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Q9Z0P7

- SUFU_MOUSE

UniProt

Q9Z0P7 - SUFU_MOUSE

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Protein

Suppressor of fused homolog

Gene

Sufu

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli

Functioni

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). Required for the proper formation of hair follicles and the control of epidermal differentiation.5 Publications

GO - Molecular functioni

  1. beta-catenin binding Source: MGI
  2. transcription factor binding Source: MGI

GO - Biological processi

  1. cytoplasmic sequestering of transcription factor Source: MGI
  2. determination of left/right symmetry Source: MGI
  3. heart looping Source: MGI
  4. negative regulation of protein ubiquitination involved in ubiquitin-dependent protein catabolic process Source: MGI
  5. negative regulation of smoothened signaling pathway Source: MGI
  6. negative regulation of smoothened signaling pathway involved in dorsal/ventral neural tube patterning Source: MGI
  7. negative regulation of transcription from RNA polymerase II promoter Source: MGI
  8. neural tube closure Source: MGI
  9. skin development Source: MGI
  10. smoothened signaling pathway involved in spinal cord motor neuron cell fate specification Source: MGI
  11. smoothened signaling pathway involved in ventral spinal cord interneuron specification Source: MGI
  12. spinal cord dorsal/ventral patterning Source: MGI
Complete GO annotation...

Names & Taxonomyi

Protein namesi
Recommended name:
Suppressor of fused homolog
Gene namesi
Name:Sufu
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589: Chromosome 19

Organism-specific databases

MGIiMGI:1345643. Sufu.

Subcellular locationi

GO - Cellular componenti

  1. cilium Source: MGI
  2. cytoplasm Source: UniProtKB
  3. nucleus Source: MGI
  4. primary cilium Source: BHF-UCL
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 484484Suppressor of fused homologPRO_0000072303Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei303 – 3031N6-acetyllysineBy similarity
Modified residuei481 – 4811PhosphoserineBy similarity

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

MaxQBiQ9Z0P7.
PaxDbiQ9Z0P7.
PRIDEiQ9Z0P7.

PTM databases

PhosphoSiteiQ9Z0P7.

Expressioni

Tissue specificityi

Widely expressed in adult and fetal tissues.2 Publications

Gene expression databases

BgeeiQ9Z0P7.
CleanExiMM_SUFU.
ExpressionAtlasiQ9Z0P7. baseline and differential.
GenevestigatoriQ9Z0P7.

Interactioni

Subunit structurei

Interacts with ULK3; inactivating the protein kinase activity of ULK3. Interacts with RAB23 (By similarity). 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 similarity6 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
Lgals3P161105EBI-3508336,EBI-3508325
Pias1O889073EBI-3508336,EBI-3508327
Rnf19aP506363EBI-3508336,EBI-3508340
Sap18O551286EBI-3508336,EBI-3508332

Protein-protein interaction databases

BioGridi204881. 21 interactions.
IntActiQ9Z0P7. 18 interactions.

Structurei

3D structure databases

ProteinModelPortaliQ9Z0P7.
SMRiQ9Z0P7. Positions 1-280, 356-481.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the SUFU family.Curated

Phylogenomic databases

eggNOGiNOG72477.
GeneTreeiENSGT00390000009747.
HOGENOMiHOG000007864.
HOVERGENiHBG061539.
InParanoidiQ9Z0P7.
KOiK06229.
OMAiGDTAITF.
OrthoDBiEOG7RV9FV.
PhylomeDBiQ9Z0P7.
TreeFamiTF324548.

Family and domain databases

InterProiIPR020941. SUFU-like_domain.
IPR024314. SUFU_C.
IPR007768. Suppressor_of_fused.
IPR016591. Suppressor_of_fused_euk.
[Graphical view]
PANTHERiPTHR10928. PTHR10928. 1 hit.
PfamiPF05076. SUFU. 1 hit.
PF12470. SUFU_C. 1 hit.
[Graphical view]
PIRSFiPIRSF011844. Suppressor_of_fused_protein. 1 hit.

