Small integral membrane protein 1 (SMIM1)

The protein contains 78 amino acids for an estimated molecular weight of 8749 Da.

 

Regulator of red blood cell formation. (updated: Jan. 31, 2018)

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, is annotated as membranous in UniProt, is predicted to be membranous by TOPCONS.

Topcons

Interpro domains
Total structural coverage: 100%
Model score: 94
MODL_ROSETTA-3.4
MODL_MODELLER-9.18
MODL_I-TASSER-2.1

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VariantDescription
Found in Vel-negative population
Found in Vel-negative population; unknown pathological significance; heterozygous with the 17-nucleotide frameshift deletion

No binding partner found

The reference OMIM entry for this protein is 615242

Small integral membrane protein 1; smim1

CLONING

Using microarrays for SNP profiling of 20 individuals with the Vel-negative blood group phenotype, followed by transcriptional network modeling, Storry et al. (2013) identified SMIM1 as a candidate for the gene underlying Vel antigen expression. By 5-prime and 3-prime RACE of Vel-positive blood mRNA, they cloned SMIM1. The deduced 78-amino acid protein has a calculated molecular mass of about 8.7 kD. SMIM1 was predicted to be a type I transmembrane protein with an approximately 50-amino acid extracellular domain containing several potential sites for O-glycosylation. The transmembrane domain contains a potential GxxxG helix-helix dimerization motif. Analysis of human microarray profiles revealed highest SMIM1 expression in CD34 (142230)-positive erythroid cultures and in bone marrow, followed by salivary gland and testis. Much lower expression was detected in several other tissues, including brain. Western blot analysis of Vel-positive blood and glycophorin A (GPA; 111300)-positive bone marrow detected SMIM1 as a monomer with an apparent molecular mass of 9 to 10 kD and as reduction-resistant homodimers of about 20 kD, consistent with the presence of the transmembrane dimerization motif. Orthologs of SMIM1 were detected in 45 other species from primates to sea squirt. Flow cytometry detected cell surface expression of SMIM1 in transfected K562 erythroleukemia cells.

GENE STRUCTURE

Storry et al. (2013) determined that the SMIM1 gene contains 4 exons. Exons 1 and 2 are noncoding, and intron 2 contains a GATA motif conserved in primates and rodents, but not in dog, bovine, or elephant.

MAPPING

By genomic sequence analysis, Storry et al. (2013) mapped the SMIM1 gene to chromosome 1p36.

GENE FUNCTION

Ballif et al. (2013) identified SMIM1 as the Vel antigen on red blood cells. A purified anti-Vel antibody detected a band of about 32 kD in red blood cell membranes extracted from Vel-positive individuals. Electrophoresis studies showed that the Vel antigen migrated at about 18 kD under reducing conditions, suggesting that it forms a molecular homodimer via disulfide bonds. Mass spectrometry, peptide sequencing, and BLAST analysis suggested that the SMIM1 encodes the Vel antigen.

MOLECULAR GENETICS

- Vel Blood Group System By SNP mapping followed by candidate gene sequencing of 20 individuals with the Vel-negative blood group phenotype (615264), Storry et al. (2013) identified a homozygous 17-bp deletion in the SMIM1 gene (615242.0001) in all individuals. The findings were confirmed in 15 additional Vel-negative individuals, predominantly of European descent. Direct genotyping identified 30 heterozygous deletion carriers among 520 Swedish blood donors. The deletion was not found in the 1000 Genomes Project data, but was found in the National Heart, Lung, and Blood Institute (NHLBI) Exome Sequencing Project (ESP) database: in 57 of 5,763 European Americans and 6 of 3,198 in African Americans, yielding heterozygote frequencies of about 1 in 50 and 1 in 267, respectively. By exome sequencing of 5 individuals negative for the Vel antigen, Cvejic et al. (2013) found that 4 were homozygous and 1 was heterozygous for a 17-bp frameshift deletion in the SMIM1 gene. Combined with a follow-up study of additional Vel-negative individuals, a total of 63 of 69 Vel-negative individuals were found to be homozygous for the deletion. Five individuals classified as Vel-negative were heterozygous for th ... More on the omim web site

The reference OMIM entry for this protein is 615264

Blood group, vel system; vel vel-null phenotype, included

A number sign (#) is used with this entry because the Vel blood group system is determined by the SMIM1 gene (615242), which encodes the Vel antigen, on chromosome 1p36.

