AiPD: Autoinhibited Protein Database

Q66H91

Gene name	Git2
Protein name	ARF GTPase-activating protein GIT2
Names	ARF GAP GIT2 , Cool-interacting tyrosine-phosphorylated protein 2 , CAT-2 , CAT2 , G protein-coupled receptor kinase-interactor 2 , GRK-interacting protein 2
Species	Rattus norvegicus (Rat)
KEGG Pathway	rno:304546
EC number
Protein Class

Descriptions

G-protein coupled receptor kinase-interacting protein (GIT, p95-APP1) proteins include an N-terminal Arf GTPase-activating protein domain (Arf-GAP domain), three ankyrin repeats, a Spa2-homology domain (SHD), a coiled-coil domain including a leucine zipper required for dimerization, and a paxillin-binding site (PBS). To autoinhibit the C-terminal domain, the N-terminal GAP domain (1-124) interacts with the C-terminal domain. In addition, the interaction between the ankyrin repeats and SHD domain is probably the main intramolecular interface to keep the inactive conformation (GAP-C terminal domain interaction) of p95-APP1. Therefore, the SHD domain is essential in mediating the intramolecular interactions between the C-terminal half of GIT1 and the N-terminal part including GAP domain and ankyrin repeats.

Autoinhibitory domains (AIDs)

1-228 (N-terminal part including GAP domain and ankyrin repeats) SS

Target domain	259-349 (C-terminal SHD domain)
Relief mechanism	Partner binding, PTM
Assay

AID

1-228 (N-terminal part including GAP domain and ankyrin repeats)

Target domain

259-349 (C-terminal SHD domain)

Relief mechanism

Partner binding (Binding of paxillin and liprin-α to PBS domain), PTM (Phosphorylation at Ser-709 within PBS domain)

Assay

Accessory elements

No accessory elements

References

Totaro A et al. (2007) "Identification of an intramolecular interaction important for the regulation of GIT1 functions", Molecular biology of the cell, 18, 5124-38

Di Cesare A et al. (2000) "p95-APP1 links membrane transport to Rac-mediated reorganization of actin", Nature cell biology, 2, 521-30

Autoinhibited structure

Activated structure

1 structures for Q66H91

Entry ID	Method	Resolution	Chain	Position	Source
AF-Q66H91-F1	Predicted				AlphaFoldDB

No variants for Q66H91

Variant ID(s)	Position	Change	Description	Diseaes Association	Provenance
No variants for Q66H91

No associated diseases with Q66H91

1 regional properties for Q66H91

Type	Name	Position	InterPro Accession
domain	Centrosomal protein of 290kDa, coiled-coil region	1289 - 1416	IPR032321

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
calyx of Held	The terminal specialization of a calyciferous axon which forms large synapses in the mammalian auditory central nervous system.
nucleoplasm	That part of the nuclear content other than the chromosomes or the nucleolus.
presynapse	The part of a synapse that is part of the presynaptic cell.
synapse	The junction between an axon of one neuron and a dendrite of another neuron, a muscle fiber or a glial cell. As the axon approaches the synapse it enlarges into a specialized structure, the presynaptic terminal bouton, which contains mitochondria and synaptic vesicles. At the tip of the terminal bouton is the presynaptic membrane; facing it, and separated from it by a minute cleft (the synaptic cleft) is a specialized area of membrane on the receiving cell, known as the postsynaptic membrane. In response to the arrival of nerve impulses, the presynaptic terminal bouton secretes molecules of neurotransmitters into the synaptic cleft. These diffuse across the cleft and transmit the signal to the postsynaptic membrane.

4 GO annotations of molecular function

Name	Definition
GTPase activator activity	Binds to and increases the activity of a GTPase, an enzyme that catalyzes the hydrolysis of GTP.
metal ion binding	Binding to a metal ion.
protein-containing complex binding	Binding to a macromolecular complex.
small GTPase binding	Binding to a small monomeric GTPase.

