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Protein

ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 1

Gene

CD38

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Synthesizes the second messagers 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.

Catalytic activityi

NAD+ + H2O = ADP-D-ribose + nicotinamide.1 Publication
NADP+ + nicotinate = nicotinate-adenine dinucleotide phosphate + nicotinamide.1 Publication

Enzyme regulationi

ATP inhibits the hydrolyzing activity.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei1191 Publication1
Active sitei2011 Publication1

GO - Molecular functioni

GO - Biological processi

  • apoptotic signaling pathway Source: ProtInc
  • B cell receptor signaling pathway Source: UniProtKB
  • female pregnancy Source: Ensembl
  • long term synaptic depression Source: Ensembl
  • negative regulation of apoptotic process Source: UniProtKB
  • negative regulation of bone resorption Source: Ensembl
  • negative regulation of transcription, DNA-templated Source: UniProtKB
  • positive regulation of B cell proliferation Source: UniProtKB
  • positive regulation of cell growth Source: Ensembl
  • positive regulation of cytosolic calcium ion concentration Source: Ensembl
  • positive regulation of insulin secretion Source: Ensembl
  • positive regulation of transcription, DNA-templated Source: UniProtKB
  • positive regulation of vasoconstriction Source: Ensembl
  • response to drug Source: UniProtKB
  • response to estradiol Source: Ensembl
  • response to hydroperoxide Source: Ensembl
  • response to hypoxia Source: Ensembl
  • response to interleukin-1 Source: Ensembl
  • response to progesterone Source: Ensembl
  • response to retinoic acid Source: Ensembl
  • signal transduction Source: ProtInc
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase, Receptor, Transferase

Keywords - Ligandi

NAD, NADP

Enzyme and pathway databases

BioCyciMetaCyc:HS00103-MONOMER.
ZFISH:HS00103-MONOMER.
BRENDAi2.4.99.20. 2681.
3.2.2.5. 2681.
SABIO-RKP28907.

Names & Taxonomyi

Protein namesi
Recommended name:
ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 1 (EC:3.2.2.6)
Alternative name(s):
2'-phospho-ADP-ribosyl cyclase
2'-phospho-ADP-ribosyl cyclase/2'-phospho-cyclic-ADP-ribose transferase (EC:2.4.99.20)
2'-phospho-cyclic-ADP-ribose transferase
ADP-ribosyl cyclase 1
Short name:
ADPRC 1
Cyclic ADP-ribose hydrolase 1
Short name:
cADPr hydrolase 1
T10
CD_antigen: CD38
Gene namesi
Name:CD38
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 4

Organism-specific databases

HGNCiHGNC:1667. CD38.

Subcellular locationi

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 21CytoplasmicSequence analysisAdd BLAST21
Transmembranei22 – 42Helical; Signal-anchor for type II membrane proteinSequence analysisAdd BLAST21
Topological domaini43 – 300ExtracellularSequence analysisAdd BLAST258

GO - Cellular componenti

  • cell surface Source: Ensembl
  • extracellular exosome Source: UniProtKB
  • integral component of membrane Source: UniProtKB-KW
  • membrane Source: ProtInc
  • nucleus Source: Ensembl
  • plasma membrane Source: ProtInc
Complete GO annotation...

Keywords - Cellular componenti

Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi119C → K: Loss of cADPr hydrolase activity. 1 Publication1
Mutagenesisi119C → R, E or A: Loss of cADPr hydrolase and ADP-ribosyl cyclase activity. 1 Publication1
Mutagenesisi160C → A: Loss of cADPr hydrolase and ADP-ribosyl cyclase activity. 1 Publication1
Mutagenesisi173C → A: Loss of cADPr hydrolase and ADP-ribosyl cyclase activity. 1 Publication1
Mutagenesisi201C → D, K or A: Loss of cADPr hydrolase and ADP-ribosyl cyclase activity. 1 Publication1
Mutagenesisi201C → E: Loss of cADPr hydrolase activity. 1 Publication1

Keywords - Diseasei

Diabetes mellitus

Organism-specific databases

DisGeNETi952.
OpenTargetsiENSG00000004468.
PharmGKBiPA26214.

Chemistry databases

ChEMBLiCHEMBL4660.
DrugBankiDB09331. Daratumumab.
GuidetoPHARMACOLOGYi2766.

Polymorphism and mutation databases

BioMutaiCD38.
DMDMi55977782.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001440661 – 300ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase 1Add BLAST300

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi67 ↔ 821 Publication
Disulfide bondi99 ↔ 1801 Publication
Glycosylationi100N-linked (GlcNAc...)1 Publication1
Disulfide bondi160 ↔ 1731 Publication
Glycosylationi164N-linked (GlcNAc...)Sequence analysis1
Glycosylationi209N-linked (GlcNAc...)1 Publication1
Glycosylationi219N-linked (GlcNAc...)2 Publications1
Disulfide bondi254 ↔ 2751 Publication
Disulfide bondi287 ↔ 2961 Publication

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

EPDiP28907.
MaxQBiP28907.
PaxDbiP28907.
PeptideAtlasiP28907.
PRIDEiP28907.

