Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Basket 0
(max 400 entries)x

Your basket is currently empty.

Select item(s) and click on "Add to basket" to create your own collection here
(400 entries max)

P10071

- GLI3_HUMAN

UniProt

P10071 - GLI3_HUMAN

Protein

Transcriptional activator GLI3

Gene

GLI3

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
    • BLAST
    • Align
    • Format
    • Add to basket
    • History
      Entry version 157 (01 Oct 2014)
      Sequence version 6 (24 Nov 2009)
      Previous versions | rss
    • Help video
    • Feedback
    • Comment

    Functioni

    Has a dual function as a transcriptional activator and a repressor of the sonic hedgehog (Shh) pathway, and plays a role in limb development. The full-length GLI3 form (GLI3FL) after phosphorylation and nuclear translocation, acts as an activator (GLI3A) while GLI3R, its C-terminally truncated form, acts as a repressor. A proper balance between the GLI3 activator and the repressor GLI3R, rather than the repressor gradient itself or the activator/repressor ratio gradient, specifies limb digit number and identity. In concert with TRPS1, plays a role in regulating the size of the zone of distal chondrocytes, in restricting the zone of PTHLH expression in distal cells and in activating chondrocyte proliferation. Binds to the minimal GLI-consensus sequence 5'-GGGTGGTC-3'.3 Publications

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Zinc fingeri480 – 50526C2H2-type 1PROSITE-ProRule annotationAdd
    BLAST
    Zinc fingeri513 – 54028C2H2-type 2PROSITE-ProRule annotationAdd
    BLAST
    Zinc fingeri546 – 57025C2H2-type 3PROSITE-ProRule annotationAdd
    BLAST
    Zinc fingeri576 – 60126C2H2-type 4PROSITE-ProRule annotationAdd
    BLAST
    Zinc fingeri607 – 63226C2H2-type 5PROSITE-ProRule annotationAdd
    BLAST

    GO - Molecular functioni

    1. beta-catenin binding Source: UniProtKB
    2. chromatin binding Source: Ensembl
    3. histone acetyltransferase binding Source: UniProtKB
    4. histone deacetylase binding Source: UniProtKB
    5. metal ion binding Source: UniProtKB-KW
    6. protein binding Source: UniProtKB
    7. RNA polymerase II core promoter proximal region sequence-specific DNA binding Source: MGI
    8. sequence-specific DNA binding transcription factor activity Source: UniProtKB

    GO - Biological processi

    1. anterior/posterior pattern specification Source: Ensembl
    2. anterior semicircular canal development Source: Ensembl
    3. artery development Source: Ensembl
    4. axon guidance Source: Ensembl
    5. branching involved in ureteric bud morphogenesis Source: Ensembl
    6. camera-type eye morphogenesis Source: Ensembl
    7. cell differentiation involved in kidney development Source: Ensembl
    8. cerebral cortex radial glia guided migration Source: Ensembl
    9. developmental growth Source: Ensembl
    10. embryonic digestive tract development Source: BHF-UCL
    11. embryonic digestive tract morphogenesis Source: Ensembl
    12. embryonic digit morphogenesis Source: BHF-UCL
    13. embryonic skeletal system morphogenesis Source: Ensembl
    14. forebrain dorsal/ventral pattern formation Source: Ensembl
    15. forebrain radial glial cell differentiation Source: Ensembl
    16. frontal suture morphogenesis Source: Ensembl
    17. heart development Source: Ensembl
    18. hindgut morphogenesis Source: Ensembl
    19. in utero embryonic development Source: Ensembl
    20. lambdoid suture morphogenesis Source: Ensembl
    21. lateral ganglionic eminence cell proliferation Source: Ensembl
    22. lateral semicircular canal development Source: Ensembl
    23. limb morphogenesis Source: UniProtKB
    24. lung development Source: Ensembl
    25. mammary gland specification Source: Ensembl
    26. melanocyte differentiation Source: Ensembl
    27. metanephros development Source: Ensembl
    28. negative regulation of alpha-beta T cell differentiation Source: BHF-UCL
    29. negative regulation of apoptotic process Source: Ensembl
    30. negative regulation of canonical Wnt signaling pathway Source: UniProtKB
    31. negative regulation of cell proliferation Source: Ensembl
    32. negative regulation of neuron differentiation Source: Ensembl
    33. negative regulation of smoothened signaling pathway Source: BHF-UCL
    34. negative regulation of transcription, DNA-templated Source: UniProtKB
    35. negative regulation of transcription from RNA polymerase II promoter Source: UniProtKB
    36. negative thymic T cell selection Source: BHF-UCL
    37. nose morphogenesis Source: BHF-UCL
    38. odontogenesis of dentin-containing tooth Source: Ensembl
    39. oligodendrocyte differentiation Source: Ensembl
    40. optic nerve morphogenesis Source: Ensembl
    41. palate development Source: Ensembl
    42. positive regulation of alpha-beta T cell differentiation Source: BHF-UCL
    43. positive regulation of chondrocyte differentiation Source: Ensembl
    44. positive regulation of neuroblast proliferation Source: Ensembl
    45. positive regulation of osteoblast differentiation Source: Ensembl
    46. positive regulation of protein import into nucleus Source: Ensembl
    47. positive regulation of transcription, DNA-templated Source: UniProtKB
    48. positive regulation of transcription from RNA polymerase II promoter Source: UniProtKB
    49. protein processing Source: Ensembl
    50. proximal/distal pattern formation Source: Ensembl
    51. response to estrogen Source: Ensembl
    52. sagittal suture morphogenesis Source: Ensembl
    53. smoothened signaling pathway Source: BHF-UCL
    54. smoothened signaling pathway involved in dorsal/ventral neural tube patterning Source: Ensembl
    55. smoothened signaling pathway involved in spinal cord motor neuron cell fate specification Source: Ensembl
    56. smoothened signaling pathway involved in ventral spinal cord interneuron specification Source: Ensembl
    57. T cell differentiation in thymus Source: BHF-UCL
    58. thymocyte apoptotic process Source: BHF-UCL
    59. tongue development Source: Ensembl
    60. transcription, DNA-templated Source: UniProtKB-KW
    61. wound healing Source: Ensembl

