AiPD: Autoinhibited Protein Database

Q9BIG5

Gene name	gpa-4 (T07A9.7)
Protein name	Guanine nucleotide-binding protein alpha-4 subunit
Names
Species	Caenorhabditis elegans
KEGG Pathway	cel:CELE_T07A9.7
EC number
Protein Class

Descriptions

The Gα subunits of heterotrimeric G proteins are GTP hydrolyases which, upon receptor activation, bind to GTP and regulate effector molecules. Gα-catalyzed hydrolysis of GTP to GDP releases the Gα-GDP product complex from effector and allows its sequestration by inhibitory Gβγ subunits. In Gia1-GppNHp complex, Gln204 of Gia1 interacts with nucleophilic water (Wnuc), participating directly in the Gia1-GTP ground state but must reorient to stabilize the transition state. RGS4, a member of the RGS family of G protein stimulatory factors, accelerates hydrolysis of GTP by Gia1 by destabilizing the ground-state conformation of Gln204. Insertion of Asn128 of RGS4 into the active site enhances catalysis by aiding in binding, orienting, and polarizing Wnuc in the pre-transition state complex. Asn128 of RGS4 displaces the side chain of Gln204 from its anti-catalytic position in the ground state, freeing it to participate in stabilization of the transition state.

Autoinhibitory domains (AIDs)

207-208 (Gln204) SS

Target domain	182-354 (P-loop containing nucleoside triphosphate hydrolase domain)
Relief mechanism	Partner binding
Assay

AID

207-208 (Gln204)

Target domain

182-354 (P-loop containing nucleoside triphosphate hydrolase domain)

Relief mechanism

Partner binding (RGS4 binding)

Assay

61-180 (α-H domain) SS

Target domain	187-353 (Ras-like domain)
Relief mechanism	Ligand binding, Partner binding
Assay

AID

61-180 (α-H domain)

Target domain

187-353 (Ras-like domain)

Relief mechanism

Ligand binding (GTP binding), Partner binding(Binding of activated GPCR)

Assay

Accessory elements

No accessory elements

References

Coleman DE et al. (1999) "Structure of Gialpha1.GppNHp, autoinhibition in a galpha protein-substrate complex", The Journal of biological chemistry, 274, 16669-72

Lutz S et al. (2007) "Structure of Galphaq-p63RhoGEF-RhoA complex reveals a pathway for the activation of RhoA by GPCRs", Science (New York, N.Y.), 318, 1923-7

Goricanec D et al. (2016) "Conformational dynamics of a G-protein α subunit is tightly regulated by nucleotide binding", Proceedings of the National Academy of Sciences of the United States of America, 113, E3629-38

Autoinhibited structure

Activated structure

1 structures for Q9BIG5

Entry ID	Method	Resolution	Chain	Position	Source
AF-Q9BIG5-F1	Predicted				AlphaFoldDB

No variants for Q9BIG5

Variant ID(s)	Position	Change	Description	Diseaes Association	Provenance
No variants for Q9BIG5

No associated diseases with Q9BIG5

2 regional properties for Q9BIG5

Type	Name	Position	InterPro Accession
domain	Ubiquitin-conjugating enzyme E2	30 - 175	IPR000608
active_site	Ubiquitin-conjugating enzyme, active site	103 - 118	IPR023313

Functions

		Description
EC Number
Subcellular Localization
PANTHER Family
PANTHER Subfamily
PANTHER Protein Class
PANTHER Pathway Category	No pathway information available

4 GO annotations of cellular component

Name	Definition
cilium	A specialized eukaryotic organelle that consists of a filiform extrusion of the cell surface and of some cytoplasmic parts. Each cilium is largely bounded by an extrusion of the cytoplasmic (plasma) membrane, and contains a regular longitudinal array of microtubules, anchored to a basal body.
cytoplasm	The contents of a cell excluding the plasma membrane and nucleus, but including other subcellular structures.
heterotrimeric G-protein complex	Any of a family of heterotrimeric GTP-binding and hydrolyzing proteins; they belong to a superfamily of GTPases that includes monomeric proteins such as EF-Tu and RAS. Heterotrimeric G-proteins consist of three subunits; the alpha subunit contains the guanine nucleotide binding site and possesses GTPase activity; the beta and gamma subunits are tightly associated and function as a beta-gamma heterodimer; extrinsic plasma membrane proteins (cytoplasmic face) that function as a complex to transduce signals from G protein-coupled receptors to an effector protein.
non-motile cilium	A cilium which may have a variable array of axonemal microtubules but does not contain molecular motors.

