AiPD: Autoinhibited Protein Database

P93163

Gene name	GPA2 (GA2)
Protein name	Guanine nucleotide-binding protein alpha-2 subunit
Names	GP-alpha-2
Species	Glycine max (Soybean) (Glycine hispida)
KEGG Pathway	gmx:547977
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)

224-225 (Gln204) SS

Target domain	193-380 (P-loop containing nucleoside triphosphate hydrolase domain)
Relief mechanism	Partner binding
Assay

AID

224-225 (Gln204)

Target domain

193-380 (P-loop containing nucleoside triphosphate hydrolase domain)

Relief mechanism

Partner binding (RGS4 binding)

Assay

69-191 (α-H domain) SS

Target domain	198-379 (Ras-like domain)
Relief mechanism	Ligand binding, Partner binding
Assay

AID

69-191 (α-H domain)

Target domain

198-379 (Ras-like domain)

Relief mechanism

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

Assay

Accessory elements

No accessory elements

References

Yeon JH et al. (2016) "Systems-wide Identification of cis-Regulatory Elements in Proteins", Cell systems, 2, 89-100

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 P93163

Entry ID	Method	Resolution	Chain	Position	Source
AF-P93163-F1	Predicted				AlphaFoldDB

No variants for P93163

Variant ID(s)	Position	Change	Description	Diseaes Association	Provenance
No variants for P93163

No associated diseases with P93163

No regional properties for P93163

Type	Name	Position	InterPro Accession
No domain, repeats, and functional sites for P93163

Functions

		Description
EC Number
Subcellular Localization
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.
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.

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).

