUMAN
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 03-AUG-2022, entry version 236.
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.
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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; CCDS332.1; -. [P11171-3]
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. [P11171-5]
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; 92.
DR CORUM; P11171; -.
DR DIP; DIP-17032N; -.
DR IntAct; P11171; 24.
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-Linked glycan (2 sites).
DR GlyGen; P11171; 4 sites, 1 O-linked glycan (4 sites).
DR iPTMnet; P11171; -.
DR MetOSite; P11171; -.
DR PhosphoSitePlus; P11171; -.
DR BioMuta; EPB41; -.
DR DMDM; 90101808; -.
DR EPD; P11171; -.
DR jPOST; P11171; -.
DR MassIVE; P11171; -.
DR MaxQB; P11171; -.
DR PaxDb; P11171; -.
DR PeptideAtlas; P11171; -.
DR PRIDE; 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 Antibodypedia; 30998; 361 antibodies from 30 providers.
DR DNASU; 2035; -.
DR Ensembl; ENST00000343067.9; ENSP00000345259.4; ENSG00000159023.22. [P11171-1]
DR Ensembl; ENST00000347529.7; ENSP00000290100.6; ENSG00000159023.22. [P11171-5]
DR Ensembl; ENST00000373797.2; ENSP00000362903.1; ENSG00000159023.22. [P11171-7]
DR Ensembl; ENST00000373798.5; ENSP00000362904.1; ENSG00000159023.22. [P11171-1]
DR Ensembl; ENST00000373800.7; ENSP00000362906.3; ENSG00000159023.22. [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 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; EHHTFFX; -.
DR OrthoDB; 1011028at2759; -.
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; 15 hits in 1085 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 175 other tissues.
DR ExpressionAtlas; P11171; baseline and differential.
DR Genevisible; P11171; HS.
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: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:0008022; F:protein C-terminus binding; IMP:CAFA.
DR GO; GO:0047485; F:protein N-terminus binding; IMP:CAFA.
DR GO; GO:0030507; F:spectrin binding; TAS:BHF-UCL.
DR GO; GO:0005200; F:structural constituent of cytoskeleton; TAS:ProtInc.
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:0051924; P:regulation of calcium ion transport; ISS:UniProtKB.
DR GO; GO:0008360; P:regulation of cell shape; IMP:CAFA.
DR GO; GO:1904478; P:regulation of intestinal absorption; ISS:UniProtKB.
DR CDD; cd14473; FERM_B-lobe; 1.
DR DisProt; DP00678; -.
DR Gene3D; 1.20.80.10; -; 1.
DR Gene3D; 2.30.29.30; -; 1.
DR InterPro; IPR008379; Band_4.1_C.
DR InterPro; IPR019749; Band_41_domain.
DR InterPro; IPR021187; Band_41_protein_chordates.
DR InterPro; IPR000798; Ez/rad/moesin-like.
DR InterPro; IPR014847; FERM-adjacent.
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:SF12; PTHR23280:SF12; 2.
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 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; SSF47031; SSF47031; 1.
DR SUPFAM; SSF54236; SSF54236; 1.
DR PROSITE; PS00660; FERM_1; 1.
DR PROSITE; PS00661; FERM_2; 1.
DR PROSITE; PS50057; FERM_3; 1.
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
