Human Gene UMOD (uc002dha.3)
  Description: Homo sapiens uromodulin (UMOD), transcript variant 2, mRNA.
RefSeq Summary (NM_001008389): The protein encoded by this gene is the most abundant protein in mammalian urine under physiological conditions. Its excretion in urine follows proteolytic cleavage of the ectodomain of its glycosyl phosphatidylinosital-anchored counterpart that is situated on the luminal cell surface of the loop of Henle. This protein may act as a constitutive inhibitor of calcium crystallization in renal fluids. Excretion of this protein in urine may provide defense against urinary tract infections caused by uropathogenic bacteria. Defects in this gene are associated with the renal disorders medullary cystic kidney disease-2 (MCKD2), glomerulocystic kidney disease with hyperuricemia and isosthenuria (GCKDHI), and familial juvenile hyperuricemic nephropathy (FJHN). Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Jul 2013].
Transcript (Including UTRs)
   Position: hg19 chr16:20,344,373-20,364,037 Size: 19,665 Total Exon Count: 11 Strand: -
Coding Region
   Position: hg19 chr16:20,344,636-20,362,059 Size: 17,424 Coding Exon Count: 10 

Page IndexSequence and LinksUniProtKB CommentsPrimersGenetic AssociationsMalaCards
CTDGene AllelesRNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein Structure
Other SpeciesGO AnnotationsmRNA DescriptionsPathwaysOther NamesGeneReviews
Model InformationMethods
Data last updated at UCSC: 2013-06-14

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr16:20,344,373-20,364,037)mRNA (may differ from genome)Protein (640 aa)
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neXtProtOMIMPubMedReactomeTreefamUniProtKB
WikipediaBioGrid CRISPR DB

-  Comments and Description Text from UniProtKB
  ID: UROM_HUMAN
DESCRIPTION: RecName: Full=Uromodulin; AltName: Full=Tamm-Horsfall urinary glycoprotein; Short=THP; Contains: RecName: Full=Uromodulin, secreted form; Flags: Precursor;
FUNCTION: Uromodulin: Functions in biogenesis and organization of the apical membrane of epithelial cells of the thick ascending limb of Henle's loop (TALH), where it promotes formation of complex filamentous gel-like structure providing the water barrier permeability. May serve as a receptor for binding and endocytosis for cytokines (IL-1, IL-2) and TNF. Facilitates neutrophil migration across renal epithelial.
FUNCTION: Uromodulin, secreted form: Secreted into urine after proteolytically cleaveage. Into the urine, may contribute to colloid osmotic pressure, retards passage of positively charged electrolytes, prevents urinary tract infection and modulates formation of supersaturated salts and their crystals.
SUBCELLULAR LOCATION: Apical cell membrane; Lipid-anchor, GPI- anchor. Basolateral cell membrane; Lipid-anchor, GPI-anchor. Cell projection, cilium membrane. Note=Only a small fraction is sort to the basolateral pole of tubular epithelial cells compared to apical localization. Secreted into urine after cleavage. Colocalized with NPHP1 and KIF3A.
SUBCELLULAR LOCATION: Uromodulin, secreted form: Secreted.
TISSUE SPECIFICITY: Synthesized exclusively in the kidney. Expressed exclusively by epithelial cells of the thick ascending limb of Henle's loop (TALH) and of distal convoluted tubule lumen. Most abundant protein in normal urine.
DOMAIN: The ZP domain is involved in the polymerization of the protein to promote the formation of complex gel-like structure.
PTM: N-glycosylated. N-glycan heterogeneity at Asn-232: Hex7HexNAc6 (major) and dHex1Hex7HexNAc6 (minor); at Asn-322: dHex1Hex6HexNAc5 (minor), dHex1Hex7HexNAc6 (major) and dHex1Hex8HexNAc7 (minor); at Asn-396: Hex6HexNAc5 (major), dHex1Hex6HexNAc5 (minor) and Hex7HexNAc6 (minor).
PTM: Proteolytically cleaved at a conserved C-terminal proteolytic cleavage site to generate the secreted form found into urine.
DISEASE: Defects in UMOD are the cause of familial juvenile hyperuricemic nephropathy type 1 (HNFJ1) [MIM:162000]. HNFJ1 is a renal disease characterized by juvenil onset of hyperuricemia, polyuria, progressive renal failure, and gout. The disease is associated with interstitial pathological changes resulting in fibrosis.
DISEASE: Defects in UMOD are the cause of medullary cystic kidney disease type 2 (MCKD2) [MIM:603860]. MCKD2 is a form of tubulointerstitial nephropathy characterized by formation of renal cysts at the corticomedullary junction. It is characterized by adult onset of impaired renal function and salt wasting resulting in end-stage renal failure by the sixth decade.
DISEASE: Defects in UMOD are the cause of glomerulocystic kidney disease with hyperuricemia and isosthenuria (GCKDHI) [MIM:609886]. GCKDHI is a renal disorder characterized by a cystic dilation of Bowman space, a collapse of glomerular tuft, and hyperuricemia due to low fractional excretion of uric acid and severe impairment of urine concentrating ability.
MISCELLANEOUS: A specific, but as yet unidentified, protease(s) cleaves off and releases UMOD into urine.
SIMILARITY: Contains 3 EGF-like domains.
SIMILARITY: Contains 1 ZP domain.
WEB RESOURCE: Name=GeneReviews; URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/UMOD";