77 homologous proteins in AiPD

UniProt AC	Gene Name	Protein Name	Species	Evidence Code
P04695	GNAT1	Guanine nucleotide-binding protein G	Bos taurus (Bovine)	SS
P04696	GNAT2	Guanine nucleotide-binding protein G	Bos taurus (Bovine)	SS
P08239	GNAO1	Guanine nucleotide-binding protein G	Bos taurus (Bovine)	SS
P0C7Q4	GNAT3	Guanine nucleotide-binding protein G	Bos taurus (Bovine)	SS
P63097	GNAI1	Guanine nucleotide-binding protein G	Bos taurus (Bovine)	SS
P04896	GNAS	Guanine nucleotide-binding protein G(s) subunit alpha isoforms short	Bos taurus (Bovine)	PR
P38408	GNA14	Guanine nucleotide-binding protein subunit alpha-14	Bos taurus (Bovine)	PR
P50147	GNAI2	Guanine nucleotide-binding protein G	Gallus gallus (Chicken)	SS
P50146	GNAI1	Guanine nucleotide-binding protein G	Gallus gallus (Chicken)	SS
P38400	GNAI2	Guanine nucleotide-binding protein G(i) subunit alpha-2	Canis lupus familiaris (Dog) (Canis familiaris)	PR
Q28294	GNAQ	Guanine nucleotide-binding protein G(q) subunit alpha	Canis lupus familiaris (Dog) (Canis familiaris)	PR
P63091	GNAS	Guanine nucleotide-binding protein G(s) subunit alpha	Canis lupus familiaris (Dog) (Canis familiaris)	PR
P20353	Galphai	G protein alpha i subunit	Drosophila melanogaster (Fruit fly)	SS
P25157	cta	Guanine nucleotide-binding protein subunit alpha homolog	Drosophila melanogaster (Fruit fly)	SS
P23625	Galphaq	G protein alpha q subunit	Drosophila melanogaster (Fruit fly)	PR
P16378	Galphao	G protein alpha o subunit	Drosophila melanogaster (Fruit fly)	SS
A8MTJ3	GNAT3	Guanine nucleotide-binding protein G	Homo sapiens (Human)	SS
P08754	GNAI3	Guanine nucleotide-binding protein G	Homo sapiens (Human)	SS
P11488	GNAT1	Guanine nucleotide-binding protein G	Homo sapiens (Human)	SS
P19086	GNAZ	Guanine nucleotide-binding protein G	Homo sapiens (Human)	SS
P19087	GNAT2	Guanine nucleotide-binding protein G	Homo sapiens (Human)	SS
Q14344	GNA13	Guanine nucleotide-binding protein subunit alpha-13	Homo sapiens (Human)	SS
P29992	GNA11	Guanine nucleotide-binding protein subunit alpha-11	Homo sapiens (Human)	SS
P30679	GNA15	Guanine nucleotide-binding protein subunit alpha-15	Homo sapiens (Human)	SS
P50148	GNAQ	Guanine nucleotide-binding protein G	Homo sapiens (Human)	SS
P38405	GNAL	Guanine nucleotide-binding protein G	Homo sapiens (Human)	SS
O95837	GNA14	Guanine nucleotide-binding protein subunit alpha-14	Homo sapiens (Human)	SS
P04899	GNAI2	Guanine nucleotide-binding protein G	Homo sapiens (Human)	SS
P63096	GNAI1	Guanine nucleotide-binding protein G	Homo sapiens (Human)	EV
Q03113	GNA12	Guanine nucleotide-binding protein subunit alpha-12	Homo sapiens (Human)	SS
P09471	GNAO1	Guanine nucleotide-binding protein G	Homo sapiens (Human)	SS
B2RSH2	Gnai1	Guanine nucleotide-binding protein G	Mus musculus (Mouse)	SS
O70443	Gnaz	Guanine nucleotide-binding protein G	Mus musculus (Mouse)	SS
P08752	Gnai2	Guanine nucleotide-binding protein G	Mus musculus (Mouse)	SS
P20612	Gnat1	Guanine nucleotide-binding protein G	Mus musculus (Mouse)	SS
P27600	Gna12	Guanine nucleotide-binding protein subunit alpha-12	Mus musculus (Mouse)	SS
P27601	Gna13	Guanine nucleotide-binding protein subunit alpha-13	Mus musculus (Mouse)	SS
P50149	Gnat2	Guanine nucleotide-binding protein G	Mus musculus (Mouse)	SS
Q3V3I2	Gnat3	Guanine nucleotide-binding protein G	Mus musculus (Mouse)	SS
Q9DC51	Gnai3	Guanine nucleotide-binding protein G	Mus musculus (Mouse)	SS
P21279	Gnaq	Guanine nucleotide-binding protein G(q) subunit alpha	Mus musculus (Mouse)	PR
P30678	Gna15	Guanine nucleotide-binding protein subunit alpha-15	Mus musculus (Mouse)	PR
P18872	Gnao1	Guanine nucleotide-binding protein G	Mus musculus (Mouse)	SS
Q2PKF4	GNAQ	Guanine nucleotide-binding protein G(q) subunit alpha	Sus scrofa (Pig)	PR
P29797	GNAS	Guanine nucleotide-binding protein G(s) subunit alpha	Sus scrofa (Pig)	PR
P93564	GPA1	Guanine nucleotide-binding protein alpha-1 subunit	Solanum tuberosum (Potato)	SS
P04897	Gnai2	Guanine nucleotide-binding protein G	Rattus norvegicus (Rat)	SS
P08753	Gnai3	Guanine nucleotide-binding protein G	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
Q63210	Gna12	Guanine nucleotide-binding protein subunit alpha-12	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
P82471	Gnaq	Guanine nucleotide-binding protein G	Rattus norvegicus (Rat)	SS
O88302	Gna15	Guanine nucleotide-binding protein subunit alpha-15	Rattus norvegicus (Rat)	SS
Q9JID2	Gna11	Guanine nucleotide-binding protein subunit alpha-11	Rattus norvegicus (Rat)	SS
P38406	Gnal	Guanine nucleotide-binding protein G	Rattus norvegicus (Rat)	SS
P59215	Gnao1	Guanine nucleotide-binding protein G	Rattus norvegicus (Rat)	SS
Q63803	Gnas	Guanine nucleotide-binding protein G	Rattus norvegicus (Rat)	SS
Q0DJ33	GPA1	Guanine nucleotide-binding protein alpha-1 subunit	Oryza sativa subsp. japonica (Rice)	SS
O76584	gpa-11	Guanine nucleotide-binding protein alpha-11 subunit	Caenorhabditis elegans	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
Q9BIG5	gpa-4	Guanine nucleotide-binding protein alpha-4 subunit	Caenorhabditis elegans	SS
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
P49084	GPA1	Guanine nucleotide-binding protein alpha-1 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
MGLLCSRNRR	YNDADAEENA	QTAEIERRIE	VRNERAEKHI	QKLLLLGAGE	SGKSTIFKQI
70	80	90	100	110	120
KLLFQTGFDE	AELKSYLPVI	HANVYQTIKL	LHDGSKEFAQ	NDVDSSKYVI	SNENKEIGEK
130	140	150	160	170	180
LLEIGGRLDY	PYLSKELAQE	IENLWKDPAI	QETYARGSEL	QIPDCTDYFM	ENLQRLSDAN
190	200	210	220	230	240
YVPTKEDVLY	ARVRTTGVVE	IQFSPVGENK	KSDEVYRLFD	VGGQRNERRK	WIHLFEGVSA
250	260	270	280	290	300
VIFCAAISEY	DQTLFEDENR	NRMMETKELF	EWILKQPCFE	KTSFMLFLNK	FDIFEKKILK
310	320	330	340	350	360
VPLNVCEWFK	DYQPVSTGKQ	EIEHAYEFVK	KKFEESYFQS	TAPDRVDRVF	KIYRTTALDQ
370	380
KVVKKTFKLV	DETLRRRNLL	EAGLL