VGFR2_RAT
ID VGFR2_RAT Reviewed; 1343 AA.
AC O08775;
DT 01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-1997, sequence version 1.
DT 03-AUG-2022, entry version 179.
DE RecName: Full=Vascular endothelial growth factor receptor 2 {ECO:0000305};
DE Short=VEGFR-2;
DE EC=2.7.10.1 {ECO:0000250|UniProtKB:P35968};
DE AltName: Full=Fetal liver kinase 1;
DE Short=FLK-1;
DE AltName: Full=Protein-tyrosine kinase receptor flk-1;
DE AltName: CD_antigen=CD309;
DE Flags: Precursor;
GN Name=Kdr {ECO:0000312|RGD:2965}; Synonyms=Flk1;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Retina;
RA Wen Y., Edelman J.L., De Vries G.W., Sachs G.;
RL Submitted (MAR-1997) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RX PubMed=10878616;
RX DOI=10.1002/1097-0177(200007)218:3<507::aid-dvdy1012>3.0.co;2-5;
RA Pepper M.S., Baetens D., Mandriota S.J., Di Sanza C., Oikemus S.,
RA Lane T.F., Soriano J.V., Montesano R., Iruela-Arispe M.L.;
RT "Regulation of VEGF and VEGF receptor expression in the rodent mammary
RT gland during pregnancy, lactation, and involution.";
RL Dev. Dyn. 218:507-524(2000).
RN [3]
RP PROTEIN SEQUENCE OF 1040-1047, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC STRAIN=Sprague-Dawley; TISSUE=Brain;
RA Lubec G., Kang S.U.;
RL Submitted (JUL-2007) to UniProtKB.
RN [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-978 AND SER-980, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
CC -!- FUNCTION: Tyrosine-protein kinase that acts as a cell-surface receptor
CC for VEGFA, VEGFC and VEGFD. Plays an essential role in the regulation
CC of angiogenesis, vascular development, vascular permeability, and
CC embryonic hematopoiesis. Promotes proliferation, survival, migration
CC and differentiation of endothelial cells. Promotes reorganization of
CC the actin cytoskeleton. Isoforms lacking a transmembrane domain may
CC function as decoy receptors for VEGFA, VEGFC and/or VEGFD. Modulates
CC FLT1 and FLT4 signaling by forming heterodimers. Binding of vascular
CC growth factors to isoform 1 leads to the activation of several
CC signaling cascades. Activation of PLCG1 leads to the production of the
CC cellular signaling molecules diacylglycerol and inositol-1,4,5-
CC trisphosphate and the activation of protein kinase C. Mediates
CC activation of MAPK1/ERK2, MAPK3/ERK1 and the MAP kinase signaling
CC pathway, as well as of the AKT1 signaling pathway. Mediates
CC phosphorylation of PIK3R1, the regulatory subunit of
CC phosphatidylinositol 3-kinase, reorganization of the actin cytoskeleton
CC and activation of PTK2/FAK1. Required for VEGFA-mediated induction of
CC NOS2 and NOS3, leading to the production of the signaling molecule
CC nitric oxide (NO) by endothelial cells. Phosphorylates PLCG1. Promotes
CC phosphorylation of FYN, NCK1, NOS3, PIK3R1, PTK2/FAK1 and SRC (By
CC similarity). {ECO:0000250}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-tyrosyl-[protein] = ADP + H(+) + O-phospho-L-tyrosyl-
CC [protein]; Xref=Rhea:RHEA:10596, Rhea:RHEA-COMP:10136, Rhea:RHEA-
CC COMP:10137, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616, ChEBI:CHEBI:46858,
CC ChEBI:CHEBI:82620, ChEBI:CHEBI:456216; EC=2.7.10.1;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU10028};
CC -!- ACTIVITY REGULATION: Present in an inactive conformation in the absence
CC of bound ligand. Binding of VEGFA, VEGFC or VEGFD leads to dimerization
CC and activation by autophosphorylation on tyrosine residues. May be
CC regulated by hydrogen sulfide (H(2)S) levels via a sensitive
CC intracellular disulfide bond (By similarity). {ECO:0000250}.