7 GO annotations of biological process

Name	Definition
behavioral response to pain	Any process that results in a change in the behavior of an organism as a result of a pain stimulus. Pain stimuli cause activation of nociceptors, peripheral receptors for pain, include receptors which are sensitive to painful mechanical stimuli, extreme heat or cold, and chemical stimuli.
brain development	The process whose specific outcome is the progression of the brain over time, from its formation to the mature structure. Brain development begins with patterning events in the neural tube and ends with the mature structure that is the center of thought and emotion. The brain is responsible for the coordination and control of bodily activities and the interpretation of information from the senses (sight, hearing, smell, etc.).
presynaptic modulation of chemical synaptic transmission	Any process, acting in the presynapse that results in modulation of chemical synaptic transmission.
regulation of ARF protein signal transduction	Any process that modulates the frequency, rate or extent of ARF protein signal transduction.
regulation of G protein-coupled receptor signaling pathway	Any process that modulates the frequency, rate or extent of G protein-coupled receptor signaling pathway.
regulation of synaptic vesicle exocytosis	Any process that modulates the frequency, rate or extent of synaptic vesicle exocytosis.
synaptic vesicle recycling	The trafficking of synaptic vesicles from the pre-synaptic membrane so the vesicle can dock and prime for another round of exocytosis and neurotransmitter release. Recycling occurs after synaptic vesicle exocytosis, and is necessary to replenish presynaptic vesicle pools, sustain transmitter release and preserve the structural integrity of the presynaptic membrane. Recycling can occur following transient fusion with the presynaptic membrane (kiss and run), or via endocytosis of presynaptic membrane.

7 homologous proteins in AiPD

UniProt AC	Gene Name	Protein Name	Species	Evidence Code
Q9DG15		p95-APP1	Gallus gallus (Chicken)	EV
Q95RG8	Git	ARF GTPase-activating protein Git	Drosophila melanogaster (Fruit fly)	SS
Q9Y2X7	GIT1	ARF GTPase-activating protein GIT1	Homo sapiens (Human)	SS
Q14161	GIT2	ARF GTPase-activating protein GIT2	Homo sapiens (Human)	SS
Q68FF6	Git1	ARF GTPase-activating protein GIT1	Mus musculus (Mouse)	SS
Q9JLQ2	Git2	ARF GTPase-activating protein GIT2	Mus musculus (Mouse)	SS
Q9Z272	Git1	ARF GTPase-activating protein GIT1	Rattus norvegicus (Rat)	SS

10	20	30	40	50	60
MSKRLRSNDV	CADCSGPDPS	WASVNRGTLI	CDECCSVHRS	LGRHISQVRH	LKHTPWPPTL
70	80	90	100	110	120
LQMVETLYSN	GANSIWEHSL	LDPASVMSGR	RKANPQDKVH	PNKAEFIRAK	YQMLAFVHRL
130	140	150	160	170	180
PCRDDDSVTA	KDLSKQLHSS	VRTGNLETCL	RLLSLGAQAN	FFHPEKGSTP	LHVASKAGQI
190	200	210	220	230	240
LQAELLAVYG	ADPGTHDSSG	KTPVDYARQG	GHRELAERLV	EIQYELTDRL	AFYLCGRKPD
250	260	270	280	290	300
HKNGQHFIIP	QMADSSLDLS	ELAKAAKKKL	QSLSNHLFEE	LAMDVYDEVD	RRETDAVWLA
310	320	330	340	350	360
TQNHSTLVTE	TTVVPFLPVN	PEYSSTRNQG	RQKLARFNAH	EFATLVIDIL	SDAKRRQQGS
370	380	390	400	410	420
PLSRSKDNVE	LILRTVSNQH	STESQDNDQP	DYDSVASDED	TDVETRASRT	NRQKSLDSDL
430	440	450	460	470	480
SDGPVTVQEF	MEVKHALVAS	EAKRQQLMKV	NNNLSGELRI	MQKKLQTLQS	ENSSLRRQAT
490	500	510	520	530	540
ASACQVQTAS	DHKDTVSHSS	LKRRPSARGS	RPMSMYETGS	GQKPYLPMGE	ANHPEESRTR
550	560	570	580	590	600
LQPFPTHIGR	SALVTSSSSL	PSFPSTLSWS	RDESTRRASR	LEKQNSTPES	DYDNTAYDPE
610	620	630	640	650	660
PDDTVSGRKG	RQRSMLWQGD	GPLPDTAEPH	AVPSPALPST	EDVIRKTEQI	TKNIQELLRA
670	680	690	700	710	720
AQENKHDSYI	PCSERIHAAV	TEMAALFPKK	PKSDTVRTSL	RLLTASAYRL	QSECRKALPG
730	740	750
DSSLPTDVQL	VTQQVIQCAY	DIAKAAKQLV	TITTKENSS