Human Gene MKRN1 (uc003vvu.4) Description and Page Index
  Description: Homo sapiens makorin ring finger protein 1 (MKRN1), transcript variant 2, mRNA.
RefSeq Summary (NM_001145125): This gene encodes a protein that belongs to a novel class of zinc finger proteins. The encoded protein functions as a transcriptional co-regulator, and as an E3 ubiquitin ligase that promotes the ubiquitination and proteasomal degradation of target proteins. The protein encoded by this gene is thought to regulate RNA polymerase II-catalyzed transcription. Substrates for this protein's E3 ubiquitin ligase activity include the capsid protein of the West Nile virus and the catalytic subunit of the telomerase ribonucleoprotein. This protein controls cell cycle arrest and apoptosis by regulating p21, a cell cycle regulator, and the tumor suppressor protein p53. Pseudogenes of this gene are present on chromosomes 1, 3, 9, 12 and 20, and on the X chromosome. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Apr 2014].
Transcript (Including UTRs)
   Position: hg19 chr7:140,155,983-140,179,369 Size: 23,387 Total Exon Count: 7 Strand: -
Coding Region
   Position: hg19 chr7:140,156,448-140,171,804 Size: 15,357 Coding Exon Count: 4 

Page IndexSequence and LinksUniProtKB CommentsGenetic AssociationsMalaCardsCTD
Gene AllelesRNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther Species
GO AnnotationsmRNA DescriptionsPathwaysOther NamesModel InformationMethods
Data last updated: 2013-06-15

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr7:140,155,983-140,179,369)mRNA (may differ from genome)Protein (265 aa)
Gene SorterGenome BrowserOther Species FASTAVisiGeneGene interactionsTable Schema
BioGPSCGAPEnsemblEntrez GeneExonPrimerGeneCards
H-INVHGNCLynxMGIneXtProtOMIM
PubMedReactomeStanford SOURCEUniProtKB

-  Comments and Description Text from UniProtKB
  ID: MKRN1_HUMAN
DESCRIPTION: RecName: Full=E3 ubiquitin-protein ligase makorin-1; EC=6.3.2.-; AltName: Full=RING finger protein 61;
FUNCTION: E3 ubiquitin ligase catalyzing the covalent attachment of ubiquitin moieties onto substrate proteins. These substrates include FILIP1, p53/TP53, CDKN1A and TERT. Keeps cells alive by suppressing p53/TP53 under normal conditions, but stimulates apoptosis by repressing CDKN1A under stress conditions. Acts as a negative regulator of telomerase. Has negative and positive effects on RNA polymerase II-dependent transcription.
PATHWAY: Protein modification; protein ubiquitination.
SUBUNIT: Interacts with p53/TP53 and CDKN1A. Interacts with TERT, modulating telomere length homeostasis.
TISSUE SPECIFICITY: Ubiquitous.
INDUCTION: Frequently induced in esophageal squamous cell carcinoma (SCC) tissues.
PTM: Auto-ubiquitinated; which leads to proteasomal degradation.
SIMILARITY: Contains 4 C3H1-type zinc fingers.
SIMILARITY: Contains 1 RING-type zinc finger.

-  Genetic Association Studies of Complex Diseases and Disorders
  Genetic Association Database (archive): MKRN1
CDC HuGE Published Literature: MKRN1

-  MalaCards Disease Associations
  MalaCards Gene Search: MKRN1
Diseases sorted by gene-association score: west nile virus (6)

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

+  Common Gene Haplotype Alleles
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-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 53.73 RPKM in Testis
Total median expression: 1017.59 RPKM



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

+  Microarray Expression Data
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-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -250.94579-0.433 Picture PostScript Text
3' UTR -111.55465-0.240 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
IPR026290 - Makorin-related
IPR000571 - Znf_CCCH
IPR001841 - Znf_RING
IPR013083 - Znf_RING/FYVE/PHD
IPR017907 - Znf_RING_CS

Pfam Domains:
PF00097 - Zinc finger, C3HC4 type (RING finger)
PF00642 - Zinc finger C-x8-C-x5-C-x3-H type (and similar)
PF13445 - RING-type zinc-finger
PF14608 - RNA-binding, Nab2-type zinc finger

SCOP Domains:
57850 - RING/U-box

ModBase Predicted Comparative 3D Structure on Q9UHC7
FrontTopSide
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 DetailsGene Details    
Gene SorterGene Sorter    
 RGD    
 Protein Sequence    
 Alignment    

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0003723 RNA binding
GO:0004842 ubiquitin-protein transferase activity
GO:0005515 protein binding
GO:0016740 transferase activity
GO:0046872 metal ion binding
GO:0061630 ubiquitin protein ligase activity

