ALK_MOUSE
ID ALK_MOUSE Reviewed; 1621 AA.
AC P97793; E9QKV3;
DT 27-MAR-2002, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 2.
DT 03-AUG-2022, entry version 183.
DE RecName: Full=ALK tyrosine kinase receptor {ECO:0000305};
DE EC=2.7.10.1 {ECO:0000250|UniProtKB:Q9UM73};
DE AltName: Full=Anaplastic lymphoma kinase {ECO:0000303|PubMed:9053841};
DE AltName: CD_antigen=CD246;
DE Flags: Precursor;
GN Name=Alk {ECO:0000303|PubMed:9053841, ECO:0000312|MGI:MGI:103305};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Brain, and Testis;
RX PubMed=9053841; DOI=10.1038/sj.onc.1200849;
RA Iwahara T., Fujimoto J., Wen D., Cupples R., Bucay N., Arakawa T., Mori S.,
RA Ratzkin B., Yamamoto T.;
RT "Molecular characterization of ALK, a receptor tyrosine kinase expressed
RT specifically in the nervous system.";
RL Oncogene 14:439-449(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [3]
RP PHOSPHORYLATION, INTERACTION WITH CBL; IRS1; PIK3R1; PLCG1 AND SHC1, AND
RP FUNCTION IN PHOSPHORYLATION OF CBL; IRS1 AND SHC1.
RX PubMed=15226403; DOI=10.1242/jcs.01183;
RA Motegi A., Fujimoto J., Kotani M., Sakuraba H., Yamamoto T.;
RT "ALK receptor tyrosine kinase promotes cell growth and neurite outgrowth.";
RL J. Cell Sci. 117:3319-3329(2004).
RN [4]
RP TISSUE SPECIFICITY, AND FUNCTION.
RX PubMed=16458083; DOI=10.1016/j.modgep.2005.11.006;
RA Vernersson E., Khoo N.K., Henriksson M.L., Roos G., Palmer R.H.,
RA Hallberg B.;
RT "Characterization of the expression of the ALK receptor tyrosine kinase in
RT mice.";
RL Gene Expr. Patterns 6:448-461(2006).
RN [5]
RP INTERACTION WITH IRS1 AND SHC, PHOSPHORYLATION AT TYR-1096, AND FUNCTION.
RX PubMed=16878150; DOI=10.1038/sj.onc.1209840;
RA Kuo A.H., Stoica G.E., Riegel A.T., Wellstein A.;
RT "Recruitment of insulin receptor substrate-1 and activation of NF-kappaB
RT essential for midkine growth signaling through anaplastic lymphoma
RT kinase.";
RL Oncogene 26:859-869(2007).
RN [6]
RP DISRUPTION PHENOTYPE.
RX PubMed=17487225; DOI=10.1038/sj.npp.1301446;
RA Bilsland J.G., Wheeldon A., Mead A., Znamenskiy P., Almond S., Waters K.A.,
RA Thakur M., Beaumont V., Bonnert T.P., Heavens R., Whiting P.,
RA McAllister G., Munoz-Sanjuan I.;
RT "Behavioral and neurochemical alterations in mice deficient in anaplastic
RT lymphoma kinase suggest therapeutic potential for psychiatric
RT indications.";
RL Neuropsychopharmacology 33:685-700(2008).
RN [7]
RP FUNCTION.
RX PubMed=19200234; DOI=10.1111/j.1460-9568.2008.06593.x;
RA Degoutin J., Brunet-de Carvalho N., Cifuentes-Diaz C., Vigny M.;
RT "ALK (Anaplastic Lymphoma Kinase) expression in DRG neurons and its
RT involvement in neuron-Schwann cells interaction.";
RL Eur. J. Neurosci. 29:275-286(2009).
RN [8]
RP DISRUPTION PHENOTYPE.
RX PubMed=22079349; DOI=10.1016/j.pbb.2011.10.024;
RA Weiss J.B., Xue C., Benice T., Xue L., Morris S.W., Raber J.;
RT "Anaplastic lymphoma kinase and leukocyte tyrosine kinase: functions and
RT genetic interactions in learning, memory and adult neurogenesis.";
RL Pharmacol. Biochem. Behav. 100:566-574(2012).
RN [9]
RP REVIEW ON FUNCTION.
