ID EPHB2_HUMAN Reviewed; 1055 AA. AC P29323; O43477; Q5T0U6; Q5T0U7; Q5T0U8; DT 01-DEC-1992, integrated into UniProtKB/Swiss-Prot. DT 27-SEP-2005, sequence version 5. DT 27-MAR-2024, entry version 256. DE RecName: Full=Ephrin type-B receptor 2; DE EC=2.7.10.1; DE AltName: Full=Developmentally-regulated Eph-related tyrosine kinase; DE AltName: Full=ELK-related tyrosine kinase; DE AltName: Full=EPH tyrosine kinase 3; DE AltName: Full=EPH-like kinase 5; DE Short=EK5; DE Short=hEK5; DE AltName: Full=Renal carcinoma antigen NY-REN-47; DE AltName: Full=Tyrosine-protein kinase TYRO5; DE AltName: Full=Tyrosine-protein kinase receptor EPH-3; DE Contains: DE RecName: Full=EphB2/CTF1 {ECO:0000250|UniProtKB:P54763}; DE Contains: DE RecName: Full=EphB2/CTF2 {ECO:0000250|UniProtKB:P54763}; DE Flags: Precursor; GN Name=EPHB2; Synonyms=DRT, EPHT3, EPTH3, ERK, HEK5, TYRO5; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). RX PubMed=8033077; RA Kiyokawa E., Takai S., Tanaka M., Iwase T., Suzuki M., Xiang Y.Y., RA Naito Y., Yamada K., Sugimura H., Kino I.; RT "Overexpression of ERK, an EPH family receptor protein tyrosine kinase, in RT various human tumors."; RL Cancer Res. 54:3645-3650(1994). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3). RC TISSUE=Fetal brain; RX PubMed=8589679; DOI=10.1093/hmg/4.11.2033; RA Ikegaki N., Tang X.X., Liu X.-G., Biegel J.A., Allen C., Yoshioka A., RA Sulman E.P., Brodeur G.M., Pleasure D.E.; RT "Molecular characterization and chromosomal localization of DRT (EPHT3): a RT developmentally regulated human protein-tyrosine kinase gene of the EPH RT family."; RL Hum. Mol. Genet. 4:2033-2045(1995). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RC TISSUE=Fetal brain; RX PubMed=9696046; DOI=10.1038/sj.onc.1201960; RA Tang X.X., Pleasure D.E., Brodeur G.M., Ikegaki N.; RT "A variant transcript encoding an isoform of the human protein tyrosine RT kinase EPHB2 is generated by alternative splicing and alternative use of RT polyadenylation signals."; RL Oncogene 17:521-526(1998). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16710414; DOI=10.1038/nature04727; RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K., RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.; RT "The DNA sequence and biological annotation of human chromosome 1."; RL Nature 441:315-321(2006). RN [5] RP NUCLEOTIDE SEQUENCE [MRNA] OF 15-986 (ISOFORM 2). RC TISSUE=Brain; RX PubMed=7898931; RA Fox G.M., Holst P.L., Chute H.T., Lindberg R.A., Janssen A.M., Basu R., RA Welcher A.A.; RT "cDNA cloning and tissue distribution of five human EPH-like receptor RT protein-tyrosine kinases."; RL Oncogene 10:897-905(1995). RN [6] RP NUCLEOTIDE SEQUENCE [MRNA] OF 509-986 (ISOFORM 2). RC TISSUE=Fetal brain; RX PubMed=7601466; DOI=10.1016/0888-7543(95)80224-a; RA Saito T., Seki N., Matsuda Y., Kitahara M., Murata M., Kanda N., Nomura N., RA Yamamoto T., Hori T.-A.; RT "Identification of the human ERK gene as a putative receptor tyrosine RT kinase and its chromosomal localization to 1p36.1: a comparative mapping of RT human, mouse, and rat chromosomes."; RL Genomics 26:382-384(1995). RN [7] RP NUCLEOTIDE SEQUENCE [MRNA] OF 640-986 (ISOFORM 2). RC TISSUE=Gastric carcinoma; RX PubMed=7688222; DOI=10.1006/bbrc.1993.1878; RA Iwase T., Tanaka M., Suzuki M., Naito Y., Sugimura H., Kino I.; RT "Identification of protein-tyrosine kinase genes preferentially expressed RT in embryo stomach and gastric cancer."; RL Biochem. Biophys. Res. Commun. 194:698-705(1993). RN [8] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 652-712. RX PubMed=1648701; RA Chan J., Watt V.M.; RT "eek and erk, new members of the eph subclass of receptor protein-tyrosine RT kinases."; RL Oncogene 6:1057-1061(1991). RN [9] RP NOMENCLATURE. RX PubMed=9267020; DOI=10.1016/s0092-8674(00)80500-0; RG Eph nomenclature committee; RT "Unified nomenclature for Eph family receptors and their ligands, the RT ephrins."; RL Cell 90:403-404(1997). RN [10] RP IDENTIFICATION AS A RENAL CANCER ANTIGEN. RC TISSUE=Renal cell carcinoma; RX PubMed=10508479; RX DOI=10.1002/(sici)1097-0215(19991112)83:4<456::aid-ijc4>3.0.co;2-5; RA Scanlan M.J., Gordan J.D., Williamson B., Stockert E., Bander N.H., RA Jongeneel C.V., Gure A.O., Jaeger D., Jaeger E., Knuth A., Chen Y.