DESCRIPTION

The Vel blood group system is defined by the presence of the Vel antigen on red blood cells. Vel is a high frequency antigen that shows variable strength, ranging from strong to weak. The rare Vel-negative blood type is inherited as an autosomal recessive trait and is typically unveiled when Vel-negative individuals develop anti-Vel antibodies after transfusion or pregnancy; Vel alloantibodies are never 'naturally occurring.' Individuals with anti-Vel antibodies may develop severe acute hemolytic transfusion reactions when transfused with Vel-positive blood. Individuals negative for the Vel antigen are rare and are required for the safe transfusion of patients with antibodies to Vel (summary by Daniels, 2002; Storry et al., 2013; Cvejic et al., 2013; Ballif et al., 2013).

CLINICAL FEATURES

Sussman and Miller (1952) first described the Vel-negative blood group phenotype in a 66-year-old woman who developed a severe acute intravascular hemolytic episode after a blood transfusion due to antibodies against a newly defined antigen named 'Vel.' She had a history of 3 pregnancies and colon cancer requiring transfusions. Levine et al. (1961) reported a family in which 7 individuals spanning 3 generations were negative for the Vel red blood cell antigen. The proband was a woman who had been pregnant 6 times and received blood transfusions at least twice. She developed a severe transfusion reaction and was found to carry the Vel antibody in her serum, whereas her red cells lacked the Vel antigen. The other Vel-negative family members did not have serum anti-Vel antibodies. Subsequent reports of hemolytic reactions after transfusion of Vel-positive RBCs to Vel-negative individuals with antibody to Vel, as well as hemolytic disease of the newborns of Vel-negative mothers, established Vel as a clinically important blood group antigen (summary by Storry et al., 2013).

MAPPING

By SNP analysis of 20 Vel-negative individuals primarily of Swedish origin, including 5 individuals from 2 families, Storry et al. (2013) identified a 97-kb haplotype block on chromosome 1p36 that segregated with the phenotype. A homozygous founder mutation was postulated.

MOLECULAR GENETICS

By SNP mapping followed by candidate gene sequencing of 20 Vel-negative individuals, Storry et al. (2013) identified a homozygous 17-bp deletion in the SMIM1 gene (615242.0001) in all individuals. The findings were confirmed in 15 additional Vel-negative individuals, predominantly of European descent. Direct genotyping identified 30 heterozygous deletion carriers among 520 Swedish blood donors. The deletion was not found in the 1000 Genomes Project data, but was found in the National Heart, Lung, and Blood Institute (NHLBI) Exome Sequencing Project (ESP) database: 57 of 5,763 European Americans and 6 of 3,198 in African Americans, yielding heterozygote frequencies of about 1 in 50 and 1 in 267, respectively. By exome sequencing of 5 individuals negative for the Vel antigen, Cvejic et al. (2013) found that 4 were homozygous and 1 was heterozygous for a 17-bp frameshift deletion in the SMIM1 gene. Combined with a follow-up study of additional Vel-negative individuals, a total of 63 of 69 Vel-negative individuals were found to be homozygous for the deletion. Five individua ... More on the omim web site

Subscribe to this protein entry history

July 2, 2021: Protein entry updated
Automatic update: OMIM entry 615242 was added.

July 2, 2021: Protein entry updated
Automatic update: OMIM entry 615264 was added.

April 12, 2021: Protein entry updated
Automatic update: OMIM entry 615242 was added.

April 12, 2021: Protein entry updated
Automatic update: OMIM entry 615264 was added.

Feb. 17, 2021: Protein entry updated
Automatic update: OMIM entry 615242 was added.

Feb. 17, 2021: Protein entry updated
Automatic update: OMIM entry 615264 was added.

Oct. 21, 2020: Protein entry updated
Automatic update: OMIM entry 615242 was added.

Oct. 21, 2020: Protein entry updated
Automatic update: OMIM entry 615264 was added.

Aug. 25, 2020: Protein entry updated
Automatic update: OMIM entry 615242 was added.

Aug. 25, 2020: Protein entry updated
Automatic update: OMIM entry 615264 was added.

June 30, 2020: Protein entry updated
Automatic update: OMIM entry 615242 was added.

June 30, 2020: Protein entry updated
Automatic update: OMIM entry 615264 was added.

April 26, 2020: Protein entry updated
Automatic update: OMIM entry 615242 was added.

April 26, 2020: Protein entry updated
Automatic update: OMIM entry 615264 was added.

March 4, 2020: Protein entry updated
Automatic update: OMIM entry 615242 was added.

