Human Gene SUFU (uc001kvy.2) Description and Page Index
  Description: Homo sapiens suppressor of fused homolog (Drosophila) (SUFU), transcript variant 1, mRNA.
RefSeq Summary (NM_016169): The Hedgehog signaling pathway plays an important role in early human development. The pathway is a signaling cascade that plays a role in pattern formation and cellular proliferation during development. This gene encodes a negative regulator of the hedgehog signaling pathway. Defects in this gene are a cause of medulloblastoma. Alternative splicing results in multiple transcript variants.[provided by RefSeq, May 2010].
Transcript (Including UTRs)
   Position: hg19 chr10:104,263,719-104,393,214 Size: 129,496 Total Exon Count: 12 Strand: +
Coding Region
   Position: hg19 chr10:104,263,910-104,389,912 Size: 126,003 Coding Exon Count: 12 

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

-  Sequence and Links to Tools and Databases
Genomic Sequence (chr10:104,263,719-104,393,214)mRNA (may differ from genome)Protein (484 aa)
Gene SorterGenome BrowserOther Species FASTAVisiGeneGene interactionsTable Schema
BioGPSCGAPEnsemblEntrez GeneExonPrimerGeneCards
neXtProtOMIMPubMedReactomeStanford SOURCETreefam

-  Comments and Description Text from UniProtKB
DESCRIPTION: RecName: Full=Suppressor of fused homolog; Short=SUFUH;
FUNCTION: Negative regulator in the hedgehog signaling pathway. Down-regulates GLI1-mediated transactivation of target genes. Part of a corepressor complex that acts on DNA-bound GLI1. May also act by linking GLI1 to BTRC and thereby targeting GLI1 to degradation by the proteasome. Sequesters GLI1, GLI2 and GLI3 in the cytoplasm, this effect is overcome by binding of STK36 to both SUFU and a GLI protein. Negative regulator of beta-catenin signaling. Regulates the formation of either the repressor form (GLI3R) or the activator form (GLI3A) of the full length form of GLI3 (GLI3FL). GLI3FL is complexed with SUFU in the cytoplasm and is maintained in a neutral state. Without the Hh signal, the SUFU- GLI3 complex is recruited to cilia, leading to the efficient processing of GLI3FL into GLI3R. When Hh signaling is initiated, SUFU dissociates from GLI3FL and the latter translocates to the nucleus, where it is phosphorylated, destabilized, and converted to a transcriptional activator (GLI3A).
SUBUNIT: May form homodimers. Part of a DNA-bound corepressor complex containing SAP18, GLI1 and SIN3. Part of a complex containing CTNNB1. Binds BTRC, GLI2, GLI3, SAP18 and STK36. Binds both free and DNA-bound GLI1. Interacts with KIF7. Interacts with GLI3FL and this interaction regulates the formation of either repressor or activator forms of GLI3. Its association with GLI3FL is regulated by Hh signaling and dissociation of the SUFU-GLI3 interaction requires the presence of the ciliary motor KIF3A (By similarity). Interacts with ULK3; inactivating the protein kinase activity of ULK3.
INTERACTION: P08151:GLI1; NbExp=4; IntAct=EBI-740621, EBI-308084; Q7Z412:PEX26; NbExp=2; IntAct=EBI-740595, EBI-752057; Q96D15:RCN3; NbExp=2; IntAct=EBI-740595, EBI-746283; Q9NRP7:STK36; NbExp=2; IntAct=EBI-740595, EBI-863797;
TISSUE SPECIFICITY: Ubiquitous in adult tissues. Detected in osteoblasts of the perichondrium in the developing limb of 12-week old embryos. Isoform 1 is detected in fetal brain, lung, kidney and testis. Isoform 2 is detected in fetal testis, and at much lower levels in fetal brain, lung and kidney.
DISEASE: Defects in SUFU are a cause of medulloblastoma (MDB) [MIM:155255]. MDB is a malignant, invasive embryonal tumor of the cerebellum with a preferential manifestation in children. Defects in SUFU play a role in predisposition to desmoplastic MDB. These tumors make up about 20 to 30% of medulloblastomas, have a more nodular architecture than 'classical' medulloblastoma, and may have a better prognosis.
SIMILARITY: Belongs to the SUFU family.

