RAF1_BOVIN
ID RAF1_BOVIN Reviewed; 648 AA.
AC A7E3S4; A7YY51;
DT 02-SEP-2008, integrated into UniProtKB/Swiss-Prot.
DT 11-SEP-2007, sequence version 1.
DT 03-AUG-2022, entry version 111.
DE RecName: Full=RAF proto-oncogene serine/threonine-protein kinase;
DE EC=2.7.11.1 {ECO:0000250|UniProtKB:P04049};
DE AltName: Full=Proto-oncogene c-RAF;
DE Short=cRaf;
DE AltName: Full=Raf-1;
GN Name=RAF1 {ECO:0000312|EMBL:ABS45011.1};
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1] {ECO:0000305, ECO:0000312|EMBL:ABS45011.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RX PubMed=16305752; DOI=10.1186/1471-2164-6-166;
RA Harhay G.P., Sonstegard T.S., Keele J.W., Heaton M.P., Clawson M.L.,
RA Snelling W.M., Wiedmann R.T., Van Tassell C.P., Smith T.P.L.;
RT "Characterization of 954 bovine full-CDS cDNA sequences.";
RL BMC Genomics 6:166-166(2005).
RN [2] {ECO:0000305, ECO:0000312|EMBL:AAI51320.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC STRAIN=Hereford {ECO:0000312|EMBL:AAI51320.1};
RC TISSUE=Heart ventricle {ECO:0000312|EMBL:AAI51320.1};
RG NIH - Mammalian Gene Collection (MGC) project;
RL Submitted (JUL-2007) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Serine/threonine-protein kinase that acts as a regulatory
CC link between the membrane-associated Ras GTPases and the MAPK/ERK
CC cascade, and this critical regulatory link functions as a switch
CC determining cell fate decisions including proliferation,
CC differentiation, apoptosis, survival and oncogenic transformation. RAF1
CC activation initiates a mitogen-activated protein kinase (MAPK) cascade
CC that comprises a sequential phosphorylation of the dual-specific MAPK
CC kinases (MAP2K1/MEK1 and MAP2K2/MEK2) and the extracellular signal-
CC regulated kinases (MAPK3/ERK1 and MAPK1/ERK2). The phosphorylated form
CC of RAF1 (on residues Ser-338 and Ser-339, by PAK1) phosphorylates
CC BAD/Bcl2-antagonist of cell death at 'Ser-75'. Phosphorylates adenylyl
CC cyclases: ADCY2, ADCY5 and ADCY6, resulting in their activation.
CC Phosphorylates PPP1R12A resulting in inhibition of the phosphatase
CC activity. Phosphorylates TNNT2/cardiac muscle troponin T. Can promote
CC NF-kB activation and inhibit signal transducers involved in motility
CC (ROCK2), apoptosis (MAP3K5/ASK1 and STK3/MST2), proliferation and
CC angiogenesis (RB1). Can protect cells from apoptosis also by
CC translocating to the mitochondria where it binds BCL2 and displaces
CC BAD/Bcl2-antagonist of cell death. Regulates Rho signaling and
CC migration, and is required for normal wound healing. Plays a role in
CC the oncogenic transformation of epithelial cells via repression of the
CC TJ protein, occludin (OCLN) by inducing the up-regulation of a
CC transcriptional repressor SNAI2/SLUG, which induces down-regulation of
CC OCLN. Restricts caspase activation in response to selected stimuli,
CC notably Fas stimulation, pathogen-mediated macrophage apoptosis, and
CC erythroid differentiation (By similarity).
