M00124
type: Enzyme
rlcp: p1162
cath: Jelly Rolls
cath: http://ezcatdb.cbrc.jp/EzCatDB/cath/-.-.-.-
cath: Immunoglobulin-like
cath: Phosphorylase Kinase; domain 1
cath: Transferase(Phosphotransferase); domain 1
cath: DNA polymerase; domain 1
ec: https://purl.uniprot.org/enzyme/2.7.10.1
uniprot: P54763
uniprot: P28693
kegg enzyme: receptor protein-tyrosine kinase
kegg enzyme: AATK
kegg enzyme: AATYK
kegg enzyme: AATYK2
kegg enzyme: AATYK3
kegg enzyme: ACH
kegg enzyme: ALK
kegg enzyme: anaplastic lymphoma kinase
kegg enzyme: ARK
kegg enzyme: ATP:protein-tyrosine O-phosphotransferase (ambiguous)
kegg enzyme: AXL
kegg enzyme: Bek
kegg enzyme: Bfgfr
kegg enzyme: BRT
kegg enzyme: Bsk
kegg enzyme: C-FMS
kegg enzyme: CAK
kegg enzyme: CCK4
kegg enzyme: CD115
kegg enzyme: CD135
kegg enzyme: CDw135
kegg enzyme: Cek1
kegg enzyme: Cek10
kegg enzyme: Cek11
kegg enzyme: Cek2
kegg enzyme: Cek3
kegg enzyme: Cek5
kegg enzyme: Cek6
kegg enzyme: Cek7
kegg enzyme: CFD1
kegg enzyme: CKIT
kegg enzyme: CSF1R
kegg cofactor: Magnesium
kegg substrate: ATP
kegg substrate: [Protein]-L-tyrosine
kegg product: ADP
kegg product: [Protein]-L-tyrosine phosphate
pdb: 1nukA
pdb: 1kgyA
pdb: 1kgyB
pdb: 1kgyC
pdb: 1kgyD
pdb: 1jpaA01
pdb: 1jpaB01
pdb: 1jpaA02
pdb: 1jpaB02
pdb: 1sggA
references: Self-association studies on the EphB2 receptor SAM domain using analytical ultracentrifugation.
references: Olfactory marker protein (OMP) exhibits a beta-clam fold in solution: implications for target peptide interaction and olfactory signal transduction.
references: Juxtamembrane tyrosine residues couple the Eph family receptor EphB2/Nuk to specific SH2 domain proteins in neuronal cells.
references: Crystal structure of the ligand-binding domain of the receptor tyrosine kinase EphB2.
references: PDZ proteins bind, cluster, and synaptically colocalize with Eph receptors and their ephrin ligands.
references: Complex formation between EphB2 and Src requires phosphorylation of tyrosine 611 in the EphB2 juxtamembrane region.
references: alphaPIX nucleotide exchange factor is activated by interaction with phosphatidylinositol 3-kinase.
references: Signal transfer by Eph receptors.
references: Isolation and characterization of Dek, a Drosophila eph receptor protein tyrosine kinase.
references: Solution structure of a conserved C-terminal domain of p73 with structural homology to the SAM domain.
references: The crystal structure of an Eph receptor SAM domain reveals a mechanism for modular dimerization.
references: Solution structure of the receptor tyrosine kinase EphB2 SAM domain and identification of two distinct homotypic interaction sites.
references: Oligomeric structure of the human EphB2 receptor SAM domain.
references: Phosphorylation of tyrosine residues in the kinase domain and juxtamembrane region regulates the biological and catalytic activities of Eph receptors.
references: Complementary expression of transmembrane ephrins and their receptors in the mouse spinal cord: a possible role in constraining the orientation of longitudinally projecting axons.
references: Structural basis for autoinhibition of the Ephb2 receptor tyrosine kinase by the unphosphorylated juxtamembrane region.
references: Crystal structure of an Eph receptor-ephrin complex.
references: The crystal structure of the olfactory marker protein at 2.3 A resolution.
references: The role of the Eph-ephrin signalling system in the regulation of developmental patterning.
references: Regulation and targets of receptor tyrosine kinases.
references: Eph family functions from an evolutionary perspective.
comment: The E.C. was transferred from 2.7.1.112 to 2.7.10.1. The Eph receptor tyrosine kinase family is regulated by autophosphorylation within the juxtamembrane region and the kinase activation segment. This receptor enzyme has N-terminal extracellular region, which is composed of ligand-binding domain, Cys-rich domain, and two fibronectine type-III domain, transmembrane region, and cytoplasmic region, which is composed of juxtamembrane region, protein kinase domain, and SAM domain. PDB structures, 1nuk & 1kgy, correspond to the first domain of this enzyme, ligand-binding domain, the other structure, 1jpa, comprises the fifth domain, juxtamembrane region, and the sixth domain, protein kinase domain. PDB structure, 1sgg, corresponds to the last domain, SAM. However, tertiary structures of the rest of domains, the second domain, Cys-rich domain, the third and fourth domains, two fibronectin type-III domains, have not been determined yet. The last domain is sterile alpha motif (SAM) domain, which was found in various signaling proteins such as tyrosine and serine/threonine protein kinases, regulators of lipid metabolism, and GTPases, according to the literature [9]. The SAM domain is involved in protein-protein interaction, rather than catalysis, through the ability to oligomerize with other SAM domains [9]. This SAM domain has a conserved tyrosine (Tyr25, PDB;1sgg), which was reported to be essential for the interaction with SH2 domains after its phosphorylation (see paper [10]). Although the tertiary structure of the catalytic domain has been determined, its catalytic mechanism is still unclear. However, since the structure is homologous to other kinase domains with complete conservation of active site residues, the mechanism can be similar to those ones (see M00129).