    Keywords - Molecular functioni

    Activator, Repressor

    Keywords - Biological processi

    Transcription, Transcription regulation

    Keywords - Ligandi

    DNA-binding, Metal-binding, Zinc

    Enzyme and pathway databases

    SignaLinkiP10071.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Transcriptional activator GLI3
    Alternative name(s):
    GLI3 form of 190 kDa
    Short name:
    GLI3-190
    GLI3 full length protein
    Short name:
    GLI3FL
    Cleaved into the following chain:
    Alternative name(s):
    GLI3 C-terminally truncated form
    GLI3 form of 83 kDa
    Short name:
    GLI3-83
    Gene namesi
    Name:GLI3
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 7

    Organism-specific databases

    HGNCiHGNC:4319. GLI3.

    Subcellular locationi

    Nucleus. Cytoplasm. Cell projectioncilium
    Note: GLI3FL is localized predominantly in the cytoplasm while GLI3R resides mainly in the nucleus. Ciliary accumulation requires the presence of KIF7 and SMO. Translocation to the nucleus is promoted by interaction with ZIC1.

    GO - Cellular componenti

    1. cilium Source: UniProtKB
    2. cytoplasm Source: UniProtKB
    3. cytosol Source: UniProtKB
    4. nuclear speck Source: Ensembl
    5. nucleus Source: UniProtKB
    6. primary cilium Source: Ensembl
    7. transcriptional repressor complex Source: Ensembl

    Keywords - Cellular componenti

    Cell projection, Cilium, Cytoplasm, Nucleus

    Pathology & Biotechi

    Involvement in diseasei

    Greig cephalo-poly-syndactyly syndrome (GCPS) [MIM:175700]: Autosomal dominant disorder affecting limb and craniofacial development. It is characterized by pre- and postaxial polydactyly, syndactyly of fingers and toes, macrocephaly and hypertelorism.4 Publications
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti515 – 5151C → G in GCPS. 1 Publication
    VAR_010053
    Natural varianti520 – 5201C → Y in GCPS. 1 Publication
    VAR_010054
    Natural varianti625 – 6251R → W in GCPS. 1 Publication
    VAR_021481
    Natural varianti707 – 7071P → S in GCPS. 1 Publication
    VAR_010055
    Natural varianti808 – 8081I → M in GCPS. 1 Publication
    Corresponds to variant rs62622373 [ dbSNP | Ensembl ].
    VAR_010056
    Natural varianti934 – 9341A → P in GCPS; the patient was originally classifed as being affected by acrocallosal syndrome due to the absence of corpus callosum. 1 Publication
    Corresponds to variant rs28933372 [ dbSNP | Ensembl ].
    VAR_021482
    Pallister-Hall syndrome 1 (PHS1) [MIM:146510]: An autosomal dominant disorder characterized by a wide range of clinical manifestations. Clinical features include hypothalamic hamartoma, pituitary dysfunction, central or postaxial polydactyly, and syndactyly. Malformations are frequent in the viscera, e.g. anal atresia, bifid uvula, congenital heart malformations, pulmonary or renal dysplasia.
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    Polydactyly, postaxial A1 (PAPA1) [MIM:174200]: A condition characterized by the occurrence of supernumerary digits in the upper and/or lower extremities. In postaxial polydactyly type A, the extra digit is well-formed and articulates with the fifth or a sixth metacarpal/metatarsal.1 Publication
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti727 – 7271G → R in PAPA1 and PAPB. 1 Publication
    Corresponds to variant rs121917710 [ dbSNP | Ensembl ].
    VAR_009876
    Polydactyly, postaxial B (PAPB) [MIM:174200]: A condition characterized by an extra digit in the occurrence of supernumerary digits in the upper and/or lower extremities. In postaxial polydactyly type B the extra digit is not well formed and is frequently in the form of a skin.1 Publication
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti727 – 7271G → R in PAPA1 and PAPB. 1 Publication
    Corresponds to variant rs121917710 [ dbSNP | Ensembl ].
    VAR_009876
    Polydactyly preaxial 4 (POP4) [MIM:174700]: Preaxial polydactyly (i.e., polydactyly on the radial/tibial side of the hand/foot) covers a heterogeneous group of entities. In preaxial polydactyly type IV, the thumb shows only the mildest degree of duplication, and syndactyly of various degrees affects fingers 3 and 4.
    Note: The disease is caused by mutations affecting the gene represented in this entry.

