. Author manuscript; available in PMC: 2020 Sep 1.

Published in final edited form as: Chem Rev. 2018 Dec 14;118(24):11707–11794. doi: 10.1021/acs.chemrev.8b00333

Table 1.

Engineered genetically encoded fluorescent biosensors are organized by their signaling targets. For each signaling target, the different published biosensors are organized into families of related variants (with the family or group name shown in bold). The different read-out mechanisms utilized are shown with the different icons indicating the type of readout for a given biosensor. The different readout mechanisms shown in this table are: Bioluminescence intensity (●), BRET (◓), Intensity-based FRET ( Inline graphic ), FLIM-FRET (♣), FLINC (), Intensity (), Ratiometric (with a reference FP) (◧), Excitation Ratiometric (★), Emission Ratiometric (☆), and Translocation (). Additional details, including biosensor components and FPs involved, etc., can be found in the supplemental materials and at BiosensorDB.ucsd.edu

Target	Readout Mech	Variants
Cell Cycle
Cell Cycle Phases	Inten. ()	Fucci: Fucci(CA)2.1 (2017)²⁰⁷ Fucci4 (2016)²⁰⁸NIR Fucci (2016)²⁰⁹ NIR cell cycle reporter (2016)²¹⁰ Fucci2.1 (2013)²¹¹Fucci2 (2011)²¹²zFucci(2009)²¹³S/G2/M-X(NC) (2008)²¹⁴Fucci (2008)²¹⁵
G1 Phase	Trans. ()	G1 Phase Biosensor (2009)²¹⁶
S Phase	Trans. ()	S Phase Biosensor (2009)²¹⁶
Cell Environment
Mechanical Strain	FRET () Ex. Rat.(★)	HP35: HP35st-TS (2015)²¹⁷HP35-TS (2015)²¹⁷ PriSSM (2008)²¹⁸ ★ stFRET: cpstFRET (2012)²¹⁹sstFRET(2011)²²⁰stFRET (2008)²²¹ TSMod: TSMod F25 (2016)²²²TSMod (2010)²²³
pH	Em. Rat. (☆) Rat. (◧) FRET () Inten. () Ex. Rat.(★)	deGFP: deGFP family (2002)¹³⁰☆ Dual pH and Cl sensor: ClopHensor(2010)¹³⁸◧ E^xGFP: E¹GFP (2007)¹³⁷ ◧ E²GFP (2006)¹³⁴ ◧ FluBpH: FluBpH 7.5 (2017)²²⁴ FluBpH 6.1 (2017)²²⁴ FluBpH 5.7 (2017)²²⁴ mtAlpHi (2004)²²⁵ Native FP pH Sensitivity: mNect (2009)²²⁶pHVenus(2007)¹²⁵ CFP-YFP pH FRET (2004)²²⁷ EYFP (1998)¹²¹ EGFP (1998)¹²⁰ pHCEC: pHCECSensor01 (2008)²²⁸ ◧ pHluorins: pHluorin2 (2011)²²⁹ ★Superecliptic-pHluorin (2000)¹²² ratiometric-pHluorin (1998)¹¹⁷★ Ecliptic-pHluorin (1998)¹¹⁷ pHRed (2011)²³⁰★ pHTomato (2012)¹²³ pHuji (2014)²³¹ pHusion (2012)²³²◧ SypHer (2011)²³³ XFpH: YFpH (2001)²³⁴ GFpH (2001)²³⁴
Membrane Voltage (V⁺)	Inten. () BRET(◓) Rat. (◧) FRET ()	ArcLight Species Variants: Human Q193 ArcLight (2013)²³⁵ Zebrafish Q175 ArcLight (2013)²³⁵ Chicken Q175 ArcLight (2013)²³⁵ Frog Q174 ArcLight (2013)²³⁵ Ci-VSP based: VSD-FR189–188 (2017)²³⁶ LOTUS-V (2017)²³⁷ ◓ Marina (2017)²³⁸ tdFlicR1 Δ110AR (2016)²³⁹ FlicGR1 (2016)²³⁹ ASAP2f (2016)¹⁷⁶ tdFlicR-VK-ASAP (2016)²³⁹ ◧ FlicR1 (2016)¹⁷⁷ Bongwoori (2015)²⁴⁰ ArcLightning (2015)²⁴¹ Nabi2.213 (2015)²⁴² ASAP1 (2014)¹⁶⁷ Chimeric VSFP-Butterfly