AiPD: Autoinhibited Protein Database

P63097

Gene name	GNAI1
Protein name	Guanine nucleotide-binding protein G
Names	i subunit alpha-1 , Adenylate cyclase-inhibiting G alpha protein
Species	Bos taurus (Bovine)
KEGG Pathway	bta:281790
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)

204-205 (Gln204) SS

Target domain	179-349 (P-loop containing nucleoside triphosphate hydrolase domain)
Relief mechanism	Partner binding
Assay

AID

204-205 (Gln204)

Target domain

179-349 (P-loop containing nucleoside triphosphate hydrolase domain)

Relief mechanism

Partner binding (RGS4 binding)

Assay

62-177 (α-H domain) SS

Target domain	184-348 (Ras-like domain)
Relief mechanism	Ligand binding, Partner binding
Assay

AID

62-177 (α-H domain)

Target domain

184-348 (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

7 structures for P63097

Entry ID	Method	Resolution	Chain	Position	Source
6K42	EM	410 A	A	1-354	PDB
6NBF	EM	300 A	A	61-184	PDB
6NBH	EM	350 A	A	61-184	PDB
6NBI	EM	400 A	A	61-184	PDB
7D68	EM	300 A	A	61-184	PDB
7EQ1	EM	330 A			PDB
AF-P63097-F1	Predicted				AlphaFoldDB

No variants for P63097

Variant ID(s)	Position	Change	Description	Diseaes Association	Provenance
No variants for P63097

No associated diseases with P63097

3 regional properties for P63097

Type	Name	Position	InterPro Accession
domain	Ras-associating domain	141 - 253	IPR000159
domain	Dilute domain	594 - 895	IPR002710
domain	Rasip1/Radil, cargo-binding domain	545 - 911	IPR037983

Functions

		Description
EC Number
Subcellular Localization	Nucleus Cytoplasm Cell membrane ; Peripheral membrane protein ; Cytoplasmic side Cytoplasm, cytoskeleton, microtubule organizing center, centrosome Cytoplasm, cell cortex Membrane ; Lipid-anchor	Localizes in the centrosomes of interphase and mitotic cells, but not in centrosomes during cytokinesis Detected at the cleavage furrow or the midbody Localized at the plasma membrane throughout mitosis Colocalizes with RIC8A and RGS14 at the plasma membrane
PANTHER Family
PANTHER Subfamily
PANTHER Protein Class
PANTHER Pathway Category	No pathway information available

7 GO annotations of cellular component

Name	Definition
cell cortex	The region of a cell that lies just beneath the plasma membrane and often, but not always, contains a network of actin filaments and associated proteins.
centrosome	A structure comprised of a core structure (in most organisms, a pair of centrioles) and peripheral material from which a microtubule-based structure, such as a spindle apparatus, is organized. Centrosomes occur close to the nucleus during interphase in many eukaryotic cells, though in animal cells it changes continually during the cell-division cycle.
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.
midbody	A thin cytoplasmic bridge formed between daughter cells at the end of cytokinesis. The midbody forms where the contractile ring constricts, and may persist for some time before finally breaking to complete cytokinesis.
nucleus	A membrane-bounded organelle of eukaryotic cells in which chromosomes are housed and replicated. In most cells, the nucleus contains all of the cell's chromosomes except the organellar chromosomes, and is the site of RNA synthesis and processing. In some species, or in specialized cell types, RNA metabolism or DNA replication may be absent.
plasma membrane	The membrane surrounding a cell that separates the cell from its external environment. It consists of a phospholipid bilayer and associated proteins.

7 GO annotations of molecular function

Name	Definition
G protein-coupled receptor binding	Binding to a G protein-coupled receptor.
G protein-coupled serotonin receptor binding	Binding to a metabotropic serotonin receptor.
G-protein beta/gamma-subunit complex binding	Binding to a complex of G-protein beta/gamma subunits.
GDP binding	Binding to GDP, guanosine 5'-diphosphate.
GTP binding	Binding to GTP, guanosine triphosphate.
GTPase activity	Catalysis of the reaction
magnesium ion binding	Binding to a magnesium (Mg) ion.

