dbPTM

M3K5_MOUSE - PTM Information in dbPTM

Basic Information of Protein

Overview of Protein Modification Sites with Functional and Structural Information
UniProt ID	M3K5_MOUSE
UniProt AC	O35099
Protein Name	Mitogen-activated protein kinase kinase kinase 5
Gene Name	Map3k5
Organism	Mus musculus (Mouse).
Sequence Length	1380
Subcellular Localization	Cytoplasm. Endoplasmic reticulum. Interaction with 14-3-3 proteins alters the distribution of MAP3K5/ASK1 and restricts it to the perinuclear endoplasmic reticulum region..
Protein Description	Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. Plays an important role in the cascades of cellular responses evoked by changes in the environment. Mediates signaling for determination of cell fate such as differentiation and survival. Plays a crucial role in the apoptosis signal transduction pathway through mitochondria-dependent caspase activation. MAP3K5/ASK1 is required for the innate immune response, which is essential for host defense against a wide range of pathogens. Mediates signal transduction of various stressors like oxidative stress as well as by receptor-mediated inflammatory signals, such as the tumor necrosis factor (TNF) or lipopolysaccharide (LPS). Once activated, acts as an upstream activator of the MKK/JNK signal transduction cascade and the p38 MAPK signal transduction cascade through the phosphorylation and activation of several MAP kinase kinases like MAP2K4/SEK1, MAP2K3/MKK3, MAP2K6/MKK6 and MAP2K7/MKK7. These MAP2Ks in turn activate p38 MAPKs and c-jun N-terminal kinases (JNKs). Both p38 MAPK and JNKs control the transcription factors activator protein-1 (AP-1)..
Protein Sequence	MGTEAGEGITFSVPPFASVGFCTIPEGGSCRRGGGAATAAEGEPSLQPLLVPPPPPPPGSFWNVESAAAPGTSCPTTAPGSSATRGRGNSGSGGGRRTTVAYVINEASQGQLVVAESEALQSLREACEAVGATLETLHFGKLDFGETAVLDRFYNADIAVVEMSDAFRQPSLFYHLGVRESFSMANNIILYCDTNSDSLQSLKEIICQKNTVCTGNYTFIPYMVTPHNKVYCCDSSFMKGLTELMQPNFELLLGPICLPLVDRFVQLLKVAQASSSQYFRESILSDIRKARNLYTGKELAAELARIRQRVDNIEVLTADIVINLLLSYRDIQDYDSIVKLVETLEKLPTFDLASHHHVKFHYAFALNRRNLPGDRAKALDIMIPMVQSEEQVASDMYCLVGRIYKDMFLDSNFTDTESRDHGASWFKKAFESEPTLQSGINYAVLLLAAGHQFESSFELRKVGVKLSSLLGKKGNLEKLQSYWEVGFFLGASVLANDHLRVIQASEKLFRLKTPAWYLKSIVETILIYKHFVKLTTEQPSAKQELVDFWMDFLVEATKTDVTVVRFPVLILEPTKIYQPSYLSINNEVEEKTISIWHVLPDDKKGIHEWNFGASSVRGVSISKFEERCCFLYVLHNSDDFQIYFCTELHCKRFFEMVNTITEEKGRGAEDGDCEGDSLEYDYEYDENGDRVVLGKGTYGIVYAGRDLSNQVRIAIKEIPERDSRYSQPLHEEIALHKHLKHKNIVQYLGSFSENGFIKIFMEQVPGGSLSALLRSKWGPLKDNEQTIGFYTKQILEGLKYLHDNQIVHRDIKGDNVLINTYSGVLKISDFGTSKRLAGINPCTETFTGTLQYMAPEIIDKGPRGYGKAADIWSLGCTIIEMATGKPPFYELGEPQAAMFKVGMFKVHPEIPESMSAEAKAFILKCFEPDPDKRACANDLLIDEFLKVSSKKKKTQPKLSALSTGSNEYLRSISLPVPVLVEDTSSSSEYGSVSPDTELKADPFSFKARAKSCGEKDGKGIRTLFLGIPDENFEDHSAPPSPEEKDSGFFMLRKDSERRATLHRILTEDQDKVVRNLMESLAQGAEEPKLKWEHITTLISSLREFVRSTDRKIIATTLSKLKLELDFDSHGISQVQVVLFGFQDAVNKVLRNHNIKPHWMFALDSIIRKAVQTAITILVPELRPHFSLASESDTADPEDLDVEDEHEELSSNQTVRRPQAITEDAVATSGVSTLSSTVSHDSQNAHRSLNVQLGRMKIETNRLLEELVRKERELQALLHQAIEEKDQEIRHLKLKSQPIDIPGFPVCHLNSPGTTTEDSELPGWLRENGADEDTISRFLAEDYTLVDVLYYVTRDDLKCLRLRGGMLCTLWKAIIDFRNKC