5 GO annotations of molecular function

Name	Definition
G protein-coupled receptor binding	Binding to a G protein-coupled receptor.
G-protein beta/gamma-subunit complex binding	Binding to a complex of G-protein beta/gamma subunits.
GTP binding	Binding to GTP, guanosine triphosphate.
GTPase activity	Catalysis of the reaction
metal ion binding	Binding to a metal ion.

1 GO annotations of biological process

Name	Definition
adenylate cyclase-modulating G protein-coupled receptor signaling pathway	A G protein-coupled receptor signaling pathway in which the signal is transmitted via the activation or inhibition of adenylyl cyclase activity and a subsequent change in the intracellular concentration of cyclic AMP (cAMP).

57 homologous proteins in AiPD

UniProt AC	Gene Name	Protein Name	Species	Evidence Code
P0C7Q4	GNAT3	Guanine nucleotide-binding protein G	Bos taurus (Bovine)	SS
P04696	GNAT2	Guanine nucleotide-binding protein G	Bos taurus (Bovine)	SS
P04695	GNAT1	Guanine nucleotide-binding protein G	Bos taurus (Bovine)	SS
P08239	GNAO1	Guanine nucleotide-binding protein G	Bos taurus (Bovine)	SS
P63097	GNAI1	Guanine nucleotide-binding protein G	Bos taurus (Bovine)	SS
P50147	GNAI2	Guanine nucleotide-binding protein G	Gallus gallus (Chicken)	SS
P50146	GNAI1	Guanine nucleotide-binding protein G	Gallus gallus (Chicken)	SS
P16378	Galphao	G protein alpha o subunit	Drosophila melanogaster (Fruit fly)	SS
P25157	cta	Guanine nucleotide-binding protein subunit alpha homolog	Drosophila melanogaster (Fruit fly)	SS
P20353	Galphai	G protein alpha i subunit	Drosophila melanogaster (Fruit fly)	SS
P11488	GNAT1	Guanine nucleotide-binding protein G	Homo sapiens (Human)	SS
P19087	GNAT2	Guanine nucleotide-binding protein G	Homo sapiens (Human)	SS
P09471	GNAO1	Guanine nucleotide-binding protein G	Homo sapiens (Human)	SS
Q03113	GNA12	Guanine nucleotide-binding protein subunit alpha-12	Homo sapiens (Human)	SS
P04899	GNAI2	Guanine nucleotide-binding protein G	Homo sapiens (Human)	SS
P08754	GNAI3	Guanine nucleotide-binding protein G	Homo sapiens (Human)	SS
A8MTJ3	GNAT3	Guanine nucleotide-binding protein G	Homo sapiens (Human)	SS
Q14344	GNA13	Guanine nucleotide-binding protein subunit alpha-13	Homo sapiens (Human)	SS
P19086	GNAZ	Guanine nucleotide-binding protein G	Homo sapiens (Human)	SS
P63096	GNAI1	Guanine nucleotide-binding protein G	Homo sapiens (Human)	EV
Q9DC51	Gnai3	Guanine nucleotide-binding protein G	Mus musculus (Mouse)	SS
P27600	Gna12	Guanine nucleotide-binding protein subunit alpha-12	Mus musculus (Mouse)	SS
P20612	Gnat1	Guanine nucleotide-binding protein G	Mus musculus (Mouse)	SS
P27601	Gna13	Guanine nucleotide-binding protein subunit alpha-13	Mus musculus (Mouse)	SS
Q3V3I2	Gnat3	Guanine nucleotide-binding protein G	Mus musculus (Mouse)	SS
O70443	Gnaz	Guanine nucleotide-binding protein G	Mus musculus (Mouse)	SS
P50149	Gnat2	Guanine nucleotide-binding protein G	Mus musculus (Mouse)	SS
P08752	Gnai2	Guanine nucleotide-binding protein G	Mus musculus (Mouse)	SS
P18872	Gnao1	Guanine nucleotide-binding protein G	Mus musculus (Mouse)	SS