YR (2014)²⁴³ Chimeric VSFP-Butterfly CY (2014)²⁴³ Mermaid2 (2013)²⁴⁴ ArcLight A242 (2012)²⁴⁵ Chimera Cx (2012)²⁴⁶ VSFP-CR (2012)²⁴⁷ ElectricPk (2012)¹⁷⁴ VSFP Butterfly 1.2 (2012)²⁴⁸ VSFP2.3 (2010)²⁴⁹ VSFP2.42 (2010)²⁵⁰ VSFP2.4 (2009)²⁵¹ VSFP3.1 (2008)¹⁷² Mermaid (2008)²⁵² VSFP2.1 (2007)²⁵³ Danio VSP based: Zahara 2 SE (227D) (2015)²⁵⁴ Zahra 1 SE (227D) series (2015)²⁵⁴ Zahra 1 (2012)²⁵⁵ Zahra 2 (2012)²⁵⁵ Kv based: FlaSH (CFP) + FlaSh (YFP) (2002)²⁵⁶ FlaSh L366A (2002)²⁵⁶ FlaSh IR (2002)²⁵⁶ VSFP1 (2001)²⁵⁷ FlaSh (1997)¹⁶⁸ Na Channel based: SPARC (2002)¹⁶⁹ Nematostella VSP based: Nema (2012)²⁵⁵ Rhodopsin based: Archon1 (2018)²⁵⁸ Archon2 (2018)²⁵⁸ FRET-opsin Ace1Q-mNeon (2015)²⁵⁹ FRET-opsin Ace2N-mNeon (2015)²⁵⁹ QuasAr2 (2014)²⁶⁰ QuasAr1 (2014)²⁶⁰ Archer1 (2014)²⁶¹ eFRET GEVI (2014)²⁶² FRET-opsin Mac-mCitrine (2014)²⁶³ Arch-EEx variants (2013)²⁶⁴ PROPS (2011)²⁶⁵ Arch(D95N) (2011)²⁶⁶
Cellular Analytes
2-Oxoglutarate	Inten. ()	mOGsor (2014)²⁶⁷
Ammonium	Rat. (◧) Inten. ()	AmTrac: AmTryoshika1;3-LS-F138I -T78H (2017)²⁰⁶◧ AmTryoshika1;3-LS-F138I (2017)²⁰⁶◧ AmTrac (2013)²⁶⁸
Arabinose	FRET ()	FLIPara: FLIPara-250n (2008)²⁶⁹
Arginine	FRET ()	FRET Arg Reporter (2007)²⁷⁰
ATP	BRET(◓) FRET () Inten. () Biolum. (●) Ex. Rat.(★)	ATeam: BTeam (2016)²⁷¹◓ ATeam1.03NL (2013)²⁷² GO-Ateam (2011)²⁷³ ATeam3.10 (2009)²⁷⁴ ATeam1.03 (2009)²⁷⁴ EAF-ATP (2013)²⁷⁵ Nano-lantern ATP (2012)²⁷⁶● Perceval: PercevalHR (2013)²⁷⁷★ Perceval (2009)²⁷⁸★ QUEEN: QUEEN-2m (2014)²⁷⁹★ QUEEN-7mu (2014)²⁷⁹★ Syn-ATP (2014)²⁸⁰●
BDNF	FRET ()	Bescell (2008)²⁸¹
cAMP	Inten. () FRET () BRET(◓) Rat. (◧) Biolum. (●)	cADDis: cADDis-green (2016)¹⁸² Camps: Epac2-camps300-cit (2010)²⁸² Epac2-camps300 (2009)²⁸³ HCN2-camps (2006)²⁸⁴Epac2-camps (2004)²⁸⁵ Epac1-camps (2004)²⁸⁵ PKA-camps (2004)²⁸⁵ CAMYEL (2007)²⁸⁶◓ CUTie (2017)²⁸⁷ Epac-S: Epac-S H188 (2015)²⁸⁸ Epac-S H187 (2015)²⁸⁸ H74 (2011)²⁸⁹ H96 (2011)²⁸⁹ H84: CFP(nd)-EPAC(dDEP/CD)-Venus(d) (2008)²⁹⁰ H81: GFP(nd)-EPAC(ΔDEP)-mRFP (2008)²⁹⁰ H90: CFP(nd)-EPAC(ΔDEP/CD)-cp173Venus(d) (2008)²⁹⁰ Epac1 (ΔDEP-CD) based: CEPAC* (2011)²⁹¹ CFP-Epac(ΔDEP-CD)-YFP (2004)²⁹² Flamindo: Pink Flamindo (2017)¹⁸³ Flamindo2 (2014)¹⁸⁰ Flamindo (2013)¹⁶³ FPX: pPHT-PKA (2015)²⁹³◧ ICUE: ICUPID (2011)²⁹⁴ ICUE-YR (2011)²⁹⁴ ICUE3 (2009)²⁹⁵ Rluc-EPAC-YFP (2008)²⁹⁶◓ ICUE2 (2008)²⁹⁷ ICUE1 (2004)²⁹⁸ mCRIS based: cit-mCNBD-cer (2013)²⁹⁹ mICNBD-FRET (2016)³⁰⁰ Nano-lantern cAMP: Nano-lantern cAMP1.6 (2012)²⁷⁶● R1α #7 (2016)³⁰¹ Split Luc cAMP biosensor: 22F (2011)³⁰²● Split Luc cAMP biosensor (2008)³⁰³● YFP-PKAc + CFP-PKAr: ΔPKA RIIb-CFP + PKAc-YFP (2006)³⁰⁴ R2-Rluc + GFP-C (2006)³⁰⁵◓ R1-Rluc + GFP-C (2006)³⁰⁵◓ YFP-PKAc + CFP-PKAr(R230K) (2004)³⁰⁶ YFP-PKAc + CFP-PKAr (2002)³⁰⁷ PKAc-S65T + PKArII-EBFP (2000)³⁰⁸
