Semaphorin-7A (SEMA7A)

The protein contains 666 amino acids for an estimated molecular weight of 74824 Da.

 

Plays an important role in integrin-mediated signaling and functions both in regulating cell migration and immune responses. Promotes formation of focal adhesion complexes, activation of the protein kinase PTK2/FAK1 and subsequent phosphorylation of MAPK1 and MAPK3. Promotes production of proinflammatory cytokines by monocytes and macrophages. Plays an important role in modulating inflammation and T-cell-mediated immune responses. Promotes axon growth in the embryonic olfactory bulb. Promotes attachment, spreading and dendrite outgrowth in melanocytes. (updated: Jan. 7, 2015)

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.

This protein is annotated as membranous in Gene Ontology, is annotated as membranous in UniProt, is predicted to be membranous by TOPCONS.


Interpro domains
Total structural coverage: 89%
Model score: 100
No model available.

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VariantDescription
dbSNP:rs16968733
Results in JMH-variant phenotype
Results in JMH-variant phenotype
Results in JMH-variant phenotype
Results in JMH-variant phenotype
Results in JMH-variant phenotype

The reference OMIM entry for this protein is 607961

Semaphorin 7a; sema7a
Semaphorin l; semal
Semaphorin k1; semak1
Cdw108

DESCRIPTION

SEMA7A is an 80-kD membrane-bound semaphorin that associates with cell surfaces via a glycosylphosphatidylinositol (GPI) linkage. It is preferentially expressed on activated lymphocytes and erythrocytes. SEMA7A carries the John Milton Hagen (JMH) blood group antigens (see 614745) (summary by Yamada et al., 1999).

CLONING

By PCR using primers designed from alcelaphine herpesvirus-1 (AHV) sema, followed by 5-prime and 3-prime RACE, Lange et al. (1998) cloned full-length SEMA7A, which they designated SEMAL, from a placenta cDNA library. The deduced 666-amino acid protein has a calculated molecular mass of about 75 kD, and the unglycosylated protein has a calculated molecular mass of about 70 kD following signal peptide cleavage. SEMA7A contains a 44-amino acid N-terminal signal sequence, a semaphorin domain of about 500 amino acids, an immunoglobulin-like motif, and a C-terminal hydrophobic domain that lacks a significant intracellular tail. The semaphorin domain has several conserved cysteine residues and an RGD motif. SEMA7A also contains 5 N-glycosylation sites and several myristoylation sites. Northern blot analysis detected a 3.2-kb transcript expressed predominantly in spleen, thymus, testis, and ovary. Little or no expression was detected in prostate, small intestine, colon, and peripheral blood leukocytes. RNA dot blot analysis detected expression in placenta, spleen, and gonadal tissue, but not in neuronal or muscular tissue. By searching an EST database using AHV sema as probe, Xu et al. (1998) identified SEMA7A, which they designated SEMAK1. SEMA7A shares about 50% amino acid identity with AHV sema and less than 30% identity with other semaphorins. Northern blot analysis of adult mouse tissues detected a 4.4-kb Sema7a transcript expressed at high levels in brain, spinal cord, lung, and testis. In situ hybridization detected weak but dynamic expression of Sema7a in spinal cord, cerebellum, and cortex during embryonic development. In adult mice, Sema7a was expressed in several brain structures and cell layers. By PCR using primers based on the N-terminal amino acid sequence of SEMA7A, followed by screening a leukemic T-cell line cDNA library and a placenta cDNA library, Yamada et al. (1999) cloned SEMA7A, which they called CDW108. Northern blot analysis detected a 3.5-kb transcript expressed at highest levels in placenta, testis, and spleen, with low levels in brain and thymus. Yamada et al. (1999) detected 5 differentially glycosylated forms of SEMA7A by SDS-PAGE of a transfected esophageal cancer cell line. The largest protein had an apparent molecular mass of about 80 kD. Treatment with peptide-N-glycosidase revealed a deglycosylated protein with an apparent molecular mass of about 65 kD. Sato and Takahashi (1998) cloned mouse Sema7a. They noted that the immunoglobulin-like domain of the deduced 664-amino acid protein is of the C2 type. Human and mouse SEMA7A share 89.5% identity. Northern blot analysis of rat tissues detected highest expression in the nervous system, and expression in the cerebellum and brain stem increased during development. Moderate expression was detected in thymus and spleen.

