AiPD: Autoinhibited Protein Database

P46109

Gene name	CRKL
Protein name	Crk-like protein
Names
Species	Homo sapiens (Human)
KEGG Pathway	hsa:1399
EC number
Protein Class

Descriptions

CRK-like protein may mediate the transduction of intracellular signals, and composed of three domains (SH3, nSH3, and cSH3) as CRK does. According to CRK autoinhibition studies including mouse CRK, the SH2 and nSH3 domains are used to recruit their target proteins. The interaction between SH2 and inter-domain linker between nSH3 and cSH3 detaches the SH2-targeting proteins. In addition, cSH3 negatively regulates the function of nSH3.

Autoinhibitory domains (AIDs)

184-296 (C-terminal SH3 domain) SS

Target domain	123-183 (N-terminal SH3 domain)
Relief mechanism	PTM
Assay

AID

184-296 (C-terminal SH3 domain)

Target domain

123-183 (N-terminal SH3 domain)

Relief mechanism

PTM (Phosphorylation at Tyr221)

Assay

Accessory elements

No accessory elements

References

Kobashigawa Y et al. (2007) "Structural basis for the transforming activity of human cancer-related signaling adaptor protein CRK", Nature structural & molecular biology, 14, 503-10

Ogawa S et al. (1994) "The C-terminal SH3 domain of the mouse c-Crk protein negatively regulates tyrosine-phosphorylation of Crk associated p130 in rat 3Y1 cells", Oncogene, 9, 1669-78

Sriram G et al. (2012) "Commentary: The carboxyl-terminal Crk SH3 domain: Regulatory strategies and new perspectives", FEBS letters, 586, 2615-8

Takeuchi K et al. (2010) "Autoinhibitory interaction in the multidomain adaptor protein Nck: possible roles in improving specificity and functional diversity", Biochemistry, 49, 5634-41

Autoinhibited structure

Activated structure

7 structures for P46109

Entry ID	Method	Resolution	Chain	Position	Source
2BZX	X-ray	280 A	A	237-303	PDB
2BZY	X-ray	250 A	A/B	237-303	PDB
2DBK	NMR	-	A	229-303	PDB
2EO3	NMR	-	A	1-104	PDB
2LQN	NMR	-	A	1-303	PDB
2LQW	NMR	-	A	1-303	PDB
AF-P46109-F1	Predicted				AlphaFoldDB