Biological Process:
GO:0000209 protein polyubiquitination
GO:0016567 protein ubiquitination

Cellular Component:
GO:0005575 cellular_component
GO:0005829 cytosol


-  Descriptions from all associated GenBank mRNAs
  BC064838 - Homo sapiens makorin ring finger protein 1, mRNA (cDNA clone MGC:74655 IMAGE:6173715), complete cds.
AB209298 - Homo sapiens mRNA for makorin, ring finger protein, 1 variant protein.
AK027137 - Homo sapiens cDNA: FLJ23484 fis, clone KAIA04822, highly similar to AF192784 Homo sapiens makorin 1 (MKRN1) mRNA.
BC037400 - Homo sapiens makorin ring finger protein 1, mRNA (cDNA clone MGC:35287 IMAGE:5176176), complete cds.
AL136812 - Homo sapiens mRNA; cDNA DKFZp434J1822 (from clone DKFZp434J1822).
BC025955 - Homo sapiens makorin ring finger protein 1, mRNA (cDNA clone MGC:39197 IMAGE:4869484), complete cds.
AK127030 - Homo sapiens cDNA FLJ45086 fis, clone BRAWH3028796, highly similar to Makorin-1.
AF192784 - Homo sapiens makorin 1 (MKRN1) mRNA, complete cds.
AK297361 - Homo sapiens cDNA FLJ58200 complete cds, highly similar to Makorin-1.
DQ892404 - Synthetic construct clone IMAGE:100005034; FLH186030.01X; RZPDo839A0371D makorin, ring finger protein, 1 (MKRN1) gene, encodes complete protein.
AK315552 - Homo sapiens cDNA, FLJ96622, highly similar to Homo sapiens makorin, ring finger protein, 1 (MKRN1), mRNA.
EU176516 - Synthetic construct Homo sapiens clone IMAGE:100011492; FLH186029.01L; RZPDo839A06253D makorin, ring finger protein, 1 (MKRN1) gene, encodes complete protein.
AB527778 - Synthetic construct DNA, clone: pF1KB5840, Homo sapiens MKRNP6 gene for Makorin-1 (RING finger protein 61), without stop codon, in Flexi system.
BC051821 - Homo sapiens makorin ring finger protein 1, mRNA (cDNA clone IMAGE:5764073), with apparent retained intron.
BC012398 - Homo sapiens makorin, ring finger protein, 1, mRNA (cDNA clone IMAGE:3860953), partial cds.
AF117233 - Homo sapiens znf-xp protein mRNA, complete cds.
AM236048 - Homo sapiens mRNA for makorin-1 (MKRN1 gene).
JD029986 - Sequence 11010 from Patent EP1572962.
BC127216 - Homo sapiens makorin ring finger protein 1, mRNA (cDNA clone IMAGE:40107880), partial cds.

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

Protein Q9UHC7 (Reactome details) participates in the following event(s):

R-HSA-8948757 AKT phosphorylates MKRN1
R-HSA-983157 Interaction of E3 with substrate and E2-Ub complex
R-HSA-983147 Release of E3 from polyubiquitinated substrate
R-HSA-8948775 MKRN1 polyubiquitinates PTEN
R-HSA-983140 Transfer of Ub from E2 to substrate and release of E2
R-HSA-198323 AKT phosphorylates targets in the cytosol
R-HSA-8948751 Regulation of PTEN stability and activity
R-HSA-983168 Antigen processing: Ubiquitination & Proteasome degradation
R-HSA-1257604 PIP3 activates AKT signaling
R-HSA-6807070 PTEN Regulation
R-HSA-983169 Class I MHC mediated antigen processing & presentation
R-HSA-9006925 Intracellular signaling by second messengers
R-HSA-1280218 Adaptive Immune System
R-HSA-162582 Signal Transduction
R-HSA-168256 Immune System

-  Other Names for This Gene
  Alternate Gene Symbols: A4D1T7, B3KXB4, BC051821, MKRN1_HUMAN, NM_001145125, NP_001138597, Q256Y7, Q59G11, Q6GSF1, Q9H0G0, Q9UEZ7, Q9UHC7, Q9UHW2, RNF61
UCSC ID: uc003vvu.4
RefSeq Accession: NM_001145125
Protein: Q9UHC7 (aka MKRN1_HUMAN or MKR1_HUMAN)

-  Gene Model Information
 
category: coding nonsense-mediated-decay: no RNA accession: BC051821.1
exon count: 7CDS single in 3' UTR: no RNA size: 1707
ORF size: 798CDS single in intron: no Alignment % ID: 99.88
txCdsPredict score: 1338.00frame shift in genome: no % Coverage: 94.84
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: 469# 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.