Ankyrin-1 (ANK1)

The protein contains 1881 amino acids for an estimated molecular weight of 206265 Da.

 

Attaches integral membrane proteins to cytoskeletal elements; binds to the erythrocyte membrane protein band 4.2, to Na-K ATPase, to the lymphocyte membrane protein GP85, and to the cytoskeletal proteins fodrin, tubulin, vimentin and desmin. Erythrocyte ankyrins also link spectrin (beta chain) to the cytoplasmic domain of the erythrocytes anion exchange protein; they retain most or all of these binding functions.', 'Together with obscurin in skeletal muscle may provide a molecular link between the sarcoplasmic reticulum and myofibrils. (updated: Dec. 11, 2019)

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. Wilson and co-workers. (2016) Comparison of the Proteome of Adult and Cord Erythroid Cells, and Changes in the Proteome Following Reticulocyte Maturation. Mol Cell Proteomics. 15(6), 1938-1946.
  5. Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
  6. D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
  7. Chu and co-workers. (2018) Quantitative mass spectrometry of human reticulocytes reveal proteome-wide modifications during maturation. Br J Haematol. 180(1), 118-133.

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: 33%
Model score: 0
No model available.

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VariantDescription
empty
SPH1
a breast cancer sample; somatic mutation
SPH1
Brueggen
dbSNP:rs11778936
empty
dbSNP:rs34523608
empty
dbSNP:rs758454168
SPH1
dbSNP:rs35213384
dbSNP:rs504465
dbSNP:rs486770
empty
dbSNP:rs10093583
empty
dbSNP:rs1060130
Duesseldorf

The reference OMIM entry for this protein is 182900

Spherocytosis, type 1; sph1
Spherocytosis, hereditary, 1; hs1
Sph; hs

A number sign (#) is used with this entry because of evidence that spherocytosis type 1 is caused by heterozygous, compound heterozygous, or homozygous mutation in the gene encoding ankyrin (ANK1; 612641) on chromosome 8p11.

DESCRIPTION

Hereditary spherocytosis refers to a group of heterogeneous disorders that are characterized by the presence of spherical-shaped erythrocytes (spherocytes) on the peripheral blood smear. The disorders are characterized clinically by anemia, jaundice, and splenomegaly, with variable severity. Common complications include cholelithiasis, hemolytic episodes, and aplastic crises (review by Perrotta et al., 2008). Elgsaeter et al. (1986) gave an extensive review of the molecular basis of erythrocyte shape with a discussion of the role of spectrin and other proteins such as ankyrin, actin (102630), band 4.1 (130500), and band 3 (109270), all of which is relevant to the understanding of spherocytosis and elliptocytosis (see 611904). See Delaunay (2007) for a discussion of the molecular basis of hereditary red cell membrane disorders. - Genetic Heterogeneity of Hereditary Spherocytosis Also see spherocytosis type 2 (see 182870), caused by mutation in the SPTB gene (182870) on chromosome 14q22-q23; spherocytosis type 3 (270970), caused by mutation in the SPTBA gene (182860) on chromosome 1q21; spherocytosis type 4 (612653), caused by mutation in the SLC4A1 gene (109270) on chromosome 17q21-q22; and spherocytosis type 5 (612690), caused by mutation in the EPB42 gene (177070) on chromosome 15q15.

CLINICAL FEATURES

MacKinney et al. (1962) and Morton et al. (1962) studied 26 families. They concluded that after the initial case in a family has been identified, 4 tests suffice for the diagnosis in other family members: smear, reticulocyte count, hemoglobin, and bilirubin. The fragility test (increased osmotic fragility characterizes the disease) is unnecessary after the diagnosis has been made in the proband. It was estimated that the prevalence is 2.2 per 10,000, that the mutation rate is 0.000022 and that about one-fourth of cases are sporadic. No evidence of reproductive compensation or of increased prenatal and infant mortality was found. No enzyme defect was identified (Miwa et al., 1962). Several observations suggest that more than one type of hereditary spherocytosis exists in man (review by Zail et al., 1967). Barry et al. (1968) pointed out that hemochromatosis is a serious complication of untreated spherocytosis. Fargion et al. (1986) described 2 brothers who were thought to be heterozygous for the hemochromatosis gene and who also were affected with hereditary spherocytosis. Both had severe iron overload whereas all relatives without hereditary spherocytosis, including those with HLA haplotypes identical to those of the 2 brothers, had normal iron stores. Montes-Cano et al. (2003) reported a similar situation in a Spanish family: 3 members of different generations were diagnosed with hereditary spherocytosis and 1 of them, 44 years of age, presented iron overload with hepatic deposit and required treatment with periodic phlebotomies. Other members of the family showed normal values in iron metabolism. The patient with iron overload was a compound heterozygote for the H63D (235200.0002) and C282Y (235200.0001) mutations in the HFE gene. In a family with 6 persons affected in 3 generations, Wiley and Firkin (1970) found a form of hereditary spherocytosis with unusual features; other repor ... More on the omim web site

Subscribe to this protein entry history

Jan. 22, 2020: Protein entry updated
Automatic update: Entry updated from uniprot information.

June 7, 2019: 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

Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated

March 16, 2016: Protein entry updated
Automatic update: OMIM entry 182900 was added.