AiPD: Autoinhibited Protein Database

P46108

Gene name	CRK
Protein name	Adapter molecule crk
Names	Proto-oncogene c-Crk, p38
Species	Homo sapiens (Human)
KEGG Pathway	hsa:1398
EC number
Protein Class	SH2-SH3 ADAPTOR PROTEIN-RELATED (PTHR19969)

Descriptions

CRK regulates transcription and cytoskeletal reorganization for cell growth and motility by linking tyrosine kinases to small G proteins. The SH2 and nSH3 domains are used to recruit their target proteins. In CRKII, the intramolecular interactions of the SH domains with the inter-domain linker between nSH3 and cSH3 (inter-SH3 region) result in a compact structure.The binding site of SH2 in CRKII is exposed, but nSH3 is masked by SH2. In addition, cSH3 acts as a stabilizer of the assembled structure and thus as a negative regulator of CRKII function. Mutations disrupting the core structure of CRKII disturb the assembly of the SH domains, allowing nSH3 to effectively bind target proteins and transmit signals, thus promoting cell growth and motility.

Autoinhibitory domains (AIDs)

Target domain	135-189 (N-terminal Src Homology 3 domain of Ct10 Regulator of Kinase adaptor proteins)
Relief mechanism	PTM
Assay	Mutagenesis experiment, Structural analysis

AID

238-293 (cSH3 domain)

Target domain

135-189 (N-terminal Src Homology 3 domain of Ct10 Regulator of Kinase adaptor proteins)

Relief mechanism

PTM (Phosphorylation at Tyr221)

Assay

Mutagenesis experiment, Structural analysis

Target domain	135-189 (N-terminal Src Homology 3 domain of Ct10 Regulator of Kinase adaptor proteins)
Relief mechanism	PTM
Assay	Deletion assay, Mutagenesis experiment, Structural analysis

AID

224-237 (inter-SH3 region)

Target domain

135-189 (N-terminal Src Homology 3 domain of Ct10 Regulator of Kinase adaptor proteins)

Relief mechanism

PTM (Phosphorylation at Tyr221)

Assay

Deletion assay, Mutagenesis experiment, Structural analysis

Target domain	135-189 (N-terminal Src Homology 3 domain of Ct10 Regulator of Kinase adaptor proteins)
Relief mechanism	PTM
Assay	Deletion assay, Mutagenesis experiment, Structural analysis

AID

10-120 (SH2 region)

Target domain

135-189 (N-terminal Src Homology 3 domain of Ct10 Regulator of Kinase adaptor proteins)

Relief mechanism

PTM (Phosphorylation at Tyr221)

Assay

Deletion assay, Mutagenesis experiment, Structural analysis

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

Autoinhibited structure

Activated structure

11 structures for P46108

Entry ID	Method	Resolution	Chain	Position	Source
1JU5	NMR	-	A	12-120	PDB
2DVJ	NMR	-	A	1-228	PDB
2EYV	NMR	-	A	6-124	PDB
2EYW	NMR	-	A	125-198	PDB
2EYX	NMR	-	A	232-298	PDB
2EYY	NMR	-	A	1-204	PDB
2EYZ	NMR	-	A	1-304	PDB
2MS4	NMR	-	B	216-224	PDB
5UL6	X-ray	145 A	A	134-191	PDB
6ATV	X-ray	175 A	A	134-191	PDB
AF-P46108-F1	Predicted				AlphaFoldDB

