Descriptions

MOB1A is a multifunctional protein involved in key signaling pathways like Hippo and NDR pathway signaling in metazoans and the Mitotic Exit Network in yeast. It regulates protein interactions by binding to upstream kinases MST1 and MST2 and downstream AGC group kinases LATS1, LATS2, NDR1, and NDR2. The autoinhibition of MOB1A occurs when its nonphosphorylated N-terminal extension binds to the core domain, blocking the kinase-binding site. This inhibitory interaction is relieved upon phosphorylation at specific sites (T12 and T35), which induces a conformational change that exposes the kinase-binding surface. Phosphorylation of MOB1A at T12 and T35 is crucial for regulating its interactions with both upstream and downstream kinases. The phosphorylation status dictates the binding affinity of MOB1A, enabling or inhibiting interactions with other proteins. The phosphorylation-dependent conformational changes in MOB1A are essential for the proper functioning of the Hippo signaling pathway, which is critical for cell proliferation and tissue growth regulation.

Autoinhibitory domains (AIDs)

Target domain

52-216 (MOB1A core domain)

Relief mechanism

PTM

Assay

Structural analysis, Mutagenesis experiment, Deletion assay

Accessory elements

No accessory elements

Autoinhibited structure

Activated structure

12 structures for Q9H8S9

Entry ID Method Resolution Chain Position Source
1PI1 X-ray 200 A A 33-216 PDB
4J1V X-ray 195 A A/C 33-216 PDB
4JIZ X-ray 210 A A 40-211 PDB
5BRK X-ray 230 A A 1-216 PDB
5BRM X-ray 265 A A/B/C/D/E/F 41-216 PDB
5TWF X-ray 314 A A/B 1-216 PDB
5TWG X-ray 230 A A 1-216 PDB
5TWH X-ray 250 A A 1-216 PDB
5XQZ X-ray 210 A A/B 33-216 PDB
6MCP X-ray 250 A B/D 33-216 PDB
6MCQ X-ray 257 A B/D 33-216 PDB
AF-Q9H8S9-F1 Predicted AlphaFoldDB