-T., RA Old L.J.; RT "Antigens recognized by autologous antibody in patients with renal-cell RT carcinoma."; RL Int. J. Cancer 83:456-464(1999). RN [11] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007; RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., RA Greff Z., Keri G., Stemmann O., Mann M.; RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the RT kinome across the cell cycle."; RL Mol. Cell 31:438-448(2008). RN [12] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-983 (ISOFORM 2), RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-984 (ISOFORM 3), AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19369195; DOI=10.1074/mcp.m800588-mcp200; RA Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., RA Mann M., Daub H.; RT "Large-scale proteomics analysis of the human kinome."; RL Mol. Cell. Proteomics 8:1751-1764(2009). RN [13] RP POLYUBIQUITINATION, AND INTERACTION WITH SPSB1 AND SPSB4. RX PubMed=28931592; DOI=10.1091/mbc.e17-07-0450; RA Okumura F., Joo-Okumura A., Obara K., Petersen A., Nishikimi A., Fukui Y., RA Nakatsukasa K., Kamura T.; RT "Ubiquitin ligase SPSB4 diminishes cell repulsive responses mediated by RT EphB2."; RL Mol. Biol. Cell 28:3532-3541(2017). RN [14] RP UBIQUITINATION BY RNF186, AND MUTAGENESIS OF LYS-787 AND LYS-891. RX PubMed=33280498; DOI=10.1080/15548627.2020.1851496; RA Zhang H., Cui Z., Cheng D., Du Y., Guo X., Gao R., Chen J., Sun W., He R., RA Ma X., Peng Q., Martin B.N., Yan W., Rong Y., Wang C.; RT "RNF186 regulates EFNB1 (ephrin B1)-EPHB2-induced autophagy in the colonic RT epithelial cells for the maintenance of intestinal homeostasis."; RL Autophagy 17:3030-3047(2021). RN [15] RP X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS) OF 910-986 (ISOFORM SHORT). RX PubMed=9933164; DOI=10.1126/science.283.5403.833; RA Thanos C.D., Goodwill K.E., Bowie J.U.; RT "Oligomeric structure of the human EphB2 receptor SAM domain."; RL Science 283:833-836(1999). RN [16] RP X-RAY CRYSTALLOGRAPHY (2.30 ANGSTROMS) OF 20-195 OF HOMODIMER IN COMPLEX RP WITH ANTAGONISTIC PEPTIDE, DISULFIDE BOND, AND SUBUNIT. RX PubMed=17897949; DOI=10.1074/jbc.m706340200; RA Chrencik J.E., Brooun A., Recht M.I., Nicola G., Davis L.K., Abagyan R., RA Widmer H., Pasquale E.B., Kuhn P.; RT "Three-dimensional structure of the EphB2 receptor in complex with an RT antagonistic peptide reveals a novel mode of inhibition."; RL J. Biol. Chem. 282:36505-36513(2007). RN [17] RP VARIANTS PROSTATE CANCER HIS-199; SER-279; ASN-679 AND MET-909, AND RP FUNCTION AS A TUMOR SUPPRESSOR. RX PubMed=15300251; DOI=10.1038/ng1408; RA Huusko P., Ponciano-Jackson D., Wolf M., Kiefer J.A., Azorsa D.O., RA Tuzmen S., Weaver D., Robbins C., Moses T., Allinen M., Hautaniemi S., RA Chen Y., Elkahloun A., Basik M., Bova G.S., Bubendorf L., Lugli A., RA Sauter G., Schleutker J., Ozcelik H., Elowe S., Pawson T., Trent J.M., RA Carpten J.D., Kallioniemi O.-P., Mousses S.; RT "Nonsense-mediated decay microarray analysis identifies mutations of EPHB2 RT in human prostate cancer."; RL Nat. Genet. 36:979-983(2004). RN [18] RP VARIANTS PROSTATE CANCER SER-279; ALA-650 AND VAL-883. RX PubMed=16155194; DOI=10.1136/jmg.2005.035790; RA Kittles R.A., Baffoe-Bonnie A.B., Moses T.Y., Robbins C.M., Ahaghotu C., RA Huusko P., Pettaway C., Vijayakumar S., Bennett J., Hoke G., Mason T., RA Weinrich S., Trent J.M., Collins F.S., Mousses S., Bailey-Wilson J., RA Furbert-Harris P., Dunston G., Powell I.J., Carpten J.D.; RT "A common nonsense mutation in EphB2 is associated with prostate cancer RT risk in African American men with a positive family history."; RL J. Med. Genet. 43:507-511(2006). RN [19] RP VARIANTS [LARGE SCALE ANALYSIS] SER-279; GLY-289; VAL-361; ASN-678 AND RP TRP-844. RX PubMed=17344846; DOI=10.1038/nature05610; RA Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., RA Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., RA Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G., RA Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., RA Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., RA Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., RA Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., RA Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., RA Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., RA Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., RA Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., RA Futreal P.A., Stratton M.R.; RT "Patterns of somatic mutation in human cancer genomes."; RL Nature 446:153-158(2007). RN [20] RP VARIANT BDPLT22 CYS-745, INVOLVEMENT IN BDPLT22, AND FUNCTION. RX PubMed=30213874; DOI=10.1182/blood-2018-04-845644; RA Berrou E., Soukaseum C., Favier R., Adam F., Elaib Z., Kauskot A., RA Bordet J.C., Ballerini P., Loyau S., Feng M., Dias K., Muheidli A., RA Girault S., Nurden A.T., Turro E., Ouwehand W.H., Denis C.V., RA Jandrot-Perrus M., Rosa J.P., Nurden P., Bryckaert M.; RT "A mutation of the human EPHB2 gene leads to a major platelet functional RT defect."; RL Blood 132:2067-2077(2018). CC -!