8 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).
cell cycle	The progression of biochemical and morphological phases and events that occur in a cell during successive cell replication or nuclear replication events. Canonically, the cell cycle comprises the replication and segregation of genetic material followed by the division of the cell, but in endocycles or syncytial cells nuclear replication or nuclear division may not be followed by cell division.
cell division	The process resulting in division and partitioning of components of a cell to form more cells; may or may not be accompanied by the physical separation of a cell into distinct, individually membrane-bounded daughter cells.
cellular response to forskolin	Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a forskolin stimulus.
G protein-coupled receptor signaling pathway	The series of molecular signals initiated by a ligand binding to its receptor, in which the activated receptor promotes the exchange of GDP for GTP on the alpha-subunit of an associated heterotrimeric G-protein complex. The GTP-bound activated alpha-G-protein then dissociates from the beta- and gamma-subunits to further transmit the signal within the cell. The pathway begins with receptor-ligand interaction, and ends with regulation of a downstream cellular process. The pathway can start from the plasma membrane, Golgi or nuclear membrane.
positive regulation of protein localization to cell cortex	Any process that activates or increases the frequency, rate or extent of protein localization to cell cortex.
regulation of cAMP-mediated signaling	Any process which modulates the frequency, rate or extent of cAMP-mediated signaling.
regulation of mitotic spindle organization	Any process that modulates the rate, frequency or extent of the assembly, arrangement of constituent parts, or disassembly of the microtubule spindle during a mitotic cell cycle.

59 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
P38408	GNA14	Guanine nucleotide-binding protein subunit alpha-14	Bos taurus (Bovine)	PR
P04896	GNAS	Guanine nucleotide-binding protein G(s) subunit alpha isoforms short	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
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
O76584	gpa-11	Guanine nucleotide-binding protein alpha-11 subunit	Caenorhabditis elegans	SS
P51875	goa-1	Guanine nucleotide-binding protein G	Caenorhabditis elegans	SS
Q18434	odr-3	Guanine nucleotide-binding protein alpha-17 subunit	Caenorhabditis elegans	SS
Q9BIG4	gpa-10	Guanine nucleotide-binding protein alpha-10 subunit	Caenorhabditis elegans	PR
P28052	gpa-3	Guanine nucleotide-binding protein alpha-3 subunit	Caenorhabditis elegans	SS
Q9XTB2	gpa-13	Guanine nucleotide-binding protein alpha-13 subunit	Caenorhabditis elegans	SS
Q93743	gpa-6	Guanine nucleotide-binding protein alpha-6 subunit	Caenorhabditis elegans	SS
Q20907	gpa-8	Guanine nucleotide-binding protein alpha-8 subunit	Caenorhabditis elegans	PR
P91907	gpa-15	Guanine nucleotide-binding protein alpha-15 subunit	Caenorhabditis elegans	SS
Q21917	gpa-7	Guanine nucleotide-binding protein alpha-7 subunit	Caenorhabditis elegans	SS
P28051	gpa-1	Guanine nucleotide-binding protein alpha-1 subunit	Caenorhabditis elegans	SS
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
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
MGCTLSAEDK	AAVERSKMID	RNLREDGEKA	AREVKLLLLG	AGESGKSTIV	KQMKIIHEAG
70	80	90	100	110	120
YSEEECKQYK	AVVYSNTIQS	IIAIIRAMGR	LKIDFGDSAR	ADDARQLFVL	AGAAEEGFMT
130	140	150	160	170	180
AELAGVIKRL	WKDSGVQACF	NRSREYQLND	SAAYYLNDLD	RIAQPNYIPT	QQDVLRTRVK
190	200	210	220	230	240
TTGIVETHFT	FKDLHFKMFD	VGGQRSERKK	WIHCFEGVTA	IIFCVALSDY	DLVLAEDEEM
250	260	270	280	290	300
NRMHESMKLF	DSICNNKWFT	DTSIILFLNK	KDLFEEKIKK	SPLTICYPEY	AGSNTYEEAA
310	320	330	340	350
AYIQCQFEDL	NKRKDTKEIY	THFTCATDTK	NVQFVFDAVT	DVIIKNNLKD	CGLF