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Protein

Uroporphyrinogen decarboxylase

Gene

UROD

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

Functioni

Catalyzes the decarboxylation of four acetate groups of uroporphyrinogen-III to yield coproporphyrinogen-III.

Catalytic activityi

Uroporphyrinogen III = coproporphyrinogen + 4 CO2.

Pathwayi: protoporphyrin-IX biosynthesis

This protein is involved in step 4 of the subpathway that synthesizes coproporphyrinogen-III from 5-aminolevulinate.
Proteins known to be involved in the 4 steps of the subpathway in this organism are:
  1. Delta-aminolevulinic acid dehydratase (ALAD)
  2. Porphobilinogen deaminase (HMBS)
  3. Uroporphyrinogen-III synthase (UROS)
  4. Uroporphyrinogen decarboxylase (UROD), Uroporphyrinogen decarboxylase (UROD)
This subpathway is part of the pathway protoporphyrin-IX biosynthesis, which is itself part of Porphyrin-containing compound metabolism.
View all proteins of this organism that are known to be involved in the subpathway that synthesizes coproporphyrinogen-III from 5-aminolevulinate, the pathway protoporphyrin-IX biosynthesis and in Porphyrin-containing compound metabolism.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei55Substrate1
Binding sitei85Substrate1
Binding sitei86Substrate1
Sitei86Transition state stabilizer1
Binding sitei164Substrate1
Binding sitei219Substrate1
Binding sitei339Substrate1

GO - Molecular functioni

  • uroporphyrinogen decarboxylase activity Source: UniProtKB

GO - Biological processi

Keywordsi

Molecular functionDecarboxylase, Lyase
Biological processHeme biosynthesis, Porphyrin biosynthesis

Enzyme and pathway databases

BioCyciMetaCyc:HS04993-MONOMER
BRENDAi4.1.1.37 2681
ReactomeiR-HSA-189451 Heme biosynthesis
UniPathwayiUPA00251; UER00321

Names & Taxonomyi

Protein namesi
Recommended name:
Uroporphyrinogen decarboxylase (EC:4.1.1.37)
Short name:
UPD
Short name:
URO-D
Gene namesi
Name:UROD
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

EuPathDBiHostDB:ENSG00000126088.12
HGNCiHGNC:12591 UROD
MIMi613521 gene
neXtProtiNX_P06132