RX PubMed=19459784; DOI=10.1042/bj20090387;
RA Palmer R.H., Vernersson E., Grabbe C., Hallberg B.;
RT "Anaplastic lymphoma kinase: signalling in development and disease.";
RL Biochem. J. 420:345-361(2009).
RN [10]
RP FUNCTION.
RX PubMed=30497772; DOI=10.1016/j.neuron.2018.10.051;
RA Tang C., Wang M., Wang P., Wang L., Wu Q., Guo W.;
RT "Neural Stem Cells Behave as a Functional Niche for the Maturation of
RT Newborn Neurons through the Secretion of PTN.";
RL Neuron 101:32-44(2019).
RN [11]
RP FUNCTION, DISRUPTION PHENOTYPE, TISSUE SPECIFICITY, AND INDUCTION BY
RP FEEDING.
RX PubMed=32442405; DOI=10.1016/j.cell.2020.04.034;
RA Orthofer M., Valsesia A., Maegi R., Wang Q.P., Kaczanowska J.,
RA Kozieradzki I., Leopoldi A., Cikes D., Zopf L.M., Tretiakov E.O.,
RA Demetz E., Hilbe R., Boehm A., Ticevic M., Noukas M., Jais A., Spirk K.,
RA Clark T., Amann S., Lepamets M., Neumayr C., Arnold C., Dou Z., Kuhn V.,
RA Novatchkova M., Cronin S.J.F., Tietge U.J.F., Mueller S., Pospisilik J.A.,
RA Nagy V., Hui C.C., Lazovic J., Esterbauer H., Hagelkruys A., Tancevski I.,
RA Kiefer F.W., Harkany T., Haubensak W., Neely G.G., Metspalu A., Hager J.,
RA Gheldof N., Penninger J.M.;
RT "Identification of ALK in Thinness.";
RL Cell 181:1246-1262.e22(2020).
CC -!- FUNCTION: Neuronal receptor tyrosine kinase that is essentially and
CC transiently expressed in specific regions of the central and peripheral
CC nervous systems and plays an important role in the genesis and
CC differentiation of the nervous system (PubMed:15226403,
CC PubMed:16458083, PubMed:16878150, PubMed:19200234, PubMed:30497772).
CC Also acts as a key thinness protein involved in the resistance to
CC weight gain: in hypothalamic neurons, controls energy expenditure
CC acting as a negative regulator of white adipose tissue lipolysis and
CC sympathetic tone to fine-tune energy homeostasis (PubMed:32442405).
CC Following activation by ALKAL2 ligand at the cell surface, transduces
CC an extracellular signal into an intracellular response. In contrast,
CC ALKAL1 is not a potent physiological ligand for ALK. Ligand-binding to
CC the extracellular domain induces tyrosine kinase activation, leading to
CC activation of the mitogen-activated protein kinase (MAPK) pathway.
CC Phosphorylates almost exclusively at the first tyrosine of the Y-x-x-x-
CC Y-Y motif. Induces tyrosine phosphorylation of CBL, FRS2, IRS1 and
CC SHC1, as well as of the MAP kinases MAPK1/ERK2 and MAPK3/ERK1. ALK
CC activation may also be regulated by pleiotrophin (PTN) and midkine
CC (MDK). PTN-binding induces MAPK pathway activation, which is important
CC for the anti-apoptotic signaling of PTN and regulation of cell
CC proliferation. MDK-binding induces phosphorylation of the ALK target
CC insulin receptor substrate (IRS1), activates mitogen-activated protein
CC kinases (MAPKs) and PI3-kinase, resulting also in cell proliferation
CC induction. Drives NF-kappa-B activation, probably through IRS1 and the
CC activation of the AKT serine/threonine kinase. Recruitment of IRS1 to
CC activated ALK and the activation of NF-kappa-B are essential for the
CC autocrine growth and survival signaling of MDK (By similarity).
CC {ECO:0000250|UniProtKB:Q9UM73, ECO:0000269|PubMed:15226403,
CC ECO:0000269|PubMed:16458083, ECO:0000269|PubMed:16878150,
CC ECO:0000269|PubMed:19200234, ECO:0000269|PubMed:30497772,
CC ECO:0000269|PubMed:32442405}.
