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Protein

Suppressor of fused homolog

Gene

SUFU

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Negative regulator in the hedgehog/smoothened signaling pathway. Down-regulates GLI1-mediated transactivation of target genes (PubMed:15367681, PubMed:24311597, PubMed:24217340). Down-regulates GLI2-mediated transactivation of target genes (PubMed:24311597, PubMed:24217340). 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 (PubMed:10806483, PubMed:24217340). 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 normal embryonic development. Required for the proper formation of hair follicles and the control of epidermal differentiation (By similarity).By similarity10 Publications

GO - Molecular functioni

  • beta-catenin binding Source: Ensembl
  • protein kinase binding Source: UniProtKB
  • transcription corepressor activity Source: UniProtKB
  • transcription factor binding Source: MGI

GO - Biological processi

Keywordsi

Molecular functionDevelopmental protein

Enzyme and pathway databases

ReactomeiR-HSA-5610780 Degradation of GLI1 by the proteasome
R-HSA-5610783 Degradation of GLI2 by the proteasome
R-HSA-5610785 GLI3 is processed to GLI3R by the proteasome
R-HSA-5610787 Hedgehog 'off' state
R-HSA-5632684 Hedgehog 'on' state
SignaLinkiQ9UMX1
SIGNORiQ9UMX1

Names & Taxonomyi

Protein namesi
Recommended name:
Suppressor of fused homolog
Short name:
SUFUH
Gene namesi
Name:SUFU
ORF Names:UNQ650/PRO1280
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 10

Organism-specific databases

EuPathDBiHostDB:ENSG00000107882.11
HGNCiHGNC:16466 SUFU
MIMi607035 gene
neXtProtiNX_Q9UMX1

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Involvement in diseasei

Medulloblastoma (MDB)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionMalignant, invasive embryonal tumor of the cerebellum with a preferential manifestation in children.
See also OMIM:155255
Joubert syndrome 32 (JBTS32)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA form of Joubert syndrome, a disorder presenting with cerebellar ataxia, oculomotor apraxia, hypotonia, neonatal breathing abnormalities and psychomotor delay. Neuroradiologically, it is characterized by cerebellar vermian hypoplasia/aplasia, thickened and reoriented superior cerebellar peduncles, and an abnormally large interpeduncular fossa, giving the appearance of a molar tooth on transaxial slices (molar tooth sign). Additional variable features include retinal dystrophy, renal disease, liver fibrosis, and polydactyly. JBTS32 inheritance is autosomal recessive.
See also OMIM:617757
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_080421176H → R in JBTS32; decreased stability; no effect on nuclear and cytoplasmic localization; decreased interaction with GLI3; no effect on interaction with GLI1; decreased repression of the hedgehog/smoothened signaling pathway. 1 Publication1
Natural variantiVAR_080426406I → T in JBTS32; decreased stability; forms cytoplasmic aggregates; decreased interaction with GLI3; no effect on interaction with GLI1; decreased repression of the hedgehog/smoothened signaling pathway. 1 Publication1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi106E → A: No effect on down-regulation of GLI1 activity. 1 Publication1
Mutagenesisi111D → A: No effect on down-regulation of GLI1 activity. 1 Publication1
Mutagenesisi128T → A or D: No effect on down-regulation of GLI1 activity. 1 Publication1
Mutagenesisi147Y → R: Impairs interaction with GLI1 and GLI2. Abolishes interaction with GLI1 and GLI2; when associated with R-159 and R-380. 1 Publication1
Mutagenesisi152E → A: No effect on down-regulation of GLI1 activity. 1 Publication1
Mutagenesisi159D → A: Abolishes down-regulation of GLI1 activity. Has only slight effect on GLI1 binding. 1 Publication1
Mutagenesisi159D → R: Impairs interaction with GLI1 and GLI2. Abolishes interaction with GLI1 and GLI2; when associated with R-147 and R-380. 1 Publication1
Mutagenesisi181E → A: No effect on down-regulation of GLI1 activity. 1 Publication1
Mutagenesisi221E → A: No effect on down-regulation of GLI1 activity. 1 Publication1
Mutagenesisi262D → A: No effect on down-regulation of GLI1 activity. 1 Publication1
Mutagenesisi380L → R: Impairs interaction with GLI1 and GLI2. Abolishes interaction with GLI1 and GLI2; when associated with R-147 and R-159. 1 Publication1