CC -!- SUBUNIT: Homodimer in the presence of bound dimeric VEGFA, VEGFC or
CC VEGFD ligands; monomeric in the absence of bound ligands. Can also form
CC heterodimers with FLT1/VEGFR1 and KDR/VEGFR2. Interacts (tyrosine
CC phosphorylated) with LFYN, NCK1, PLCG1. Interacts (tyrosine-
CC phosphorylated active form preferentially) with DAB2IP (via C2 domain
CC and active form preferentially); the interaction occurs at the late
CC phase of VEGFA response and inhibits KDR/VEGFR2 activity. Interacts
CC with SHBSH2D2A/TSAD, GRB2, MYOF, CBL and PDCD6. Interacts (via C-
CC terminus domain) with ERN1 (via kinase domain); the interaction is
CC facilitated in a XBP1- and vascular endothelial growth factor (VEGF)-
CC dependent manner in endothelial cells (By similarity). Interacts (via
CC juxtamembrane region) with chaperone PDCL3 (via thioredoxin fold
CC region); the interaction leads to increased KDR/VEGFR2 abundance
CC through inhibition of its ubiquitination and degradation (By
CC similarity). Interacts (tyrosine phosphorylated) with CCDC88A/GIV (via
CC SH2-like region); binding requires autophosphorylation of the
CC KDR/VEGFR2 C-terminal region (By similarity). Interacts with isoform 2
CC of BSG (By similarity). {ECO:0000250|UniProtKB:P35968}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:P35968};
CC Single-pass type I membrane protein {ECO:0000250}. Cytoplasm
CC {ECO:0000250}. Nucleus {ECO:0000250}. Cytoplasmic vesicle
CC {ECO:0000250}. Early endosome {ECO:0000250}. Cell junction
CC {ECO:0000250}. Endoplasmic reticulum {ECO:0000250|UniProtKB:P35968}.
CC Note=Detected on caveolae-enriched lipid rafts at the cell surface. Is
CC recycled from the plasma membrane to endosomes and back again.
CC Phosphorylation triggered by VEGFA binding promotes internalization and
CC subsequent degradation. VEGFA binding triggers internalization and
CC translocation to the nucleus. Localized with RAP1A at cell-cell
CC junctions. Colocalizes with ERN1 and XBP1 in the endoplasmic reticulum
CC in endothelial cells in a vascular endothelial growth factor (VEGF)-
CC dependent manner (By similarity). {ECO:0000250|UniProtKB:P35968}.
CC -!- TISSUE SPECIFICITY: Expressed in the post-pubertal mammary glands.
CC {ECO:0000269|PubMed:10878616}.
CC -!- DEVELOPMENTAL STAGE: Increases during pregnancy (1.6-fold at 4 days)
CC and lactation (3.8-fold at 7 days). Decreases in the early phases of
CC involution (45%, 50% and 34% on days 1, 2, and 3 respectively).
CC {ECO:0000269|PubMed:10878616}.
CC -!- DOMAIN: The second and third Ig-like C2-type (immunoglobulin-like)
CC domains are sufficient for VEGFC binding. {ECO:0000250}.
CC -!- PTM: N-glycosylated. {ECO:0000250}.
CC -!- PTM: Ubiquitinated. Tyrosine phosphorylation of the receptor promotes
CC its poly-ubiquitination, leading to its degradation via the proteasome
CC or lysosomal proteases (By similarity). {ECO:0000250}.
CC -!- PTM: Autophosphorylated on tyrosine residues upon ligand binding.
CC Autophosphorylation occurs in trans, i.e. one subunit of the dimeric
CC receptor phosphorylates tyrosine residues on the other subunit.
