CRK_CHICK
ID CRK_CHICK Reviewed; 305 AA.
AC Q04929;
DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1995, sequence version 1.
DT 03-AUG-2022, entry version 142.
DE RecName: Full=Adapter molecule crk;
DE AltName: Full=Proto-oncogene c-Crk;
DE AltName: Full=p38;
GN Name=CRK;
OS Gallus gallus (Chicken).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Archelosauria; Archosauria; Dinosauria; Saurischia; Theropoda;
OC Coelurosauria; Aves; Neognathae; Galloanserae; Galliformes; Phasianidae;
OC Phasianinae; Gallus.
OX NCBI_TaxID=9031;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=1329926;
RA Reichman C.T., Mayer B.J., Khawer S., Hanafusa H.;
RT "The product of the cellular crk gene consists primarily of SH2 and SH3
RT regions.";
RL Cell Growth Differ. 3:451-460(1992).
RN [2]
RP STRUCTURE BY NMR OF 135-297, AND ISOMERIZATION AT PRO-238.
RX PubMed=21131971; DOI=10.1038/nchembio.494;
RA Sarkar P., Saleh T., Tzeng S.R., Birge R.B., Kalodimos C.G.;
RT "Structural basis for regulation of the Crk signaling protein by a proline
RT switch.";
RL Nat. Chem. Biol. 7:51-57(2011).
CC -!- FUNCTION: May mediate attachment-induced MAPK8 activation, membrane
CC ruffling and cell motility in a Rac-dependent manner. Involved in
CC phagocytosis of apoptotic cells and cell motility (By similarity).
CC Involved in cell branching and adhesion (By similarity). May regulate
CC the EFNA5-EPHA3 signaling (By similarity). {ECO:0000250,
CC ECO:0000250|UniProtKB:P46108, ECO:0000250|UniProtKB:Q64010}.
CC -!- SUBUNIT: Interacts with ABL1, C3G, SOS, MAP4K1, MAPK8 and DOCK1 via its
CC first SH3 domain. Interacts with BCAR1, CBL, PXN and GAB1 via its SH2
CC domain upon stimulus-induced tyrosine phosphorylation. Interacts with
CC several tyrosine-phosphorylated growth factor receptors such as EGFR,
CC PDGFR and INSR via its SH2 domain (By similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Cell membrane
CC {ECO:0000250}. Note=Translocated to the plasma membrane upon cell
CC adhesion. {ECO:0000250}.
CC -!- PTM: Phosphorylated on Tyr-222 upon cell adhesion. Results in the
CC negative regulation of the association with SH2- and SH3-binding
CC partners, possibly by the formation of an intramolecular interaction of
CC phosphorylated Tyr-222 with the SH2 domain. This leads finally to the
CC down-regulation of the Crk signaling pathway (By similarity).
CC {ECO:0000250}.
CC -!- PTM: Proline isomerization at Pro-238 by PPIA acts as a switch between
CC two conformations: an autoinhibitory conformation in the cis form,
CC where the tandem SH3 domains interact intramolecularly, and an
CC activated conformation in the trans form.
CC {ECO:0000269|PubMed:21131971}.
CC -!- SIMILARITY: Belongs to the CRK family. {ECO:0000305}.
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DR EMBL; L08168; AAA49001.1; -; mRNA.
DR PIR; A49011; A49011.
DR RefSeq; NP_001007847.1; NM_001007846.1.
DR RefSeq; XP_015151517.1; XM_015296031.1.
DR PDB; 2L3P; NMR; -; A=220-297.
DR PDB; 2L3Q; NMR; -; A=220-297.
DR PDB; 2L3S; NMR; -; A=135-297.
DR PDBsum; 2L3P; -.
DR PDBsum; 2L3Q; -.
DR PDBsum; 2L3S; -.
DR AlphaFoldDB; Q04929; -.
DR BMRB; Q04929; -.
DR SMR; Q04929; -.
DR BioGRID; 678886; 2.
DR IntAct; Q04929; 3.
DR MINT; Q04929; -.
DR STRING; 9031.ENSGALP00000004174; -.
DR iPTMnet; Q04929; -.
DR PaxDb; Q04929; -.
DR Ensembl; ENSGALT00000004183; ENSGALP00000004174; ENSGALG00000002656.
DR VEuPathDB; HostDB:geneid_107054794; -.
DR eggNOG; KOG4792; Eukaryota.
DR GeneTree; ENSGT00820000127055; -.
DR HOGENOM; CLU_060542_0_1_1; -.
DR InParanoid; Q04929; -.
DR OMA; WWNAEDG; -.
DR OrthoDB; 1414461at2759; -.
DR PhylomeDB; Q04929; -.
DR TreeFam; TF321436; -.
DR Reactome; R-GGA-170984; ARMS-mediated activation.
DR Reactome; R-GGA-186763; Downstream signal transduction.
DR Reactome; R-GGA-2029482; Regulation of actin dynamics for phagocytic cup formation.
DR Reactome; R-GGA-372708; p130Cas linkage to MAPK signaling for integrins.
DR Reactome; R-GGA-4420097; VEGFA-VEGFR2 Pathway.
DR Reactome; R-GGA-8849471; PTK6 Regulates RHO GTPases, RAS GTPase and MAP kinases.
DR Reactome; R-GGA-8875555; MET activates RAP1 and RAC1.