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi773 – 7731K → R: Loss of proteolytic processing. 1 Publication
    Mutagenesisi779 – 7791K → R: Loss of proteolytic processing. 1 Publication
    Mutagenesisi784 – 7841K → R: Loss of proteolytic processing. 1 Publication
    Mutagenesisi800 – 8001K → R: Loss of proteolytic processing. 1 Publication
    Mutagenesisi849 – 8491S → A: Loss of phosphorylation and proteolytic processing. 2 Publications
    Mutagenesisi855 – 8551S → A: Loss of proteolytic processing. 1 Publication
    Mutagenesisi856 – 8561S → A: Loss of proteolytic processing. 1 Publication
    Mutagenesisi861 – 8611S → A: Loss of proteolytic processing. 1 Publication
    Mutagenesisi864 – 8641S → A: Loss of proteolytic processing. 1 Publication
    Mutagenesisi865 – 8651S → A: Loss of phosphorylation and proteolytic processing. 1 Publication
    Mutagenesisi873 – 8731S → A: Loss of proteolytic processing. 1 Publication
    Mutagenesisi877 – 8771S → A: Loss of phosphorylation and proteolytic processing. 2 Publications
    Mutagenesisi903 – 9031S → A: Loss of proteolytic processing. 1 Publication
    Mutagenesisi907 – 9071S → A: Loss of phosphorylation and proteolytic processing. 2 Publications
    Mutagenesisi980 – 9801S → A: Loss of phosphorylation and proteolytic processing. 1 Publication
    Mutagenesisi1006 – 10061S → A: Loss of phosphorylation and proteolytic processing. 1 Publication

    Keywords - Diseasei

    Disease mutation

    Organism-specific databases

    MIMi146510. phenotype.
    174200. phenotype.
    174700. phenotype.
    175700. phenotype.
    Orphaneti36. Acrocallosal syndrome.
    380. Greig cephalopolysyndactyly syndrome.
    672. Pallister-Hall syndrome.
    295161. Polysyndactyly, bilateral.
    295159. Polysyndactyly, unilateral.
    295165. Postaxial polydactyly type A, bilateral.
    295163. Postaxial polydactyly type A, unilateral.
    295169. Postaxial polydactyly type B, bilateral.
    295167. Postaxial polydactyly type B, unilateral.
    PharmGKBiPA28722.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 15801580Transcriptional activator GLI3PRO_0000047202Add
    BLAST
    Chaini1 – ?Transcriptional repressor GLI3RPRO_0000406137

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei1 – 11N-acetylmethionine1 Publication
    Modified residuei664 – 6641Phosphoserine1 Publication
    Cross-linki773 – 773Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)2 Publications
    Cross-linki779 – 779Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)2 Publications
    Cross-linki784 – 784Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)2 Publications
    Cross-linki800 – 800Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin)2 Publications
    Modified residuei849 – 8491Phosphoserine; by PKA1 Publication
    Modified residuei865 – 8651Phosphoserine; by PKA1 Publication
    Modified residuei877 – 8771Phosphoserine; by PKA1 Publication
    Modified residuei907 – 9071Phosphoserine; by PKA1 Publication
    Modified residuei980 – 9801Phosphoserine; by PKA1 Publication
    Modified residuei1006 – 10061Phosphoserine; by PKA1 Publication