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Involvement in diseasei

Familial porphyria cutanea tarda (FPCT)10 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA form of porphyria. Porphyrias are inherited defects in the biosynthesis of heme, resulting in the accumulation and increased excretion of porphyrins or porphyrin precursors. They are classified as erythropoietic or hepatic, depending on whether the enzyme deficiency occurs in red blood cells or in the liver. Familial porphyria cutanea tarda is an autosomal dominant disorder characterized by light-sensitive dermatitis, with onset in later life. It is associated with the excretion of large amounts of uroporphyrin in the urine. Iron overload is often present in association with varying degrees of liver damage.
See also OMIM:176100
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_02256725G → E in FPCT; insoluble protein. 1 PublicationCorresponds to variant dbSNP:rs764268015Ensembl.1
Natural variantiVAR_02256980A → S in FPCT; decrease of activity. 2 PublicationsCorresponds to variant dbSNP:rs376921379Ensembl.1
Natural variantiVAR_010985142R → Q in FPCT. 1 Publication1
Natural variantiVAR_022570144R → P in FPCT; decrease of activity. 1 Publication1
Natural variantiVAR_022571156G → D in FPCT; decrease of activity. 1 PublicationCorresponds to variant dbSNP:rs762617943Ensembl.1
Natural variantiVAR_010986161L → Q in FPCT. 1 Publication1
Natural variantiVAR_007911165M → R in FPCT; activity < 2%. 2 PublicationsCorresponds to variant dbSNP:rs121918063Ensembl.1
Natural variantiVAR_022572193R → P in FPCT; insoluble protein. 1 PublicationCorresponds to variant dbSNP:rs143823335Ensembl.1
Natural variantiVAR_007912195L → F in FPCT. 1 PublicationCorresponds to variant dbSNP:rs121918064Ensembl.1
Natural variantiVAR_022573216L → Q in FPCT. 1 Publication1
Natural variantiVAR_022574218E → K in FPCT; significant decrease of activity. 1 Publication1
Natural variantiVAR_010987219S → F in FPCT. 1 PublicationCorresponds to variant dbSNP:rs982293378Ensembl.1
Natural variantiVAR_009106229F → L in FPCT. 1 Publication1
Natural variantiVAR_022575232F → L in FPCT; decrease of activity. 1 Publication1
Natural variantiVAR_010988235P → S in FPCT. 1 PublicationCorresponds to variant dbSNP:rs141312224Ensembl.1
Natural variantiVAR_007913253L → Q in FPCT; decrease of activity. 2 PublicationsCorresponds to variant dbSNP:rs36033115Ensembl.1
Natural variantiVAR_022576260I → T in FPCT; decrease of activity. 1 Publication1
Natural variantiVAR_007716281G → V in FPCT. 2 PublicationsCorresponds to variant dbSNP:rs121918057Ensembl.1
Natural variantiVAR_022577282L → R in FPCT. 1 Publication1
Natural variantiVAR_022578303G → S in FPCT. 1 PublicationCorresponds to variant dbSNP:rs964670864Ensembl.1
Natural variantiVAR_007914304N → K in FPCT. 1 PublicationCorresponds to variant dbSNP:rs121918065Ensembl.1
Natural variantiVAR_007915318G → R in FPCT. 2 PublicationsCorresponds to variant dbSNP:rs116233118Ensembl.1
Natural variantiVAR_009108324M → T in FPCT. 1 Publication1
Natural variantiVAR_007916332R → H in FPCT. 1 PublicationCorresponds to variant dbSNP:rs121918066Ensembl.1
Natural variantiVAR_007917334I → T in FPCT. 1 Publication1
Hepatoerythropoietic porphyria (HEP)10 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA form of porphyria. Porphyrias are inherited defects in the biosynthesis of heme, resulting in the accumulation and increased excretion of porphyrins or porphyrin precursors. They are classified as erythropoietic or hepatic, depending on whether the enzyme deficiency occurs in red blood cells or in the liver. HEP is a cutaneous porphyria that presents in infancy. It is characterized biochemically by excessive excretion of acetate-substituted porphyrins and accumulation of protoporphyrin in erythrocytes. Uroporphyrinogen decarboxylase levels are very low in erythrocytes and cultured skin fibroblasts.
See also OMIM:176100
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_02256846F → L in HEP; mild phenotype; strong decrease of activity. 2 PublicationsCorresponds to variant dbSNP:rs769378741Ensembl.1
Natural variantiVAR_00910362P → L in HEP. 1 PublicationCorresponds to variant dbSNP:rs121918060Ensembl.1
Natural variantiVAR_00791080A → G in HEP. 1 PublicationCorresponds to variant dbSNP:rs776907084Ensembl.1
Natural variantiVAR_065558168G → R in HEP; relative activity of 65% of wild-type towards uroporphyrinogen III. 1 Publication1
Natural variantiVAR_065559170G → D in HEP; relative activity of 17% and 60% of wild-type towards uroporphyrinogen I and III respectively. 1 Publication1
Natural variantiVAR_009105220H → P in HEP; mild form. 1 Publication1
Natural variantiVAR_007717292R → G in HEP. 1 PublicationCorresponds to variant dbSNP:rs121918059Ensembl.1
Natural variantiVAR_009107311Y → C in HEP. 1 PublicationCorresponds to variant dbSNP:rs121918061Ensembl.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi86D → E: 5-10% of wild-type activity. 1 Publication1
Mutagenesisi86D → G: Very low activity. Binds substrate with similar geometry as wild-type. 1 Publication1
Mutagenesisi86D → N: No activity. Unable to bind substrate. 1 Publication1
Mutagenesisi164Y → F: 25-30% of wild-type activity. 1 Publication1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi7389
GeneReviewsiUROD
MalaCardsiUROD
MIMi176100 phenotype
OpenTargetsiENSG00000126088
Orphaneti95159 Hepatoerythropoietic porphyria
101330 Porphyria cutanea tarda
PharmGKBiPA37221

Chemistry databases

ChEMBLiCHEMBL1681619
DrugBankiDB03727 Coproporphyrin I
DB04461 Coproporphyrin Iii

Polymorphism and mutation databases

BioMutaiUROD
DMDMi2507533

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001875691 – 367Uroporphyrinogen decarboxylaseAdd BLAST367

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei1N-acetylmethionineCombined sources1

Keywords - PTMi

Acetylation

Proteomic databases

EPDiP06132
MaxQBiP06132
PaxDbiP06132
PeptideAtlasiP06132
PRIDEiP06132
TopDownProteomicsiP06132