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:0000250|UniProtKB:Q9UM73, ECO:0000255|PROSITE-
CC ProRule:PRU10028};
CC -!- ACTIVITY REGULATION: Activated upon ALKAL2 ligand-binding. ALKAL2-
CC driven activation is coupled with heparin-binding (By similarity).
CC Following ligand-binding, homodimerizes and autophosphorylates,
CC activating its kinase activity (By similarity). Inactivated through
CC dephosphorylation by receptor protein tyrosine phosphatase beta and
CC zeta complex (PTPRB/PTPRZ1) when there is no stimulation by a ligand
CC (By similarity). {ECO:0000250|UniProtKB:Q9UM73}.
CC -!- SUBUNIT: Homodimer; homodimerizes following heparin- and ligand-binding
CC (By similarity). Interacts with CBL, IRS1, PIK3R1 and PLCG1
CC (PubMed:15226403, PubMed:16878150). Interacts with FRS2 and SHC1
CC (PubMed:15226403, PubMed:16878150). Interacts with PTN and MDK (By
CC similarity). {ECO:0000250|UniProtKB:Q9UM73,
CC ECO:0000269|PubMed:15226403, ECO:0000269|PubMed:16878150}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:Q9UM73};
CC Single-pass type I membrane protein {ECO:0000250|UniProtKB:Q9UM73}.
CC Note=Membrane attachment is essential for promotion of neuron-like
CC differentiation and cell proliferation arrest through specific
CC activation of the MAP kinase pathway. {ECO:0000250|UniProtKB:Q9UM73}.
CC -!- TISSUE SPECIFICITY: Mainly expressed in central nervous system (CNS)
CC and other parts of the brain such as the paraventricular nucleus (PVN)
CC of the hypothalamus. Expression is also found in peripheral nervous
CC systems, eye, nasal epithelium, olfactory nerve, tongue, skin, tissue
CC surrounding the esophagus, stomach, midgut, as well as testis and
CC ovary. {ECO:0000269|PubMed:16458083, ECO:0000269|PubMed:32442405}.
CC -!- INDUCTION: In the hypothalamus, expression is induced in response to
CC feeding. {ECO:0000269|PubMed:32442405}.
CC -!- DOMAIN: The EGF-like region drives the cytokine specificity for ALKAL2.
CC {ECO:0000250|UniProtKB:Q9UM73}.
CC -!- DOMAIN: The heparin-binding region binds heparin glycosaminoglycan.
CC Heparin-binding is required for ALKAL2-driven activation.
CC {ECO:0000250|UniProtKB:Q9UM73}.
CC -!- PTM: Phosphorylated at tyrosine residues by autocatalysis, which
CC activates kinase activity. In cells not stimulated by a ligand,
CC receptor protein tyrosine phosphatase beta and zeta complex
CC (PTPRB/PTPRZ1) dephosphorylates ALK at the sites in ALK that are
CC undergoing autophosphorylation through autoactivation.
CC {ECO:0000250|UniProtKB:Q9UM73}.
CC -!- DISRUPTION PHENOTYPE: Mice display a decrease in newborn neurons and
CC defects in brain function (PubMed:17487225, PubMed:22079349). Mice show
CC an age-dependent increase in basal hippocampal progenitor proliferation
CC and alterations in behavioral tests (PubMed:17487225). Mice lacking
CC both Alk and Ltk show a strong reduction in newborn neurons
CC (PubMed:22079349). Mutants develop a thin phenotype at the age of 5
CC weeks, persisting into adulthood with reduced body adiposity, elevated
CC adiponectin levels and improved glucose homeostasis, while having
CC unaltered food intake and activity (PubMed:32442405). They show a
CC marked resistance to diet- and leptin-mutation-induced obesity and
CC exhibit increased adipose tissue lipolysis (PubMed:32442405).
CC {ECO:0000269|PubMed:17487225, ECO:0000269|PubMed:22079349,
CC ECO:0000269|PubMed:32442405}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein
CC kinase family. Insulin receptor subfamily. {ECO:0000255|PROSITE-
CC ProRule:PRU00159}.
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DR EMBL; D83002; BAA11673.1; -; mRNA.
DR EMBL; AC122746; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC151265; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC154458; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC154602; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC154659; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC155242; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS37688.1; -.
DR PIR; T30200; T30200.
DR RefSeq; NP_031465.2; NM_007439.2.
DR AlphaFoldDB; P97793; -.