CC Phosphorylation at Tyr-947 is important for interaction with
CC SH2D2A/TSAD and VEGFA-mediated reorganization of the actin
CC cytoskeleton. Phosphorylation at Tyr-1171 is important for interaction
CC with PLCG1 and SHB. Phosphorylation at Tyr-1210 is important for
CC interaction with NCK1 and FYN. Dephosphorylated by PTPRB.
CC Dephosphorylated by PTPRJ at Tyr-797, Tyr-947, Tyr-992, Tyr-1050, Tyr-
CC 1055, Tyr-1171 and Tyr-1210 (By similarity).
CC {ECO:0000250|UniProtKB:P35968}.
CC -!- PTM: The inhibitory disulfide bond between Cys-1020 and Cys-1041 may
CC serve as a specific molecular switch for H(2)S-induced modification
CC that regulates KDR/VEGFR2 function. {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein
CC kinase family. CSF-1/PDGF receptor subfamily. {ECO:0000255|PROSITE-
CC ProRule:PRU00159}.
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DR EMBL; U93306; AAB97508.1; -; mRNA.
DR EMBL; U93307; AAB97509.1; -; mRNA.
DR RefSeq; NP_037194.1; NM_013062.1.
DR AlphaFoldDB; O08775; -.
DR SMR; O08775; -.
DR IntAct; O08775; 1.
DR MINT; O08775; -.
DR STRING; 10116.ENSRNOP00000066886; -.
DR BindingDB; O08775; -.
DR GlyGen; O08775; 16 sites.
DR iPTMnet; O08775; -.
DR PhosphoSitePlus; O08775; -.
DR jPOST; O08775; -.
DR PaxDb; O08775; -.
DR PRIDE; O08775; -.
DR GeneID; 25589; -.
DR KEGG; rno:25589; -.
DR CTD; 3791; -.
DR RGD; 2965; Kdr.
DR eggNOG; KOG0200; Eukaryota.
DR InParanoid; O08775; -.
DR OrthoDB; 236292at2759; -.
DR PhylomeDB; O08775; -.
DR BRENDA; 2.7.10.1; 5301.
DR Reactome; R-RNO-194306; Neurophilin interactions with VEGF and VEGFR.
DR Reactome; R-RNO-195399; VEGF binds to VEGFR leading to receptor dimerization.
DR Reactome; R-RNO-216083; Integrin cell surface interactions.
DR Reactome; R-RNO-4420097; VEGFA-VEGFR2 Pathway.
DR Reactome; R-RNO-5218921; VEGFR2 mediated cell proliferation.
DR PRO; PR:O08775; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-SubCell.
DR GO; GO:0030054; C:cell junction; ISS:UniProtKB.
DR GO; GO:0071944; C:cell periphery; ISO:RGD.
DR GO; GO:0009986; C:cell surface; ISO:RGD.
DR GO; GO:0005737; C:cytoplasm; IDA:RGD.
DR GO; GO:0005769; C:early endosome; ISO:RGD.
DR GO; GO:0005783; C:endoplasmic reticulum; ISS:UniProtKB.
DR GO; GO:0005768; C:endosome; ISO:RGD.
DR GO; GO:0009897; C:external side of plasma membrane; ISO:RGD.
DR GO; GO:0005794; C:Golgi apparatus; ISO:RGD.
DR GO; GO:0005887; C:integral component of plasma membrane; ISS:UniProtKB.
DR GO; GO:0045121; C:membrane raft; ISO:RGD.
DR GO; GO:0043005; C:neuron projection; IDA:RGD.
DR GO; GO:0043025; C:neuronal cell body; IDA:RGD.
DR GO; GO:0005634; C:nucleus; ISO:RGD.
DR GO; GO:0005886; C:plasma membrane; IDA:RGD.
DR GO; GO:0043235; C:receptor complex; IBA:GO_Central.
DR GO; GO:0097443; C:sorting endosome; ISO:RGD.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0045296; F:cadherin binding; ISO:RGD.