Keywords - Diseasei

Ciliopathy, Disease mutation, Joubert syndrome, Tumor suppressor

Organism-specific databases

DisGeNETi51684
MalaCardsiSUFU
MIMi155255 phenotype
617757 phenotype
OpenTargetsiENSG00000107882
Orphaneti251863 Desmoplastic/nodular medulloblastoma
263662 Familial multiple meningioma
251858 Medulloblastoma with extensive nodularity
PharmGKBiPA38146

Chemistry databases

ChEMBLiCHEMBL5390

Polymorphism and mutation databases

BioMutaiSUFU
DMDMi62511179

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000723021 – 484Suppressor of fused homologAdd BLAST484

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei301PhosphoserineCombined sources1
Modified residuei303N6-acetyllysineCombined sources1
Cross-linki321Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Modified residuei342PhosphoserineCombined sources1
Modified residuei346PhosphoserineCombined sources1
Modified residuei481PhosphoserineCombined sources1

Keywords - PTMi

Acetylation, Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ9UMX1
PaxDbiQ9UMX1
PeptideAtlasiQ9UMX1
PRIDEiQ9UMX1
ProteomicsDBi85217
85218 [Q9UMX1-2]
85219 [Q9UMX1-3]

PTM databases

iPTMnetiQ9UMX1
PhosphoSitePlusiQ9UMX1

Expressioni

Tissue specificityi

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.2 Publications

Gene expression databases

BgeeiENSG00000107882
CleanExiHS_SUFU
GenevisibleiQ9UMX1 HS

Organism-specific databases

HPAiHPA008700

Interactioni

Subunit structurei

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 (PubMed:20643644). Interacts with RAB23 (PubMed:22365972).By similarity9 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • beta-catenin binding Source: Ensembl
  • protein kinase binding Source: UniProtKB
  • transcription factor binding Source: MGI

Protein-protein interaction databases

BioGridi119676, 44 interactors
ComplexPortaliCPX-148 GLI2-SUFU complex
CPX-149 GLI2-SUFU complex
CPX-150 GLI3-SUFU complex
CPX-56 GLI1-SUFU complex
CORUMiQ9UMX1
ELMiQ9UMX1
IntActiQ9UMX1, 41 interactors
MINTiQ9UMX1
STRINGi9606.ENSP00000358918

Structurei

Secondary structure

1484
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi27 – 29Combined sources3
Helixi32 – 44Combined sources13
Beta strandi52 – 55Combined sources4
Helixi60 – 62Combined sources3
Beta strandi69 – 76Combined sources8
Helixi80 – 82Combined sources3
Beta strandi87 – 96Combined sources10
Beta strandi101 – 105Combined sources5
Beta strandi110 – 125Combined sources16
Helixi136 – 151Combined sources16
Beta strandi160 – 162Combined sources3
Beta strandi169 – 171Combined sources3
Beta strandi176 – 181Combined sources6
Beta strandi188 – 190Combined sources3
Beta strandi193 – 203Combined sources11
Helixi205 – 213Combined sources9
Helixi216 – 224Combined sources9
Helixi227 – 229Combined sources3
Turni230 – 234Combined sources5
Helixi244 – 247Combined sources4
Helixi250 – 262Combined sources13
Beta strandi266 – 276Combined sources11
Beta strandi363 – 367Combined sources5
Beta strandi369 – 373Combined sources5
Helixi375 – 378Combined sources4
Helixi381 – 387Combined sources7
Helixi389 – 391Combined sources3
Beta strandi395 – 403Combined sources9
Beta strandi405 – 409Combined sources5
Beta strandi420 – 422Combined sources3
Beta strandi424 – 427Combined sources4
Beta strandi430 – 434Combined sources5
Helixi437 – 446Combined sources10
Turni447 – 449Combined sources3
Beta strandi460 – 464Combined sources5
Helixi465 – 467Combined sources3
Beta strandi469 – 473Combined sources5
Helixi476 – 479Combined sources4