-  Primer design for this transcript
 

Primer3Plus can design qPCR Primers that straddle exon-exon-junctions, which amplify only cDNA, not genomic DNA.
Click here to load the transcript sequence and exon structure into Primer3Plus

Exonprimer can design one pair of Sanger sequencing primers around every exon, located in non-genic sequence.
Click here to open Exonprimer with this transcript

To design primers for a non-coding sequence, zoom to a region of interest and select from the drop-down menu: View > In External Tools > Primer3


-  Genetic Association Studies of Complex Diseases and Disorders
  Genetic Association Database (archive): UMOD
CDC HuGE Published Literature: UMOD
Positive Disease Associations: Creatinine , Hypertension , Kidney Diseases , Kidney Failure, Chronic , Osteoporosis , renal function and chronic kidney disease , Waist Circumference
Related Studies:
  1. Creatinine
    Anna Kottgen et al. Nature genetics 2009, Multiple loci associated with indices of renal function and chronic kidney disease., Nature genetics. [PubMed 19430482]
  2. Hypertension
    Sandosh Padmanabhan et al. PLoS genetics 2010, Genome-wide association study of blood pressure extremes identifies variant near UMOD associated with hypertension., PLoS genetics. [PubMed 21082022]
  3. Kidney Diseases
    Anna Kottgen et al. Nature genetics 2010, New loci associated with kidney function and chronic kidney disease., Nature genetics. [PubMed 20383146]
           more ... click here to view the complete list

-  MalaCards Disease Associations
  MalaCards Gene Search: UMOD
Diseases sorted by gene-association score: hyperuricemic nephropathy, familial juvenile 1* (1681), medullary cystic kidney disease 2* (1252), glomerulocystic kidney disease with hyperuricemia and isosthenuria* (1242), autosomal dominant medullary cystic kidney disease with hyperuricemia* (750), autosomal dominant tubulointerstitial kidney disease, umod-related* (500), familial juvenile hyperuricaemic nephropathy* (419), hyperuricemia (67), cystic kidney disease (42), kidney disease (37), gout (37), end stage renal failure (35), urinary system disease (16), cystitis (16), interstitial nephritis (13), nephrolithiasis, calcium oxalate (10), chronic pyelonephritis (10), vesicoureteral reflux (10), acute kidney tubular necrosis (9), nephrolithiasis (8), fabry disease (7), urinary tract obstruction (7), interstitial cystitis (7), xanthinuria, type i (7), nephronophthisis (7), pyelonephritis (6), bartter disease (5), congenital disorder of glycosylation, type in (5), chronic kidney failure (3)
* = Manually curated disease association

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

+  Common Gene Haplotype Alleles
  Press "+" in the title bar above to open this section.

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 271.11 RPKM in Kidney - Cortex
Total median expression: 273.14 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -22.5066-0.341 Picture PostScript Text
3' UTR -80.70263-0.307 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR000742 - EG-like_dom
IPR001881 - EGF-like_Ca-bd
IPR013032 - EGF-like_CS
IPR000152 - EGF-type_Asp/Asn_hydroxyl_site
IPR018097 - EGF_Ca-bd_CS
IPR024731 - EGF_dom_MSP1-like
IPR009030 - Growth_fac_rcpt
IPR001507 - ZP_dom
IPR017977 - ZP_dom_CS

Pfam Domains:
PF00008 - EGF-like domain
PF00100 - Zona pellucida-like domain
PF07645 - Calcium-binding EGF domain
PF12661 - Human growth factor-like EGF
PF12947 - EGF domain

SCOP Domains:
57196 - EGF/Laminin
57184 - Growth factor receptor domain

ModBase Predicted Comparative 3D Structure on P07911
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The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
No orthologGenome BrowserNo orthologNo orthologNo orthologNo ortholog
 Gene Details    
 Gene Sorter    
 RGD    
 Protein Sequence    
 Alignment    

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0005509 calcium ion binding
GO:0019864 IgG binding

