Human Gene EPB41 (uc001brm.2)
  Description: Homo sapiens erythrocyte membrane protein band 4.1 (elliptocytosis 1, RH-linked) (EPB41), transcript variant 1, mRNA.
RefSeq Summary (NM_001166005): The protein encoded by this gene, together with spectrin and actin, constitute the red cell membrane cytoskeletal network. This complex plays a critical role in erythrocyte shape and deformability. Mutations in this gene are associated with type 1 elliptocytosis (EL1). Alternatively spliced transcript variants encoding different isoforms have been described for this gene.[provided by RefSeq, Oct 2009].
Transcript (Including UTRs)
   Position: hg19 chr1:29,213,603-29,446,558 Size: 232,956 Total Exon Count: 21 Strand: +
Coding Region
   Position: hg19 chr1:29,313,950-29,442,309 Size: 128,360 Coding Exon Count: 19 

Page IndexSequence and LinksUniProtKB CommentsGenetic AssociationsMalaCardsCTD
Gene AllelesRNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther Species
GO AnnotationsmRNA DescriptionsPathwaysOther NamesModel InformationMethods
Data last updated at UCSC: 2013-06-14

-  Sequence and Links to Tools and Databases
Genomic Sequence (chr1:29,213,603-29,446,558)mRNA (may differ from genome)Protein (864 aa)
Gene SorterGenome BrowserOther Species FASTAVisiGeneGene interactionsTable Schema
AlphaFoldBioGPSCGAPEnsemblEntrez GeneExonPrimer

-  Comments and Description Text from UniProtKB
  ID: 41_HUMAN
DESCRIPTION: RecName: Full=Protein 4.1; Short=P4.1; AltName: Full=4.1R; AltName: Full=Band 4.1; AltName: Full=EPB4.1;
FUNCTION: Protein 4.1 is a major structural element of the erythrocyte membrane skeleton. It plays a key role in regulating membrane physical properties of mechanical stability and deformability by stabilizing spectrin-actin interaction. Recruits DLG1 to membranes.
SUBUNIT: Binds with a high affinity to glycophorin and with lower affinity to band III protein. Associates with the nuclear mitotic apparatus. Binds calmodulin, CENPJ and DLG1. Also found to associate with contractile apparatus and tight junctions.
SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton. Cytoplasm, cell cortex. Nucleus.
PTM: Phosphorylated at multiple sites by different protein kinases and each phosphorylation event selectively modulates the protein's functions.
PTM: Phosphorylation on Tyr-660 reduces the ability of 4.1 to promote the assembly of the spectrin/actin/4.1 ternary complex.
PTM: O-glycosylated; contains N-acetylglucosamine side chains in the C-terminal domain.
DISEASE: Defects in EPB41 are the cause of elliptocytosis type 1 (EL1) [MIM:611804]. EL1 is a Rhesus-linked form of hereditary elliptocytosis, a genetically heterogeneous, autosomal dominant, hematologic disorder. It is characterized by variable hemolytic anemia and elliptical or oval red cell shape.
DISEASE: Defects in EPB41 are a cause of hereditary pyropoikilocytosis (HPP) [MIM:266140]. HPP is an autosomal recessive hematologic disorder characterized by hemolytic anemia, microspherocytosis, poikilocytosis, and an unusual thermal sensitivity of red cells.
SIMILARITY: Contains 1 FERM domain.

-  Genetic Association Studies of Complex Diseases and Disorders
  Genetic Association Database (archive): EPB41
CDC HuGE Published Literature: EPB41
Positive Disease Associations: Sleep
Related Studies:
  1. Sleep
    Daniel J Gottlieb et al. BMC medical genetics 2007, Genome-wide association of sleep and circadian phenotypes., BMC medical genetics. [PubMed 17903308]
    This analysis confirms prior reports of significant heritability of sleepiness, usual bedtime, and usual sleep duration. Several genetic loci with suggestive linkage to these traits are identified, including linkage peaks containing circadian clock-related genes. Association tests identify NPSR1 and PDE4D as possible mediators of bedtime and sleepiness.

