WD repeat-containing protein 1 (WDR1)

The protein contains 606 amino acids for an estimated molecular weight of 66194 Da.

 

Induces disassembly of actin filaments in conjunction with ADF/cofilin family proteins (PubMed:15629458, PubMed:27557945, PubMed:29751004). Enhances cofilin-mediated actin severing (By similarity). Involved in cytokinesis. Involved in chemotactic cell migration by restricting lamellipodial membrane protrusions (PubMed:18494608). Involved in myocardium sarcomere organization. Required for cardiomyocyte growth and maintenance (By similarity). Involved in megakaryocyte maturation and platelet shedding. Required for the establishment of planar cell polarity (PCP) during follicular epithelium development and for cell shape changes during PCP; the function seems to implicate cooperation with CFL1 and/or DSTN/ADF. Involved in the generation/maintenance of cortical tension (By similarity). Involved in assembly and maintenance of epithelial apical cell junctions and plays a role in the organization of the perijunctional actomyosin belt (PubMed:25792565). (updated: June 2, 2021)

Protein identification was indicated in the following studies:

  1. Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
  2. Lange and co-workers. (2014) Annotating N termini for the human proteome project: N termini and Nα-acetylation status differentiate stable cleaved protein species from degradation remnants in the human erythrocyte proteome. J Proteome Res. 13(4), 2028-2044.
  3. Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
  4. Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
  5. D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.

Methods

The following articles were analysed to gather the proteome content of erythrocytes.

The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.

PublicationIdentification 1Uniprot mapping 2Not mapped /
Obsolete		TrEMBLSwiss-Prot
Goodman (2013)2289 (gene list)227853205992269
Lange (2014)123412347281224
Hegedus (2015)2638262202352387
Wilson (2016)165815281702911068
d'Alessandro (2017)18261817201815
Bryk (2017)20902060101081942
Chu (2018)18531804553621387

1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry

The compilation of older studies can be retrieved from the Red Blood Cell Collection database.

The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.

No sequence conservation computed yet.
Protein sequence (FASTA)
Protein coevolution profile (FreeContact)
Multiple Sequence Alignment (Muscle)

This protein is annotated as membranous in Gene Ontology.


Interpro domains
Total structural coverage: 98%
Model score: 40
MODL_MODELLER-9.18

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VariantDescription
dbSNP:rs13441
PFITS; unknown pathological significance
PFITS; unknown pathological significance
PFITS; unknown pathological significance; almost complete loss of protein expression in peripheral blood mononuclear cells
PFITS; unknown pathological significance
PFITS; contrary to wild-type, which shows a uniform distribution throughout the cytoplasm, forms cytoplasmic aggregates, which contain pyrin/MEFV, hen
PFITS; unknown pathological significance
PFITS; unknown pathological significance; almost complete loss of protein expression in peripheral blood mononuclear cells
PFITS; almost complete loss of protein expression in peripheral blood mononuclear cells

The reference OMIM entry for this protein is 604734

Wd repeat-containing protein 1; wdr1
Actin-interacting protein 1; aip1

CLONING

WD repeats are approximately 30- to 40-amino acid domains containing several conserved residues, including a trp-asp at the C-terminal end. These domains are involved in protein-protein interactions. WD repeats have been found in heterotrimeric G proteins and regulatory proteins, such as those involved in cell division, cell-fate determination, gene transcription, mRNA modification, transmembrane signaling, and vesicle fusion. WD repeats typically occur multiple times within a protein. To identify processes that may play a role in avian inner ear repair, Adler et al. (1999) used differential display of mRNA to isolate genes that are upregulated in the avian basilar papilla after acoustic overstimulation. They identified a chicken gene encoding a protein composed almost entirely of 9 WD repeats; thus, they named the protein 'WD repeat protein-1' (Wdr1). By searching an EST database using the sequence of a chicken Wdr1 cDNA as the query, Adler et al. (1999) identified human and mouse orthologs of WDR1. Like chicken Wdr1, the predicted human and mouse WDR1 proteins contain 9 WD repeats. The deduced 606-amino acid human WDR1 protein shares 95% amino acid sequence identity with mouse Wdr1 and 86% identity with chicken Wdr1. Chicken Wdr1 has high sequence identity to S. cerevisiae and P. polycephalum WD repeat-containing proteins that bind actin, suggesting that WDR1 proteins may interact with actin. Adler et al. (1999) deposited the sequence of a human WDR1 splicing variant that encodes a protein lacking 72 C-terminal amino acids into GenBank (GENBANK AF020260).

MAPPING

By radiation hybrid mapping, Adler et al. (1999) mapped the WDR1 gene to chromosome 4p. They noted that an EST cluster composed of sequences identical to the WDR1 gene had been mapped between 22 and 24 cM from the telomere of chromosome 4p.

ANIMAL MODEL

By generating an allelic series for mouse Wdr1, Kile et al. (2007) found that reductions in Wdr1 function produced a phenotype gradient. Severe loss of function caused embryonic lethality, whereas hypomorphic alleles caused macrothrombocytopenia due to defective megakaryocyte maturation and autoinflammatory disease due to massive neutrophil infiltration in lesions. Fluorescence and electron microscopy showed that Wdr1 was essential for normal motility and actin depolymerization kinetics, probably through interaction with cofilin (CFL1; 601442). Kile et al. (2007) concluded that WDR1 is required for megakaryocytes and neutrophils and that cofilin-mediated actin dynamics are important to development and function of both cell types. ... More on the omim web site

Subscribe to this protein entry history

July 1, 2021: Protein entry updated
Automatic update: Entry updated from uniprot information.

Feb. 10, 2018: Protein entry updated
Automatic update: Entry updated from uniprot information.

Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated

Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated

June 20, 2017: Protein entry updated
Automatic update: comparative model was added.

March 16, 2016: Protein entry updated
Automatic update: OMIM entry 604734 was added.