- FUNCTION: Receptor tyrosine kinase which binds promiscuously CC transmembrane ephrin-B family ligands residing on adjacent cells, CC leading to contact-dependent bidirectional signaling into neighboring CC cells. The signaling pathway downstream of the receptor is referred to CC as forward signaling while the signaling pathway downstream of the CC ephrin ligand is referred to as reverse signaling. Functions in axon CC guidance during development. Involved in the guidance of commissural CC axons, that form a major interhemispheric connection between the 2 CC temporal lobes of the cerebral cortex. Also involved in guidance of CC contralateral inner ear efferent growth cones at the midline and of CC retinal ganglion cell axons to the optic disk. In addition to axon CC guidance, also regulates dendritic spines development and maturation CC and stimulates the formation of excitatory synapses. Upon activation by CC EFNB1, abolishes the ARHGEF15-mediated negative regulation on CC excitatory synapse formation. Controls other aspects of development CC including angiogenesis, palate development and in inner ear development CC through regulation of endolymph production. Forward and reverse CC signaling through the EFNB2/EPHB2 complex regulate movement and CC adhesion of cells that tubularize the urethra and septate the cloaca. CC May function as a tumor suppressor. May be involved in the regulation CC of platelet activation and blood coagulation (PubMed:30213874). CC {ECO:0000269|PubMed:15300251, ECO:0000269|PubMed:30213874}. 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 -!- SUBUNIT: Heterotetramer upon binding of the ligand (By similarity). The CC heterotetramer is composed of an ephrin dimer and a receptor dimer CC (PubMed:17897949). Interacts (via PDZ-binding motif) with GRIP1 and CC PICK1 (via PDZ domain) (By similarity). Interacts with ARHGEF15; CC mediates ARHGEF15 phosphorylation, ubiquitination and degradation by CC the proteasome (By similarity). Interacts with AQP1; involved in CC endolymph production in the inner ear (By similarity). Interacts with CC SPSB1 and SPSB4 (PubMed:28931592). The phosphorylated form interacts CC with RASA1 (via SH2 domain 1) (By similarity). Interacts with EFNA5 (By CC similarity). Interacts with SH2D3C (By similarity). CC {ECO:0000250|UniProtKB:P54763, ECO:0000269|PubMed:17897949, CC ECO:0000269|PubMed:28931592}. CC -!- INTERACTION: CC P29323; P07333: CSF1R; NbExp=2; IntAct=EBI-1059294, EBI-2835440; CC P29323; P54764: EPHA4; NbExp=3; IntAct=EBI-1059294, EBI-5773557; CC P29323; Q15375: EPHA7; NbExp=2; IntAct=EBI-1059294, EBI-1383428; CC P29323; P49790: NUP153; NbExp=2; IntAct=EBI-1059294, EBI-286779; CC P29323-3; Q9NWW5: CLN6; NbExp=3; IntAct=EBI-25838727, EBI-6165897; CC P29323-3; P21964-2: COMT; NbExp=3; IntAct=EBI-25838727, EBI-10200977; CC P29323-3; Q8WXH2: JPH3; NbExp=3; IntAct=EBI-25838727, EBI-1055254; CC P29323-3; O14832: PHYH; NbExp=3; IntAct=EBI-25838727, EBI-721853; CC P29323-3; Q7Z699: SPRED1; NbExp=3; IntAct=EBI-25838727, EBI-5235340; CC P29323-3; Q13148: TARDBP; NbExp=6; IntAct=EBI-25838727, EBI-372899; CC -!- SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane CC protein. Cell projection, axon {ECO:0000250}. Cell projection, dendrite CC {ECO:0000250}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; Synonyms=EPHB2v, Long; CC IsoId=P29323-1; Sequence=Displayed; CC Name=2; Synonyms=Short; CC IsoId=P29323-2; Sequence=VSP_003016, VSP_003017; CC Name=3; CC IsoId=P29323-3; Sequence=VSP_015713, VSP_003016, VSP_003017; CC -!- TISSUE SPECIFICITY: Brain, heart, lung, kidney, placenta, pancreas, CC liver and skeletal muscle. Preferentially expressed in fetal brain. CC -!- PTM: Autophosphorylated; ligand binding stimulates autophosphorylation CC on tyrosine residues. {ECO:0000250|UniProtKB:P54763}. CC -!- PTM: Polyubiquitinated; ligand binding stimulates ubiquitination CC (PubMed:28931592). Ubiquitinated by RNF186 at Lys-891, mainly through CC 'Lys-27'-linked polyubiquitin chains (PubMed:33280498). CC {ECO:0000269|PubMed:28931592, ECO:0000269|PubMed:33280498}. CC -!- PTM: Ligand binding induces cleavage by matrix metalloproteinases CC (MMPs) such as MMP7/MMP9, producing an EphB2/N-terminal fragment (NTF) CC and a C-terminal long fragment (EphB2-LF). EphB2-LF is further cleaved CC by MMPs, producing EphB2/CTF1 which is further cleaved by the CC PS1/gamma-secretase producing EphB2/CTF2. CC {ECO:0000250|UniProtKB:P54763}. CC -!