Jelly Rolls
type: Cath
references: http://www.cathdb.info/version/latest/superfamily/2.60.120.260

Immunoglobulin-like
type: Cath
references: http://www.cathdb.info/version/latest/superfamily/2.60.40.30

Phosphorylase Kinase; domain 1
type: Cath
references: http://www.cathdb.info/version/latest/superfamily/3.30.200.20

Transferase(Phosphotransferase); domain 1
type: Cath
references: http://www.cathdb.info/version/latest/superfamily/1.10.510.10
catalytic domain: index.html

DNA polymerase; domain 1
type: Cath
references: http://www.cathdb.info/version/latest/superfamily/1.10.150.50

Magnesium
type: KeggCofactor
references: KEGG:C00305
compound type: divalent metal (Ca2+, Mg2+)
references: CHEBI:18420
references: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi

ATP
type: KeggSubstrate
references: KEGG:C00002
compound type: amine group
compound type: nucleotide
references: CHEBI:15422
references: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi

[Protein]-L-tyrosine
type: KeggSubstrate
references: KEGG:C00585
compound type: aromatic ring (only carbon atom)
compound type: peptide/protein

ADP
type: KeggProduct
references: KEGG:C00008
compound type: amine group
compound type: nucleotide
references: CHEBI:16761
references: http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi

[Protein]-L-tyrosine phosphate
type: KeggProduct
references: KEGG:C01167
compound type: aromatic ring (only carbon atom)
compound type: peptide/protein
compound type: phosphate group/phosphate ion

1jpaA01
type: Pdb
references: 1jpa
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1jpa
comment: mutant Y604F, Y610F

1jpaB01
type: Pdb
references: 1jpa
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1jpa
comment: mutant Y604F, Y610F

1jpaA02
type: Pdb
references: 1jpa
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1jpa
catalytic residue: ASP 754;ARG 758
cofactor binding residue: ASN 759;ASP 772(Magnesium binding)

1jpaB02
type: Pdb
references: 1jpa
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1jpa
catalytic residue: ASP 754;ARG 758
cofactor binding residue: ASN 759;ASP 772(Magnesium binding)

1sggA
type: Pdb
references: 1sgg
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl
references: PDB:1sgg
modified residue: TYR 25 (Phospholylated)

Self-association studies on the EphB2 receptor SAM domain using analytical ultracentrifugation.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/11718293
journal: Eur Biophys J
volume: 30
pages: 411-5
published year: 2001
authors:
  item: Behlke J
  item: Labudde D
  item: Ristau O

Olfactory marker protein (OMP) exhibits a beta-clam fold in solution: implications for target peptide interaction and olfactory signal transduction.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/12054873
journal: J Mol Biol
volume: 319
pages: 823-37
published year: 2002
authors:
  item: Baldisseri DM
  item: Margolis JW
  item: Weber DJ
  item: Koo JH
  item: Margolis FL

Juxtamembrane tyrosine residues couple the Eph family receptor EphB2/Nuk to specific SH2 domain proteins in neuronal cells.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/9233798
journal: EMBO J
volume: 16
pages: 3877-88
published year: 1997
authors:
  item: Holland SJ
  item: Gale NW
  item: Gish GD
  item: Roth RA
  item: Songyang Z
  item: Cantley LC
  item: Henkemeyer M
  item: Yancopoulos GD
  item: Pawson T

