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Protein Page:
KHS2 (human)
p Phosphorylation
ac Acetylation
me Methylation
m1 Mono-methylation
m2 Di-methylation
m3 Tri-methylation
ub Ubiquitylation
sm Sumoylation
ne Neddylation
gl O-GlcNAc
ga O-GalNAc
pa Palmitoylation
ad Adenylation
sn S-Nitrosylation
ca Caspase cleavage
sc Succinylation

Overview
KHS2 an ubiquitous protein kinase of the STE20 family. May play a role in the response to environmental stress. Regulated by amino acids and acts upstream of mTORC1 and JNK. Required for maximal S6K and 4E-BP1 phosphorylation. Interacts with PPP2R5E, a regulatory subunit of PP2A. Following amino acid withdrawal, pS170 is dephosphorylated via PP2A. The dephosphorylation of pS170 by PP2A in response to amino acid restriction inhibits mTORC1 signaling. The inhibition of PPP2R5E expression prevents the dephosphorylation of KHS2 pS170, impairing mTORC1 inhibition during amino acid withdrawal. Three alternatively spliced isoforms have been described. Note: This description may include information from UniProtKB.
Protein type: EC 2.7.11.1; Protein kinase, Ser/Thr (non-receptor); Protein kinase, STE; Kinase, protein; STE group; STE20 family; KHS subfamily
Chromosomal Location of Human Ortholog: 2p22.1
Cellular Component: cytoplasm
Molecular Function: protein serine/threonine kinase activity; protein binding; ATP binding; protein kinase activity; receptor signaling protein serine/threonine kinase activity
Biological Process: regulation of catalytic activity; JNK cascade; protein amino acid phosphorylation; response to UV
Reference #:  Q8IVH8 (UniProtKB)
Alt. Names/Synonyms: germinal center kinase-like kinase; Germinal center kinase-related protein kinase; GLK; M4K3; MAP4K3; MAPK/ERK kinase kinase kinase 3; MAPKKKK3; MEK kinase kinase 3; MEKKK 3; Mitogen-activated protein kinase kinase kinase kinase 3; RAB8IPL1
Gene Symbols: MAP4K3
Molecular weight: 101,316 Da
Basal Isoelectric point: 7.38  Predict pI for various phosphorylation states
Protein-Specific Antibodies or siRNAs from Cell Signaling Technology® Total Proteins
Select Structure to View Below

KHS2

Protein Structure Not Found.


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Sites Implicated In
enzymatic activity, induced: S170‑p

Modification Sites and Domains Show Modification Legend
Click here to view phosphorylation modifications only

Modification Sites in Parent Protein, Orthologs, and Isoforms Show Modification Legend
 

Show Multiple Sequence Alignment


 LTP 

LTP: The number of records in which this modification site was determined using site-specific methods. SS methods include amino acid sequencing, site-directed mutagenesis, modification site-specific antibodies, specific MS strategies, etc.


 HTP 

HTP: The number of records in which this modification site was assigned using ONLY proteomic discovery-mode mass spectrometry.