Sequences (4)i

Sequence statusi: Complete.

This entry describes 4 isoformsi produced by alternative splicing. Align

Isoform 1 (identifier: Q9Z0P7-1) [UniParc]FASTAAdd to Basket

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.

« Hide

        10         20         30         40         50
MAELRPSVAP GPAAPPASGP SAPPAFASLF PPGLHAIYGE CRRLYPDQPN
60 70 80 90 100
PLQVTAIVKY WLGGPDPLDY VSMYRNMGSP SANIPEHWHY ISFGLSDLYG
110 120 130 140 150
DNRVHEFTGT DGPSGFGFEL TFRLKRETGE SAPPTWPAEL MQGLARYVFQ
160 170 180 190 200
SENTFCSGDH VSWHSPLDNS ESRIQHMLLT EDPQMQPVRT PFGVVTFLQI
210 220 230 240 250
VGVCTEELHS AQQWNGQGIL ELLRTVPIAG GPWLITDMRR GETIFEIDPH
260 270 280 290 300
LQERVDKGIE TDGSNLSGVS AKCAWDDLSR PPEDEEDSRS ICLGTQPRRL
310 320 330 340 350
SGKDTEQIRE TLRRGLEINS KPVLPPINSQ RQNGLTHDRA PSRKDSLGSD
360 370 380 390 400
SSTAIIPHEL IRTRQLESVH LKFNQESGAL IPLCLRGRLL HGRHFTYKSI
410 420 430 440 450
TGDMAITFVS TGVEGAFATE EHPYAAHGPW LQILLTEEFV EKMLEDLEDL
460 470 480
TSPEEFKLPK EYSWPEKKLK VSILPDVVFD SPLH
Length:484
Mass (Da):53,957
Last modified:May 1, 1999 - v1
Checksum:i6ED5666BC4D4AFB5
GO
Isoform 2 (identifier: Q9Z0P7-2) [UniParc]FASTAAdd to Basket

The sequence of this isoform differs from the canonical sequence as follows:
     62-106: Missing.
     252-252: Q → QQ

Note: No experimental confirmation available.

Show »
Length:440
Mass (Da):48,994
Checksum:i1C36B0D3382C1F95
GO
Isoform 3 (identifier: Q9Z0P7-3) [UniParc]FASTAAdd to Basket

The sequence of this isoform differs from the canonical sequence as follows:
     252-252: Q → QQ
     433-484: ILLTEEFVEK...PDVVFDSPLH → VRRSLSSFSSSSCSSLAACPPLPHHPKDRPLWLPC

Show »
Length:468
Mass (Da):51,759
Checksum:i98B0F3F09CA85B8A
GO
Isoform 4 (identifier: Q9Z0P7-4) [UniParc]FASTAAdd to Basket

Also known as: SU(FU)-XL

The sequence of this isoform differs from the canonical sequence as follows:
     252-252: Q → QQ

Show »
Length:485
Mass (Da):54,085
Checksum:iF9387714357EC8E4
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti79 – 791S → C in AAF61412. (PubMed:10531011)Curated
Sequence conflicti220 – 2201L → Q in AAF61412. (PubMed:10531011)Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei62 – 10645Missing in isoform 2. 1 PublicationVSP_013281Add
BLAST
Alternative sequencei252 – 2521Q → QQ in isoform 2, isoform 3 and isoform 4. 2 PublicationsVSP_013282
Alternative sequencei433 – 48452ILLTE…DSPLH → VRRSLSSFSSSSCSSLAACP PLPHHPKDRPLWLPC in isoform 3. 1 PublicationVSP_013283Add
BLAST

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
AF134893 mRNA. Translation: AAF61412.1.
AJ131692 mRNA. Translation: CAB38081.1.
AJ308625 mRNA. Translation: CAC34257.1.
AJ308626 mRNA. Translation: CAC34258.1.
AJ308627
, AJ308628, AJ308629, AJ308630, AJ308632, AJ308634, AJ308635, AJ308633, AJ308631 Genomic DNA. Translation: CAC34271.1.
AK015885 mRNA. Translation: BAB30017.1.
AK047603 mRNA. Translation: BAC33095.1.
BC048168 mRNA. Translation: AAH48168.1.
BC056997 mRNA. Translation: AAH56997.1.
CCDSiCCDS29879.1. [Q9Z0P7-1]
CCDS38008.1. [Q9Z0P7-4]
RefSeqiNP_001020562.1. NM_001025391.2. [Q9Z0P7-1]
NP_056567.2. NM_015752.3. [Q9Z0P7-4]
UniGeneiMm.41210.

