dbPTM

DYRK2_HUMAN - PTM Information in dbPTM

Basic Information of Protein

Overview of Protein Modification Sites with Functional and Structural Information
UniProt ID	DYRK2_HUMAN
UniProt AC	Q92630
Protein Name	Dual specificity tyrosine-phosphorylation-regulated kinase 2
Gene Name	DYRK2
Organism	Homo sapiens (Human).
Sequence Length	601
Subcellular Localization	Cytoplasm. Nucleus. Translocates into the nucleus following DNA damage.
Protein Description	Serine/threonine-protein kinase involved in the regulation of the mitotic cell cycle, cell proliferation, apoptosis, organization of the cytoskeleton and neurite outgrowth. Functions in part via its role in ubiquitin-dependent proteasomal protein degradation. Functions downstream of ATM and phosphorylates p53/TP53 at 'Ser-46', and thereby contributes to the induction of apoptosis in response to DNA damage. Phosphorylates NFATC1, and thereby inhibits its accumulation in the nucleus and its transcription factor activity. Phosphorylates EIF2B5 at 'Ser-544', enabling its subsequent phosphorylation and inhibition by GSK3B. Likewise, phosphorylation of NFATC1, CRMP2/DPYSL2 and CRMP4/DPYSL3 promotes their subsequent phosphorylation by GSK3B. May play a general role in the priming of GSK3 substrates. Inactivates GYS1 by phosphorylation at 'Ser-641', and potentially also a second phosphorylation site, thus regulating glycogen synthesis. Mediates EDVP E3 ligase complex formation and is required for the phosphorylation and subsequent degradation of KATNA1. Phosphorylates TERT at 'Ser-457', promoting TERT ubiquitination by the EDVP complex. Phosphorylates SIAH2, and thereby increases its ubiquitin ligase activity. Promotes the proteasomal degradation of MYC and JUN, and thereby regulates progress through the mitotic cell cycle and cell proliferation. Promotes proteasomal degradation of GLI2 and GLI3, and thereby plays a role in smoothened and sonic hedgehog signaling. Plays a role in cytoskeleton organization and neurite outgrowth via its phosphorylation of DCX and DPYSL2. Phosphorylates CRMP2/DPYSL2, CRMP4/DPYSL3, DCX, EIF2B5, EIF4EBP1, GLI2, GLI3, GYS1, JUN, MDM2, MYC, NFATC1, p53/TP53, TAU/MAPT and KATNA1. Can phosphorylate histone H1, histone H3 and histone H2B (in vitro). Can phosphorylate CARHSP1 (in vitro)..
Protein Sequence	MLTRKPSAAAPAAYPTGRGGDSAVRQLQASPGLGAGATRSGVGTGPPSPIALPPLRASNAAAAAHTIGGSKHTMNDHLHVGSHAHGQIQVQQLFEDNSNKRTVLTTQPNGLTTVGKTGLPVVPERQLDSIHRRQGSSTSLKSMEGMGKVKATPMTPEQAMKQYMQKLTAFEHHEIFSYPEIYFLGLNAKKRQGMTGGPNNGGYDDDQGSYVQVPHDHVAYRYEVLKVIGKGSFGQVVKAYDHKVHQHVALKMVRNEKRFHRQAAEEIRILEHLRKQDKDNTMNVIHMLENFTFRNHICMTFELLSMNLYELIKKNKFQGFSLPLVRKFAHSILQCLDALHKNRIIHCDLKPENILLKQQGRSGIKVIDFGSSCYEHQRVYTYIQSRFYRAPEVILGARYGMPIDMWSLGCILAELLTGYPLLPGEDEGDQLACMIELLGMPSQKLLDASKRAKNFVSSKGYPRYCTVTTLSDGSVVLNGGRSRRGKLRGPPESREWGNALKGCDDPLFLDFLKQCLEWDPAVRMTPGQALRHPWLRRRLPKPPTGEKTSVKRITESTGAITSISKLPPPSSSASKLRTNLAQMTDANGNIQQRTVLPKLVS