- DISEASE: Prostate cancer (PC) [MIM:176807]: A malignancy originating in CC tissues of the prostate. Most prostate cancers are adenocarcinomas that CC develop in the acini of the prostatic ducts. Other rare histopathologic CC types of prostate cancer that occur in approximately 5% of patients CC include small cell carcinoma, mucinous carcinoma, prostatic ductal CC carcinoma, transitional cell carcinoma, squamous cell carcinoma, basal CC cell carcinoma, adenoid cystic carcinoma (basaloid), signet-ring cell CC carcinoma and neuroendocrine carcinoma. {ECO:0000269|PubMed:15300251, CC ECO:0000269|PubMed:16155194}. Note=The gene represented in this entry CC may be involved in disease pathogenesis. EPHB2 mutations have been CC found in a prostate cancer cell line derived from a brain metastasis. CC -!- DISEASE: Bleeding disorder, platelet-type, 22 (BDPLT22) [MIM:618462]: CC An autosomal recessive disorder characterized by increased bleeding CC tendency due to platelet dysfunction. Clinical features include CC epistaxis, hematomas, bleeding after minor injuries, and menorrhagia. CC {ECO:0000269|PubMed:30213874}. Note=The disease may be caused by CC variants affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein CC kinase family. Ephrin receptor subfamily. {ECO:0000255|PROSITE- CC ProRule:PRU00159}. 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; D31661; BAA06506.1; -; mRNA. DR EMBL; L41939; AAA99310.1; -; mRNA. DR EMBL; AF025304; AAB94602.1; -; mRNA. DR EMBL; AL035704; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL158086; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AL512444; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; L36643; AAA74244.1; -; mRNA. DR EMBL; D37827; BAA07073.1; -; mRNA. DR EMBL; D14717; BAA03537.1; -; mRNA. DR EMBL; X59292; CAA41981.1; -; Genomic_DNA. DR CCDS; CCDS229.2; -. [P29323-2] DR CCDS; CCDS230.1; -. [P29323-3] DR CCDS; CCDS81279.1; -. [P29323-1] DR PIR; A57174; A57174. DR PIR; I78842; I78842. DR RefSeq; NP_001296122.1; NM_001309193.1. [P29323-1] DR RefSeq; NP_004433.2; NM_004442.7. [P29323-3] DR RefSeq; NP_059145.2; NM_017449.4. [P29323-2] DR PDB; 1B4F; X-ray; 1.95 A; A/B/C/D/E/F/G/H=908-985. DR PDB; 1F0M; X-ray; 2.20 A; A=908-985. DR PDB; 2QBX; X-ray; 2.30 A; A/B=20-196. DR PDB; 3ZFM; X-ray; 2.27 A; A=604-898. DR PDB; 8EBL; X-ray; 1.37 A; C/D=1042-1055. DR PDBsum; 1B4F; -. DR PDBsum; 1F0M; -. DR PDBsum; 2QBX; -. DR PDBsum; 3ZFM; -. DR PDBsum; 8EBL; -. DR AlphaFoldDB; P29323; -. DR BMRB; P29323; -. DR SMR; P29323; -. DR BioGRID; 108362; 209. DR DIP; DIP-1162N; -. DR IntAct; P29323; 141. DR MINT; P29323; -. DR STRING; 9606.ENSP00000383053; -. DR BindingDB; P29323; -. DR ChEMBL; CHEMBL3290; -. DR DrugBank; DB12010; Fostamatinib. DR DrugBank; DB12843; Oleandrin. DR DrugBank; DB04395; Phosphoaminophosphonic Acid-Adenylate Ester. DR DrugCentral; P29323; -. DR GuidetoPHARMACOLOGY; 1831; -. DR GlyCosmos; P29323; 4 sites, No reported glycans. DR GlyGen; P29323; 5 sites, 1 O-linked glycan (1 site). DR iPTMnet; P29323; -. DR PhosphoSitePlus; P29323; -. DR SwissPalm; P29323; -. DR BioMuta; EPHB2; -. DR DMDM; 76803654; -. DR CPTAC; CPTAC-2786; -. DR CPTAC; CPTAC-3205; -. DR EPD; P29323; -. DR jPOST; P29323; -. DR MassIVE; P29323; -. DR MaxQB; P29323; -. DR PaxDb; 9606-ENSP00000363763; -. DR PeptideAtlas; P29323; -. DR ProteomicsDB; 54540; -. [P29323-1] DR ProteomicsDB; 54541; -. [P29323-2] DR ProteomicsDB; 54542; -. [P29323-3] DR Pumba; P29323; -. DR Antibodypedia; 30106; 748 antibodies from 41 providers. DR DNASU; 2048; -. DR Ensembl; ENST00000374630.8; ENSP00000363761.3; ENSG00000133216.17. [P29323-2] DR Ensembl; ENST00000374632.7; ENSP00000363763.3; ENSG00000133216.17. [P29323-3] DR Ensembl; ENST00000400191.7; ENSP00000383053.3; ENSG00000133216.17. [P29323-1] DR GeneID; 2048; -. DR KEGG; hsa:2048; -. DR MANE-Select; ENST00000374630.8; ENSP00000363761.3; NM_017449.5; NP_059145.2. [P29323-2] DR UCSC; uc001bge.4; human. [P29323-1] DR AGR; HGNC:3393; -. DR CTD; 2048; -. DR DisGeNET; 2048; -. DR GeneCards; EPHB2; -. DR HGNC; HGNC:3393; EPHB2. DR HPA; ENSG00000133216; Tissue enhanced (intestine). DR MalaCards; EPHB2; -. DR MIM; 176807; phenotype. DR MIM; 600997; gene. DR MIM; 603688; phenotype. DR MIM; 618462; phenotype. DR neXtProt; NX_P29323; -. DR OpenTargets; ENSG00000133216; -. DR Orphanet; 1331; Familial prostate cancer. DR PharmGKB; PA27825; -. DR VEuPathDB; HostDB:ENSG00000133216; -. DR eggNOG; KOG0196; Eukaryota. DR GeneTree; ENSGT00940000155503; -. DR InParanoid; P29323; -. DR OMA; GAINCIC; -. DR OrthoDB; 1614410at2759; -. DR PhylomeDB; P29323; -. DR TreeFam; TF315608; -. DR BRENDA; 2.7.10.1; 2681. DR PathwayCommons; P29323; -. DR