2D gel databases

OGPiP06132

PTM databases

iPTMnetiP06132
PhosphoSitePlusiP06132

Expressioni

Gene expression databases

BgeeiENSG00000126088
CleanExiHS_UROD
ExpressionAtlasiP06132 baseline and differential
GenevisibleiP06132 HS

Organism-specific databases

HPAiHPA027468
HPA028668
HPA030350

Interactioni

Subunit structurei

Homodimer.3 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
FAM84BQ96KN15EBI-2871776,EBI-9057780

Protein-protein interaction databases

BioGridi11323519 interactors.
IntActiP06132 11 interactors.
MINTiP06132
STRINGi9606.ENSP00000246337

Structurei

Secondary structure

1367
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi18 – 24Combined sources7
Beta strandi38 – 40Combined sources3
Helixi44 – 51Combined sources8
Helixi55 – 59Combined sources5
Helixi62 – 75Combined sources14
Helixi89 – 93Combined sources5
Beta strandi99 – 101Combined sources3
Turni102 – 104Combined sources3
Beta strandi105 – 107Combined sources3
Helixi115 – 120Combined sources6
Helixi124 – 126Combined sources3
Helixi127 – 130Combined sources4
Helixi132 – 145Combined sources14
Beta strandi151 – 156Combined sources6
Helixi158 – 167Combined sources10
Helixi175 – 183Combined sources9
Helixi185 – 208Combined sources24
Beta strandi212 – 218Combined sources7
Helixi221 – 223Combined sources3
Helixi226 – 232Combined sources7
Helixi234 – 250Combined sources17
Beta strandi258 – 262Combined sources5
Helixi266 – 268Combined sources3
Helixi269 – 272Combined sources4
Turni273 – 276Combined sources4
Beta strandi278 – 281Combined sources4
Helixi288 – 295Combined sources8
Beta strandi297 – 305Combined sources9
Helixi307 – 311Combined sources5
Helixi314 – 328Combined sources15
Beta strandi330 – 339Combined sources10
Helixi347 – 365Combined sources19

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1JPHX-ray2.10A1-367[»]
1JPIX-ray2.30A1-367[»]
1JPKX-ray2.20A1-367[»]
1R3QX-ray1.70A1-367[»]
1R3RX-ray1.85A1-367[»]
1R3SX-ray1.65A1-367[»]
1R3TX-ray1.70A1-367[»]
1R3VX-ray1.90A1-367[»]
1R3WX-ray1.70A1-367[»]
1R3YX-ray1.75A1-367[»]
1UROX-ray1.80A1-367[»]
2Q6ZX-ray2.00A11-366[»]
2Q71X-ray1.90A11-366[»]
3GVQX-ray2.10A1-367[»]
3GVRX-ray2.20A1-367[»]
3GVVX-ray2.80A1-367[»]
3GVWX-ray2.80A1-367[»]
3GW0X-ray2.00A1-367[»]
3GW3X-ray1.70A1-367[»]
DisProtiDP00308
ProteinModelPortaliP06132
SMRiP06132
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP06132

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni37 – 41Substrate binding5

Sequence similaritiesi

Phylogenomic databases

eggNOGiKOG2872 Eukaryota
COG0407 LUCA
GeneTreeiENSGT00390000018302
HOVERGENiHBG000229
InParanoidiP06132
KOiK01599
OMAiSWAGQLS
OrthoDBiEOG091G0EUA
PhylomeDBiP06132
TreeFamiTF300744

Family and domain databases

CDDicd00717 URO-D, 1 hit
Gene3Di3.20.20.2101 hit
HAMAPiMF_00218 URO_D, 1 hit
InterProiView protein in InterPro
IPR038071 UROD/MetE-like_sf
IPR006361 Uroporphyrinogen_deCO2ase_HemE
IPR000257 Uroporphyrinogen_deCOase
PfamiView protein in Pfam
PF01208 URO-D, 1 hit
SUPFAMiSSF51726 SSF51726, 1 hit
TIGRFAMsiTIGR01464 hemE, 1 hit
PROSITEiView protein in PROSITE
PS00906 UROD_1, 1 hit
PS00907 UROD_2, 1 hit

Sequencei

Sequence statusi: Complete.