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
7	Phosphorylation	-MLTRKPSAAAPAAY -CCCCCCCCCCCCCC	33.31	28348404
14	Phosphorylation	SAAAPAAYPTGRGGD CCCCCCCCCCCCCCH	11.93	23312004
16	Phosphorylation	AAPAAYPTGRGGDSA CCCCCCCCCCCCHHH	27.17	23312004
18	Methylation	PAAYPTGRGGDSAVR CCCCCCCCCCHHHHH	48.69	-
30	Phosphorylation	AVRQLQASPGLGAGA HHHHHHCCCCCCCCC	13.41	30266825
40	Phosphorylation	LGAGATRSGVGTGPP CCCCCCCCCCCCCCC	33.21	30266825
44	Phosphorylation	ATRSGVGTGPPSPIA CCCCCCCCCCCCCCC	44.07	30266825
48	Phosphorylation	GVGTGPPSPIALPPL CCCCCCCCCCCCCCC	31.88	30266825
98	Phosphorylation	QQLFEDNSNKRTVLT EHHHCCCCCCCEEEE	56.93	22468782
106	Phosphorylation	NKRTVLTTQPNGLTT CCCEEEEECCCCCEE	37.56	22817900
136	Phosphorylation	SIHRRQGSSTSLKSM HHHHCCCCCCCCHHH	23.31	29978859
137	Phosphorylation	IHRRQGSSTSLKSME HHHCCCCCCCCHHHC	28.92	29978859
138	Phosphorylation	HRRQGSSTSLKSMEG HHCCCCCCCCHHHCC	39.51	29978859
139	Phosphorylation	RRQGSSTSLKSMEGM HCCCCCCCCHHHCCC	35.43	29978859
142	Phosphorylation	GSSTSLKSMEGMGKV CCCCCCHHHCCCCCC	27.62	29978859
292	Phosphorylation	IHMLENFTFRNHICM HHHHHHCCCCCCHHH	33.01	25690035
309	Phosphorylation	ELLSMNLYELIKKNK HHHHCCHHHHHHHCC	12.04	19664995
331	Phosphorylation	LVRKFAHSILQCLDA HHHHHHHHHHHHHHH	22.89	29116813
347	S-nitrosylation	HKNRIIHCDLKPENI HHCCEEECCCCHHHE	4.64	24105792
373	S-nitrosylation	VIDFGSSCYEHQRVY EEECCCCHHCHHHHH	5.04	24105792
380	Phosphorylation	CYEHQRVYTYIQSRF HHCHHHHHHHHHHHH	8.94	24260401
381	Phosphorylation	YEHQRVYTYIQSRFY HCHHHHHHHHHHHHC	15.99	27794612
382	Phosphorylation	EHQRVYTYIQSRFYR CHHHHHHHHHHHHCC	4.54	19664994
385	Phosphorylation	RVYTYIQSRFYRAPE HHHHHHHHHHCCCCH	18.13	22617229
442	Phosphorylation	IELLGMPSQKLLDAS HHHHCCCCHHHHHHH	30.93	22817900
449	Phosphorylation	SQKLLDASKRAKNFV CHHHHHHHHHHHHHH	23.49	23362280
464	Phosphorylation	SSKGYPRYCTVTTLS HCCCCCCEEEEEECC	6.48	19664995
466	Phosphorylation	KGYPRYCTVTTLSDG CCCCCEEEEEECCCC	16.38	29083192
468	Phosphorylation	YPRYCTVTTLSDGSV CCCEEEEEECCCCCE	12.13	29083192
469	Phosphorylation	PRYCTVTTLSDGSVV CCEEEEEECCCCCEE	21.67	29083192
471	Phosphorylation	YCTVTTLSDGSVVLN EEEEEECCCCCEEEC	37.52	29083192
474	Phosphorylation	VTTLSDGSVVLNGGR EEECCCCCEEECCCC	17.65	29083192
525	Phosphorylation	WDPAVRMTPGQALRH CCCCCCCCCCCHHCC	17.44	19413330
544	Phosphorylation	RRLPKPPTGEKTSVK HCCCCCCCCCCCCEE	67.51	28348404
554	Phosphorylation	KTSVKRITESTGAIT CCCEEEEHHCCCCEE	28.10	28270605
556	Phosphorylation	SVKRITESTGAITSI CEEEEHHCCCCEEEH	24.40	28270605
557	Phosphorylation	VKRITESTGAITSIS EEEEHHCCCCEEEHH	25.13	28270605
561	Phosphorylation	TESTGAITSISKLPP HHCCCCEEEHHHCCC	21.34	28270605
562	Phosphorylation	ESTGAITSISKLPPP HCCCCEEEHHHCCCC	20.82	28270605
564	Phosphorylation	TGAITSISKLPPPSS CCCEEEHHHCCCCCC	28.10	28270605