CC {ECO:0000250|UniProtKB:P04049}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-
CC [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-
CC COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.1;
CC Evidence={ECO:0000250|UniProtKB:P04049};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:17990;
CC Evidence={ECO:0000250|UniProtKB:P04049};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-
CC threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060,
CC Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216;
CC EC=2.7.11.1; Evidence={ECO:0000250|UniProtKB:P04049};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46609;
CC Evidence={ECO:0000250|UniProtKB:P04049};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000250|UniProtKB:P04049};
CC Note=Binds 2 Zn(2+) ions per subunit. {ECO:0000250|UniProtKB:P04049};
CC -!- ACTIVITY REGULATION: Regulation is a highly complex process involving
CC membrane recruitment, protein-protein interactions, dimerization, and
CC phosphorylation/dephosphorylation events. Ras-GTP recruits RAF1 to the
CC membrane, thereby promoting its activation. The inactive conformation
CC of RAF1 is maintained by autoinhibitory interactions occurring between
CC the N-terminal regulatory and the C-terminal catalytic domains and by
CC the binding of a 14-3-3 protein that contacts two phosphorylation
CC sites, Ser-259 and Ser-621. Upon mitogenic stimulation, Ras and PPP2R1A
CC cooperate to release autoinhibition and the subsequent phosphorylation
CC of activating sites: Ser-338, Tyr-341, Thr-491, and Ser-494, yields a
CC fully active kinase. Through a negative feedback mechanism involving
CC MAPK1/ERK2, RAF1 is phosphorylated on Ser-29, Ser-43, Ser-289, Ser-296,
CC Ser-301 and Ser-642 by MAPK1/ERK2, which yields an inactive,
CC desensitized kinase. The signaling-competent conformation of RAF1 is
CC finally re-established by the coordinated action of PIN1, a prolyl
CC isomerase that converts pSer and pThr residues from the cis to the
CC trans conformation, which is preferentially recognized and
CC dephosphorylated by PPP2R1A. Activated by homodimerization and
CC heterodimerization (with BRAF). Also regulated through association with
CC other proteins such as KSR2, CNKSR1/CNK1, PEBP1/RKIP, PHB/prohibitin
CC and SPRY4. PEBP1/RKIP acts by dissociating RAF1 from its substrates
CC MAP2K1/MEK1 and MAP2K2/MEK2. PHB/prohibitin facilitates the
CC displacement of 14-3-3 from RAF1 by activated Ras, thereby promoting
CC cell membrane localization and phosphorylation of RAF1 at the
CC activating Ser-338. SPRY4 inhibits Ras-independent, but not Ras-
CC dependent, activation of RAF1. CNKSR1/CNK1 regulates Src-mediated RAF1
CC activation (By similarity). {ECO:0000250}.
CC -!- SUBUNIT: Monomer. Homodimer. Heterodimerizes with BRAF and this
CC heterodimer possesses a highly increased kinase activity compared to
CC the respective homodimers or monomers. Heterodimerization is mitogen-
CC regulated and enhanced by 14-3-3 proteins. MAPK1/ERK2 activation can
CC induce a negative feedback that promotes the dissociation of the
CC heterodimer. Forms a multiprotein complex with Ras (M-Ras/MRAS), SHOC2
CC and protein phosphatase 1 (PPP1CA, PPP1CB and PPP1CC). Interacts with
CC LZTR1. Interacts with Ras proteins; the interaction is antagonized by
CC RIN1 (By similarity). Weakly interacts with RIT1. Interacts (via N-
CC terminus) with RGS14 (via RBD domains); the interaction mediates the
CC formation of a ternary complex with BRAF, a ternary complex inhibited
CC by GNAI1 (By similarity). Probably forms a complex composed of
CC chaperones HSP90 and HSP70, co-chaperones CDC37, PPP5C, TSC1 and client
CC protein TSC2, CDK4, AKT, RAF1 and NR3C1; this complex does not contain
CC co-chaperones STIP1/HOP and PTGES3/p23. Interacts with STK3/MST2; the
CC interaction inhibits its pro-apoptotic activity. Interacts (when
CC phosphorylated at Ser-259) with YWHAZ (unphosphorylated at 'Thr-232')
CC (By similarity). Interacts with MAP2K1/MEK1 and MAP2K2/MEK2 (By
CC similarity). Interacts with MAP3K5/ASF1 (via N-terminus) and this
CC interaction inhibits the proapoptotic function of MAP3K5/ASK1.
CC Interacts with PAK1 (via kinase domain) (By similarity). The
CC phosphorylated form interacts with PIN1 (By similarity). The Ser-338
CC and Ser-339 phosphorylated form (by PAK1) interacts with BCL2.
CC Interacts with PEBP1/RKIP and this interaction is enhanced if RAF1 is
CC phosphorylated on residues Ser-338, Ser-339, Tyr-340 and Tyr-341.
CC Interacts with ADCY2, ADCY5, ADCY6, DGKH, RCAN1/DSCR1, PPP1R12A,
CC PKB/AKT1, PPP2CA, PPP2R1B, SPRY2, SPRY4, CNKSR1/CNK1, KSR2 and
CC PHB/prohibitin (By similarity). Interacts with ROCK2 (By similarity).
CC In its active form, interacts with PRMT5. Interacts with FAM83B;
CC displaces 14-3-3 proteins from RAF1 and activates RAF1. Interacts with
CC PDE8A; the interaction promotes RAF1 activity. Interacts with MFHAS1
CC (By similarity). Interacts with GLS (By similarity). Interacts with
CC NEK10 and MAP2K1; the interaction is direct with NEK10 and required for
CC ERK1/2-signaling pathway activation in response to UV irradiation (By
CC similarity). {ECO:0000250|UniProtKB:P04049,
CC ECO:0000250|UniProtKB:P11345, ECO:0000250|UniProtKB:Q99N57}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Cell membrane
CC {ECO:0000250}. Mitochondrion {ECO:0000250}. Nucleus {ECO:0000250}.
