SPY2_MACFA
ID SPY2_MACFA Reviewed; 315 AA.
AC Q2PFN5;
DT 24-JUL-2007, integrated into UniProtKB/Swiss-Prot.
DT 07-FEB-2006, sequence version 1.
DT 03-AUG-2022, entry version 51.
DE RecName: Full=Protein sprouty homolog 2;
DE Short=Spry-2;
GN Name=SPRY2; ORFNames=QtrA-10142;
OS Macaca fascicularis (Crab-eating macaque) (Cynomolgus monkey).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini;
OC Cercopithecidae; Cercopithecinae; Macaca.
OX NCBI_TaxID=9541;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Temporal cortex;
RA Kobayashi M., Tanuma R., Hirata M., Osada N., Kusuda J., Sugano S.,
RA Hashimoto K.;
RT "Analysis of gene expression in cynomolgus monkey tissues by macaque cDNA
RT oligo-chips.";
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Antagonist of fibroblast growth factor (FGF) pathways via
CC inhibition of FGF-mediated phosphorylation of ERK1/2 (By similarity).
CC Thereby acts as an antagonist of FGF-induced retinal lens fiber
CC differentiation, may inhibit limb bud outgrowth and may negatively
CC modulate respiratory organogenesis (By similarity). Inhibits TGFB-
CC induced epithelial-to-mesenchymal transition in retinal lens epithelial
CC cells (By similarity). Inhibits CBL/C-CBL-mediated EGFR ubiquitination
CC (By similarity). {ECO:0000250|UniProtKB:O43597,
CC ECO:0000250|UniProtKB:Q9QXV8}.
CC -!- SUBUNIT: Forms heterodimers with SPRY1 (By similarity). Forms a
CC tripartite complex containing GAB1, METTL13 and SPRY2 (By similarity).
CC Within the complex interacts with METTL13 (By similarity). Interacts
CC with RAF1 (By similarity). Interacts (via C-terminus) with TESK1 (via
CC C-terminus); the interaction disrupts SPRY2 interaction with GRB2,
CC potentially via disruption of SPRY2 serine dephosphorylation (By
CC similarity). Interacts with PPP2R1A/PP2A-A and PPP2CA/PP2A-C; the
CC interaction with PPP2CA/PP2A-C is inhibited by interaction with TESK1,
CC possibly by vesicular sequestration of SPRY2 (By similarity).
CC Inhibition of the interaction with the serine/threonine-protein
CC phosphatase 2A (PP2A) holoenzyme results in loss of PP2A-mediated
CC dephosphorylation, resulting in the loss of SPRY2 interaction with GRB2
CC (By similarity). Interacts with GRB2 (By similarity). Interacts with
CC CBL/C-CBL; the interaction inhibits CBL-mediated ubiquitination of EGFR
CC (By similarity). Interacts (via C-terminus) with CAV1 (via C-terminus)
CC (By similarity). {ECO:0000250|UniProtKB:O43597,
CC ECO:0000250|UniProtKB:Q9QXV8}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytoskeleton
CC {ECO:0000250|UniProtKB:O43597}. Cell projection, ruffle membrane
CC {ECO:0000250|UniProtKB:O43597}. Note=Associated with microtubules in
CC unstimulated cells but is translocated to the membrane ruffles in cells
CC stimulated ith EGF (epidermal growth factor).
CC {ECO:0000250|UniProtKB:O43597}.
CC -!- DOMAIN: The Cys-rich domain is responsible for the localization of the
CC protein to the membrane ruffles. {ECO:0000250}.
CC -!- PTM: Cleaved at Pro-144 by the prolyl endopeptidase FAP (seprase)
CC activity (in vitro). {ECO:0000250|UniProtKB:O43597}.
CC -!- SIMILARITY: Belongs to the sprouty family. {ECO:0000305}.
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DR EMBL; AB220552; BAE73085.1; -; mRNA.
DR RefSeq; NP_001306528.1; NM_001319599.1.
DR AlphaFoldDB; Q2PFN5; -.
DR SMR; Q2PFN5; -.
DR STRING; 9541.XP_005586130.1; -.
DR GeneID; 102141523; -.
DR CTD; 10253; -.
DR eggNOG; ENOG502QTG8; Eukaryota.
DR Proteomes; UP000233100; Unplaced.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-KW.
DR GO; GO:0005874; C:microtubule; IEA:UniProtKB-KW.
DR GO; GO:0032587; C:ruffle membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0010719; P:negative regulation of epithelial to mesenchymal transition; ISS:UniProtKB.
DR GO; GO:0070373; P:negative regulation of ERK1 and ERK2 cascade; ISS:UniProtKB.
DR GO; GO:1902747; P:negative regulation of lens fiber cell differentiation; ISS:UniProtKB.
DR GO; GO:0031397; P:negative regulation of protein ubiquitination; ISS:UniProtKB.
DR GO; GO:0046580; P:negative regulation of Ras protein signal transduction; IEA:InterPro.
DR GO; GO:0030512; P:negative regulation of transforming growth factor beta receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0042127; P:regulation of cell population proliferation; IEA:InterPro.
DR InterPro; IPR007875; Sprouty.
DR InterPro; IPR030780; SPRY2.
DR PANTHER; PTHR12365:SF8; PTHR12365:SF8; 1.
DR Pfam; PF05210; Sprouty; 1.
DR PROSITE; PS51227; SPR; 1.
PE 2: Evidence at transcript level;
KW Cell membrane; Cell projection; Cytoplasm; Cytoskeleton;
KW Developmental protein; Membrane; Microtubule; Reference proteome.
FT CHAIN 1..315
FT /note="Protein sprouty homolog 2"
FT /id="PRO_0000295301"
FT DOMAIN 177..291
FT /note="SPR"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00572"
FT REGION 1..39
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 51..140
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 118..315
FT /note="Required for interaction with CAV1"
FT /evidence="ECO:0000250|UniProtKB:Q9QXV8"
FT REGION 178..315
FT /note="Required for interaction with TESK1"
FT /evidence="ECO:0000250|UniProtKB:O43597"
FT COMPBIAS 1..18
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 73..94
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 95..140
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 144..145
FT /note="Cleavage; by FAP"
FT /evidence="ECO:0000250|UniProtKB:O43597"
SQ SEQUENCE 315 AA; 34616 MW; 8CC5903FCA6C4C9E CRC64;
MEARAQSGNG SQPLLQTPRD GGRQRGEPDP RDALTQQVHV LSLDQIRAIR NTNEYTEGPT
VVPRPGLKPA PRPSTQHKHE RLHGLPEHRQ PPRLQHSQVH SSARAPLSRS ISTVSSGSRS
STRTSTSSSS SEQRLLGSSF SSGPVADGII RVQPKSELKP GELKPLSKED LGLHAYRCED
CGKCKCKECT YPRPLPSDWI CDKQCLCSAQ NVIDYGTCVC CVKGLFYHCS NDDGDNCADN
PCSCSQSHCC TRWSAMGVMS LFLPCLWCYL PAKGCLKLCQ GCYDRVNRPG CRCKNSNTVC
CKVPTVPPRN FEKPT