171 variants for P46109

Variant ID(s)	Position	Change	Description	Diseaes Association	Provenance
CA10117262 rs745921293	2	S>F		No	ClinGen ExAC TOPMed gnomAD
CA410765205 rs1463139007	3	S>F		No	ClinGen gnomAD
CA410765207 rs1378084235	4	A>T		No	ClinGen TOPMed
rs1394048815 CA410765212	4	A>V		No	ClinGen gnomAD
rs1467146233 CA410765213	5	R>G		No	ClinGen gnomAD
CA410765218 rs778958922	5	R>S		No	ClinGen ExAC TOPMed gnomAD
CA10117264 rs778958922	5	R>S		No	ClinGen ExAC TOPMed gnomAD
rs1388023973 CA410765236	8	S>P		No	ClinGen TOPMed
CA410765246 COSM1751748 rs1430434565	9	S>L	urinary_tract [Cosmic]	No	ClinGen cosmic curated gnomAD
rs547899646 CA10117266	10	D>V		No	ClinGen 1000Genomes ExAC gnomAD
rs567876179 CA10117267	11	R>H		No	ClinGen 1000Genomes ExAC gnomAD
rs567876179 CA322296275	11	R>L		No	ClinGen 1000Genomes ExAC gnomAD
rs1458100931 CA410765259	12	S>P		No	ClinGen TOPMed
rs770480792 CA10117269	13	A>T		No	ClinGen ExAC gnomAD
rs776257196 CA10117270	13	A>V		No	ClinGen ExAC gnomAD
rs865927265 CA322296294	16	M>V		No	ClinGen Ensembl
CA10117271 rs758939601	17	G>R		No	ClinGen ExAC gnomAD
rs138882903 CA322296307	18	P>L		No	ClinGen ESP ExAC TOPMed gnomAD
CA10117272 rs138882903	18	P>R		No	ClinGen ESP ExAC TOPMed gnomAD
rs1180503338 CA410765306	19	V>G		No	ClinGen TOPMed
CA10117273 rs775929456	19	V>L		No	ClinGen ExAC gnomAD
CA10117274 rs763322278	22	Q>H		No	ClinGen ExAC TOPMed gnomAD
CA322296324 rs62238487	22	Q>K		No	ClinGen Ensembl
CA410765330 rs1460095339	23	E>G		No	ClinGen gnomAD
CA322296351 rs888463667	26	T>A		No	ClinGen TOPMed gnomAD
CA10117276 rs751864009	26	T>I		No	ClinGen ExAC gnomAD
CA410765350 rs751864009	26	T>S		No	ClinGen ExAC gnomAD
rs1601669816 CA410765365	29	Q>P		No	ClinGen Ensembl
rs756219565 CA10117280	30	G>S		No	ClinGen ExAC gnomAD
rs199641129 CA322296404	32	R>L		No	ClinGen Ensembl
rs770661007 CA10117286	35	M>I		No	ClinGen ExAC TOPMed gnomAD
rs746762587 CA10117285	35	M>L		No	ClinGen ExAC gnomAD
rs746762587 CA410765402	35	M>L		No	ClinGen ExAC gnomAD
rs1601669837 CA410765419	37	L>F		No	ClinGen Ensembl
CA410765431 rs1422177625	39	R>G		No	ClinGen gnomAD
CA322296472 rs966859460	39	R>H		No	ClinGen Ensembl
rs1364659560 CA410765435	40	D>H		No	ClinGen gnomAD
rs1601669855 CA410765454	43	T>S		No	ClinGen Ensembl
rs769136802 CA10117292	44	C>*		No	ClinGen ExAC TOPMed gnomAD
rs1157261023 CA410765463	44	C>Y		No	ClinGen gnomAD
CA10117293 rs774827798	45	P>L		No	ClinGen ExAC TOPMed gnomAD
rs1236385760 CA410765547	57	R>Q		No	ClinGen gnomAD
rs1364651927 CA410765568	59	S>C		No	ClinGen gnomAD
CA410765594 rs1278191120	61	Y>C		No	ClinGen gnomAD
CA10117298 rs766496631	64	N>S		No	ClinGen ExAC TOPMed gnomAD
rs1418708599 CA410765655	65	S>L		No	ClinGen TOPMed
CA10117299 rs753956143	67	P>S		No	ClinGen ExAC TOPMed gnomAD
CA322296521 rs973151946	68	N>H		No	ClinGen Ensembl
CA410765687 rs1397083945	68	N>S		No	ClinGen TOPMed gnomAD
rs1463918076 CA410765838	76	Q>H		No	ClinGen TOPMed gnomAD
rs745447266 CA10117305	77	E>K		No	ClinGen ExAC gnomAD
CA10117307 rs779594981	80	H>Y		No	ClinGen ExAC gnomAD
rs1327554664 CA410765964	82	P>L		No	ClinGen gnomAD
CA322296590 rs1054393986	82	P>S		No	ClinGen Ensembl
rs3180409 CA322296595	91	H>Y		No	ClinGen Ensembl
CA410766131 rs1338868128	92	Y>C		No	ClinGen gnomAD
rs773484875 CA10117313	97	T>I		No	ClinGen ExAC gnomAD