CC Note=Colocalizes with RGS14 and BRAF in both the cytoplasm and
CC membranes. Phosphorylation at Ser-259 impairs its membrane
CC accumulation. Recruited to the cell membrane by the active Ras protein.
CC Phosphorylation at Ser-338 and Ser-339 by PAK1 is required for its
CC mitochondrial localization. Retinoic acid-induced Ser-621
CC phosphorylated form of RAF1 is predominantly localized at the nucleus
CC (By similarity). {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1 {ECO:0000269|PubMed:16305752};
CC IsoId=A7E3S4-1; Sequence=Displayed;
CC Name=2;
CC IsoId=A7E3S4-2; Sequence=VSP_052844;
CC -!- PTM: Phosphorylation at Thr-269, Ser-338, Tyr-341, Thr-491 and Ser-494
CC results in its activation. Phosphorylation at Ser-29, Ser-43, Ser-289,
CC Ser-296, Ser-301 and Ser-642 by MAPK1/ERK2 results in its inactivation.
CC Phosphorylation at Ser-259 induces the interaction with YWHAZ and
CC inactivates kinase activity. Dephosphorylation of Ser-259 by the
CC complex containing protein phosphatase 1, SHOC2 and M-Ras/MRAS relieves
CC inactivation, leading to stimulate RAF1 activity. Phosphorylation at
CC Ser-338 by PAK1 and PAK5 and Ser-339 by PAK1 is required for its
CC mitochondrial localization (By similarity). Phosphorylation at Ser-621
CC in response to growth factor treatment stabilizes the protein, possibly
CC by preventing proteasomal degradation. Phosphorylation at Ser-289, Ser-
CC 296, Ser-301, Ser-338 and Ser-621 are somehow linked to the methylation
CC potential of cells. Treatment of cells with HGF in the presence of the
CC methylation inhibitor 5'-methylthioadenosine (MTA) results in increased
CC phosphorylation at Ser-338 and Ser-621 and decreased phosphorylation at
CC Ser-296, Ser-301 and Ser-338. Dephosphorylation at SER-338 by PPP5C
CC results in a decreased of activity (By similarity). {ECO:0000250}.
CC -!- PTM: Methylated at Arg-563 in response to EGF treatment. This
CC modification leads to destabilization of the protein, possibly through
CC proteasomal degradation. {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. TKL Ser/Thr
CC protein kinase family. RAF subfamily. {ECO:0000255}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; BT030695; ABS45011.1; -; mRNA.
DR EMBL; BC151319; AAI51320.1; -; mRNA.
DR RefSeq; NP_001095975.1; NM_001102505.1. [A7E3S4-2]
DR RefSeq; XP_005223216.2; XM_005223159.2.
DR RefSeq; XP_015324294.1; XM_015468808.1.
DR AlphaFoldDB; A7E3S4; -.
DR BMRB; A7E3S4; -.
DR SMR; A7E3S4; -.
DR IntAct; A7E3S4; 1.
DR STRING; 9913.ENSBTAP00000005930; -.
DR PaxDb; A7E3S4; -.
DR PRIDE; A7E3S4; -.
DR Ensembl; ENSBTAT00000005930; ENSBTAP00000005930; ENSBTAG00000045748. [A7E3S4-2]
DR Ensembl; ENSBTAT00000054270; ENSBTAP00000048678; ENSBTAG00000045748. [A7E3S4-1]
DR Ensembl; ENSBTAT00000081792; ENSBTAP00000060802; ENSBTAG00000045748. [A7E3S4-1]
DR GeneID; 521196; -.
DR KEGG; bta:521196; -.
DR CTD; 5894; -.
DR VEuPathDB; HostDB:ENSBTAG00000045748; -.
DR eggNOG; KOG0193; Eukaryota.
DR GeneTree; ENSGT00940000156084; -.
DR InParanoid; A7E3S4; -.
DR OMA; SWCHRFW; -.
DR OrthoDB; 243095at2759; -.
DR ChiTaRS; RAF1; cattle.
DR Proteomes; UP000009136; Chromosome 22.
DR Bgee; ENSBTAG00000045748; Expressed in neutrophil and 105 other tissues.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; IEA:Ensembl.
DR GO; GO:0005794; C:Golgi apparatus; IEA:Ensembl.