DR GO; GO:0019838; F:growth factor binding; IMP:RGD.
DR GO; GO:0042802; F:identical protein binding; ISO:RGD.
DR GO; GO:0005178; F:integrin binding; ISO:RGD.
DR GO; GO:0004713; F:protein tyrosine kinase activity; ISO:RGD.
DR GO; GO:0004714; F:transmembrane receptor protein tyrosine kinase activity; IBA:GO_Central.
DR GO; GO:0038085; F:vascular endothelial growth factor binding; ISO:RGD.
DR GO; GO:0005021; F:vascular endothelial growth factor receptor activity; IMP:RGD.
DR GO; GO:0007568; P:aging; IEP:RGD.
DR GO; GO:0001525; P:angiogenesis; IBA:GO_Central.
DR GO; GO:0001569; P:branching involved in blood vessel morphogenesis; ISO:RGD.
DR GO; GO:0048754; P:branching morphogenesis of an epithelial tube; ISO:RGD.
DR GO; GO:0055074; P:calcium ion homeostasis; ISO:RGD.
DR GO; GO:0035584; P:calcium-mediated signaling using intracellular calcium source; ISS:UniProtKB.
DR GO; GO:0045165; P:cell fate commitment; ISO:RGD.
DR GO; GO:0048469; P:cell maturation; ISO:RGD.
DR GO; GO:0016477; P:cell migration; ISO:RGD.
DR GO; GO:0002042; P:cell migration involved in sprouting angiogenesis; ISO:RGD.
DR GO; GO:1904881; P:cellular response to hydrogen sulfide; ISO:RGD.
DR GO; GO:0035924; P:cellular response to vascular endothelial growth factor stimulus; ISS:UniProtKB.
DR GO; GO:0035162; P:embryonic hemopoiesis; ISS:UniProtKB.
DR GO; GO:0003157; P:endocardium development; ISO:RGD.
DR GO; GO:0003416; P:endochondral bone growth; IMP:RGD.
DR GO; GO:0045446; P:endothelial cell differentiation; ISO:RGD.
DR GO; GO:0061154; P:endothelial tube morphogenesis; IMP:RGD.
DR GO; GO:0003158; P:endothelium development; ISS:UniProtKB.
DR GO; GO:0070371; P:ERK1 and ERK2 cascade; ISO:RGD.
DR GO; GO:0002244; P:hematopoietic progenitor cell differentiation; IBA:GO_Central.
DR GO; GO:0030097; P:hemopoiesis; ISO:RGD.
DR GO; GO:0048286; P:lung alveolus development; ISO:RGD.
DR GO; GO:0030324; P:lung development; ISO:RGD.
DR GO; GO:0001945; P:lymph vessel development; ISO:RGD.
DR GO; GO:0008584; P:male gonad development; IDA:RGD.
DR GO; GO:0043066; P:negative regulation of apoptotic process; ISS:UniProtKB.
DR GO; GO:2000352; P:negative regulation of endothelial cell apoptotic process; ISS:UniProtKB.
DR GO; GO:0010629; P:negative regulation of gene expression; ISO:RGD.
DR GO; GO:0043524; P:negative regulation of neuron apoptotic process; IMP:RGD.
DR GO; GO:0003085; P:negative regulation of systemic arterial blood pressure; IGI:RGD.
DR GO; GO:0048812; P:neuron projection morphogenesis; IMP:RGD.
DR GO; GO:0001541; P:ovarian follicle development; ISO:RGD.
DR GO; GO:0038083; P:peptidyl-tyrosine autophosphorylation; ISO:RGD.
DR GO; GO:0018108; P:peptidyl-tyrosine phosphorylation; ISS:UniProtKB.
DR GO; GO:0045766; P:positive regulation of angiogenesis; IDA:RGD.
DR GO; GO:0043536; P:positive regulation of blood vessel endothelial cell migration; ISO:RGD.
