Structure Flashcards
(16 cards)
SLAP1 Cbl binding sequence
hu - LRESASYLSLTSEDNTSF
ms- LRESASYLSLTGDDSSSF
SLAP2
hu - LRESLSFYSLNDEAVSLD
ms- LRESLSSUSLAEDP__LD
Comparison between SLAP1/2 Cbl binding
hu1 - LRES_ASYLSLTSEDNTSF
hu2- LRESLSFY_SLNDEAVSLD
ms1 - LRES_ASYLSLTGDDSSSF
ms2- LRESLSSY_SLAEDP__LD
Chromosomal Location msSLAP1
Chromosome 15
Chromosomal Location huSLAP1
Chromosome 8q22.3 embedded in the thyroglobulin gene locus
Chromosomal Location msSLAP2
Chromosome 2
Chromosomal location of huSLAP2
Chromosome 20q11.23
SLAP2 size
256 AA, 25-28 kDA depending on splice variants
SLAP2 isoforms
splice variants
Identification of SLAP1/cbl interaction
Yeast-2-hybrid screen
Bait: residues 25-351 of c-Cbl
Prey: cDNA Library from PHA stimulated human leukocytes
Mapping shows that if you knock out the charged part of the SLAP1 c-terminal region
Interaction between cbl and zap70
nterminal PTB domain of cbl and pY292 of Zap70
SLAP1 size
276AA 34 kDa
SLAP1 cTerminal region
aa210-241 = leucine rich hydrophobic region aa240-276 = Highly charged (arginine C-CH2C00-) (Glutamic acid - C-CH2-CH2-COO) (Lys C-(CH2)4-NH3+) (Arginine C-(CH2)3-NH-CNH2NH2+)
LOF mutation in SLAP1 SH2
R111K
SLAP Preferential binding sequence
pY+3: Aliphatic residues (V,I,P)
pY+1: Small (A,S,T)
Acidic Residues (E,D,Q,H)
ITAM Motif
18aa
YxxL/I-X(6-8)-YxxL/I
pY is position zero
The specificity of an SH2 domain for a given ITAM motif is determined by the flanking residues, usually at the -2 to +3