DR GO; GO:0005739; C:mitochondrion; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0031143; C:pseudopodium; IEA:Ensembl.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0042802; F:identical protein binding; IEA:Ensembl.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004672; F:protein kinase activity; IBA:GO_Central.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IEA:UniProtKB-KW.
DR GO; GO:0031267; F:small GTPase binding; IEA:Ensembl.
DR GO; GO:0007190; P:activation of adenylate cyclase activity; IEA:Ensembl.
DR GO; GO:0030154; P:cell differentiation; IEA:Ensembl.
DR GO; GO:0071550; P:death-inducing signaling complex assembly; IEA:Ensembl.
DR GO; GO:0008625; P:extrinsic apoptotic signaling pathway via death domain receptors; IEA:Ensembl.
DR GO; GO:0060324; P:face development; IEA:Ensembl.
DR GO; GO:0035773; P:insulin secretion involved in cellular response to glucose stimulus; IEA:Ensembl.
DR GO; GO:0045104; P:intermediate filament cytoskeleton organization; IEA:Ensembl.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; IEA:Ensembl.
DR GO; GO:1902042; P:negative regulation of extrinsic apoptotic signaling pathway via death domain receptors; IEA:Ensembl.
DR GO; GO:0031333; P:negative regulation of protein-containing complex assembly; IEA:Ensembl.
DR GO; GO:0048011; P:neurotrophin TRK receptor signaling pathway; IEA:Ensembl.
DR GO; GO:0043410; P:positive regulation of MAPK cascade; IEA:Ensembl.
DR GO; GO:0033138; P:positive regulation of peptidyl-serine phosphorylation; IEA:Ensembl.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IEA:Ensembl.
DR GO; GO:0006468; P:protein phosphorylation; IEA:InterPro.
DR GO; GO:0035994; P:response to muscle stretch; IEA:Ensembl.
DR GO; GO:0007165; P:signal transduction; IBA:GO_Central.
DR GO; GO:0035019; P:somatic stem cell population maintenance; IEA:Ensembl.
DR GO; GO:0048538; P:thymus development; IEA:Ensembl.
DR GO; GO:0030878; P:thyroid gland development; IEA:Ensembl.
DR CDD; cd00029; C1; 1.
DR InterPro; IPR046349; C1-like_sf.
DR InterPro; IPR020454; DAG/PE-bd.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR002219; PE/DAG-bd.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR003116; RBD_dom.
DR InterPro; IPR001245; Ser-Thr/Tyr_kinase_cat_dom.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR InterPro; IPR029071; Ubiquitin-like_domsf.
DR Pfam; PF00130; C1_1; 1.
DR Pfam; PF07714; PK_Tyr_Ser-Thr; 1.
DR Pfam; PF02196; RBD; 1.
DR PRINTS; PR00008; DAGPEDOMAIN.
DR SMART; SM00109; C1; 1.
DR SMART; SM00455; RBD; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF54236; SSF54236; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR SUPFAM; SSF57889; SSF57889; 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
DR PROSITE; PS50898; RBD; 1.
DR PROSITE; PS00479; ZF_DAG_PE_1; 1.
DR PROSITE; PS50081; ZF_DAG_PE_2; 1.
PE 2: Evidence at transcript level;
KW Alternative splicing; ATP-binding; Cell membrane; Cytoplasm; Kinase;
KW Membrane; Metal-binding; Methylation; Mitochondrion; Nucleotide-binding;
KW Nucleus; Phosphoprotein; Proto-oncogene; Reference proteome;
KW Serine/threonine-protein kinase; Transferase; Zinc; Zinc-finger.
