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Protein

Serine/threonine-protein kinase greatwall

Gene

MASTL

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Serine/threonine kinase that plays a key role in M phase by acting as a regulator of mitosis entry and maintenance. Acts by promoting the inactivation of protein phosphatase 2A (PP2A) during M phase: does not directly inhibit PP2A but acts by mediating phosphorylation and subsequent activation of ARPP19 and ENSA at 'Ser-62' and 'Ser-67', respectively. ARPP19 and ENSA are phosphatase inhibitors that specifically inhibit the PPP2R2D (PR55-delta) subunit of PP2A. Inactivation of PP2A during M phase is essential to keep cyclin-B1-CDK1 activity high. Following DNA damage, it is also involved in checkpoint recovery by being inhibited. Phosphorylates histone protein in vitro; however such activity is unsure in vivo. May be involved in megakaryocyte differentiation.5 Publications

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei62ATPPROSITE-ProRule annotation1
Active sitei156Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi41 – 49ATPPROSITE-ProRule annotation9

GO - Molecular functioni

  • ATP binding Source: UniProtKB-KW
  • kinase activity Source: UniProtKB
  • protein phosphatase 2A binding Source: UniProtKB
  • protein serine/threonine kinase activity Source: UniProtKB

GO - Biological processi

  • cell division Source: UniProtKB-KW
  • cellular response to DNA damage stimulus Source: UniProtKB
  • female meiosis II Source: Ensembl
  • G2/M transition of mitotic cell cycle Source: UniProtKB
  • intracellular signal transduction Source: GO_Central
  • mitotic nuclear division Source: UniProtKB
  • negative regulation of protein phosphatase type 2A activity Source: UniProtKB
  • peptidyl-serine phosphorylation Source: GO_Central
  • positive regulation of ubiquitin-protein ligase activity involved in meiotic cell cycle Source: Ensembl
  • regulation of cell cycle Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Serine/threonine-protein kinase, Transferase

Keywords - Biological processi

Cell cycle, Cell division, Mitosis

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

BioCyciZFISH:HS04407-MONOMER.
ReactomeiR-HSA-2465910. MASTL Facilitates Mitotic Progression.
SignaLinkiQ96GX5.
SIGNORiQ96GX5.

Names & Taxonomyi

Protein namesi
Recommended name:
Serine/threonine-protein kinase greatwall (EC:2.7.11.1)
Short name:
GW
Short name:
GWL
Short name:
hGWL
Alternative name(s):
Microtubule-associated serine/threonine-protein kinase-like
Short name:
MAST-L
Gene namesi
Name:MASTL
Synonyms:GW, GWL, THC2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 10

Organism-specific databases

HGNCiHGNC:19042. MASTL.

Subcellular locationi

GO - Cellular componenti

  • centrosome Source: UniProtKB
  • cleavage furrow Source: UniProtKB
  • cytoplasm Source: UniProtKB-KW
  • nucleoplasm Source: HPA
  • nucleus Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Cytoskeleton, Nucleus

Pathology & Biotechi

Involvement in diseasei

Thrombocytopenia 2 (THC2)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionThrombocytopenia is defined by a decrease in the number of platelets in circulating blood, resulting in the potential for increased bleeding and decreased ability for clotting.
See also OMIM:188000
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_022838167E → D in THC2. 1 PublicationCorresponds to variant rs28941470dbSNPEnsembl.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi72K → M: Hyperactive form. 1 Publication1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi84930.
MalaCardsiMASTL.
MIMi188000. phenotype.
OpenTargetsiENSG00000120539.
Orphaneti168629. Autosomal thrombocytopenia with normal platelets.
PharmGKBiPA134943781.

Polymorphism and mutation databases

BioMutaiMASTL.
DMDMi68565604.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000863151 – 879Serine/threonine-protein kinase greatwallAdd BLAST879

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei1N-acetylmethionineCombined sources1
Modified residuei207PhosphothreonineCombined sources1
Modified residuei222PhosphothreonineCombined sources1
Modified residuei293PhosphoserineCombined sources1
Modified residuei370PhosphoserineCombined sources1
Modified residuei453PhosphoserineCombined sources1
Modified residuei519PhosphothreonineCombined sources1
Modified residuei552PhosphoserineCombined sources1
Modified residuei556PhosphoserineCombined sources1
Modified residuei631PhosphoserineCombined sources1
Modified residuei657PhosphoserineCombined sources1
Modified residuei668PhosphoserineCombined sources1
Modified residuei722PhosphothreonineCombined sources1
Modified residuei725PhosphoserineCombined sources1
Modified residuei741PhosphothreonineCombined sources1
Modified residuei875PhosphoserineCombined sources1
Modified residuei878PhosphoserineCombined sources1