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1M1LX-ray2.65A/B/C/D27-262[»]
4BL8X-ray3.04A/B32-483[»]
4BL9X-ray2.80A/B/C/D32-278[»]
A/B/C/D361-483[»]
4BLAX-ray3.50A/B/C/D32-278[»]
A/B/C/D361-483[»]
4BLBX-ray2.80A/B/C/D32-278[»]
A/B/C/D361-483[»]
4BLDX-ray2.80A/B/C/D32-278[»]
A/B/C/D361-483[»]
4KM8X-ray2.26A1-484[»]
4KM9X-ray3.19A1-484[»]
4KMDX-ray1.70A1-484[»]
4KMHX-ray3.04A/B1-484[»]
ProteinModelPortaliQ9UMX1
SMRiQ9UMX1
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ9UMX1

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni279 – 360Intrinsically disordered1 PublicationAdd BLAST82

Sequence similaritiesi

Belongs to the SUFU family.Curated

Phylogenomic databases

eggNOGiENOG410IFRJ Eukaryota
ENOG410XRUC LUCA
GeneTreeiENSGT00390000009747
HOVERGENiHBG061539
InParanoidiQ9UMX1
KOiK06229
OMAiGDNIPWR
OrthoDBiEOG091G132G
PhylomeDBiQ9UMX1
TreeFamiTF324548

Family and domain databases

Gene3Di3.30.1360.230, 1 hit
InterProiView protein in InterPro
IPR020941 SUFU-like_domain
IPR024314 SUFU_C
IPR038489 SUFU_C_sf
IPR037181 SUFU_N
IPR007768 Suppressor_of_fused
IPR016591 Suppressor_of_fused_euk
PANTHERiPTHR10928 PTHR10928, 1 hit
PfamiView protein in Pfam
PF05076 SUFU, 1 hit
PF12470 SUFU_C, 1 hit
PIRSFiPIRSF011844 Suppressor_of_fused_protein, 1 hit
SUPFAMiSSF103359 SSF103359, 1 hit

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q9UMX1-1) [UniParc]FASTAAdd to basket
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.

« Hide

        10         20         30         40         50
MAELRPSGAP GPTAPPAPGP TAPPAFASLF PPGLHAIYGE CRRLYPDQPN
60 70 80 90 100
PLQVTAIVKY WLGGPDPLDY VSMYRNVGSP SANIPEHWHY ISFGLSDLYG
110 120 130 140 150
DNRVHEFTGT DGPSGFGFEL TFRLKRETGE SAPPTWPAEL MQGLARYVFQ
160 170 180 190 200
SENTFCSGDH VSWHSPLDNS ESRIQHMLLT EDPQMQPVQT PFGVVTFLQI
210 220 230 240 250
VGVCTEELHS AQQWNGQGIL ELLRTVPIAG GPWLITDMRR GETIFEIDPH
260 270 280 290 300
LQERVDKGIE TDGSNLSGVS AKCAWDDLSR PPEDDEDSRS ICIGTQPRRL
310 320 330 340 350
SGKDTEQIRE TLRRGLEINS KPVLPPINPQ RQNGLAHDRA PSRKDSLESD
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
Note: Major isoform.
Length:484
Mass (Da):53,947
Last modified:April 12, 2005 - v2
Checksum:i4A9CD1CF75FC179A
GO
Isoform 2 (identifier: Q9UMX1-2) [UniParc]FASTAAdd to basket
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.

