P11172 (UMPS_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Uridine 5'-monophosphate synthase
Short name=UMP synthase

Including the following 2 domains:

1. Orotate phosphoribosyltransferase
   Short name=OPRT
   Short name=OPRTase
   EC=2.4.2.10
2. Orotidine 5'-phosphate decarboxylase
   Short name=ODC
   EC=4.1.1.23
   Alternative name(s):
   OMPdecase

Gene names

Name:	UMPS
ORF Names:	OK/SW-cl.21

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	480 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Catalytic activity	Orotidine 5'-phosphate + diphosphate = orotate + 5-phospho-alpha-D-ribose 1-diphosphate. Orotidine 5'-phosphate = UMP + CO2.
Pathway	Pyrimidine metabolism; UMP biosynthesis via de novo pathway; UMP from orotate: step 1/2. Pyrimidine metabolism; UMP biosynthesis via de novo pathway; UMP from orotate: step 2/2.
Subunit structure	Homodimer. Ref.15
Involvement in disease	Defects in UMPS are the cause of orotic aciduria type 1 (ORAC1) [MIM:258900]. A disorder of pyrimidine metabolism resulting in megaloblastic anemia and orotic acid crystalluria that is frequently associated with some degree of physical and mental retardation. A minority of cases have additional features, particularly congenital malformations and immune deficiencies. Ref.3
Sequence similarities	In the N-terminal section; belongs to the purine/pyrimidine phosphoribosyltransferase family. In the C-terminal section; belongs to the OMP decarboxylase family.
Sequence caution	The sequence CAB45710.3 differs from that shown. Reason: Erroneous termination at position 430. Translated as Gln.

Ontologies

Keywords
Biological process	Pyrimidine biosynthesis
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Disease mutation
Molecular function	Decarboxylase Glycosyltransferase Lyase Transferase
PTM	Acetylation Phosphoprotein
Technical term	3D-structure Complete proteome Multifunctional enzyme Reference proteome
Gene Ontology (GO)
Biological process	'de novo' UMP biosynthetic process Inferred from electronic annotation. Source: InterPro 'de novo' pyrimidine base biosynthetic process Inferred from electronic annotation. Source: InterPro pyrimidine nucleoside biosynthetic process Traceable author statement. Source: Reactome
Cellular component	cytosol Traceable author statement. Source: Reactome nucleus Inferred from direct assay. Source: UniProtKB
Molecular function	orotate phosphoribosyltransferase activity Inferred from direct assay. Source: UniProtKB orotidine-5'-phosphate decarboxylase activity Inferred from direct assay. Source: UniProtKB
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P11172-1)

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: P11172-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-178: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed

Chain

2 – 480

479

Uridine 5'-monophosphate synthase

PRO_0000139649

Regions

Region

2 – 214

213

OPRTase

Region

215 – 220

6

Domain linker

Region

221 – 480

260

OMPdecase

Sites

Active site

312

1

For OMPdecase activity Ref.15

Active site

314

1

For OMPdecase activity Ref.15

Active site

317

1

For OMPdecase activity Ref.15

Amino acid modifications

Modified residue

2

1

N-acetylalanine Ref.12

Modified residue

37

1

Phosphotyrosine Ref.10

Modified residue

162

1

N6-acetyllysine Ref.13

Modified residue

214

1

Phosphoserine Ref.11

Natural variations

Alternative sequence

1 – 178

178

Missing in isoform 2.

VSP_009273

Natural variant

30

1

S → G. Ref.7
Corresponds to variant rs17843776 [ dbSNP | Ensembl ].

VAR_020614

Natural variant

96

1

R → G in ORAC1. Ref.3

VAR_006807

Natural variant

109

1

V → G in ORAC1. Ref.3

VAR_006808

Natural variant

213

1

G → A. Ref.3 Ref.7
Corresponds to variant rs1801019 [ dbSNP | Ensembl ].

VAR_006809

Natural variant

429

1

G → R in ORAC1. Ref.3

VAR_006810

Natural variant

446

1

I → V. Ref.7
Corresponds to variant rs3772809 [ dbSNP | Ensembl ].

VAR_020615

Experimental info

Mutagenesis

312

1

D → N: Loss of OMPdecase activity. Ref.15

Sequence conflict

13

1

T → G in AAA61256. Ref.9

Sequence conflict

377

1

L → Q in AAA61256. Ref.9

Secondary structure

1

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480

Helix Strand Turn

Details...