159 variants for P46108

Variant ID(s)	Position	Change	Description	Diseaes Association	Provenance
CA397536663 rs774008957	4	N>I		No	ClinGen ExAC gnomAD
CA397536659 rs1242640031	4	N>K		No	ClinGen TOPMed
CA8266560 rs774008957	4	N>S		No	ClinGen ExAC gnomAD
CA8266561 rs774008957	4	N>T		No	ClinGen ExAC gnomAD
CA286802918 rs889227428	7	S>L		No	ClinGen Ensembl
rs748457687 CA8266558	9	E>D		No	ClinGen ExAC gnomAD
CA286802916 rs1029064679	9	E>K		No	ClinGen TOPMed gnomAD
rs1281300310 CA397536570	10	R>G		No	ClinGen TOPMed gnomAD
CA397536563 rs1222327170	10	R>Q		No	ClinGen gnomAD
CA397536567 rs1281300310	10	R>W		No	ClinGen TOPMed gnomAD
rs781767989 CA8266557	11	S>G		No	ClinGen ExAC gnomAD
CA8266556 rs755532427	11	S>R		No	ClinGen ExAC gnomAD
CA286802913 rs996619270	14	Y>F		No	ClinGen TOPMed
rs2229075 CA286802908	17	R>G		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
CA8266554 rs779969139	18	L>V		No	ClinGen ExAC gnomAD
rs765456902 CA8266551	21	Q>P		No	ClinGen ExAC gnomAD
rs1413934422 CA397536310	23	A>T		No	ClinGen gnomAD
rs775103823 CA8266546	26	L>R		No	ClinGen ExAC TOPMed gnomAD
CA397536133 rs1598308740	33	G>R		No	ClinGen Ensembl
rs773880876 CA8266543	34	V>E		No	ClinGen ExAC gnomAD
rs1317489137 CA397536116	34	V>L		No	ClinGen gnomAD
rs770651188 CA8266542	39	D>E		No	ClinGen ExAC TOPMed gnomAD
rs1567504480 CA397536021	39	D>V		No	ClinGen Ensembl
CA397535870 rs1346380897	47	Y>C		No	ClinGen gnomAD
rs1164473030 CA397535745	56	R>C		No	ClinGen gnomAD
rs1008110814 CA286802847	57	V>I		No	ClinGen TOPMed gnomAD
rs1181134938 CA397535675	58	S>C		No	ClinGen gnomAD
rs1181134938 CA397535659	58	S>F		No	ClinGen gnomAD
CA286802839 rs1046738642	62	I>M		No	ClinGen TOPMed
rs1291990121 CA397535551	65	S>G		No	ClinGen gnomAD
CA397535542 rs897819678	65	S>I		No	ClinGen TOPMed
CA286802823 rs897819678	65	S>N		No	ClinGen TOPMed
CA286802807 rs532720077	67	P>R		No	ClinGen 1000Genomes
CA397535502 rs1247693524	68	R>C		No	ClinGen gnomAD
CA8266532 rs201145609	68	R>P		No	ClinGen ExAC gnomAD
rs756091066 CA8266530	70	P>L		No	ClinGen ExAC gnomAD
CA397535443 rs1291174190	71	V>L		No	ClinGen TOPMed gnomAD
CA397535450 rs1291174190	71	V>M		No	ClinGen TOPMed gnomAD
CA8266528 rs767423900	72	P>L		No	ClinGen ExAC gnomAD
rs767423900 CA286802791	72	P>Q		No	ClinGen ExAC gnomAD
CA8266529 rs752609926	72	P>S		No	ClinGen ExAC gnomAD
CA286802788 rs927840235	76	A>T		No	ClinGen Ensembl
CA8266527 rs758982759	76	A>V		No	ClinGen ExAC TOPMed gnomAD
CA8266525 rs766205321	77	Q>H		No	ClinGen ExAC gnomAD
rs766205321 CA8266526	77	Q>H		No	ClinGen ExAC gnomAD
rs762667910 CA8266524	78	P>S		No	ClinGen ExAC gnomAD
CA8266521 rs761058721	80	P>L		No	ClinGen ExAC TOPMed gnomAD
rs770045198 CA8266494	82	V>A		No	ClinGen ExAC gnomAD
CA286794549 rs897014160	82	V>M		No	ClinGen TOPMed gnomAD
rs747960532 CA8266493	84	P>L		No	ClinGen ExAC TOPMed gnomAD
rs1035514589 CA286794548	85	S>F		No	ClinGen Ensembl
rs781014005 CA8266492	85	S>T		No	ClinGen ExAC gnomAD
rs200440102 CA8266491	86	R>G		No	ClinGen ExAC gnomAD
rs1462597299 CA397532695	87	L>F		No	ClinGen TOPMed