Post-translational modificationi

Phosphorylation at Thr-741 by CDK1 during M phase activates its kinase activity (By similarity). Maximum phosphorylation occurs in prometaphase.By similarity2 Publications

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiQ96GX5.
MaxQBiQ96GX5.
PaxDbiQ96GX5.
PeptideAtlasiQ96GX5.
PRIDEiQ96GX5.

PTM databases

iPTMnetiQ96GX5.
PhosphoSitePlusiQ96GX5.

Expressioni

Gene expression databases

BgeeiENSG00000120539.
CleanExiHS_MASTL.
ExpressionAtlasiQ96GX5. baseline and differential.
GenevisibleiQ96GX5. HS.

Organism-specific databases

HPAiHPA027175.
HPA054273.

Interactioni

GO - Molecular functioni

Protein-protein interaction databases

BioGridi124364. 23 interactors.
IntActiQ96GX5. 20 interactors.
STRINGi9606.ENSP00000365107.

Structurei

Secondary structure

1879
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi32 – 34Combined sources3
Beta strandi35 – 40Combined sources6
Beta strandi48 – 56Combined sources9
Beta strandi58 – 65Combined sources8
Turni66 – 68Combined sources3
Beta strandi96 – 98Combined sources3
Beta strandi103 – 111Combined sources9
Helixi118 – 125Combined sources8
Helixi130 – 149Combined sources20
Turni159 – 161Combined sources3
Beta strandi162 – 164Combined sources3
Beta strandi170 – 172Combined sources3
Beta strandi174 – 177Combined sources4
Helixi747 – 750Combined sources4
Helixi758 – 773Combined sources16
Helixi783 – 792Combined sources10
Helixi800 – 802Combined sources3
Helixi806 – 815Combined sources10
Helixi826 – 830Combined sources5
Helixi833 – 835Combined sources3
Helixi840 – 845Combined sources6

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
5LOHX-ray3.10A/B1-194[»]
A/B740-879[»]
ProteinModelPortaliQ96GX5.
SMRiQ96GX5.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini35 – 835Protein kinasePROSITE-ProRule annotationAdd BLAST801
Domaini836 – 879AGC-kinase C-terminalAdd BLAST44

Sequence similaritiesi

Contains 1 AGC-kinase C-terminal domain.Curated
Contains 1 protein kinase domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiENOG410IUCW. Eukaryota.
ENOG410ZHM9. LUCA.
GeneTreeiENSGT00530000063286.
HOVERGENiHBG074267.
InParanoidiQ96GX5.
KOiK16309.
OMAiCAYSGSY.
OrthoDBiEOG091G01J6.
PhylomeDBiQ96GX5.
TreeFamiTF313149.

Family and domain databases

InterProiIPR000961. AGC-kinase_C.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamiPF00069. Pkinase. 2 hits.
[Graphical view]
SMARTiSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 2 hits.
PROSITEiPS51285. AGC_KINASE_CTER. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

