ID   CRK_XENLA               Reviewed;         296 AA.
AC   P87378;
DT   15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT   01-MAY-1997, sequence version 1.
DT   03-AUG-2022, entry version 106.
DE   RecName: Full=Adapter molecule crk;
DE   AltName: Full=CRK2;
DE   AltName: Full=SH2/SH3 adaptor crk;
GN   Name=crk;
OS   Xenopus laevis (African clawed frog).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Amphibia;
OC   Batrachia; Anura; Pipoidea; Pipidae; Xenopodinae; Xenopus; Xenopus.
OX   NCBI_TaxID=8355;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], AND FUNCTION.
RX   PubMed=9029144; DOI=10.1093/emboj/16.2.230;
RA   Evans E.K., Lu W., Strum S.L., Mayer B.J., Kornbluth S.;
RT   "Crk is required for apoptosis in Xenopus egg extracts.";
RL   EMBO J. 16:230-241(1997).
CC   -!- FUNCTION: Required for apoptosis in Xenopus egg extracts
CC       (PubMed:9029144). Involved in cell branching and adhesion (By
CC       similarity). May mediate attachment-induced mapk8 activation, membrane
CC       ruffling and cell motility in a Rac-dependent manner. May regulate the
CC       efna5-epha3 signaling (By similarity). {ECO:0000250|UniProtKB:P46108,
CC       ECO:0000269|PubMed:9029144}.
CC   -!- SUBUNIT: Interacts with abl, 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-214 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-214 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-230 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. {ECO:0000250}.
CC   -!- SIMILARITY: Belongs to the CRK family. {ECO:0000305}.
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DR   EMBL; U89774; AAB49698.1; -; mRNA.
DR   RefSeq; NP_001083483.1; NM_001090014.1.
DR   AlphaFoldDB; P87378; -.
DR   SMR; P87378; -.
DR   GeneID; 398951; -.
DR   KEGG; xla:398951; -.
DR   CTD; 398951; -.
DR   Xenbase; XB-GENE-996363; crk.L.
DR   Proteomes; UP000186698; Chromosome 2L.
DR   Bgee; 398951; Expressed in blastula and 19 other tissues.
DR   GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR   GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
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   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   2: Evidence at transcript level;
KW   Cell membrane; Cytoplasm; Membrane; Phosphoprotein; Reference proteome;
KW   Repeat; SH2 domain; SH3 domain.
FT   CHAIN           1..296
FT                   /note="Adapter molecule crk"
FT                   /id="PRO_0000079354"
FT   DOMAIN          13..112
FT                   /note="SH2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00191"
FT   DOMAIN          125..185
FT                   /note="SH3 1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00192"
FT   DOMAIN          228..289
FT                   /note="SH3 2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00192"
FT   REGION          180..221
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   SITE            230
FT                   /note="Proline switch"
FT                   /evidence="ECO:0000250"
FT   MOD_RES         214
FT                   /note="Phosphotyrosine"
FT                   /evidence="ECO:0000250"
SQ   SEQUENCE   296 AA;  33409 MW;  544F11F4A1F75A66 CRC64;
     MAGNFDSEDR ASWYWGKQNR QEAVNLLQGQ RHGVFLVRDS TTIPGDYVLS VSENSKVSHY
     IINSVTNNRQ SSTAGMVQSR FRIGDQEFDS LPTLLEFYKI HYLDTTTLIE PVSKSKQSGV
     IQRQEEVEYL RALFDFIGND DEDLPFKKGD ILRIREKPEE QWWNAEDSDG RRGMIPVPYV
     EKYRPPSSPG SALIGGNQEN SHPQPLGGPE PGPYAQPSVN TPLPNLQNGP IFARVIQKRV
     PNAYDKTALA LEVGDLVKVT KINVSGQWEG ECNGKYGHFP FTHVRLLEQN PEEDFS