    Post-translational modificationi

    Phosphorylated on multiple sites by protein kinase A (PKA) and phosphorylation by PKA primes further phosphorylation by CK1 and GSK3. Phosphorylated by DYRK2 (in vitro). Phosphorylation is essential for its proteolytic processing.
    Transcriptional repressor GLI3R, a C-terminally truncated form, is generated from the full-length GLI3 protein (GLI3FL/GLI3-190) through proteolytic processing. This process requires PKA-primed phosphorylation of GLI3, ubiquitination of GLI3 and the presence of BTRC. 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. GLI3R formation leads to its dissociation from SUFU, allowing it to translocate into the nucleus, and repress Hh target genes. When Hh signaling is initiated, SUFU dissociates from GLI3FL and this has two consequences. First, GLI3R production is halted. Second, free GLI3FL translocates to the nucleus, where it is phosphorylated, destabilized, and converted to a transcriptional activator (GLI3A). Phosphorylated in vitro by ULK3.2 Publications

    Keywords - PTMi

    Acetylation, Isopeptide bond, Phosphoprotein, Ubl conjugation

    Proteomic databases

    MaxQBiP10071.
    PaxDbiP10071.
    PRIDEiP10071.

    PTM databases

    PhosphoSiteiP10071.

    Expressioni

    Tissue specificityi

    Is expressed in a wide variety of normal adult tissues, including lung, colon, spleen, placenta, testis, and myometrium.

    Gene expression databases

    ArrayExpressiP10071.
    BgeeiP10071.
    CleanExiHS_GLI3.
    GenevestigatoriP10071.

    Organism-specific databases

    HPAiHPA005534.

    Interactioni

    Subunit structurei

    The full-length GLI3 form (GLI3FL) interacts with SUFU and this interaction regulates the formation of either repressor or activator forms of GLI3. Its association with SUFU is regulated by Hh signaling and dissociation of the SUFU-GLI3 interaction requires the presence of the ciliary motor KIF3A By similarity. Interacts with KIF7. The activator form of GLI3 (GLI3A) but not the repressor form (GLI3R) can interact with TRPS1. The phosphorylated form interacts with BTRC. Interacts with ZIC1. Interacts with ZIC3 (via C2H2-type domains 3, 4 and 5); the interaction enhances its transcriptional activity.By similarity6 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    STK36Q9NRP72EBI-308055,EBI-863797
    Zic1P466842EBI-308055,EBI-308006From a different organism.
    Zic2Q625202EBI-308055,EBI-308076From a different organism.

    Protein-protein interaction databases

    BioGridi108999. 20 interactions.
    DIPiDIP-32538N.
    IntActiP10071. 10 interactions.
    MINTiMINT-189869.
    STRINGi9606.ENSP00000379255.

    Structurei

    Secondary structure

    1
    1580
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Beta strandi334 – 3374

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    4BLDX-ray2.80E/F/G/H328-344[»]
    ProteinModelPortaliP10071.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Compositional bias

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Compositional biasi1492 – 151221Asp/Glu-rich (acidic)Add
    BLAST

    Sequence similaritiesi

    Contains 5 C2H2-type zinc fingers.PROSITE-ProRule annotation

    Zinc finger

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Zinc fingeri480 – 50526C2H2-type 1PROSITE-ProRule annotationAdd
    BLAST
    Zinc fingeri513 – 54028C2H2-type 2PROSITE-ProRule annotationAdd
    BLAST
    Zinc fingeri546 – 57025C2H2-type 3PROSITE-ProRule annotationAdd
    BLAST
    Zinc fingeri576 – 60126C2H2-type 4PROSITE-ProRule annotationAdd
    BLAST
    Zinc fingeri607 – 63226C2H2-type 5PROSITE-ProRule annotationAdd
    BLAST

    Keywords - Domaini

    Repeat, Zinc-finger

    Phylogenomic databases

    eggNOGiCOG5048.
    HOVERGENiHBG005844.
    InParanoidiP10071.
    KOiK06230.
    OMAiPRDSGSH.
    OrthoDBiEOG7X6KZ8.
    PhylomeDBiP10071.
    TreeFamiTF350216.

    Family and domain databases

    Gene3Di3.30.160.60. 5 hits.
    InterProiIPR007087. Znf_C2H2.
    IPR015880. Znf_C2H2-like.
    IPR013087. Znf_C2H2/integrase_DNA-bd.
    [Graphical view]
    PfamiPF00096. zf-C2H2. 1 hit.
    [Graphical view]
    SMARTiSM00355. ZnF_C2H2. 5 hits.
    [Graphical view]
    PROSITEiPS00028. ZINC_FINGER_C2H2_1. 4 hits.
    PS50157. ZINC_FINGER_C2H2_2. 5 hits.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    Sequence processingi: The displayed sequence is further processed into a mature form.

