FBXW5_HUMAN - PTM Information in dbPTM

Basic Information of Protein

• UniProt ID: FBXW5_HUMAN
• UniProt AC: Q969U6
• Protein Name: F-box/WD repeat-containing protein 5
• Gene Name: FBXW5
• Organism: Homo sapiens (Human).
• Sequence Length: 566
• Subcellular Localization: Cytoplasm .
• Protein Description: Substrate recognition component of both SCF (SKP1-CUL1-F-box protein) and DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complexes. Substrate recognition component of the SCF(FBXW5) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of SASS6 during S phase, leading to prevent centriole reduplication. The SCF(FBXW5) complex also mediates ubiquitination and degradation of actin-regulator EPS8 during G2 phase, leading to the transient degradation of EPS8 and subsequent cell shape changes required to allow mitotic progression. Substrate-specific adapter of the DCX(FBXW5) E3 ubiquitin-protein ligase complex which mediates the polyubiquitination and subsequent degradation of TSC2. May also act as a negative regulator of MAP3K7/TAK1 signaling in the interleukin-1B (IL1B) signaling pathway..
• Protein Sequence: MDEGGTPLLPDSLVYQIFLSLGPADVLAAGLVCRQWQAVSRDEFLWREQFYRYYQVARDVPRHPAAMSWYEEFQRLYDTVPCVEVQTLREHTDQVLHLSFSHSGYQFASCSKDCTVKIWSNDLTISLLHSADMRPYNWSYTQFSQFNKDDSLLLASGVFLGPHNSSSGEIAVISLDSFALLSRVRNKPYDVFGCWLTETSLISGNLHRIGDITSCSVLWLNNAFQDVESENVNVVKRLFKIQNLNASTVRTVMVADCSRFDSPDLLLEAGDPATSPCRIFDLGSDNEEVVAGPAPAHAKEGLRHFLDRVLEGRAQPQLSERMLETKVAELLAQGHTKPPERSATGAKSKYLIFTTGCLTYSPHQIGIKQILPHQMTTAGPVLGEGRGSDAFFDALDHVIDIHGHIIGMGLSPDNRYLYVNSRAWPNGAVVADPMQPPPIAEEIDLLVFDLKTMREVRRALRAHRAYTPNDECFFIFLDVSRDFVASGAEDRHGYIWDRHYNICLARLRHEDVVNSVVFSPQEQELLLTASDDATIKAWRSPRTMRVLQAPRPRPRTFFSWLASQRR

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
151	Phosphorylation	SQFNKDDSLLLASGV HHCCCCCCEEEEEEE	30.93	21725316
187	Ubiquitination	LLSRVRNKPYDVFGC HHHHHHCCCCCEEEE	34.10	-
240	Ubiquitination	NVVKRLFKIQNLNAS HHHHHHHHHCCCCCC	48.23	21890473
240 (in isoform 1)	Ubiquitination	-	48.23	21890473
240	Ubiquitination	NVVKRLFKIQNLNAS HHHHHHHHHCCCCCC	48.23	21890473
240 (in isoform 2)	Ubiquitination	-	48.23	21890473
274	Phosphorylation	LEAGDPATSPCRIFD CCCCCCCCCCEEEEE	38.29	23663014
275	Phosphorylation	EAGDPATSPCRIFDL CCCCCCCCCEEEEEC	24.90	30278072
284	Phosphorylation	CRIFDLGSDNEEVVA EEEEECCCCCCEEEC	44.55	30266825
299	Ubiquitination	GPAPAHAKEGLRHFL CCCCCHHHHHHHHHH	42.31	21890473
299 (in isoform 2)	Ubiquitination	-	42.31	21890473
299	Ubiquitination	GPAPAHAKEGLRHFL CCCCCHHHHHHHHHH	42.31	21890473
299 (in isoform 1)	Ubiquitination	-	42.31	21890473
326	Ubiquitination	SERMLETKVAELLAQ HHHHHHHHHHHHHHC	30.03	21906983
326 (in isoform 1)	Ubiquitination	-	30.03	21890473
326 (in isoform 2)	Ubiquitination	-	30.03	21890473
337	Ubiquitination	LLAQGHTKPPERSAT HHHCCCCCCCCCCCC	53.56	2190698
337 (in isoform 1)	Ubiquitination	-	53.56	21890473
337 (in isoform 2)	Ubiquitination	-	53.56	21890473
376	Phosphorylation	QILPHQMTTAGPVLG HHCCCCCCCCCCCCC	13.61	-
377	Phosphorylation	ILPHQMTTAGPVLGE HCCCCCCCCCCCCCC	25.03	-

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
151	S	Phosphorylation	Kinase	PLK4	O00444	Uniprot

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Function	Reference
151	S	Phosphorylation	Phosphorylated at Ser-151 by PLK4 during the G1/S transition, leading to inhibit its ability to ubiquitinate SASS6.	21725316
151	S	ubiquitylation	Phosphorylated at Ser-151 by PLK4 during the G1/S transition, leading to inhibit its ability to ubiquitinate SASS6.	21725316

Disease-associated PTM Sites based on SAP

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

Oops, there are no SNP-PTM records of FBXW5_HUMAN !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
KR412_HUMAN	KRTAP4-12	physical	16189514
DDB1_HUMAN	DDB1	physical	18381890
CUL4A_HUMAN	CUL4A	physical	18381890
TSC1_HUMAN	TSC1	physical	18381890
TSC2_HUMAN	TSC2	physical	18381890
CDC20_HUMAN	CDC20	physical	21725316
SAS6_HUMAN	SASS6	physical	21725316
PLK4_HUMAN	PLK4	physical	21725316
SKP1_HUMAN	SKP1	physical	22388891
REST_HUMAN	REST	physical	18354482
SKP1_HUMAN	SKP1	physical	15070733
CUL1_HUMAN	CUL1	physical	14603323
RHG07_HUMAN	DLC1	physical	24082123
TP8L1_HUMAN	TNFAIP8L1	physical	24444419
TP8L1_HUMAN	TNFAIP8L1	physical	24372178
TSC2_HUMAN	TSC2	physical	24372178
CUL1_HUMAN	CUL1	physical	23319600
SKP1_HUMAN	SKP1	physical	23319600
CUL1_HUMAN	CUL1	physical	25143387
ATL4_HUMAN	ADAMTSL4	physical	25416956
KRA94_HUMAN	KRTAP9-4	physical	25416956
K1C40_HUMAN	KRT40	physical	25416956
KR108_HUMAN	KRTAP10-8	physical	25416956
KR103_HUMAN	KRTAP10-3	physical	25416956
NT2NL_HUMAN	NOTCH2NL	physical	25416956
CUL1_HUMAN	CUL1	physical	25515538
S100B_HUMAN	S100B	physical	21516116
SKP1_HUMAN	SKP1	physical	26087183

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.

Related Literatures of Post-Translational Modification

Phosphorylation

"The SCF-FBXW5 E3-ubiquitin ligase is regulated by PLK4 and targetsHsSAS-6 to control centrosome duplication.";
Puklowski A., Homsi Y., Keller D., May M., Chauhan S., Kossatz U.,Grunwald V., Kubicka S., Pich A., Manns M.P., Hoffmann I., Gonczy P.,Malek N.P.;
Nat. Cell Biol. 13:1004-1009(2011).
Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH SASS6 AND CDC20,IDENTIFICATION IN A SCF PROTEIN LIGASE COMPLEX, DEVELOPMENTAL STAGE,UBIQUITINATION, PHOSPHORYLATION AT SER-151, AND MUTAGENESIS OFSER-151.
PubMed: 21725316