rs1257146277 CA410766256	99	I>L		No	ClinGen TOPMed
CA410766262 rs1257146277	99	I>V		No	ClinGen TOPMed
CA410766275 rs1569130085	100	E>Q		No	ClinGen Ensembl
CA10117316 rs776895332	103	P>H		No	ClinGen ExAC gnomAD
rs766688775 CA10117315	103	P>S		No	ClinGen ExAC
rs1399022200 CA410766342	104	R>G		No	ClinGen TOPMed
CA410761882 rs1213587964	106	P>A		No	ClinGen TOPMed gnomAD
CA410761884 rs775637595	106	P>L		No	ClinGen ExAC gnomAD
CA10117337 rs775637595	106	P>R		No	ClinGen ExAC gnomAD
rs761713297 CA10117338	107	S>G		No	ClinGen ExAC TOPMed gnomAD
CA10117340 rs767466740	107	S>R		No	ClinGen ExAC gnomAD
rs755863490 CA10117341	108	P>S		No	ClinGen ExAC gnomAD
CA410761899 rs1188009275	109	P>S		No	ClinGen TOPMed
CA10117342 rs200265850	110	M>V		No	ClinGen ExAC gnomAD
CA10117343 rs753427288 COSM1751749	114	S>L	urinary_tract [Cosmic]	No	ClinGen cosmic curated ExAC gnomAD
CA410761936 rs1378195752	115	A>S		No	ClinGen gnomAD
rs925122172 CA322269072	115	A>V		No	ClinGen Ensembl
rs376691633 CA10117344	116	P>T		No	ClinGen ESP ExAC gnomAD
CA10117345 rs778350864	117	N>K		No	ClinGen ExAC TOPMed gnomAD
rs936540793 CA322269077	117	N>S		No	ClinGen TOPMed gnomAD
CA322269075 rs3180410	117	N>Y		No	ClinGen Ensembl
rs1451933601 CA410761961	120	T>A		No	ClinGen Ensembl
rs1447468704 CA410761965	120	T>I		No	ClinGen gnomAD
CA410761968 rs1301110218	121	A>T		No	ClinGen gnomAD
CA10117346 rs752232310	122	E>G		No	ClinGen ExAC gnomAD
rs148491827 CA322269082	122	E>K		No	ClinGen Ensembl
rs1276902404 CA410761986	124	N>H		No	ClinGen TOPMed
CA410761990 rs1220289351	124	N>S		No	ClinGen TOPMed
CA410761999 rs1344311195	126	E>K		No	ClinGen gnomAD
rs758872714 CA10117347	127	Y>C		No	ClinGen ExAC TOPMed gnomAD
rs1309018634 CA410762030	130	T>S		No	ClinGen gnomAD
rs1221209545 CA410762032 COSM579733	131	L>V	lung [Cosmic]	No	ClinGen cosmic curated gnomAD
CA10117348 rs778388431	137	N>S		No	ClinGen ExAC gnomAD
rs747404847 CA10117349	139	A>D		No	ClinGen ExAC TOPMed gnomAD
rs747404847 CA410762090	139	A>V		No	ClinGen ExAC TOPMed gnomAD
rs781570771 CA10117351	143	P>S		No	ClinGen ExAC gnomAD
rs770045446 CA10117353	145	K>E		No	ClinGen ExAC
rs775479004 CA10117354	146	K>N		No	ClinGen ExAC gnomAD
CA10117356 rs771933873	152	I>V		No	ClinGen ExAC gnomAD
rs1276223674 CA410762284	153	I>T		No	ClinGen gnomAD
CA410762496 rs1235946709	162	S>N		No	ClinGen gnomAD
CA410762531 rs760471921	164	R>G		No	ClinGen ExAC gnomAD
CA10117359 rs200712124	164	R>Q		No	ClinGen ExAC TOPMed gnomAD
CA10117358 rs760471921	164	R>W		No	ClinGen ExAC gnomAD
rs373785511 CA322269138	169	R>Q		No	ClinGen ESP TOPMed
CA410762620 rs1356309955	169	R>W		No	ClinGen gnomAD
rs759166693 CA10117361	175	V>L		No	ClinGen ExAC gnomAD
rs535421669 CA10117362	178	V>I		No	ClinGen 1000Genomes ExAC gnomAD
rs1217926975 CA410762779	179	E>G		No	ClinGen gnomAD
CA410762771 rs1260646700	179	E>K		No	ClinGen Ensembl
rs1307610334 CA410762804	181	L>F		No	ClinGen gnomAD
rs952900119 CA322269152	181	L>P		No	ClinGen Ensembl
CA410762814 rs1253813166	182	V>L		No	ClinGen TOPMed
rs1253813166 CA410762811	182	V>M		No	ClinGen TOPMed
CA410762884 rs1451107236	185	S>L		No	ClinGen TOPMed
rs147576993 CA10117366	186	P>A		No	ClinGen ESP ExAC TOPMed gnomAD
CA322269176 rs147576993	186	P>S		No	ClinGen ESP ExAC TOPMed gnomAD
rs757836194 CA10117367	187	H>Y		No	ClinGen ExAC gnomAD