DR GO; GO:0030513; P:positive regulation of BMP signaling pathway; ISO:RGD.
DR GO; GO:0050850; P:positive regulation of calcium-mediated signaling; IMP:RGD.
DR GO; GO:0030335; P:positive regulation of cell migration; IMP:RGD.
DR GO; GO:0090050; P:positive regulation of cell migration involved in sprouting angiogenesis; ISO:RGD.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; IMP:RGD.
DR GO; GO:0007204; P:positive regulation of cytosolic calcium ion concentration; IMP:RGD.
DR GO; GO:0038033; P:positive regulation of endothelial cell chemotaxis by VEGF-activated vascular endothelial growth factor receptor signaling pathway; ISO:RGD.
DR GO; GO:0010595; P:positive regulation of endothelial cell migration; ISO:RGD.
DR GO; GO:0001938; P:positive regulation of endothelial cell proliferation; IMP:RGD.
DR GO; GO:0050679; P:positive regulation of epithelial cell proliferation; ISO:RGD.
DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; ISS:UniProtKB.
DR GO; GO:0051894; P:positive regulation of focal adhesion assembly; ISO:RGD.
DR GO; GO:0033674; P:positive regulation of kinase activity; IBA:GO_Central.
DR GO; GO:0048170; P:positive regulation of long-term neuronal synaptic plasticity; IMP:RGD.
DR GO; GO:0016239; P:positive regulation of macroautophagy; ISO:RGD.
DR GO; GO:0043410; P:positive regulation of MAPK cascade; ISS:UniProtKB.
DR GO; GO:0002053; P:positive regulation of mesenchymal cell proliferation; ISO:RGD.
DR GO; GO:0051901; P:positive regulation of mitochondrial depolarization; ISO:RGD.
DR GO; GO:0090141; P:positive regulation of mitochondrial fission; ISO:RGD.
DR GO; GO:0050769; P:positive regulation of neurogenesis; IEP:RGD.
DR GO; GO:0051770; P:positive regulation of nitric-oxide synthase biosynthetic process; ISS:UniProtKB.
DR GO; GO:0014068; P:positive regulation of phosphatidylinositol 3-kinase signaling; IMP:RGD.
DR GO; GO:0050927; P:positive regulation of positive chemotaxis; ISO:RGD.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; ISS:UniProtKB.
DR GO; GO:0032008; P:positive regulation of TOR signaling; IMP:RGD.
DR GO; GO:2001214; P:positive regulation of vasculogenesis; ISS:UniProtKB.
DR GO; GO:0048597; P:post-embryonic camera-type eye morphogenesis; ISO:RGD.
DR GO; GO:0046777; P:protein autophosphorylation; IDA:RGD.
DR GO; GO:0043491; P:protein kinase B signaling; ISO:RGD.
DR GO; GO:1903010; P:regulation of bone development; ISO:RGD.
DR GO; GO:0008360; P:regulation of cell shape; ISO:RGD.
DR GO; GO:1901532; P:regulation of hematopoietic progenitor cell differentiation; ISO:RGD.
DR GO; GO:0001666; P:response to hypoxia; IMP:RGD.
DR GO; GO:0070482; P:response to oxygen levels; IEP:RGD.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IMP:RGD.
DR GO; GO:0043129; P:surfactant homeostasis; ISO:RGD.
DR GO; GO:0007169; P:transmembrane receptor protein tyrosine kinase signaling pathway; IBA:GO_Central.
DR GO; GO:0048010; P:vascular endothelial growth factor receptor signaling pathway; IMP:RGD.
DR GO; GO:0036324; P:vascular endothelial growth factor receptor-2 signaling pathway; ISO:RGD.
DR GO; GO:0038084; P:vascular endothelial growth factor signaling pathway; ISO:RGD.
DR GO; GO:0061042; P:vascular wound healing; ISO:RGD.
