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)
Target domain |
266-356 (C-terminal SHD domain) |
Relief mechanism |
Partner binding, PTM |
Assay |
|
Accessory elements
No accessory elements
References
Autoinhibited structure
Activated structure
2 structures for Q68FF6
| Entry ID | Method | Resolution | Chain | Position | Source |
|---|---|---|---|---|---|
| 6JMU | X-ray | 200 A | A/B | 640-770 | PDB |
| AF-Q68FF6-F1 | Predicted | AlphaFoldDB |
37 variants for Q68FF6
| Variant ID(s) | Position | Change | Description | Diseaes Association | Provenance |
|---|---|---|---|---|---|
| rs3389145670 | 131 | K>I | No | EVA | |
| rs3389195048 | 165 | E>A | No | EVA | |
| rs3389152083 | 184 | E>G | No | EVA | |
| rs3389191991 | 222 | C>S | No | EVA | |
| rs3389180470 | 253 | D>V | No | EVA | |
| rs3389176939 | 260 | M>I | No | EVA | |
| rs3389169392 | 318 | R>H | No | EVA | |
| rs3389169341 | 335 | N>H | No | EVA | |
| rs244957694 | 380 | A>V | No | EVA | |
| rs3389145682 | 384 | S>G | No | EVA | |
| rs3389177820 | 391 | D>N | No | EVA | |
| rs3548741218 | 416 | R>C | No | EVA | |
| rs3389156094 | 424 | D>G | No | EVA | |
| rs3389169353 | 449 | V>L | No | EVA | |
| rs3389185726 | 485 | G>E | No | EVA | |
| rs3389117916 | 487 | V>L | No | EVA | |
| rs3389145629 | 489 | P>Q | No | EVA | |
| rs3389169388 | 493 | P>T | No | EVA | |
| rs3389176947 | 501 | L>F | No | EVA | |
| rs3389181708 | 516 | F>I | No | EVA | |
| rs3389195014 | 535 | E>D | No | EVA | |
| rs3389191985 | 550 | D>N | No | EVA | |
| rs3389181688 | 558 | V>I | No | EVA | |
| rs259601134 | 561 | G>S | No | EVA | |
| rs3389145684 | 588 | E>D | No | EVA | |
| rs248356521 | 593 | A>V | No | EVA | |
| rs3389191981 | 612 | S>N | No | EVA | |
| rs3389182955 | 613 | G>R | No | EVA | |
| rs3389182955 | 613 | G>W | No | EVA | |
| rs3389177812 | 680 | F>I | No | EVA | |
| rs3389195008 | 691 | V>L | No | EVA | |
| rs3389195000 | 708 | R>C | No | EVA | |
| rs3389152129 | 711 | L>P | No | EVA | |
| rs3389185700 | 724 | E>A | No | EVA | |
| rs3389181747 | 741 | L>M | No | EVA | |
| rs3389117893 | 747 | I>F | No | EVA | |
| rs3389180484 | 751 | Y>C | No | EVA |
No associated diseases with Q68FF6
9 regional properties for Q68FF6
| Type | Name | Position | InterPro Accession |
|---|---|---|---|
| domain | Protein kinase domain | 725 - 1017 | IPR000719 |
| domain | Serine-threonine/tyrosine-protein kinase, catalytic domain | 726 - 1006 | IPR001245 |
| domain | Cadherin-like | 168 - 273 | IPR002126 |
| active_site | Tyrosine-protein kinase, active site | 871 - 883 | IPR008266 |
| binding_site | Protein kinase, ATP binding site | 731 - 759 | IPR017441 |
| domain | Tyrosine-protein kinase, catalytic domain | 725 - 1006 | IPR020635 |
| domain | Tyrosine-protein kinase receptor Ret, cadherin like domain 3 | 266 - 380 | IPR040667 |
| domain | Ret, cadherin like domain 1 | 29 - 154 | IPR041163 |
| domain | RET, cadherin-like domain 4 | 407 - 509 | IPR041317 |
Functions
18 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. |
| 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. |
| cytosol | The part of the cytoplasm that does not contain organelles but which does contain other particulate matter, such as protein complexes. |
| dendrite | A neuron projection that has a short, tapering, morphology. Dendrites receive and integrate signals from other neurons or from sensory stimuli, and conduct nerve impulses towards the axon or the cell body. In most neurons, the impulse is conveyed from dendrites to axon via the cell body, but in some types of unipolar neuron, the impulse does not travel via the cell body. |
| endosome | A vacuole to which materials ingested by endocytosis are delivered. |
| excitatory synapse | A synapse in which an action potential in the presynaptic cell increases the probability of an action potential occurring in the postsynaptic cell. |
| focal adhesion | A cell-substrate junction that anchors the cell to the extracellular matrix and that forms a point of termination of actin filaments. In insects focal adhesion has also been referred to as hemi-adherens junction (HAJ). |
| GABA-ergic synapse | A synapse that uses GABA as a neurotransmitter. These synapses are typically inhibitory. |
| glutamatergic synapse | A synapse that uses glutamate as a neurotransmitter. |
