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P28907 (CD38_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 151. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
ADP-ribosyl cyclase 1

EC=3.2.2.5
Alternative name(s):
Cyclic ADP-ribose hydrolase 1
Short name=cADPr hydrolase 1
T10
CD_antigen=CD38
Gene names
Name:CD38
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length300 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Synthesizes cyclic ADP-ribose, a second messenger for glucose-induced insulin secretion. Also has cADPr hydrolase activity. Also moonlights as a receptor in cells of the immune system.

Catalytic activity

NAD+ + H2O = ADP-D-ribose + nicotinamide.

Enzyme regulation

ATP inhibits the hydrolyzing activity.

Subcellular location

Membrane; Single-pass type II membrane protein.

Tissue specificity

Expressed at high levels in pancreas, liver, kidney, brain, testis, ovary, placenta, malignant lymphoma and neuroblastoma. Ref.2

Developmental stage

Preferentially expressed at both early and late stages of the B and T-cell maturation. It is also detected on erythroid and myeloid progenitors in bone marrow, where the level of surface expression was shown to decrease during differentiation of blast-forming unit E to colony-forming unit E.

Sequence similarities

Belongs to the ADP-ribosyl cyclase family.

Ontologies

Keywords
   Cellular componentMembrane
   Coding sequence diversityAlternative splicing
Polymorphism
   DiseaseDiabetes mellitus
   DomainSignal-anchor
Transmembrane
Transmembrane helix
   LigandNAD
   Molecular functionHydrolase
Receptor
   PTMDisulfide bond
Glycoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processB cell receptor signaling pathway

Inferred from mutant phenotype PubMed 17875758. Source: UniProtKB

apoptotic signaling pathway

Traceable author statement PubMed 10777496. Source: ProtInc

female pregnancy

Inferred from electronic annotation. Source: Ensembl

long term synaptic depression

Inferred from electronic annotation. Source: Ensembl

negative regulation of apoptotic process

Inferred from mutant phenotype PubMed 17875758. Source: UniProtKB

negative regulation of bone resorption

Inferred from electronic annotation. Source: Ensembl

negative regulation of transcription, DNA-templated

Inferred from mutant phenotype PubMed 17875758. Source: UniProtKB

positive regulation of B cell proliferation

Inferred from mutant phenotype PubMed 17875758. Source: UniProtKB

positive regulation of cell growth

Inferred from electronic annotation. Source: Ensembl

positive regulation of cytosolic calcium ion concentration

Inferred from electronic annotation. Source: Ensembl

positive regulation of insulin secretion

Inferred from electronic annotation. Source: Ensembl

positive regulation of transcription, DNA-templated

Inferred from mutant phenotype PubMed 17875758. Source: UniProtKB

positive regulation of vasoconstriction

Inferred from electronic annotation. Source: Ensembl

response to drug

Inferred from mutant phenotype PubMed 17875758. Source: UniProtKB

response to estradiol

Inferred from electronic annotation. Source: Ensembl

response to hydroperoxide

Inferred from electronic annotation. Source: Ensembl

response to hypoxia

Inferred from electronic annotation. Source: Ensembl

response to interleukin-1

Inferred from electronic annotation. Source: Ensembl

response to progesterone

Inferred from electronic annotation. Source: Ensembl

response to retinoic acid

Inferred from electronic annotation. Source: Ensembl

signal transduction

Non-traceable author statement Ref.5. Source: ProtInc

   Cellular_componentcell surface

Inferred from electronic annotation. Source: Ensembl

integral component of membrane

Inferred from electronic annotation. Source: UniProtKB-KW

membrane

Traceable author statement Ref.5. Source: ProtInc

nucleus

Inferred from electronic annotation. Source: Ensembl

plasma membrane

Traceable author statement Ref.5. Source: ProtInc

   Molecular_functionNAD+ nucleosidase activity

Inferred from electronic annotation. Source: UniProtKB-EC

phosphorus-oxygen lyase activity

Inferred from electronic annotation. Source: Ensembl

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P28907-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: P28907-2)

The sequence of this isoform differs from the canonical sequence as follows:
     122-122: I → K
     123-300: Missing.
Note: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 300300ADP-ribosyl cyclase 1
PRO_0000144066

Regions

Topological domain1 – 2121Cytoplasmic Potential
Transmembrane22 – 4221Helical; Signal-anchor for type II membrane protein; Potential
Topological domain43 – 300258Extracellular Potential

Sites

Active site1191 Ref.6
Active site2011 Ref.6

Amino acid modifications

Glycosylation1001N-linked (GlcNAc...) Ref.8
Glycosylation1641N-linked (GlcNAc...) Potential
Glycosylation2091N-linked (GlcNAc...) Ref.8
Glycosylation2191N-linked (GlcNAc...) Ref.8 Ref.9
Disulfide bond67 ↔ 82 Ref.11
Disulfide bond99 ↔ 180 Ref.11
Disulfide bond160 ↔ 173 Ref.11
Disulfide bond254 ↔ 275 Ref.11
Disulfide bond287 ↔ 296 Ref.11

