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Updated November 2019

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Nomenclature

Short Name:
Haspin
Full Name:
Serine-threonine-protein kinase Haspin
Alias:
  • EC 2.7.11.1
  • Germ cell-specific gene 2 protein
  • Haploid germ cell-specific nuclear protein kinase
  • GSG2
  • HASP

Classification

Type:
Protein-serine/threonine kinase
Group:
Other
Family:
Haspin
SubFamily:
NA
 
 

Specific Links

Entrez-Gene Entry: 83903
Entrez-Protein Entry: NP_114171
KinBASE Entry: HASPIN
OMIM Entry: 609240
Pfam Entry: Q8TF76
PhosphoNET Entry: Q8TF76
Phosphosite Plus Entry: 2185
Protein Data Bank Entry: 2VUW
ScanSite Entry: Q8TF76
UCSD-Nature Entry: A003132
UniProt Entry: Q8TF76

General Links

ClustalW2
GPS-Cuckoo
Human Protein Atlas
Kinase.com
Kinase Research
Kinasource
Kinomer
Netphorest
NetworKIN
Phosida
PhosphoElm
Protein Blast
ScanSite
String

Structure

Mol. Mass (Da):
88495
# Amino Acids:
798
# mRNA Isoforms:
2
mRNA Isoforms:
88,495 Da (798 AA; Q8TF76); 33,850 Da (314 AA; Q8TF76-2)
4D Structure:
NA
1D Structure:
Retrieve Gene Sequence
Retrieve Full Protein Sequence
Retrieve Catalytic Domain Sequence
 
3D Image (rendered using PV Viewer):

PDB ID
2VUW

Subfamily Alignment
subfamily domain
 
Domain Distribution:
Start End Domain
484 797 Pkinase
 

Post-translation Modifications

For detailed information on phosphorylation of this kinase go to PhosphoNET
Serine phosphorylated:

S58, S93+, S108, S140, S143+, S147, S151, S216, S220, S251, S287, S288, S340, S366, S387, S389.
Threonine phosphorylated:

T97, T110, T112, T128, T191, T253, T289, T373.
 

Distribution

Based on gene microarray analysis from the NCBI
Human Tissue Distribution
% Max Expression:

Mean Expression:

Number of Samples:

Standard Deviation:
% Max Expression:

Mean Expression:

Number of Samples:

Standard Deviation:
  • adipose
    100

    1462

    9

    1168

  • adrenal
    0.3

    5

    4

    7

  • bladder
    -

    -

    -

    -

  • brain
    3

    46

    26

    26

  • breast
    25

    361

    13

    330

  • cervix
    1.3

    19

    9

    7

  • colon
    0.8

    11

    13

    7

  • heart
    0.3

    4

    3

    3

  • intestine
    0.4

    6

    3

    1

  • kidney
    5

    79

    27

    53

  • liver
    0.3

    5

    3

    3

  • lung
    51

    751

    9

    560

  • lymphnode
    -

    -

    -

    -

  • ovary
    0.2

    3

    3

    0

  • pancreas
    0.3

    5

    3

    2

  • pituitary
    0.8

    11

    5

    9

  • prostate
    0.8

    12

    7

    16

  • salivarygland
    0.3

    4

    3

    2

  • skeletalmuscle"
    8

    114

    21

    61

  • skin
    27

    391

    31

    245

  • spinalcord
    0.2

    3

    3

    1

  • spleen
    0.1

    2

    3

    0

  • stomach
    -

    -

    -

    -

  • testis
    3

    41

    3

    4

  • thymus
    1.2

    18

    3

    4

  • thyroid
    33

    484

    19

    483

  • tonsil
    0.5

    7

    3

    1

  • trachea
    0.1

    2

    3

    0

  • uterus
    0.1

    2

    3

    1

  • reticulocytes"
    24

    357

    14

    103

  • t-lymphocytes
    48

    707

    12

    68

  • b-lymphocytes
    4

    59

    11

    68

  • neutrophils
    0.2

    3

    12

    0

  • macrophages
    48

    707

    26

    609

  • sperm
    12

    177

    22

    91

 

