O96007 (MOC2B_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Molybdopterin synthase catalytic subunit
EC=2.8.1.12

Alternative name(s):
MOCO1-B
Molybdenum cofactor synthesis protein 2 large subunit
Molybdenum cofactor synthesis protein 2B
Short name=MOCS2B
Molybdopterin-synthase large subunit
Short name=MPT synthase large subunit

Gene names

Name:	MOCS2
Synonyms:	MCBPE, MOCO1

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	188 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Catalytic subunit of the molybdopterin synthase complex, a complex that catalyzes the conversion of precursor Z into molybdopterin. Acts by mediating the incorporation of 2 sulfur atoms from thiocarboxylated MOCS2A into precursor Z to generate a dithiolene group. Ref.8 Ref.9
Catalytic activity	Cyclic pyranopterin monophosphate + 2 [molybdopterin-synthase sulfur-carrier protein]-Gly-NH-CH(2)-C(O)SH + H2O = molybdopterin + 2 [molybdopterin-synthase sulfur-carrier protein]. Ref.8 Ref.9
Pathway	Cofactor biosynthesis; molybdopterin biosynthesis.
Subunit structure	Heterotetramer; composed of 2 small (MOCS2A) and 2 large (MOCS2B) subunits By similarity. Ref.8 Ref.9
Subcellular location	Cytoplasm › cytosol Ref.9.
Tissue specificity	Highest levels are found in heart and skeletal muscle. Lower levels are present in brain, kidney and pancreas. Very low levels are found in lung and peripheral blood leukocytes. Ref.1
Involvement in disease	Molybdenum cofactor deficiency type B (MOCOD type B) [MIM:252150]: Autosomal recessive disease which leads to the pleiotropic loss of all molybdoenzyme activities and is characterized by severe neurological damage, neonatal seizures and early childhood death. Note: The disease is caused by mutations affecting the gene represented in this entry.
Miscellaneous	This protein is produced by a bicistronic gene which also produces the small subunit (MOCS2A) from an overlapping reading frame. Expression of these 2 proteins are related since a mutation that removes the start codon of the small subunit (MOCS2A) also impairs expression of the large subunit (MOCS2B).
Sequence similarities	Belongs to the MoaE family. MOCS2B subfamily.

Ontologies

Keywords
Biological process	Molybdenum cofactor biosynthesis
Cellular component	Cytoplasm
Coding sequence diversity	Polymorphism
Disease	Disease mutation
Molecular function	Transferase
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	water-soluble vitamin metabolic process Traceable author statement. Source: Reactome
Cellular_component	cytosol Inferred from direct assay Ref.9. Source: UniProtKB molybdopterin synthase complex Inferred from physical interaction Ref.8. Source: UniProtKB nucleus Inferred from direct assay. Source: HPA
Molecular_function	Mo-molybdopterin synthase activity Inferred from direct assay Ref.8Ref.9. Source: UniProtKB transferase activity Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 188

188

Molybdopterin synthase catalytic subunit

PRO_0000163111

Regions

Region

143 – 144

2

Substrate binding By similarity

Region

166 – 168

3

Substrate binding By similarity

Sites

Binding site

159

1

Substrate By similarity

Amino acid modifications

Modified residue

20

1

Phosphoserine Ref.10 Ref.11 Ref.12 Ref.13 Ref.14

Natural variations

Natural variant

50

1

T → A.
Corresponds to variant rs2233213 [ dbSNP | Ensembl ].

VAR_050091

Natural variant

77

1

T → A.
Corresponds to variant rs2233215 [ dbSNP | Ensembl ].

VAR_050092

Natural variant

123

1

H → Y.
Corresponds to variant rs2233218 [ dbSNP | Ensembl ].

VAR_050093

Natural variant

168

1

E → K in MOCOD type B. Ref.16

VAR_012765

Natural variant

187

1

N → S.
Corresponds to variant rs2233221 [ dbSNP | Ensembl ].

VAR_050094

Secondary structure

1

.

.

.

.

.

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.

.

.

.

.

.

.

.

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.

.

.

.

.

.

.

188

Helix Strand Turn

Details...

