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ankyrin repeat-rich membrane spanning protein (kinase D-interacting substrate of 220 kD, ARMS, KIAA1250, KIDINS220)
Function:
- promotes a prolonged MAP-kinase signaling by neurotrophins through activation of a Rap1-dependent mechanism
- provides a docking site for the CRKL-C3G complex, resulting in Rap1-dependent sustained ERK activation
- may play role in regulating postsynaptic signal transduction through syntrophin-mediated localization of receptor tyrosine kinases such as EPHA4
- in cooperation with SNTA1 can enhance EPHA4-induced JAK/STAT activation
- may play a role in neurotrophin- & ephrin-mediated neuronal outgrowth & in axon guidance during neural development & in neuronal regeneration (putative)
- modulates stress-induced apoptosis of melanoma cells via regulation of the MEK/ERK signaling pathway
- interacts with NTRK1, NTRK2, NTRK3, ERKL & NGFR
- can form a ternary complex with NGFR & NTRK1 & this complex is affected by the expression levels of ARMS
- an increase in ARMS expression leads to a decreased association of NGFR & NTRK1
- interacts with SNTA1 & SNTB2 & binds to their PDZ domains
- interacts with EPHA4 & PRKD1 (putative)
- tyrosine phosphorylated by NTRK1, NTRK2, EPHB2 & EPHA4
- phosphorylation at Ser-918 is induced by phorbol ester
- phosphorylation by NTRK2 is induced by BDNF & neurotrophin-4/5
- phosphorylation by NTRK1 is induced by nerve growth factor (NGF) (putative)
Structure:
- transmembrane domain mediates interaction with NTRK1
- contains 12 ANK repeats
Compartment: membrane (putative)
Alternative splicing: named isoforms=5
Expression:
- abundant in developing & adult neural tissues
Pathology: overexpressed in melanoma & melanoma cell lines
General
ankyrin repeat domain protein (ANKRD)
membrane protein
phosphoprotein
Properties
SIZE: entity length = 1771 aa
MW = 197 kD
COMPARTMENT: cytoplasm
MOTIF: cytoplasmic domain {1-499}
MOTIF: ankyrin repeat
NAME: ankyrin repeat
SITE: 4-33
ankyrin repeat
NAME: ankyrin repeat
SITE: 37-66
ankyrin repeat
NAME: ankyrin repeat
SITE: 70-99
ankyrin repeat
NAME: ankyrin repeat
SITE: 103-132
ankyrin repeat
NAME: ankyrin repeat
SITE: 136-165
ankyrin repeat
NAME: ankyrin repeat
SITE: 169-198
ankyrin repeat
NAME: ankyrin repeat
SITE: 202-231
ankyrin repeat
NAME: ankyrin repeat
SITE: 235-264
ankyrin repeat
NAME: ankyrin repeat
SITE: 268-297
ankyrin repeat
NAME: ankyrin repeat
SITE: 301-330
ankyrin repeat
NAME: ankyrin repeat
SITE: 334-363
ankyrin repeat
NAME: ankyrin repeat
SITE: 367-396
transmembrane domain {500-520}
exoplasmic loop {521-524}
transmembrane domain {525-545}
cytoplasmic loop {546-659}
transmembrane domain {660-680}
exoplasmic loop {681-685}
transmembrane domain {686-706}
cytoplasmic domain {707-1771}
MOTIF: Ser phosphorylation site {S918}
Mediates interaction with CRKL {1089-1092}
Mediates interaction with SNTA1 {1767-1771}
Database Correlations
UniProt Q9ULH0
PFAM correlations
Kegg hsa:5749
References
UniProt :accession Q9ULH0