DR BMRB; P97793; -.
DR SMR; P97793; -.
DR BioGRID; 198070; 17.
DR STRING; 10090.ENSMUSP00000083840; -.
DR BindingDB; P97793; -.
DR ChEMBL; CHEMBL5771; -.
DR GlyGen; P97793; 16 sites.
DR iPTMnet; P97793; -.
DR PhosphoSitePlus; P97793; -.
DR MaxQB; P97793; -.
DR PaxDb; P97793; -.
DR PRIDE; P97793; -.
DR ProteomicsDB; 296099; -.
DR Antibodypedia; 2099; 1350 antibodies from 41 providers.
DR DNASU; 11682; -.
DR Ensembl; ENSMUST00000086639; ENSMUSP00000083840; ENSMUSG00000055471.
DR GeneID; 11682; -.
DR KEGG; mmu:11682; -.
DR UCSC; uc008dnb.1; mouse.
DR CTD; 238; -.
DR MGI; MGI:103305; Alk.
DR VEuPathDB; HostDB:ENSMUSG00000055471; -.
DR eggNOG; KOG1095; Eukaryota.
DR GeneTree; ENSGT00940000159280; -.
DR HOGENOM; CLU_001878_2_2_1; -.
DR InParanoid; P97793; -.
DR OMA; TDRFWLQ; -.
DR OrthoDB; 40108at2759; -.
DR PhylomeDB; P97793; -.
DR TreeFam; TF351636; -.
DR BRENDA; 2.7.10.1; 3474.
DR Reactome; R-MMU-201556; Signaling by ALK.
DR BioGRID-ORCS; 11682; 3 hits in 77 CRISPR screens.
DR ChiTaRS; Alk; mouse.
DR PRO; PR:P97793; -.
DR Proteomes; UP000000589; Chromosome 17.
DR RNAct; P97793; protein.
DR Bgee; ENSMUSG00000055471; Expressed in inferior vagus X ganglion and 124 other tissues.
DR Genevisible; P97793; MM.
DR GO; GO:0030424; C:axon; ISO:MGI.
DR GO; GO:0044297; C:cell body; ISO:MGI.
DR GO; GO:0005887; C:integral component of plasma membrane; ISS:MGI.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0032991; C:protein-containing complex; ISO:MGI.
DR GO; GO:0043235; C:receptor complex; IBA:GO_Central.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0008201; F:heparin binding; ISS:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR GO; GO:0004713; F:protein tyrosine kinase activity; ISO:MGI.
DR GO; GO:0030298; F:receptor signaling protein tyrosine kinase activator activity; ISS:UniProtKB.
DR GO; GO:0004714; F:transmembrane receptor protein tyrosine kinase activity; ISS:MGI.
DR GO; GO:0030534; P:adult behavior; IMP:MGI.
DR GO; GO:0007420; P:brain development; IMP:MGI.
DR GO; GO:0097009; P:energy homeostasis; IMP:UniProtKB.
DR GO; GO:0021766; P:hippocampus development; IMP:MGI.
DR GO; GO:0050995; P:negative regulation of lipid catabolic process; IMP:UniProtKB.
DR GO; GO:0007399; P:nervous system development; ISO:MGI.
DR GO; GO:0048666; P:neuron development; IEA:InterPro.
DR GO; GO:0038083; P:peptidyl-tyrosine autophosphorylation; ISS:UniProtKB.
DR GO; GO:0016310; P:phosphorylation; ISO:MGI.
DR GO; GO:1900006; P:positive regulation of dendrite development; IMP:UniProtKB.
DR GO; GO:0033674; P:positive regulation of kinase activity; IBA:GO_Central.
DR GO; GO:0043410; P:positive regulation of MAPK cascade; IEA:InterPro.
DR GO; GO:0046777; P:protein autophosphorylation; ISO:MGI.
DR GO; GO:0042127; P:regulation of cell population proliferation; IMP:MGI.
DR GO; GO:0060159; P:regulation of dopamine receptor signaling pathway; IMP:MGI.
DR GO; GO:0045664; P:regulation of neuron differentiation; IBA:GO_Central.
DR GO; GO:0090648; P:response to environmental enrichment; IMP:MGI.
DR GO; GO:0036269; P:swimming behavior; IMP:MGI.