B2RSH2	Gnai1	Guanine nucleotide-binding protein G	Mus musculus (Mouse)	SS
P93564	GPA1	Guanine nucleotide-binding protein alpha-1 subunit	Solanum tuberosum (Potato)	SS
Q63210	Gna12	Guanine nucleotide-binding protein subunit alpha-12	Rattus norvegicus (Rat)	SS
P19627	Gnaz	Guanine nucleotide-binding protein G	Rattus norvegicus (Rat)	SS
P29348	Gnat3	Guanine nucleotide-binding protein G	Rattus norvegicus (Rat)	SS
P04897	Gnai2	Guanine nucleotide-binding protein G	Rattus norvegicus (Rat)	SS
P59215	Gnao1	Guanine nucleotide-binding protein G	Rattus norvegicus (Rat)	SS
P08753	Gnai3	Guanine nucleotide-binding protein G	Rattus norvegicus (Rat)	SS
Q6Q7Y5	Gna13	Guanine nucleotide-binding protein subunit alpha-13	Rattus norvegicus (Rat)	SS
P10824	Gnai1	Guanine nucleotide-binding protein G subunit alpha-1	Rattus norvegicus (Rat)	EV
Q0DJ33	GPA1	Guanine nucleotide-binding protein alpha-1 subunit	Oryza sativa subsp. japonica (Rice)	SS
P28051	gpa-1	Guanine nucleotide-binding protein alpha-1 subunit	Caenorhabditis elegans	SS
P28052	gpa-3	Guanine nucleotide-binding protein alpha-3 subunit	Caenorhabditis elegans	SS
P51875	goa-1	Guanine nucleotide-binding protein G	Caenorhabditis elegans	SS
P91907	gpa-15	Guanine nucleotide-binding protein alpha-15 subunit	Caenorhabditis elegans	SS
Q18434	odr-3	Guanine nucleotide-binding protein alpha-17 subunit	Caenorhabditis elegans	SS
Q20907	gpa-8	Guanine nucleotide-binding protein alpha-8 subunit	Caenorhabditis elegans	PR
Q21917	gpa-7	Guanine nucleotide-binding protein alpha-7 subunit	Caenorhabditis elegans	SS
Q93743	gpa-6	Guanine nucleotide-binding protein alpha-6 subunit	Caenorhabditis elegans	SS
Q9BIG4	gpa-10	Guanine nucleotide-binding protein alpha-10 subunit	Caenorhabditis elegans	PR
Q9N2V6	gpa-16	Guanine nucleotide-binding protein alpha-16 subunit	Caenorhabditis elegans	SS
Q9XTB2	gpa-13	Guanine nucleotide-binding protein alpha-13 subunit	Caenorhabditis elegans	SS
O76584	gpa-11	Guanine nucleotide-binding protein alpha-11 subunit	Caenorhabditis elegans	SS
P49084	GPA1	Guanine nucleotide-binding protein alpha-1 subunit	Glycine max (Soybean) (Glycine hispida)	SS
P93163	GPA2	Guanine nucleotide-binding protein alpha-2 subunit	Glycine max (Soybean) (Glycine hispida)	SS
O80462	XLG1	Extra-large guanine nucleotide-binding protein 1	Arabidopsis thaliana (Mouse-ear cress)	PR
P18064	GPA1	Guanine nucleotide-binding protein alpha-1 subunit	Arabidopsis thaliana (Mouse-ear cress)	SS
P26981	GPA1	Guanine nucleotide-binding protein alpha-1 subunit	Solanum lycopersicum (Tomato) (Lycopersicon esculentum)	SS

10	20	30	40	50	60
MGCFHSTGSE	AKKRSKLIDE	QLRHDHERCV	GEIKLLLLGA	GESGKSTIVR	QMRILHETGF
70	80	90	100	110	120
NKQEQMAYRP	VVFSNMVQSM	LAILKAMQPL	NISFTDAARE	EDARMFISHF	LHVNNAELSE
130	140	150	160	170	180
AFSLELSDLM	KQLWMDEGVK	KCVKRAHEYQ	LNDSAEYYFN	ALDRISSSSY	LPTQDDILRA
190	200	210	220	230	240
RVKSTGIVET	TFMYKDLCFK	MFDVGGQRSE	RKKWIHCFDS	VTAVIFCVAL	SEYDLRLAED
250	260	270	280	290	300
QTMNRMHESM	QLFDSIVNNC	WFTETSIILF	LNKMDIFEER	IRYTPLTVCF	PEYQGGMTIT
310	320	330	340	350
ETSTFIQSRF	EILNKRQTPA	QKEIYSHFTC	ATDTNNIRFV	FDAVTDIIIR	NNLYLCGLY