rs780103155 CA8266489	88	R>Q		No	ClinGen ExAC TOPMed gnomAD
rs757985067 CA8266488	91	D>N		No	ClinGen ExAC gnomAD
rs1398022661 CA397532615	93	E>A		No	ClinGen TOPMed
CA397532578 rs1420488676	96	S>T		No	ClinGen TOPMed gnomAD
rs749892558 CA8266487	106	I>V		No	ClinGen ExAC TOPMed gnomAD
CA286794546 rs11544140	107	H>R		No	ClinGen Ensembl
rs1041967 CA286794545	109	L>W		No	ClinGen Ensembl
CA397532295 rs1343545080	113	T>A		No	ClinGen TOPMed gnomAD
CA397532291 rs1255487598	113	T>M		No	ClinGen gnomAD
CA397532268 rs753041568	115	I>R		No	ClinGen ExAC TOPMed gnomAD
rs753041568 CA8266484	115	I>T		No	ClinGen ExAC TOPMed gnomAD
CA286794544 rs905572417	115	I>V		No	ClinGen Ensembl
rs767900527 CA8266483	116	E>A		No	ClinGen ExAC gnomAD
CA8266481 rs774845596	122	R>S		No	ClinGen ExAC TOPMed gnomAD
CA397532177 rs1267204398	122	R>T		No	ClinGen TOPMed
rs766815891 CA8266480	123	Q>R		No	ClinGen ExAC gnomAD
CA8266479 rs763079680	125	S>N		No	ClinGen ExAC gnomAD
CA8266476 rs748384553	126	G>E		No	ClinGen ExAC TOPMed gnomAD
rs769953070 CA8266477	126	G>R		No	ClinGen ExAC TOPMed gnomAD
rs748384553 CA397532121	126	G>V		No	ClinGen ExAC TOPMed gnomAD
rs776671383 CA8266475	128	I>T		No	ClinGen ExAC gnomAD
rs1301251656 CA397532101	129	L>V		No	ClinGen TOPMed gnomAD
rs904025018 CA286794543	130	R>M		No	ClinGen TOPMed
CA286794542 rs947045345	132	E>Q		No	ClinGen Ensembl
rs375463605 CA286794541	134	A>T		No	ClinGen gnomAD
rs772107356 CA8266472	134	A>V		No	ClinGen ExAC gnomAD
rs745434190 CA8266470	137	V>M		No	ClinGen ExAC gnomAD
CA8266469 rs778455201	138	R>Q		No	ClinGen ExAC TOPMed gnomAD
rs1242359268 CA397531900	148	E>Q		No	ClinGen gnomAD
CA397531850 rs1318927794	152	P>S		No	ClinGen gnomAD
CA286794538 rs745921349	158	I>V		No	ClinGen gnomAD
CA286794537 rs187208794	161	I>V		No	ClinGen 1000Genomes
rs1332350809 COSM1479244 CA397531706	162	R>Q	breast [Cosmic]	No	ClinGen cosmic curated TOPMed
CA8266465 rs755350622	162	R>W		No	ClinGen ExAC TOPMed gnomAD
rs1223714291 CA397531664	165	P>L		No	ClinGen TOPMed
CA8266462 rs763419842	175	S>G		No	ClinGen ExAC gnomAD
rs773332314 CA397531481	175	S>R		No	ClinGen ExAC TOPMed gnomAD
rs867650824 CA286794535	176	E>A		No	ClinGen Ensembl
CA8266460 rs370837590	176	E>K		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD
rs761760691 CA8266459	183	P>A		No	ClinGen ExAC gnomAD
rs776920144 CA8266458	187	V>I		No	ClinGen ExAC gnomAD
rs145983279 CA8266456	188	E>K		No	ClinGen ESP ExAC TOPMed gnomAD
rs1200376984 CA397531169	192	P>L		No	ClinGen TOPMed
rs1270600646 CA397531150	194	S>F		No	ClinGen gnomAD
CA8266453 rs745777068	195	A>T		No	ClinGen ExAC TOPMed gnomAD
rs372978924 CA8266449	198	S>L		No	ClinGen ESP ExAC TOPMed gnomAD
rs748690203 CA8266450	198	S>P		No	ClinGen ExAC TOPMed gnomAD
CA397531071 rs1490963705	201	I>F		No	ClinGen gnomAD
CA397530969 rs1422122098	207	G>C		No	ClinGen gnomAD
CA397530941 rs1568014296	208	S>F		No	ClinGen Ensembl
rs758717980 CA8266445	209	H>P		No	ClinGen ExAC gnomAD
rs1307021911 CA397530915	210	P>R		No	ClinGen TOPMed
rs765599295 CA8266443	212	P>L		No	ClinGen ExAC TOPMed gnomAD