Biological Process:
GO:0006968 cellular defense response
GO:0007157 heterophilic cell-cell adhesion via plasma membrane cell adhesion molecules
GO:0007159 leukocyte cell-cell adhesion
GO:0007588 excretion
GO:0008285 negative regulation of cell proliferation
GO:0048878 chemical homeostasis
GO:0050801 ion homeostasis
GO:0072218 metanephric ascending thin limb development
GO:0072221 metanephric distal convoluted tubule development
GO:0072233 metanephric thick ascending limb development
GO:1990266 neutrophil migration

Cellular Component:
GO:0000922 spindle pole
GO:0005576 extracellular region
GO:0005796 Golgi lumen
GO:0005886 plasma membrane
GO:0005929 cilium
GO:0016020 membrane
GO:0016323 basolateral plasma membrane
GO:0016324 apical plasma membrane
GO:0019898 extrinsic component of membrane
GO:0031225 anchored component of membrane
GO:0042995 cell projection
GO:0060170 ciliary membrane
GO:0070062 extracellular exosome


-  Descriptions from all associated GenBank mRNAs
  M17778 - Human uromodulin (Tamm-Horsfall glycoprotein) mRNA, complete cds.
AK127643 - Homo sapiens cDNA FLJ45741 fis, clone KIDNE2015987, highly similar to Uromodulin precursor.
AK055722 - Homo sapiens cDNA FLJ31160 fis, clone KIDNE1000015, highly similar to UROMODULIN PRECURSOR.
AK091961 - Homo sapiens cDNA FLJ34642 fis, clone KIDNE2016918, highly similar to UROMODULIN PRECURSOR.
AK096043 - Homo sapiens cDNA FLJ38724 fis, clone KIDNE2010151, highly similar to UROMODULIN PRECURSOR.
AX747279 - Sequence 804 from Patent EP1308459.
M15881 - Human uromodulin (Tamm-Horsfall glycoprotein) mRNA, complete cds.
AK127648 - Homo sapiens cDNA FLJ45746 fis, clone KIDNE2018727, highly similar to Uromodulin precursor.
BC035975 - Homo sapiens uromodulin, mRNA (cDNA clone MGC:32619 IMAGE:4556427), complete cds.
JD075690 - Sequence 56714 from Patent EP1572962.
JD402899 - Sequence 383923 from Patent EP1572962.
JD537622 - Sequence 518646 from Patent EP1572962.
JD231069 - Sequence 212093 from Patent EP1572962.
JD277850 - Sequence 258874 from Patent EP1572962.
JD251636 - Sequence 232660 from Patent EP1572962.
AB590834 - Synthetic construct DNA, clone: pFN21AE2038, Homo sapiens UMOD gene for uromodulin, without stop codon, in Flexi system.
JD020697 - Sequence 1721 from Patent EP1572962.
JD033330 - Sequence 14354 from Patent EP1572962.
CU690246 - Synthetic construct Homo sapiens gateway clone IMAGE:100022010 5' read UMOD mRNA.
JD079103 - Sequence 60127 from Patent EP1572962.

-  Biochemical and Signaling Pathways
  Reactome (by CSHL, EBI, and GO)

Protein P07911 (Reactome details) participates in the following event(s):

R-HSA-8855954 B4GALNT2 transfers GalNAc from UDP-GalNAc to Sial-Gal-GlcNAc-Gal to form the Sd(a) antigen on UMOD
R-HSA-446203 Asparagine N-linked glycosylation
R-HSA-597592 Post-translational protein modification
R-HSA-392499 Metabolism of proteins

-  Other Names for This Gene
  Alternate Gene Symbols: B3KP48, B3KRN9, NM_001008389, NP_003352, P07911, Q540J6, Q6ZS84, Q8IYG0, UROM_HUMAN
UCSC ID: uc002dha.3
RefSeq Accession: NM_001008389
Protein: P07911 (aka UROM_HUMAN)
CCDS: CCDS10583.1, CCDS61876.1

-  GeneReviews for This Gene
  GeneReviews article(s) related to gene UMOD:
mckd2 (Autosomal Dominant Tubulointerstitial Kidney Disease -- UMOD)

-  Gene Model Information
 
category: coding nonsense-mediated-decay: no RNA accession: NM_001008389.1
exon count: 11CDS single in 3' UTR: no RNA size: 2264
ORF size: 1923CDS single in intron: no Alignment % ID: 100.00
txCdsPredict score: 4046.00frame shift in genome: no % Coverage: 99.47
has start codon: yes stop codon in genome: no # of Alignments: 1
has end codon: yes retained intron: no # AT/AC introns 0
selenocysteine: no end bleed into intron: 0# strange splices: 0
Click here for a detailed description of the fields of the table above.

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.