Reactome; R-HSA-2682334; EPH-Ephrin signaling. DR Reactome; R-HSA-373760; L1CAM interactions. DR Reactome; R-HSA-3928662; EPHB-mediated forward signaling. DR Reactome; R-HSA-3928664; Ephrin signaling. DR Reactome; R-HSA-3928665; EPH-ephrin mediated repulsion of cells. DR SignaLink; P29323; -. DR SIGNOR; P29323; -. DR BioGRID-ORCS; 2048; 11 hits in 1193 CRISPR screens. DR ChiTaRS; EPHB2; human. DR EvolutionaryTrace; P29323; -. DR GeneWiki; EPH_receptor_B2; -. DR GenomeRNAi; 2048; -. DR Pharos; P29323; Tchem. DR PRO; PR:P29323; -. DR Proteomes; UP000005640; Chromosome 1. DR RNAct; P29323; Protein. DR Bgee; ENSG00000133216; Expressed in ganglionic eminence and 165 other cell types or tissues. DR ExpressionAtlas; P29323; baseline and differential. DR GO; GO:0030424; C:axon; ISS:UniProtKB. DR GO; GO:0009986; C:cell surface; IEA:Ensembl. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0030425; C:dendrite; ISS:UniProtKB. DR GO; GO:0043197; C:dendritic spine; IEA:Ensembl. DR GO; GO:0005576; C:extracellular region; TAS:Reactome. DR GO; GO:0098978; C:glutamatergic synapse; IEA:Ensembl. DR GO; GO:0098686; C:hippocampal mossy fiber to CA3 synapse; IEA:Ensembl. DR GO; GO:0043025; C:neuronal cell body; IEA:Ensembl. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005886; C:plasma membrane; IDA:HPA. DR GO; GO:0098794; C:postsynapse; TAS:ARUK-UCL. DR GO; GO:0045211; C:postsynaptic membrane; IEA:Ensembl. DR GO; GO:0042734; C:presynaptic membrane; IEA:Ensembl. DR GO; GO:0001540; F:amyloid-beta binding; ISS:ARUK-UCL. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0008046; F:axon guidance receptor activity; IEA:Ensembl. DR GO; GO:0042802; F:identical protein binding; IEA:Ensembl. DR GO; GO:0004713; F:protein tyrosine kinase activity; ISS:UniProtKB. DR GO; GO:0044877; F:protein-containing complex binding; ISS:ARUK-UCL. DR GO; GO:0005102; F:signaling receptor binding; IEA:Ensembl. DR GO; GO:0005005; F:transmembrane-ephrin receptor activity; ISS:UniProtKB. DR GO; GO:0001525; P:angiogenesis; ISS:UniProtKB. DR GO; GO:0007411; P:axon guidance; ISS:UniProtKB. DR GO; GO:0007413; P:axonal fasciculation; ISS:UniProtKB. DR GO; GO:0042113; P:B cell activation; IMP:ARUK-UCL. DR GO; GO:0048593; P:camera-type eye morphogenesis; IEA:Ensembl. DR GO; GO:1904646; P:cellular response to amyloid-beta; IEA:Ensembl. DR GO; GO:0071222; P:cellular response to lipopolysaccharide; IEA:Ensembl. DR GO; GO:0021952; P:central nervous system projection neuron axonogenesis; IEA:Ensembl. DR GO; GO:0071679; P:commissural neuron axon guidance; ISS:UniProtKB. DR GO; GO:0022038; P:corpus callosum development; ISS:UniProtKB. DR GO; GO:0060996; P:dendritic spine development; ISS:UniProtKB. DR GO; GO:0060997; P:dendritic spine morphogenesis; ISS:UniProtKB. DR GO; GO:0048013; P:ephrin receptor signaling pathway; ISS:UniProtKB. DR GO; GO:0021934; P:hindbrain tangential cell migration; IEA:Ensembl. DR GO; GO:0042472; P:inner ear morphogenesis; ISS:UniProtKB. DR GO; GO:0007612; P:learning; ISS:ARUK-UCL. DR GO; GO:0007611; P:learning or memory; ISS:ARUK-UCL. DR GO; GO:0050771; P:negative regulation of axonogenesis; IEA:Ensembl. DR GO; GO:0007162; P:negative regulation of cell adhesion; IMP:ARUK-UCL. DR GO; GO:1900016; P:negative regulation of cytokine production involved in inflammatory response; IEA:Ensembl. DR GO; GO:0070373; P:negative regulation of ERK1 and ERK2 cascade; ISS:ARUK-UCL. DR GO; GO:1904782; P:negative regulation of NMDA glutamate receptor activity; ISS:ARUK-UCL. DR GO; GO:0006469; P:negative regulation of protein kinase activity; ISS:ARUK-UCL. DR GO; GO:0001933; P:negative regulation of protein phosphorylation; ISS:ARUK-UCL. DR GO; GO:0046580; P:negative regulation of Ras protein signal transduction; ISS:ARUK-UCL. DR GO; GO:0007399; P:nervous system development; TAS:UniProtKB. DR GO; GO:0106028; P:neuron projection retraction; IEA:Ensembl. DR GO; GO:0021631; P:optic nerve morphogenesis; IEA:Ensembl. DR GO; GO:0018108; P:peptidyl-tyrosine phosphorylation; ISS:UniProtKB. DR GO; GO:0016310; P:phosphorylation; ISS:UniProtKB. DR GO; GO:0030890; P:positive regulation of B cell proliferation; IMP:ARUK-UCL. DR GO; GO:0030335; P:positive regulation of cell migration; IGI:ARUK-UCL. DR GO; GO:0061003; P:positive regulation of dendritic spine morphogenesis; IEA:Ensembl. DR GO; GO:0010628; P:positive regulation of gene expression; ISS:ARUK-UCL. DR GO; GO:0002639; P:positive regulation of immunoglobulin production; IMP:ARUK-UCL. DR GO; GO:0048170; P:positive regulation of long-term neuronal synaptic plasticity; IEA:Ensembl. DR GO; GO:1900273; P:positive regulation of long-term