Carbonic anhydrase 2 (CA2)

The protein contains 260 amino acids for an estimated molecular weight of 29246 Da.

 

Essential for bone resorption and osteoclast differentiation (By similarity). Reversible hydration of carbon dioxide. Can hydrate cyanamide to urea. Involved in the regulation of fluid secretion into the anterior chamber of the eye. Contributes to intracellular pH regulation in the duodenal upper villous epithelium during proton-coupled peptide absorption. Stimulates the chloride-bicarbonate exchange activity of SLC26A6. (updated: April 1, 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.
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.


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

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VariantDescription
Jogjakarta
OPTB3
OPTB3; partial loss of activity
OPTB3
OPTB3; complete loss of activity
Melbourne
dbSNP:rs2228063

The reference OMIM entry for this protein is 259730

Osteopetrosis, autosomal recessive 3; optb3
Osteopetrosis with renal tubular acidosis
Carbonic anhydrase ii deficiency
Guibaud-vainsel syndrome
Marble brain disease

A number sign (#) is used with this entry because this form of autosomal recessive osteopetrosis is caused by homozygous or compound heterozygous mutation in the gene encoding carbonic anhydrase II (CA2; 611492) on chromosome 8q22. For a general phenotypic description and a discussion of genetic heterogeneity of autosomal recessive osteopetrosis, see OPTB1 (259700).

CLINICAL FEATURES

Sly et al. (1972) described 3 sisters, aged 22, 17, and 15 years, born to normal unrelated North American parents, with a form of osteopetrosis distinct from both the malignant form (see OPTB1, 259700) and the benign autosomal dominant form (see OPTA1, 607634). The disorder was manifest in the first 2 years because of fractures. Other features were short stature, mental retardation, dental malocclusion, and visual impairment from optic nerve compression. Mild anemia in infancy improved later and radiographic features of osteopetrosis improved some at puberty. Serum acid phosphatase was elevated and electrolyte changes suggested mild tubular acidosis. Whyte et al. (1980) provided a definitive report of these sibs. During adolescence basal ganglion calcification developed in 2. Renal tubular acidosis (type I) was diagnosed in each in early adulthood. Electron microscopy of bone suggested that osteoclasts failed to form 'ruffled membranes' characteristic of active bone resorbing cells. Chronic systemic acidosis may have ameliorated the skeletal manifestations. Guibaud et al. (1972) described 2 brothers with renal tubular acidosis and mild osteopetrosis. The unaffected parents, from North Africa, were cousins. Ohlsson et al. (1980) observed the syndrome, which they referred to as marble brain disease, in children of 3 Saudi families. They had striking facial similarities and cerebral calcifications. Bourke et al. (1981) observed this syndrome in 2 Kuwaiti Bedouin sibs. One sib showed basal ganglion calcification and mental subnormality. The major clinical manifestation in both was periodic hypokalemic paresis. Consanguinity was present in 9 of 12 pedigrees reported by Sly et al. (1985). More than half the known cases have been in families from Kuwait, Saudi Arabia, and North Africa. Ohlsson et al. (1986) described the findings in 4 new Saudi Arabian cases from 2 families, including the first description in a neonate. They reviewed the 17 previously reported cases. Cochat et al. (1987) added a case and reviewed the findings in 30 reported patients. Al Rajeh et al. (1988) described 2 affected sisters in a Saudi Arabian family. Strisciuglio et al. (1990) described 3 affected Italian sibs, the offspring of first cousins once removed. They had osteopetrosis with fractures and severe mental retardation. Whereas most previous patients had a mixed (proximal and distal) renal tubular acidosis, these patients had only proximal tubular acidosis. Aramaki et al. (1993) reported in detail the findings in 3 unrelated Japanese patients with CA II deficiency. Two of the 3 were born of first-cousin parents. All exhibited poor activity and poor appetite in the neonatal period and then developed psychomotor retardation. Two of them were diagnosed as having osteopetrosis at 10 months and 36 years of age, respectively, and the third as having osteomalacia at 28 years of age. All 3 had recurrent episodes of muscle weakness. Their parents exhibited approximately 50% normal levels of CA II activity in protein. The development of osteomalacia was considered to be related to t ... More on the omim web site

Subscribe to this protein entry history

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 259730 was added.

Jan. 27, 2016: Protein entry updated
Automatic update: model status changed

Jan. 24, 2016: Protein entry updated
Automatic update: model status changed