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

Isoform 1 (identifier: Q96GX5-1) [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
MDPTAGSKKE PGGGAATEEG VNRIAVPKPP SIEEFSIVKP ISRGAFGKVY
60 70 80 90 100
LGQKGGKLYA VKVVKKADMI NKNMTHQVQA ERDALALSKS PFIVHLYYSL
110 120 130 140 150
QSANNVYLVM EYLIGGDVKS LLHIYGYFDE EMAVKYISEV ALALDYLHRH
160 170 180 190 200
GIIHRDLKPD NMLISNEGHI KLTDFGLSKV TLNRDINMMD ILTTPSMAKP
210 220 230 240 250
RQDYSRTPGQ VLSLISSLGF NTPIAEKNQD PANILSACLS ETSQLSQGLV
260 270 280 290 300
CPMSVDQKDT TPYSSKLLKS CLETVASNPG MPVKCLTSNL LQSRKRLATS
310 320 330 340 350
SASSQSHTFI SSVESECHSS PKWEKDCQES DEALGPTMMS WNAVEKLCAK
360 370 380 390 400
SANAIETKGF NKKDLELALS PIHNSSALPT TGRSCVNLAK KCFSGEVSWE
410 420 430 440 450
AVELDVNNIN MDTDTSQLGF HQSNQWAVDS GGISEEHLGK RSLKRNFELV
460 470 480 490 500
DSSPCKKIIQ NKKTCVEYKH NEMTNCYTNQ NTGLTVEVQD LKLSVHKSQQ
510 520 530 540 550
NDCANKENIV NSFTDKQQTP EKLPIPMIAK NLMCELDEDC EKNSKRDYLS
560 570 580 590 600
SSFLCSDDDR ASKNISMNSD SSFPGISIME SPLESQPLDS DRSIKESSFE
610 620 630 640 650
ESNIEDPLIV TPDCQEKTSP KGVENPAVQE SNQKMLGPPL EVLKTLASKR
660 670 680 690 700
NAVAFRSFNS HINASNNSEP SRMNMTSLDA MDISCAYSGS YPMAITPTQK
710 720 730 740 750
RRSCMPHQQT PNQIKSGTPY RTPKSVRRGV APVDDGRILG TPDYLAPELL
760 770 780 790 800
LGRAHGPAVD WWALGVCLFE FLTGIPPFND ETPQQVFQNI LKRDIPWPEG
810 820 830 840 850
EEKLSDNAQS AVEILLTIDD TKRAGMKELK RHPLFSDVDW ENLQHQTMPF
860 870
IPQPDDETDT SYFEARNTAQ HLTVSGFSL
Length:879
Mass (Da):97,319
Last modified:December 1, 2001 - v1
Checksum:iE6533029D1CE58B4
GO
Isoform 2 (identifier: Q96GX5-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     708-708: Missing.
     756-793: Missing.

Note: No experimental confirmation available.
Show »
Length:840
Mass (Da):92,861
Checksum:i72CD7A9036188FE1
GO
Isoform 3 (identifier: Q96GX5-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     708-708: Missing.

Show »
Length:878
Mass (Da):97,191
Checksum:iD04E9C47F8615FCE
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti634K → E in BAC11218 (PubMed:14702039).Curated1
Sequence conflicti685C → R in BAB55321 (PubMed:14702039).Curated1
Sequence conflicti731A → P in BAC11218 (PubMed:14702039).Curated1
Sequence conflicti865A → T in BAB55321 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_022838167E → D in THC2. 1 PublicationCorresponds to variant rs28941470dbSNPEnsembl.1
Natural variantiVAR_040792337T → K.1 PublicationCorresponds to variant rs36121140dbSNPEnsembl.1
Natural variantiVAR_057103606D → Y.Corresponds to variant rs35413630dbSNPEnsembl.1
Natural variantiVAR_040793610V → I.1 PublicationCorresponds to variant rs35571315dbSNPEnsembl.1
Natural variantiVAR_022839620P → A.1 PublicationCorresponds to variant rs3802526dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_014574708Missing in isoform 2 and isoform 3. 1 Publication1
Alternative sequenceiVSP_014575756 – 793Missing in isoform 2. 1 PublicationAdd BLAST38

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK027719 mRNA. Translation: BAB55321.1.
AK074804 mRNA. Translation: BAC11218.1.
AL160291 Genomic DNA. Translation: CAI16908.1.
AL160291 Genomic DNA. Translation: CAI16909.1.
AL160291 Genomic DNA. Translation: CAI16910.1.
BC009107 mRNA. Translation: AAH09107.1.
CCDSiCCDS53502.1. [Q96GX5-1]
CCDS53503.1. [Q96GX5-2]
CCDS7153.1. [Q96GX5-3]
RefSeqiNP_001165774.1. NM_001172303.2. [Q96GX5-1]
NP_001165775.1. NM_001172304.2. [Q96GX5-2]
NP_116233.2. NM_032844.4. [Q96GX5-3]
UniGeneiHs.276905.