cGMP	Inten. () FRET () Ex. Rat.(★)	cGES: Cygnus (2010)³⁰⁹ cGES-DE5 (2006)³¹⁰ cGKI based: cGi family (2007)³¹¹ cGull: Green-cGull (2017)¹⁶⁴ CGY: CGY-del1 (2000)³¹² cygnet: cygnet-2.1 (2005)³¹³ cygnet-2 (2001)³¹⁴ FlincG: H6-FGA^M (2013)³¹⁵ H6-FGB (2013)³¹⁵ δ-FlincG (2008)¹⁶⁵★
Citrate	FRET ()	FLIP-Cit: FLIP-Cit-Y (2011)³¹⁶
Carbon monoxide (CO)	Inten. ()	COSer (2012)³¹⁷
Glucose	FRET ()	FLIPglu: FLII¹²Pglu-Y Series (2008)³¹⁸ FLIPglu-YΔ13 (2006)³¹⁹ FLII^XPglu-Y Series (2005)³²⁰ FLIPglu-600u-Δ(X) series (2005)³²⁰ FLIPglu-Y series (2003)³²¹ GIP: AcGFP1-GBPcys-mCherry (2010)³²² GIP C₀Y_i (2008)³²³ GIP (2003)³²⁴
Glutamine	FRET ()	FLIPQ: FLIPQ-TV3.0 (2012)³²⁵
Heme	FRET () Rat. (◧) Inten. ()	CHY: CH49Y (2017)³²⁶ CISDY: CISDY-9 (2015)³²⁷ Fluorescence quenching Heme: HS1 (2016)³²⁸◧ HS1–M7A (2016)³²⁸◧ CG6 (2012)³²⁹
Histidine	FRET ()	FLIP-HisJ: FLIP-cpHisJ194 (2009)³³⁰
Insulin	Rat. (◧)	RINS: RINS1 (2017)³³¹◧
Lactate	FRET ()	Laconic (2013)³³²
Maltose	BRET(◓) FRET () Inten. ()	FLIPmal: GFP2-MBP-RLuc2 (2013)³³³◓ FLIPmal-YΔ1 (2008)²⁶⁹ FLIPmal-Y Series (2002)³³⁴ MBP: PPYF-green (2011)¹⁹³
NADH	Inten. () Rat. (◧) Ex. Rat.(★)	Frex: RexYFP (2014)³³⁵ FrexH (2011)³³⁶ Frex (2011)³³⁶ NAD+ Biosensor (2016)³³⁷ Peredox (2011)²⁰¹◧ SoNar (2015)¹⁹⁷★
NADPH	FRET () Ex. Rat.(★)	Apollo-NADP⁺ (2016)³³⁸ iNap: iNap3 (2017)¹⁹⁸★ iNap2 (2017)¹⁹⁸★ iNap1 (2017)¹⁹⁸★ NADPsor (2016)³³⁹
O₂	Inten. () FRET ()	dUnOHR hypoxia-reoxygenation sensor (2016)³⁴⁰ FluBO (2012)³⁴¹
Phosphonate	Inten. ()	EcPhnD based: EcPhnD-cpGFP (2011)¹⁹⁴
Pyruvate	FRET ()	Pyronic: Pyronic (2014)³⁴²
Ribose	FRET ()	FLIPrib: FLIPrib-Y family (2003)³⁴³
Sucrose	FRET ()	FLIPsuc: FLIPsuc-Y family (2006)³⁴⁴
Trehalose	FRET ()	FLIP: FLIPSuc90μΔ1Venus (2016)³⁴⁵
Tryptophan	FRET ()	FLIPW (2007)³⁴⁶
Ions
Ca²⁺	BRET(◓) FRET () Inten. () Rat. (D) Ex. Rat.(★) Em. Rat. (☆) Biolum. (®)	Ca²⁺ Snapshot: FLARE(2017)³⁴⁷Cal-Light(2017)³⁴⁸ Cameleons: D3 BRET (2015)³⁴⁹◓ D1GO-Cam (2012)³⁵⁰ CaYang1 (2011)³⁵¹ CaYin1 (2011)³⁵¹ YC-Nano (2010)³⁵² D3cpv (2006)³⁵³ D4cpV (2006)³⁵³ D1 (2004)³⁵⁴ YC3.60 (2004)³⁵⁵ YC2.12 (2002)³⁵⁶ YC6.1 (2001)³⁵⁷ YC2.1 (1999)³⁵⁸ Split-Cameleon (1997)³⁵⁹ Cameleon 3 (1997)³⁵⁹ Camgaroo: Camgaroo2 (2001)³⁶⁰Camgaroo1 (1999)¹⁴⁴ CaMPARI: CaMPARI (2015)³⁶¹ CASE: Case16 (2007)³⁶²Case12 (2007)³⁶² CatchER (2011)³⁶³ ddFP Ca²⁺ sensor (2012)³⁶⁴ ER-GCaMP: ER-GCaMP6-150(2017)³⁶⁵ER-GCaMP6a-210(2017)³⁶⁵ ER-GCaMP3–373 / GCaMPer-10.19(2015)³⁶⁶ CEPIA1er (2014)³⁶⁷ ER-GECO: R-CEPIA1er (2014)³⁶⁷ GEM-CEPIA1er (2014)³⁶⁷☆ G-CEPIA1er (2014)³⁶⁷ FPX Ca²⁺ sensors: tripartate FPX Ca²⁺ Sensor (2015)²⁹³◧ single polypeptide FPX Ca²⁺ sensor (2015)²⁹³◧ GAP: GAP3 (2016)³⁶⁸GAP1 (2014)³⁶⁹ GCaMP: MatryoshCaMP6s (2017)²⁰⁶◧ sfMatryoshCaMP6s (2017)²⁰⁶◧ sfMatryoshCaMP6s-T78H (2017)²⁰⁶◧ GCaMP-R-3 (2017)²⁰²◧ GCaMP-R-6f (2017)²⁰²◧ GCaMP-R-6s (2017)²⁰²◧ GCaMP3bright (2015)³⁷⁰ GCaMP3fast³⁷⁰ GCaMP2.2Low (2014)³⁷¹ GCaMP6f (2013)¹⁵⁶ GCaMP6s (2013)¹⁵⁶ GCaMP6m (2013)¹⁵⁶ GCaMP5G (2012)¹⁵⁵ G-CaMP 3–8 (Nakai Variants) (2012)³⁷²GCaMP-HS(2011)³⁷³ GCaMP3 (2009)¹⁵⁴ GCaMP2 (2006)¹⁵³ GCaMP (2001)¹⁵⁰ GECO: K-GECO1(2018)³⁷⁴ jRGECO1a (2016)¹⁶² REX-GECO (2014)¹⁹⁶★ LAR-GECO (2014)³⁷⁵ GR-GECO (2013)³⁷⁶ R-GECO1.2 (2013)¹⁵⁹ O-GECO (2013)¹⁵⁹ CAR-GECO (2013)¹⁵⁹ G-GECO1 (2011)¹⁵⁸ B-GECO (2011)¹⁵⁸ G-GECO1.2 (2011)¹⁵⁸ R-GECO1 (2011)¹⁵⁸ GEM-GECO (2011)¹⁵⁸☆ GEX-GECO (2011)¹⁵⁸★ G-GECO1.1 (2011)¹⁵⁸ Nano-lantern Ca²⁺: GeNL(Ca²⁺) (2016)³⁷⁷◓ ONL(Ca²⁺)(2015)³⁷⁸◓ CNL(Ca²⁺)(2015)³⁷⁸◓ Nano-lantern Ca²⁺ (2012)²⁷⁶● Pericam: ratiometric-pericam (2001)¹⁴⁸◧ inverse-pericam (2001)¹⁴⁸ flash-pericam (2001)¹⁴⁸ RCaMP: jRCaMP1b (2016)¹⁶² jRCaMP1a (2016)¹⁶² R-CaMP2 (2015)³⁷⁹ RCaMP1h (2013)¹⁶⁰ R-CaMP1.07 (2012)³⁸⁰ TN Ca²⁺ Sensors: CalfluxVTN (2016)³⁸¹◓ Twitch series (2014)³⁸² YO-TnC1.0 (2012)³⁸³ TN-XXL (2008)³⁸⁴ TN-XL (2006)³⁸⁵ TN-humTnC (2004)³⁸⁶ TN-L15 (2004)³⁸⁶
Cd²⁺	FRET ()	Cd-FRET: Cd-FRET2 (2011)¹⁴²
Cu⁺	FRET ()	Yeast Copper regulator based: Ace1-FRET (2011)³⁸⁷ Mac1-FRET (2011)³⁸⁷ Amt1-FRET (2010)³⁸⁸
Halide Ions (Cl⁻, I⁻)	FRET () Inten. ()	Clomeleon: SuperClomeleon (2013)³⁸⁹ Cl-sensor (2008)¹³⁶ Clomeleon (2000)¹³⁵ Dual pH and Cl sensor: ClopHensor(2010)¹³⁸ ◧ Halide Sensitive Fluorescent Proteins: Cl-YFP (2014)¹²⁹ YFP(H148Q, I152L) (2001)¹²⁸ YFP(H148Q) (2000)¹²⁶
Hg(II)	Inten. ()	eGFP based: eGFP205C (2008)³⁹⁰ IFP based: IFP based Hg sensor (2011)³⁹¹
Phosphate	FRET ()	FLIPPi: FLIPPi-5μ (2006)³⁹² FLIPPi-30m (2006)³⁹²
Zn²⁺	BRET(◓) FRET ()	Atox1 WD4 Based: BLCALWY-1 (2016)³⁹³◓ redCALWY (2013)³⁹⁴ eCALWY series (2009)³⁹⁵ CALWY (2007)³⁹⁶ CFP-Atox1 + WD4-YFP (2006)³⁹⁷ Minimal Zinc Finger based: mito-ZifCY1.173(2012)³⁹⁸His4-Zn²⁺ sensor (2009)³⁹⁹ Cys2Hys2 - Zn²⁺ Sensor (2009)³⁹⁹ Zap1 based: ZapCY1 (2011)⁴⁰⁰ZF1/2-FRET (2006)⁴⁰¹ ZinCh: BLZinCh-2 (2016)³⁹³◓ BLZinCh-3 (2016)³⁹³◓ eZinCh-2 (2015)⁴⁰² eZinCh-1 (2011)¹⁴² Cly9–2His (2008)⁴⁰³ ZinCh-x (2007)¹⁴¹
Kinases/Phosphatases
Abl	FRET ()	Abl Indicator: Crk-based Reporter (2001)⁴⁰⁴
Akt	FRET () Trans. () FLIM (♣)	Akind (2006)⁴⁰⁵ Akt translocation Reporters: Akt-FoxO3a-KTR-EGFP (2016)¹¹⁰ FoxO1-clover (2015)¹⁰⁹ AktAR: AktAR2 (2015)⁴⁰⁶ AktAR (2008)⁴⁰⁷ AktUS (2003)⁴⁰⁸ BKAR: BKAR v2 (2014)⁴⁰⁹ BKAR (2005)⁴¹⁰ Dual Labeled Akt: GFP-PKB-RFP (2007)⁴¹¹ GFP-AKT-YFP (2003)⁴¹²♣ Eevee-Akt: Eevee-iAkt (2014)⁴¹³ Eevee-Akt (2011)⁴¹⁴ ReAktion: ReAktion1 (2007)⁴¹⁵
AMPK	FRET ()	AMPKAR: bimABKAR (2015)⁴¹⁶ ABKAR (2015)⁴¹⁷ AMPKAR (2011)⁴¹⁸
ATM kinase	FRET ()	ATOMIC (2007)⁴¹⁹
Aurora B kinase	FRET ()	Aurora B sensor: Aurora B sensor (Chu) (2011)⁴²⁰Aurora B Sensor (Fuller) (2008)⁴²¹