DR Reactome; R-GGA-8875656; MET receptor recycling.
DR Reactome; R-GGA-912631; Regulation of signaling by CBL.
DR EvolutionaryTrace; Q04929; -.
DR PRO; PR:Q04929; -.
DR Proteomes; UP000000539; Chromosome 19.
DR Bgee; ENSGALG00000002656; Expressed in lung and 13 other tissues.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0016020; C:membrane; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0030971; F:receptor tyrosine kinase binding; IBA:GO_Central.
DR GO; GO:0035591; F:signaling adaptor activity; IBA:GO_Central.
DR GO; GO:0016477; P:cell migration; IBA:GO_Central.
DR GO; GO:0048013; P:ephrin receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0032956; P:regulation of actin cytoskeleton organization; ISS:UniProtKB.
DR GO; GO:0043087; P:regulation of GTPase activity; ISS:UniProtKB.
DR GO; GO:0007165; P:signal transduction; IBA:GO_Central.
DR CDD; cd11759; SH3_CRK_C; 1.
DR CDD; cd11758; SH3_CRK_N; 1.
DR Gene3D; 3.30.505.10; -; 1.
DR InterPro; IPR035458; CRK_SH3_C.
DR InterPro; IPR035457; CRK_SH3_N.
DR InterPro; IPR000980; SH2.
DR InterPro; IPR036860; SH2_dom_sf.
DR InterPro; IPR036028; SH3-like_dom_sf.
DR InterPro; IPR001452; SH3_domain.
DR Pfam; PF00017; SH2; 1.
DR Pfam; PF00018; SH3_1; 1.
DR Pfam; PF07653; SH3_2; 1.
DR PRINTS; PR00401; SH2DOMAIN.
DR PRINTS; PR00452; SH3DOMAIN.
DR SMART; SM00252; SH2; 1.
DR SMART; SM00326; SH3; 2.
DR SUPFAM; SSF50044; SSF50044; 2.
DR SUPFAM; SSF55550; SSF55550; 1.
DR PROSITE; PS50001; SH2; 1.
DR PROSITE; PS50002; SH3; 2.
PE 1: Evidence at protein level;
KW 3D-structure; Cell membrane; Cytoplasm; Membrane; Phosphoprotein;
KW Proto-oncogene; Reference proteome; Repeat; SH2 domain; SH3 domain.
FT CHAIN 1..305
FT /note="Adapter molecule crk"
FT /id="PRO_0000079349"
FT DOMAIN 13..119
FT /note="SH2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00191"
FT DOMAIN 133..193
FT /note="SH3 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192"
FT DOMAIN 236..297
FT /note="SH3 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192"
FT REGION 194..231
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 194..212
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 238
FT /note="Proline switch"
FT /evidence="ECO:0000269|PubMed:21131971"
FT MOD_RES 222
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250"
FT STRAND 137..140
FT /evidence="ECO:0007829|PDB:2L3S"
FT STRAND 148..151
FT /evidence="ECO:0007829|PDB:2L3S"
FT STRAND 156..164
FT /evidence="ECO:0007829|PDB:2L3S"
FT STRAND 166..174
FT /evidence="ECO:0007829|PDB:2L3S"
FT STRAND 176..178
FT /evidence="ECO:0007829|PDB:2L3S"
FT STRAND 180..184
FT /evidence="ECO:0007829|PDB:2L3S"
FT HELIX 185..187
FT /evidence="ECO:0007829|PDB:2L3S"
FT STRAND 200..203
FT /evidence="ECO:0007829|PDB:2L3S"
FT STRAND 226..228
FT /evidence="ECO:0007829|PDB:2L3P"
FT STRAND 234..236
FT /evidence="ECO:0007829|PDB:2L3P"
FT STRAND 239..245
FT /evidence="ECO:0007829|PDB:2L3P"
FT STRAND 253..255
FT /evidence="ECO:0007829|PDB:2L3P"
FT STRAND 263..269
FT /evidence="ECO:0007829|PDB:2L3P"
FT STRAND 272..274
FT /evidence="ECO:0007829|PDB:2L3P"
FT STRAND 277..280
FT /evidence="ECO:0007829|PDB:2L3P"
FT STRAND 283..286
FT /evidence="ECO:0007829|PDB:2L3P"
FT HELIX 289..291
FT /evidence="ECO:0007829|PDB:2L3Q"
FT STRAND 292..295
FT /evidence="ECO:0007829|PDB:2L3Q"
SQ SEQUENCE 305 AA; 33806 MW; 0A79AD232E824768 CRC64;
MAGQFDSEDR GSWYWGRLSR GDAVSLLQGQ RHGTFLVRDS GSIPGDFVLS VSESSRVSHY
IVNSLGPAGG RRAGGEGPGA PGLNPTRFRI GDQEFDSLPS LLEFYKIHYL DTTTLIEPVS
RSRQNSGVIL RQEEVEYVRA LFDFNGNDDE DLPFKKGDIL KIRDKPEEQW WNAEDMDGKR
GMIPVPYVEK CRPSSASVST LTGGNQDSSH PQPLGGPEPG PYAQPSINTP LPNLQNGPFY
ARVIQKRVPN AYDKTALALE VGELVKVTKI NMSGQWEGEC NGKRGHFPFT HVRLLDQQNP
DEDFS