-  MalaCards Disease Associations
  MalaCards Gene Search: EPB41
Diseases sorted by gene-association score: elliptocytosis-1* (1038), hereditary elliptocytosis* (448), serous labyrinthitis (17), purulent labyrinthitis (16), hereditary spherocytosis (9), artemis deficiency (7), spinal cord ependymoma (7), malignant ependymoma (5), norum disease (4)
* = Manually curated disease association

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene

+  Common Gene Haplotype Alleles
  Press "+" in the title bar above to open this section.

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 17.91 RPKM in Brain - Cerebellar Hemisphere
Total median expression: 149.36 RPKM

View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -55.40127-0.436 Picture PostScript Text
3' UTR -1097.843234-0.339 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR008379 - Band_4.1_C
IPR019749 - Band_41_domain
IPR019750 - Band_41_fam
IPR021187 - Band_41_protein
IPR000798 - Ez/rad/moesin
IPR014847 - FERM-adjacent
IPR014352 - FERM/acyl-CoA-bd_prot_3-hlx
IPR019748 - FERM_central
IPR019747 - FERM_CS
IPR000299 - FERM_domain
IPR018979 - FERM_N
IPR018980 - FERM_PH-like_C
IPR011993 - PH_like_dom
IPR007477 - SAB

Pfam Domains:
PF00373 - FERM central domain
PF04382 - SAB domain
PF05902 - 4.1 protein C-terminal domain (CTD)
PF08736 - FERM adjacent (FA)
PF09379 - FERM N-terminal domain
PF09380 - FERM C-terminal PH-like domain

SCOP Domains:
47031 - Second domain of FERM
50729 - PH domain-like
54236 - Ubiquitin-like

Protein Data Bank (PDB) 3-D Structure
MuPIT help
1GG3 - X-ray MuPIT 2RQ1 - NMR MuPIT 3QIJ - X-ray MuPIT

ModBase Predicted Comparative 3D Structure on P11171
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
No orthologNo orthologNo orthologNo orthologNo orthologNo ortholog
Gene Details     
Gene Sorter     

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0003779 actin binding
GO:0005198 structural molecule activity
GO:0005200 structural constituent of cytoskeleton
GO:0005515 protein binding
GO:0005516 calmodulin binding
GO:0005545 1-phosphatidylinositol binding
GO:0008022 protein C-terminus binding
GO:0008092 cytoskeletal protein binding
GO:0030507 spectrin binding
GO:0047485 protein N-terminus binding
GO:0051219 phosphoprotein binding

Biological Process:
GO:0007049 cell cycle
GO:0008360 regulation of cell shape
GO:0030036 actin cytoskeleton organization
GO:0030866 cortical actin cytoskeleton organization
GO:0031032 actomyosin structure organization
GO:0032092 positive regulation of protein binding
GO:0051301 cell division
GO:0065003 macromolecular complex assembly
GO:1904778 positive regulation of protein localization to cell cortex

Cellular Component:
GO:0005634 nucleus
GO:0005737 cytoplasm
GO:0005829 cytosol
GO:0005856 cytoskeleton
GO:0005886 plasma membrane
GO:0005938 cell cortex
GO:0009898 cytoplasmic side of plasma membrane
GO:0014069 postsynaptic density
GO:0014731 spectrin-associated cytoskeleton
GO:0016020 membrane
GO:0030054 cell junction
GO:0030863 cortical cytoskeleton
GO:0032991 macromolecular complex
GO:0099738 cell cortex region