Aurora Kinase A	FRET ()	AURKA Biosensor (2016)⁴²²
B-Raf	FRET ()	Prin-BRaf (2006)⁴²³
Bcr-Abl	FRET ()	Pickles: Pickles-2.3 (2010)⁴²⁴
C-Raf	FRET ()	Prin-CRaf (2005)⁴²⁵
CaMKII	FLIM (♣) FRET ()	Camui: Camuiα-mRmC (2016)⁴²⁶♣ ShadowG-Camuiα (2015)⁴²⁷♣ Camuiα-CR (2012)²⁴⁷ green-Camuiα (2009)⁴²⁸♣ mRFP/GFP-Camuiα (2008)⁴²⁹♣ Camuiα (2005)⁴³⁰
CaN	FRET ()	CaNAR: CaNAR2 (2014)⁴³¹ CaNAR1 (2008)⁴³² CaNARi (2014)⁴³¹ DuoCaN: UniCaN (2015)⁴³³ DuoCaN (2015)⁴³³
CDK1	FRET ()	CyclinB1-Cdk1 activity sensor: CyclinB1-Cdk1 activity sensor V2 (2014)⁴⁰⁹ CyclinB1-Cdk1 activity sensor V1 (2010)⁴³⁴
CDK2	Trans. ()	CDK2 Translocation Reporter: DHB-Ven (2013)¹⁰⁷
DAPK1	FRET ()	DAPK1(2011)⁴³⁵
EGFR	FRET ()	ECaus (2008)²⁸¹ EGFR Reporter (2001)⁴⁰⁴^ FLAME: PTB-EYFP, EGFR-ECFP (2004)⁴³⁶ FLAME (2004)⁴³⁶ Picchu-Z (2005)⁴³⁷
ERK	FRET () FLIM (♣) BRET (◓) Trans. () FLINC () Rat. (◧)	EAS: EAS3 (2005)⁴³⁸ EKAR: EKAR^dual (2017)⁴³⁹♣ bimEKAR (2015)⁴¹⁶ EKAR3 (2015)⁴⁴⁰ EKAREV-TVV (2014)⁴⁴¹ EKAR-TVV (2014)⁴⁴¹ REV (2013)⁴⁴²◓ EKAR2G (2013)⁴⁴³ EKAREV (2011)⁴¹⁴ EKAR (2008)⁴⁴⁴ ERK-KTR (2014)¹¹² Erkus (2007)⁴⁴⁵ ERKy (2012)⁴⁴⁶ FLINC-EKAR1 (2017)⁴⁴⁷ FPX EKAR (2015)²⁹³◧ Miu2 (2006)⁴⁴⁸
FAK	FRET ()	FAK Activation Biosensor: CYFAK413 (2008)⁴⁴⁹ FAK Autophosphorylation Biosensor (2008)⁴⁴⁹ FAK sensor (2011)⁴⁵⁰
Fus3	Trans. ()	Far1-SKARS (2015)¹¹³
GCK	FRET ()	GCK Activation Biosensors: FRET-GCK (cp173-mCer3/mVen) (2016)⁴⁵¹FRET-GCK (mCer/mVen) (2011)⁴⁵²Cerulean-GCK-mCit (2004)¹⁷³FRET-GCK (2002)⁴⁵³
H3–S28p	FRET ()	Histone Phosphorylation reporter (2004)⁴⁵⁴
INSR	BRET(◓) FRET () Inten. ()	Insulin Receptor Activation BRET assay (2001)⁴⁵⁵◓ Phocus: Phocus-2pp nes (2002)⁴⁵⁶Phocus2 (2002)⁴⁵⁶ Sinphos: yellow-sinphos (2004)⁴⁵⁷green-sinphos (2004)⁴⁵⁷cyan-sinphos (2004)⁴⁵⁷
JNK	FRET () Trans. ()	dJUN-FRET (2008)⁴⁵⁸ JNK-KTR (2014)¹¹² JNKAR: bimJNKAR (2015)⁴¹⁶ JNKAR1EV (2011)⁴¹⁴ JNKAR1 (2010)⁴⁵⁹ JuCKY (2010)⁴⁶⁰
Kss1	Trans. ()	Ste7-SKARS: Ste7-SKARS (2015)¹¹³
LATS	Biolum. (●)	LATS-BS(2018)⁴⁶¹ ●
Lck	FRET ()	Lck Activation sensor: CLckY-2 (2009)⁴⁶²
MAPK/MK2	FRET ()	GMB (2001)⁴⁶³
MARK	FRET ()	MARK sensor: MARK-AR1 (2011)⁴⁶⁴
Mpk1	Trans. ()	Mkk2-SKARS (2015)¹¹³
mTORC1	FRET ()	TORCAR (2015)⁴⁰⁶
p38	FRET () Trans. ()	p38 activity reporter (2015)⁴⁶⁵ p38-KTR (2014)¹¹²
PAK1	FRET ()	Pakabi (2009)⁴⁶⁶
PDGFR	FRET ()	PDGFR Biosensor: PDGFR Biosensor(2017)⁴⁶⁷
PDK1	FRET ()	PARE (2011)⁴⁶⁸
PKA	FLIM (♣) FRET () Biolum. (●) FLINC () Trans. () Inten. ()	AKAR: AKAR^dual (2017)⁴³⁹♣ AKAR5(2017)⁴⁶⁹♣ AKAR4.1 (2015)⁴⁷⁰ FLIM-AKAR (2014)⁴⁷¹♣ AKAR-CR (2012)²⁴⁷ bimAKAR (2011)⁴⁷² LumAKAR (2011)⁴⁷²● AKAR3EV (2011)⁴¹⁴ AKAR4 (2011)⁴⁷³ ICUPID (2011)²⁹⁴ AKAR-GR (2011)²⁹⁴ CRY-AKAR (2008)⁴⁷⁴ AKAR3 (2006)⁴⁷⁵ AKAR2 (2005)⁴⁷⁶ AKAR1 (2001)⁴⁷⁷ ART (2000)⁴⁷⁸ FLINC-AKAR1 (2017)⁴⁴⁷ PKA-KTR (2014)¹¹² RLuc-PCA PKA (2007)⁴⁷⁹● Single Color PKA sensor: GAk (2014)⁴⁸⁰