Genome annotation databases

EnsembliENSMUST00000039922; ENSMUSP00000049109; ENSMUSG00000025231. [Q9Z0P7-1]
ENSMUST00000111867; ENSMUSP00000107498; ENSMUSG00000025231. [Q9Z0P7-4]
ENSMUST00000120778; ENSMUSP00000112653; ENSMUSG00000025231.
GeneIDi24069.
KEGGimmu:24069.
UCSCiuc008htn.1. mouse. [Q9Z0P7-2]
uc008hto.1. mouse. [Q9Z0P7-3]
uc008htq.1. mouse. [Q9Z0P7-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
AF134893 mRNA. Translation: AAF61412.1 .
AJ131692 mRNA. Translation: CAB38081.1 .
AJ308625 mRNA. Translation: CAC34257.1 .
AJ308626 mRNA. Translation: CAC34258.1 .
AJ308627
, AJ308628 , AJ308629 , AJ308630 , AJ308632 , AJ308634 , AJ308635 , AJ308633 , AJ308631 Genomic DNA. Translation: CAC34271.1 .
AK015885 mRNA. Translation: BAB30017.1 .
AK047603 mRNA. Translation: BAC33095.1 .
BC048168 mRNA. Translation: AAH48168.1 .
BC056997 mRNA. Translation: AAH56997.1 .
CCDSi CCDS29879.1. [Q9Z0P7-1 ]
CCDS38008.1. [Q9Z0P7-4 ]
RefSeqi NP_001020562.1. NM_001025391.2. [Q9Z0P7-1 ]
NP_056567.2. NM_015752.3. [Q9Z0P7-4 ]
UniGenei Mm.41210.

3D structure databases

ProteinModelPortali Q9Z0P7.
SMRi Q9Z0P7. Positions 1-280, 356-481.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 204881. 21 interactions.
IntActi Q9Z0P7. 18 interactions.

PTM databases

PhosphoSitei Q9Z0P7.

Proteomic databases

MaxQBi Q9Z0P7.
PaxDbi Q9Z0P7.
PRIDEi Q9Z0P7.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSMUST00000039922 ; ENSMUSP00000049109 ; ENSMUSG00000025231 . [Q9Z0P7-1 ]
ENSMUST00000111867 ; ENSMUSP00000107498 ; ENSMUSG00000025231 . [Q9Z0P7-4 ]
ENSMUST00000120778 ; ENSMUSP00000112653 ; ENSMUSG00000025231 .
GeneIDi 24069.
KEGGi mmu:24069.
UCSCi uc008htn.1. mouse. [Q9Z0P7-2 ]
uc008hto.1. mouse. [Q9Z0P7-3 ]
uc008htq.1. mouse. [Q9Z0P7-1 ]

Organism-specific databases

CTDi 51684.
MGIi MGI:1345643. Sufu.

Phylogenomic databases

eggNOGi NOG72477.
GeneTreei ENSGT00390000009747.
HOGENOMi HOG000007864.
HOVERGENi HBG061539.
InParanoidi Q9Z0P7.
KOi K06229.
OMAi GDTAITF.
OrthoDBi EOG7RV9FV.
PhylomeDBi Q9Z0P7.
TreeFami TF324548.

Miscellaneous databases

NextBioi 304049.
PROi Q9Z0P7.
SOURCEi Search...

Gene expression databases

Bgeei Q9Z0P7.
CleanExi MM_SUFU.
ExpressionAtlasi Q9Z0P7. baseline and differential.
Genevestigatori Q9Z0P7.