    P10071-1 [UniParc]FASTAAdd to Basket

    « Hide

    MEAQSHSSTT TEKKKVENSI VKCSTRTDVS EKAVASSTTS NEDESPGQTY     50
    HRERRNAITM QPQNVQGLSK VSEEPSTSSD ERASLIKKEI HGSLPHVAEP 100
    SVPYRGTVFA MDPRNGYMEP HYHPPHLFPA FHPPVPIDAR HHEGRYHYDP 150
    SPIPPLHMTS ALSSSPTYPD LPFIRISPHR NPTAASESPF SPPHPYINPY 200
    MDYIRSLHSS PSLSMISATR GLSPTDAPHA GVSPAEYYHQ MALLTGQRSP 250
    YADIIPSAAT AGTGAIHMEY LHAMDSTRFS SPRLSARPSR KRTLSISPLS 300
    DHSFDLQTMI RTSPNSLVTI LNNSRSSSSA SGSYGHLSAS AISPALSFTY 350
    SSAPVSLHMH QQILSRQQSL GSAFGHSPPL IHPAPTFPTQ RPIPGIPTVL 400
    NPVQVSSGPS ESSQNKPTSE SAVSSTGDPM HNKRSKIKPD EDLPSPGARG 450
    QQEQPEGTTL VKEEGDKDES KQEPEVIYET NCHWEGCARE FDTQEQLVHH 500
    INNDHIHGEK KEFVCRWLDC SREQKPFKAQ YMLVVHMRRH TGEKPHKCTF 550
    EGCTKAYSRL ENLKTHLRSH TGEKPYVCEH EGCNKAFSNA SDRAKHQNRT 600
    HSNEKPYVCK IPGCTKRYTD PSSLRKHVKT VHGPEAHVTK KQRGDIHPRP 650
    PPPRDSGSHS QSRSPGRPTQ GALGEQQDLS NTTSKREECL QVKTVKAEKP 700
    MTSQPSPGGQ SSCSSQQSPI SNYSNSGLEL PLTDGGSIGD LSAIDETPIM 750
    DSTISTATTA LALQARRNPA GTKWMEHVKL ERLKQVNGMF PRLNPILPPK 800
    APAVSPLIGN GTQSNNTCSL GGPMTLLPGR SDLSGVDVTM LNMLNRRDSS 850
    ASTISSAYLS SRRSSGISPC FSSRRSSEAS QAEGRPQNVS VADSYDPIST 900
    DASRRSSEAS QSDGLPSLLS LTPAQQYRLK AKYAAATGGP PPTPLPNMER 950
    MSLKTRLALL GDALEPGVAL PPVHAPRRCS DGGAHGYGRR HLQPHDAPGH 1000
    GVRRASDPVR TGSEGLALPR VPRFSSLSSC NPPAMATSAE KRSLVLQNYT 1050
    RPEGGQSRNF HSSPCPPSIT ENVTLESLTM DADANLNDED FLPDDVVQYL 1100
    NSQNQAGYEQ HFPSALPDDS KVPHGPGDFD APGLPDSHAG QQFHALEQPC 1150
    PEGSKTDLPI QWNEVSSGSA DLSSSKLKCG PRPAVPQTRA FGFCNGMVVH 1200
    PQNPLRSGPA GGYQTLGENS NPYGGPEHLM LHNSPGSGTS GNAFHEQPCK 1250
    APQYGNCLNR QPVAPGALDG ACGAGIQASK LKSTPMQGSG GQLNFGLPVA 1300
    PNESAGSMVN GMQNQDPVGQ GYLAHQLLGD SMQHPGAGRP GQQMLGQISA 1350
    TSHINIYQGP ESCLPGAHGM GSQPSSLAVV RGYQPCASFG GSRRQAMPRD 1400
    SLALQSGQLS DTSQTCRVNG IKMEMKGQPH PLCSNLQNYS GQFYDQTVGF 1450
    SQQDTKAGSF SISDASCLLQ GTSAKNSELL SPGANQVTST VDSLDSHDLE 1500
    GVQIDFDAII DDGDHSSLMS GALSPSIIQN LSHSSSRLTT PRASLPFPAL 1550
    SMSTTNMAIG DMSSLLTSLA EESKFLAVMQ 1580
    Length:1,580
    Mass (Da):169,863
    Last modified:November 24, 2009 - v6
    Checksum:i423B7495FCE3C37C
    GO

    Sequence cautioni

    The sequence AAA52564.1 differs from that shown. Reason: Frameshift at position 1549.