GENE STRUCTURE

Lange et al. (1998) determined that the SEMA7A gene contains at least 13 exons and spans about 9 kb. Seltsam et al. (2007) stated that the SEMA7A gene contains 14 exons.

MAPPING

By FISH, Lange et al. (1998) mapped the SEMA7A gene to chromosome 15q22.2-q23. Using r ... More on the omim web site

The reference OMIM entry for this protein is 614745

Blood group, john milton hagen system
John milton hagen blood group system
Jmh blood group system

A number sign (#) is used with this entry because the John Milton Hagen (JMH) blood group system is based, at least partly, on variation in the gene encoding semaphorin-7A (SEMA7A; 607961) on chromosome 15q22.2-q23.

DESCRIPTION

JMH blood group antigens are carried by SEMA7A, a membrane-associated protein that plays important roles in the nervous system and immune responses. Three different JMH phenotypes have been identified based on the presence or absence of the high-frequency JMH (or JMH1) antigen: JMH-weak, JMH-negative, and JMH-variant. The JMH-weak and -negative phenotypes can be either acquired or inherited and are characterized by a reduction or complete loss of JMH expression on red blood cells (RBCs), often with concomitant occurrence of JMH antibodies. Acquired JMH-weak or -negative phenotypes are typically found in elderly persons and can be transient. The JMH antibodies present in the acquired phenotypes have autoimmune characteristics and are clinically irrelevant. The inherited JMH-negative phenotype has been found in only 1 family. Mechanisms underlying the JMH-weak and -negative phenotypes have yet to be identified. Individuals with the JMH-variant phenotype are usually JMH-positive and have alloantibodies compatible with JMH-negative RBCs. The JMH-variant phenotype results from rare missense mutations in the SEMA7A gene (summary by Seltsam et al. (2007) and Richard et al. (2011)).

CLINICAL FEATURES

Seltsam et al. (2007) identified 3 different RBC phenotypes with unusual JMH expression in 33 of 44 individuals with abnormal JMH blood groups and their family members. Eleven individuals had a JMH-variant phenotype lacking single JMH epitopes, 18 individuals had a JMH-negative phenotype, and 4 individuals had a JMH-weak phenotype. In most cases, these JMH phenotypes were associated with the presence of JMH or JMH-like antibodies in serum. The 11 remaining individuals, who were family members of individuals with JMH-variant or JMH-negative phenotypes, had normal JHM blood groups. - JMH-Variant Phenotype Seltsam et al. (2007) identified 5 propositi with JMH-variant phenotype from Canada, Germany, Japan, Poland, and the U.S. The JMH-variant phenotype was also present in 6 of 14 family members of the propositi. Determination of variant JMH status was based on variably positive or negative reactions of RBCs with anti-JMH serum samples. JMH-like antibodies were only present in the serum of the propositi, which reacted positive with all but JMH-negative RBCs, the propositus's own RBCs, and RBCs of compatible JMH-positive sibs. - JMH-Negative Phenotype Seltsam et al. (2007) identified 18 individuals with JMH-negative phenotype from Canada, Germany, Israel, Sweden, Switzerland, and the U.S. The ages of the RBH-negative individuals, as far as known, ranged from 54 to 82 years. The JMH-negative phenotype was identified by negative reaction of the individuals' RBCs with JMH antisera from immunized patients. In addition, no JMH antigen was detected on the surface of JMH-negative RBCs by flow cytometric and immunoblot analyses. JMH antibodies were detected in 14 of the JMH-negative individuals. Four JMH-negative individuals belonged to an apparently healthy family in which the JMH-negative phenotype had been detected in 3 generations. The other JMH-negative individuals were unrelated and information about inheritance was not available. However, in 2 of these individuals, who were apparently healthy, JMH-negative sta ... More on the omim web site

Subscribe to this protein entry history

July 2, 2021: Protein entry updated
Automatic update: OMIM entry 607961 was added.

July 2, 2021: Protein entry updated
Automatic update: OMIM entry 614745 was added.

April 11, 2021: Protein entry updated
Automatic update: OMIM entry 607961 was added.

April 11, 2021: Protein entry updated
Automatic update: OMIM entry 614745 was added.

Feb. 17, 2021: Protein entry updated
Automatic update: OMIM entry 607961 was added.

Feb. 17, 2021: Protein entry updated
Automatic update: OMIM entry 614745 was added.

Oct. 21, 2020: Protein entry updated
Automatic update: OMIM entry 607961 was added.