-  Descriptions from all associated GenBank mRNAs
  AB209649 - Homo sapiens mRNA for Protein 4.1 variant protein.
M14993 - Human structural protein 4.1 mRNA, complete cds.
M61733 - Homo sapiens erythroid membrane protein 4.1 mRNA, complete cds.
J03796 - Human erythroid isoform protein 4.1 mRNA, complete cds.
BC039079 - Homo sapiens erythrocyte membrane protein band 4.1 (elliptocytosis 1, RH-linked), mRNA (cDNA clone MGC:34494 IMAGE:5167140), complete cds.
AK310655 - Homo sapiens cDNA, FLJ17697.
EU176300 - Synthetic construct Homo sapiens clone IMAGE:100006409; FLH180168.01X; RZPDo839E03251D erythrocyte membrane protein band 4.1 (elliptocytosis 1, RH-linked) (EPB41) gene, encodes complete protein.
AB527230 - Synthetic construct DNA, clone: pF1KB4879, Homo sapiens EPB41 gene for erythrocyte membrane protein band 4.1, without stop codon, in Flexi system.
AF156225 - Homo sapiens protein 4.1 (EPB4.1) mRNA, complete cds.
BC096104 - Homo sapiens erythrocyte membrane protein band 4.1 (elliptocytosis 1, RH-linked), mRNA (cDNA clone IMAGE:40001728), partial cds.
BC096105 - Homo sapiens erythrocyte membrane protein band 4.1 (elliptocytosis 1, RH-linked), mRNA (cDNA clone MGC:116747 IMAGE:40001729), complete cds.
BC113841 - Homo sapiens erythrocyte membrane protein band 4.1 (elliptocytosis 1, RH-linked), mRNA (cDNA clone IMAGE:40001733), partial cds.
BC114450 - Homo sapiens erythrocyte membrane protein band 4.1 (elliptocytosis 1, RH-linked), mRNA (cDNA clone IMAGE:40001732), partial cds.
KJ901407 - Synthetic construct Homo sapiens clone ccsbBroadEn_10801 EPB41 gene, encodes complete protein.
JD357515 - Sequence 338539 from Patent EP1572962.
JD098166 - Sequence 79190 from Patent EP1572962.
JD364004 - Sequence 345028 from Patent EP1572962.
JD362317 - Sequence 343341 from Patent EP1572962.
JD492452 - Sequence 473476 from Patent EP1572962.
JD303864 - Sequence 284888 from Patent EP1572962.
JD078886 - Sequence 59910 from Patent EP1572962.
JD446314 - Sequence 427338 from Patent EP1572962.
JD316760 - Sequence 297784 from Patent EP1572962.
JD042406 - Sequence 23430 from Patent EP1572962.
JD063405 - Sequence 44429 from Patent EP1572962.
JD036416 - Sequence 17440 from Patent EP1572962.
AK299093 - Homo sapiens cDNA FLJ50624 complete cds.
AK299736 - Homo sapiens cDNA FLJ50645 complete cds.
AK307816 - Homo sapiens cDNA, FLJ97764.
AL833483 - Homo sapiens mRNA; cDNA DKFZp686E1929 (from clone DKFZp686E1929).
JD286233 - Sequence 267257 from Patent EP1572962.
JD070093 - Sequence 51117 from Patent EP1572962.
JD346865 - Sequence 327889 from Patent EP1572962.
JD224121 - Sequence 205145 from Patent EP1572962.
JD493236 - Sequence 474260 from Patent EP1572962.
JD307689 - Sequence 288713 from Patent EP1572962.
JD296780 - Sequence 277804 from Patent EP1572962.
JD235346 - Sequence 216370 from Patent EP1572962.
JD509378 - Sequence 490402 from Patent EP1572962.
JD234485 - Sequence 215509 from Patent EP1572962.
JD038463 - Sequence 19487 from Patent EP1572962.
JD552970 - Sequence 533994 from Patent EP1572962.
JD249368 - Sequence 230392 from Patent EP1572962.
JD243040 - Sequence 224064 from Patent EP1572962.
JD245045 - Sequence 226069 from Patent EP1572962.
JD562479 - Sequence 543503 from Patent EP1572962.
JD524831 - Sequence 505855 from Patent EP1572962.
JD412931 - Sequence 393955 from Patent EP1572962.
JD302683 - Sequence 283707 from Patent EP1572962.
JD048715 - Sequence 29739 from Patent EP1572962.
JD286310 - Sequence 267334 from Patent EP1572962.
JD264933 - Sequence 245957 from Patent EP1572962.
JD298807 - Sequence 279831 from Patent EP1572962.
JD394094 - Sequence 375118 from Patent EP1572962.
JD219361 - Sequence 200385 from Patent EP1572962.
JD192714 - Sequence 173738 from Patent EP1572962.
JD321957 - Sequence 302981 from Patent EP1572962.
JD255955 - Sequence 236979 from Patent EP1572962.
JD426750 - Sequence 407774 from Patent EP1572962.
JD489081 - Sequence 470105 from Patent EP1572962.
JD514021 - Sequence 495045 from Patent EP1572962.
JD069948 - Sequence 50972 from Patent EP1572962.
JD397261 - Sequence 378285 from Patent EP1572962.
JD415211 - Sequence 396235 from Patent EP1572962.
JD072152 - Sequence 53176 from Patent EP1572962.
JD207046 - Sequence 188070 from Patent EP1572962.
JD087842 - Sequence 68866 from Patent EP1572962.
AK172796 - Homo sapiens cDNA FLJ23957 fis, clone HEP12337.
JD503744 - Sequence 484768 from Patent EP1572962.
JD061570 - Sequence 42594 from Patent EP1572962.
JD528916 - Sequence 509940 from Patent EP1572962.
JD214240 - Sequence 195264 from Patent EP1572962.
BC009063 - Homo sapiens erythrocyte membrane protein band 4.1 (elliptocytosis 1, RH-linked), mRNA (cDNA clone IMAGE:3873720), partial cds.
JD242009 - Sequence 223033 from Patent EP1572962.
JD282997 - Sequence 264021 from Patent EP1572962.
JD283852 - Sequence 264876 from Patent EP1572962.
JD485265 - Sequence 466289 from Patent EP1572962.
JD450083 - Sequence 431107 from Patent EP1572962.
JD298560 - Sequence 279584 from Patent EP1572962.
JD235149 - Sequence 216173 from Patent EP1572962.