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti169 – 1691P → L in a colorectal cancer sample; somatic mutation. 1 Publication
    VAR_035560
    Natural varianti183 – 1831T → A.3 Publications
    Corresponds to variant rs846266 [ dbSNP | Ensembl ].
    VAR_028276
    Natural varianti440 – 4401D → E.1 Publication
    VAR_010052
    Natural varianti515 – 5151C → G in GCPS. 1 Publication
    VAR_010053
    Natural varianti520 – 5201C → Y in GCPS. 1 Publication
    VAR_010054
    Natural varianti625 – 6251R → W in GCPS. 1 Publication
    VAR_021481
    Natural varianti707 – 7071P → S in GCPS. 1 Publication
    VAR_010055
    Natural varianti727 – 7271G → R in PAPA1 and PAPB. 1 Publication
    Corresponds to variant rs121917710 [ dbSNP | Ensembl ].
    VAR_009876
    Natural varianti808 – 8081I → M in GCPS. 1 Publication
    Corresponds to variant rs62622373 [ dbSNP | Ensembl ].
    VAR_010056
    Natural varianti934 – 9341A → P in GCPS; the patient was originally classifed as being affected by acrocallosal syndrome due to the absence of corpus callosum. 1 Publication
    Corresponds to variant rs28933372 [ dbSNP | Ensembl ].
    VAR_021482
    Natural varianti998 – 9981P → L.3 Publications
    Corresponds to variant rs929387 [ dbSNP | Ensembl ].
    VAR_028278
    Natural varianti1304 – 13041S → P in a colorectal cancer sample; somatic mutation. 1 Publication
    VAR_035561
    Natural varianti1336 – 13361G → E.
    Corresponds to variant rs35280470 [ dbSNP | Ensembl ].
    VAR_034865
    Natural varianti1537 – 15371R → C.1 Publication
    Corresponds to variant rs35364414 [ dbSNP | Ensembl ].
    VAR_010057

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    M57609 mRNA. Translation: AAA52564.1. Frameshift.
    AJ250408 Genomic DNA. Translation: CAB59315.1.
    AC005026 Genomic DNA. Translation: AAP21869.1.
    AC005028 Genomic DNA. Translation: AAS01998.1.
    AC005158 Genomic DNA. Translation: AAS02015.1.
    AC073852 Genomic DNA. No translation available.
    CH236951 Genomic DNA. Translation: EAL24002.1.
    M20674 Genomic DNA. No translation available.
    BC113616 mRNA. Translation: AAI13617.1.
    BC117168 mRNA. Translation: AAI17169.1.
    CCDSiCCDS5465.1.
    PIRiA35927.
    RefSeqiNP_000159.3. NM_000168.5.
    XP_005249760.1. XM_005249703.1.
    XP_005249761.1. XM_005249704.1.
    UniGeneiHs.21509.

    Genome annotation databases

    EnsembliENST00000395925; ENSP00000379258; ENSG00000106571.
    GeneIDi2737.
    KEGGihsa:2737.
    UCSCiuc011kbg.2. human.

    Polymorphism databases

    DMDMi269849770.

    Keywords - Coding sequence diversityi

    Polymorphism

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    M57609 mRNA. Translation: AAA52564.1 . Frameshift.
    AJ250408 Genomic DNA. Translation: CAB59315.1 .
    AC005026 Genomic DNA. Translation: AAP21869.1 .
    AC005028 Genomic DNA. Translation: AAS01998.1 .
    AC005158 Genomic DNA. Translation: AAS02015.1 .
    AC073852 Genomic DNA. No translation available.
    CH236951 Genomic DNA. Translation: EAL24002.1 .
    M20674 Genomic DNA. No translation available.
    BC113616 mRNA. Translation: AAI13617.1 .
    BC117168 mRNA. Translation: AAI17169.1 .
    CCDSi CCDS5465.1.
    PIRi A35927.
    RefSeqi NP_000159.3. NM_000168.5.
    XP_005249760.1. XM_005249703.1.
    XP_005249761.1. XM_005249704.1.
    UniGenei Hs.21509.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    4BLD X-ray 2.80 E/F/G/H 328-344 [» ]
    ProteinModelPortali P10071.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 108999. 20 interactions.
    DIPi DIP-32538N.
    IntActi P10071. 10 interactions.
    MINTi MINT-189869.
    STRINGi 9606.ENSP00000379255.

    PTM databases

    PhosphoSitei P10071.

    Polymorphism databases

    DMDMi 269849770.

    Proteomic databases

    MaxQBi P10071.
    PaxDbi P10071.
    PRIDEi P10071.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000395925 ; ENSP00000379258 ; ENSG00000106571 .
    GeneIDi 2737.
    KEGGi hsa:2737.
    UCSCi uc011kbg.2. human.

    Organism-specific databases

    CTDi 2737.
    GeneCardsi GC07M041970.
    GeneReviewsi GLI3.
    H-InvDB HIX0033636.
    HGNCi HGNC:4319. GLI3.
    HPAi HPA005534.
    MIMi 146510. phenotype.
    165240. gene.
    174200. phenotype.
    174700. phenotype.
    175700. phenotype.
    neXtProti NX_P10071.
    Orphaneti 36. Acrocallosal syndrome.
    380. Greig cephalopolysyndactyly syndrome.
    672. Pallister-Hall syndrome.
    295161. Polysyndactyly, bilateral.
    295159. Polysyndactyly, unilateral.
    295165. Postaxial polydactyly type A, bilateral.
    295163. Postaxial polydactyly type A, unilateral.
    295169. Postaxial polydactyly type B, bilateral.
    295167. Postaxial polydactyly type B, unilateral.
    PharmGKBi PA28722.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi COG5048.
    HOVERGENi HBG005844.
    InParanoidi P10071.
    KOi K06230.
    OMAi PRDSGSH.
    OrthoDBi EOG7X6KZ8.
    PhylomeDBi P10071.
    TreeFami TF350216.