DR GO; GO:0007169; P:transmembrane receptor protein tyrosine kinase signaling pathway; IBA:GO_Central.
DR CDD; cd00112; LDLa; 1.
DR CDD; cd06263; MAM; 2.
DR Gene3D; 4.10.400.10; -; 1.
DR InterPro; IPR026830; ALK.
DR InterPro; IPR013320; ConA-like_dom_sf.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR036055; LDL_receptor-like_sf.
DR InterPro; IPR002172; LDrepeatLR_classA_rpt.
DR InterPro; IPR000998; MAM_dom.
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; IPR002011; Tyr_kinase_rcpt_2_CS.
DR PANTHER; PTHR24416:SF276; PTHR24416:SF276; 1.
DR Pfam; PF00629; MAM; 2.
DR Pfam; PF07714; PK_Tyr_Ser-Thr; 1.
DR PRINTS; PR00109; TYRKINASE.
DR SMART; SM00192; LDLa; 1.
DR SMART; SM00219; TyrKc; 1.
DR SUPFAM; SSF49899; SSF49899; 2.
DR SUPFAM; SSF56112; SSF56112; 1.
DR SUPFAM; SSF57424; SSF57424; 1.
DR PROSITE; PS50060; MAM_2; 2.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00109; PROTEIN_KINASE_TYR; 1.
DR PROSITE; PS00239; RECEPTOR_TYR_KIN_II; 1.
PE 1: Evidence at protein level;
KW ATP-binding; Cell membrane; Disulfide bond; Glycoprotein; Kinase; Membrane;
KW Nucleotide-binding; Phosphoprotein; Receptor; Reference proteome; Repeat;
KW Signal; Transferase; Transmembrane; Transmembrane helix;
KW Tyrosine-protein kinase.
FT SIGNAL 1..18
FT /evidence="ECO:0000255"
FT CHAIN 19..1621
FT /note="ALK tyrosine kinase receptor"
FT /id="PRO_0000016741"
FT TOPO_DOM 19..1042
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 1043..1063
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1064..1621
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 268..431
FT /note="MAM 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00128"
FT DOMAIN 441..477
FT /note="LDL-receptor class A"
FT DOMAIN 482..640
FT /note="MAM 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00128"
FT DOMAIN 1120..1396
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 48..70
FT /note="Heparin-binding region"
FT /evidence="ECO:0000250|UniProtKB:Q9UM73"
FT REGION 991..1029
FT /note="EGF-like"
FT /evidence="ECO:0000250|UniProtKB:Q9UM73"
FT REGION 1412..1556
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 1253
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10028"
FT BINDING 1126..1134
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 1128
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 1154
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 1201..1203
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 1274
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 1082
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q9UM73"
FT MOD_RES 1096
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000269|PubMed:16878150"
FT MOD_RES 1100
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q9UM73"
FT MOD_RES 1135
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q9UM73"
FT MOD_RES 1282
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q9UM73"
FT MOD_RES 1516
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q9UM73"
FT CARBOHYD 174
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 248
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 289
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 328
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 415
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 428
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 449