DR GO; GO:0001570; P:vasculogenesis; ISS:UniProtKB.
DR GO; GO:0042311; P:vasodilation; IGI:RGD.
DR Gene3D; 2.60.40.10; -; 7.
DR InterPro; IPR007110; Ig-like_dom.
DR InterPro; IPR036179; Ig-like_dom_sf.
DR InterPro; IPR013783; Ig-like_fold.
DR InterPro; IPR013098; Ig_I-set.
DR InterPro; IPR003599; Ig_sub.
DR InterPro; IPR003598; Ig_sub2.
DR InterPro; IPR013151; Immunoglobulin.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR001245; Ser-Thr/Tyr_kinase_cat_dom.
DR InterPro; IPR008266; Tyr_kinase_AS.
DR InterPro; IPR020635; Tyr_kinase_cat_dom.
DR InterPro; IPR001824; Tyr_kinase_rcpt_3_CS.
DR InterPro; IPR041348; VEGFR-2_TMD.
DR InterPro; IPR009136; VEGFR2_rcpt.
DR Pfam; PF07679; I-set; 2.
DR Pfam; PF00047; ig; 1.
DR Pfam; PF07714; PK_Tyr_Ser-Thr; 1.
DR Pfam; PF17988; VEGFR-2_TMD; 1.
DR PRINTS; PR01834; VEGFRECEPTR2.
DR SMART; SM00409; IG; 7.
DR SMART; SM00408; IGc2; 5.
DR SMART; SM00219; TyrKc; 1.
DR SUPFAM; SSF48726; SSF48726; 7.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS50835; IG_LIKE; 5.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00109; PROTEIN_KINASE_TYR; 1.
DR PROSITE; PS00240; RECEPTOR_TYR_KIN_III; 1.
PE 1: Evidence at protein level;
KW Angiogenesis; ATP-binding; Cell junction; Cell membrane; Cytoplasm;
KW Cytoplasmic vesicle; Developmental protein; Differentiation;
KW Direct protein sequencing; Disulfide bond; Endoplasmic reticulum; Endosome;
KW Glycoprotein; Immunoglobulin domain; Kinase; Membrane; Nucleotide-binding;
KW Nucleus; Phosphoprotein; Receptor; Reference proteome; Repeat; Signal;
KW Transferase; Transmembrane; Transmembrane helix; Tyrosine-protein kinase;
KW Ubl conjugation.
FT SIGNAL 1..19
FT /evidence="ECO:0000255"
FT CHAIN 20..1343
FT /note="Vascular endothelial growth factor receptor 2"
FT /id="PRO_0000016773"
FT TOPO_DOM 20..760
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 761..781
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 782..1343
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 46..109
FT /note="Ig-like C2-type 1"
FT DOMAIN 141..207
FT /note="Ig-like C2-type 2"
FT DOMAIN 224..320
FT /note="Ig-like C2-type 3"
FT DOMAIN 328..414
FT /note="Ig-like C2-type 4"
FT DOMAIN 421..540
FT /note="Ig-like C2-type 5"
FT DOMAIN 547..654
FT /note="Ig-like C2-type 6"
FT DOMAIN 663..749
FT /note="Ig-like C2-type 7"
FT DOMAIN 830..1158
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 1267..1314
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1288..1314
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 1024
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10028"
FT BINDING 836..844
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 864
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT SITE 1171
FT /note="Interaction with SHB"
FT /evidence="ECO:0000250"
FT MOD_RES 797
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P35968"
FT MOD_RES 947
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:P35968"
FT MOD_RES 978
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 980
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 992
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:P35968"
FT MOD_RES 1050
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:P35968"
FT MOD_RES 1055
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:P35968"
FT MOD_RES 1171
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:P35968"
FT MOD_RES 1210
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:P35968"