Natural variations

Alternative sequence1221I → K in isoform 2.
VSP_000707
Alternative sequence123 – 300178Missing in isoform 2.
VSP_000708
Natural variant1401R → W Seems to contribute to the development of type II diabetes; 50% reduction in activity. Ref.12
Corresponds to variant rs1800561 [ dbSNP | Ensembl ].
VAR_001323

Experimental info

Mutagenesis1191C → K: Loss of cADPr hydrolase activity.
Mutagenesis1191C → R, E or A: Loss of cADPr hydrolase and ADP-ribosyl cyclase activity.
Mutagenesis1601C → A: Loss of cADPr hydrolase and ADP-ribosyl cyclase activity.
Mutagenesis1731C → A: Loss of cADPr hydrolase and ADP-ribosyl cyclase activity.
Mutagenesis2011C → D, K or A: Loss of cADPr hydrolase and ADP-ribosyl cyclase activity.
Mutagenesis2011C → E: Loss of cADPr hydrolase activity.
Sequence conflict491Q → T in AAA68482. Ref.1

Secondary structure

........................................................... 300
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified November 23, 2004. Version 2.
Checksum: 47BBE38C3DE3E6AA

FASTA30034,328
        10         20         30         40         50         60 
MANCEFSPVS GDKPCCRLSR RAQLCLGVSI LVLILVVVLA VVVPRWRQQW SGPGTTKRFP 

        70         80         90        100        110        120 
ETVLARCVKY TEIHPEMRHV DCQSVWDAFK GAFISKHPCN ITEEDYQPLM KLGTQTVPCN 

       130        140        150        160        170        180 
KILLWSRIKD LAHQFTQVQR DMFTLEDTLL GYLADDLTWC GEFNTSKINY QSCPDWRKDC 

       190        200        210        220        230        240 
SNNPVSVFWK TVSRRFAEAA CDVVHVMLNG SRSKIFDKNS TFGSVEVHNL QPEKVQTLEA 

       250        260        270        280        290        300 
WVIHGGREDS RDLCQDPTIK ELESIISKRN IQFSCKNIYR PDKFLQCVKN PEDSSCTSEI 

« Hide

Isoform 2 [UniParc].

Checksum: 06312C3A52C6ED5C
Show »

FASTA12213,788

References

« Hide 'large scale' references
[1]"Isolation of a cDNA encoding the human CD38 (T10) molecule, a cell surface glycoprotein with an unusual discontinuous pattern of expression during lymphocyte differentiation."
Jackson D.G., Bell J.I.
J. Immunol. 144:2811-2815(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]"Human gene encoding CD38 (ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase): organization, nucleotide sequence and alternative splicing."
Nata K., Takamura T., Karasawa T., Kumagai T., Hashioka W., Tohgo A., Yonekura H., Takasawa S., Nakamura S., Okamoto H.
Gene 186:285-292(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), TISSUE SPECIFICITY.
Tissue: Esophageal carcinoma and Pancreas.
[3]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: B-cell.
[4]"Similarities in amino acid sequences of Aplysia ADP-ribosyl cyclase and human lymphocyte antigen CD38."
States D.J., Walseth T.F., Lee H.C.
Trends Biochem. Sci. 17:495-495(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: SIMILARITY TO NADASE.
[5]"Synthesis and hydrolysis of cyclic ADP-ribose by human leukocyte antigen CD38 and inhibition of the hydrolysis by ATP."
Takasawa S., Tohgo A., Noguchi N., Koguma T., Nata K., Sugimoto T., Yonekura H., Okamoto H.
J. Biol. Chem. 268:26052-26054(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: CHARACTERIZATION.
[6]"Essential cysteine residues for cyclic ADP-ribose synthesis and hydrolysis by CD38."
Tohgo A., Takasawa S., Noguchi N., Koguma T., Nata K., Sugimoto T., Furuya Y., Yonekura H., Okamoto H.
J. Biol. Chem. 269:28555-28557(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: ACTIVE SITE.
[7]"An unappreciated role for RNA surveillance."
Hillman R.T., Green R.E., Brenner S.E.
Genome Biol. 5:R8.1-R8.16(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: SPLICE ISOFORM(S) THAT ARE POTENTIAL NMD TARGET(S).
[8]"Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry."
Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.
J. Proteome Res. 8:651-661(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-100; ASN-209 AND ASN-219.
Tissue: Liver.
[9]"Mass-spectrometric identification and relative quantification of N-linked cell surface glycoproteins."
Wollscheid B., Bausch-Fluck D., Henderson C., O'Brien R., Bibel M., Schiess R., Aebersold R., Watts J.D.
Nat. Biotechnol. 27:378-386(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-219.
Tissue: Leukemic T-cell.
[10]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[11]"Crystal structure of human CD38 extracellular domain."
Liu Q., Kriksunov I.A., Graeff R., Munshi C., Lee H.C., Hao Q.
Structure 13:1331-1339(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.91 ANGSTROMS) OF 45-300, DISULFIDE BONDS.
[12]"A missense mutation in the CD38 gene, a novel factor for insulin secretion: association with Type II diabetes mellitus in Japanese subjects and evidence of abnormal function when expressed in vitro."
Yagui K., Shimada F., Mimura M., Hashimoto N., Suzuki Y., Tokuyama Y., Nata K., Tohgo A., Ikehata F., Takasawa S., Okamoto H., Makino H., Saito Y., Kanatsuka A.
Diabetologia 41:1024-1028(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT TRP-140.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
M34461 mRNA. Translation: AAA68482.1.
D84276 mRNA. Translation: BAA18964.1.
D84277 mRNA. Translation: BAA18965.1.
D84284 Genomic DNA. Translation: BAA18966.1.
BC007964 mRNA. Translation: AAH07964.1.
PIRA43521.
RefSeqNP_001766.2. NM_001775.2.
UniGeneHs.479214.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1YH3X-ray1.91A/B45-300[»]
1ZVMX-ray2.20A/B/C/D45-300[»]
2EF1X-ray2.40A/B45-300[»]
2HCTX-ray1.95A/B45-300[»]
2I65X-ray1.90A/B45-300[»]
2I66X-ray1.70A/B45-300[»]
2I67X-ray1.71A/B45-300[»]
2O3QX-ray1.98A/B45-300[»]
2O3RX-ray1.75A/B45-300[»]
2O3SX-ray1.50A/B46-300[»]
2O3TX-ray1.68A/B45-300[»]
2O3UX-ray2.11A/B45-300[»]
2PGJX-ray1.71A/B45-300[»]
2PGLX-ray1.76A/B45-300[»]
3DZFX-ray2.01A/B/C/D/E/F45-300[»]
3DZGX-ray1.65A/B45-300[»]
3DZHX-ray1.60A/B45-300[»]
3DZIX-ray1.73A/B45-300[»]
3DZJX-ray1.90A/B45-300[»]
3DZKX-ray1.81A/B45-300[»]
3F6YX-ray1.45A46-300[»]
3I9MX-ray1.75A/B45-300[»]
3I9NX-ray2.01A/B45-300[»]
3OFSX-ray2.20A/B/C/D/E/F46-300[»]
3RAJX-ray3.04A46-300[»]
3ROKX-ray1.65A/B45-296[»]
3ROMX-ray2.04A/B45-296[»]
3ROPX-ray1.94A/B45-296[»]
3ROQX-ray2.10A/B45-296[»]
3U4HX-ray1.88A/B45-300[»]
3U4IX-ray2.12A/B45-300[»]
4F45X-ray2.10A/B46-300[»]
4F46X-ray1.69A/B46-300[»]
ProteinModelPortalP28907.
SMRP28907. Positions 45-291.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid107390. 6 interactions.
MINTMINT-4536880.
STRING9606.ENSP00000226279.