Crystal structure of the ligand-binding domain of the receptor tyrosine kinase EphB2.
type: BibliographicResource
comment: X-ray crystallography
references: http://www.ncbi.nlm.nih.gov/pubmed/9853759
journal: Nature
volume: 396
pages: 486-91
published year: 1998
authors:
  item: Himanen JP
  item: Henkemeyer M
  item: Nikolov DB
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl

PDZ proteins bind, cluster, and synaptically colocalize with Eph receptors and their ephrin ligands.
type: BibliographicResource
comment: INTERACTION WITH PRKCABP
medline id: 99098206
references: http://www.ncbi.nlm.nih.gov/pubmed/9883737
journal: Neuron
volume: 21
pages: 1453-63
published year: 1998
authors:
  item: Torres R
  item: Firestein BL
  item: Dong H
  item: Staudinger J
  item: Olson EN
  item: Huganir RL
  item: Bredt DS
  item: Gale NW
  item: Yancopoulos GD
references: P54763

Complex formation between EphB2 and Src requires phosphorylation of tyrosine 611 in the EphB2 juxtamembrane region.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/9632142
journal: Oncogene
volume: 16
pages: 2657-70
published year: 1998
authors:
  item: Zisch AH
  item: Kalo MS
  item: Chong LD
  item: Pasquale EB

alphaPIX nucleotide exchange factor is activated by interaction with phosphatidylinositol 3-kinase.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/10523848
journal: Oncogene
volume: 18
pages: 5680-90
published year: 1999
authors:
  item: Yoshii S
  item: Tanaka M
  item: Otsuki Y
  item: Wang DY
  item: Guo RJ
  item: Zhu Y
  item: Takeda R
  item: Hanai H
  item: Kaneko E
  item: Sugimura H

Signal transfer by Eph receptors.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/10555534
journal: Cell Tissue Res
volume: 298
pages: 1-9
published year: 1999
authors:
  item: Kalo MS
  item: Pasquale EB

Isolation and characterization of Dek, a Drosophila eph receptor protein tyrosine kinase.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/10356296
journal: Mol Cell Neurosci
volume: 13
pages: 337-47
published year: 1999
authors:
  item: Scully AL
  item: McKeown M
  item: Thomas JB

Solution structure of a conserved C-terminal domain of p73 with structural homology to the SAM domain.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/10449409
journal: EMBO J
volume: 18
pages: 4438-45
published year: 1999
authors:
  item: Chi SW
  item: Ayed A
  item: Arrowsmith CH

The crystal structure of an Eph receptor SAM domain reveals a mechanism for modular dimerization.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/9886291
journal: Nat Struct Biol
volume: 6
pages: 44-9
published year: 1999
authors:
  item: Stapleton D
  item: Balan I
  item: Pawson T
  item: Sicheri F

Solution structure of the receptor tyrosine kinase EphB2 SAM domain and identification of two distinct homotypic interaction sites.
type: BibliographicResource
comment: NMR Structures
references: http://www.ncbi.nlm.nih.gov/pubmed/10548040
journal: Protein Sci
volume: 8
pages: 1954-61
published year: 1999
authors:
  item: Smalla M
  item: Schmieder P
  item: Kelly M
  item: Ter Laak A
  item: Krause G
  item: Ball L
  item: Wahl M
  item: Bork P
  item: Oschkinat H
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl

Oligomeric structure of the human EphB2 receptor SAM domain.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/9933164
journal: Science
volume: 283
pages: 833-6
published year: 1999
authors:
  item: Thanos CD
  item: Goodwill KE
  item: Bowie JU

Phosphorylation of tyrosine residues in the kinase domain and juxtamembrane region regulates the biological and catalytic activities of Eph receptors.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/10848605
journal: Mol Cell Biol
volume: 20
pages: 4791-805
published year: 2000
authors:
  item: Binns KL
  item: Taylor PP
  item: Sicheri F
  item: Pawson T
  item: Holland SJ

Complementary expression of transmembrane ephrins and their receptors in the mouse spinal cord: a possible role in constraining the orientation of longitudinally projecting axons.
type: BibliographicResource
comment: FUNCTION
medline id: 20171264
references: http://www.ncbi.nlm.nih.gov/pubmed/10704386
journal: Development
volume: 127
pages: 1397-410
published year: 2000
authors:
  item: Imondi R
  item: Wideman C
  item: Kaprielian Z
references: P54763

Structural basis for autoinhibition of the Ephb2 receptor tyrosine kinase by the unphosphorylated juxtamembrane region.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/11572780
journal: Cell
volume: 106
pages: 745-57
published year: 2001
authors:
  item: Wybenga-Groot LE
  item: Baskin B
  item: Ong SH
  item: Tong J
  item: Pawson T
  item: Sicheri F
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl

Crystal structure of an Eph receptor-ephrin complex.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/11780069
journal: Nature
volume: 414
pages: 933-8
published year: 2001
authors:
  item: Himanen JP
  item: Rajashankar KR
  item: Lackmann M
  item: Cowan CA
  item: Henkemeyer M
  item: Nikolov DB
references: http://www.ebi.ac.uk/thornton-srv/databases/cgi-bin/pdbsum/GetPage.pl

The crystal structure of the olfactory marker protein at 2.3 A resolution.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/12054872
journal: J Mol Biol
volume: 319
pages: 807-21
published year: 2002
authors:
  item: Smith PC
  item: Firestein S
  item: Hunt JF

The role of the Eph-ephrin signalling system in the regulation of developmental patterning.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/12141423
journal: Int J Dev Biol
volume: 46
pages: 375-84
published year: 2002
authors:
  item: Coulthard MG
  item: Duffy S
  item: Down M
  item: Evans B
  item: Power M
  item: Smith F
  item: Stylianou C
  item: Kleikamp S
  item: Oates A
  item: Lackmann M
  item: Burns GF
  item: Boyd AW

Regulation and targets of receptor tyrosine kinases.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/12528767
journal: Eur J Cancer
volume: 38 Suppl 5
pages: S3-10
published year: 2002
authors:
  item: Pawson T

Eph family functions from an evolutionary perspective.
type: BibliographicResource
references: http://www.ncbi.nlm.nih.gov/pubmed/12100883
journal: Curr Opin Genet Dev
volume: 12
pages: 397-402
published year: 2002
authors:
  item: Drescher U