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

-  MalaCards Disease Associations
  MalaCards Gene Search: SUFU
Diseases sorted by gene-association score: medulloblastoma* (980), basal cell nevus syndrome* (967), meningioma, familial* (271), medulloblastoma, sufu-related* (100), meningioma, familial susceptibility* (100), infundibulocystic basal cell carcinoma (24), nodular medulloblastoma (23), atypical choroid plexus papilloma (16), basal cell carcinoma (13), childhood medulloblastoma (11), infratentorial cancer (10), cerebellum cancer (7), cerebellar liponeurocytoma (7), microform holoprosencephaly* (6), split foot (6), adult medulloblastoma (6), split hand-split foot malformation (6), keratocystic odontogenic tumor (5), split-hand/foot malformation 5 (5), split hand-foot malformation 2 (5), split-hand/foot malformation 4 (5), split-hand/foot malformation 3 (5)
* = 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: 7.85 RPKM in Skin - Sun Exposed (Lower leg)
Total median expression: 190.70 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 -71.90191-0.376 Picture PostScript Text
3' UTR -1315.233302-0.398 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
IPR007768 - SUFU-like
IPR024314 - SUFU_C
IPR020941 - SUFU_domain
IPR016591 - Suppressor_of_fused_protein

Pfam Domains:
PF05076 - Suppressor of fused protein (SUFU)
PF12470 - Suppressor of Fused Gli/Ci N terminal binding domain

SCOP Domains:
103359 - Suppressor of Fused, N-terminal domain

Protein Data Bank (PDB) 3-D Structure
MuPIT help

- X-ray MuPIT

ModBase Predicted Comparative 3D Structure on Q9UMX1
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 orthologGenome BrowserNo orthologNo ortholog
 Gene Details Gene Details  
 Gene Sorter Gene Sorter  
 RGD FlyBase  
 Protein Sequence Protein Sequence  
 Alignment Alignment  

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0003714 transcription corepressor activity
GO:0004871 signal transducer activity
GO:0005515 protein binding
GO:0008013 beta-catenin binding
GO:0008134 transcription factor binding
GO:0019901 protein kinase binding

Biological Process:
GO:0000122 negative regulation of transcription from RNA polymerase II promoter
GO:0001501 skeletal system development
GO:0001843 neural tube closure
GO:0001947 heart looping
GO:0003281 ventricular septum development
GO:0006355 regulation of transcription, DNA-templated
GO:0006508 proteolysis
GO:0007165 signal transduction
GO:0007275 multicellular organism development
GO:0007368 determination of left/right symmetry
GO:0021513 spinal cord dorsal/ventral patterning
GO:0021775 smoothened signaling pathway involved in ventral spinal cord interneuron specification
GO:0021776 smoothened signaling pathway involved in spinal cord motor neuron cell fate specification
GO:0035904 aorta development
GO:0042308 negative regulation of protein import into nucleus
GO:0042994 cytoplasmic sequestering of transcription factor
GO:0043433 negative regulation of sequence-specific DNA binding transcription factor activity
GO:0043588 skin development
GO:0045668 negative regulation of osteoblast differentiation
GO:0045879 negative regulation of smoothened signaling pathway
GO:0060976 coronary vasculature development
GO:1901621 negative regulation of smoothened signaling pathway involved in dorsal/ventral neural tube patterning
GO:2000059 negative regulation of protein ubiquitination involved in ubiquitin-dependent protein catabolic process

Cellular Component:
GO:0005634 nucleus
GO:0005737 cytoplasm
GO:0005829 cytosol
GO:0005929 cilium
GO:0097542 ciliary tip
GO:0097546 ciliary base