rs1273441505 CA397530854	215	G>V		No	ClinGen gnomAD
rs1451293325 CA397530856	215	G>W		No	ClinGen TOPMed gnomAD
CA8266441 rs753846735	216	P>L		No	ClinGen ExAC TOPMed gnomAD
CA8266439 rs774455135	222	A>D		No	ClinGen ExAC TOPMed gnomAD
rs980590664 CA286794531	222	A>T		No	ClinGen TOPMed gnomAD
rs1272608968 CA397530735	224	P>R		No	ClinGen gnomAD
CA8266437 rs772014783	226	V>I		No	ClinGen ExAC gnomAD
rs911274067 CA286794530	227	N>K		No	ClinGen TOPMed gnomAD
rs774348217 CA8266435	227	N>S		No	ClinGen ExAC TOPMed gnomAD
rs748897674 COSM975638 CA8266433	229	P>L	endometrium [Cosmic]	No	ClinGen cosmic curated ExAC TOPMed gnomAD
CA397530621 rs1225277427	233	L>F		No	ClinGen TOPMed gnomAD
rs747824545 CA8266430	237	P>L		No	ClinGen ExAC gnomAD
rs747824545 CA397530592	237	P>R		No	ClinGen ExAC gnomAD
rs372495262 CA286794529	238	I>M		No	ClinGen TOPMed gnomAD
rs1180209088 CA397530587	238	I>T		No	ClinGen gnomAD
CA8266428 rs569957933	238	I>V		No	ClinGen 1000Genomes ExAC TOPMed gnomAD
CA397530573 rs1237445672	240	A>G		No	ClinGen gnomAD
rs1204201258 CA397530551	244	Q>*		No	ClinGen gnomAD
rs750699283 CA8266427	244	Q>R		No	ClinGen ExAC TOPMed gnomAD
CA8266426 rs779528692	246	R>*		No	ClinGen ExAC TOPMed gnomAD
CA8266425 rs757697743	246	R>Q		No	ClinGen ExAC gnomAD
CA8266424 rs753987675	249	N>S		No	ClinGen ExAC TOPMed gnomAD
rs1378140776 CA397530505	251	Y>C		No	ClinGen TOPMed
rs760787562 CA8266422	252	D>N		No	ClinGen ExAC gnomAD
CA8266421 rs752999684	253	K>Q		No	ClinGen ExAC gnomAD
CA8266420 rs767779302	257	A>S		No	ClinGen ExAC
rs771230814 CA8266383	261	G>A		No	ClinGen ExAC TOPMed gnomAD
CA286792522 rs771230814	261	G>D		No	ClinGen ExAC TOPMed gnomAD
CA8266384 rs775156732	261	G>S		No	ClinGen ExAC gnomAD
rs1460550029 CA397527853	264	V>L		No	ClinGen gnomAD
rs954838481 CA286792521	267	T>M		No	ClinGen TOPMed gnomAD
CA397527817 rs1598290683	267	T>S		No	ClinGen Ensembl
rs145094200 CA286792520	270	N>D		No	ClinGen ESP
rs1260863082 CA397527699	276	E>K		No	ClinGen gnomAD
CA397527679 rs1398231816	277	G>E		No	ClinGen gnomAD
rs748279653 CA8266379	279	C>Y		No	ClinGen ExAC gnomAD
CA8266378 rs781401346	280	N>S		No	ClinGen ExAC gnomAD
CA8266376 rs751763519	281	G>D		No	ClinGen ExAC TOPMed gnomAD
rs755037548 CA8266377	281	G>S		No	ClinGen ExAC gnomAD
rs766559218 CA8266375	283	R>Q		No	ClinGen ExAC TOPMed gnomAD
CA397527576 rs1568005864	287	P>S		No	ClinGen Ensembl
rs1477228518 CA397527562	289	T>A		No	ClinGen gnomAD
rs765221724 CA8266372	292	R>C		No	ClinGen ExAC TOPMed gnomAD
CA8266371 rs761704148	292	R>H		No	ClinGen ExAC gnomAD
rs765221724 CA397527524	292	R>S		No	ClinGen ExAC TOPMed gnomAD
rs1421174730 CA397527512	293	L>P		No	ClinGen TOPMed
rs963953252 CA286792518	295	D>H		No	ClinGen TOPMed
CA8266370 rs371718957	296	Q>H		No	ClinGen ESP ExAC TOPMed gnomAD
rs1278918643 CA397527442	298	N>T		No	ClinGen gnomAD
rs140388019 CA286792517	300	D>N		No	ClinGen ESP TOPMed gnomAD
CA8266367 rs775008230	301	E>K		No	ClinGen ExAC gnomAD
rs146555797 CA8266366	304	S>N		No	ClinGen 1000Genomes ESP ExAC TOPMed gnomAD