CA10117369 rs746219908	188	G>R		No	ClinGen ExAC gnomAD
CA322269196 rs199907840	190	H>R		No	ClinGen 1000Genomes TOPMed
rs1267925221 CA410762971	192	N>S		No	ClinGen TOPMed
CA322269203 rs748247058	196	N>S		No	ClinGen TOPMed gnomAD
CA10117372 rs749349384	197	S>G		No	ClinGen ExAC gnomAD
CA410763061 rs1569134891	202	E>K		No	ClinGen Ensembl
CA10117375 rs200629140	203	P>A		No	ClinGen ExAC gnomAD
CA10117376 rs770839945	204	A>S		No	ClinGen ExAC gnomAD
rs1601679635 CA410763076	204	A>V		No	ClinGen Ensembl
CA322269260 COSM1415033 rs976691655	205	H>R	large_intestine [Cosmic]	No	ClinGen cosmic curated Ensembl
rs1363256176 CA410763133	213	T>A		No	ClinGen gnomAD
rs1323862187 CA410763143	214	T>I		No	ClinGen TOPMed
rs1336540725 CA410763149	215	P>L		No	ClinGen gnomAD
rs764823179 CA10117380	217	P>S		No	ClinGen ExAC gnomAD
rs1479479199 CA410763162	218	A>S		No	ClinGen TOPMed gnomAD
CA10117382 rs762375550	218	A>V		No	ClinGen ExAC gnomAD
CA410763169 rs1385927465	219	V>A		No	ClinGen TOPMed
rs145813322 CA10117384	221	G>S		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
rs757890975 CA10117385	221	G>V		No	ClinGen ExAC TOPMed gnomAD
rs768104683 CA10117386	222	S>F		No	ClinGen ExAC gnomAD
rs1421511528 CA410763188	223	P>S		No	ClinGen gnomAD
CA10117387 rs750783216	225	A>T		No	ClinGen ExAC gnomAD
rs1165973049 CA410763203	226	A>T		No	ClinGen gnomAD
CA10117388 rs756451346	226	A>V		No	ClinGen ExAC TOPMed gnomAD
CA410763209 rs1404011600	227	I>V		No	ClinGen gnomAD
CA410763216 rs1477769854	228	T>A		No	ClinGen TOPMed
CA410763215 rs1477769854	228	T>P		No	ClinGen TOPMed
rs1320625946 CA410763227	230	L>M		No	ClinGen gnomAD
rs1601679701 CA410763244	232	S>C		No	ClinGen Ensembl
CA10117389 rs780153751	233	T>P		No	ClinGen ExAC gnomAD
CA410763262 rs1201043851	235	N>T		No	ClinGen TOPMed
rs1469767752 CA410763286	239	F>L		No	ClinGen TOPMed gnomAD
rs749456958 CA10117390	240	A>V		No	ClinGen ExAC gnomAD
CA10117392 rs557938965	243	I>V		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
rs1233334173 CA410763322	244	Q>R		No	ClinGen gnomAD
CA410763357 rs1283293456	248	P>T		No	ClinGen gnomAD
CA410763475 rs1284642010	257	A>P		No	ClinGen gnomAD
rs1184315163 CA410765848	263	I>T		No	ClinGen gnomAD
CA322278252 rs564684352	266	V>I		No	ClinGen 1000Genomes gnomAD
rs138367739 CA322278271	268	R>K		No	ClinGen ESP TOPMed
rs1397431974 CA410765990	270	N>S		No	ClinGen TOPMed gnomAD
rs1171503635 CA410766034	272	N>K		No	ClinGen gnomAD
rs1375676692 CA410766205	282	R>C		No	ClinGen gnomAD
CA410766211 COSM182541 rs1444326760	282	R>H	large_intestine [Cosmic]	No	ClinGen cosmic curated gnomAD
rs1305274368 CA410766345	289	T>S		No	ClinGen gnomAD
CA322278343 rs1001709647	291	V>I		No	ClinGen TOPMed gnomAD
rs1034579377 CA322278364	293	I>M		No	ClinGen Ensembl
CA410766425 rs1197627340	293	I>T		No	ClinGen gnomAD
rs774096605 CA10117422	296	P>L		No	ClinGen ExAC gnomAD
CA410766467 rs1457428290	296	P>S		No	ClinGen gnomAD
rs568979801 CA10117423	297	Q>*		No	ClinGen ExAC gnomAD
rs766986280 CA10117425	299	P>A		No	ClinGen ExAC gnomAD
CA10117424 rs766986280	299	P>S		No	ClinGen ExAC gnomAD
CA410766502 rs766986280	299	P>T		No	ClinGen ExAC gnomAD
CA10117428 rs201830706	301	E>D		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
rs1004094172 CA322278385	301	E>G		No	ClinGen TOPMed gnomAD