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
3	Phosphorylation	-----MGTEAGEGIT -----CCCCCCCCCE	34.22	28059163
12	Phosphorylation	AGEGITFSVPPFASV CCCCCEEECCCCCEE	25.68	28059163
90	Phosphorylation	ATRGRGNSGSGGGRR CCCCCCCCCCCCCCC	36.84	22817900
432	Phosphorylation	WFKKAFESEPTLQSG HHHHHHCCCCCHHHH	42.28	-
438	Phosphorylation	ESEPTLQSGINYAVL CCCCCHHHHCHHHHH	44.76	-
725	Phosphorylation	IPERDSRYSQPLHEE CCCCCCCCCCCHHHH	18.66	-
820	Phosphorylation	GDNVLINTYSGVLKI CCCEEEEEECCEEEH	16.45	-
832	Phosphorylation	LKISDFGTSKRLAGI EEHHHCCCCCCCCCC	30.94	28464351
833	Phosphorylation	KISDFGTSKRLAGIN EHHHCCCCCCCCCCC	19.02	28285833
843	Phosphorylation	LAGINPCTETFTGTL CCCCCCCCCCCCCCH	39.04	22322096
845	Phosphorylation	GINPCTETFTGTLQY CCCCCCCCCCCCHHH	14.35	22399290
847	Phosphorylation	NPCTETFTGTLQYMA CCCCCCCCCCHHHHC	36.35	23984901
849	Phosphorylation	CTETFTGTLQYMAPE CCCCCCCCHHHHCHH	13.97	11920685
962	Phosphorylation	QPKLSALSTGSNEYL CCCCHHCCCCCCHHH	30.36	24719451
963	Phosphorylation	PKLSALSTGSNEYLR CCCHHCCCCCCHHHH	45.54	25266776
965	Phosphorylation	LSALSTGSNEYLRSI CHHCCCCCCHHHHHC	26.95	21082442
968	Phosphorylation	LSTGSNEYLRSISLP CCCCCCHHHHHCCCC	16.21	26643407
971	Phosphorylation	GSNEYLRSISLPVPV CCCHHHHHCCCCCCE	17.59	27087446
973	Phosphorylation	NEYLRSISLPVPVLV CHHHHHCCCCCCEEE	28.06	30352176
983	Phosphorylation	VPVLVEDTSSSSEYG CCEEEECCCCCCCCC	19.59	-
989	Phosphorylation	DTSSSSEYGSVSPDT CCCCCCCCCCCCCCC	19.35	26745281
991	Phosphorylation	SSSSEYGSVSPDTEL CCCCCCCCCCCCCCC	20.65	29472430
993	Phosphorylation	SSEYGSVSPDTELKA CCCCCCCCCCCCCCC	20.82	27180971
996	Phosphorylation	YGSVSPDTELKADPF CCCCCCCCCCCCCCC	46.75	29899451
1022	Phosphorylation	KDGKGIRTLFLGIPD CCCCCEEEEEECCCC	21.68	27087446
1036	Phosphorylation	DENFEDHSAPPSPEE CCCCCCCCCCCCHHH	55.59	24925903
1040	Phosphorylation	EDHSAPPSPEEKDSG CCCCCCCCHHHCCCC	43.83	25521595
1066	Phosphorylation	ATLHRILTEDQDKVV HHHHHHHCCCHHHHH	34.83	-
1079	Phosphorylation	VVRNLMESLAQGAEE HHHHHHHHHHCCCCC	18.29	21659604
1099	Phosphorylation	EHITTLISSLREFVR HHHHHHHHHHHHHHH	26.82	25159016
1100	Phosphorylation	HITTLISSLREFVRS HHHHHHHHHHHHHHH	25.18	25159016
1231	Phosphorylation	AVATSGVSTLSSTVS HHHCCCCCHHHHCCC	27.44	28973931
1232	Phosphorylation	VATSGVSTLSSTVSH HHCCCCCHHHHCCCC	28.40	28973931
1238	Phosphorylation	STLSSTVSHDSQNAH CHHHHCCCCCCCCCC	22.97	28973931
1241	Phosphorylation	SSTVSHDSQNAHRSL HHCCCCCCCCCCHHH	21.65	28973931
1247	Phosphorylation	DSQNAHRSLNVQLGR CCCCCCHHHHHHHHC	17.90	30352176
1310	Phosphorylation	FPVCHLNSPGTTTED CCEEECCCCCCCCCC	30.94	22817900
1313	Phosphorylation	CHLNSPGTTTEDSEL EECCCCCCCCCCCCC	33.65	21082442
1314	Phosphorylation	HLNSPGTTTEDSELP ECCCCCCCCCCCCCC	33.82	29899451
1368	Phosphorylation	LRGGMLCTLWKAIID HCCCHHHHHHHHHHH	31.52	29899451