synaptic potentiation; ISS:ARUK-UCL. DR GO; GO:1904783; P:positive regulation of NMDA glutamate receptor activity; ISS:ARUK-UCL. DR GO; GO:2000010; P:positive regulation of protein localization to cell surface; IEA:Ensembl. DR GO; GO:1903078; P:positive regulation of protein localization to plasma membrane; ISS:ARUK-UCL. DR GO; GO:0051965; P:positive regulation of synapse assembly; ISS:UniProtKB. DR GO; GO:0031915; P:positive regulation of synaptic plasticity; ISS:ARUK-UCL. DR GO; GO:0032760; P:positive regulation of tumor necrosis factor production; IMP:ARUK-UCL. DR GO; GO:0097104; P:postsynaptic membrane assembly; IEA:Ensembl. DR GO; GO:2000785; P:regulation of autophagosome assembly; IDA:UniProt. DR GO; GO:2000822; P:regulation of behavioral fear response; IEA:Ensembl. DR GO; GO:0030193; P:regulation of blood coagulation; IMP:UniProtKB. DR GO; GO:0050878; P:regulation of body fluid levels; ISS:UniProtKB. DR GO; GO:0051489; P:regulation of filopodium assembly; IEA:Ensembl. DR GO; GO:0048168; P:regulation of neuronal synaptic plasticity; ISS:ARUK-UCL. DR GO; GO:0046425; P:regulation of receptor signaling pathway via JAK-STAT; IEA:Ensembl. DR GO; GO:2000316; P:regulation of T-helper 17 type immune response; IEA:Ensembl. DR GO; GO:0031290; P:retinal ganglion cell axon guidance; IEA:Ensembl. DR GO; GO:0060021; P:roof of mouth development; ISS:UniProtKB. DR GO; GO:0120192; P:tight junction assembly; IEA:Ensembl. DR GO; GO:0099557; P:trans-synaptic signaling by trans-synaptic complex, modulating synaptic transmission; IEA:Ensembl. DR GO; GO:0001655; P:urogenital system development; ISS:UniProtKB. DR GO; GO:0110077; P:vesicle-mediated intercellular transport; IEA:Ensembl. DR CDD; cd10477; EphR_LBD_B2; 1. DR CDD; cd00063; FN3; 2. DR CDD; cd05065; PTKc_EphR_B; 1. DR CDD; cd09552; SAM_EPH-B2; 1. DR CDD; cd00185; TNFRSF; 1. DR Gene3D; 2.60.40.1770; ephrin a2 ectodomain; 1. DR Gene3D; 2.60.120.260; Galactose-binding domain-like; 1. DR Gene3D; 2.60.40.10; Immunoglobulins; 2. DR Gene3D; 1.10.150.50; Transcription Factor, Ets-1; 1. DR Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 1. DR Gene3D; 2.10.50.10; Tumor Necrosis Factor Receptor, subunit A, domain 2; 1. DR InterPro; IPR027936; Eph_TM. DR InterPro; IPR034238; EphB2_rcpt_lig-bd. DR InterPro; IPR001090; Ephrin_rcpt_lig-bd_dom. DR InterPro; IPR003961; FN3_dom. DR InterPro; IPR036116; FN3_sf. DR InterPro; IPR008979; Galactose-bd-like_sf. DR InterPro; IPR009030; Growth_fac_rcpt_cys_sf. DR InterPro; IPR013783; Ig-like_fold. DR InterPro; IPR011009; Kinase-like_dom_sf. DR InterPro; IPR000719; Prot_kinase_dom. DR InterPro; IPR017441; Protein_kinase_ATP_BS. DR InterPro; IPR001660; SAM. DR InterPro; IPR013761; SAM/pointed_sf. DR InterPro; IPR001245; Ser-Thr/Tyr_kinase_cat_dom. DR InterPro; IPR011641; Tyr-kin_ephrin_A/B_rcpt-like. DR InterPro; IPR008266; Tyr_kinase_AS. DR InterPro; IPR020635; Tyr_kinase_cat_dom. DR InterPro; IPR016257; Tyr_kinase_ephrin_rcpt. DR InterPro; IPR001426; Tyr_kinase_rcpt_V_CS. DR PANTHER; PTHR46877; EPH RECEPTOR A5; 1. DR PANTHER; PTHR46877:SF11; EPHRIN TYPE-B RECEPTOR 2; 1. DR Pfam; PF14575; EphA2_TM; 1. DR Pfam; PF01404; Ephrin_lbd; 1. DR Pfam; PF07699; Ephrin_rec_like; 1. DR Pfam; PF00041; fn3; 2. DR Pfam; PF07714; PK_Tyr_Ser-Thr; 1. DR Pfam; PF00536; SAM_1; 1. DR PIRSF; PIRSF000666; TyrPK_ephrin_receptor; 1. DR PRINTS; PR00014; FNTYPEIII. DR PRINTS; PR00109; TYRKINASE. DR SMART; SM00615; EPH_lbd; 1. DR SMART; SM01411; Ephrin_rec_like; 1. DR SMART; SM00060; FN3; 2. DR SMART; SM00454; SAM; 1. DR SMART; SM00219; TyrKc; 1. DR SUPFAM; SSF49265; Fibronectin type III; 1. DR SUPFAM; SSF49785; Galactose-binding domain-like; 1. DR SUPFAM; SSF57184; Growth factor receptor domain; 1. DR SUPFAM; SSF56112; Protein kinase-like (PK-like); 1. DR SUPFAM; SSF47769; SAM/Pointed domain; 1. DR PROSITE; PS51550; EPH_LBD; 1. DR PROSITE; PS50853; FN3; 2. DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1. DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1. DR PROSITE; PS00109; PROTEIN_KINASE_TYR; 1. DR PROSITE; PS00790; RECEPTOR_TYR_KIN_V_1; 1. DR PROSITE; PS00791; RECEPTOR_TYR_KIN_V_2; 1. DR PROSITE; PS50105; SAM_DOMAIN; 1. DR Genevisible; P29323; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; ATP-binding; Cell membrane; KW Cell projection; Developmental protein; Disease variant; Disulfide bond; KW Glycoprotein; Isopeptide bond; Kinase; Membrane; Neurogenesis; KW Nucleotide-binding; Phosphoprotein; Receptor; Reference proteome; Repeat; KW Signal; Transferase; Transmembrane; Transmembrane helix; Tumor suppressor; KW Tyrosine-protein kinase; Ubl conjugation. FT