PKC	FRET ()	CKAR (2003)⁴⁸¹ Eevee-PKC (2011)⁴¹⁴ KCP: KCAP-1 (2006)⁴⁸²KCP-2 (2006)⁴⁸² KCP-1 (2004)⁴⁸³
PKD	FRET ()	DKAR (2007)⁴⁸⁴ G-PKDrep: G-PKDrep live (2012)⁴⁸⁵ G-PKDrep (2009)⁴⁸⁶
PKM2	FRET ()	PKAR: PKAR2.3 (2013)⁴⁸⁷
PTEN	BRET(◓)	Rluc-PTEN-YFP (2014)⁴⁸⁸◓
ROCK	FRET ()	Eevee-ROCK (2017)⁴⁸⁹
RSK	FRET ()	Eevee-RSK: Eevee-RSK (2011)⁴¹⁴
RTK	FRET ()	Picchu: PicchuEV (2011)⁴¹⁴ Picchu (2001)⁴⁹⁰
S6K	FRET ()	Eevee-S6K: Eevee-S6K(2011)⁴¹⁴
SAP3K	FRET ()	SAP3K (2009)⁴⁹¹
Src	FRET ()	Src Indicator: BG-Src1.0 (2013)⁴⁹² Y0-Src1.0 (2012)³⁸³ Src Reporter (ECFP/YPet) (2008)⁴⁹³ Src Reporter (2005)⁴⁹⁴ Src Indicator (2001)⁴⁰⁴ Srcus (2007)⁴⁹⁵
ZAP-70	FRET ()	ROZA (2008)⁴⁹⁶
Neurotransmitters
5-HT	FRET ()	5-HT 3A CNiFER: 5-HT 3A LGIC CNiFER (2011)⁴⁹⁷
ACh	FRET ()	ACh CNiFER: α402-nAChR LGIC CNiFER (2011)⁴⁹⁷ α7 LGIC CNiFER (2011)⁴⁹⁷ M1-CNiFER (2010)⁴⁹⁸
Dopamine	FRET ()	Dopamine CNiFER: D2 CNiFER (2014)⁴⁹⁹
Glutamate	FRET () Inten. ()	FLIP Glt: FLIP-cpGltI210 (2009)³³⁰ FLIPE: FLII⁸¹PE-1u (2005)³²⁰FLIPE-Y Surface series (2005)⁵⁰⁰FLIPE-Y Series (2005)⁵⁰⁰ GluSnFR: superGluSnFR (2008)⁵⁰¹ iGluSnFR (2013)¹⁶⁶ QBP based: Gln D157N reporter (2010)⁵⁰²
NE	FRET ()	NE CNiFER: α1A CNiFER (2014)⁴⁹⁹
Phosphoinositides/Lipids
3’ IP	Trans. () FRET ()	GFP AKT domains: GFP-Akt(1999)⁸⁷GFP-AH(1999)⁸⁷ Homo FRET mCherry-Akt-PH: mCherry-Akt-PH (2015)⁵⁰³ InPAkt (2005)⁵⁰⁴
DAG	Trans. () FRET ()	Cys1-GFP: C1₂-GFP(1998)⁹⁴ Cys1-GFP (1998)⁹² Daglas: Daglas-mit1(2006)⁵⁰⁵ Daglas-em1(2006)⁵⁰⁵ Daglas-pm1(2006)⁵⁰⁵ DAGR (2003)⁴⁸¹ Digda (2008)⁵⁰⁶
IP₃	FRET () BRET(◓) Trans. ()	FIRE: FIRE-3 (2006)⁵⁰⁷ FIRE-2 (2006)⁵⁰⁷FIRE-1 (2006)⁵⁰⁷ fretino: fretino (2015)³⁴⁹◓FRET InsP3 sensor (2015)³⁴⁹fretino-2 (2005)⁵⁰⁸ GFP-PH: GFP-PHD (1999)⁵⁰⁹ IRIS: IRIS-1 (2006)⁵¹⁰ LIBRA: LIBRAvI (2009)⁵¹¹ LIBRAvII (2009)⁵¹¹ LIBRAVIIIS (2009)⁵¹¹ LIBRAvIII (2009)⁵¹¹ LIBRA (2004)⁵¹²
PA	FRET ()	Pii: Pii-DK (2010)⁵¹³
PI(4)P	BRET(◓) FRET ()	BRET PI(4)P sensors: SidM-2xP4M (2016)⁵¹⁴◓0SH2–2xPH (2016)⁵¹⁴◓ Pippi: Pippi-PI(4)P (2008)⁵⁰⁶
PI(3)P	Trans. ()	GFP-FYVE: GFP-FYVE (FENS-1)(2001)⁹⁰GFP-Pib1p(1998)⁸⁶GFP-EEA1 (FYVE)(1998)⁸⁶ GFP-PX: GFP-PX(2001)⁹⁰
PI(3,4)P₂	FRET ()	Pippi-PI(3,4)P2 (2006)⁴⁰⁵
PI(3,5)P₂	Trans. ()	GFP-MLN1 (2013)⁵¹⁵
PI(4,5)P₂	FRET () Trans. () Rat. (◧)	CAY (2004)⁵¹⁶ CYPHR (2003)⁴⁸¹ FP-Tubby (2001)⁵¹⁷ FPX PIP2 sensor (2015)²⁹³◧ PH(PLCδ): PH(PLCδ)-CFP/YFP (2001)⁵¹⁸ PH(PLCδ) - GFP (1998)⁸⁸ GFP-PH (1998)⁵¹⁹ Pippi-PI(4,5)P2 (2008)⁵⁰⁶
PIP₃	FRET () Trans. () BRET (◓)	FLLIP (2003)⁵²⁰ Labeled PH domains: PH(PKB)-GFP (1999)⁸⁹ PH(GRP1)-GFP (1999)⁸⁹ PIP3 BRET sensor (2012)⁵²¹◓
PS	Trans. ()	2xPH(Evectin2) (2011)⁵²² cPLA2–C2: cPLA2-C2-GFP(2003)⁹⁵ Lact-C2: mRFP - Lact-C2 (2008)⁹⁷GFP - Lact-C2 (2008)⁹⁷ PKC-C2: PKCα-C2-EGFP(2003)⁹⁵ C2-GFP(1998)⁹⁴ PLCδ1-C2: PLCδ1-C2-EGFP(2002)⁹⁶