No associated diseases with P46109

7 regional properties for P46109

Type	Name	Position	InterPro Accession
domain	C2 domain	656 - 784	IPR000008
domain	Phosphatidylinositol-specific phospholipase C, X domain	316 - 468	IPR000909
domain	Phospholipase C, phosphatidylinositol-specific, Y domain	540 - 656	IPR001711
domain	Phospholipase C-beta, C-terminal domain	1004 - 1173	IPR014815
domain	Phosphoinositide-specific phospholipase C, EF-hand-like domain	216 - 307	IPR015359
domain	1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1, EF hand motif	153 - 303	IPR028400
domain	PLC-beta, PH domain	18 - 148	IPR037862

Functions

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

5 GO annotations of cellular component

Name	Definition
cytosol	The part of the cytoplasm that does not contain organelles but which does contain other particulate matter, such as protein complexes.
extrinsic component of postsynaptic membrane	The component of the postsynaptic membrane consisting of gene products and protein complexes that are loosely bound to one of its surfaces, but not integrated into the hydrophobic region.
neuromuscular junction	The junction between the axon of a motor neuron and a muscle fiber. In response to the arrival of action potentials, the presynaptic button releases molecules of neurotransmitters into the synaptic cleft. These diffuse across the cleft and transmit the signal to the postsynaptic membrane of the muscle fiber, leading to a change in post-synaptic potential.
nucleoplasm	That part of the nuclear content other than the chromosomes or the nucleolus.
protein-containing complex	A stable assembly of two or more macromolecules, i.e. proteins, nucleic acids, carbohydrates or lipids, in which at least one component is a protein and the constituent parts function together.

7 GO annotations of molecular function

Name	Definition
cadherin binding	Binding to cadherin, a type I membrane protein involved in cell adhesion.
identical protein binding	Binding to an identical protein or proteins.
phosphotyrosine residue binding	Binding to a phosphorylated tyrosine residue within a protein.
receptor tyrosine kinase binding	Binding to a receptor that possesses protein tyrosine kinase activity.
RNA binding	Binding to an RNA molecule or a portion thereof.
RNA polymerase II-specific DNA-binding transcription factor binding	Binding to a sequence-specific DNA binding RNA polymerase II transcription factor, any of the factors that interact selectively and non-covalently with a specific DNA sequence in order to modulate transcription.
signaling adaptor activity	The binding activity of a molecule that brings together two or more molecules in a signaling pathway, permitting those molecules to function in a coordinated way. Adaptor molecules themselves do not have catalytic activity.

