AiPD: Autoinhibited Protein Database

Q5F3L1

Gene name	RPS6KA5 (RCJMB04_14g1)
Protein name	Ribosomal protein S6 kinase alpha-5
Names	S6K-alpha-5 , EC 2.7.11.1
Species	Gallus gallus (Chicken)
KEGG Pathway	gga:423408
EC number	2.7.11.1: Protein-serine/threonine kinases
Protein Class

Descriptions

The 90-kDa ribosomal S6 kinase 2 (RSK2) is broadly expressed in response to growth factors, peptide hormones, neurotransmitters, chemokines and other stimuli. RSK2 is a serine/threonine kinase containing two distinct catalytically functional kinase domains connected by a linker region. The C-terminal domain (CTD) phosphorylates the linker region and regulates the N-terminal domain, which phosphorylates various substrates. The scaffold of the RSK2 CTD is stabilized by the αL-helix, which is located underneath the catalytic cleft and embedded in the kinase scaffold. On the basis of this structure of the CTD of RSK2, ERKs are likely to be involved in abolishing the autoinhibitory function of the CTD. The ERKs binding site (residues 726-735) is located at the RSK2 C terminus close to the αL-helix (residues 697-712). Efficient activation of RSK2 requires interaction with extracellular signal-regulated protein kinases (ERKs) at a docking site in the RSK2 C terminus (residues 726-735) and subsequent phosphorylation of Thr-577 in the CTD T-activation loop.

Autoinhibitory domains (AIDs)

699-714 (Putative autoinhibitory alpha helix) SS

Target domain	402-677 (Protein kinase domain)
Relief mechanism	PTM, Partner binding
Assay

AID

699-714 (Putative autoinhibitory alpha helix)

Target domain

402-677 (Protein kinase domain)

Relief mechanism

PTM (Phosphorylation by ERK1/2), Partner binding (Binding of ERKs to C-terminal ERK-binding site (726-735))

Assay

Accessory elements

184-208 (Activation loop from InterPro)

Target domain	39-309 (Protein kinase domain)
Relief mechanism
Assay

554-577 (Activation loop from InterPro)

Target domain	415-678 (Protein kinase domain)
Relief mechanism
Assay

References

Li D et al. (2012) "Structural basis for the autoinhibition of the C-terminal kinase domain of human RSK1", Acta crystallographica. Section D, Biological crystallography, 68, 680-5

Li D et al. (2013) "The prometastatic ribosomal S6 kinase 2-cAMP response element-binding protein (RSK2-CREB) signaling pathway up-regulates the actin-binding protein fascin-1 to promote tumor metastasis", The Journal of biological chemistry, 288, 32528-32538

Malakhova M et al. (2008) "Structural basis for activation of the autoinhibitory C-terminal kinase domain of p90 RSK2", Nature structural & molecular biology, 15, 112-3

Poteet-Smith CE et al. (1999) "Generation of constitutively active p90 ribosomal S6 kinase in vivo. Implications for the mitogen-activated protein kinase-activated protein kinase family", The Journal of biological chemistry, 274, 22135-8

Autoinhibited structure

Activated structure

1 structures for Q5F3L1

Entry ID	Method	Resolution	Chain	Position	Source
AF-Q5F3L1-F1	Predicted				AlphaFoldDB

2 variants for Q5F3L1

Variant ID(s)	Position	Change	Description	Diseaes Association	Provenance
rs739083772	649	E>G		No	EVA
rs738683446	652	E>G		No	EVA

No associated diseases with Q5F3L1

8 regional properties for Q5F3L1

Type	Name	Position	InterPro Accession
domain	Protein kinase domain	39 - 308	IPR000719-1
domain	Protein kinase domain	416 - 677	IPR000719-2
domain	AGC-kinase, C-terminal	309 - 377	IPR000961
active_site	Serine/threonine-protein kinase, active site	163 - 175	IPR008271-1
active_site	Serine/threonine-protein kinase, active site	530 - 542	IPR008271-2
binding_site	Protein kinase, ATP binding site	45 - 71	IPR017441-1
binding_site	Protein kinase, ATP binding site	422 - 445	IPR017441-2
domain	Protein kinase, C-terminal	329 - 367	IPR017892

Functions

		Description
EC Number	2.7.11.1	Protein-serine/threonine kinases
Subcellular Localization	Nucleus
PANTHER Family
PANTHER Subfamily
PANTHER Protein Class
PANTHER Pathway Category	No pathway information available

2 GO annotations of cellular component

Name	Definition
cytoplasm	The contents of a cell excluding the plasma membrane and nucleus, but including other subcellular structures.
nucleoplasm	That part of the nuclear content other than the chromosomes or the nucleolus.

8 GO annotations of molecular function

Name	Definition
ATP binding	Binding to ATP, adenosine 5'-triphosphate, a universally important coenzyme and enzyme regulator.
histone H2AS1 kinase activity	Catalysis of the reaction
histone H3S10 kinase activity	Catalysis of the reaction
histone H3S28 kinase activity	Catalysis of the reaction
magnesium ion binding	Binding to a magnesium (Mg) ion.
protein serine kinase activity	Catalysis of the reactions
protein serine/threonine kinase activity	Catalysis of the reactions
protein tyrosine kinase activity	Catalysis of the reaction