Upstream regulatory proteins (kinases for phosphorylation sites, E3 ubiquitin ligases of ubiquitination sites, ...)

Modified Location	Modified Residue	Modification	Type of Upstream Proteins	Gene Name of Upstream Proteins	UniProt AC of Upstream Proteins	Sources
106	T	Phosphorylation	Kinase	ATM	Q13315	Uniprot
381	T	Phosphorylation	Kinase	MLK2	Q02779	PSP
442	S	Phosphorylation	Kinase	ATM	Q13315	Uniprot
449	S	Phosphorylation	Kinase	MLK2	Q02779	PSP
-	K	Ubiquitination	E3 ubiquitin ligase	MDM2	Q00987	PMID:19965871
-	K	Ubiquitination	E3 ubiquitin ligase	SIAH2	O43255	PMID:22199232

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Reference
106	T	Phosphorylation	19965871
Phosphorylated at Thr-106 and Ser-442 by ATM in response to genotoxic stress.
106	T	Phosphorylation	19965871
Phosphorylation on Thr-106 and Ser-442 by ATM in response to genotoxic stress disrupts MDM2 binding and prevents MDM2-mediated ubiquitination and subsequent proteasomal degradation.
106	T	ubiquitylation	19965871
Phosphorylation on Thr-106 and Ser-442 by ATM in response to genotoxic stress disrupts MDM2 binding and prevents MDM2-mediated ubiquitination and subsequent proteasomal degradation.
442	S	Phosphorylation	19965871
Phosphorylated at Thr-106 and Ser-442 by ATM in response to genotoxic stress.
442	S	Phosphorylation	19965871
Phosphorylation on Thr-106 and Ser-442 by ATM in response to genotoxic stress disrupts MDM2 binding and prevents MDM2-mediated ubiquitination and subsequent proteasomal degradation.
442	S	ubiquitylation	19965871
Phosphorylation on Thr-106 and Ser-442 by ATM in response to genotoxic stress disrupts MDM2 binding and prevents MDM2-mediated ubiquitination and subsequent proteasomal degradation.

Disease-associated PTM Sites based on SAP

* Distance = the distance between SAP position and PTM sites.