FT MOD_RES 1227
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P35918"
FT MOD_RES 1231
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P35918"
FT MOD_RES 1234
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P35918"
FT MOD_RES 1301
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:P35968"
FT MOD_RES 1305
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:P35968"
FT MOD_RES 1315
FT /note="Phosphotyrosine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:P35968"
FT CARBOHYD 46
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 96
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 143
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 158
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 245
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 318
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 374
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 395
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 507
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 576
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 609
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 615
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 627
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 671
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 700
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 717
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 53..103
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 150..200
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 246..307
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 445..526
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 567..638
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 684..733
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
FT DISULFID 1020..1041
FT /note="Redox-active"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00114"
SQ SEQUENCE 1343 AA; 150394 MW; AD7E509EB62D3FF4 CRC64;
MESRALLAVA LWFCVETRAA SVGLPGDSLH PPKLSTQKDI LTILANTTLQ ITCRGQRDLD
WLWPNTPRDS EERVLVTECG DSIFCKTLTV PRVVGNDTGA YKCFYRDTDV SSIVYVYVQD
HRSPFIASVS DEHGIVYITE NKNKTVVIPC RGSISNLNVS LCARYPEKRF VPDGNRISWD
SEKGFTIPSY MISYAGMVFC EAKINDETYQ SIMYIVLVVG YRIYDVVLSP PHEIELSAGE
KLVLNCTART ELNVGLDFSW QFPSSKHQHK KIVNRDVKSL PGTVAKMFLS TLTIDSVTKS
DQGEYTCTAY SGLMTKKNKT FVRVHTKPFI AFGSGMKSLV EATVGSQVRI PVKYLSYPAP
DIKWYRNGRP IESNYTMIVG DELTIMEVSE RDAGNYTVIL TNPISMEKQS HMVSLVVNVP
PQIGEKALIS PMDSYQYGTM QTLTCTVYAN PPLHHIQWYW QLEEACSYRP SQTNPYTCKE
WRHVKDFQGG NKIEVTKNQY ALIEGKNKTV STLVIQAAYV SALYKCEAIN KAGRGERVIS
FHVIRGPEIT VQPATQPTER ESMSLLCTAD RNTFENLTWY KLGSQATSVH MGESLTPVCK
NLDALWKLNG TVFSNSTNDI LIVAFQNASL QDQGNYVCSA QDKKTKKRHC LVKQLVILER
MAPMITGNLE NQTTTIGETI EVVCPTSGNP TPLITWFKDN ETLVEDSGIV LKDGNRNLTI
RRVRKEDGGL YTCQACNVLG CARAETLFII EGVQEKTNLE VIILVGTAVI AMFFWLLLVI
LVRTVKRANE GELKTGYLSI VMDPDELPLD ERCERLPYDA SKWEFPRDRL KLGKPLGRGA
FGQVIEADAF GIDKTATCKT VAVKMLKEGA THSEHRALMS ELKILIHIGH HLNVVNLLGA
CTKPGGPLMV IVEFCKFGNL STYLRGKRNE FVPYKSKGAR FRSGKDYVGE LSVDLKRRLD
SITSSQSSAS SGFVEEKSLS DVEEEEASEE LYKDFLTLEH LICYSFQVAK GMEFLASRKC
IHRDLAARNI LLSEKNVVKI CDFGLARDIY KDPDYVRKGD PRLPLKWMAP ETIFDRIYTI
QSGVWSFGVL LWEIFSLGAS PYPGVKIDEK FCRRLKEGTR MRAPDYTTPE MYQTMLDCWH
EDPNQRPAFS ELVEHLGNLL QANAQQDGKD YIVLPMSETL SMEEDSGLSL PTSPVSCMEE
EEVCDPKFHY DNTAGISHYL QNSKRKSRPV SVKTFEDIPL EEPEVKVIPD DSQTDSGMVL
ASEELKTLED RNKLSPSFGG MMPSKSRESV ASEGSNQTSG YQSGYHSDDT DTTVYSSDEA
GLLKLVDVAG HVDSGTTLRS SPV