No associated diseases with P46108

19 regional properties for P46108

Type	Name	Position	InterPro Accession
domain	CARD domain	1 - 90	IPR001315
repeat	WD40 repeat	606 - 645	IPR001680-1
repeat	WD40 repeat	648 - 734	IPR001680-2
repeat	WD40 repeat	737 - 785	IPR001680-3
repeat	WD40 repeat	795 - 827	IPR001680-4
repeat	WD40 repeat	830 - 870	IPR001680-5
repeat	WD40 repeat	873 - 921	IPR001680-6
repeat	WD40 repeat	944 - 994	IPR001680-7
repeat	WD40 repeat	997 - 1121	IPR001680-8
repeat	WD40 repeat	1124 - 1172	IPR001680-9
repeat	WD40 repeat	1176 - 1212	IPR001680-10
repeat	WD40 repeat	1215 - 1254	IPR001680-11
domain	NB-ARC	136 - 374	IPR002182
conserved_site	WD40 repeat, conserved site	674 - 688	IPR019775
repeat	G-protein beta WD-40 repeat	899 - 913	IPR020472-1
repeat	G-protein beta WD-40 repeat	1023 - 1037	IPR020472-2
repeat	G-protein beta WD-40 repeat	1066 - 1080	IPR020472-3
domain	APAF-1 helical domain	456 - 589	IPR041452
domain	Apoptotic protease-activating factor 1, winged-helix domain	380 - 447	IPR048975

Functions

		Description
EC Number
Subcellular Localization	Cytoplasm Cell membrane	Translocated to the plasma membrane upon cell adhesion
PANTHER Family	PTHR19969	SH2-SH3 ADAPTOR PROTEIN-RELATED
PANTHER Subfamily	PTHR19969:SF8	ADAPTER MOLECULE CRK
PANTHER Protein Class	scaffold/adaptor protein
PANTHER Pathway Category	Integrin signalling pathway Crk CCKR signaling map CRK Angiogenesis Crk

9 GO annotations of cellular component

Name	Definition
actin cytoskeleton	The part of the cytoskeleton (the internal framework of a cell) composed of actin and associated proteins. Includes actin cytoskeleton-associated complexes.
cytoplasm	The contents of a cell excluding the plasma membrane and nucleus, but including other subcellular structures.
cytosol	The part of the cytoplasm that does not contain organelles but which does contain other particulate matter, such as protein complexes.
extracellular exosome	A vesicle that is released into the extracellular region by fusion of the limiting endosomal membrane of a multivesicular body with the plasma membrane. Extracellular exosomes, also simply called exosomes, have a diameter of about 40-100 nm.
membrane	A lipid bilayer along with all the proteins and protein complexes embedded in it an attached to it.
membrane raft	Any of the small (10-200 nm), heterogeneous, highly dynamic, sterol- and sphingolipid-enriched membrane domains that compartmentalize cellular processes. Small rafts can sometimes be stabilized to form larger platforms through protein-protein and protein-lipid interactions.
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.
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.

15 GO annotations of molecular function

Name	Definition
cytoskeletal protein binding	Binding to a protein component of a cytoskeleton (actin, microtubule, or intermediate filament cytoskeleton).
ephrin receptor binding	Binding to an ephrin receptor.
insulin-like growth factor receptor binding	Binding to an insulin-like growth factor receptor.
kinase binding	Binding to a kinase, any enzyme that catalyzes the transfer of a phosphate group.
phosphotyrosine residue binding	Binding to a phosphorylated tyrosine residue within a protein.
protein phosphorylated amino acid binding	Binding to a phosphorylated amino acid residue within a protein.
protein self-association	Binding to a domain within the same polypeptide.
protein tyrosine kinase binding	Binding to protein tyrosine kinase.
receptor tyrosine kinase binding	Binding to a receptor that possesses protein tyrosine kinase activity.
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.
SH2 domain binding	Binding to a SH2 domain (Src homology 2) of a protein, a protein domain of about 100 amino-acid residues and belonging to the alpha + beta domain class.
SH3 domain binding	Binding to a SH3 domain (Src homology 3) of a protein, small protein modules containing approximately 50 amino acid residues found in a great variety of intracellular or membrane-associated proteins.
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.
signaling receptor complex adaptor activity	The binding activity of a molecule that provides a physical support for the assembly of a multiprotein receptor signaling complex.
ubiquitin protein ligase binding	Binding to a ubiquitin protein ligase enzyme, any of the E3 proteins.