-  Descriptions from all associated GenBank mRNAs
  AK312319 - Homo sapiens cDNA, FLJ92629, highly similar to Homo sapiens suppressor of fused homolog (Drosophila) (SUFU), mRNA.
BC013291 - Homo sapiens suppressor of fused homolog (Drosophila), mRNA (cDNA clone MGC:3346 IMAGE:3533158), complete cds.
AF175770 - Homo sapiens suppressor of fused mRNA, complete cds.
AF144231 - Homo sapiens Suppressor of Fused mRNA, alternatively spliced, complete cds.
AY358550 - Homo sapiens clone DNA33455 SUFU (UNQ650) mRNA, complete cds.
AF159447 - Homo sapiens Suppressor of Fused mRNA, alternatively spliced form 2, complete cds.
AF222345 - Homo sapiens suppressor of fused variant 3 mRNA, alternatively spliced, complete cds.
KJ905478 - Synthetic construct Homo sapiens clone ccsbBroadEn_15072 SUFU gene, encodes complete protein.
AB590231 - Synthetic construct DNA, clone: pFN21AB5844, Homo sapiens SUFU gene for suppressor of fused homolog, without stop codon, in Flexi system.
DQ895804 - Synthetic construct Homo sapiens clone IMAGE:100010264; FLH187795.01L; RZPDo839D03149D suppressor of fused homolog (Drosophila) (SUFU) gene, encodes complete protein.
DQ892586 - Synthetic construct clone IMAGE:100005216; FLH187799.01X; RZPDo839D03150D suppressor of fused homolog (Drosophila) (SUFU) gene, encodes complete protein.
KX708747 - Homo sapiens cell line SW1990 suppressor of fused (SUFU) mRNA, complete cds, alternatively spliced.
AF172319 - Homo sapiens suppressor of fused mRNA, partial cds.
JD322113 - Sequence 303137 from Patent EP1572962.
JD126113 - Sequence 107137 from Patent EP1572962.
AK307370 - Homo sapiens cDNA, FLJ97318.
AK311503 - Homo sapiens cDNA, FLJ18545.
AL137465 - Homo sapiens mRNA; cDNA DKFZp434E2022 (from clone DKFZp434E2022); partial cds.
JD129699 - Sequence 110723 from Patent EP1572962.
JD307394 - Sequence 288418 from Patent EP1572962.
JD445023 - Sequence 426047 from Patent EP1572962.
JD098525 - Sequence 79549 from Patent EP1572962.
JD107026 - Sequence 88050 from Patent EP1572962.
JD318161 - Sequence 299185 from Patent EP1572962.
JD126906 - Sequence 107930 from Patent EP1572962.
JD148928 - Sequence 129952 from Patent EP1572962.
JD410690 - Sequence 391714 from Patent EP1572962.
JD540168 - Sequence 521192 from Patent EP1572962.
JD133543 - Sequence 114567 from Patent EP1572962.
JD399671 - Sequence 380695 from Patent EP1572962.
JD271243 - Sequence 252267 from Patent EP1572962.
JD445530 - Sequence 426554 from Patent EP1572962.
JD371407 - Sequence 352431 from Patent EP1572962.
JD562576 - Sequence 543600 from Patent EP1572962.
JD510565 - Sequence 491589 from Patent EP1572962.
JD062788 - Sequence 43812 from Patent EP1572962.
JD406403 - Sequence 387427 from Patent EP1572962.
JD473068 - Sequence 454092 from Patent EP1572962.
JD530969 - Sequence 511993 from Patent EP1572962.
JD221422 - Sequence 202446 from Patent EP1572962.
JD054442 - Sequence 35466 from Patent EP1572962.
JD322901 - Sequence 303925 from Patent EP1572962.
JD067585 - Sequence 48609 from Patent EP1572962.
JD253004 - Sequence 234028 from Patent EP1572962.
JD113275 - Sequence 94299 from Patent EP1572962.
JD544863 - Sequence 525887 from Patent EP1572962.
JD117690 - Sequence 98714 from Patent EP1572962.
JD136463 - Sequence 117487 from Patent EP1572962.
JD161240 - Sequence 142264 from Patent EP1572962.
JD039789 - Sequence 20813 from Patent EP1572962.
JD157465 - Sequence 138489 from Patent EP1572962.
JD381420 - Sequence 362444 from Patent EP1572962.
JD047819 - Sequence 28843 from Patent EP1572962.
JD448581 - Sequence 429605 from Patent EP1572962.
JD334705 - Sequence 315729 from Patent EP1572962.
JD450192 - Sequence 431216 from Patent EP1572962.
JD245855 - Sequence 226879 from Patent EP1572962.
JD218067 - Sequence 199091 from Patent EP1572962.
JD464300 - Sequence 445324 from Patent EP1572962.
JD122638 - Sequence 103662 from Patent EP1572962.
JD261043 - Sequence 242067 from Patent EP1572962.
JD422712 - Sequence 403736 from Patent EP1572962.
JD261269 - Sequence 242293 from Patent EP1572962.
JD155607 - Sequence 136631 from Patent EP1572962.
JD473692 - Sequence 454716 from Patent EP1572962.
JD318481 - Sequence 299505 from Patent EP1572962.
JD372779 - Sequence 353803 from Patent EP1572962.
JD444477 - Sequence 425501 from Patent EP1572962.
JD123945 - Sequence 104969 from Patent EP1572962.
JD122067 - Sequence 103091 from Patent EP1572962.
JD321816 - Sequence 302840 from Patent EP1572962.
JD427339 - Sequence 408363 from Patent EP1572962.
JD449306 - Sequence 430330 from Patent EP1572962.
JD467280 - Sequence 448304 from Patent EP1572962.
JD162436 - Sequence 143460 from Patent EP1572962.
JD195342 - Sequence 176366 from Patent EP1572962.
JD098196 - Sequence 79220 from Patent EP1572962.
JD370473 - Sequence 351497 from Patent EP1572962.
JD053300 - Sequence 34324 from Patent EP1572962.
JD093687 - Sequence 74711 from Patent EP1572962.
JD408064 - Sequence 389088 from Patent EP1572962.
JD215191 - Sequence 196215 from Patent EP1572962.
JD109547 - Sequence 90571 from Patent EP1572962.
JD135409 - Sequence 116433 from Patent EP1572962.
JD488552 - Sequence 469576 from Patent EP1572962.
JD077761 - Sequence 58785 from Patent EP1572962.
JD210539 - Sequence 191563 from Patent EP1572962.
JD413865 - Sequence 394889 from Patent EP1572962.
JD560009 - Sequence 541033 from Patent EP1572962.
JD127303 - Sequence 108327 from Patent EP1572962.
JD403911 - Sequence 384935 from Patent EP1572962.
JD519213 - Sequence 500237 from Patent EP1572962.
JD126297 - Sequence 107321 from Patent EP1572962.
JD195650 - Sequence 176674 from Patent EP1572962.
JD514595 - Sequence 495619 from Patent EP1572962.
JD277322 - Sequence 258346 from Patent EP1572962.
JD488053 - Sequence 469077 from Patent EP1572962.
JD050578 - Sequence 31602 from Patent EP1572962.
JD563300 - Sequence 544324 from Patent EP1572962.
FW573323 - JP 2010529847-A/44: Oligonucleotides for modulation of target RNA activity.
JD136062 - Sequence 117086 from Patent EP1572962.
JD489565 - Sequence 470589 from Patent EP1572962.
JD555891 - Sequence 536915 from Patent EP1572962.

