Skip Header

 
Contribute Send feedback
Read comments (0) or add your own

Reviewed, UniProtKB/Swiss-Prot Q9UMX1 (SUFU_HUMAN)

Last modified July 7, 2009. Version 60. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Alternative products · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents

Names and origin

Protein namesRecommended name:
    Suppressor of fused homolog
      Short name=SUFUH
Gene names
Name: SUFU
ORF Names: UNQ650/PRO1280
OrganismHomo sapiens (Human) [Complete proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length484 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is not processed.
Protein existenceEvidence at protein level.

General annotation (Comments)

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. Ref.1 Ref.2 Ref.3 Ref.9

Subunit structure

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. Ref.1

Subcellular location

Cytoplasm. Nucleus. Ref.1 Ref.2

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. Ref.1 Ref.2

Involvement in 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.

Sequence similarities

Belongs to the SUFU family.

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q9UMX1-1)

Also known as: Su(fu)484;

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Note: Major isoform.
Isoform 2 (identifier: Q9UMX1-2)

Also known as: Su(fu)433;

The sequence of this isoform differs from the canonical sequence as follows:
     433-433: I → L
     434-484: Missing.
Isoform 3 (identifier: Q9UMX1-3)

The sequence of this isoform differs from the canonical sequence as follows:
     433-484: ILLTEEFVEK...PDVVFDSPLH → VRRPFFFSLL...LMDSGPGACV

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 484484Suppressor of fused homolog
PRO_0000072302

Amino acid modifications

Modified residue4811Phosphoserine Ref.10

Natural variations

Alternative sequence433 – 48452ILLTE…DSPLH → VRRPFFFSLLPFIDFLAHPS SSPLAALDGTPSWGAGHECL MDSGPGACV in isoform 3.
VSP_013280
Alternative sequence4331I → L in isoform 2.
VSP_013278
Alternative sequence434 – 48451Missing in isoform 2.
VSP_013279
Natural variant151P → L Ref.3
VAR_021566
Natural variant3401A → S Ref.3
VAR_021567

Experimental info

Mutagenesis1061E → A: No effect on down-regulation of GLI1 activity. Ref.11
Mutagenesis1111D → A: No effect on down-regulation of GLI1 activity. Ref.11
Mutagenesis1281T → A or D: No effect on down-regulation of GLI1 activity. Ref.11
Mutagenesis1521E → A: No effect on down-regulation of GLI1 activity. Ref.11
Mutagenesis1591D → A: Abolishes down-regulation of GLI1 activity. Has only slight effect on GLI1 binding. Ref.11
Mutagenesis1811E → A: No effect on down-regulation of GLI1 activity. Ref.11
Mutagenesis2211E → A: No effect on down-regulation of GLI1 activity. Ref.11
Mutagenesis2621D → A: No effect on down-regulation of GLI1 activity. Ref.11
Sequence conflict3361A → P in AAD50501. Ref.2

Secondary structure

........................................ 484
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (Su(fu)484) [UniParc].

Last modified April 12, 2005. Version 2.
Checksum: 4A9CD1CF75FC179A

FASTA48453,947
        10         20         30         40         50         60 
MAELRPSGAP GPTAPPAPGP TAPPAFASLF PPGLHAIYGE CRRLYPDQPN PLQVTAIVKY 

        70         80         90        100        110        120 
WLGGPDPLDY VSMYRNVGSP SANIPEHWHY ISFGLSDLYG DNRVHEFTGT DGPSGFGFEL 

       130        140        150        160        170        180 
TFRLKRETGE SAPPTWPAEL MQGLARYVFQ SENTFCSGDH VSWHSPLDNS ESRIQHMLLT 

       190        200        210        220        230        240 
EDPQMQPVQT PFGVVTFLQI VGVCTEELHS AQQWNGQGIL ELLRTVPIAG GPWLITDMRR 

       250        260        270        280        290        300 
GETIFEIDPH LQERVDKGIE TDGSNLSGVS AKCAWDDLSR PPEDDEDSRS ICIGTQPRRL 

       310        320        330        340        350        360 
SGKDTEQIRE TLRRGLEINS KPVLPPINPQ RQNGLAHDRA PSRKDSLESD SSTAIIPHEL 

       370        380        390        400        410        420 
IRTRQLESVH LKFNQESGAL IPLCLRGRLL HGRHFTYKSI TGDMAITFVS TGVEGAFATE 

       430        440        450        460        470        480 
EHPYAAHGPW LQILLTEEFV EKMLEDLEDL TSPEEFKLPK EYSWPEKKLK VSILPDVVFD 


SPLH 

« Hide

Isoform 2 (Su(fu)433).

