Human Gene ULK3 (uc010bkf.1) Description and Page Index
  Description: Homo sapiens unc-51-like kinase 3 (C. elegans) (ULK3), mRNA.
Transcript (Including UTRs)
   Position: hg19 chr15:75,128,459-75,135,552 Size: 7,094 Total Exon Count: 16 Strand: -
Coding Region
   Position: hg19 chr15:75,129,569-75,135,446 Size: 5,878 Coding Exon Count: 16 

Page IndexSequence and LinksUniProtKB CommentsGenetic AssociationsCTDGene Alleles
RNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther SpeciesGO Annotations
mRNA DescriptionsPathwaysOther NamesModel InformationMethods
Data last updated: 2013-06-14

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr15:75,128,459-75,135,552)mRNA (may differ from genome)Protein (472 aa)
Gene SorterGenome BrowserOther Species FASTAVisiGeneGene interactionsTable Schema
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GeneNetworkH-INVHGNCHPRDLynxMGI
neXtProtOMIMPubMedReactomeStanford SOURCEUniProtKB

-  Comments and Description Text from UniProtKB
  ID: ULK3_HUMAN
DESCRIPTION: RecName: Full=Serine/threonine-protein kinase ULK3; EC=2.7.11.1; AltName: Full=Unc-51-like kinase 3;
FUNCTION: Serine/threonine protein kinase that acts as a regulator of Sonic hedgehog (SHH) signaling and autophagy. Acts as a negative regulator of SHH signaling in the absence of SHH ligand: interacts with SUFU, thereby inactivating the protein kinase activity and preventing phosphorylation of GLI proteins (GLI1, GLI2 and/or GLI3). Positively regulates SHH signaling in the presence of SHH: dissociates from SUFU, autophosphorylates and mediates phosphorylation of GLI2, activating it and promoting its nuclear translocation. Phosphorylates in vitro GLI2, as well as GLI1 and GLI3, although less efficiently. Also acts as a regulator of autophagy: following cellular senescence, able to induce autophagy.
CATALYTIC ACTIVITY: ATP + a protein = ADP + a phosphoprotein.
SUBUNIT: Interacts (via protein kinase domain) with SUFU.
SUBCELLULAR LOCATION: Cytoplasm. Note=Localizes to pre- autophagosomal structure during cellular senescence.
TISSUE SPECIFICITY: Widely expressed. Highest levels observed in fetal brain. In adult tissues, high levels in brain, liver and kidney, moderate levels in testis and adrenal gland and low levels in heart, lung, stomach, thymus, prostate and placenta. In the brain, highest expression in the hippocampus, high levels also detected in the cerebellum, olfactory bulb and optic nerve. In the central nervous system, lowest levels in the spinal cord.
INDUCTION: Up-regulated during senescence.
PTM: Autophosphorylated. Autophosphorylation is blocked by interaction with SUFU.
SIMILARITY: Belongs to the protein kinase superfamily. Ser/Thr protein kinase family. APG1/unc-51/ULK1 subfamily.
SIMILARITY: Contains 2 MIT domains.
SIMILARITY: Contains 1 protein kinase domain.
SEQUENCE CAUTION: Sequence=CAB55955.2; Type=Erroneous initiation; Note=Translation N-terminally shortened;

-  Genetic Association Studies of Complex Diseases and Disorders
  Genetic Association Database (archive): ULK3
CDC HuGE Published Literature: ULK3
Positive Disease Associations: Diastolic blood pressure
Related Studies:
  1. Diastolic blood pressure
    Levy ,et al. 2009, Genome-wide association study of blood pressure and hypertension, Nature genetics 2009 . [PubMed 19430479]

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene

+  Common Gene Haplotype Alleles
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-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 104.35 RPKM in Brain - Cerebellum
Total median expression: 1456.18 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 -61.50106-0.580 Picture PostScript Text
3' UTR -436.901110-0.394 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
IPR011009 - Kinase-like_dom
IPR007330 - MIT
IPR000719 - Prot_kinase_cat_dom
IPR017441 - Protein_kinase_ATP_BS
IPR002290 - Ser/Thr_dual-sp_kinase_dom
IPR008271 - Ser/Thr_kinase_AS

Pfam Domains:
PF00069 - Protein kinase domain
PF04212 - MIT (microtubule interacting and transport) domain
PF07714 - Protein tyrosine kinase

SCOP Domains:
56112 - Protein kinase-like (PK-like)

ModBase Predicted Comparative 3D Structure on Q6PHR2
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 orthologNo orthologGenome BrowserNo orthologNo orthologNo ortholog
Gene Details     
Gene Sorter     
  Ensembl   
  Protein Sequence   
  Alignment   

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0000166 nucleotide binding
GO:0004672 protein kinase activity
GO:0004674 protein serine/threonine kinase activity
GO:0005515 protein binding
GO:0005524 ATP binding
GO:0016301 kinase activity
GO:0016740 transferase activity

