ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 1 (CD38)

The protein contains 300 amino acids for an estimated molecular weight of 34328 Da.

 

Synthesizes the second messengers cyclic ADP-ribose and nicotinate-adenine dinucleotide phosphate, the former a second messenger for glucose-induced insulin secretion. Also has cADPr hydrolase activity. Also moonlights as a receptor in cells of the immune system. (updated: July 3, 2019)

Protein identification was indicated in the following studies:

  1. Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
  2. D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.

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 predicted to be membranous by TOPCONS.


Interpro domains
Total structural coverage: 83%
Model score: 0
No model available.

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VariantDescription
Seems to contribute to the development of type II diabetes

No binding partner found

The reference OMIM entry for this protein is 107270

Cd38 antigen; cd38
Adp-ribosyl cyclase/cyclic adp-ribose hydrolase
Ecto-nicotinamide adenine dinucleotide glycohydrolase

CLONING

By immunoscreening a lymphocyte cDNA library transiently expressed in COS cells, Jackson and Bell (1990) obtained a cDNA encoding CD38. Immunoprecipitation and SDS-PAGE analysis showed expression of a 46-kD protein under reducing conditions and a 42-kD protein under nonreducing conditions, both of which are larger than the predicted 34-kD protein, suggesting that CD38 is glycosylated. Northern blot analysis detected various transcripts in B and T lymphoblast cell lines, but no expression was found in resting lymphocytes. The predicted 300-amino acid type II transmembrane protein has a short N-terminal cytoplasmic tail and 4 C-terminal extracellular N-glycosylation sites. It lacks homology to immunoglobulin (Ig) superfamily or major histocompatibility complex (MHC) molecules.

GENE FUNCTION

Cyclic ADP-ribose is generated in pancreatic islets by glucose stimulation, serving as a second messenger for Ca(2+) mobilization in the endoplasmic reticulum for secretion of insulin (Takasawa et al., 1993). Takasawa et al. (1993) demonstrated the synthesis and hydrolysis of cADPR by CD38, which had previously been used as a human leukocyte differentiation marker.

GENE STRUCTURE

Southern blot analysis by Jackson and Bell (1990) suggested that the 20-kb CD38 gene may have long intronic sequences. Ferrero and Malavasi (1997) reported that the CD38 gene is present in single copy and extends over more than 62 kb; it consists of 8 exons and 7 introns, including a very long intron that interrupts the 5-prime coding region. They pointed out structural similarities to bone marrow stromal cell antigen-1 (BST1; 600387). The proteins encoding these 2 genes have related functions. The authors suggested that the 2 genes may have evolved from a common ancestor through gene duplication before the divergence of humans and rodents.

MAPPING

Katz et al. (1983) used hybrids formed between human acute lymphoblastic leukemia (ALL) cells and mouse myeloma cells to determine the chromosomal location of genes required for the expression of several monoclonal antibody-defined cell surface antigens on ALL cells. Two antigens could definitely be mapped: OKT10/p45 (CD38) to chromosome 4 and BA-2/p24 (CD9) to chromosome 12. The latter monoclonal reacted with the same protein as did another monoclonal antibody designated 609-29, an antiteratocarcinoma antibody (see 143030). Thus, this is a confirmed assignment. By fluorescence in situ hybridization, Nakagawara et al. (1995) mapped the CD38 gene to 4p15.

MOLECULAR GENETICS

Ferrero et al. (1999) investigated the genetic variability and linkage of the human CD38 gene. They reported that (1) the restriction endonuclease Pvu II identifies a biallelic polymorphism formed by the alleles CD38*A (12 kb) and CD38*B (9 kb); (2) the frequency of these alleles in the healthy Italian Caucasian population is 14% and 86%, respectively; (3) the polymorphic Pvu II site is located at the 5-prime end of the first intron of the CD38 gene; (4) in conjunction with the polymorphic site, they identified a 900-bp CpG island associated with the CD38 gene, with 2 potential Sp1 binding sites; (5) the CpG island may play a role in the regulation of CD38 expression and is hypomethylated in various cell lines; and (6) by pulsed-field gel electrophoresis, they showed that CD38 and its paralog BST1 map to the same 800-kb Avi II fragment, indicating that the 2 human ecto-NADase genes are closely linked. ... More on the omim web site

Subscribe to this protein entry history

July 4, 2019: Protein entry updated
Automatic update: Entry updated from uniprot information.

Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).

Oct. 19, 2018: Protein entry updated
Automatic update: OMIM entry 107270 was added.