49 GO annotations of biological process

Name	Definition
acetylcholine receptor signaling pathway	The series of molecular signals generated as a consequence of an acetylcholine receptor binding to one of its physiological ligands.
activation of GTPase activity	Any process that initiates the activity of an inactive GTPase through the replacement of GDP by GTP.
anterior/posterior pattern specification	The regionalization process in which specific areas of cell differentiation are determined along the anterior-posterior axis. The anterior-posterior axis is defined by a line that runs from the head or mouth of an organism to the tail or opposite end of the organism.
B cell apoptotic process	Any apoptotic process in a B cell, a lymphocyte of B lineage with the phenotype CD19-positive and capable of B cell mediated immunity.
blood vessel development	The process whose specific outcome is the progression of a blood vessel over time, from its formation to the mature structure. The blood vessel is the vasculature carrying blood.
cell chemotaxis	The directed movement of a motile cell guided by a specific chemical concentration gradient. Movement may be towards a higher concentration (positive chemotaxis) or towards a lower concentration (negative chemotaxis).
cell migration	The controlled self-propelled movement of a cell from one site to a destination guided by molecular cues. Cell migration is a central process in the development and maintenance of multicellular organisms.
cellular response to interleukin-7	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 interleukin-7 stimulus.
cellular response to transforming growth factor beta 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 a transforming growth factor beta stimulus.
cellular response to xenobiotic 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 a stimulus from a xenobiotic, a compound foreign to the organism exposed to it. It may be synthesized by another organism (like ampicilin) or it can be a synthetic chemical.
cerebellar neuron development	The process whose specific outcome is the progression of a cerebellar neuron over time, from initial commitment of the cell to a specific fate, to the fully functional differentiated cell.
cerebral cortex development	The progression of the cerebral cortex over time from its initial formation until its mature state. The cerebral cortex is the outer layered region of the telencephalon.
cranial skeletal system development	The process whose specific outcome is the progression of a cranial skeletal system over time, from its formation to the mature structure. The cranial skeletal system is the skeletal subdivision of the head, and includes the skull (cranium plus mandible), pharyngeal and/or hyoid apparatus.
dendrite development	The process whose specific outcome is the progression of the dendrite over time, from its formation to the mature structure.
endothelin receptor signaling pathway	A G protein-coupled receptor signaling pathway initiated by endothelin binding to its receptor on the surface of a target cell, and ending with the regulation of a downstream cellular process, e.g. transcription.
establishment of cell polarity	The specification and formation of anisotropic intracellular organization or cell growth patterns.
fibroblast growth factor receptor signaling pathway	The series of molecular signals generated as a consequence of a fibroblast growth factor receptor binding to one of its physiological ligands.
helper T cell diapedesis	The passage of a helper T cell between the tight junctions of endothelial cells lining blood vessels, typically the fourth and final step of cellular extravasation.
hippocampus development	The progression of the hippocampus over time from its initial formation until its mature state.
intracellular signal transduction	The process in which a signal is passed on to downstream components within the cell, which become activated themselves to further propagate the signal and finally trigger a change in the function or state of the cell.
JNK cascade	An intracellular protein kinase cascade containing at least a JNK (a MAPK), a JNKK (a MAPKK) and a JUN3K (a MAP3K). The cascade can also contain an additional tier: the upstream MAP4K. The kinases in each tier phosphorylate and activate the kinases in the downstream tier to transmit a signal within a cell.
lipid metabolic process	The chemical reactions and pathways involving lipids, compounds soluble in an organic solvent but not, or sparingly, in an aqueous solvent. Includes fatty acids; neutral fats, other fatty-acid esters, and soaps; long-chain (fatty) alcohols and waxes; sphingoids and other long-chain bases; glycolipids, phospholipids and sphingolipids; and carotenes, polyprenols, sterols, terpenes and other isoprenoids.
male gonad development	The process whose specific outcome is the progression of the male gonad over time, from its formation to the mature structure.
negative regulation of gene expression	Any process that decreases the frequency, rate or extent of gene expression. Gene expression is the process in which a gene's coding sequence is converted into a mature gene product (protein or RNA).
negative regulation of protein phosphorylation	Any process that stops, prevents or reduces the rate of addition of phosphate groups to amino acids within a protein.
neuron migration	The characteristic movement of an immature neuron from germinal zones to specific positions where they will reside as they mature.
outflow tract morphogenesis	The process in which the anatomical structures of the outflow tract are generated and organized. The outflow tract is the portion of the heart through which blood flows into the arteries.
parathyroid gland development	The process whose specific outcome is the progression of the parathyroid gland over time, from its formation to the mature structure. The parathyroid gland is an organ specialised for secretion of parathyroid hormone.
pharynx development	The biological process whose specific outcome is the progression of a pharynx from an initial condition to its mature state. The pharynx is the part of the digestive system immediately posterior to the mouth.
positive regulation of cell population proliferation	Any process that activates or increases the rate or extent of cell proliferation.
positive regulation of ERK1 and ERK2 cascade	Any process that activates or increases the frequency, rate or extent of signal transduction mediated by the ERK1 and ERK2 cascade.
positive regulation of glial cell migration	Any process that activates or increases the frequency, rate or extent of glial cell migration.
positive regulation of protein phosphorylation	Any process that activates or increases the frequency, rate or extent of addition of phosphate groups to amino acids within a protein.
positive regulation of substrate adhesion-dependent cell spreading	Any process that activates or increases the frequency, rate or extent of substrate adhesion-dependent cell spreading.
Ras protein signal transduction	The series of molecular signals within the cell that are mediated by a member of the Ras superfamily of proteins switching to a GTP-bound active state.
reelin-mediated signaling pathway	The series of molecular signals initiated by the binding of reelin (a secreted glycoprotein) to a receptor on the surface of a target cell, and ending with the regulation of a downstream cellular process, e.g. transcription.
regulation of cell adhesion mediated by integrin	Any process that modulates the frequency, rate, or extent of cell adhesion mediated by integrin.
regulation of cell growth	Any process that modulates the frequency, rate, extent or direction of cell growth.
regulation of dendrite development	Any process that modulates the frequency, rate or extent of dendrite development.
regulation of skeletal muscle acetylcholine-gated channel clustering	Any process that modulates the frequency, rate or extent of skeletal muscle acetylcholine-gated channel clustering.
regulation of T cell migration	Any process that modulates the frequency, rate or extent of T cell migration.
retinoic acid receptor signaling pathway	The series of molecular signals generated as a consequence of a retinoic acid receptor binding to one of its physiological ligands.
signal transduction	The cellular process in which a signal is conveyed to trigger a change in the activity or state of a cell. Signal transduction begins with reception of a signal (e.g. a ligand binding to a receptor or receptor activation by a stimulus such as light), or for signal transduction in the absence of ligand, signal-withdrawal or the activity of a constitutively active receptor. Signal transduction ends with regulation of a downstream cellular process, e.g. regulation of transcription or regulation of a metabolic process. Signal transduction covers signaling from receptors located on the surface of the cell and signaling via molecules located within the cell. For signaling between cells, signal transduction is restricted to events at and within the receiving cell.
single fertilization	The union of male and female gametes to form a zygote.
spermatogenesis	The developmental process by which male germ line stem cells self renew or give rise to successive cell types resulting in the development of a spermatozoa.
synapse assembly	The aggregation, arrangement and bonding together of a set of components to form a synapse. This process ends when the synapse is mature (functional).
T cell receptor signaling pathway	The series of molecular signals initiated by the cross-linking of an antigen receptor on a T cell.
thymus development	The process whose specific outcome is the progression of the thymus over time, from its formation to the mature structure. The thymus is a symmetric bi-lobed organ involved primarily in the differentiation of immature to mature T cells, with unique vascular, nervous, epithelial, and lymphoid cell components.
urogenital system development	The process whose specific outcome is the progression of the urogenital system over time, from its formation to the mature structure.