Checksum: 40CF1CDD5F526102
Show »

FASTA43347,932
Isoform 3.

Checksum: 7B312507FF653923
Show »

FASTA48152,977

References

« Hide 'large scale' references
[1]"Characterization of the human suppressor of fused, a negative regulator of the zinc-finger transcription factor Gli."
Stone D.M., Murone M., Luoh S.-M., Ye W., Armanini M.P., Gurney A., Phillips H., Brush J., Goddard A., deSauvage F.J., Rosenthal A.
J. Cell Sci. 112:4437-4448(1999) [PubMed: 10564661] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2 AND 3), FUNCTION, INTERACTION WITH GLI1; GLI2; GLI3 AND BTRC, HOMODIMERIZATION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
Tissue: Fetal kidney, Fetal lung and Fetal testis.
[2]"Mammalian suppressor-of-fused modulates nuclear-cytoplasmic shuttling of Gli-1."
Kogerman P., Grimm T., Kogerman L., Krause D., Unden A.B., Sandstedt B., Toftgaard R., Zaphiropoulos P.G.
Nat. Cell Biol. 1:312-319(1999) [PubMed: 10559945] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, INTERACTION WITH GLI1, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
[3]"Mutations in SUFU predispose to medulloblastoma."
Taylor M.D., Liu L., Raffel C., Hui C.-C., Mainprize T.G., Zhang X., Agatep R., Chiappa S., Gao L., Lowrance A., Hao A., Goldstein A.M., Stavrou T., Scherer S.W., Dura W.T., Wainwright B., Squire J.A., Rutka J.T., Hogg D.
Nat. Genet. 31:306-310(2002) [PubMed: 12068298] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, VARIANTS LEU-15 AND SER-340, ROLE IN THE DEVELOPMENT OF MEDULLOBLASTOMA.
[4]"The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment."
Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J., Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P., Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E. expand/collapse author list , Heldens S., Huang A., Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D., Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L., Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C., Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J., Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.
Genome Res. 13:2265-2270(2003) [PubMed: 12975309] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
[5]"The DNA sequence and comparative analysis of human chromosome 10."
Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L., Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K., Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L., Taylor A., Battles J. expand/collapse author list , Bird C.P., Ainscough R., Almeida J.P., Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A., Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P., Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D., Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.
Nature 429:375-381(2004) [PubMed: 15164054] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Muscle.
[7]"Suppressor of fused gene involved in hedgehog signal transduction in Drosophila melanogaster is conserved in mammals."
Delattre M., Briand S., Paces-Fessy M., Blanchet-Tournier M.-F.
Dev. Genes Evol. 209:294-300(1999) [PubMed: 11252182] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 3-484 (ISOFORM 1).
Tissue: Neuron.
[8]"The full-ORF clone resource of the German cDNA consortium."
Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Blocker H., Heubner D., Hoerlein A., Michel G., Wedler H., Kohrer K., Ottenwalder B., Poustka A., Wiemann S., Schupp I.
BMC Genomics 8:399-399(2007) [PubMed: 17974005] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 442-484 (ISOFORM 1).
Tissue: Testis.
[9]"Gli regulation by the opposing activities of fused and suppressor of fused."
Murone M., Luoh S.-L., Stone D., Li W., Gurney A., Armanini M., Grey C., Rosenthal A., de Sauvage F.J.
Nat. Cell Biol. 2:310-312(2000) [PubMed: 10806483] [Abstract]
Cited for: FUNCTION, INTERACTION WITH STK36.
[10]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed: 18669648] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-481, MASS SPECTROMETRY.
[11]"Suppressor of fused regulates Gli activity through a dual binding mechanism."
Merchant M., Vajdos F.F., Ultsch M., Maun H.R., Wendt U., Cannon J., Desmarais W., Lazarus R.A., de Vos A.M., de Sauvage F.J.
Mol. Cell. Biol. 24:8627-8641(2004) [PubMed: 15367681] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.65 ANGSTROMS) OF 27-268, INTERACTION WITH GLI1, MUTAGENESIS OF GLU-106; ASP-111; THR-128; GLU-152; ASP-159; GLU-181; GLU-221 AND ASP-262.