139 variants for Q9H8S9

Variant ID(s) Position Change Description Diseaes Association Provenance
rs1250022055 3 F>L No TOPMed
gnomAD
rs1469354327 4 L>F No TOPMed
gnomAD
rs2103738442 4 L>LGPSPPL* No Ensembl
rs1304393866 6 S>T No TOPMed
rs1185114816 8 R>C No gnomAD
rs770969409 8 R>H No ExAC
TOPMed
gnomAD
rs1693330248 9 S>F No TOPMed
rs1233046382 10 S>Y No gnomAD
rs1693330072 12 T>A No Ensembl
TCGA novel 14 K>E Variant assessed as Somatic; MODERATE impact. [NCI-TCGA] No NCI-TCGA
rs760953308 14 K>R No ExAC
gnomAD
rs1474290057
COSM3840027
COSM1022914
16 K>N Variant assessed as Somatic; MODERATE impact. endometrium breast [NCI-TCGA, Cosmic] No NCI-TCGA Cosmic
cosmic curated
NCI-TCGA
TOPMed
rs1693329547 16 K>R No gnomAD
rs772455023 17 K>N No ExAC
gnomAD
rs748472204 18 N>H No ExAC
gnomAD
rs377027159 19 I>N No ESP
ExAC
gnomAD
rs1572965395 19 I>V No Ensembl
rs755662573 23 S>A No ExAC
gnomAD
rs745417977 23 S>F No ExAC
gnomAD
rs1693328301 24 H>P No TOPMed
rs1156969421 25 Q>* No gnomAD
rs1414793790 26 Y>* No Ensembl
rs1325937338 26 Y>C No TOPMed
gnomAD
rs776279017 31 H>L No ExAC
TOPMed
gnomAD
rs1693327590 31 H>Q No Ensembl
rs776279017 31 H>R No ExAC
TOPMed
gnomAD
rs143456810 32 A>P No 1000Genomes
ExAC
gnomAD
rs143456810 32 A>T No 1000Genomes
ExAC
gnomAD
rs1458319631 34 A>E No gnomAD
rs913820829 37 G>V No TOPMed
gnomAD
rs1693326824 38 S>N No TOPMed
rs1572965312 43 Q>* No Ensembl
rs752622205 44 A>T No ExAC
gnomAD
rs766531438 45 V>I No ExAC
gnomAD
rs770623026 46 M>I No ExAC
TOPMed
gnomAD
rs760795980 46 M>K No ExAC
TOPMed
gnomAD
rs933331119 46 M>L No TOPMed
gnomAD
rs760795980 46 M>R No ExAC
TOPMed
gnomAD
rs760795980 46 M>T No ExAC
TOPMed
gnomAD
COSM3799186
COSM3799187
48 P>S Variant assessed as Somatic; MODERATE impact. [NCI-TCGA] No NCI-TCGA Cosmic
rs370328955 49 E>D No ESP
ExAC
TOPMed
gnomAD
rs1318749100 49 E>G No gnomAD
rs762129084 50 G>R No ExAC
TOPMed
gnomAD
rs1277019900 52 D>G No gnomAD
rs1348763891 52 D>N No gnomAD
rs1442033474 53 L>F No gnomAD
rs768953660 54 N>S No ExAC
gnomAD
TCGA novel 56 W>* Variant assessed as Somatic; HIGH impact. [NCI-TCGA] No NCI-TCGA
rs1259703688 61 T>A No TOPMed
gnomAD
COSM262050 64 F>L Variant assessed as Somatic; MODERATE impact. [NCI-TCGA] No NCI-TCGA Cosmic
rs1469274652 65 F>C No Ensembl
rs1427997054 66 N>K No gnomAD
rs750460617 67 Q>E No ExAC
gnomAD
rs1558835307 75 I>V No Ensembl
rs774478473 76 T>R No ExAC
gnomAD
rs764410010 80 T>A No ExAC
TOPMed
gnomAD
rs763181628 80 T>I No ExAC
TOPMed
gnomAD
rs1693151010 82 A>T No TOPMed
rs1186035771 83 S>I No gnomAD
rs1693150310 85 P>L No Ensembl
rs775938462 85 P>S No ExAC
TOPMed
gnomAD
rs868387594 86 V>F No Ensembl
rs1693149590 87 M>T No TOPMed
rs760105956 89 A>V No ExAC
gnomAD
rs776103020 91 P>A No ExAC
gnomAD
rs770473912 91 P>L No ExAC
TOPMed
gnomAD
rs1192511528 94 E>K No TOPMed
gnomAD
rs1240906324 96 H>Y No TOPMed
rs753060505 97 W>G No ExAC
gnomAD
rs2103713513 103 I>V No Ensembl
COSM4907937
COSM3372870