Helix

227 – 230

4

Helix

238 – 250

13

Beta strand

254 – 257

4

Helix

263 – 273

11

Helix

274 – 276

3

Beta strand

278 – 282

5

Helix

284 – 286

3

Helix

292 – 305

14

Beta strand

308 – 315

8

Helix

319 – 327

9

Turn

329 – 331

3

Helix

333 – 335

3

Beta strand

338 – 344

7

Helix

349 – 358

10

Turn

359 – 362

4

Beta strand

364 – 368

5

Helix

380 – 392

13

Turn

393 – 396

4

Beta strand

397 – 401

5

Beta strand

412 – 416

5

Beta strand

421 – 423

3

Helix

435 – 440

6

Beta strand

445 – 450

6

Helix

451 – 454

4

Helix

459 – 478

20

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified July 1, 1989. Version 1. Checksum: D985CD566B72F5CA	FASTA	480	52,222
	10 20 30 40 50 60 MAVARAALGP LVTGLYDVQA FKFGDFVLKS GLSSPIYIDL RGIVSRPRLL SQVADILFQT 70 80 90 100 110 120 AQNAGISFDT VCGVPYTALP LATVICSTNQ IPMLIRRKET KDYGTKRLVE GTINPGETCL 130 140 150 160 170 180 IIEDVVTSGS SVLETVEVLQ KEGLKVTDAI VLLDREQGGK DKLQAHGIRL HSVCTLSKML 190 200 210 220 230 240 EILEQQKKVD AETVGRVKRF IQENVFVAAN HNGSPLSIKE APKELSFGAR AELPRIHPVA 250 260 270 280 290 300 SKLLRLMQKK ETNLCLSADV SLARELLQLA DALGPSICML KTHVDILNDF TLDVMKELIT 310 320 330 340 350 360 LAKCHEFLIF EDRKFADIGN TVKKQYEGGI FKIASWADLV NAHVVPGSGV VKGLQEVGLP 370 380 390 400 410 420 LHRGCLLIAE MSSTGSLATG DYTRAAVRMA EEHSEFVVGF ISGSRVSMKP EFLHLTPGVQ 430 440 450 460 470 480 LEAGGDNLGQ QYNSPQEVIG KRGSDIIIVG RGIISAADRL EAAEMYRKAA WEAYLSRLGV
	Isoform 2 [UniParc]. Checksum: 4B88EE5A8DC6FA65	FASTA	302	33,051
	10 20 30 40 50 60 MLEILEQQKK VDAETVGRVK RFIQENVFVA ANHNGSPLSI KEAPKELSFG ARAELPRIHP 70 80 90 100 110 120 VASKLLRLMQ KKETNLCLSA DVSLARELLQ LADALGPSIC MLKTHVDILN DFTLDVMKEL 130 140 150 160 170 180 ITLAKCHEFL IFEDRKFADI GNTVKKQYEG GIFKIASWAD LVNAHVVPGS GVVKGLQEVG 190 200 210 220 230 240 LPLHRGCLLI AEMSSTGSLA TGDYTRAAVR MAEEHSEFVV GFISGSRVSM KPEFLHLTPG 250 260 270 280 290 300 VQLEAGGDNL GQQYNSPQEV IGKRGSDIII VGRGIISAAD RLEAAEMYRK AAWEAYLSRL GV