Genome annotation databases

EnsembliENST00000342386; ENSP00000343446; ENSG00000120539. [Q96GX5-2]
ENST00000375940; ENSP00000365107; ENSG00000120539. [Q96GX5-1]
ENST00000375946; ENSP00000365113; ENSG00000120539. [Q96GX5-3]
GeneIDi84930.
KEGGihsa:84930.
UCSCiuc001itl.3. human. [Q96GX5-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK027719 mRNA. Translation: BAB55321.1.
AK074804 mRNA. Translation: BAC11218.1.
AL160291 Genomic DNA. Translation: CAI16908.1.
AL160291 Genomic DNA. Translation: CAI16909.1.
AL160291 Genomic DNA. Translation: CAI16910.1.
BC009107 mRNA. Translation: AAH09107.1.
CCDSiCCDS53502.1. [Q96GX5-1]
CCDS53503.1. [Q96GX5-2]
CCDS7153.1. [Q96GX5-3]
RefSeqiNP_001165774.1. NM_001172303.2. [Q96GX5-1]
NP_001165775.1. NM_001172304.2. [Q96GX5-2]
NP_116233.2. NM_032844.4. [Q96GX5-3]
UniGeneiHs.276905.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
5LOHX-ray3.10A/B1-194[»]
A/B740-879[»]
ProteinModelPortaliQ96GX5.
SMRiQ96GX5.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi124364. 23 interactors.
IntActiQ96GX5. 20 interactors.
STRINGi9606.ENSP00000365107.

PTM databases

iPTMnetiQ96GX5.
PhosphoSitePlusiQ96GX5.

Polymorphism and mutation databases

BioMutaiMASTL.
DMDMi68565604.

Proteomic databases

EPDiQ96GX5.
MaxQBiQ96GX5.
PaxDbiQ96GX5.
PeptideAtlasiQ96GX5.
PRIDEiQ96GX5.

Protocols and materials databases

DNASUi84930.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000342386; ENSP00000343446; ENSG00000120539. [Q96GX5-2]
ENST00000375940; ENSP00000365107; ENSG00000120539. [Q96GX5-1]
ENST00000375946; ENSP00000365113; ENSG00000120539. [Q96GX5-3]
GeneIDi84930.
KEGGihsa:84930.
UCSCiuc001itl.3. human. [Q96GX5-1]

Organism-specific databases

CTDi84930.
DisGeNETi84930.
GeneCardsiMASTL.
HGNCiHGNC:19042. MASTL.
HPAiHPA027175.
HPA054273.
MalaCardsiMASTL.
MIMi188000. phenotype.
608221. gene.
neXtProtiNX_Q96GX5.
OpenTargetsiENSG00000120539.
Orphaneti168629. Autosomal thrombocytopenia with normal platelets.
PharmGKBiPA134943781.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IUCW. Eukaryota.
ENOG410ZHM9. LUCA.
GeneTreeiENSGT00530000063286.
HOVERGENiHBG074267.
InParanoidiQ96GX5.
KOiK16309.
OMAiCAYSGSY.
OrthoDBiEOG091G01J6.
PhylomeDBiQ96GX5.
TreeFamiTF313149.

Enzyme and pathway databases

BioCyciZFISH:HS04407-MONOMER.
ReactomeiR-HSA-2465910. MASTL Facilitates Mitotic Progression.
SignaLinkiQ96GX5.
SIGNORiQ96GX5.

Miscellaneous databases

GeneWikiiMASTL.
GenomeRNAii84930.
PROiQ96GX5.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000120539.
CleanExiHS_MASTL.
ExpressionAtlasiQ96GX5. baseline and differential.
GenevisibleiQ96GX5. HS.

Family and domain databases

InterProiIPR000961. AGC-kinase_C.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamiPF00069. Pkinase. 2 hits.
[Graphical view]
SMARTiSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 2 hits.
PROSITEiPS51285. AGC_KINASE_CTER. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiGWL_HUMAN
AccessioniPrimary (citable) accession number: Q96GX5
Secondary accession number(s): Q5T8D5
, Q5T8D7, Q8NCD6, Q96SJ5
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 5, 2005
Last sequence update: December 1, 2001
Last modified: November 30, 2016
This is version 147 of the entry and version 1 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

Miscellaneous

Reduced levels of MASTL by RNAi causes mitotic abnormalities that consist of delay in G2 phase and slow chromosome condensation. Cells that enter and progress through mitosis often fail to completely separate their sister chromatids in anaphase leading to the formation of 4N G1 cells subsequent to failure of cytokinesis (PubMed:20818157 and PubMed:20538976).

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 10
    Human chromosome 10: 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. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  7. 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.