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 567
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 575
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 631
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 673
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 713
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 812
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 868
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 890
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 990
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 692..705
FT /evidence="ECO:0000250|UniProtKB:Q9UM73"
FT DISULFID 787..798
FT /evidence="ECO:0000250|UniProtKB:Q9UM73"
FT DISULFID 910..932
FT /evidence="ECO:0000250|UniProtKB:Q9UM73"
FT DISULFID 991..999
FT /evidence="ECO:0000250|UniProtKB:Q9UM73"
FT DISULFID 994..1010
FT /evidence="ECO:0000250|UniProtKB:Q9UM73"
FT DISULFID 1012..1025
FT /evidence="ECO:0000250|UniProtKB:Q9UM73"
FT CONFLICT 138..139
FT /note="KL -> NV (in Ref. 1; BAA11673)"
FT /evidence="ECO:0000305"
FT CONFLICT 232
FT /note="M -> L (in Ref. 1; BAA11673)"
FT /evidence="ECO:0000305"
FT CONFLICT 857
FT /note="T -> R (in Ref. 1; BAA11673)"
FT /evidence="ECO:0000305"
FT CONFLICT 1075..1076
FT /note="ME -> IQ (in Ref. 1; BAA11673)"
FT /evidence="ECO:0000305"
FT CONFLICT 1522
FT /note="E -> A (in Ref. 1; BAA11673)"
FT /evidence="ECO:0000305"
FT CONFLICT 1586
FT /note="G -> P (in Ref. 1; BAA11673)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1621 AA; 174948 MW; 72D1022E117F303E CRC64;
MGAAGFLWLL PPLLLAAASY SGAATDQRAG SPASGPPLQP REPLSYSRLQ RKSLAVDFVV
PSLFRVYARD LLLPQPRSPS EPEAGGLEAR GSLALDCEPL LRLLGPLPGI SWADGASSPS
PEAGPTLSRV LKGGSVRKLR RAKQLVLELG EETILEGCIG PPEEVAAVGI LQFNLSELFS
WWILHGEGRL RIRLMPEKKA SEVGREGRLS SAIRASQPRL LFQIFGTGHS SMESPSETPS
PPGTFMWNLT WTMKDSFPFL SHRSRYGLEC SFDFPCELEY SPPLHNHGNQ SWSWRHVPSE
EASRMNLLDG PEAEHSQEMP RGSFLLLNTS ADSKHTILSP WMRSSSDHCT LAVSVHRHLQ
PSGRYVAQLL PHNEAGREIL LVPTPGKHGW TVLQGRVGRP ANPFRVALEY ISSGNRSLSA
VDFFALKNCS EGTSPGSKMA LQSSFTCWNG TVLQLGQACD FHQDCAQGED EGQLCSKLPA
GFYCNFENGF CGWTQSPLSP HMPRWQVRTL RDAHSQGHQG RALLLSTTDI LASEGATVTS
ATFPAPMKNS PCELRMSWLI RGVLRGNVSL VLVENKTGKE QSRTVWHVAT DEGLSLWQHT
VLSLLDVTDR FWLQIVTWWG PGSRATVGFD NISISLDCYL TISGEEKMSL NSVPKSRNLF
EKNPNKESKS WANISGPTPI FDPTVHWLFT TCGASGPHGP TQAQCNNAYQ NSNLSVVVGS
EGPLKGVQIW KVPATDTYSI SGYGAAGGKG GKNTMMRSHG VSVLGIFNLE KGDTLYILVG
QQGEDACPRA NQLIQKVCVG ENNVIEEEIR VNRSVHEWAG GGGGGGGATY VFKMKDGVPV
PLIIAAGGGG RAYGAKTETF HPERLESNSS VLGLNGNSGA AGGGGGWNDN TSLLWAGKSL
LEGAAGGHSC PQAMKKWGWE TRGGFGGGGG GCSSGGGGGG YIGGNAASNN DPEMDGEDGV
SFISPLGILY TPALKVMEGH GEVNIKHYLN CSHCEVDECH MDPESHKVIC FCDHGTVLAD
DGVSCIVSPT PEPHLPLSLI LSVVTSALVA ALVLAFSGIM IVYRRKHQEL QAMQMELQSP
EYKLSKLRTS TIMTDYNPNY CFAGKTSSIS DLKEVPRKNI TLIRGLGHGA FGEVYEGQVS
GMPNDPSPLQ VAVKTLPEVC SEQDELDFLM EALIISKFNH QNIVRCIGVS LQALPRFILL
ELMAGGDLKS FLRETRPRPN QPTSLAMLDL LHVARDIACG CQYLEENHFI HRDIAARNCL
LTCPGAGRIA KIGDFGMARD IYRASYYRKG GCAMLPVKWM PPEAFMEGIF TSKTDTWSFG
VLLWEIFSLG YMPYPSKSNQ EVLEFVTSGG RMDPPKNCPG PVYRIMTQCW QHQPEDRPNF
AIILERIEYC TQDPDVINTA LPIEYGPVVE EEEKVPMRPK DPEGMPPLLV SPQPAKHEEA
SAAPQPAALT APGPSVKKPP GAGAGAGAGA GAGPVPRGAA DRGHVNMAFS QPNPPPELHK
GPGSRNKPTS LWNPTYGSWF TEKPAKKTHP PPGAEPQARA GAAEGGWTGP GAGPRRAEAA
LLLEPSALSA TMKEVPLFRL RHFPCGNVNY GYQQQGLPLE ATAAPGDTML KSKNKVTQPG
P