SIGNAL 1..18 FT /evidence="ECO:0000255" FT CHAIN 19..1055 FT /note="Ephrin type-B receptor 2" FT /id="PRO_0000016827" FT CHAIN 536..986 FT /note="EphB2/CTF1" FT /evidence="ECO:0000250|UniProtKB:P54763" FT /id="PRO_0000445961" FT CHAIN 562..986 FT /note="EphB2/CTF2" FT /evidence="ECO:0000250|UniProtKB:P54763" FT /id="PRO_0000445962" FT TOPO_DOM 19..543 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 544..564 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 565..1055 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT DOMAIN 20..202 FT /note="Eph LBD" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00883" FT DOMAIN 324..434 FT /note="Fibronectin type-III 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316" FT DOMAIN 435..530 FT /note="Fibronectin type-III 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00316" FT DOMAIN 621..884 FT /note="Protein kinase" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT DOMAIN 913..977 FT /note="SAM" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00184" FT REGION 990..1055 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOTIF 984..986 FT /note="PDZ-binding (in isoform 2)" FT /evidence="ECO:0000255" FT COMPBIAS 999..1049 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT ACT_SITE 746 FT /note="Proton acceptor" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159, FT ECO:0000255|PROSITE-ProRule:PRU10028" FT BINDING 627..635 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT BINDING 653 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT SITE 535..536 FT /note="Cleavage; by a metalloproteinase" FT /evidence="ECO:0000250|UniProtKB:P54763" FT SITE 561..562 FT /note="Cleavage; by gamma-secretase/PS1" FT /evidence="ECO:0000250|UniProtKB:P54763" FT CARBOHYD 265 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 336 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 482 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT DISULFID 62..184 FT /evidence="ECO:0000269|PubMed:17897949" FT DISULFID 97..107 FT /evidence="ECO:0000269|PubMed:17897949" FT CROSSLNK 891 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in ubiquitin)" FT /evidence="ECO:0000269|PubMed:33280498" FT VAR_SEQ 568 FT /note="R -> RR (in isoform 3)" FT /evidence="ECO:0000303|PubMed:8589679" FT /id="VSP_015713" FT VAR_SEQ 986 FT /note="G -> V (in isoform 2 and isoform 3)" FT /evidence="ECO:0000303|PubMed:7601466, FT ECO:0000303|PubMed:7688222, ECO:0000303|PubMed:7898931, FT ECO:0000303|PubMed:8033077, ECO:0000303|PubMed:8589679" FT /id="VSP_003016" FT VAR_SEQ 987..1055 FT /note="Missing (in isoform 2 and isoform 3)" FT /evidence="ECO:0000303|PubMed:7601466, FT ECO:0000303|PubMed:7688222, ECO:0000303|PubMed:7898931, FT ECO:0000303|PubMed:8033077, ECO:0000303|PubMed:8589679" FT /id="VSP_003017" FT VARIANT 199 FT /note="R -> H (in prostate cancer; dbSNP:rs201754821)" FT /evidence="ECO:0000269|PubMed:15300251" FT /id="VAR_032853" FT VARIANT 279 FT /note="A -> S (in prostate cancer; dbSNP:rs35882952)" FT /evidence="ECO:0000269|PubMed:15300251, FT ECO:0000269|PubMed:16155194, ECO:0000269|PubMed:17344846" FT /id="VAR_032854" FT VARIANT 289 FT /note="C -> G" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_042172" FT VARIANT 361 FT /note="I -> V (in dbSNP:rs56180036)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_042173" FT VARIANT 650 FT /note="V -> A (in prostate cancer; dbSNP:rs142173175)" FT /evidence="ECO:0000269|PubMed:16155194" FT /id="VAR_032855" FT VARIANT 678 FT /note="D -> N (in dbSNP:rs28936395)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_042174" FT VARIANT 679 FT /note="H -> N (in prostate cancer)" FT /evidence="ECO:0000269|PubMed:15300251" FT /id="VAR_032856" FT VARIANT 745 FT /note="R -> C (in BDPLT22; dbSNP:rs761749948)" FT /evidence="ECO:0000269|PubMed:30213874" FT /id="VAR_082702" FT VARIANT 844 FT /note="R -> W (in dbSNP:rs55826626)" FT /evidence="ECO:0000269|PubMed:17344846" FT /id="VAR_042175" FT VARIANT 883 FT /note="M -> V (in prostate cancer; dbSNP:rs372653137)" FT /evidence="ECO:0000269|PubMed:16155194" FT /id="VAR_032857" FT VARIANT 909 FT /note="I -> M (in prostate cancer)" FT /evidence="ECO:0000269|PubMed:15300251" FT /id="VAR_032858" FT MUTAGEN 787 FT /note="K->R: No loss of ubiquitination by RNF186." FT /evidence="ECO:0000269|PubMed:33280498" FT MUTAGEN 891 FT /note="K->R: Complete loss of ubiquitination by RNF186." FT /evidence="ECO:0000269|PubMed:33280498" FT CONFLICT 1..20 FT /note="MALRRLGAALLLLPLLAAVE -> MWVPVLALPVCTYA (in Ref. 1; FT BAA06506)" FT /evidence="ECO:0000305" FT CONFLICT 154 FT /note="G -> D (in Ref. 1; BAA06506)" FT /evidence="ECO:0000305" FT CONFLICT 476 FT /note="K -> KQ (in Ref. 1; BAA06506)" FT /evidence="ECO:0000305" FT CONFLICT 495..496 FT /note="Missing (in Ref. 5; AAA74244)" FT /evidence="ECO:0000305" FT CONFLICT 532 FT /note="E -> D (in Ref. 1; BAA06506)" FT /evidence="ECO:0000305" FT CONFLICT 589 FT /note="M -> I (in Ref. 5; AAA74244)" FT /evidence="ECO:0000305" FT CONFLICT 671 FT /note="A -> R (in Ref. 7; BAA03537)" FT /evidence="ECO:0000305" FT CONFLICT 788 FT /note="I -> F (in Ref. 5; AAA74244)" FT /evidence="ECO:0000305" FT CONFLICT 853 FT /note="S -> A (in Ref. 1; BAA06506, 6; BAA07073 and 7; FT BAA03537)" FT /evidence="ECO:0000305" FT CONFLICT 923 FT /note="E -> K (in Ref. 1; BAA06506, 6; BAA07073 and 7; FT BAA03537)" FT /evidence="ECO:0000305" FT CONFLICT 958 FT /note="V -> L (in Ref. 2; AAA99310)" FT /evidence="ECO:0000305" FT STRAND 21..25 FT /evidence="ECO:0007829|PDB:2QBX" FT HELIX 26..28 FT /evidence="ECO:0007829|PDB:2QBX" FT STRAND 36..39 FT /evidence="ECO:0007829|PDB:2QBX" FT STRAND 44..49 FT /evidence="ECO:0007829|PDB:2QBX" FT STRAND 55..61 FT /evidence="ECO:0007829|PDB:2QBX" FT STRAND 66..68 FT /evidence="ECO:0007829|PDB:2QBX" FT STRAND 71..74 FT /evidence="ECO:0007829|PDB:2QBX" FT STRAND 84..94 FT /evidence="ECO:0007829|PDB:2QBX" FT HELIX 97..99 FT /evidence="ECO:0007829|PDB:2QBX" FT STRAND 111..120 FT /evidence="ECO:0007829|PDB:2QBX" FT STRAND 130..132 FT /evidence="ECO:0007829|PDB:2QBX" FT STRAND 135..141 FT /evidence="ECO:0007829|PDB:2QBX" FT STRAND 148..152 FT /evidence="ECO:0007829|PDB:2QBX" FT STRAND 155..166 FT /evidence="ECO:0007829|PDB:2QBX" FT STRAND 171..183 FT /evidence="ECO:0007829|PDB:2QBX" FT STRAND 185..194 FT /evidence="ECO:0007829|PDB:2QBX" FT HELIX 618..620 FT /evidence="ECO:0007829|PDB:3ZFM" FT STRAND 621..626 FT /evidence="ECO:0007829|PDB:3ZFM" FT STRAND 635..640 FT /evidence="ECO:0007829|PDB:3ZFM" FT STRAND 648..655 FT /evidence="ECO:0007829|PDB:3ZFM" FT HELIX 661..674 FT /evidence="ECO:0007829|PDB:3ZFM" FT STRAND 685..689 FT /evidence="ECO:0007829|PDB:3ZFM" FT STRAND 691..700 FT /evidence="ECO:0007829|PDB:3ZFM" FT HELIX 707..712 FT /evidence="ECO:0007829|PDB:3ZFM" FT TURN 713..716 FT /evidence="ECO:0007829|PDB:3ZFM" FT HELIX 720..739 FT /evidence="ECO:0007829|PDB:3ZFM" FT HELIX 749..751 FT /evidence="ECO:0007829|PDB:3ZFM" FT STRAND 752..754 FT /evidence="ECO:0007829|PDB:3ZFM" FT STRAND 760..762 FT /evidence="ECO:0007829|PDB:3ZFM" FT HELIX 790..792 FT /evidence="ECO:0007829|PDB:3ZFM" FT HELIX 795..800 FT /evidence="ECO:0007829|PDB:3ZFM" FT HELIX 805..820 FT /evidence="ECO:0007829|PDB:3ZFM" FT TURN 826..829 FT /evidence="ECO:0007829|PDB:3ZFM" FT HELIX 832..840 FT /evidence="ECO:0007829|PDB:3ZFM" FT HELIX 853..862 FT /evidence="ECO:0007829|PDB:3ZFM" FT HELIX 873..885 FT /evidence="ECO:0007829|PDB:3ZFM" FT HELIX 887..890 FT /evidence="ECO:0007829|PDB:3ZFM" FT HELIX 918..924 FT /evidence="ECO:0007829|PDB:1B4F" FT HELIX 928..930 FT /evidence="ECO:0007829|PDB:1B4F" FT HELIX 931..936 FT /evidence="ECO:0007829|PDB:1B4F" FT HELIX 942..945 FT /evidence="ECO:0007829|PDB:1B4F" FT HELIX 950..955 FT /evidence="ECO:0007829|PDB:1B4F" FT HELIX 961..982 FT /evidence="ECO:0007829|PDB:1B4F" FT HELIX 1050..1052 FT /evidence="ECO:0007829|PDB:8EBL" FT MOD_RES P29323-2:983 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:19369195" FT MOD_RES P29323-3:984 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:19369195" SQ SEQUENCE 1055 AA; 117493 MW; 4F8BFEDC45986483 CRC64; MALRRLGAAL LLLPLLAAVE ETLMDSTTAT AELGWMVHPP SGWEEVSGYD ENMNTIRTYQ VCNVFESSQN NWLRTKFIRR RGAHRIHVEM KFSVRDCSSI PSVPGSCKET FNLYYYEADF DSATKTFPNW MENPWVKVDT IAADESFSQV DLGGRVMKIN TEVRSFGPVS RSGFYLAFQD YGGCMSLIAV RVFYRKCPRI IQNGAIFQET LSGAESTSLV AARGSCIANA EEVDVPIKLY CNGDGEWLVP IGRCMCKAGF EAVENGTVCR GCPSGTFKAN QGDEACTHCP INSRTTSEGA TNCVCRNGYY RADLDPLDMP CTTIPSAPQA VISSVNETSL MLEWTPPRDS GGREDLVYNI ICKSCGSGRG ACTRCGDNVQ YAPRQLGLTE PRIYISDLLA HTQYTFEIQA VNGVTDQSPF SPQFASVNIT TNQAAPSAVS IMHQVSRTVD SITLSWSQPD QPNGVILDYE LQYYEKELSE YNATAIKSPT NTVTVQGLKA GAIYVFQVRA RTVAGYGRYS GKMYFQTMTE AEYQTSIQEK LPLIIGSSAA GLVFLIAVVV IAIVCNRRGF ERADSEYTDK LQHYTSGHMT PGMKIYIDPF TYEDPNEAVR EFAKEIDISC VKIEQVIGAG EFGEVCSGHL KLPGKREIFV AIKTLKSGYT EKQRRDFLSE ASIMGQFDHP NVIHLEGVVT KSTPVMIITE FMENGSLDSF LRQNDGQFTV IQLVGMLRGI AAGMKYLADM NYVHRDLAAR NILVNSNLVC KVSDFGLSRF LEDDTSDPTY TSALGGKIPI RWTAPEAIQY RKFTSASDVW SYGIVMWEVM SYGERPYWDM TNQDVINAIE QDYRLPPPMD CPSALHQLML DCWQKDRNHR PKFGQIVNTL DKMIRNPNSL KAMAPLSSGI NLPLLDRTIP DYTSFNTVDE WLEAIKMGQY KESFANAGFT SFDVVSQMMM EDILRVGVTL AGHQKKILNS IQVMRAQMNQ IQSVEGQPLA RRPRATGRTK RCQPRDVTKK TCNSNDGKKK GMGKKKTDPG RGREIQGIFF KEDSHKESND CSCGG //