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
90	S	Phosphorylation	Kinase	AKT1	P31749	PSP
90	S	Phosphorylation	Kinase	AKT1	P31750	Uniprot
90	S	Phosphorylation	Kinase	AKT2	Q60823	Uniprot
90	S	Phosphorylation	Kinase	PIM1	P06803	Uniprot
845	T	Phosphorylation	Kinase	MAP3K5	O35099	GPS
845	T	Phosphorylation	Kinase	MAP3K6	O95382	GPS
845	T	Phosphorylation	Kinase	MAP3K6	Q9WTR2	Uniprot
845	T	Phosphorylation	Kinase	MELK	Q61846	Uniprot
845	T	Phosphorylation	Kinase	PDPK1	O15530	GPS
849	T	Phosphorylation	Kinase	MAP3K5	O35099	GPS
973	S	Phosphorylation	Kinase	PDPK1	O15530	GPS

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Reference
90	S	Phosphorylation	11920685
Ser-90 and Ser-1040 are inactivating phosphorylation sites, the former of which is phosphorylated by AKT1 and AKT2 (By similarity).
845	T	Phosphorylation	11920685
Phosphorylated at Thr-845 through autophosphorylation and by MAP3K6/ASK2 which leads to activation.
845	T	Phosphorylation	11920685
Thr-845 is dephosphorylated by PPP5C.
973	S	Oxidation	16648474
Phosphorylation at Ser-973 in response to oxidative stress is negatively regulated by PPIA/CYPA (By similarity).
973	S	Phosphorylation	16648474
Phosphorylated at Ser-973 which induces association of MAP3K5/ASK1 with the 14-3-3 family proteins and suppresses MAP3K5/ASK1 activity.
973	S	Phosphorylation	16648474
Phosphorylation at Ser-973 in response to oxidative stress is negatively regulated by PPIA/CYPA (By similarity).
1040	S	Phosphorylation	11920685
Ser-90 and Ser-1040 are inactivating phosphorylation sites, the former of which is phosphorylated by AKT1 and AKT2 (By similarity).

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 M3K5_MOUSE !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
DAXX_MOUSE	Daxx	physical	9743501
RBCC1_MOUSE	Rb1cc1	physical	17015619
TRAF2_MOUSE	Traf2	physical	17015619
PARK7_MOUSE	Park7	physical	17331951
MBP_HUMAN	MBP	physical	17331951

Drug and Disease Associations

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

Regulatory Network of M3K5_MOUSE

Related Literatures of Post-Translational Modification

Phosphorylation
Reference	PubMed
"Large-scale phosphorylation analysis of mouse liver."; Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.; Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-965, AND MASSSPECTROMETRY.	17242355 [Abstract]
"Murine protein serine/threonine kinase 38 activates apoptosis signal-regulating kinase 1 via Thr 838 phosphorylation."; Jung H., Seong H.A., Ha H.; J. Biol. Chem. 283:34541-34553(2008). Cited for: PHOSPHORYLATION AT THR-845.	18948261 [Abstract]
"Activation of apoptosis signal-regulating kinase 1 by the stress-induced activating phosphorylation of pre-formed oligomer."; Tobiume K., Saitoh M., Ichijo H.; J. Cell. Physiol. 191:95-104(2002). Cited for: PHOSPHORYLATION AT THR-845 AND THR-849, AND ENZYME REGULATION.	11920685 [Abstract]

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