Protease
Atg4a	FRET ()	FRET-LC3B (2012)⁵²³
Atg4b	FRET ()	FRET-GATE-16 (2012)⁵²³
Caspase1	Rat. (◧)	FPX caspase 1 sensor: single polypeptide FPX caspase 1 sensor (2015)²⁹³◧
Caspase3	Rat. (◧) Inten. () FRET ()	ddFP based: single polypeptide FPX Caspase 3 sensor (2015)²⁹³◧Bimolecular FPX Caspase 3 reporter (2015)²⁹³◧ddRFP-A1B1-DEVD (2012)³⁶⁴ DEVD: mCitrine-DEVD-mTFP1 (2008)⁵²⁴mAmetrine-DEVD-tdTomato (2008)⁵²⁴ BFP-DEVD-GFP(2002)⁵²⁵ Sensor C3(2001)⁵²⁶CFP-DEVD-YFP(2000)⁵²⁷ DEVK: MiCy-DEVK-mKO (2004)⁵²⁸ EC-RP (2008)⁵²⁹ Far-Red Caspase sensors: mKate2-DEVD-iRFP (2016)⁵³⁰ iProtease: iCasper (2015)⁵³¹ SCAT3: SCAT3 (2003)⁵³² yDMQDc: yDMQDc (2006)⁵³³
Caspase8	FRET () Rat. (◧)	Bid cleavage sensor (2002)⁵³⁴ FPX caspase 8 sensor: single polypeptide FPX caspase 8 sensor (2015)²⁹³◧ IC-RP (2008)⁵²⁹
Caspase9	FRET ()	SCAT9 (2003)⁵³²
MT1-MMP	FRET ()	MT1-MMP Biosensor: MT1-MMP Biosensor (mCherry/mOrange2) (2010)⁵³⁵MT1-MMP Biosensor (2008)⁵³⁶
Receptors/GPCRs
A1R	FRET ()	A1R SPASM: A1R - FL Gαs SPASM (2017)⁵³⁷A1R - FL Gαi SPASM (2017)⁵³⁷
β2-AR	BRET (◓) FRET () Trans. ()	BRET² β2-AR Activation Probes: β2AR-RLuc Gαs-GFP10 (2005)⁵³⁸◓ β2AR-RLuc GFP-Gβ1 (2005)⁵³⁸◓ β2AR-RLuc GFP-Gγ2 (2005)⁵³⁸◓ β2-AR SPASM: β2-AR FL Gαq SPASM (2017)⁵³⁷ β2-AR FL Gαs SPASM (2017)⁵³⁷ β2-AR-Gα SPASM (2013)⁵³⁹ Nb80: Nb80-GFP (2013)¹⁰⁵
Dictyostelium GPCR	FRET ()	Labeled G proteins: Gβ-YFP + Gα2-CFP(2001)⁵⁴⁰
DRD2	Inten ()	iTango: DRD2-iTango(2017)⁵⁴¹
Gαi	FRET ()	Gαi Sensor: Gαil Sensor v2 (2016)⁵⁴²Gαi3 Sensor v2 (2016)⁵⁴²Gαi2 Sensor v2 (2016)⁵⁴²Gαi3 v1 (2006)⁵⁴³Gαi1 v1 (2006)⁵⁴³Gαi2 v1 (2006)⁵⁴³Bunemann Gαi-Gγ2 (2003)⁵⁴⁴Bunemann Gαi-Gβ1 (2003)⁵⁴⁴
Gαq	FRET ()	Gαq Sensor: Gαq Sensor (v2) (2011)⁵⁴⁵Gαq Sensor (vl) (2009)⁵⁴⁶
Gαs	FRET () BRET(◓) Trans. ()	Gαs Sensor (2006)⁵⁴⁷ Gs Activation BRET Assay: RLucII-117-Gαs + GFPl0-Gγ1(20l 6)⁵⁴⁸◓ Nb37 based: Nb37-YFP(2017)¹⁰⁶
α1-AR	FRET ()	α1-AR SPASM: α1-AR FL Gαq SPASM (2017)⁵³⁷
α2A-AR	FRET () BRET(◓)	α2-AR SPASM: α2-AR FL Gαs SPASM (2017)⁵³⁷α2-AR FL Gαi SPASM (2017)⁵³⁷ α2A-AR + labeled G protein: α2A-AR-Venus + Gα_i1-122Rluc(2006)⁵⁴⁹◓α2A-AR-Venus + Gα_i1-91Rluc(2006)⁵⁴⁹◓α2A-AR-Venus + RLuc-Gγ2(2006)⁵⁴⁹◓ α2A-YFP + CFP-Gγ2(2005)⁵⁵⁰ α2A-AR activation sensor: α2A-AR-cam (2003)⁵⁵¹
M1R	FRET ()	M1R Activation Sensor: M1R-EYFP-Cerulean (2009)⁵⁴⁶
Odr-10	BRET(◓)	OGOR (2011)⁵⁵²◓
Opsin	FRET ()	Opsin SPASM: Opsin-Gα SPASM (2013)⁵³⁹
PTHR	FRET ()	PTHR activation sensor: PTHR-cam (2003)⁵⁵¹
VEGF	BRET (◓)	BRET VEGF biosensor (2016)⁵⁵³◓
Redox
H₂O₂	Ex. Rat.(★) Inten. () FRET ()	HyPer: HyPerRed (2014)⁵⁵⁴★ HyPer-3 (2013)⁵⁵⁵★HyPer-2 (2011)⁵⁵⁶★ HyPer (2006)⁵⁵⁷★ roGFP based: roGFP2-Tsa2ΔC_PΔC_R (2016)⁵⁵⁸★ roGFP2-Tsa2 ΔC_R (2016)⁵⁵⁸★ roGFP2-GPx4 (2009)⁵⁵⁹★ roGFP2-Orp1 (2009)⁵⁵⁹★ Unnatural Amino Acid based: UFP-Tyr66pBoPhe (2012)⁵⁶⁰ Yap1 based: PerFRET (2013)⁵⁶¹ OxyFRET (2013)⁵⁶¹
