Reviewed, UniProtKB/Swiss-Prot P28907 (CD38_HUMAN)

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	300 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence 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-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 component	Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Diabetes mellitus
Domain	Signal-anchor Transmembrane
Ligand	NAD
Molecular function	Hydrolase Receptor
PTM	Disulfide bond Glycoprotein
Technical term	3D-structure Complete proteome
Gene Ontology (GO)
Biological process	induction of apoptosis by extracellular signals Traceable author statement. Source: ProtInc metabolic process Inferred from electronic annotation. Source: InterPro signal transduction Ref.5 Non-traceable author statement. Source: ProtInc
Cellular component	integral to membrane Inferred from electronic annotation. Source: UniProtKB-SubCell membrane fraction Ref.5 Traceable author statement. Source: ProtInc plasma membrane Ref.5 Traceable author statement. Source: ProtInc
Molecular function	NAD+ nucleosidase activity Inferred from electronic annotation. Source: EC binding Inferred from electronic annotation. Source: InterPro receptor activity Inferred from electronic annotation. Source: UniProtKB-KW
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 key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 300

300

ADP-ribosyl cyclase 1

PRO_0000144066

Regions

Topological domain

1 – 21

21

Cytoplasmic Potential

Transmembrane

22 – 42

21

Signal-anchor for type II membrane protein Potential

Topological domain

43 – 300

258

Extracellular Potential

Sites

Active site

119

1

Ref.6

Active site

201

1

Ref.6

Amino acid modifications

Glycosylation

100

1

N-linked (GlcNAc...) Ref.9

Glycosylation

164

1

N-linked (GlcNAc...) Potential

Glycosylation

209

1

N-linked (GlcNAc...) Ref.9

Glycosylation

219

1

N-linked (GlcNAc...) Ref.9 Ref.10

Disulfide bond

67 ↔ 82

Ref.11

Disulfide bond

99 ↔ 180

Ref.11

Disulfide bond

160 ↔ 173

Ref.11

Disulfide bond

254 ↔ 275

Ref.11

Disulfide bond

287 ↔ 296

Ref.11

Natural variations

Alternative sequence

122

1

I → K in isoform 2.

VSP_000707

Alternative sequence

123 – 300

178

Missing in isoform 2.

VSP_000708

Natural variant

140

1

R → W Seems to contribute to the development of type II diabetes; 50% reduction in activity. dbSNP rs1800561. Ref.12

VAR_001323

Experimental info

Mutagenesis

119

1

C → K: Loss of cADPr hydrolase activity.

Mutagenesis

119

1

C → R, E or A: Loss of cADPr hydrolase and ADP-ribosyl cyclase activity.

Mutagenesis

160

1

C → A: Loss of cADPr hydrolase and ADP-ribosyl cyclase activity.

Mutagenesis

173

1

C → A: Loss of cADPr hydrolase and ADP-ribosyl cyclase activity.

Mutagenesis

201

1

C → D, K or A: Loss of cADPr hydrolase and ADP-ribosyl cyclase activity.

Mutagenesis

201

1

C → E: Loss of cADPr hydrolase activity.

Sequence conflict

49

1

Q → T in AAA68482. Ref.1

Secondary structure

1

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300

Helix Strand Turn

Details...

Beta strand

49 – 53

5

Helix

59 – 73

15

Helix

75 – 77

3

Helix

82 – 91

10

Turn

92 – 95

4

Helix

103 – 106

4

Helix

107 – 112

6

Helix

119 – 121

3

Beta strand

122 – 127

6

Helix

129 – 137

9

Helix

145 – 147

3

Helix

149 – 154

6

Beta strand

163 – 167

5

Beta strand

171 – 173

3

Turn

176 – 179

4

Helix

184 – 199

16

Beta strand

202 – 209

8

Beta strand

212 – 216

5

Helix

221 – 224

4

Helix

226 – 228

3

Turn

232 – 234

3

Beta strand

235 – 243

9

Helix

253 – 255

3

Helix

257 – 268

12

Beta strand

272 – 279

8

Helix

281 – 289

9

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified November 23, 2004. Version 2. Checksum: 47BBE38C3DE3E6AA	FASTA	300	34,328
	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
	Isoform 2. Checksum: 06312C3A52C6ED5C	FASTA	122	13,788
	10 20 30 40 50 60 MANCEFSPVS GDKPCCRLSR RAQLCLGVSI LVLILVVVLA VVVPRWRQQW SGPGTTKRFP 70 80 90 100 110 120 ETVLARCVKY TEIHPEMRHV DCQSVWDAFK GAFISKHPCN ITEEDYQPLM KLGTQTVPCN KK