Modified Location	Modification	Variant Position (Distance <= 10)	Residue Change	SAP	Related Disease	Reference
Oops, there are no SNP-PTM records of DYRK2_HUMAN !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
FSBP_HUMAN	RAD54B	physical	16189514
RA54B_HUMAN	RAD54B	physical	16189514
MDM2_HUMAN	MDM2	physical	19965871
UBR5_HUMAN	UBR5	physical	19287380
DDB1_HUMAN	DDB1	physical	19287380
DCAF1_HUMAN	VPRBP	physical	19287380
GRP78_HUMAN	HSPA5	physical	19287380
HSP7C_HUMAN	HSPA8	physical	19287380
ODO2_HUMAN	DLST	physical	19287380
XPP3_HUMAN	XPNPEP3	physical	19287380
RS2_HUMAN	RPS2	physical	19287380
ODPB_HUMAN	PDHB	physical	19287380
RL7_HUMAN	RPL7	physical	19287380
RL4_HUMAN	RPL4	physical	19287380
HNRPU_HUMAN	HNRNPU	physical	19287380
SSBP2_HUMAN	SSBP2	physical	19287380
TBA1C_HUMAN	TUBA1C	physical	19287380
RLA0_HUMAN	RPLP0	physical	19287380
NPM_HUMAN	NPM1	physical	19287380
MPCP_HUMAN	SLC25A3	physical	19287380
RL7A_HUMAN	RPL7A	physical	19287380
HS90A_HUMAN	HSP90AA1	physical	19287380
RT29_HUMAN	DAP3	physical	19287380
TBA3C_HUMAN	TUBA3C	physical	19287380
RMXL2_HUMAN	RBMXL2	physical	19287380
RFA1_HUMAN	RPA1	physical	19287380
PIMT_HUMAN	PCMT1	physical	19287380
HSP76_HUMAN	HSPA6	physical	19287380
RL18_HUMAN	RPL18	physical	19287380
KTNA1_HUMAN	KATNA1	physical	19287380
SIAH2_HUMAN	SIAH2	physical	22878263
A4_HUMAN	APP	physical	21832049
TERT_HUMAN	TERT	physical	23362280
DYRK4_HUMAN	DYRK4	physical	23602568
TITIN_HUMAN	TTN	physical	23602568
RBCC1_HUMAN	RB1CC1	physical	23602568
NR1I2_HUMAN	NR1I2	physical	24438055
IKZF1_HUMAN	IKZF1	physical	25416956
KXDL1_HUMAN	KXD1	physical	25416956
LZTS2_HUMAN	LZTS2	physical	25416956
ZBTB9_HUMAN	ZBTB9	physical	25416956
WDR62_HUMAN	WDR62	physical	25416956
UB2D1_HUMAN	UBE2D1	physical	23362280
DCAF5_HUMAN	DCAF5	physical	19287380
TBK1_HUMAN	TBK1	physical	26407194
RNF8_HUMAN	RNF8	physical	28194753
SAV1_HUMAN	SAV1	physical	27173435
KIF3C_HUMAN	KIF3C	physical	27173435
KIF3B_HUMAN	KIF3B	physical	27173435
UBR5_HUMAN	UBR5	physical	28242748
DCAF1_HUMAN	VPRBP	physical	28242748
DDB1_HUMAN	DDB1	physical	28242748
CEP78_HUMAN	CEP78	physical	28242748

Drug and Disease Associations

Kegg Disease
There are no disease associations of PTM sites.
OMIM Disease
There are no disease associations of PTM sites.
Kegg Drug
There are no disease associations of PTM sites.
DrugBank
There are no disease associations of PTM sites.

Regulatory Network of DYRK2_HUMAN

Related Literatures of Post-Translational Modification

Phosphorylation
Reference	PubMed
"ATM augments nuclear stabilization of DYRK2 by inhibiting MDM2 in theapoptotic response to DNA damage."; Taira N., Yamamoto H., Yamaguchi T., Miki Y., Yoshida K.; J. Biol. Chem. 285:4909-4919(2010). Cited for: SUBCELLULAR LOCATION, PHOSPHORYLATION AT THR-106 AND SER-442 BY ATM,UBIQUITINATION BY MDM2, INTERACTION WITH MDM2, MUTAGENESIS OF THR-106;SER-442 AND 189-LYS--ARG-191, NUCLEAR LOCALIZATION SIGNAL, ANDINDUCTION BY DNA DAMAGE.	19965871 [Abstract]
"A quantitative atlas of mitotic phosphorylation."; Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,Elledge S.J., Gygi S.P.; Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-382, AND MASSSPECTROMETRY.	18669648 [Abstract]
"Global survey of phosphotyrosine signaling identifies oncogenickinases in lung cancer."; Rikova K., Guo A., Zeng Q., Possemato A., Yu J., Haack H., Nardone J.,Lee K., Reeves C., Li Y., Hu Y., Tan Z., Stokes M., Sullivan L.,Mitchell J., Wetzel R., Macneill J., Ren J.M., Yuan J.,Bakalarski C.E., Villen J., Kornhauser J.M., Smith B., Li D., Zhou X.,Gygi S.P., Gu T.-L., Polakiewicz R.D., Rush J., Comb M.J.; Cell 131:1190-1203(2007). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-382, AND MASSSPECTROMETRY.	18083107 [Abstract]

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