Reviewed, UniProtKB/Swiss-Prot Q16878 (CDO1_HUMAN)

Names and origin

Protein names

Recommended name:
    Cysteine dioxygenase type 1
    EC=1.13.11.20
Alternative name(s):
    Cysteine dioxygenase type I
      Short name=CDO-I
      Short name=CDO

Gene names

Name:

CDO1

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

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

Protein attributes

Sequence length	200 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Initiates several important metabolic pathways related to pyruvate and several sulfurate compounds including sulfate, hypotaurine and taurine. Critical regulator of cellular cysteine concentrations. Has an important role in maintaining the hepatic concentation of intracellular free cysteine within a proper narrow range.
Catalytic activity	L-cysteine + O(2) = 3-sulfinoalanine.
Cofactor	Binds 1 iron ion per subunit. Zinc to a much lesser extent.
Pathway	Organosulfur biosynthesis; taurine biosynthesis; hypotaurine from L-cysteine: step 1/2.
Subunit structure	Monomer.
Tissue specificity	Highly expressed in liver and placenta. Low expression in heart, brain and pancreas. Also detected in hepatoblastoma HepG2 cells.
Induction	In hepatoblastoma HepG2 cells, down-regulated by phorbol 12-myristate 13-acetate.
Post-translational modification	The thioether cross-link between Cys-93 and Tyr-157 plays a structural role through stabilizing the ferrous ion, and prevents the production of highly damaging free hydroxyl radicals by holding the oxygen radical via hydroxyl hydrogen.
Sequence similarities	Belongs to the cysteine dioxygenase family.

Ontologies

Keywords
Coding sequence diversity	Polymorphism
Ligand	Iron Metal-binding
Molecular function	Dioxygenase Oxidoreductase
PTM	Phosphoprotein Thioether bond
Technical term	3D-structure
Gene Ontology (GO)
Biological process	L-cysteine metabolic process Inferred from electronic annotation. Source: InterPro inflammatory response Traceable author statement. Source: UniProtKB oxidation reduction Traceable author statement. Source: UniProtKB sulfur amino acid biosynthetic process Traceable author statement. Source: UniProtKB taurine biosynthetic process Traceable author statement. Source: UniProtKB
Cellular component	cytosol Traceable author statement. Source: UniProtKB
Molecular function	cysteine dioxygenase activity Inferred from sequence or structural similarity. Source: UniProtKB iron ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 200

200

Cysteine dioxygenase type 1

PRO_0000206606

Sites

Metal binding

86

1

Iron; catalytic

Metal binding

88

1

Iron; catalytic

Metal binding

140

1

Iron; catalytic

Amino acid modifications

Modified residue

59

1

Phosphothreonine

Cross-link

93 ↔ 157

3'-(S-cysteinyl)-tyrosine (Cys-Tyr)

Natural variations

Natural variant

45

1

T → I: dbSNP rs1042867.

VAR_023536

Natural variant

143

1

E → Q in a colorectal cancer sample; somatic mutation.

VAR_036170

Experimental info

Mutagenesis

60

1

R → Q: Reduces enzyme activity by 70%. Reduces iron and zinc incorporation by 50%

Mutagenesis

93

1

C → S: Reduces enzyme activity and iron incorporation by 50%. Zinc incorporation increased by 20%

Mutagenesis

157

1

Y → F: Almost total loss of enzyme activity and iron incorporation. Reduces zinc incorporation by 20%

Mutagenesis

164

1

C → S: Reduces enzyme activity by 20%. Little effect on iron incorporation. No effect on zinc incorporation

Sequence conflict

137

1

I → V in AAH24241. Ref.5

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

200

Helix Strand Turn

Details...

Helix

12 – 22

11

Helix

30 – 39

10

Helix

44 – 47

4

Helix

48 – 50

3

Beta strand

55 – 57

3

Beta strand

59 – 64

6

Helix

66 – 68

3

Beta strand

71 – 77

7

Beta strand

92 – 100

9

Beta strand

102 – 107

6

Beta strand

119 – 124

6

Beta strand

130 – 133

4

Turn

135 – 137

3

Beta strand

139 – 144

6

Beta strand

147 – 149

3

Beta strand

151 – 159

9

Beta strand

162 – 167

6

Turn

169 – 171

3

Beta strand

174 – 178

5

Beta strand

182 – 184

3

Sequences

	Sequence		Length	Mass (Da)
	Q16878-1 [UniParc]. Last modified September 27, 2005. Version 2. Checksum: E4EF87221D05C14D	FASTA	200	22,972
	10 20 30 40 50 60 MEQTEVLKPR TLADLIRILH QLFAGDEVNV EEVQAIMEAY ESDPTEWAMY AKFDQYRYTR 70 80 90 100 110 120 NLVDQGNGKF NLMILCWGEG HGSSIHDHTN SHCFLKMLQG NLKETLFAWP DKKSNEMVKK 130 140 150 160 170 180 SERVLRENQC AYINDSIGLH RVENISHTEP AVSLHLYSPP FDTCHAFDQR TGHKNKVTMT 190 200 FHSKFGIRTP NATSGSLENN