DAlk
type: KeggEnzyme

DDR1
type: KeggEnzyme

DDR2
type: KeggEnzyme

Dek
type: KeggEnzyme

DKFZp434C1418
type: KeggEnzyme

Drosophila Eph kinase
type: KeggEnzyme

DRT
type: KeggEnzyme

DTK
type: KeggEnzyme

Ebk
type: KeggEnzyme

ECK
type: KeggEnzyme

EDDR1
type: KeggEnzyme

Eek
type: KeggEnzyme

EGFR
type: KeggEnzyme

Ehk2
type: KeggEnzyme

Ehk3
type: KeggEnzyme

Elk
type: KeggEnzyme

EPH
type: KeggEnzyme

EPHA1
type: KeggEnzyme

EPHA2
type: KeggEnzyme

EPHA6
type: KeggEnzyme

EPHA7
type: KeggEnzyme

EPHA8
type: KeggEnzyme

EPHB1
type: KeggEnzyme

EPHB2
type: KeggEnzyme

EPHB3
type: KeggEnzyme

EPHB4
type: KeggEnzyme

EphB5
type: KeggEnzyme

ephrin-B3 receptor tyrosine kinase
type: KeggEnzyme

EPHT
type: KeggEnzyme

EPHT2
type: KeggEnzyme

EPHT3
type: KeggEnzyme

EPHX
type: KeggEnzyme

ERBB
type: KeggEnzyme

ERBB1
type: KeggEnzyme

ERBB2
type: KeggEnzyme

ERBB3
type: KeggEnzyme

ERBB4
type: KeggEnzyme

ERK
type: KeggEnzyme

Eyk
type: KeggEnzyme

FGFR1
type: KeggEnzyme

FGFR2
type: KeggEnzyme

FGFR3
type: KeggEnzyme

FGFR4
type: KeggEnzyme

FLG
type: KeggEnzyme

FLK1
type: KeggEnzyme

FLK2
type: KeggEnzyme

FLT1
type: KeggEnzyme

FLT2
type: KeggEnzyme

FLT3
type: KeggEnzyme

FLT4
type: KeggEnzyme

FMS
type: KeggEnzyme

Fv2
type: KeggEnzyme

HBGFR
type: KeggEnzyme

HEK11
type: KeggEnzyme

HEK2
type: KeggEnzyme

HEK3
type: KeggEnzyme

HEK5
type: KeggEnzyme

HEK6
type: KeggEnzyme

HEP
type: KeggEnzyme

HER2
type: KeggEnzyme

HER3
type: KeggEnzyme

HER4
type: KeggEnzyme

HGFR
type: KeggEnzyme

HSCR1
type: KeggEnzyme

HTK
type: KeggEnzyme

IGF1R
type: KeggEnzyme

INSR
type: KeggEnzyme

INSRR
type: KeggEnzyme

insulin receptor protein-tyrosine kinase
type: KeggEnzyme

IR
type: KeggEnzyme

IRR
type: KeggEnzyme

JTK12
type: KeggEnzyme

JTK13
type: KeggEnzyme

JTK14
type: KeggEnzyme

JWS
type: KeggEnzyme

K-SAM
type: KeggEnzyme

KDR
type: KeggEnzyme

KGFR
type: KeggEnzyme

KIA0641
type: KeggEnzyme

KIAA1079
type: KeggEnzyme

KIAA1459
type: KeggEnzyme

Kil
type: KeggEnzyme

Kin15
type: KeggEnzyme

Kin16
type: KeggEnzyme

KIT
type: KeggEnzyme

KLG
type: KeggEnzyme

LTK
type: KeggEnzyme

MCF3
type: KeggEnzyme

Mdk1
type: KeggEnzyme

Mdk2
type: KeggEnzyme

Mdk5
type: KeggEnzyme

MEhk1
type: KeggEnzyme

MEN2A/B
type: KeggEnzyme

Mep
type: KeggEnzyme

MER
type: KeggEnzyme

MERTK
type: KeggEnzyme

MET
type: KeggEnzyme

Mlk1
type: KeggEnzyme

Mlk2
type: KeggEnzyme

Mrk
type: KeggEnzyme

MST1R
type: KeggEnzyme

MTC1
type: KeggEnzyme

MUSK
type: KeggEnzyme

Myk1
type: KeggEnzyme

N-SAM
type: KeggEnzyme

NEP
type: KeggEnzyme

NET
type: KeggEnzyme

Neu
type: KeggEnzyme

neurite outgrowth regulating kinase
type: KeggEnzyme

NGL
type: KeggEnzyme

NOK
type: KeggEnzyme

nork
type: KeggEnzyme

novel oncogene with kinase-domain
type: KeggEnzyme

Nsk2
type: KeggEnzyme

NTRK1
type: KeggEnzyme

NTRK2
type: KeggEnzyme

NTRK3
type: KeggEnzyme

NTRK4
type: KeggEnzyme

NTRKR1
type: KeggEnzyme

NTRKR2
type: KeggEnzyme

NTRKR3
type: KeggEnzyme

Nuk
type: KeggEnzyme

NYK
type: KeggEnzyme

PCL
type: KeggEnzyme

PDGFR
type: KeggEnzyme

PDGFRA
type: KeggEnzyme

PDGFRB
type: KeggEnzyme

PHB6
type: KeggEnzyme

protein-tyrosine kinase (ambiguous)
type: KeggEnzyme

protein tyrosine kinase (ambiguous)
type: KeggEnzyme

PTK
type: KeggEnzyme

PTK3
type: KeggEnzyme

PTK7
type: KeggEnzyme

receptor protein tyrosine kinase
type: KeggEnzyme

RET
type: KeggEnzyme

RON
type: KeggEnzyme

ROR1
type: KeggEnzyme

ROR2
type: KeggEnzyme

ROS1
type: KeggEnzyme

RSE
type: KeggEnzyme

RTK
type: KeggEnzyme

RYK
type: KeggEnzyme

SEA
type: KeggEnzyme

Sek2
type: KeggEnzyme

Sek3
type: KeggEnzyme

Sek4
type: KeggEnzyme

Sfr
type: KeggEnzyme

SKY
type: KeggEnzyme

STK
type: KeggEnzyme

STK1
type: KeggEnzyme

TEK
type: KeggEnzyme

TIE
type: KeggEnzyme

TIE1
type: KeggEnzyme

TIE2
type: KeggEnzyme

TIF
type: KeggEnzyme

TKT
type: KeggEnzyme

TRK
type: KeggEnzyme

TRKA
type: KeggEnzyme

TRKB
type: KeggEnzyme

TRKC
type: KeggEnzyme

TRKE
type: KeggEnzyme

TYK1
type: KeggEnzyme

TYRO10
type: KeggEnzyme

Tyro11
type: KeggEnzyme

TYRO3
type: KeggEnzyme

Tyro5
type: KeggEnzyme

Tyro6
type: KeggEnzyme

TYRO7
type: KeggEnzyme

UFO
type: KeggEnzyme

VEGFR1
type: KeggEnzyme

VEGFR2
type: KeggEnzyme

VEGFR3
type: KeggEnzyme

Vik
type: KeggEnzyme

YK1
type: KeggEnzyme

Yrk
type: KeggEnzyme

Analogue
compound: ADP
pdb: 1jpaA01
ligand het code: ANP

Analogue
compound: ADP
pdb: 1jpaB01
ligand het code: ANP

ReferenceForCatalyticMechanism
reference index: 9

ReferenceForCatalyticMechanism
reference index: 10