Guanine nucleotide-binding protein subunit alpha-11 (GNA11)

The protein contains 359 amino acids for an estimated molecular weight of 42123 Da.

 

Guanine nucleotide-binding proteins (G proteins) are involved as modulators or transducers in various transmembrane signaling systems. Acts as an activator of phospholipase C. Transduces FFAR4 signaling in response to long-chain fatty acids (LCFAs). (updated: April 22, 2020)

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. 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.
  3. 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.
  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.
  6. 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.


Interpro domains
Total structural coverage: 98%
Model score: 0
No model available.

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VariantDescription
HYPOC2
HHC2
HYPOC2
HYPOC2
HYPOC2

The reference OMIM entry for this protein is 139313

Guanine nucleotide-binding protein, alpha-11; gna11

CLONING

Strathmann and Simon (1991) described the Gna11 gene in the mouse. The human gene was cloned by Jiang et al. (1991) and found to be 359 amino acids long. Mouse Gna11 and Gna15 (139314) are tandemly duplicated in a head-to-tail array. Davignon et al. (1996) showed that the upstream gene, Gna11, is ubiquitously expressed, whereas expression of the downstream gene, Gna15, is restricted to hematopoietic cells. There was no evidence for alternative splicing within the coding sequence of either gene.

GENE STRUCTURE

Strathmann and Simon (1991) found that mouse Gna11 and Gna15 (139314) are tandemly duplicated in a head-to-tail array, spanning approximately 43 kb. Davignon et al., 1996 further studied the genomic structure of mouse Gna11 and Gna15. Gna11 and Gna15 each contain 7 exons interposed by 6 introns. Gna11 is upstream of Gna15, and the region separating the 2 genes is 6 kb long. Phylogenetic trees revealed an approximately 6-fold higher rate of change in Gna15 than in Gna11.

MAPPING

Wilkie et al. (1992) demonstrated that the GNA11 gene is located on mouse chromosome 10 (by the study of RFLVs in an interspecific backcross) and on human 19p13 (by in situ hybridization).

GENE FUNCTION

Using mice lacking G-alpha subunits specifically in smooth muscle cells, Wirth et al. (2008) found that G-alpha-q (GNAQ; 600998) and G-alpha-11 were required for maintenance of basal blood pressure and for development of salt-induced hypertension. In contrast, lack of G-alpha-12 (GNA12; 604394) and G-alpha-13 (GNA13; 604406) and their effector, Larg (ARHGEF12; 604763), did not alter normal blood pressure regulation, but blocked development of salt-induced hypertension.

MOLECULAR GENETICS

In the proband from a 4-generation kindred with hypocalciuric hypercalcemia mapping to chromosome 19p13 (HHC2; 145981) and an unrelated proband with HHC, Nesbit et al. (2013) identified heterozygosity for a 3-bp in-frame deletion and a missense mutation, respectively (139313.0001-139313.0002). In addition, 2 unrelated patients with hypocalcemia (HYPOC2; 615361) were found to be heterozygous for missense mutations in GNA11 (139313.0003 and 139313.0004). All 4 GNA11 mutations predicted disrupted protein structures, and functional analysis in HEK293 cells showed that family hypocalciuric hypercalcemia type II-associated mutations decrease the sensitivity of cells expressing calcium-sensing receptors to changes in extracellular calcium concentrations, whereas autosomal dominant hypocalcemia 2-associated mutations increase cell sensitivity. In affected members of 2 unrelated 4-generation families segregating autosomal dominant hypocalcemia, Mannstadt et al. (2013) identified heterozygous missense mutations (139313.0005 and 139313.0006) that segregated with disease in each family. In affected members of a large 4-generation family segregating autosomal dominant hypocalcemia, Li et al. (2014) identified a heterozygous missense mutation in the GNA11 gene (R60L; 139313.0007) that segregated with disease in the family and was not found in 1,200 in-house whole-exome sequencing samples. - Somatic Mutations By gene sequencing of exon 5 of the GNA11 gene, Van Raamsdonk et al. (2010) identified somatic mutations affecting residue Q209 in 7% of blue nevi (603670), 32% of primary uveal melanomas (155720), and 57% of uveal melanoma metastases. Mutations in the same codon (Q209) of the paralogue gene GNAQ (600998) were found in 55% ... More on the omim web site

Subscribe to this protein entry history

April 25, 2020: 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 139313 was added.