Chemistry

BindingDBP28907.
ChEMBLCHEMBL4660.

PTM databases

PhosphoSiteP28907.

Polymorphism databases

DMDM55977782.

Proteomic databases

PaxDbP28907.
PeptideAtlasP28907.
PRIDEP28907.

Protocols and materials databases

DNASU952.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000226279; ENSP00000226279; ENSG00000004468. [P28907-1]
ENST00000502843; ENSP00000427277; ENSG00000004468. [P28907-2]
GeneID952.
KEGGhsa:952.
UCSCuc003gol.1. human. [P28907-1]

Organism-specific databases

CTD952.
GeneCardsGC04P015779.
HGNCHGNC:1667. CD38.
HPACAB002493.
CAB025255.
HPA022132.
HPA052381.
MIM107270. gene.
neXtProtNX_P28907.
PharmGKBPA26214.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG42596.
HOGENOMHOG000293141.
HOVERGENHBG005277.
InParanoidP28907.
KOK01242.
OMAQTVPCNK.
OrthoDBEOG7RBZ9B.
PhylomeDBP28907.
TreeFamTF332530.

Enzyme and pathway databases

BioCycMetaCyc:HS00103-MONOMER.
SABIO-RKP28907.

Gene expression databases

ArrayExpressP28907.
BgeeP28907.
CleanExHS_CD38.
GenevestigatorP28907.

Family and domain databases

Gene3D3.40.50.720. 1 hit.
InterProIPR003193. ADP-ribosyl_cyclase.
IPR016040. NAD(P)-bd_dom.
[Graphical view]
PANTHERPTHR10912. PTHR10912. 1 hit.
PfamPF02267. Rib_hydrolayse. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP28907.
GeneWikiCD38.
GenomeRNAi952.
NextBio3962.
PROP28907.
SOURCESearch...

Entry information

Entry nameCD38_HUMAN
AccessionPrimary (citable) accession number: P28907
Secondary accession number(s): O00121, O00122, Q96HY4
Entry history
Integrated into UniProtKB/Swiss-Prot: December 1, 1992
Last sequence update: November 23, 2004
Last modified: April 16, 2014
This is version 151 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 4

Human chromosome 4: entries, gene names and cross-references to MIM

Human cell differentiation molecules

CD nomenclature of surface proteins of human leucocytes and list of entries