FT CHAIN 1..648
FT /note="RAF proto-oncogene serine/threonine-protein kinase"
FT /id="PRO_0000348937"
FT DOMAIN 56..131
FT /note="RBD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00262"
FT DOMAIN 349..609
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT ZN_FING 138..184
FT /note="Phorbol-ester/DAG-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00226"
FT REGION 218..335
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 331..349
FT /note="Interaction with PEBP1/RKIP"
FT /evidence="ECO:0000250"
FT COMPBIAS 226..267
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 284..310
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 468
FT /note="Proton acceptor"
FT /evidence="ECO:0000250|UniProtKB:P04049,
FT ECO:0000255|PROSITE-ProRule:PRU00159, ECO:0000255|PROSITE-
FT ProRule:PRU10027"
FT BINDING 139
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P04049"
FT BINDING 152
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P04049"
FT BINDING 155
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P04049"
FT BINDING 165
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P04049"
FT BINDING 168
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P04049"
FT BINDING 173
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P04049"
FT BINDING 176
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P04049"
FT BINDING 184
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P04049"
FT BINDING 355..363
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P12931,
FT ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 375
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P12931,
FT ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 29
FT /note="Phosphoserine; by MAPK1"
FT /evidence="ECO:0000250|UniProtKB:Q99N57"
FT MOD_RES 43
FT /note="Phosphoserine; by PKA and MAPK1"
FT /evidence="ECO:0000250|UniProtKB:P04049"
FT MOD_RES 233
FT /note="Phosphoserine; by PKA"
FT /evidence="ECO:0000250|UniProtKB:P04049"
FT MOD_RES 252
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P04049"
FT MOD_RES 259
FT /note="Phosphoserine; by PKA, PKC and PKB/AKT1"
FT /evidence="ECO:0000250|UniProtKB:P04049"
FT MOD_RES 269
FT /note="Phosphothreonine; by PKA"
FT /evidence="ECO:0000250|UniProtKB:P04049"
FT MOD_RES 289
FT /note="Phosphoserine; by MAPK1"
FT /evidence="ECO:0000250|UniProtKB:P04049"
FT MOD_RES 296
FT /note="Phosphoserine; by MAPK1"
FT /evidence="ECO:0000250|UniProtKB:Q99N57"
FT MOD_RES 301
FT /note="Phosphoserine; by MAPK1"
FT /evidence="ECO:0000250|UniProtKB:P04049"
FT MOD_RES 338
FT /note="Phosphoserine; by PAK1, PAK2, PAK3 and PAK5"
FT /evidence="ECO:0000250|UniProtKB:P04049"
FT MOD_RES 339
FT /note="Phosphoserine; by PAK1, PAK2 and PAK3"
FT /evidence="ECO:0000250|UniProtKB:P04049"
FT MOD_RES 340
FT /note="Phosphotyrosine; by SRC"
FT /evidence="ECO:0000250|UniProtKB:P04049"
FT MOD_RES 341
FT /note="Phosphotyrosine; by SRC"
FT /evidence="ECO:0000250|UniProtKB:P04049"
FT MOD_RES 471
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P04049"
FT MOD_RES 491
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P04049"
FT MOD_RES 494
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P04049"
FT MOD_RES 497
FT /note="Phosphoserine; by PKC"
FT /evidence="ECO:0000250|UniProtKB:P04049"
FT MOD_RES 499
FT /note="Phosphoserine; by PKC"
FT /evidence="ECO:0000250|UniProtKB:P04049"
FT MOD_RES 563
FT /note="Symmetric dimethylarginine; by PRMT5"
FT /evidence="ECO:0000250|UniProtKB:P04049"
FT MOD_RES 621
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P04049"
FT MOD_RES 642
FT /note="Phosphoserine; by MAPK1"
FT /evidence="ECO:0000250|UniProtKB:P04049"
FT VAR_SEQ 278
FT /note="E -> ENNSLNASPRAWSRRFCVRGR (in isoform 2)"
FT /evidence="ECO:0000303|Ref.2"
FT /id="VSP_052844"
SQ SEQUENCE 648 AA; 72874 MW; 283F6CEBFD9274E4 CRC64;
MEHIQGAWKT ISNGFGFKDT VFDGTSCISP TIVQQFGYQR RASDDGKLTD PSKTSNTIRV
FLPNKQRTVV NVRNGMSLHD CLMKALKVRG LQPECCAVFR LLHEHKGKKA RLDWNTDAAS
LIGEELQVDF LDHVPLTTHN FARKTFLKLA FCDICQKFLL NGFRCQTCGY KFHEHCSTKV
PTMCVDWSNI RQLLLFPNST VGDGGVPALP SLTMRRMRES VSRIPPGSQH RYSTPHAFTF
SASSPSSEGS LSQRQRSTST PNVHMVSATL PVDSRMIEDA IRSHSESGSP SALSSSPNNL
SPTGWSQPKT PAPAQRERAP GSSTQEKNKI RPRGQRDSSY YWEIEASEVM LSTRIGSGSF
GTVYKGKWHG DVAVKILKVV DPTPEQFQAF RNEVAVLRKT RHVNILLFMG YMTKDNLAIV
TQWCEGSSLY KHLHVQETKF QMFQLIDIAR QTAQGMDYLH AKNIIHRDMK SNNIFLHEGL
TVKIGDFGLA TVKSRWSGSQ QVEQPTGSIL WMAPEVIRMQ DNNPFSFQSD VYSYGIVLYE
LMTGELPYSH INNRDQIIFM VGRGYASPDL SKLYKNCPKA MKRLVADCVK KVKEERPLFP
QILSSIELLQ HSLPKINRSA SEPSLHRAAH TEDINACTLT TSPRLPVF
