ELM - Detail for LIG_SxIP_EBH

Accession:	ELME000254
Functional site class:	SxIP motif
Functional site description:	End binding homology (EBH) domains recognize SxIP motifs embedded within basic and Pro/Ser rich sequence regions of microtubule plus-end tracking proteins (+TIPs). The EBH-SxIP interaction is used by numerous +TIPs to target end binding (EB) proteins at growing microtubule ends.
ELM Description:	SxIP motifs within basic and Pro/Ser rich sequence regions bind to EBH domains of EB proteins. Both, the SxIP sequence as well as basic, not strictly conserved, residues in the vicinity of the motif site contribute to the EBH-SxIP binding affinity. Some SxIP motifs are known to be regulated by phosphorylation while acidic residues are strongly disfavoured in the local regions. The current regular expression partially captures this context. There must be either no negative charge within 5 residues or else a basic residue closer to the SxIP than an acidic residue. All SxIP motifs reported by Honnappa,2009 are detected by the pattern. There is one report of a functional SxLP motif in a strongly basic sequence context (Fong,2009). For the moment, the ELM pattern excludes Leu until binding affinities and sequence context of SxLP motifs are better described. Difficult to predict SxIP in entire Proteomes. Possible to predict in proteins known to bind directly to EBs and associated with microtubules.
Pattern:	`([KR][^ED]{0,5}[ST].IP[^ED]{5,5})\|([^ED]{5,5}[ST].IP[^ED]{0,5}[KR])`
Pattern Probability:	`0.0002096`
Present in taxon:	Eukaryota
Interaction Domain:	EB1 (PF03271) EB1-like C-terminal motif (Stochiometry: 1 : 1) PDB Structure: 3GJO

SxIP motif

End binding homology (EBH) domains recognize SxIP motifs embedded within basic and Pro/Ser rich sequence regions of microtubule plus-end tracking proteins (+TIPs). The EBH-SxIP interaction is used by numerous +TIPs to target end binding (EB) proteins at growing microtubule ends.

ELM Description:

SxIP motifs within basic and Pro/Ser rich sequence regions bind to EBH domains of EB proteins. Both, the SxIP sequence as well as basic, not strictly conserved, residues in the vicinity of the motif site contribute to the EBH-SxIP binding affinity. Some SxIP motifs are known to be regulated by phosphorylation while acidic residues are strongly disfavoured in the local regions. The current regular expression partially captures this context. There must be either no negative charge within 5 residues or else a basic residue closer to the SxIP than an acidic residue. All SxIP motifs reported by Honnappa,2009 are detected by the pattern. There is one report of a functional SxLP motif in a strongly basic sequence context (Fong,2009). For the moment, the ELM pattern excludes Leu until binding affinities and sequence context of SxLP motifs are better described. Difficult to predict SxIP in entire Proteomes. Possible to predict in proteins known to bind directly to EBs and associated with microtubules.

Pattern:

([KR][^ED]{0,5}[ST].IP[^ED]{5,5})|([^ED]{5,5}[ST].IP[^ED]{0,5}[KR])

Pattern Probability:

0.0002096

Present in taxon:

Eukaryota

Interaction Domain:

EB1 (PF03271) EB1-like C-terminal motif (Stochiometry: 1 : 1)

PDB Structure: 3GJO

The end binding homology (EBH) domain (PF03271) is a small, approximately 50-residue protein module highly conserved in organisms from yeast to man. It is exclusively found in end binding (EB) proteins. EB proteins autonomously track growing microtubule plus ends and act as a hub within dynamic microtubule plus-end tracking protein (+TIP) networks. +TIPs constitute a diverse group of evolutionarily conserved microtubule-associated proteins that specifically accumulate at the ends of growing microtubules. They play important roles in essential cellular activities, including chromosome segregation, cell polarization and migration, organelle transport, and intracellular signalling.
The C-terminal EBH domain of EB proteins binds to an array of structurally and functionally unrelated +TIP binding partners, including the adenomatous polyposis coli (APC) tumor suppressor protein, the microtubule-actin crosslinking factor (MACF), the cytoplasmic linker protein (CLIP170), CLIP-associated proteins (CLASPs), the transmembrane protein stromal interaction molecule-1 (STIM1), the dynactin large subunit p150glued, and the mitotic centromere-associated kinesin (MCAK). SxIP motifs embedded within basic and Pro/Ser rich sequence regions of numerous +TIPs specifically bind to highly conserved residues shaping a hydrophobic groove in the EBH domain. Thus EBH domains are SxIP recognition domains. The EBH-SxIP interaction is used to target +TIPs to EBs at growing microtubule ends. Therefore, SxIP motifs act as general microtubule tip localization signals (MtLS).

Biological Process:
Microtubule Cytoskeleton Organization And Biogenesis (also annotated in these classes: )
Microtubule-Based Movement (also annotated in these classes: )
Establishment And/Or Maintenance Of Microtubule Cytoskeleton Polarity (also annotated in these classes: )
Microtubule Polymerization Or Depolymerization (also annotated in these classes: )
Cytoplasmic Microtubule Organization And Biogenesis (also annotated in these classes: LIG_CAP-Gly_2 )
Regulation Of Microtubule-Based Process (also annotated in these classes: )
Plus-End Directed Microtubule Sliding (also annotated in these classes: )
Microtubule-Based Process (also annotated in these classes: LIG_CAP-Gly_1 )
Cellular Compartment:
Cytosol (also annotated in these classes: )
Microtubule (also annotated in these classes: )
Molecular Function:
Microtubule Plus-End Binding (also annotated in these classes: )

Acc., Gene-, Name	Start	End	Subsequence	Logic	#Ev.	Organism	Notes
Q6PGN9 PSRC1 PSRC1_HUMAN	276	289	SSSQLPIPSAIPRPASRMPL	TP	1	Homo sapiens (Human)
Q91V27 Mlph MELPH_MOUSE	493	506	PSGKPRRKSGIPIFLPRVTE	TP	1	Mus musculus (House mouse)
Q9C0H9 SRCIN1 SRCN1_HUMAN	1032	1046	SEKPSASRTSIPVLTSFGAR	TP	1	Homo sapiens (Human)
Q99661 KIF2C KIF2C_HUMAN	93	104	QKQKRRSVNSKIPAPKESLR	TP	4	Homo sapiens (Human)	1
Q13586 STIM1 STIM1_HUMAN	637	651	ALQASRNTRIPHLAGKKAVA	TP	4	Homo sapiens (Human)
O75122 CLASP2 CLAP2_HUMAN	515	525	LSVARSSRIPRPSVSQGCSR	TP	4	Homo sapiens (Human)	1
O75122 CLASP2 CLAP2_HUMAN	492	502	ASAQKRSKIPRSQGCSREAS	TP	4	Homo sapiens (Human)
Q03001 DST DYST_HUMAN	7545	7558	SRPSTAKPSKIPTPQRKSPA	TP	6	Homo sapiens (Human)	3GJO 3GJO
P25054 APC APC_HUMAN	2801	2811	STSARPSQIPTPVNNNTKKR	TP	6	Homo sapiens (Human)	1

Acc., Gene-, Name

Start

End

Subsequence

Logic

#Ev.

Organism

Notes

Q6PGN9 PSRC1
PSRC1_HUMAN

276

289

SSSQLPIPSAIPRPASRMPL