Beta strand

45 – 52

8

Helix

56 – 62

7

Beta strand

69 – 77

9

Beta strand

80 – 82

3

Beta strand

85 – 96

12

Helix

98 – 113

16

Beta strand

116 – 124

9

Beta strand

126 – 129

4

Beta strand

132 – 143

12

Helix

144 – 161

18

Beta strand

164 – 170

7

Sequences

	Sequence		Length	Mass (Da)
	O96007 [UniParc]. Last modified May 1, 1999. Version 1. Checksum: F405256D85621146	FASTA	188	20,944
	10 20 30 40 50 60 MSSLEISSSC FSLETKLPLS PPLVEDSAFE PSRKDMDEVE EKSKDVINFT AEKLSVDEVS 70 80 90 100 110 120 QLVISPLCGA ISLFVGTTRN NFEGKKVISL EYEAYLPMAE NEVRKICSDI RQKWPVKHIA 130 140 150 160 170 180 VFHRLGLVPV SEASIIIAVS SAHRAASLEA VSYAIDTLKA KVPIWKKEIY EESSTWKGNK ECFWASNS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Human molybdopterin synthase gene: identification of a bicistronic transcript with overlapping reading frames." Stallmeyer B., Drugeon G., Reiss J., Haenni A.L., Mendel R.R. Am. J. Hum. Genet. 64:698-705(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], IDENTIFICATION OF BICISTRONIC GENE, TISSUE SPECIFICITY. Tissue: Liver.
[2]	"The two subunits of human molybdopterin synthase: evidence for a bicistronic messenger RNA with overlapping reading frames." Sloan J., Kinghorn J.R., Unkles S.E. Nucleic Acids Res. 27:854-858(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	Huang C., Huang Q., Wu T., Peng Y., Gu Y., Zhang L., Jiang C., Li Y., Han Z., Wang Y., Chen Z., Fu G. Submitted (JUN-1999) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Adrenal gland.
[4]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Uterus.
[5]	"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)." Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B. Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[6]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	"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]. Tissue: Duodenum.
[8]	"Mechanistic studies of human molybdopterin synthase reaction and characterization of mutants identified in group B patients of molybdenum cofactor deficiency." Leimkuehler S., Freuer A., Araujo J.A., Rajagopalan K.V., Mendel R.R. J. Biol. Chem. 278:26127-26134(2003) [PubMed] [Europe PMC] [Abstract] Cited for: ENZYME ACTIVITY, FUNCTION, SUBUNIT.
[9]	"Evidence for the physiological role of a rhodanese-like protein for the biosynthesis of the molybdenum cofactor in humans." Matthies A., Rajagopalan K.V., Mendel R.R., Leimkuehler S. Proc. Natl. Acad. Sci. U.S.A. 101:5946-5951(2004) [PubMed] [Europe PMC] [Abstract] Cited for: ENZYME ACTIVITY, FUNCTION, SUBUNIT, SUBCELLULAR LOCATION.
[10]	"A probability-based approach for high-throughput protein phosphorylation analysis and site localization." Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P. Nat. Biotechnol. 24:1285-1292(2006) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-20, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[11]	"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle." Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M. Mol. Cell 31:438-448(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-20, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[12]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-20, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[13]	"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions." Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K. Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-20, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[14]	"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis." Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M. Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-20, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[15]	"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].
[16]	"Human molybdopterin synthase gene: genomic structure and mutations in molybdenum cofactor deficiency type B." Reiss J., Dorche C., Stallmeyer B., Mendel R.R., Cohen N., Zabot M.-T. Am. J. Hum. Genet. 64:706-711(1999) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT MOCOD TYPE B LYS-168.
[17]	"Ten novel mutations in the molybdenum cofactor genes MOCS1 and MOCS2 and in vitro characterization of a MOCS2 mutation that abolishes the binding ability of molybdopterin synthase." Leimkuehler S., Charcosset M., Latour P., Dorche C., Kleppe S., Scaglia F., Szymczak I., Schupp P., Hahnewald R., Reiss J. Hum. Genet. 117:565-570(2005) [PubMed] [Europe PMC] [Abstract] Cited for: INVOLVEMENT IN MOCOD TYPE B.
[18]	"A novel MOCS2 mutation reveals coordinated expression of the small and large subunit of molybdopterin synthase." Hahnewald R., Leimkuehler S., Vilaseca A., Acquaviva-Bourdain C., Lenz U., Reiss J. Mol. Genet. Metab. 89:210-213(2006) [PubMed] [Europe PMC] [Abstract] Cited for: INVOLVEMENT IN MOCOD TYPE B.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AF091871 mRNA. Translation: AAD14599.1.
AF117815 mRNA. Translation: AAD13297.1.
AF155659 mRNA. Translation: AAF67478.1.
AK312887 mRNA. Translation: BAG35735.1.
CR457172 mRNA. Translation: CAG33453.1.
CH471123 Genomic DNA. Translation: EAW54874.1.
BC046097 mRNA. Translation: AAH46097.1.

IPI

IPI00005218.

PIR

B59370.

RefSeq

NP_004522.1. NM_004531.3.

UniGene

Hs.163645.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
4AP8	X-ray	2.78	A/B/C/D	38-172	[»]

ProteinModelPortal

O96007.

ModBase

Search...

Protein-protein interaction databases

IntAct

O96007. 3 interactions.

STRING

9606.ENSP00000339580.

PTM databases

PhosphoSite

O96007.

Proteomic databases

PRIDE

O96007.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000396954; ENSP00000380157; ENSG00000164172.

GeneID

4338.

KEGG

hsa:4338.

UCSC

uc003joz.3. human.

Organism-specific databases

CTD

4338.

GeneCards

GC05M052429.

HGNC

HGNC:7193. MOCS2.

HPA

HPA037680.

MIM

252150. phenotype.
603708. gene.

neXtProt

NX_O96007.

PharmGKB

PA30903.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

HOG000280991.

InParanoid

O96007.

KO

K03635.

OMA

PMAENEI.

OrthoDB

EOG4V439D.

PhylomeDB

O96007.

Enzyme and pathway databases

BioCyc

MetaCyc:HS09033-MONOMER.

Reactome

REACT_111217. Metabolism.

UniPathway

UPA00344.

Gene expression databases

ArrayExpress

O96007.

Bgee

O96007.

CleanEx

HS_MOCS2.

Genevestigator

O96007.

GermOnline

ENSG00000164172. Homo sapiens.

Family and domain databases

Gene3D

3.90.1170.40. 1 hit.

InterPro

IPR003448. Mopterin_biosynth_MoaE.
[Graphical view]

PANTHER

PTHR23404:SF2. PTHR23404:SF2. 1 hit.

Pfam

PF02391. MoaE. 1 hit.
[Graphical view]

SUPFAM

SSF54690. Mb_biosynth_MoaE. 1 hit.

ProtoNet

Search...

Other

GenomeRNAi

4338.

NextBio

17072.

SOURCE

Search...

Entry information

Entry name

MOC2B_HUMAN

Accession

Primary (citable) accession number: O96007
Secondary accession number(s): Q6IAI3

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 11, 2002
Last sequence update:	May 1, 1999
Last modified:	May 1, 2013
This is version 108 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

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.