References

	« Hide 'large scale' referencesShow '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: 2319135] [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: 9074508] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), TISSUE SPECIFICITY. Tissue: Oesophageal 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: 15489334] [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: 1471258] [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: 8253715] [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: 7961800] [Abstract] Cited for: ACTIVE SITE.
[7]	"An unappreciated role for RNA surveillance." Hillman R.T., Green R.E., Brenner S.E. Genome Biol. 5:RESEARCH008.1-RESEARCH008.16(2004) [PubMed: 14759258] [Abstract] Cited for: SPLICE ISOFORM(S) THAT ARE POTENTIAL NMD TARGET(S).
[8]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[9]	"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: 19159218] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-100; ASN-209 AND ASN-219, MASS SPECTROMETRY. Tissue: Liver.
[10]	"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: 19349973] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-219, MASS SPECTROMETRY.
[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: 16154090] [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: 9754820] [Abstract] Cited for: VARIANT TRP-140.
+	Additional computationally mapped references.

Web resources

Wikipedia

CD38 entry

Cross-references

Sequence databases

EMBLGenBankDDBJ

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.

IPI

IPI00006071.
IPI00395006.

PIR

A43521.

RefSeq

NP_001766.2.

UniGene

Hs.479214

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1YH3	X-ray	1.91	A/B	45-300	[»]
1ZVM	X-ray	2.20	A/B/C/D	45-300	[»]
2EF1	X-ray	2.40	A/B	45-300	[»]
2HCT	X-ray	1.95	A/B	45-300	[»]
2I65	X-ray	1.90	A/B	45-300	[»]
2I66	X-ray	1.70	A/B	45-300	[»]
2I67	X-ray	1.71	A/B	45-300	[»]
2O3Q	X-ray	1.98	A/B	45-300	[»]
2O3R	X-ray	1.75	A/B	45-300	[»]
2O3S	X-ray	1.50	A/B	46-300	[»]
2O3T	X-ray	1.68	A/B	45-300	[»]
2O3U	X-ray	2.11	A/B	45-300	[»]
2PGJ	X-ray	1.71	A/B	45-300	[»]
2PGL	X-ray	1.76	A/B	45-300	[»]
3DZF	X-ray	2.01	A/B/C/D/E/F	45-300	[»]
3DZG	X-ray	1.65	A/B	45-300	[»]
3DZH	X-ray	1.60	A/B	45-300	[»]
3DZI	X-ray	1.73	A/B	45-300	[»]
3DZJ	X-ray	1.90	A/B	45-300	[»]
3DZK	X-ray	1.81	A/B	45-300	[»]
3F6Y	X-ray	1.45	A	46-300	[»]
3I9M	X-ray	1.75	A/B	45-300	[»]
3I9N	X-ray	2.01	A/B	45-300	[»]

ModBase

Search...

Protein-protein interaction databases

STRING

P28907.

Proteomic databases

PeptideAtlas

P28907.

PRIDE

P28907.

Genome annotation databases

Ensembl

ENST00000226279; ENSP00000226279; ENSG00000004468; Homo sapiens. [Genome view]

GeneID

952.

KEGG

hsa:952.

NMPDR

fig|9606.3.peg.23952.

UCSC

uc003goj.1. human.
uc003gol.1. human.

Organism-specific databases

CTD

952.

GeneCards

GC04P015457.

H-InvDB

HIX0004112.
HIX0004113.

HGNC

HGNC:1667. CD38.

HPA

CAB002493.
CAB025255.
HPA022132.

MIM

107270. gene.

PharmGKB

PA26214.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

P28907.

HOVERGEN

P28907.

OMA

QCVKNPE.

Enzyme and pathway databases

BRENDA

3.2.2.5. 247.

Gene expression databases

ArrayExpress

P28907.

Bgee

P28907.

CleanEx

HS_CD38.

Genevestigator

P28907.

GermOnline

ENSG00000004468. Homo sapiens.

Family and domain databases

InterPro

IPR003193. ADP-ribosyl_cyclase.
IPR016040. NAD(P)-bd_dom.
[Graphical view]

Gene3D

G3DSA:3.40.50.720. NAD(P)-bd. 1 hit.

PANTHER

PTHR10912. Rib_hydrolayse. 1 hit.

Pfam

PF02267. Rib_hydrolayse. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

NextBio

3962.

SOURCE

Search...

Entry information

Entry name

CD38_HUMAN

Accession

Primary (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:	November 3, 2009
This is version 106 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

Disclaimer

Any 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.