Evolution

Species Conservation
PhosphoNET % Identity:
PhosphoNET % Similarity:
Homologene %
Identity:
PhosphoNET % Identity:
PhosphoNET % Similarity:
Homologene %
Identity:
  • tableheader
    100

    100

    100
  • tableheader
    98.6

    99.1

    99
  • tableheader
    92.3

    95

    92
  • tableheader
    -

    -

    72
  • tableheader
    -

    -

    88
  • tableheader
    73.2

    80.7

    74.5
  • tableheader
    -

    -

    -
  • tableheader
    61.9

    73.1

    64
  • tableheader
    62.7

    72.8

    66
  • tableheader
    -

    -

    -
  • tableheader
    -

    -

    -
  • tableheader
    42.5

    57.7

    42
  • tableheader
    -

    -

    60
  • tableheader
    36.2

    47.7

    -
  • tableheader
    -

    -

    -
  • tableheader
    26.3

    43

    40
  • tableheader
    21.3

    37.8

    -
  • tableheader
    23.2

    40.1

    -
  • tableheader
    30.1

    47.1

    -
  • tableheader
    -

    -

    -
  • tableheader
    26.1

    39.5

    -
  • tableheader
    -

    -

    -
  • tableheader
    26.2

    40.5

    -
  • tableheader
    -

    -

    -
  • tableheader
    -

    -

    -
For a wider analysis go to PhosphoNET Evolution in PhosphoNET
 

Regulation

Activation:
NA
Inhibition:
NA
Synthesis:
NA
Degradation:
NA
 

Known Upstream Kinases

For further details on these substrates click on the Substrate Short Name or UniProt ID. Phosphosite Location is hyperlinked to PhosphoNET predictions.
Based on in vitro and/or in vivo phosphorylation data

Kinase Short Name UniProt ID (Human) Phosphosite Location Phosphosite Sequence Effect of Phosphorylation
AurB Q96GD4 S93 RVPKDRPSLTVTPKR +
AurB Q96GD4 S143 PPFPSRDSGRLSPDL +
 

Known Downstream Substrates

For further details on these substrates click on the Substrate Short Name or UniProt ID. Phosphosite Location is hyperlinked to PhosphoNET predictions.
Based on in vitro and/or in vivo phosphorylation data

Substrate Short Name UniProt ID (Human) Phosphosite Location Phosphosite Sequence Effect of Phosphorylation
H3.1 P68431 T3 _____ARTKQTARKS +
 

Protein Kinase Specificity

Matrix of observed frequency (%) of amino acids in aligned protein substrate phosphosites

Kinections GIF
Matrix Type:
Predicted from the application of the Kinexus Kinase Substrate Predictor Version 2.0 algorithm, which was trained with over 10,000 kinase-protein substrate pairs and 8,000 kinase-peptide substrate pairs.
Domain #:
1
 