H₂S	Inten.()	pAzF H2S sensors: hsGFP (2014)⁵⁶² cpGFP-Tyr66pAzF (2012)⁵⁶³
NO	FRET ()	FRET-MT (2000)⁵⁶⁴ sGC based: Piccell (2006)⁵⁶⁵ NOA-1 (2005)⁵⁶⁶
Organic Hyrdroperoxides	Inten.()	OHSer (2010)⁵⁶⁷
ONOO⁻	Inten.()	pnGFP (2013)⁵⁶⁸
Redox status	FRET () Ex. Rat.(★) Inten.()	HSP33: HSP-FRET (2006)⁵⁶⁹ redox-sensitive linker: CY-RL7 (2011)⁵⁷⁰ RedoxFluor (2010)⁵⁷¹ ECFP-RL-EYFP (2008)⁵⁷² roGFP: roGFP1-iX (2008)⁵⁷³★ Grx1-roGFP2 (2008)⁵⁷⁴★ roGFP1-Rx Family (2006)⁵⁷⁵★ roGFP2 (2004)¹³⁹★ roGFP1 (2004)¹³⁹★ rxRFP: TrxRFP1 (2017)⁵⁷⁶ rxRFP1.X Sensitivity series (2016)⁵⁷⁷ rxRFP (2015)⁵⁷⁸ rxYFP: rxYFP-Grx1p (2006)⁵⁷⁹ rxYFP¹⁴⁹₂₀₂ (2001)⁵⁸⁰
Superoxide	Inten.()	mt-cpYFP (2008)⁵⁸¹
Small G-Protein
Cdc42	FRET () FLIM (♣)	(CDC42) GEF Sensor (2003)⁵⁸² CDC42 Biosensor (2014)⁵⁸³ Cdc42 FRET (2016)⁴²⁶♣ CDC42 Raichu: CDC42 Raichu (2002)⁵⁸⁴CRIB Raichu (2002)⁵⁸⁴ Cdc42–2G: Cdc42–2G(2016)⁵⁸⁵ GDI Cdc42 FLARE (2016)⁵⁸⁶
Rab5	FRET ()	Rab5 Raichu (2008)⁵⁸⁷
Racl	FRET ()	FLAIR (2000)⁵⁸⁸ GDI Rac1 FLARE (2016)⁵⁸⁵ Rac1 Raichu: Rac1 Raichu EV (2011)⁴¹⁴ CRIB Raichu (2002)⁵⁸⁴ Rac1 Raichu (2002)⁵⁸⁴ Rac1–2G (2015)⁵⁸⁹
Ral	FRET ()	Raichu-Ral: Raichu-RalB (2004)⁵⁹⁰ Raichu-RalA (2004)⁵⁹⁰
Ran	FRET ()	Ran FRET probes: YIC (2002)⁵⁹¹ YRC (2002)⁵⁹¹
Rapl	FRET ()	Rap1 Raichu (2001)⁵⁹²
Ras	FRET () FLIM (♣)	DORA Ras (2015)⁵⁹³ FRas: ShadowY H-Ras Sensor (2017)⁵⁹⁴♣ ShadowG FRas2-M (2015)⁴²⁷♣ FRas2-M (2013)⁵⁹⁵♣ FRas2-F (2013)⁵⁹⁵♣ FRas-F (2006)⁵⁹⁶♣ FRas (2006)⁵⁹⁶♣ Ras Raichu: Ras Raichu EV (2011)⁴¹⁴ Ras Raichu (2001)⁵⁹²
RhoA	FRET () FLIM (♣)	RhoA FLARE: RhoA DORA (2015)⁵⁹⁷ RhoA2G (2013)⁴⁴³ RhoA FLARE \| RhoA1G (2006)⁵⁹⁸ RhoA FRET (2016)⁴²⁶♣ RhoA Raichu: RhoA Raichu CR (2012)²⁴⁷ RBD Raichu (2006)⁵⁹⁹RhoA Raichu (2003)⁶⁰⁰
RhoC	FRET ()	RhoC FLARE (2013)⁶⁰¹
RhoQ	FRET ()	TC10 Raichu (2006)⁶⁰²
RRas	FRET ()	RRas Raichu (2007)⁶⁰³
Other Post-Translational Modifications
βArrestin 2	BRET(◓)	βArrestin 2 ubiquitination biosensor (2004)⁶⁰⁴◓
Histone Acetylation	FRET ()	Histac: Histac-H3K9/14 (2016)⁶⁰⁵Histac-H4K12 (2011)⁶⁰⁶Histac-H4K5/8 (2009)⁶⁰⁷
K27H3 methyltransf.	FRET ()	K27 Reporter (2004)⁶⁰⁸
K9H3 methyltransf.	FRET ()	K9 Reporter (2004)⁶⁰⁸
O-GlcNAc transferase	FRET ()	O-GlcNAc Sensor (2006)⁶⁰⁹
Ubiquitination	Inten. ()	REACh-Ubiquitin (2006)⁶¹⁰
Other Signaling Proteins
Annexin 4	FRET ()	NEX4: ORNEX4 (2008)⁶¹¹ CYNEX4 (2006)⁶¹²
Bax	Trans. ()	Bax Translocation reporter (2016)⁵³⁰
CaM	FRET ()	BSCaM: BSCaM2 (1999)⁶¹³ BSCaM1 (1997)⁶¹⁴ MLCK-FIP (2002)⁶¹⁵
CRAC	Trans. ()	PH(crac)-GFP (2002)⁶¹⁶
CREB	FRET ()	ICAP (2010)⁶¹⁷
N-WASP	FRET ()	N-WASP BS (2004)⁶¹⁸
Plasma Membrane ATPase	FRET ()	PMCA Activity Sensor: BFP-PMCA-GFP (2007)⁶¹⁹