41 GO annotations of biological process

Name	Definition
actin cytoskeleton organization	A process that is carried out at the cellular level which results in the assembly, arrangement of constituent parts, or disassembly of cytoskeletal structures comprising actin filaments and their associated proteins.
activation of GTPase activity	Any process that initiates the activity of an inactive GTPase through the replacement of GDP by GTP.
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 endothelin	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 endothelin stimulus. Endothelin is any of three secretory vasoconstrictive peptides (endothelin-1, -2, -3).
cellular response to insulin-like 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 insulin-like growth factor stimulus.
cellular response to nerve growth factor stimulus	A 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 nerve growth factor stimulus.
cellular response to nitric oxide	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 nitric oxide 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.
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.
dendrite development	The process whose specific outcome is the progression of the dendrite over time, from its formation to the mature structure.
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.
establishment of cell polarity	The specification and formation of anisotropic intracellular organization or cell growth patterns.
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.
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.
negative regulation of cell motility	Any process that stops, prevents, or reduces the frequency, rate or extent of cell motility.
negative regulation of natural killer cell mediated cytotoxicity	Any process that stops, prevents, or reduces the rate of natural killer mediated cytotoxicity.
negative regulation of wound healing	Any process that decreases the rate, frequency, or extent of the series of events that restore integrity to a damaged tissue, following an injury.
neuron migration	The characteristic movement of an immature neuron from germinal zones to specific positions where they will reside as they mature.
positive regulation of cell growth	Any process that activates or increases the frequency, rate, extent or direction of cell growth.
positive regulation of smooth muscle cell migration	Any process that activates, maintains or increases the frequency, rate or extent of smooth muscle cell migration.
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.
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 actin cytoskeleton organization	Any process that modulates the frequency, rate or extent of the formation, arrangement of constituent parts, or disassembly of cytoskeletal structures comprising actin filaments and their associated proteins.
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 shape	Any process that modulates the surface configuration of a cell.
regulation of dendrite development	Any process that modulates the frequency, rate or extent of dendrite development.
regulation of GTPase activity	Any process that modulates the rate of GTP hydrolysis by a GTPase.
regulation of intracellular signal transduction	Any process that modulates the frequency, rate or extent of intracellular signal transduction.
regulation of protein binding	Any process that modulates the frequency, rate or extent of protein binding.
regulation of Rac protein signal transduction	Any process that modulates the frequency, rate or extent of Rac protein signal transduction.
regulation of signal transduction	Any process that modulates the frequency, rate or extent of signal transduction.
regulation of T cell migration	Any process that modulates the frequency, rate or extent of T cell migration.
regulation of transcription by RNA polymerase II	Any process that modulates the frequency, rate or extent of transcription mediated by RNA polymerase II.
response to cholecystokinin	Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a cholecystokinin stimulus.
response to hepatocyte growth factor	Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a hepatocyte growth factor stimulus.
response to hydrogen peroxide	Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a hydrogen peroxide (H2O2) stimulus.
response to yeast	Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a stimulus from a yeast species.
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.

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
P46109	CRKL	Crk-like protein	Homo sapiens (Human)	SS
P47941	Crkl	Crk-like protein	Mus musculus (Mouse)	SS
Q64010	Crk	Adapter molecule crk	Mus musculus (Mouse)	EV SS
Q5U2U2	Crkl	Crk-like protein	Rattus norvegicus (Rat)	SS
Q63768	Crk	Adapter molecule crk	Rattus norvegicus (Rat)	SS
Q9NHC3	ced-2	Cell death abnormality protein 2	Caenorhabditis elegans	SS

10	20	30	40	50	60
MAGNFDSEER	SSWYWGRLSR	QEAVALLQGQ	RHGVFLVRDS	STSPGDYVLS	VSENSRVSHY
70	80	90	100	110	120
IINSSGPRPP	VPPSPAQPPP	GVSPSRLRIG	DQEFDSLPAL	LEFYKIHYLD	TTTLIEPVSR
130	140	150	160	170	180
SRQGSGVILR	QEEAEYVRAL	FDFNGNDEED	LPFKKGDILR	IRDKPEEQWW	NAEDSEGKRG
190	200	210	220	230	240
MIPVPYVEKY	RPASASVSAL	IGGNQEGSHP	QPLGGPEPGP	YAQPSVNTPL	PNLQNGPIYA
250	260	270	280	290	300
RVIQKRVPNA	YDKTALALEV	GELVKVTKIN	VSGQWEGECN	GKRGHFPFTH	VRLLDQQNPD

EDFS