       human

► Hide Isoforms
 
0 3 S24-p ELIQRIGsGtyGDVy
0 2 T26-p IQRIGsGtyGDVyKA
0 4 Y27-p QRIGsGtyGDVyKAR
0 2 Y31-p sGtyGDVyKARNVNT
0 1 S158-p KLADFGVsAQITATI
1 8 S170-p ATIAKRKsFIGTPYW
0 1 S280-p VTQHLTRsLAIELLD
0 3 T327-p RNVREEKtRsEITFG
0 7 S329-p VREEKtRsEITFGQV
0 1 S361 DSDGFLDSSEEIyyT
0 1 S362 SDGFLDSSEEIyyTA
0 51 Y366-p LDSSEEIyyTARSNL
0 4 Y367-p DSSEEIyyTARSNLD
0 1 S371 EIyyTARSNLDLQLE
0 5 Y379-p NLDLQLEyGQGHQGG
0 5 Y387-p GQGHQGGyFLGANKS
0 1 S394 yFLGANKSLLKsVEE
0 10 S398-p ANKSLLKsVEEELHQ
0 2 S422-p DEGDDDEsKHSTLKA
0 1 T458 TEDENQGTIKRCPMS
0 1 M464 GTIKRCPMSGsPAKP
0 1 S465 TIKRCPMSGsPAKPS
0 2 S467-p KRCPMSGsPAKPSQV
0 1 S507-p LNGERDGsLCQQQNE
0 1 K530-ac KEKKDVPkPIsNGLP
0 2 S533-p KDVPkPIsNGLPPtP
0 2 T539-p IsNGLPPtPkVHMGA
0 1 K541-ac NGLPPtPkVHMGACF
0 3 S616-p VMNNCLLsIsGKASQ
0 1 S618-p NNCLLsIsGKASQLY
0 1 K641 DYARQMQKLPVAIPA
0 1 Y735-p LVVPEQEyPLVCVGV
0 1 S743-p PLVCVGVsRGRDFNQ
0 1 S864 RIFRLLGSDRVVVLE
0 1 P874 VVVLESRPTDNPTAN
  KHS2 iso2  
S14 ELIQRIGSGTYGDVY
T16 IQRIGSGTYGDVYKA
Y17 QRIGSGTYGDVYKAR
Y21 SGTYGDVYKARNVNT
S148 KLADFGVSAQITATI
S160 ATIAKRKSFIGTPYW
S270 VTQHLTRSLAIELLD
T317 RNVREEKTRSEITFG
S319 VREEKTRSEITFGQV
S351 DSDGFLDSSEEIYYT
S352 SDGFLDSSEEIYYTA
Y356 LDSSEEIYYTARSNL
Y357 DSSEEIYYTARSNLD
S361 EIYYTARSNLDLQLE
Y369 NLDLQLEYGQGHQGG
Y377 GQGHQGGYFLGANKS
S384 YFLGANKSLLKSVEE
S388 ANKSLLKSVEEELHQ
S412 DEGDDDESKHSTLKA
T448 TEDENQGTIKRCPMS
M454 GTIKRCPMSGSPAKP
S455 TIKRCPMSGSPAKPS
S457 KRCPMSGSPAKPSQV
S497 LNGERDGSLCQQQNE
K520 KEKKDVPKPISNGLP
S523 KDVPKPISNGLPPTP
T529 ISNGLPPTPKVHMGA
K531 NGLPPTPKVHMGACF
S606 VMNNCLLSISGKASQ
S608 NNCLLSISGKASQLY
K631 DYARQMQKLPVAIPA
Y725 LVVPEQEYPLVCVGV
S733 PLVCVGVSRGRDFNQ
S854 RIFRLLGSDRVVVLE
P864 VVVLESRPTDNPTAN
  KHS2 iso3  
S24 ELIQRIGSGTYGDVY
T26 IQRIGSGTYGDVYKA
Y27 QRIGSGTYGDVYKAR
Y31 SGTYGDVYKARNVNT
S158 KLADFGVSAQITATI
S170 ATIAKRKSFIGTPYW
S280 VTQHLTRSLAIELLD
T327 RNVREEKTRSEITFG
S329 VREEKTRSEITFGQV
- gap
- gap
- gap
- gap
- under review  
Y358 ELDLQLEYGQGHQGG
Y366-p GQGHQGGyFLGANKS
S373 yFLGANKSLLKSVEE
S377 ANKSLLKSVEEELHQ
S401 DEGDDDESKHSTLKA
T437 TEDENQGTIKRCPMS
M443 GTIKRCPMSGSPAKP
S444 TIKRCPMSGSPAKPS
S446 KRCPMSGSPAKPSQV
S486 LNGERDGSLCQQQNE
K509 KEKKDVPKPISNGLP
S512 KDVPKPISNGLPPTP
T518 ISNGLPPTPKVHMGA
K520 NGLPPTPKVHMGACF
S595 VMNNCLLSISGKASQ
S597 NNCLLSISGKASQLY
K620 DYARQMQKLPVAIPA
Y714 LVVPEQEYPLVCVGV
S722 PLVCVGVSRGRDFNQ
S843 RIFRLLGSDRVVVLE
P853 VVVLESRPTDNPTAN
  mouse