PTM databases

iPTMnetiP28907.
PhosphoSitePlusiP28907.
SwissPalmiP28907.

Expressioni

Tissue specificityi

Expressed at high levels in pancreas, liver, kidney, brain, testis, ovary, placenta, malignant lymphoma and neuroblastoma.1 Publication

Developmental stagei

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.

Gene expression databases

BgeeiENSG00000004468.
CleanExiHS_CD38.
ExpressionAtlasiP28907. baseline and differential.
GenevisibleiP28907. HS.

Organism-specific databases

HPAiCAB002493.
CAB025255.
HPA022132.
HPA052381.

Interactioni

Protein-protein interaction databases

BioGridi107390. 6 interactors.
MINTiMINT-4536880.
STRINGi9606.ENSP00000226279.

Chemistry databases

BindingDBiP28907.

Structurei

Secondary structure

1300
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi51 – 53Combined sources3
Helixi59 – 73Combined sources15
Helixi75 – 77Combined sources3
Helixi82 – 93Combined sources12
Beta strandi94 – 96Combined sources3
Helixi98 – 100Combined sources3
Helixi103 – 106Combined sources4
Helixi107 – 112Combined sources6
Helixi119 – 121Combined sources3
Beta strandi122 – 127Combined sources6
Beta strandi132 – 134Combined sources3
Helixi136 – 141Combined sources6
Beta strandi142 – 144Combined sources3
Helixi145 – 147Combined sources3
Helixi149 – 154Combined sources6
Beta strandi165 – 167Combined sources3
Beta strandi171 – 173Combined sources3
Turni176 – 179Combined sources4
Beta strandi181 – 183Combined sources3
Helixi184 – 199Combined sources16
Beta strandi202 – 209Combined sources8
Beta strandi212 – 216Combined sources5
Beta strandi218 – 220Combined sources3
Helixi221 – 224Combined sources4
Helixi227 – 229Combined sources3
Turni232 – 234Combined sources3
Beta strandi235 – 243Combined sources9
Beta strandi246 – 249Combined sources4
Helixi253 – 255Combined sources3
Helixi257 – 268Combined sources12
Beta strandi272 – 278Combined sources7
Helixi281 – 289Combined sources9
Turni291 – 293Combined sources3
Helixi294 – 296Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB 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/B45-300[»]
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-ray1.45A45-300[»]
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[»]
4CMHX-ray1.53A45-300[»]
4F45X-ray2.10A/B46-300[»]
4F46X-ray1.69A/B46-300[»]
4OGWX-ray2.05A46-300[»]
4TMFX-ray2.05A/B50-300[»]
4XJSX-ray2.80A46-300[»]
4XJTX-ray2.60A46-300[»]
5F1KX-ray2.30A/B45-300[»]
5F1OX-ray2.20A46-300[»]
5F21X-ray1.90A46-300[»]
ProteinModelPortaliP28907.
SMRiP28907.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP28907.

Family & Domainsi

Sequence similaritiesi

Belongs to the ADP-ribosyl cyclase family.Curated

Keywords - Domaini

Signal-anchor, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410IH8E. Eukaryota.
ENOG4111W33. LUCA.
GeneTreeiENSGT00390000017291.
HOGENOMiHOG000293141.
HOVERGENiHBG005277.
InParanoidiP28907.
KOiK01242.
OMAiCKNIYRP.
OrthoDBiEOG091G0GI3.
PhylomeDBiP28907.
TreeFamiTF332530.

Family and domain databases

Gene3Di3.40.50.720. 1 hit.
InterProiIPR003193. ADP-ribosyl_cyclase.
IPR033567. CD38.
IPR016040. NAD(P)-bd_dom.
[Graphical view]
PANTHERiPTHR10912. PTHR10912. 1 hit.
PTHR10912:SF5. PTHR10912:SF5. 1 hit.
PfamiPF02267. Rib_hydrolayse. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P28907-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MANCEFSPVS GDKPCCRLSR RAQLCLGVSI LVLILVVVLA VVVPRWRQQW
60 70 80 90 100
SGPGTTKRFP ETVLARCVKY TEIHPEMRHV DCQSVWDAFK GAFISKHPCN
110 120 130 140 150
ITEEDYQPLM KLGTQTVPCN KILLWSRIKD LAHQFTQVQR DMFTLEDTLL
160 170 180 190 200
GYLADDLTWC GEFNTSKINY QSCPDWRKDC SNNPVSVFWK TVSRRFAEAA
210 220 230 240 250
CDVVHVMLNG SRSKIFDKNS TFGSVEVHNL QPEKVQTLEA WVIHGGREDS
260 270 280 290 300
RDLCQDPTIK ELESIISKRN IQFSCKNIYR PDKFLQCVKN PEDSSCTSEI
Length:300
Mass (Da):34,328
Last modified:November 23, 2004 - v2
Checksum:i47BBE38C3DE3E6AA
GO
Isoform 2 (identifier: P28907-2) [UniParc]FASTAAdd to basket

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.
Show »
Length:122
Mass (Da):13,788
Checksum:i06312C3A52C6ED5C
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti49Q → T in AAA68482 (PubMed:2319135).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_001323140R → W Seems to contribute to the development of type II diabetes; 50% reduction in activity. 1 PublicationCorresponds to variant rs1800561dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_000707122I → K in isoform 2. 1 Publication1
Alternative sequenceiVSP_000708123 – 300Missing in isoform 2. 1 PublicationAdd BLAST178

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS3417.1. [P28907-1]
PIRiA43521.
RefSeqiNP_001766.2. NM_001775.3. [P28907-1]
UniGeneiHs.479214.