Cross-references

Sequence databases

AF144231 mRNA. Translation: AAF23890.1.
AF159447 mRNA. Translation: AAF23893.1.
AF222345 mRNA. Translation: AAF35866.1.
AF175770 mRNA. Translation: AAD50501.1.
AY081829 expand/collapse EMBL AC list , AY081818, AY081819, AY081820, AY081822, AY081824, AY081825, AY081821, AY081823, AY081826, AY081828, AY081827 Genomic DNA. Translation: AAM08947.1.
AY358550 mRNA. Translation: AAQ88914.1.
AL121928, AL391121, AL157386 Genomic DNA. Translation: CAI12525.1.
AL121928, AL157386, AL391121 Genomic DNA. Translation: CAI12526.1.
AL157386, AL391121, AL121928 Genomic DNA. Translation: CAI39614.1.
AL157386, AL121928, AL391121 Genomic DNA. Translation: CAI39615.1.
AL391121, AL121928, AL157386 Genomic DNA. Translation: CAI40864.1.
AL391121, AL121928, AL157386 Genomic DNA. Translation: CAI40865.1.
BC013291 mRNA. Translation: AAH13291.1.
AF172319 mRNA. Translation: AAD51655.1.
AL137465 mRNA. Translation: CAB70752.1.
IPIIPI00099179.
IPI00556458.
IPI00556521.
PIRT46409.
RefSeqNP_057253.2.
UniGeneHs.404089

3D structure databases

EntryMethodResolution (Å)ChainPositionsPDBsum
1M1LX-ray2.65A/B/C/D27-262[»]
ModBaseSearch...

Protein-protein interaction databases

IntActQ9UMX1. 15 interactions.

PTM databases

PhosphoSiteQ9UMX1.

Proteomic databases

PRIDEQ9UMX1.

Genome annotation databases

EnsemblENSG00000107882. Homo sapiens. [Contig view]
GeneID51684.
KEGGhsa:51684.
UCSCuc001kvx.2. human.
uc001kvy.1. human.

Organism-specific databases

GeneCardsGC10P104253.
H-InvDBHIX0009163.
HGNCHGNC:16466. SUFU.
HPAHPA008700.
MIM155255. phenotype.
607035. gene.
Orphanet616. Medulloblastoma.
PharmGKBPA38146.
GenAtlasSearch...

Phylogenomic databases

HOVERGENQ9UMX1.
OMAQ9UMX1. HLQQERV.

Enzyme and pathway databases

Pathway_Interaction_DBhedgehog_glipathway. Hedgehog signaling events mediated by Gli proteins.

Gene expression databases

ArrayExpressQ9UMX1.
BgeeQ9UMX1.
CleanExHS_SUFU.
GermOnlineENSG00000107882. Homo sapiens.

Family and domain databases

InterProIPR007768. SUFU.
IPR016591. Suppressor_of_fused_protein.
[Graphical view]
PANTHERPTHR10928. SUFU. 1 hit.
PfamPF05076. SUFU. 1 hit.
[Graphical view]
PIRSFPIRSF011844. Suppressor_of_fused_protein. 1 hit.
ProtoNetSearch...

Other Resources

NextBio55686.
SOURCESearch...

Entry information

Entry nameSUFU_HUMAN
AccessionPrimary (citable) accession number: Q9UMX1
Secondary accession number(s): Q7LCP7 expand/collapse secondary AC list , Q9NT90, Q9NZ07, Q9UHK2, Q9UHM8, Q9UMY0
Entry history
Integrated into UniProtKB/Swiss-Prot: April 12, 2005
Last sequence update: April 12, 2005
Last modified: July 7, 2009
This is version 60 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)

Relevant documents

Human chromosome 10

Human chromosome 10: entries, gene names and cross-references to MIM

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

SIMILARITY comments

Index of protein domains and families

Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Alternative products · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents