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Protein

Serine/threonine-protein kinase hippo

Gene

hpo

Organism
Drosophila melanogaster (Fruit fly)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Plays a key role in the Hippo/SWH (Sav/Wts/Hpo) signaling pathway, a signaling pathway that plays a pivotal role in organ size control and tumor suppression by restricting proliferation and promoting apoptosis. The core of this pathway is composed of a kinase cascade wherein Hippo (Hpo), in complex with its regulatory protein Salvador (Sav), phosphorylates and activates Warts (Wts) in complex with its regulatory protein Mats, which in turn phosphorylates and inactivates the Yorkie (Yki) oncoprotein. The Hippo/SWH signaling pathway inhibits the activity of the transcriptional complex formed by Scalloped (sd) and Yki and the target genes of this pathway include cyclin-E (cycE), diap1 and bantam. Phosphorylates Sav, Wts and Th/DIAP1. Regulates the level of Th/DIAP1 apoptosis inhibitor.5 Publications

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei71 – 711ATPPROSITE-ProRule annotation
Active sitei161 – 1611Proton acceptorPROSITE-ProRule annotation

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi48 – 569ATPPROSITE-ProRule annotation

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • kinase activity Source: FlyBase
  • protein homodimerization activity Source: FlyBase
  • protein serine/threonine kinase activity Source: UniProtKB
  • receptor signaling protein serine/threonine kinase activity Source: GO_Central

GO - Biological processi

  • activation of cysteine-type endopeptidase activity Source: FlyBase
  • apoptotic process Source: UniProtKB
  • border follicle cell migration Source: FlyBase
  • cell proliferation Source: UniProtKB
  • eye development Source: FlyBase
  • hippo signaling Source: UniProtKB
  • intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator Source: FlyBase
  • morphogenesis of an epithelial sheet Source: FlyBase
  • negative regulation of canonical Wnt signaling pathway Source: BHF-UCL
  • negative regulation of cell proliferation Source: FlyBase
  • negative regulation of glial cell proliferation Source: FlyBase
  • negative regulation of neuron apoptotic process Source: FlyBase
  • negative regulation of organ growth Source: FlyBase
  • negative regulation of transcription, DNA-templated Source: FlyBase
  • organ growth Source: FlyBase
  • peptidyl-threonine phosphorylation Source: FlyBase
  • positive regulation of apoptotic signaling pathway Source: FlyBase
  • protein autophosphorylation Source: FlyBase
  • protein phosphorylation Source: UniProtKB
  • R8 cell fate specification Source: FlyBase
  • regulation of apoptotic signaling pathway Source: FlyBase
  • regulation of cell proliferation Source: FlyBase
  • regulation of protein processing Source: FlyBase
  • response to ionizing radiation Source: FlyBase
  • retinal cell programmed cell death Source: FlyBase
  • stem cell proliferation Source: FlyBase
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Serine/threonine-protein kinase, Transferase

Keywords - Biological processi

Apoptosis

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

ReactomeiR-DME-2028269. Signaling by Hippo.
SignaLinkiQ8T0S6.

Names & Taxonomyi

Protein namesi
Recommended name:
Serine/threonine-protein kinase hippo (EC:2.7.11.1)
Alternative name(s):
Drosophila homolog of MST1 and MST2
STE20-like kinase MST
dMST
Gene namesi
Name:hpo
ORF Names:CG11228
OrganismiDrosophila melanogaster (Fruit fly)
Taxonomic identifieri7227 [NCBI]
Taxonomic lineageiEukaryotaMetazoaEcdysozoaArthropodaHexapodaInsectaPterygotaNeopteraEndopterygotaDipteraBrachyceraMuscomorphaEphydroideaDrosophilidaeDrosophilaSophophora
Proteomesi
  • UP000000803 Componenti: Chromosome 2R

Organism-specific databases

FlyBaseiFBgn0261456. hpo.

Subcellular locationi

GO - Cellular componenti

  • apical plasma membrane Source: UniProtKB-SubCell
  • cytoplasm Source: FlyBase
  • membrane Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi71 – 711K → R: Abolishes phosphorylation of Sav. 1 Publication
Mutagenesisi166 – 1716Missing in hpo42-47; null mutant.
Mutagenesisi195 – 1951T → A: Abolishes phosphorylation by Tao. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 669669Serine/threonine-protein kinase hippoPRO_0000086001Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei30 – 301Phosphoserine1 Publication
Modified residuei33 – 331Phosphoserine1 Publication
Modified residuei195 – 1951Phosphothreonine; by Tao1 Publication

Post-translational modificationi

Autophosphorylated.1 Publication

Keywords - PTMi

Phosphoprotein

Proteomic databases

PaxDbiQ8T0S6.
PRIDEiQ8T0S6.

PTM databases

iPTMnetiQ8T0S6.

Expressioni

Tissue specificityi

Expressed in CNS during embryogenesis. In third instar larvae, it is expressed throughout all imaginal disks.2 Publications

Inductioni

Transcriptionally regulated by Gcm (Glial cells missing).1 Publication

Gene expression databases

BgeeiFBgn0261456.
GenevisibleiQ8T0S6. DM.

Interactioni

Subunit structurei

Homodimer. Interacts with Sav and Wts. Interacts (via SARAH domain) with Ex. Interacts with Kibra.5 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
matsQ95RA82EBI-101858,EBI-143689
savQ9VCR62EBI-101858,EBI-145004

GO - Molecular functioni

  • protein homodimerization activity Source: FlyBase

Protein-protein interaction databases

BioGridi62905. 38 interactions.
DIPiDIP-17921N.
IntActiQ8T0S6. 9 interactions.
MINTiMINT-276917.
STRINGi7227.FBpp0304253.

Structurei

3D structure databases

ProteinModelPortaliQ8T0S6.
SMRiQ8T0S6. Positions 24-384, 627-660.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini42 – 293252Protein kinasePROSITE-ProRule annotationAdd
BLAST
Domaini608 – 65548SARAHPROSITE-ProRule annotationAdd
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi490 – 599110Gln-richAdd
BLAST
Compositional biasi490 – 50314Poly-GlnAdd
BLAST
Compositional biasi538 – 5458Poly-Gln

Sequence similaritiesi

Contains 1 protein kinase domain.PROSITE-ProRule annotation
Contains 1 SARAH domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG0574. Eukaryota.
ENOG410XP9G. LUCA.
GeneTreeiENSGT00810000125395.
InParanoidiQ8T0S6.
KOiK04412.
OMAiTMVELQS.
OrthoDBiEOG091G065P.
PhylomeDBiQ8T0S6.

Family and domain databases

InterProiIPR011009. Kinase-like_dom.
IPR024205. Mst1_SARAH_domain.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR011524. SARAH_dom.
[Graphical view]
PfamiPF11629. Mst1_SARAH. 1 hit.
PF00069. Pkinase. 1 hit.
[Graphical view]
SMARTiSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS50951. SARAH. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q8T0S6-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MSEPEVTSVV DMKSPNISSS CSFFKLKKLS EESLLQPPEK VFDIMYKLGE
60 70 80 90 100
GSYGSVYKAV HKESSSIVAI KLVPVESDLH EIIKEISIMQ QCDSPYVVRY
110 120 130 140 150
YGSYFKQYDL WICMEYCGAG SVSDIMRLRK KTLTEDEIAT ILSDTLQGLV
160 170 180 190 200
YLHLRRKIHR DIKAANILLN TEGYAKLADF GVAGQLTDTM AKRNTVIGTP
210 220 230 240 250
FWMAPEVIEE IGYDCVADIW SLGITALEMA EGKPPYGEIH PMRAIFMIPQ
260 270 280 290 300
KPPPSFREPD RWSTEFIDFV SKCLVKEPDD RATATELLEH EFIRNAKHRS
310 320 330 340 350
ILKPMLEETC AIREQQRANR SFGGVLAASQ AKSLATQENG MQQHITDNAF
360 370 380 390 400
MEDPGTLVPE KFGEYQQSSA SDATMIAHAE QGVDEGTLGP GGLRNLSKAA
410 420 430 440 450
APAAASSAAS PLDMPAVDSG TMVELESNLG TMVINSDSDD STTAKNNDDQ
460 470 480 490 500
KPRNRYRPQF LEHFDRKNAG DGRGDEKPIA TEYSPAAAEQ QQQQQQQQQQ
510 520 530 540 550
QQQDEQHLAS GANDLNNWEH NMEMQFQQIS AINQYGLQQH QQQQQVLMAY
560 570 580 590 600
PLMNEQLIAL NNQPNLLLSN AAPMGQQGIP AAAPAQPPPA YQNQHMHTQS
610 620 630 640 650
HAYVEGEFEF LKFLTFDDLN QRLCNIDHEM ELEIEQLNKK YNAKRQPIVD
660
AMNAKRKRQQ NINNNLIKI
Length:669
Mass (Da):75,110
Last modified:June 1, 2002 - v1
Checksum:iB3DDDFAF5F4E4EB3
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti503 – 5031Q → QQQQ no nucleotide entry (PubMed:12941274).Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AE013599 Genomic DNA. Translation: AAF57543.2.
AY069088 mRNA. Translation: AAL39233.1.
RefSeqiNP_001261092.1. NM_001274163.1.
NP_611427.1. NM_137583.5.
UniGeneiDm.703.

Genome annotation databases

EnsemblMetazoaiFBtr0086500; FBpp0085688; FBgn0261456.
FBtr0331920; FBpp0304253; FBgn0261456.
GeneIDi37247.
KEGGidme:Dmel_CG11228.
UCSCiCG11228-RA. d. melanogaster.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AE013599 Genomic DNA. Translation: AAF57543.2.
AY069088 mRNA. Translation: AAL39233.1.
RefSeqiNP_001261092.1. NM_001274163.1.
NP_611427.1. NM_137583.5.
UniGeneiDm.703.

3D structure databases

ProteinModelPortaliQ8T0S6.
SMRiQ8T0S6. Positions 24-384, 627-660.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi62905. 38 interactions.
DIPiDIP-17921N.
IntActiQ8T0S6. 9 interactions.
MINTiMINT-276917.
STRINGi7227.FBpp0304253.

PTM databases

iPTMnetiQ8T0S6.

Proteomic databases

PaxDbiQ8T0S6.
PRIDEiQ8T0S6.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsemblMetazoaiFBtr0086500; FBpp0085688; FBgn0261456.
FBtr0331920; FBpp0304253; FBgn0261456.
GeneIDi37247.
KEGGidme:Dmel_CG11228.
UCSCiCG11228-RA. d. melanogaster.

Organism-specific databases

CTDi37247.
FlyBaseiFBgn0261456. hpo.

Phylogenomic databases

eggNOGiKOG0574. Eukaryota.
ENOG410XP9G. LUCA.
GeneTreeiENSGT00810000125395.
InParanoidiQ8T0S6.
KOiK04412.
OMAiTMVELQS.
OrthoDBiEOG091G065P.
PhylomeDBiQ8T0S6.

Enzyme and pathway databases

ReactomeiR-DME-2028269. Signaling by Hippo.
SignaLinkiQ8T0S6.

Miscellaneous databases

GenomeRNAii37247.
PROiQ8T0S6.

Gene expression databases

BgeeiFBgn0261456.
GenevisibleiQ8T0S6. DM.

Family and domain databases

InterProiIPR011009. Kinase-like_dom.
IPR024205. Mst1_SARAH_domain.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR011524. SARAH_dom.
[Graphical view]
PfamiPF11629. Mst1_SARAH. 1 hit.
PF00069. Pkinase. 1 hit.
[Graphical view]
SMARTiSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS50951. SARAH. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiHIPPO_DROME
AccessioniPrimary (citable) accession number: Q8T0S6
Secondary accession number(s): Q9V8W4
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 29, 2003
Last sequence update: June 1, 2002
Last modified: September 7, 2016
This is version 130 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programDrosophila annotation project

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Drosophila
    Drosophila: entries, gene names and cross-references to FlyBase
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.