LIMK1_MOUSE - PTM Information in dbPTM

Basic Information of Protein

• UniProt ID: LIMK1_MOUSE
• UniProt AC: P53668
• Protein Name: LIM domain kinase 1
• Gene Name: Limk1
• Organism: Mus musculus (Mouse).
• Sequence Length: 647
• Subcellular Localization: Cytoplasm . Nucleus. Cell projection, lamellipodium . Predominantly found in the cytoplasm (By similarity). Localizes in the lamellipodium in a CDC42BPA, CDC42BPB and FAM89B/LRAP25-dependent manner.
• Protein Description: Serine/threonine-protein kinase that plays an essential role in the regulation of actin filament dynamics. Acts downstream of several Rho family GTPase signal transduction pathways. Activated by upstream kinases including ROCK1, PAK1 and PAK4, which phosphorylate LIMK1 on a threonine residue located in its activation loop. LIMK1 subsequently phosphorylates and inactivates the actin binding/depolymerizing factors cofilin-1/CFL1, cofilin-2/CFL2 and destrin/DSTN, thereby preventing the cleavage of filamentous actin (F-actin), and stabilizing the actin cytoskeleton. In this way LIMK1 regulates several actin-dependent biological processes including cell motility, cell cycle progression, and differentiation. Phosphorylates TPPP on serine residues, thereby promoting microtubule disassembly. axonal outgrowth and may be involved in brain development. Required for atypical chemokine receptor ACKR2-induced phosphorylation of cofilin (CFL1) (By similarity). Stimulates axonal outgrowth and may be involved in brain development..
• Protein Sequence: MRLTLLCCTWREERMGEEGSELPVCASCGQRIYDGQYLQALNADWHADCFRCCECSVSLSHQYYEKDGQLFCKKDYWARYGESCHGCSEHITKGLVMVAGELKYHPECFICLACGNFIGDGDTYTLVEHSKLYCGQCYYQTVVTPVIEQILPDSPGSHLPHTVTLVSIPASAHGKRGLSVSIDPPHGPPGCGTEHSHTVRVQGVDPGCMSPDVKNSIHVGDRILEINGTPIRNVPLDEIDLLIQETSRLLQLTLEHDPHDSLGHGPVSDPSPLSSPVHTPSGQAASSARQKPVLRSCSIDTSPGTSSLASPASQRKDLGRSESLRVVCRPHRIFRPSDLIHGEVLGKGCFGQAIKVTHRETGEVMVMKELIRFDEETQRTFLKEVKVMRCLEHPNVLKFIGVLYKDKRLNFITEYIKGGTLRGIIKNMDSQYPWSQRVSFAKDIASGMAYLHSMNIIHRDLNSHNCLVRENRNVVVADFGLARLMIDEKNQSEDLRSLKKPDRKKRYTVVGNPYWMAPEMINGRSYDEKVDVFSFGIVLCEIIGRVNADPDYLPRTMDFGLNVRGFLDRYCPPNCPPSFFPITVRCCDLDPEKRPSFVKLEQWLETLRMHLSGHLPLGPQLEQLERGFWETYRRGESSLPAHPEVPD

Overview of Protein Modification Sites with Functional and Structural Information

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
20	O-linked_Glycosylation	ERMGEEGSELPVCAS HHCCCCCCCCCEEEC	38.96	30016717
28	S-palmitoylation	ELPVCASCGQRIYDG CCCEEECCCCEEECC	2.61	28680068
210	Phosphorylation	GVDPGCMSPDVKNSI CCCCCCCCCCCCCCE	23.25	25521595
229	Phosphorylation	RILEINGTPIRNVPL EEEEECCEECCCCCH	15.85	22324799
261	Phosphorylation	LEHDPHDSLGHGPVS HCCCCCCCCCCCCCC	32.96	29899451
271	Phosphorylation	HGPVSDPSPLSSPVH CCCCCCCCCCCCCCC	43.39	22817900
274	Phosphorylation	VSDPSPLSSPVHTPS CCCCCCCCCCCCCCC	35.66	21183079
275	Phosphorylation	SDPSPLSSPVHTPSG CCCCCCCCCCCCCCC	38.33	22817900
279	Phosphorylation	PLSSPVHTPSGQAAS CCCCCCCCCCCCCCC	21.27	22817900
281	Phosphorylation	SSPVHTPSGQAASSA CCCCCCCCCCCCCCH	44.70	29899451
296	Phosphorylation	RQKPVLRSCSIDTSP HCCCEEEECCCCCCC	14.19	25521595
298	Phosphorylation	KPVLRSCSIDTSPGT CCEEEECCCCCCCCC	25.42	24925903
301	Phosphorylation	LRSCSIDTSPGTSSL EEECCCCCCCCCCCC	34.84	25619855
302	Phosphorylation	RSCSIDTSPGTSSLA EECCCCCCCCCCCCC	19.99	24925903
305	Phosphorylation	SIDTSPGTSSLASPA CCCCCCCCCCCCCCH	20.66	25619855
306	Phosphorylation	IDTSPGTSSLASPAS CCCCCCCCCCCCCHH	29.30	25619855
307	Phosphorylation	DTSPGTSSLASPASQ CCCCCCCCCCCCHHH	28.00	25619855
310	Phosphorylation	PGTSSLASPASQRKD CCCCCCCCCHHHCCC	26.71	24925903
313	Phosphorylation	SSLASPASQRKDLGR CCCCCCHHHCCCCCC	33.62	25619855
321	Phosphorylation	QRKDLGRSESLRVVC HCCCCCCCCCCEEEE	29.73	26060331
323	Phosphorylation	KDLGRSESLRVVCRP CCCCCCCCCEEEECC	23.79	25266776
337	Phosphorylation	PHRIFRPSDLIHGEV CCCCCCHHHCCCCEE	40.57	-
492	Phosphorylation	MIDEKNQSEDLRSLK HCCCCCCCHHHHHCC	42.33	27681418
497	Phosphorylation	NQSEDLRSLKKPDRK CCCHHHHHCCCCCCC	52.41	27681418
508	Phosphorylation	PDRKKRYTVVGNPYW CCCCCCEEEECCCCC	16.85	19553453

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
310	S	Phosphorylation	Kinase	MAPK14	P47811	GPS
323	S	Phosphorylation	Kinase	MAPKAPK2	P49138	Uniprot
508	T	Phosphorylation	Kinase	ROCK1	P70335	Uniprot
-	K	Ubiquitination	E3 ubiquitin ligase	Rlim	Q9WTV7	PMID:22199232
-	K	Ubiquitination	E3 ubiquitin ligase	Rnf6	Q9DBU5	PMID:22199232

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Function	Reference
323	S	Phosphorylation	Phosphorylated at Ser-323 by MAPKAPK2 during activation of VEGFA-induced signaling, which results in activation of LIMK1 and promotion of actin reorganization, cell migration, and tubule formation of endothelial cells.	-
508	T	Phosphorylation	Phosphorylated on Thr-508 by ROCK1 and PAK1, resulting in activation.	25107909

Disease-associated PTM Sites based on SAP

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

Oops, there are no SNP-PTM records of LIMK1_MOUSE !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
RNF6_MOUSE	Rnf6	physical	16204183
PAXI_MOUSE	Pxn	physical	15023529
LIMK2_MOUSE	Limk2	physical	16399995

Drug and Disease Associations

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