| growth cone | The migrating motile tip of a growing neuron projection, where actin accumulates, and the actin cytoskeleton is the most dynamic. |
| inhibitory synapse | A synapse in which an action potential in the presynaptic cell reduces the probability of an action potential occurring in the postsynaptic cell. |
| lamellipodium | A thin sheetlike process extended by the leading edge of a migrating cell or extending cell process; contains a dense meshwork of actin filaments. |
| mitochondrion | A semiautonomous, self replicating organelle that occurs in varying numbers, shapes, and sizes in the cytoplasm of virtually all eukaryotic cells. It is notably the site of tissue respiration. |
| mitotic spindle pole | Either of the ends of a mitotic spindle, a spindle that forms as part of mitosis, where spindle microtubules are organized; usually contains a microtubule organizing center and accessory molecules, spindle microtubules and astral microtubules. |
| neuron projection | A prolongation or process extending from a nerve cell, e.g. an axon or dendrite. |
| postsynapse | The part of a synapse that is part of the post-synaptic cell. |
| postsynaptic density | An electron dense network of proteins within and adjacent to the postsynaptic membrane of an asymmetric, neuron-neuron synapse. Its major components include neurotransmitter receptors and the proteins that spatially and functionally organize them such as anchoring and scaffolding molecules, signaling enzymes and cytoskeletal components. |
| 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. |
10 GO annotations of molecular function
| Name | Definition |
|---|---|
| gamma-tubulin binding | Binding to the microtubule constituent protein gamma-tubulin. |
| GTPase activator activity | Binds to and increases the activity of a GTPase, an enzyme that catalyzes the hydrolysis of GTP. |
| identical protein binding | Binding to an identical protein or proteins. |
| metal ion binding | Binding to a metal ion. |
| protein phosphatase binding | Binding to a protein phosphatase. |
| protein tyrosine kinase binding | Binding to protein tyrosine kinase. |
| protein-containing complex binding | Binding to a macromolecular complex. |
| scaffold protein binding | Binding to a scaffold protein. Scaffold proteins are crucial regulators of many key signaling pathways. Although not strictly defined in function, they are known to interact and/or bind with multiple members of a signaling pathway, tethering them into complexes. |
| small GTPase binding | Binding to a small monomeric GTPase. |
| structural constituent of postsynaptic specialization | The action of a molecule that contributes to the structural integrity of a postsynaptic specialization. |
24 GO annotations of biological process
| Name | Definition |
|---|---|
| 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.). |
| cell redox homeostasis | Any process that maintains the redox environment of a cell or compartment within a cell. |
| cellular response to epidermal growth factor stimulus | 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 an epidermal growth factor stimulus. |
| cellular response to lipopolysaccharide | 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 lipopolysaccharide stimulus; lipopolysaccharide is a major component of the cell wall of gram-negative bacteria. |
| dendritic spine development | The process whose specific outcome is the progression of the dendritic spine over time, from its formation to the mature structure. A dendritic spine is a protrusion from a dendrite and a specialized subcellular compartment involved in synaptic transmission. |
| ephrin receptor signaling pathway | The series of molecular signals initiated by ephrin binding to its receptor, and ending with the regulation of a downstream cellular process, e.g. transcription. |
| immunological synapse formation | The formation of an area of close contact between a lymphocyte (T-, B-, or natural killer cell) and a target cell through the clustering of particular signaling and adhesion molecules and their associated membrane rafts on both the lymphocyte and target cell, which facilitates activation of the lymphocyte, transfer of membrane from the target cell to the lymphocyte, and in some situations killing of the target cell through release of secretory granules and/or death-pathway ligand-receptor interaction. |