P06132-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MEANGLGPQG FPELKNDTFL RAAWGEETDY TPVWCMRQAG RYLPEFRETR
60 70 80 90 100
AAQDFFSTCR SPEACCELTL QPLRRFPLDA AIIFSDILVV PQALGMEVTM
110 120 130 140 150
VPGKGPSFPE PLREEQDLER LRDPEVVASE LGYVFQAITL TRQRLAGRVP
160 170 180 190 200
LIGFAGAPWT LMTYMVEGGG SSTMAQAKRW LYQRPQASHQ LLRILTDALV
210 220 230 240 250
PYLVGQVVAG AQALQLFESH AGHLGPQLFN KFALPYIRDV AKQVKARLRE
260 270 280 290 300
AGLAPVPMII FAKDGHFALE ELAQAGYEVV GLDWTVAPKK ARECVGKTVT
310 320 330 340 350
LQGNLDPCAL YASEEEIGQL VKQMLDDFGP HRYIANLGHG LYPDMDPEHV
360
GAFVDAVHKH SRLLRQN
Length:367
Mass (Da):40,787
Last modified:November 1, 1997 - v2
Checksum:i840510B36CFC3856
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti103G → S in AAA61258 (PubMed:3015909).Curated1
Sequence conflicti103G → S in AAB59456 (PubMed:2243121).Curated1
Sequence conflicti120R → A in AAA61258 (PubMed:3015909).Curated1
Sequence conflicti120R → A in AAB59456 (PubMed:2243121).Curated1
Sequence conflicti212 – 214Missing in AAB59456 (PubMed:2243121).Curated3