Show »
Length:433
Mass (Da):47,932
Checksum:i40CF1CDD5F526102
GO
Isoform 3 (identifier: Q9UMX1-3) [UniParc]FASTAAdd to basket

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

Show »
Length:481
Mass (Da):52,977
Checksum:i7B312507FF653923
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti336A → P in AAD50501 (PubMed:10559945).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_02156615P → L1 PublicationCorresponds to variant dbSNP:rs28942088EnsemblClinVar.1
Natural variantiVAR_08041819G → V1 Publication1
Natural variantiVAR_08041937I → V1 Publication1
Natural variantiVAR_08042077V → M1 Publication1
Natural variantiVAR_080421176H → R in JBTS32; decreased stability; no effect on nuclear and cytoplasmic localization; decreased interaction with GLI3; no effect on interaction with GLI1; decreased repression of the hedgehog/smoothened signaling pathway. 1 Publication1
Natural variantiVAR_080422289R → Q1 Publication1
Natural variantiVAR_080423293I → V1 Publication1
Natural variantiVAR_080424299 – 484Missing 1 PublicationAdd BLAST186
Natural variantiVAR_021567340A → S1 PublicationCorresponds to variant dbSNP:rs34135067EnsemblClinVar.1
Natural variantiVAR_080425382P → L1 Publication1
Natural variantiVAR_080426406I → T in JBTS32; decreased stability; forms cytoplasmic aggregates; decreased interaction with GLI3; no effect on interaction with GLI1; decreased repression of the hedgehog/smoothened signaling pathway. 1 Publication1
Natural variantiVAR_080427442K → R1 Publication1
Natural variantiVAR_080428481S → N1 Publication1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_013280433 – 484ILLTE…DSPLH → VRRPFFFSLLPFIDFLAHPS SSPLAALDGTPSWGAGHECL MDSGPGACV in isoform 3. 1 PublicationAdd BLAST52
Alternative sequenceiVSP_013278433I → L in isoform 2. 2 Publications1
Alternative sequenceiVSP_013279434 – 484Missing in isoform 2. 2 PublicationsAdd BLAST51

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF144231 mRNA Translation: AAF23890.1
AF159447 mRNA Translation: AAF23893.1
AF222345 mRNA Translation: AAF35866.1
AF175770 mRNA Translation: AAD50501.1
AY081829
, AY081818, AY081819, AY081820, AY081822, AY081824, AY081825, AY081821, AY081823, AY081826, AY081828, AY081827 Genomic DNA Translation: AAM08947.1
AY358550 mRNA Translation: AAQ88914.1
AL121928 Genomic DNA No translation available.
AL157386 Genomic DNA No translation available.
AL391121 Genomic DNA No translation available.
BC013291 mRNA Translation: AAH13291.1
AF172319 mRNA Translation: AAD51655.1
AL137465 mRNA Translation: CAB70752.1
CCDSiCCDS53571.1 [Q9UMX1-2]
CCDS7537.1 [Q9UMX1-1]
PIRiT46409
RefSeqiNP_001171604.1, NM_001178133.1 [Q9UMX1-2]
NP_057253.2, NM_016169.3 [Q9UMX1-1]
UniGeneiHs.404089

Genome annotation databases

EnsembliENST00000369899; ENSP00000358915; ENSG00000107882 [Q9UMX1-2]
ENST00000369902; ENSP00000358918; ENSG00000107882 [Q9UMX1-1]
ENST00000423559; ENSP00000411597; ENSG00000107882 [Q9UMX1-3]
GeneIDi51684
KEGGihsa:51684
UCSCiuc001kvw.3 human [Q9UMX1-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiSUFU_HUMAN
AccessioniPrimary (citable) accession number: Q9UMX1
Secondary accession number(s): Q7LCP7
, Q9NT90, Q9NZ07, Q9UHK2, Q9UHM8, Q9UMY0
Entry historyiIntegrated into UniProtKB/Swiss-Prot: April 12, 2005
Last sequence update: April 12, 2005
Last modified: June 20, 2018
This is version 158 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

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