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular cloning and nucleotide sequence for the complete coding region of human UMP synthase." Suttle D.P., Bugg B.Y., Winkler J.K., Kanalas J.J. Proc. Natl. Acad. Sci. U.S.A. 85:1754-1758(1988) [PubMed: 3279416] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]	"Molecular cloning of human UMP synthase." Suchi M., Harada N., Tsuboi T., Asai K., Okajima K., Wada Y., Takagi Y. Adv. Exp. Med. Biol. 253A:511-518(1989) [PubMed: 2624233] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]	"Molecular cloning of the human UMP synthase gene and characterization of point mutations in two hereditary orotic aciduria families." Suchi M., Mizuno H., Kawai Y., Tsuboi T., Sumi S., Okajima K., Hodgson M.E., Ogawa H., Wada Y. Am. J. Hum. Genet. 60:525-539(1997) [PubMed: 9042911] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS ORAC1 GLY-96; GLY-109 AND ARG-429, VARIANT ALA-213. Tissue: Leukocyte.
[4]	"Identification of immuno-peptidmics that are recognized by tumor-reactive CTL generated from TIL of colon cancer patients." Shichijo S., Itoh K. Submitted (MAY-2001) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Colon adenocarcinoma.
[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] (ISOFORM 1).
[6]	"The full-ORF clone resource of the German cDNA consortium." Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I. BMC Genomics 8:399-399(2007) [PubMed: 17974005] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Tissue: Fetal brain.
[7]	NIEHS SNPs program Submitted (JUL-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS GLY-30; ALA-213 AND VAL-446.
[8]	"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: Muscle.
[9]	"Molecular genetic studies on hereditary orotic aciduria: I. Purification of human orotidine 5'-monophosphate decarboxylase and cloning of its cDNA." Suchi M. Nagoya Med. J. 32:207-220(1988) Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 13-480 (ISOFORM 1).
[10]	"Global survey of phosphotyrosine signaling identifies oncogenic kinases in lung cancer." Rikova K., Guo A., Zeng Q., Possemato A., Yu J., Haack H., Nardone J., Lee K., Reeves C., Li Y., Hu Y., Tan Z., Stokes M., Sullivan L., Mitchell J., Wetzel R., Macneill J., Ren J.M. , Yuan J., Bakalarski C.E., Villen J., Kornhauser J.M., Smith B., Li D., Zhou X., Gygi S.P., Gu T.-L., Polakiewicz R.D., Rush J., Comb M.J. Cell 131:1190-1203(2007) [PubMed: 18083107] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-37, MASS SPECTROMETRY. Tissue: Lung carcinoma.
[11]	"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: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-214, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[12]	"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach." Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S. Anal. Chem. 81:4493-4501(2009) [PubMed: 19413330] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, MASS SPECTROMETRY. Tissue: Embryonic kidney.
[13]	"Lysine acetylation targets protein complexes and co-regulates major cellular functions." Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T., Olsen J.V., Mann M. Science 325:834-840(2009) [PubMed: 19608861] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-162, MASS SPECTROMETRY.
[14]	"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: 21269460] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[15]	"Structures of the human orotidine-5'-monophosphate decarboxylase support a covalent mechanism and provide a framework for drug design." Wittmann J.G., Heinrich D., Gasow K., Frey A., Diederichsen U., Rudolph M.G. Structure 16:82-92(2008) [PubMed: 18184586] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.22 ANGSTROMS) OF 224-480 IN COMPLEX WITH SUBSTRATE, SUBUNIT, ACTIVE SITE, MUTAGENESIS OF ASP-312.
+	Additional computationally mapped references.

Web resources

GeneReviews

NIEHS-SNPs

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

J03626 mRNA. Translation: AAA61255.1.
D86227 mRNA. Translation: BAA19920.1.
D86228 mRNA. Translation: BAA19921.1.
D86230 mRNA. Translation: BAA19923.1.
AB041359 Genomic DNA. Translation: BAB20663.1.
AB062285 mRNA. Translation: BAB93468.1.
CR456787 mRNA. Translation: CAG33068.1.
AL080099 mRNA. Translation: CAB45710.3. Sequence problems.
AY691629 Genomic DNA. Translation: AAT85801.1.
BC000364 mRNA. Translation: AAH00364.1.
BC007511 mRNA. Translation: AAH07511.1.
M36661 mRNA. Translation: AAA61256.1.

IPI

IPI00003923.
IPI00398067.

PIR

A30148.

RefSeq

NP_000364.1. NM_000373.3.