10 homologous proteins in AiPD

UniProt AC	Gene Name	Protein Name	Species	Evidence Code
Q04929	CRK	Adapter molecule crk	Gallus gallus (Chicken)	SS
Q9XYM0	Crk	Adapter molecule Crk	Drosophila melanogaster (Fruit fly)	SS
O43639	NCK2	Cytoplasmic protein NCK2	Homo sapiens (Human)	EV
P16333	NCK1	Cytoplasmic protein NCK1	Homo sapiens (Human)	PR
P46108	CRK	Adapter molecule crk	Homo sapiens (Human)	EV
Q64010	Crk	Adapter molecule crk	Mus musculus (Mouse)	EV SS
P47941	Crkl	Crk-like protein	Mus musculus (Mouse)	SS
Q63768	Crk	Adapter molecule crk	Rattus norvegicus (Rat)	SS
Q5U2U2	Crkl	Crk-like protein	Rattus norvegicus (Rat)	SS
Q9NHC3	ced-2	Cell death abnormality protein 2	Caenorhabditis elegans	SS

10	20	30	40	50	60
MSSARFDSSD	RSAWYMGPVS	RQEAQTRLQG	QRHGMFLVRD	SSTCPGDYVL	SVSENSRVSH
70	80	90	100	110	120
YIINSLPNRR	FKIGDQEFDH	LPALLEFYKI	HYLDTTTLIE	PAPRYPSPPM	GSVSAPNLPT
130	140	150	160	170	180
AEDNLEYVRT	LYDFPGNDAE	DLPFKKGEIL	VIIEKPEEQW	WSARNKDGRV	GMIPVPYVEK
190	200	210	220	230	240
LVRSSPHGKH	GNRNSNSYGI	PEPAHAYAQP	QTTTPLPAVS	GSPGAAITPL	PSTQNGPVFA
250	260	270	280	290	300
KAIQKRVPCA	YDKTALALEV	GDIVKVTRMN	INGQWEGEVN	GRKGLFPFTH	VKIFDPQNPD

ENE