► Hide Isoforms
 
S24 ELIQRIGSGTYGDVY
T26 IQRIGSGTYGDVYKA
Y27 QRIGSGTYGDVYKAR
Y31 SGTYGDVYKARNVNT
S158 KLADFGVSAQITATI
S170 ATIAKRKSFIGTPYW
S280 VTQPLTRSLAIELLD
T327-p RNVREEKtRsEINFG
S329-p VREEKtRsEINFGQV
S361-p DSDGFFDssEEIYYT
S362-p SDGFFDssEEIYYTA
Y366 FDssEEIYYTARsNL
Y367 DssEEIYYTARsNLD
S371-p EIYYTARsNLDLQLE
Y379 NLDLQLEYGQGHQSH
C387 GQGHQSHCFLGGNKs
S394-p CFLGGNKsLLKsVEE
S398-p GNKsLLKsVEEELHQ
S422-p DEGDDDDsKHSTMKA
T458-p AEDGNQGtIKRCPss
S464-p GtIKRCPssGsPAKP
S465-p tIKRCPssGsPAKPS
S467-p KRCPssGsPAKPSHV
S507-p LNGERDGsLYQQQSE
K530 KEKKDVPKPIsNGLP
S533-p KDVPKPIsNGLPPtP
T539-p IsNGLPPtPKVHMGA
K541 NGLPPtPKVHMGACF
S616 VMNNCLLSVSGKASQ
S618 NNCLLSVSGKASQLY
K641-ac DYARQMQkLPVAIPA
Y735 LVVPEQEYPLVCVGV
S743 PLVCVGVSRGRDFNQ
S864-p RIFRLLGsDRVVVLE
P874 VVVLESRPTDNPTAN
  KHS2 var1  
S24 ELIQRIGSGTYGDVY
T26 IQRIGSGTYGDVYKA
Y27 QRIGSGTYGDVYKAR
Y31 SGTYGDVYKARNVNT
S158 KLADFGVSAQITATI
S170 ATIAKRKSFIGTPYW
S280 VTQPLTRSLAIELLD
T327 RNVREEKTRSEINFG
S329 VREEKTRSEINFGQV
S361 DSDGFFDSSEEIYYT
S362 SDGFFDSSEEIYYTA
Y366 FDSSEEIYYTARSNL
Y367 DSSEEIYYTARSNLD
S371 EIYYTARSNLDLQLE
Y379 NLDLQLEYGQGHQSH
C387 GQGHQSHCFLGGNKS
S394 CFLGGNKSLLKSVEE
S398 GNKSLLKSVEEELHQ
S422 DEGDDDDSKHSTMKA
T458 AEDGNQGTIKRCPSS
S464 GTIKRCPSSGSPAKP
S465 TIKRCPSSGSPAKPS
S467 KRCPSSGSPAKPSHV
S507 LNGERDGSLYQQQSE
K530 KEKKDVPKPISNGLP
S533 KDVPKPISNGLPPTP
T539 ISNGLPPTPKVHMGA
K541 NGLPPTPKVHMGACF
S616 VMNNCLLSVSGKASQ
S618 NNCLLSVSGKASQLY
K641 DYARQMQKLPVAIPA
Y735 LVVPEQEYPLVCVGV
S743 PLVCVGVSRGRDFNQ
S864 RIFRLLGSDRVVVLE
R874-m2 VVVLESRrTDNPTAN
  rat

 
S24 ELIQRIGSGTYGDVy
T26 IQRIGSGTYGDVyKA
Y27 QRIGSGTYGDVyKAR
Y31-p SGTYGDVyKARNVNT
S158 KLADFGVSAQITATI
S170 ATIAKRKSFIGTPYW
S280 VTQPLTRSLAIELLD
T327 RNVREEKTRSEINFG
S329 VREEKTRSEINFGQV
- gap
- gap
- gap
- gap
- under review  
Y358 ELDLQLEYGQGHQSN
Y366 GQGHQSNYFLGGNKS
S373 YFLGGNKSLLKSVEE
S377 GNKSLLKSVEEELHQ
S401 DEGDDDDSKHSTLKA
T437 SEDSNQGTIKRCPSS
S443 GTIKRCPSSGSPAKP
S444 TIKRCPSSGSPAKPS
S446 KRCPSSGSPAKPSHV
S486 LNGERDGSVHQQQSE
K509 KEKKDVPKPISNGLP
S512 KDVPKPISNGLPPTP
T518 ISNGLPPTPKVHMGA
K520 NGLPPTPKVHMGACF
S595 VMNNCLLSVSGKASQ
S597 NNCLLSVSGKASQLY
K620 DYARQMQKLPVAIPA
Y714 LVVPEQEYPLVCVGV
S722 PLVCVGVSRGRDFNQ
S843 RIFRLLGSDRVVVLE
P853 VVVLESRPTDNPTAN
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