UniGene

Hs.2057.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2EAW	X-ray	2.88	A/B	190-480	[»]
2JGY	X-ray	1.95	A/B	224-479	[»]
2P1F	X-ray	1.76	A	190-480	[»]
2QCC	X-ray	1.85	A/B	224-480	[»]
2QCD	X-ray	2.03	A/B	224-480	[»]
2QCE	X-ray	1.43	A	224-480	[»]
2QCF	X-ray	1.22	A	224-480	[»]
2QCG	X-ray	1.75	A/B	224-480	[»]
2QCH	X-ray	1.95	A/B	224-480	[»]
2QCL	X-ray	1.85	A/B	224-480	[»]
2QCM	X-ray	1.67	A	224-480	[»]
2QCN	X-ray	1.85	A/B	224-480	[»]
2V30	X-ray	2.00	A/B	224-479	[»]
2WNS	X-ray	1.90	A/B	7-203	[»]
3BGG	X-ray	1.93	A	190-480	[»]
3BGJ	X-ray	2.00	A/B	190-480	[»]
3BK0	X-ray	1.60	A/B	223-480	[»]
3BVJ	X-ray	1.80	A/B	190-480	[»]
3DBP	X-ray	1.50	A/B	223-480	[»]
3EWU	X-ray	1.60	A/B	224-480	[»]
3EWW	X-ray	1.10	A/B	224-480	[»]
3EWX	X-ray	1.40	A	224-480	[»]
3EWY	X-ray	1.10	A	224-480	[»]
3EWZ	X-ray	1.40	A/B/C/D	224-480	[»]
3EX1	X-ray	1.40	A/B	224-480	[»]
3EX2	X-ray	1.55	A/B	224-480	[»]
3EX3	X-ray	1.45	A/B	224-480	[»]
3EX4	X-ray	1.24	A	224-480	[»]
3EX6	X-ray	1.30	A/B	224-480	[»]
3G3D	X-ray	1.70	A/B	190-480	[»]
3G3M	X-ray	1.40	A	223-480	[»]
3L0K	X-ray	1.34	A/B	224-480	[»]
3L0N	X-ray	1.74	A/B	224-480	[»]
3MI2	X-ray	1.20	A/B	223-480	[»]
3MO7	X-ray	1.35	A	223-480	[»]
3MW7	X-ray	2.32	A/B	190-480	[»]

ProteinModelPortal

P11172.

SMR

P11172. Positions 7-203, 224-479.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-29595N.

IntAct

P11172. 11 interactions.

MINT

MINT-1397000.

STRING

P11172.

PTM databases

PhosphoSite

P11172.

Polymorphism databases

DMDM

131708.

Proteomic databases

PeptideAtlas

P11172.

PRIDE

P11172.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000232607; ENSP00000232607; ENSG00000114491.

GeneID

7372.

KEGG

hsa:7372.

NMPDR

fig|9606.3.peg.23088.

UCSC

uc003ehl.2. human.
uc003ehn.2. human.

Organism-specific databases

CTD

7372.

GeneCards

GC03P124466.

H-InvDB

HIX0003622.

HGNC

HGNC:12563. UMPS.

HPA

HPA036178.
HPA036179.

MIM

258900. phenotype.
613891. gene.

neXtProt

NX_P11172.

Orphanet

30. Hereditary orotic aciduria.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG05450.

GeneTree

ENSGT00390000001856.

HOVERGEN

HBG000870.

InParanoid

P11172.

OMA

AFKFGDF.

OrthoDB

EOG4TXBRR.

PhylomeDB

P11172.

Enzyme and pathway databases

BRENDA

4.1.1.23. 2681.

Reactome

REACT_111217. Metabolism.

Gene expression databases

ArrayExpress

P11172.

Bgee

P11172.

CleanEx

HS_UMPS.

Genevestigator

P11172.

GermOnline

ENSG00000114491. Homo sapiens.

Family and domain databases

InterPro

IPR013785. Aldolase_TIM.
IPR014732. OMPdecase.
IPR018089. OMPdecase_AS.
IPR001754. OMPdeCOase_dom.
IPR004467. Or_phspho_trans_clade-1.
IPR023031. Orotate_PribosylTferase.
IPR000836. PRibTrfase.
IPR011060. RibuloseP-bd_barrel.
[Graphical view]

Gene3D

G3DSA:3.20.20.70. Aldolase_TIM. 1 hit.

KO

K13421.

Pfam

PF00215. OMPdecase. 1 hit.
PF00156. Pribosyltran. 1 hit.
[Graphical view]

SMART

SM00934. OMPdecase. 1 hit.
[Graphical view]

SUPFAM

SSF51366. RibP_bind_barrel. 1 hit.

TIGRFAMs

TIGR00336. PyrE. 1 hit.
TIGR01740. PyrF. 1 hit.

PROSITE

PS00156. OMPDECASE. 1 hit.
PS00103. PUR_PYR_PR_TRANSFER. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

NextBio

28866.

SOURCE

Search...

Entry information

Entry name

UMPS_HUMAN

Accession

Primary (citable) accession number: P11172
Secondary accession number(s): O00758 , O00759, O00760, Q16862, Q9H3Q2, Q9UG49

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 1, 1989
Last sequence update:	July 1, 1989
Last modified:	January 25, 2012
This is version 144 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.