-  Biochemical and Signaling Pathways
  KEGG - Kyoto Encyclopedia of Genes and Genomes
hsa04340 - Hedgehog signaling pathway
hsa05200 - Pathways in cancer
hsa05217 - Basal cell carcinoma

BioCarta from NCI Cancer Genome Anatomy Project
h_shhPathway - Sonic Hedgehog (Shh) Pathway

Reactome (by CSHL, EBI, and GO)

Protein Q9UMX1 (Reactome details) participates in the following event(s):

R-HSA-5610723 GLI proteins bind SUFU
R-HSA-5635839 ULK3:SUFU dissociates
R-HSA-5635859 GLI:SUFU dissociates
R-HSA-5610746 SCF(beta-TrCP) ubiquitinates p-GLI3
R-HSA-5610741 PKA phosphorylates GLI1
R-HSA-5610717 PKA phosphorylates GLI2
R-HSA-5610720 PKA phosphorylates GLI3
R-HSA-5610737 NUMB:ITCH bind and ubiquitnate GLI1
R-HSA-5610732 GSK3 phosphorylates p-GLI3
R-HSA-5610722 CK1 phosphorylates p-GLI3
R-HSA-5610745 SCF(beta-TrCP) ubiquitinates p-GLI2
R-HSA-5610730 GSK3 phosphorylates p-GLI2
R-HSA-5610718 CK1 phosphorylates p-GLI2
R-HSA-5610742 SCF(beta-TrCP) ubiquitinates p-GLI1
R-HSA-5610787 Hedgehog 'off' state
R-HSA-5632684 Hedgehog 'on' state
R-HSA-5610785 GLI3 is processed to GLI3R by the proteasome
R-HSA-5610783 Degradation of GLI2 by the proteasome
R-HSA-5610780 Degradation of GLI1 by the proteasome
R-HSA-5358351 Signaling by Hedgehog
R-HSA-162582 Signal Transduction

-  Other Names for This Gene
  Alternate Gene Symbols: NM_016169, NP_057253, Q7LCP7, Q9NT90, Q9NZ07, Q9UHK2, Q9UHM8, Q9UMX1, Q9UMY0, SUFU_HUMAN, UNQ650/PRO1280
UCSC ID: uc001kvy.2
RefSeq Accession: NM_016169
Protein: Q9UMX1 (aka SUFU_HUMAN)
CCDS: CCDS7537.1

-  GeneReviews for This Gene
  GeneReviews article(s) related to gene SUFU:
bcns (Nevoid Basal Cell Carcinoma Syndrome)

-  Gene Model Information
category: coding nonsense-mediated-decay: no RNA accession: NM_016169.3
exon count: 12CDS single in 3' UTR: no RNA size: 4994
ORF size: 1455CDS single in intron: no Alignment % ID: 99.98
txCdsPredict score: 3110.00frame shift in genome: no % Coverage: 99.08
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
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-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.