March 4, 2020: Protein entry updated
Automatic update: OMIM entry 615264 was added.

Jan. 23, 2020: Protein entry updated
Automatic update: OMIM entry 615242 was added.

Jan. 23, 2020: Protein entry updated
Automatic update: OMIM entry 615264 was added.

Dec. 3, 2019: Protein entry updated
Automatic update: OMIM entry 615242 was added.

Dec. 3, 2019: Protein entry updated
Automatic update: OMIM entry 615264 was added.

Oct. 28, 2019: Protein entry updated
Automatic update: OMIM entry 615242 was added.

Oct. 28, 2019: Protein entry updated
Automatic update: OMIM entry 615264 was added.

Sept. 23, 2019: Protein entry updated
Automatic update: OMIM entry 615242 was added.

Sept. 23, 2019: Protein entry updated
Automatic update: OMIM entry 615264 was added.

Aug. 21, 2019: Protein entry updated
Automatic update: OMIM entry 615242 was added.

Aug. 21, 2019: Protein entry updated
Automatic update: OMIM entry 615264 was added.

July 5, 2019: Protein entry updated
Automatic update: OMIM entry 615242 was added.

July 5, 2019: Protein entry updated
Automatic update: OMIM entry 615264 was added.

June 7, 2019: Protein entry updated
Automatic update: OMIM entry 615242 was added.

June 7, 2019: Protein entry updated
Automatic update: OMIM entry 615264 was added.

May 12, 2019: Protein entry updated
Automatic update: OMIM entry 615242 was added.

May 12, 2019: Protein entry updated
Automatic update: OMIM entry 615264 was added.

April 2, 2019: Protein entry updated
Automatic update: OMIM entry 615242 was added.

April 2, 2019: Protein entry updated
Automatic update: OMIM entry 615264 was added.

Feb. 23, 2019: Protein entry updated
Automatic update: OMIM entry 615264 was added.

Feb. 23, 2019: Protein entry updated
Automatic update: OMIM entry 615242 was added.

Jan. 22, 2019: Protein entry updated
Automatic update: OMIM entry 615242 was added.

Jan. 22, 2019: Protein entry updated
Automatic update: OMIM entry 615264 was added.

Dec. 10, 2018: Protein entry updated
Automatic update: OMIM entry 615242 was added.

Dec. 10, 2018: Protein entry updated
Automatic update: OMIM entry 615264 was added.

Dec. 9, 2018: Protein entry updated
Automatic update: OMIM entry 615242 was added.

Dec. 9, 2018: Protein entry updated
Automatic update: OMIM entry 615264 was added.

Nov. 17, 2018: Protein entry updated
Automatic update: OMIM entry 615242 was added.

Nov. 17, 2018: Protein entry updated
Automatic update: OMIM entry 615264 was added.

Oct. 20, 2018: Protein entry updated
Automatic update: OMIM entry 615242 was added.

Oct. 20, 2018: Protein entry updated
Automatic update: OMIM entry 615264 was added.

Oct. 2, 2018: Protein entry updated
Automatic update: OMIM entry 615242 was added.

Oct. 2, 2018: Protein entry updated
Automatic update: OMIM entry 615264 was added.

July 7, 2018: Protein entry updated
Automatic update: OMIM entry 615242 was added.

July 7, 2018: Protein entry updated
Automatic update: OMIM entry 615264 was added.

July 6, 2018: Protein entry updated
Automatic update: OMIM entry 615242 was added.

July 6, 2018: Protein entry updated
Automatic update: OMIM entry 615264 was added.

July 5, 2018: Protein entry updated
Automatic update: OMIM entry 615242 was added.

July 5, 2018: Protein entry updated
Automatic update: OMIM entry 615264 was added.

July 4, 2018: Protein entry updated
Automatic update: OMIM entry 615242 was added.

July 4, 2018: Protein entry updated
Automatic update: OMIM entry 615264 was added.

July 3, 2018: Protein entry updated
Automatic update: OMIM entry 615242 was added.

July 3, 2018: Protein entry updated
Automatic update: OMIM entry 615264 was added.

May 27, 2018: Protein entry updated
Automatic update: OMIM entry 615242 was added.

May 27, 2018: Protein entry updated
Automatic update: OMIM entry 615264 was added.

April 27, 2018: Protein entry updated
Automatic update: OMIM entry 615242 was added.

April 27, 2018: Protein entry updated
Automatic update: OMIM entry 615264 was added.

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 615242 was added.

Jan. 25, 2016: Protein entry updated
Automatic update: model status changed