Family and domain databases

InterProi IPR020941. SUFU-like_domain.
IPR024314. SUFU_C.
IPR007768. Suppressor_of_fused.
IPR016591. Suppressor_of_fused_euk.
[Graphical view ]
PANTHERi PTHR10928. PTHR10928. 1 hit.
Pfami PF05076. SUFU. 1 hit.
PF12470. SUFU_C. 1 hit.
[Graphical view ]
PIRSFi PIRSF011844. Suppressor_of_fused_protein. 1 hit.
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  1. "Mouse suppressor of fused is a negative regulator of sonic hedgehog signaling and alters the subcellular distribution of Gli1."
    Ding Q., Fukami S., Meng X., Nishizaki Y., Zhang X., Sasaki H., Dlugosz A., Nakafuku M., Hui C.
    Curr. Biol. 9:1119-1122(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 4), FUNCTION, INTERACTION WITH GLI1; GLI2 AND GLI3, TISSUE SPECIFICITY.
  2. "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] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
    Tissue: Embryo.
  3. "Genomic organization and embryonic expression of suppressor of fused, a candidate gene for the split-hand/split-foot malformation type 3."
    Grimm T., Teglund S., Tackels D., Sangiorgi E., Gurrieri F., Schwartz C., Toftgaard R.
    FEBS Lett. 505:13-17(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1), TISSUE SPECIFICITY.
    Strain: 129/SvJ and C57BL/6J.
    Tissue: Mammary gland and Testis.
  4. "The transcriptional landscape of the mammalian genome."
    Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.
    , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
    Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 2 AND 3).
    Strain: C57BL/6J.
    Tissue: Cerebellum and Testis.
  5. "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] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
    Strain: C57BL/6.
    Tissue: Brain.
  6. "Suppressor of fused negatively regulates beta-catenin signaling."
    Meng X., Poon R., Zhang X., Cheah A., Ding Q., Hui C.-C., Alman B.
    J. Biol. Chem. 276:40113-40119(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, SUBCELLULAR LOCATION, IDENTIFICATION IN A COMPLEX WITH CTNNB1.
  7. "Suppressor of fused represses Gli-mediated transcription by recruiting the SAP18-mSin3 corepressor complex."
    Cheng S.Y., Bishop J.M.
    Proc. Natl. Acad. Sci. U.S.A. 99:5442-5447(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH SAP18, IDENTIFICATION IN A DNA-BOUND SIN3 COREPRESSOR COMPLEX.
  8. "The mammalian Cos2 homolog Kif7 plays an essential role in modulating Hh signal transduction during development."
    Endoh-Yamagami S., Evangelista M., Wilson D., Wen X., Theunissen J.W., Phamluong K., Davis M., Scales S.J., Solloway M.J., de Sauvage F.J., Peterson A.S.
    Curr. Biol. 19:1320-1326(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH KIF7.
  9. "The output of Hedgehog signaling is controlled by the dynamic association between Suppressor of Fused and the Gli proteins."
    Humke E.W., Dorn K.V., Milenkovic L., Scott M.P., Rohatgi R.
    Genes Dev. 24:670-682(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH GLI3.
  10. "Kif7 regulates Gli2 through Sufu-dependent and -independent functions during skin development and tumorigenesis."
    Li Z.J., Nieuwenhuis E., Nien W., Zhang X., Zhang J., Puviindran V., Wainwright B.J., Kim P.C., Hui C.C.
    Development 139:4152-4161(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN EPIDERMAL DIFFERENTIATION, SUBCELLULAR LOCATION, INTERACTION WITH GLI2.

Entry informationi

Entry nameiSUFU_MOUSE
AccessioniPrimary (citable) accession number: Q9Z0P7
Secondary accession number(s): Q8C8B4
, Q99JG0, Q9D521, Q9JLU1
Entry historyi
Integrated into UniProtKB/Swiss-Prot: March 29, 2005
Last sequence update: May 1, 1999
Last modified: October 29, 2014
This is version 105 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3