| intramembranous ossification | Direct ossification that occurs within mesenchyme or an accumulation of relatively unspecialized cells. |
| locomotory behavior | The specific movement from place to place of an organism in response to external or internal stimuli. Locomotion of a whole organism in a manner dependent upon some combination of that organism's internal state and external conditions. |
| motor learning | Any process in which an organism acquires a novel neuromuscular action or movement as the result of experience. |
| negative regulation of ARF protein signal transduction | Any process that stops, prevents, or reduces the frequency, rate or extent of ARF protein signal transduction. |
| negative regulation of glycolytic process | Any process that stops, prevents, or reduces the frequency, rate or extent of glycolysis. |
| negative regulation of inflammatory response to wounding | Any process that stops, prevents, or reduces the frequency, rate or extent of the inflammatory response to wounding. |
| negative regulation of interleukin-1 beta production | Any process that stops, prevents, or reduces the frequency, rate, or extent of interleukin-1 beta production. |
| neuron development | The process whose specific outcome is the progression of a neuron over time, from initial commitment of the cell to a specific fate, to the fully functional differentiated cell. |
| neurotransmitter receptor localization to postsynaptic specialization membrane | A process in which a neurotransmitter is transported to, or maintained in, a location within the membrane adjacent to a postsynaptic specialization (e.g. postsynaptic density). |
| positive regulation of microtubule nucleation | Any process that increases the rate, frequency or extent of microtubule nucleation. Microtubule nucleation is the 'de novo' formation of a microtubule, in which tubulin heterodimers form metastable oligomeric aggregates, some of which go on to support formation of a complete microtubule. Microtubule nucleation usually occurs from a specific site within a cell. |
| positive regulation of receptor catabolic process | Any process that activates or increases the frequency, rate or extent of receptor catabolic process. |
| 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 cytokinesis | Any process that modulates the frequency, rate or extent of the division of the cytoplasm of a cell and its separation into two daughter cells. |
| 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 |
| Q14161 | GIT2 | ARF GTPase-activating protein GIT2 | Homo sapiens (Human) | SS |
| Q9Y2X7 | GIT1 | ARF GTPase-activating protein GIT1 | Homo sapiens (Human) | SS |
| Q9JLQ2 | Git2 | ARF GTPase-activating protein GIT2 | Mus musculus (Mouse) | SS |
| Q66H91 | Git2 | ARF GTPase-activating protein GIT2 | Rattus norvegicus (Rat) | SS |
| Q9Z272 | Git1 | ARF GTPase-activating protein GIT1 | Rattus norvegicus (Rat) | SS |
| 10 | 20 | 30 | 40 | 50 | 60 |
| MSRKGPRAEV | CADCSAPDPG | WASISRGVLV | CDECCSVHRS | LGRHISIVKH | LRHSAWPPTL |
| 70 | 80 | 90 | 100 | 110 | 120 |
| LQMVHTLASN | GANSIWEHSL | LDPAQVQSGR | RKANPQDKVH | PIKSEFIRAK | YQMLAFVHKL |
| 130 | 140 | 150 | 160 | 170 | 180 |
| PCRDDDGVTA | KDLSKQLHSS | VRTGNLETCL | RLLSLGAQAN | FFHPEKGTTP | LHVAAKAGQT |
| 190 | 200 | 210 | 220 | 230 | 240 |
| LQAELLVVYG | ADPGSPDVNG | RTPIDYARQA | GHHELAERLV | ECQYELTDRL | AFYLCGRKPD |
| 250 | 260 | 270 | 280 | 290 | 300 |
| HKNGHYIIPQ | MADRSRQKCM | SQSLDLSELA | KAAKKKLQAL | SNRLFEELAM | DVYDEVDRRE |
| 310 | 320 | 330 | 340 | 350 | 360 |
| NDAVWLATQN | HSTLVTERSA | VPFLPVNPEY | SATRNQGRQK | LARFNAREFA | TLIIDILSEA |
| 370 | 380 | 390 | 400 | 410 | 420 |
| KRRQQGKSLS | SPTDNLELSA | RSQSELDDQH | DYDSVASDED | TDQEPLPSAG | ATRNNRARSM |
| 430 | 440 | 450 | 460 | 470 | 480 |
| DSSDLSDGAV | TLQEYLELKK | ALATSEAKVQ | QLMKVNSSLS | DELRRLQREI | HKLQAENLQL |
| 490 | 500 | 510 | 520 | 530 | 540 |
| RQPPGPVPPP | SLPSERAEHT | LMGPGGSTHR | RDRQAFSMYE | PGSALKPFGG | TPGDELATRL |
| 550 | 560 | 570 | 580 | 590 | 600 |
| QPFHSTELED | DAIYSVHVPA | GLYRIRKGVS | ASSVPFTPSS | PLLSCSQEGS | RHASKLSRHG |
| 610 | 620 | 630 | 640 | 650 | 660 |
| SGADSDYENT | QSGDPLLGLE | GKRFLELSKE | DELHPELESL | DGDLDPGLPS | TEDVILKTEQ |
| 670 | 680 | 690 | 700 | 710 | 720 |
| VTKNIQELLR | AAQEFKHDSF | VPCSEKIHLA | VTEMASLFPK | RPALEPVRSS | LRLLNASAYR |
| 730 | 740 | 750 | 760 | ||
| LQSECRKTVP | PEPGAPVDFQ | LLTQQVIQCA | YDIAKAAKQL | VTITTREKKQ |