Genome annotation databases

EnsembliENST00000226279; ENSP00000226279; ENSG00000004468. [P28907-1]
ENST00000502843; ENSP00000427277; ENSG00000004468. [P28907-2]
GeneIDi952.
KEGGihsa:952.
UCSCiuc003gol.2. human. [P28907-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Web resourcesi

Wikipedia

CD38 entry

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS3417.1. [P28907-1]
PIRiA43521.
RefSeqiNP_001766.2. NM_001775.3. [P28907-1]
UniGeneiHs.479214.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB 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/B45-300[»]
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-ray1.45A45-300[»]
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[»]
4CMHX-ray1.53A45-300[»]
4F45X-ray2.10A/B46-300[»]
4F46X-ray1.69A/B46-300[»]
4OGWX-ray2.05A46-300[»]
4TMFX-ray2.05A/B50-300[»]
4XJSX-ray2.80A46-300[»]
4XJTX-ray2.60A46-300[»]
5F1KX-ray2.30A/B45-300[»]
5F1OX-ray2.20A46-300[»]
5F21X-ray1.90A46-300[»]
ProteinModelPortaliP28907.
SMRiP28907.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi107390. 6 interactors.
MINTiMINT-4536880.
STRINGi9606.ENSP00000226279.

Chemistry databases

BindingDBiP28907.
ChEMBLiCHEMBL4660.
DrugBankiDB09331. Daratumumab.
GuidetoPHARMACOLOGYi2766.

PTM databases

iPTMnetiP28907.
PhosphoSitePlusiP28907.
SwissPalmiP28907.

Polymorphism and mutation databases

BioMutaiCD38.
DMDMi55977782.

Proteomic databases

EPDiP28907.
MaxQBiP28907.
PaxDbiP28907.
PeptideAtlasiP28907.
PRIDEiP28907.

Protocols and materials databases

DNASUi952.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000226279; ENSP00000226279; ENSG00000004468. [P28907-1]
ENST00000502843; ENSP00000427277; ENSG00000004468. [P28907-2]
GeneIDi952.
KEGGihsa:952.
UCSCiuc003gol.2. human. [P28907-1]

Organism-specific databases

CTDi952.
DisGeNETi952.
GeneCardsiCD38.
HGNCiHGNC:1667. CD38.
HPAiCAB002493.
CAB025255.
HPA022132.
HPA052381.
MIMi107270. gene.
neXtProtiNX_P28907.
OpenTargetsiENSG00000004468.
PharmGKBiPA26214.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IH8E. Eukaryota.
ENOG4111W33. LUCA.
GeneTreeiENSGT00390000017291.
HOGENOMiHOG000293141.
HOVERGENiHBG005277.
InParanoidiP28907.
KOiK01242.
OMAiCKNIYRP.
OrthoDBiEOG091G0GI3.
PhylomeDBiP28907.
TreeFamiTF332530.

Enzyme and pathway databases

BioCyciMetaCyc:HS00103-MONOMER.
ZFISH:HS00103-MONOMER.
BRENDAi2.4.99.20. 2681.
3.2.2.5. 2681.
SABIO-RKP28907.

Miscellaneous databases

EvolutionaryTraceiP28907.
GeneWikiiCD38.
GenomeRNAii952.
PROiP28907.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000004468.
CleanExiHS_CD38.
ExpressionAtlasiP28907. baseline and differential.
GenevisibleiP28907. HS.

Family and domain databases

Gene3Di3.40.50.720. 1 hit.
InterProiIPR003193. ADP-ribosyl_cyclase.
IPR033567. CD38.
IPR016040. NAD(P)-bd_dom.
[Graphical view]
PANTHERiPTHR10912. PTHR10912. 1 hit.
PTHR10912:SF5. PTHR10912:SF5. 1 hit.
PfamiPF02267. Rib_hydrolayse. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiCD38_HUMAN
AccessioniPrimary (citable) accession number: P28907
Secondary accession number(s): O00121, O00122, Q96HY4
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 1, 1992
Last sequence update: November 23, 2004
Last modified: November 2, 2016
This is version 177 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human cell differentiation molecules
    CD nomenclature of surface proteins of human leucocytes and list of entries
  2. Human chromosome 4
    Human chromosome 4: entries, gene names and cross-references to MIM
  3. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  7. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.