    Enzyme and pathway databases

    SignaLinki P10071.

    Miscellaneous databases

    ChiTaRSi GLI3. human.
    GeneWikii GLI3.
    GenomeRNAii 2737.
    NextBioi 10788.
    PROi P10071.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi P10071.
    Bgeei P10071.
    CleanExi HS_GLI3.
    Genevestigatori P10071.

    Family and domain databases

    Gene3Di 3.30.160.60. 5 hits.
    InterProi IPR007087. Znf_C2H2.
    IPR015880. Znf_C2H2-like.
    IPR013087. Znf_C2H2/integrase_DNA-bd.
    [Graphical view ]
    Pfami PF00096. zf-C2H2. 1 hit.
    [Graphical view ]
    SMARTi SM00355. ZnF_C2H2. 5 hits.
    [Graphical view ]
    PROSITEi PS00028. ZINC_FINGER_C2H2_1. 4 hits.
    PS50157. ZINC_FINGER_C2H2_2. 5 hits.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "GLI3 encodes a 190-kilodalton protein with multiple regions of GLI similarity."
      Ruppert J.M., Vogelstein B., Arheden K., Kinzler K.W.
      Mol. Cell. Biol. 10:5408-5415(1990) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANTS ALA-183 AND LEU-998.
    2. Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS GCPS GLY-515; TYR-520 AND MET-808, VARIANTS ALA-183; GLU-440; LEU-998 AND CYS-1537.
    3. "The DNA sequence of human chromosome 7."
      Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H., Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K., Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A., Delehaunty K.D., Miner T.L.
      , Nash W.E., Cordes M., Du H., Sun H., Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A., Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P., Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M., Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S., Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., Strowmatt C., Latreille P., Miller N., Johnson D., Murray J., Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E., Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E., Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A., Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A., Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R., McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H., Wilson R.K.
      Nature 424:157-164(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    4. "Human chromosome 7: DNA sequence and biology."
      Scherer S.W., Cheung J., MacDonald J.R., Osborne L.R., Nakabayashi K., Herbrick J.-A., Carson A.R., Parker-Katiraee L., Skaug J., Khaja R., Zhang J., Hudek A.K., Li M., Haddad M., Duggan G.E., Fernandez B.A., Kanematsu E., Gentles S.
      , Christopoulos C.C., Choufani S., Kwasnicka D., Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z., Lu F., Zeesman S., Nowaczyk M.J., Teshima I., Chitayat D., Shuman C., Weksberg R., Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J., Rahman N., Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F., Belloni E., Shaffer L.G., Pober B., Morton C.C., Gusella J.F., Bruns G.A.P., Korf B.R., Quade B.J., Ligon A.H., Ferguson H., Higgins A.W., Leach N.T., Herrick S.R., Lemyre E., Farra C.G., Kim H.-G., Summers A.M., Gripp K.W., Roberts W., Szatmari P., Winsor E.J.T., Grzeschik K.-H., Teebi A., Minassian B.A., Kere J., Armengol L., Pujana M.A., Estivill X., Wilson M.D., Koop B.F., Tosi S., Moore G.E., Boright A.P., Zlotorynski E., Kerem B., Kroisel P.M., Petek E., Oscier D.G., Mould S.J., Doehner H., Doehner K., Rommens J.M., Vincent J.B., Venter J.C., Li P.W., Mural R.J., Adams M.D., Tsui L.-C.
      Science 300:767-772(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    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], VARIANTS ALA-183 AND LEU-998.
      Tissue: Cerebellum.
    6. "The GLI-Kruppel family of human genes."
      Ruppert J.M., Kinzler K.W., Wong A.J., Bigner S.H., Kao F.T., Law M.L., Seuanez H.N., O'Brien S.J., Vogelstein B.
      Mol. Cell. Biol. 8:3104-3113(1988) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 500-549.
    7. "Hedgehog-regulated processing of Gli3 produces an anterior/posterior repressor gradient in the developing vertebrate limb."
      Wang B., Fallon J.F., Beachy P.A.
      Cell 100:423-434(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, PROTEOLYTIC PROCESSING, PHOSPHORYLATION AT SER-849; SER-865; SER-877; SER-907; SER-980 AND SER-1006, MUTAGENESIS OF SER-849; SER-865; SER-877; SER-907; SER-980 AND SER-1006.
    8. "Physical and functional interactions between Zic and Gli proteins."
      Koyabu Y., Nakata K., Mizugishi K., Aruga J., Mikoshiba K.
      J. Biol. Chem. 276:6889-6892(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, INTERACTION WITH ZIC1, SUBCELLULAR LOCATION.