8 GO annotations of biological process

Name	Definition
interleukin-1-mediated signaling pathway	The series of molecular signals initiated by interleukin-1 binding to its receptor on the surface of a target cell, and ending with the regulation of a downstream cellular process, e.g. transcription.
intracellular signal transduction	The process in which a signal is passed on to downstream components within the cell, which become activated themselves to further propagate the signal and finally trigger a change in the function or state of the cell.
negative regulation of DNA-templated transcription	Any process that stops, prevents, or reduces the frequency, rate or extent of cellular DNA-templated transcription.
phosphorylation	The process of introducing a phosphate group into a molecule, usually with the formation of a phosphoric ester, a phosphoric anhydride or a phosphoric amide.
positive regulation of transcription by RNA polymerase II	Any process that activates or increases the frequency, rate or extent of transcription from an RNA polymerase II promoter.
post-translational protein modification	The process of covalently altering one or more amino acids in a protein after the protein has been completely translated and released from the ribosome.
regulation of DNA-templated transcription	Any process that modulates the frequency, rate or extent of cellular DNA-templated transcription.
regulation of postsynapse organization	Any process that modulates the physical form of a postsynapse.

17 homologous proteins in AiPD

UniProt AC	Gene Name	Protein Name	Species	Evidence Code
P18652	RPS6KA	Ribosomal protein S6 kinase 2 alpha	Gallus gallus (Chicken)	SS
Q9UK32	RPS6KA6	Ribosomal protein S6 kinase alpha-6	Homo sapiens (Human)	SS
O75676	RPS6KA4	Ribosomal protein S6 kinase alpha-4	Homo sapiens (Human)	SS
Q96S38	RPS6KC1	Ribosomal protein S6 kinase delta-1	Homo sapiens (Human)	PR
P51812	RPS6KA3	Ribosomal protein S6 kinase alpha-3	Homo sapiens (Human)	EV
Q15349	RPS6KA2	Ribosomal protein S6 kinase alpha-2	Homo sapiens (Human)	SS
Q15418	RPS6KA1	Ribosomal protein S6 kinase alpha-1	Homo sapiens (Human)	EV
O75582	RPS6KA5	Ribosomal protein S6 kinase alpha-5	Homo sapiens (Human)	SS
Q9WUT3	Rps6ka2	Ribosomal protein S6 kinase alpha-2	Mus musculus (Mouse)	SS
Q9Z2B9	Rps6ka4	Ribosomal protein S6 kinase alpha-4	Mus musculus (Mouse)	SS
P18654	Rps6ka3	Ribosomal protein S6 kinase alpha-3	Mus musculus (Mouse)	SS
Q8BLK9	Rps6kc1	Ribosomal protein S6 kinase delta-1	Mus musculus (Mouse)	PR
P18653	Rps6ka1	Ribosomal protein S6 kinase alpha-1	Mus musculus (Mouse)	SS
Q8C050	Rps6ka5	Ribosomal protein S6 kinase alpha-5	Mus musculus (Mouse)	PR
Q63531	Rps6ka1	Ribosomal protein S6 kinase alpha-1	Rattus norvegicus (Rat)	SS
Q21734	rskn-1	Putative ribosomal protein S6 kinase alpha-1	Caenorhabditis elegans	SS
Q18846	rskn-2	Putative ribosomal protein S6 kinase alpha-2	Caenorhabditis elegans	PR

10	20	30	40	50	60
MEGPSGSAQG	SEWPLLTVTH	ELRNANLTGH	AEKVGIENFE	LLKVLGTGAY	GKVFLVRKVS
70	80	90	100	110	120
GHDAGKLYAM	KVLKKATIVQ	KAKTTEHTRT	ERQVLEHIRQ	SPFLVTLHYA	FQTDTKLHLI
130	140	150	160	170	180
LDYINGGELF	THLSQRERFS	ENEVQIYIGE	IVLALEHLHK	LGIIYRDIKL	ENILLDSDGH
190	200	210	220	230	240
VVLTDFGLSK	EFLTDENERA	YSFCGTIEYM	APDIVRGGDT	GHDKAVDWWS	VGVLMYELLT
250	260	270	280	290	300
GASPFTVDGE	KNSQAEISRR	ILKSEPPYPQ	EMSALSKDII	QRLLMKDPKK	RLGCGPTDAD
310	320	330	340	350	360
EIKQHPFFQN	INWDDLAAKK	VPAPFKPVIR	DELDVSNFAE	EFTEMDPTYS	PAATPQTSEK
370	380	390	400	410	420
IFQGYSFVAP	SILFKRNAAT	VDPVQFYVGD	ERPGTTTIAR	SAMMKDSPFF	QHYELDLKEK
430	440	450	460	470	480
PLGEGSFSIC	RKCLHKKTSQ	EYAVKIISKR	MEANTQREIT	ALKLCEGHPN	VVKLHEVYHD
490	500	510	520	530	540
QLHTFLVMEL	LKGGELLERI	QKKQHFSETE	ASHIMRRLVS	AVSHMHDVGV	VHRDLKPENL
550	560	570	580	590	600
LFTDETDNSE	IKIIDFGFAR	LKPPDNQPLK	TPCFTLHYAA	PELFNHNGYD	ESCDLWSLGV
610	620	630	640	650	660
ILYTMLSGQV	PFQSQDKSLT	CTSALEIMKK	IKKGEFSFEG	EAWKNVSEEA	KELIQGLLTV
670	680	690	700	710	720
DPNKRIKMSS	LRYNEWLQDG	SQLSSNPLMT	PDNLGSSGAA	VHTYVKATFH	AFNKYKREGF
730	740	750	760	770	780
CLQNVDKAPL	AKRRKMKKTS	TSTETRSSSS	ESSHSSSSHS	HGKTTPTKTL	QPTNPTDSNN

PETIFQFSD