106 P>L Variant assessed as Somatic; MODERATE impact. [NCI-TCGA] No NCI-TCGA Cosmic
rs954568506 107 I>V Variant assessed as Somatic; MODERATE impact. [NCI-TCGA] No NCI-TCGA
gnomAD
TCGA novel 112 P>S Variant assessed as Somatic; MODERATE impact. [NCI-TCGA] No NCI-TCGA
rs1296209018 113 K>E No gnomAD
rs1693098987 115 I>T No Ensembl
rs1165795399 117 Y>C No gnomAD
rs1460927979 119 M>L No gnomAD
rs1460927979 119 M>V No gnomAD
rs760009975 120 T>S No ExAC
TOPMed
gnomAD
rs771497183 121 W>C No ExAC
TOPMed
gnomAD
rs1161301861 121 W>S No TOPMed
gnomAD
TCGA novel 125 Q>* Variant assessed as Somatic; HIGH impact. [NCI-TCGA] No NCI-TCGA
rs1693097676 128 D>N No gnomAD
rs1693097233 131 L>F No gnomAD
rs1175822526 131 L>P No gnomAD
rs1693096780 132 F>C No Ensembl
rs1450111466 133 P>T No TOPMed
rs1212524347 136 I>S No gnomAD
TCGA novel 137 G>= Variant assessed as Somatic; LOW impact. [NCI-TCGA] No NCI-TCGA
rs1232038450 137 G>D No gnomAD
rs1693095960 137 G>S No Ensembl
rs1232038450 137 G>V No gnomAD
rs1692892003 143 N>S No gnomAD
rs1558830933
RCV000678286
144 F>missing No ClinVar
dbSNP
rs1692891883 144 F>C No TOPMed
rs963342488 145 M>V No TOPMed
gnomAD
rs1296517593 147 V>M No gnomAD
TCGA novel 148 A>Q Variant assessed as Somatic; HIGH impact. [NCI-TCGA] No NCI-TCGA
rs184378303 151 I>V No 1000Genomes
gnomAD
rs754220663 154 R>C No ExAC
gnomAD
COSM4095717
rs766736617
154 R>H Variant assessed as Somatic; MODERATE impact. [NCI-TCGA] No NCI-TCGA Cosmic
ExAC
NCI-TCGA
gnomAD
rs1330467805 158 V>A No TOPMed
rs1692889431 161 H>R No Ensembl
rs767113013 162 I>V No ExAC
gnomAD
rs1572954258 164 H>Q No Ensembl
rs1692889134 164 H>R No Ensembl
rs1692888807 165 Q>* No TOPMed
rs1692888807 165 Q>E No TOPMed
rs1692888660 166 H>P No Ensembl
rs1259046885 167 F>L No gnomAD
rs761527866 169 S>F No ExAC
gnomAD
rs761527866 169 S>Y No ExAC
gnomAD
TCGA novel 176 E>K Variant assessed as Somatic; MODERATE impact. [NCI-TCGA] No NCI-TCGA
rs749035862 180 N>S No ExAC
gnomAD
rs1251749582 181 T>P No gnomAD
TCGA novel 189 F>C Variant assessed as Somatic; MODERATE impact. [NCI-TCGA] No NCI-TCGA
rs1416911502 189 F>S No TOPMed
gnomAD
rs1692886024 190 V>A No TOPMed
rs1692886152 190 V>I No gnomAD
rs1356284476 191 Q>E Variant assessed as Somatic; MODERATE impact. [NCI-TCGA] No NCI-TCGA
gnomAD
rs1329930751 193 F>L No gnomAD
rs1692815457 193 F>V No TOPMed
rs904481051 194 N>S No TOPMed
gnomAD
rs1398673589 196 I>T No gnomAD
rs1431882104 197 D>A No TOPMed
rs763775474 198 R>G No ExAC
gnomAD
rs1480994444 198 R>S No TOPMed
gnomAD
rs553156406 199 R>C No 1000Genomes
ExAC
TOPMed
gnomAD
rs1416732105 199 R>H No TOPMed
gnomAD
rs1161155777 202 A>T No TOPMed
gnomAD
rs1692814598 203 P>R No TOPMed
rs1233282131 204 L>V No gnomAD
COSM2999096 206 E>* Variant assessed as Somatic; HIGH impact. [NCI-TCGA] No NCI-TCGA Cosmic
rs1692814203 206 E>K No TOPMed
rs1254740854 207 L>F No TOPMed
gnomAD
rs1463549343 208 I>T No TOPMed
rs1395962003 216 R>G No TOPMed
gnomAD
rs1226863320 216 R>K No TOPMed
gnomAD
rs1285494033 217 R>Q No TOPMed