Oct. 21, 2020: Protein entry updated
Automatic update: OMIM entry 614745 was added.

Aug. 25, 2020: Protein entry updated
Automatic update: OMIM entry 607961 was added.

Aug. 25, 2020: Protein entry updated
Automatic update: OMIM entry 614745 was added.

June 30, 2020: Protein entry updated
Automatic update: OMIM entry 607961 was added.

June 30, 2020: Protein entry updated
Automatic update: OMIM entry 614745 was added.

April 26, 2020: Protein entry updated
Automatic update: OMIM entry 614745 was added.

April 26, 2020: Protein entry updated
Automatic update: OMIM entry 607961 was added.

March 4, 2020: Protein entry updated
Automatic update: OMIM entry 607961 was added.

March 4, 2020: Protein entry updated
Automatic update: OMIM entry 614745 was added.

Jan. 23, 2020: Protein entry updated
Automatic update: OMIM entry 607961 was added.

Jan. 23, 2020: Protein entry updated
Automatic update: OMIM entry 614745 was added.

Dec. 3, 2019: Protein entry updated
Automatic update: OMIM entry 607961 was added.

Dec. 3, 2019: Protein entry updated
Automatic update: OMIM entry 614745 was added.

Oct. 28, 2019: Protein entry updated
Automatic update: OMIM entry 607961 was added.

Oct. 28, 2019: Protein entry updated
Automatic update: OMIM entry 614745 was added.

Sept. 23, 2019: Protein entry updated
Automatic update: OMIM entry 607961 was added.

Sept. 23, 2019: Protein entry updated
Automatic update: OMIM entry 614745 was added.

Aug. 21, 2019: Protein entry updated
Automatic update: OMIM entry 607961 was added.

Aug. 21, 2019: Protein entry updated
Automatic update: OMIM entry 614745 was added.

July 5, 2019: Protein entry updated
Automatic update: OMIM entry 607961 was added.

July 5, 2019: Protein entry updated
Automatic update: OMIM entry 614745 was added.

June 7, 2019: Protein entry updated
Automatic update: OMIM entry 614745 was added.

June 7, 2019: Protein entry updated
Automatic update: OMIM entry 607961 was added.

May 12, 2019: Protein entry updated
Automatic update: OMIM entry 607961 was added.

May 12, 2019: Protein entry updated
Automatic update: OMIM entry 614745 was added.

Nov. 17, 2018: Protein entry updated
Automatic update: OMIM entry 607961 was added.

Nov. 17, 2018: Protein entry updated
Automatic update: OMIM entry 614745 was added.

Oct. 20, 2018: Protein entry updated
Automatic update: OMIM entry 607961 was added.

Oct. 20, 2018: Protein entry updated
Automatic update: OMIM entry 614745 was added.

Oct. 2, 2018: Protein entry updated
Automatic update: OMIM entry 607961 was added.

Oct. 2, 2018: Protein entry updated
Automatic update: OMIM entry 614745 was added.

July 7, 2018: Protein entry updated
Automatic update: OMIM entry 607961 was added.

July 7, 2018: Protein entry updated
Automatic update: OMIM entry 614745 was added.

July 6, 2018: Protein entry updated
Automatic update: OMIM entry 607961 was added.

July 6, 2018: Protein entry updated
Automatic update: OMIM entry 614745 was added.

July 5, 2018: Protein entry updated
Automatic update: OMIM entry 607961 was added.

July 5, 2018: Protein entry updated
Automatic update: OMIM entry 614745 was added.

July 4, 2018: Protein entry updated
Automatic update: OMIM entry 607961 was added.

July 4, 2018: Protein entry updated
Automatic update: OMIM entry 614745 was added.

July 3, 2018: Protein entry updated
Automatic update: OMIM entry 607961 was added.

July 3, 2018: Protein entry updated
Automatic update: OMIM entry 614745 was added.

May 27, 2018: Protein entry updated
Automatic update: OMIM entry 607961 was added.

May 27, 2018: Protein entry updated
Automatic update: OMIM entry 614745 was added.

April 27, 2018: Protein entry updated
Automatic update: OMIM entry 607961 was added.

April 27, 2018: Protein entry updated
Automatic update: OMIM entry 614745 was added.

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

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

March 16, 2016: Protein entry updated
Automatic update: OMIM entry 607961 was added.

Jan. 28, 2016: Protein entry updated
Automatic update: model status changed

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