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Human cysteine dioxygenase type I: primary structure derived from base sequencing of cDNA." McCann K.P., Akbari M.T., Williams A.C., Ramsden D.B. Biochim. Biophys. Acta 1209:107-110(1994) [PubMed: 7524679] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT ILE-45. Tissue: Liver.
[2]	"Human cysteine dioxygenase gene: structural organization, tissue-specific expression and downregulation by phorbol 12-myristate 13-acetate." Tsuboyama-Kasaoka N., Hosokawa Y., Kodama H., Matsumoto A., Oka J., Totani M. Biosci. Biotechnol. Biochem. 63:1017-1024(1999) [PubMed: 10427686] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], INDUCTION, TISSUE SPECIFICITY. Tissue: Liver.
[3]	"Human cysteine dioxygenase type I (CDO-I; EC 1.13.11.20): 5' flanking region and intron-exon structure of the gene." Ramsden D.B., Kapadi A.L., Fitch N.J., Farmer M.J., Bennett P., Williams A.C. Mol. Pathol. 50:269-271(1997) [PubMed: 9497919] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT ILE-45.
[4]	"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)." Halleck A., Ebert L., Mkoundinya M., Schick M., Eisenstein S., Neubert P., Kstrang K., Schatten R., Shen B., Henze S., Mar W., Korn B., Zuo D., Hu Y., LaBaer J. Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[5]	"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]. Tissue: Brain.
[6]	"Large-scale characterization of HeLa cell nuclear phosphoproteins." Beausoleil S.A., Jedrychowski M., Schwartz D., Elias J.E., Villen J., Li J., Cohn M.A., Cantley L.C., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 101:12130-12135(2004) [PubMed: 15302935] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-59, MASS SPECTROMETRY. Tissue: Epithelium.
[7]	"An insight into the mechanism of human cysteine dioxygenase. Key roles of the thioether-bonded tyrosine-cysteine cofactor." Ye S., Wu X., Wei L., Tang D., Sun P., Bartlam M., Rao Z. J. Biol. Chem. 282:3391-3402(2007) [PubMed: 17135237] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 2-200 OF WILD-TYPE AND MUTANTS ARG-60; CYS-93; TYR-157 AND CYS-164 IN COMPLEX WITH L-CYSTEINE AND DIVALENT METAL IONS, CROSS-LINK, SUBUNIT, MASS SPECTROMETRY.
[8]	"The consensus coding sequences of human breast and colorectal cancers." Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E. Science 314:268-274(2006) [PubMed: 16959974] [Abstract] Cited for: VARIANT [LARGE SCALE ANALYSIS] GLN-143.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBLGenBankDDBJ

Z31357 mRNA. Translation: CAA83234.1.
Z23010 mRNA. Translation: CAA80552.1.
D85782 Genomic DNA. Translation: BAA12873.1.
D85777 mRNA. Translation: BAA12872.1.
U80055, U60232, U78979 Genomic DNA. Translation: AAB58352.1.
CR536540 mRNA. Translation: CAG38777.1.
BC024241 mRNA. Translation: AAH24241.1.

PIR

S50192.

RefSeq

NP_001792.2.

UniGene

Hs.442378

3D structure databases

PDBMSD

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2IC1	X-ray	2.70	A	2-200	[»]

ModBase

Search...

PTM databases

PhosphoSite

Q16878.

Genome annotation databases

Ensembl

ENSG00000129596. Homo sapiens. [Contig view]

GeneID

1036.

KEGG

hsa:1036.

Organism-specific databases

HGNC

HGNC:1795. CDO1.

MIM

603943. gene.

PharmGKB

PA26327.

GenAtlas

Search...

GeneCards

Search...

Phylogenomic databases

HOGENOM

Q16878.

HOVERGEN

Q16878.

Gene expression databases

ArrayExpress

Q16878.

CleanEx

HS_CDO1.

GermOnline

ENSG00000129596. Homo sapiens.

Family and domain databases

InterPro

IPR010300. Cys_dOase_I.
[Graphical view]

Pfam

PF05995. CDO_I. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

DrugBank

DB00151. L-Cysteine.
DB00157. NADH.

NextBio

4353.

SOURCE

Search...

Entry information

Entry name

CDO1_HUMAN

Accession

Primary (citable) accession number: Q16878
Secondary accession number(s): P78513, Q6FHZ8, Q8TB64

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	September 27, 2005
Last modified:	November 25, 2008
This is version 69 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)