-  Biochemical and Signaling Pathways
  KEGG - Kyoto Encyclopedia of Genes and Genomes
hsa04530 - Tight junction

BioCarta from NCI Cancer Genome Anatomy Project
h_PDZsPathway - Synaptic Proteins at the Synaptic Junction

Reactome (by CSHL, EBI, and GO)

Protein P11171 (Reactome details) participates in the following event(s):

R-HSA-6797553 Protein 4.1 binds CASK
R-HSA-6797568 NRXNs bind CASK:Protein 4.1
R-HSA-6794361 Neurexins and neuroligins
R-HSA-6794362 Protein-protein interactions at synapses
R-HSA-112316 Neuronal System

-  Other Names for This Gene
  Alternate Gene Symbols: 41_HUMAN, B1ALH8, B1ALH9, D3DPM9, D3DPN0, E41P, NM_001166005, NP_001159477, P11171, P11176, Q14245, Q5TB35, Q5VXN8, Q8IXV9, Q9Y578, Q9Y579
UCSC ID: uc001brm.2
RefSeq Accession: NM_001166005
Protein: P11171 (aka 41_HUMAN)
CCDS: CCDS53288.1

-  Gene Model Information
category: coding nonsense-mediated-decay: no RNA accession: NM_001166005.1
exon count: 21CDS single in 3' UTR: no RNA size: 5961
ORF size: 2595CDS single in intron: no Alignment % ID: 100.00
txCdsPredict score: 4661.00frame shift in genome: no % Coverage: 99.92
has start codon: yes stop codon in genome: no # of Alignments: 1
has end codon: yes retained intron: no # AT/AC introns 0
selenocysteine: no end bleed into intron: 0# strange splices: 0
Click here for a detailed description of the fields of the table above.

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.