    9. "Multisite protein kinase A and glycogen synthase kinase 3beta phosphorylation leads to Gli3 ubiquitination by SCFbetaTrCP."
      Tempe D., Casas M., Karaz S., Blanchet-Tournier M.F., Concordet J.P.
      Mol. Cell. Biol. 26:4316-4326(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: PROTEOLYTIC PROCESSING, PHOSPHORYLATION, INTERACTION WITH BTRC, UBIQUITINATION AT LYS-773; LYS-779; LYS-784 AND LYS-800, MUTAGENESIS OF LYS-773; LYS-779; LYS-784; LYS-800; SER-849; SER-855; SER-856; SER-861; SER-864; SER-873; SER-877; SER-903 AND SER-907.
    10. "Evidence for the direct involvement of {beta}TrCP in Gli3 protein processing."
      Wang B., Li Y.
      Proc. Natl. Acad. Sci. U.S.A. 103:33-38(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: PROTEOLYTIC PROCESSING, PHOSPHORYLATION, POLYUBIQUITINATION, INTERACTION WITH BTRC.
    11. "Application of active and kinase-deficient kinome collection for identification of kinases regulating hedgehog signaling."
      Varjosalo M., Bjorklund M., Cheng F., Syvanen H., Kivioja T., Kilpinen S., Sun Z., Kallioniemi O., Stunnenberg H.G., He W.W., Ojala P., Taipale J.
      Cell 133:537-548(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION.
    12. "Characterization of the interactions of human ZIC3 mutants with GLI3."
      Zhu L., Zhou G., Poole S., Belmont J.W.
      Hum. Mutat. 29:99-105(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, INTERACTION WITH ZIC3.
    13. "Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach."
      Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.
      Anal. Chem. 81:4493-4501(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    14. "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: SUBCELLULAR LOCATION, INTERACTION WITH KIF7.
    15. "Trps1, a regulator of chondrocyte proliferation and differentiation, interacts with the activator form of Gli3."
      Wuelling M., Kaiser F.J., Buelens L.A., Braunholz D., Shivdasani R.A., Depping R., Vortkamp A.
      Dev. Biol. 328:40-53(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH TRPS1.
    16. "Identification of a novel serine/threonine kinase ULK3 as a positive regulator of Hedgehog pathway."
      Maloverjan A., Piirsoo M., Michelson P., Kogerman P., Osterlund T.
      Exp. Cell Res. 316:627-637(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION.
    17. "System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation."
      Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.
      Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-664, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    18. Cited for: VARIANT GCPS SER-707.
    19. "The phenotypic spectrum of GLI3 morphopathies includes autosomal dominant preaxial polydactyly type-IV and postaxial polydactyly type-A/B; no phenotype prediction from the position of GLI3 mutations."
      Radhakrishna U., Bornholdt D., Scott H.S., Patel U.C., Rossier C., Engel H., Bottani A., Chandal D., Blouin J.-L., Solanki J.V., Grzeschik K.-H., Antonarakis S.E.
      Am. J. Hum. Genet. 65:645-655(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT PAPA1 ARG-727, VARIANT PAPB ARG-727.
    20. "De novo GLI3 mutation in acrocallosal syndrome: broadening the phenotypic spectrum of GLI3 defects and overlap with murine models."
      Elson E., Perveen R., Donnai D., Wall S., Black G.C.M.
      J. Med. Genet. 39:804-806(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT GCPS PRO-934.
    21. "Variable phenotype in Greig cephalopolysyndactyly syndrome: clinical and radiological findings in 4 independent families and 3 sporadic cases with identified GLI3 mutations."
      Debeer P., Peeters H., Driess S., De Smet L., Freese K., Matthijs G., Bornholdt D., Devriendt K., Grzeschik K.-H., Fryns J.-P., Kalff-Suske M.
      Am. J. Med. Genet. A 120:49-58(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT GCPS TRP-625.
    22. Cited for: VARIANTS [LARGE SCALE ANALYSIS] LEU-169 AND PRO-1304.

    Entry informationi

    Entry nameiGLI3_HUMAN
    AccessioniPrimary (citable) accession number: P10071
    Secondary accession number(s): A4D1W1
    , O75219, Q17RW4, Q75MT0, Q75MU9, Q9UDT5, Q9UJ39
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: July 1, 1989
    Last sequence update: November 24, 2009
    Last modified: October 1, 2014
    This is version 157 of the entry and version 6 of the sequence. [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

    Documents

    1. Human chromosome 7
      Human chromosome 7: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    6. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3