Inhibitors

For further details on these inhibitors click on the Compound Name and enter it into DrugKiNET or click on the ID's
Based on in vitro and/or in vivo phosphorylation data
Compound Name KD, Ki or IC50 (nM) PubChem ID ChEMBL ID PubMed ID
SGI-1776 IC50 = 34 nM 19734450
K-252a; Nocardiopsis sp. IC50 > 50 nM 3813 281948 22037377
PKR Inhibitor IC50 > 50 nM 6490494 235641 22037377
PKR Inhibitor; Negative Control IC50 > 50 nM 16760619 22037377
Staurosporine IC50 > 50 nM 5279 22037377
Gö6976 IC50 > 150 nM 3501 302449 22037377
JAK3 Inhibitor VI IC50 > 150 nM 16760524 22037377
SB218078 IC50 > 150 nM 447446 289422 22037377
TG003 IC50 > 150 nM 1893668 408982 22037377
1;9-Pyrazoloanthrone IC50 > 250 nM 8515 7064 22037377
ACN-S001855 IC50 > 250 nM 10377751 22037377
AG-E-60384 IC50 > 250 nM 6419741 413188 22037377
AS601245 IC50 > 250 nM 11422035 191384 22037377
Flt-3 Inhibitor II IC50 > 250 nM 11601743 377193 22037377
IDR E804 IC50 > 250 nM 6419764 1802727 22037377
H-89 IC50 = 500 nM 449241 104264 22037377
JNK Inhibitor; Negative Control IC50 = 500 nM 11665831 22037377
Sunitinib IC50 = 500 nM 5329102 535 22037377
AG1024 IC50 > 1 µM 2044 22037377
Aloisine A IC50 > 1 µM 5326843 75680 22037377
BCP9000906 IC50 > 1 µM 5494425 21156 22037377
BML-275 IC50 > 1 µM 11524144 478629 22037377
Bosutinib IC50 > 1 µM 5328940 288441 22037377
Indirubin-3′-monoxime IC50 > 1 µM 5326739 22037377
Lapatinib IC50 > 1 µM 208908 554 22037377
Nilotinib IC50 > 1 µM 644241 255863 22037377
PP1 Analog II; 1NM-PP1 IC50 > 1 µM 5154691 573578 22037377
Rho Kinase Inhibitor III; Rockout IC50 > 1 µM 644354 380071 22037377
SB202474 IC50 > 1 µM 5162 278724 22037377
Syk Inhibitor II IC50 > 1 µM 16760670 22037377
Tozasertib IC50 > 1 µM 5494449 572878 22037377
 

Disease Linkage

General Disease Association:

Respiratory disorders
Specific Diseases (Non-cancerous):

Rhinotracheitis
Comments:
Rhinotracheitis is an upper respiratory disease characterized by the inflammation in the nasal cavities and trachea. The cause of the inflammation is feline herpes virus 1, which can be found in cats (particularly young kittens) and transmitted to humans. Symptoms of the disease commonly include sneezing, conjunctivitis, and increased nasal discharges.
 
Comments:
in general in human cancers,Haspin is up-regulated about 1.8-times the rate observed for most protein kinases.
 
Gene Expression in Cancers:

TranscriptoNET (www.transcriptonet.ca) analysis with mRNA expression data retrieved from the National Center for Biotechnology Information's Gene Expression Omnibus (GEO) database, which was normalized against 60 abundantly and commonly found proteins, indicated altered expression for this protein kinase as shown here as the percent change from normal tissue controls (%CFC) as supported with the Student T-test in human Ovary adenocarcinomas (%CFC= +193, p<0.004). The COSMIC website notes an up-regulated expression score for Haspin in diverse human cancers of 828, which is 1.8-fold of the average score of 462 for the human protein kinases. The down-regulated expression score of 32 for this protein kinase in human cancers was 0.5-fold of the average score of 60 for the human protein kinases.
Mutagenesis Experiments:

Insertional mutagenesis studies in mice have not yet revealed a role for this protein kinase in mouse cancer oncogenesis.
Mutation Rate in All Cancers:

Percent mutation rates per 100 amino acids length in human cancers: 0.04 % in 24691 diverse cancer specimens. This rate is -45 % lower than the average rate of 0.075 % calculated for human protein kinases in general.
Mutation Rate in Specific Cancers:

Highest percent mutation rates per 100 amino acids length in human cancers: 0.16 % in 864 skin cancers tested; 0.15 % in 603 endometrium cancers tested; 0.14 % in 1270 large intestine cancers tested; 0.12 % in 710 oesophagus cancers tested; 0.11 % in 575 stomach cancers tested; 0.09 % in 548 urinary tract cancers tested; 0.07 % in 1512 liver cancers tested; 0.03 % in 2082 central nervous system cancers tested; 0.02 % in 1634 lung cancers tested; 0.01 % in 881 prostate cancers tested.
Frequency of Mutated Sites:

Most frequent mutations with the number of reports indicated in brackets: R82C (18).
Comments:
Only 6 deletions, 2 insertions and no complex mutations are noted on the COSMIC website.
 
COSMIC Entry:
GSG2
OMIM Entry:
609240
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