Biological Process:
GO:0006468 protein phosphorylation
GO:0006914 autophagy
GO:0016310 phosphorylation
GO:0045879 negative regulation of smoothened signaling pathway
GO:0045880 positive regulation of smoothened signaling pathway
GO:0046777 protein autophosphorylation
GO:0090398 cellular senescence

Cellular Component:
GO:0000407 pre-autophagosomal structure
GO:0005737 cytoplasm
GO:0097542 ciliary tip


-  Descriptions from all associated GenBank mRNAs
  AL360256 - Homo sapiens mRNA full length insert cDNA clone EUROIMAGE 2214817.
BC056423 - Homo sapiens unc-51-like kinase 3 (C. elegans), mRNA (cDNA clone IMAGE:5219403).
BC048289 - Homo sapiens unc-51-like kinase 3 (C. elegans), mRNA (cDNA clone IMAGE:5211725).
BC036117 - Homo sapiens unc-51-like kinase 3 (C. elegans), mRNA (cDNA clone IMAGE:5310864).
AL117482 - Homo sapiens mRNA; cDNA DKFZp434C131 (from clone DKFZp434C131).
AK075047 - Homo sapiens cDNA FLJ90566 fis, clone OVARC1001338, weakly similar to AUTOPHAGY SERINE/THREONINE-PROTEIN KINASE APG1 (EC 2.7.1.-).
JD227066 - Sequence 208090 from Patent EP1572962.
BC157884 - Homo sapiens unc-51-like kinase 3 (C. elegans), mRNA (cDNA clone MGC:189709 IMAGE:8862706), complete cds.
JD394135 - Sequence 375159 from Patent EP1572962.
JD069120 - Sequence 50144 from Patent EP1572962.
JD402767 - Sequence 383791 from Patent EP1572962.
JD116237 - Sequence 97261 from Patent EP1572962.
JD098705 - Sequence 79729 from Patent EP1572962.
JD391030 - Sequence 372054 from Patent EP1572962.
AK298879 - Homo sapiens cDNA FLJ50616 complete cds, weakly similar to Serine/threonine-protein kinase ATG1 (EC 2.7.11.1).
AK294245 - Homo sapiens cDNA FLJ50476 complete cds, weakly similar to Serine/threonine-protein kinase ULK1 (EC2.7.11.1).
AK294251 - Homo sapiens cDNA FLJ50477 complete cds, weakly similar to Serine/threonine-protein kinase unc-51 (EC 2.7.11.1).
AK293181 - Homo sapiens cDNA FLJ50436 complete cds, weakly similar to Serine/threonine-protein kinase ATG1 (EC 2.7.11.1).
JD497266 - Sequence 478290 from Patent EP1572962.
JD367589 - Sequence 348613 from Patent EP1572962.
JD539681 - Sequence 520705 from Patent EP1572962.
AK299380 - Homo sapiens cDNA FLJ60836 complete cds, weakly similar to Serine/threonine-protein kinase ULK1 (EC 2.7.11.1).
AK294241 - Homo sapiens cDNA FLJ50005 complete cds, weakly similar to Serine/threonine-protein kinase unc-51 (EC 2.7.11.1).
AK316102 - Homo sapiens cDNA, FLJ79001 complete cds.
AK293650 - Homo sapiens cDNA FLJ50451 complete cds.
CU691158 - Synthetic construct Homo sapiens gateway clone IMAGE:100021641 5' read ULK3 mRNA.
KJ902402 - Synthetic construct Homo sapiens clone ccsbBroadEn_11796 ULK3 gene, encodes complete protein.
KJ905447 - Synthetic construct Homo sapiens clone ccsbBroadEn_15030 ULK3 gene, encodes complete protein.
AB528889 - Synthetic construct DNA, clone: pF1KE0639, Homo sapiens ULK3 gene for unc-51-like kinase 3, without stop codon, in Flexi system.

-  Biochemical and Signaling Pathways
  KEGG - Kyoto Encyclopedia of Genes and Genomes
hsa04140 - Regulation of autophagy
hsa04150 - mTOR signaling pathway

Reactome (by CSHL, EBI, and GO)

Protein Q6PHR2 (Reactome details) participates in the following event(s):

R-HSA-5635839 ULK3:SUFU dissociates
R-HSA-5635842 ULK3 phosphorylates GLI
R-HSA-5632684 Hedgehog 'on' state
R-HSA-5358351 Signaling by Hedgehog
R-HSA-162582 Signal Transduction

-  Other Names for This Gene
  Alternate Gene Symbols: B2RXK3, B4DRQ7, D3DW68, NM_001099436, NP_001092906, Q6PHR2, Q9NPN5, Q9UFS4, ULK3_HUMAN
UCSC ID: uc010bkf.1
RefSeq Accession: NM_001099436
Protein: Q6PHR2 (aka ULK3_HUMAN)
CCDS: CCDS45305.1

-  Gene Model Information
 
category: coding nonsense-mediated-decay: no RNA accession: NM_001099436.1
exon count: 16CDS single in 3' UTR: no RNA size: 2635
ORF size: 1419CDS single in intron: no Alignment % ID: 100.00
txCdsPredict score: 2936.00frame shift in genome: no % Coverage: 100.00
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.