No associated diseases with Q9H8S9

No regional properties for Q9H8S9

Type Name Position InterPro Accession
No domain, repeats, and functional sites for Q9H8S9

Functions

Description
EC Number
Subcellular Localization
PANTHER Family
PANTHER Subfamily
PANTHER Protein Class
PANTHER Pathway Category No pathway information available

4 GO annotations of cellular component

Name Definition
cytoplasm The contents of a cell excluding the plasma membrane and nucleus, but including other subcellular structures.
cytosol The part of the cytoplasm that does not contain organelles but which does contain other particulate matter, such as protein complexes.
extracellular exosome A vesicle that is released into the extracellular region by fusion of the limiting endosomal membrane of a multivesicular body with the plasma membrane. Extracellular exosomes, also simply called exosomes, have a diameter of about 40-100 nm.
nucleus A membrane-bounded organelle of eukaryotic cells in which chromosomes are housed and replicated. In most cells, the nucleus contains all of the cell's chromosomes except the organellar chromosomes, and is the site of RNA synthesis and processing. In some species, or in specialized cell types, RNA metabolism or DNA replication may be absent.

2 GO annotations of molecular function

Name Definition
metal ion binding Binding to a metal ion.
protein kinase activator activity Binds to and increases the activity of a protein kinase, an enzyme which phosphorylates a protein.

2 GO annotations of biological process

Name Definition
hippo signaling The series of molecular signals mediated by the serine/threonine kinase Hippo or one of its orthologs. In Drosophila, Hippo in complex with the scaffold protein Salvador (Sav), phosphorylates and activates Warts (Wts), which in turn phosphorylates and inactivates the Yorkie (Yki) transcriptional activator. The core fly components hippo, sav, wts and mats are conserved in mammals as STK4/3 (MST1/2), SAV1/WW45, LATS1/2 and MOB1.
positive regulation of protein phosphorylation Any process that activates or increases the frequency, rate or extent of addition of phosphate groups to amino acids within a protein.

13 homologous proteins in AiPD

UniProt AC Gene Name Protein Name Species Evidence Code
P43563 MOB2 CBK1 kinase activator protein MOB2 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast) PR
P40484 MOB1 DBF2 kinase activator protein MOB1 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast) SS
Q95RA8 mats MOB kinase activator-like 1 Drosophila melanogaster (Fruit fly) SS
Q70IA8 MOB3C MOB kinase activator 3C Homo sapiens (Human) SS
Q96BX8 MOB3A MOB kinase activator 3A Homo sapiens (Human) SS
Q86TA1 MOB3B MOB kinase activator 3B Homo sapiens (Human) SS
Q7L9L4 MOB1B MOB kinase activator 1B Homo sapiens (Human) SS
Q8BPB0 Mob1b MOB kinase activator 1B Mus musculus (Mouse) EV
Q8VI63 Mob2 MOB kinase activator 2 Mus musculus (Mouse) EV
Q921Y0 Mob1a MOB kinase activator 1A Mus musculus (Mouse) SS
Q3T1J9 Mob1a MOB kinase activator 1A Rattus norvegicus (Rat) SS
Q8GYX0 MOB1B MOB kinase activator-like 1B Arabidopsis thaliana (Mouse-ear cress) SS
Q9FHI1 MOB1A MOB kinase activator-like 1A Arabidopsis thaliana (Mouse-ear cress) SS
10 20 30 40 50 60
MSFLFSSRSS KTFKPKKNIP EGSHQYELLK HAEATLGSGN LRQAVMLPEG EDLNEWIAVN
70 80 90 100 110 120
TVDFFNQINM LYGTITEFCT EASCPVMSAG PRYEYHWADG TNIKKPIKCS APKYIDYLMT
130 140 150 160 170 180
WVQDQLDDET LFPSKIGVPF PKNFMSVAKT ILKRLFRVYA HIYHQHFDSV MQLQEEAHLN
190 200 210
TSFKHFIFFV QEFNLIDRRE LAPLQELIEK LGSKDR