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_06068315K → E. Corresponds to variant dbSNP:rs11541959Ensembl.1
Natural variantiVAR_02256725G → E in FPCT; insoluble protein. 1 PublicationCorresponds to variant dbSNP:rs764268015Ensembl.1
Natural variantiVAR_02256846F → L in HEP; mild phenotype; strong decrease of activity. 2 PublicationsCorresponds to variant dbSNP:rs769378741Ensembl.1
Natural variantiVAR_00910362P → L in HEP. 1 PublicationCorresponds to variant dbSNP:rs121918060Ensembl.1
Natural variantiVAR_06745777P → L3 PublicationsCorresponds to variant dbSNP:rs1131147Ensembl.1
Natural variantiVAR_00791080A → G in HEP. 1 PublicationCorresponds to variant dbSNP:rs776907084Ensembl.1
Natural variantiVAR_02256980A → S in FPCT; decrease of activity. 2 PublicationsCorresponds to variant dbSNP:rs376921379Ensembl.1
Natural variantiVAR_060684106P → L. Corresponds to variant dbSNP:rs11541962Ensembl.1
Natural variantiVAR_060685113R → T. Corresponds to variant dbSNP:rs11541963Ensembl.1
Natural variantiVAR_009104134V → Q in FPCT and HEP; requires 2 nucleotide substitutions; nearly normal activity. 4 Publications1
Natural variantiVAR_010985142R → Q in FPCT. 1 Publication1
Natural variantiVAR_022570144R → P in FPCT; decrease of activity. 1 Publication1
Natural variantiVAR_022571156G → D in FPCT; decrease of activity. 1 PublicationCorresponds to variant dbSNP:rs762617943Ensembl.1
Natural variantiVAR_010986161L → Q in FPCT. 1 Publication1
Natural variantiVAR_007911165M → R in FPCT; activity < 2%. 2 PublicationsCorresponds to variant dbSNP:rs121918063Ensembl.1
Natural variantiVAR_007714167E → K in HEP and FPCT; nearly normal activity. 2 PublicationsCorresponds to variant dbSNP:rs121918058Ensembl.1
Natural variantiVAR_065558168G → R in HEP; relative activity of 65% of wild-type towards uroporphyrinogen III. 1 Publication1
Natural variantiVAR_065559170G → D in HEP; relative activity of 17% and 60% of wild-type towards uroporphyrinogen I and III respectively. 1 Publication1
Natural variantiVAR_022572193R → P in FPCT; insoluble protein. 1 PublicationCorresponds to variant dbSNP:rs143823335Ensembl.1
Natural variantiVAR_007912195L → F in FPCT. 1 PublicationCorresponds to variant dbSNP:rs121918064Ensembl.1
Natural variantiVAR_022573216L → Q in FPCT. 1 Publication1
Natural variantiVAR_022574218E → K in FPCT; significant decrease of activity. 1 Publication1
Natural variantiVAR_010987219S → F in FPCT. 1 PublicationCorresponds to variant dbSNP:rs982293378Ensembl.1
Natural variantiVAR_009105220H → P in HEP; mild form. 1 Publication1
Natural variantiVAR_009106229F → L in FPCT. 1 Publication1
Natural variantiVAR_022575232F → L in FPCT; decrease of activity. 1 Publication1
Natural variantiVAR_010988235P → S in FPCT. 1 PublicationCorresponds to variant dbSNP:rs141312224Ensembl.1
Natural variantiVAR_007913253L → Q in FPCT; decrease of activity. 2 PublicationsCorresponds to variant dbSNP:rs36033115Ensembl.1
Natural variantiVAR_022576260I → T in FPCT; decrease of activity. 1 Publication1
Natural variantiVAR_007715281G → E in FPCT and HEP. 3 PublicationsCorresponds to variant dbSNP:rs121918057Ensembl.1
Natural variantiVAR_007716281G → V in FPCT. 2 PublicationsCorresponds to variant dbSNP:rs121918057Ensembl.1
Natural variantiVAR_022577282L → R in FPCT. 1 Publication1
Natural variantiVAR_007717292R → G in HEP. 1 PublicationCorresponds to variant dbSNP:rs121918059Ensembl.1
Natural variantiVAR_022578303G → S in FPCT. 1 PublicationCorresponds to variant dbSNP:rs964670864Ensembl.1
Natural variantiVAR_060686303G → V2 PublicationsCorresponds to variant dbSNP:rs17849533Ensembl.1
Natural variantiVAR_007914304N → K in FPCT. 1 PublicationCorresponds to variant dbSNP:rs121918065Ensembl.1
Natural variantiVAR_009107311Y → C in HEP. 1 PublicationCorresponds to variant dbSNP:rs121918061Ensembl.1
Natural variantiVAR_007915318G → R in FPCT. 2 PublicationsCorresponds to variant dbSNP:rs116233118Ensembl.1
Natural variantiVAR_009108324M → T in FPCT. 1 Publication1
Natural variantiVAR_007916332R → H in FPCT. 1 PublicationCorresponds to variant dbSNP:rs121918066Ensembl.1
Natural variantiVAR_007917334I → T in FPCT. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M14016 mRNA Translation: AAA61258.1
X89267 Genomic DNA Translation: CAA61540.1
AF047383 Genomic DNA Translation: AAC03563.1
AF104421 mRNA Translation: AAD04571.1
AF104422 mRNA Translation: AAD04572.1
AF104423 mRNA Translation: AAD04573.1
AF104424 mRNA Translation: AAD04574.1
AF104425 mRNA Translation: AAD04575.1
AF104426 mRNA Translation: AAD04576.1
AF104427 mRNA Translation: AAD04577.1
AF104428 mRNA Translation: AAD04578.1
AF104429 mRNA Translation: AAD04579.1
AF104430 mRNA Translation: AAD04580.1
AF104431 mRNA Translation: AAD04581.1
AF104432 mRNA Translation: AAD04582.1
AF104433 mRNA Translation: AAD04583.1
AF104434 mRNA Translation: AAD04584.1
AF104435 mRNA Translation: AAD04585.1
AF104436 mRNA Translation: AAD04586.1
AF104437 mRNA Translation: AAD04587.1
AF104438 mRNA Translation: AAD04588.1
AF104439 mRNA Translation: AAD04589.1
AF104440 mRNA Translation: AAD04590.1
AY292986 Genomic DNA Translation: AAP44118.1
BT006737 mRNA Translation: AAP35383.1
CR456976 mRNA Translation: CAG33257.1
CR542057 mRNA Translation: CAG46854.1
AK291877 mRNA Translation: BAF84566.1
AL359473 Genomic DNA No translation available.
CH471059 Genomic DNA Translation: EAX07007.1
BC001778 mRNA Translation: AAH01778.1
U30787 Genomic DNA Translation: AAC50482.1
M60891 Genomic DNA Translation: AAB59456.1
CCDSiCCDS518.1
PIRiA24411
G02786
RefSeqiNP_000365.3, NM_000374.4
UniGeneiHs.78601

Genome annotation databases

EnsembliENST00000246337; ENSP00000246337; ENSG00000126088
GeneIDi7389
KEGGihsa:7389
UCSCiuc001cna.3 human

Similar proteinsi

Entry informationi

Entry nameiDCUP_HUMAN
AccessioniPrimary (citable) accession number: P06132
Secondary accession number(s): A8K762
, Q16863, Q16883, Q53YB8, Q53ZP6, Q6IB28, Q9BUZ0
Entry historyiIntegrated into UniProtKB/Swiss-Prot: January 1, 1988
Last sequence update: November 1, 1997
Last modified: March 28, 2018
This is version 202 of the entry and version 2 of the sequence. See 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, Direct protein sequencing, Reference proteome