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   24-JAN-2024, entry version 148.
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; 9031-ENSGALP00000004174; -.
DR   Ensembl; ENSGALT00000004183; ENSGALP00000004174; ENSGALG00000002656.
DR   Ensembl; ENSGALT00010070926.1; ENSGALP00010043617.1; ENSGALG00010029327.1.
DR   Ensembl; ENSGALT00015055399; ENSGALP00015033483; ENSGALG00015022653.
DR   VEuPathDB; HostDB:geneid_107054794; -.
DR   eggNOG; KOG4792; Eukaryota.
DR   GeneTree; ENSGT00820000127055; -.
DR   HOGENOM; CLU_060542_0_1_1; -.
DR   InParanoid; Q04929; -.
DR   OMA; DNHMIIE; -.
DR   OrthoDB; 2900795at2759; -.
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 cell types or 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:0032991; C:protein-containing complex; IEA:Ensembl.
DR   GO; GO:0046875; F:ephrin receptor binding; IEA:Ensembl.
DR   GO; GO:0001784; F:phosphotyrosine residue binding; IEA:Ensembl.
DR   GO; GO:0043621; F:protein self-association; IEA:Ensembl.
DR   GO; GO:0030971; F:receptor tyrosine kinase binding; IBA:GO_Central.
DR   GO; GO:0042169; F:SH2 domain binding; IEA:Ensembl.
DR   GO; GO:0017124; F:SH3 domain binding; IEA:Ensembl.
DR   GO; GO:0035591; F:signaling adaptor activity; IBA:GO_Central.
DR   GO; GO:0030036; P:actin cytoskeleton organization; IEA:Ensembl.
DR   GO; GO:0016477; P:cell migration; IBA:GO_Central.
DR   GO; GO:0048013; P:ephrin receptor signaling pathway; ISS:UniProtKB.
DR   GO; GO:2000146; P:negative regulation of cell motility; IEA:Ensembl.
DR   GO; GO:0061045; P:negative regulation of wound healing; IEA:Ensembl.
DR   GO; GO:1900026; P:positive regulation of substrate adhesion-dependent cell spreading; IEA:Ensembl.
DR   GO; GO:0032956; P:regulation of actin cytoskeleton organization; ISS:UniProtKB.
DR   GO; GO:0008360; P:regulation of cell shape; IEA:Ensembl.
DR   GO; GO:0043087; P:regulation of GTPase activity; ISS:UniProtKB.
DR   GO; GO:1902531; P:regulation of intracellular signal transduction; IEA:Ensembl.
DR   GO; GO:0007165; P:signal transduction; IBA:GO_Central.
DR   CDD; cd09926; SH2_CRK_like; 1.
DR   CDD; cd11759; SH3_CRK_C; 1.
DR   CDD; cd11758; SH3_CRK_N; 1.
DR   Gene3D; 3.30.505.10; SH2 domain; 1.
DR   Gene3D; 2.30.30.40; SH3 Domains; 2.
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   PANTHER; PTHR19969:SF8; ADAPTER MOLECULE CRK; 1.
DR   PANTHER; PTHR19969; SH2-SH3 ADAPTOR PROTEIN-RELATED; 1.
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; SSF55550; SH2 domain; 1.
DR   SUPFAM; SSF50044; SH3-domain; 2.
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
//