Protein: Mitogen-activated protein kinase kinase kinase nsy-1 (EC 2.7.11.25) (Apoptosis signal-regulating kinase 1) (ASK-1) (Neuronal symmetry kinase 1) (Q21029)
Organism: Caenorhabditis elegans
Function: Serine/threonine-protein kinase which, by phosphorylating and activating sek-1, plays an important role in the activation of the p38 pathway also composed of the downstream effectors sek-1 and pmk-1. Downstream of CaMKII unc-43 and adapter protein tir-1, plays a role in determining asymmetric cell fates in olfactory AWC neurons during neuronal development. Activation results in the repression of odorant receptor str-2 expression in one of the 2 AWC neurons. Involved in resistance to pathogenic Gram-positive and Gram-negative bacterial and fungal infection. Involved in resistance to the nematotoxic C.cinerea galectin Cgl2. Probably by activating the sek1/pmk-1/skn-1 pathway, involved in the up-regulation of gcs-1 and glutathione-S-transferase gst-4 expression upon bacterial infection. Probably downstream of tir-1 and nipi-3, required for the expression of antimicrobial peptide nlp-29 in the epidermis in response to fungal infection or physical injury. Plays a role in resistance to several environmental stresses including oxidative, protein misfolding (ER) and osmotic stresses, and DNA-damaging reagents. Plays a role in the stabilization of transcription factor rnt-1 in the intestine during oxidative stress. Involved in germline apoptosis induced by heavy metals, such as Cu(2+). In addition, plays a role in the up-regulation of gcs-1 upon arsenite treatment, most likely through activation of pmk-1, to confer protection against toxicity induced by heavy metals. Plays a role downstream of tir-1 in regulating susceptibility to anoxia. Involved in egg laying.
Subcellular location: Cell projection, axon {ECO:0000269|PubMed:15625192}. Perikaryon {ECO:0000269|PubMed:15625192}. Note=Localizes to post-synaptic regions and is enriched in punctate structures in AWC neuron axon where co-localizes with tir-1. Localization is regulated by tir-1. {ECO:0000269|PubMed:15625192}.
Interaction partners:
- Dual specificity mitogen-activated protein kinase kinase sek-1
- Thioredoxin
- Thioredoxin domain-containing protein
- Serine/threonine-protein phosphatase 5
- Dual specificity mitogen-activated protein kinase kinase mek-1
- Serine/threonine-protein kinase akt-2
- Serine/threonine-protein kinase akt-1
- NAD
- BZIP domain-containing protein.
- Probable thioredoxin-2
Sequence:
MSQNNKRQVQHNHEMSNDVCPLPLPPRGAPPPTAYHASRMAATSSSTNGSFEKSAIPGNARKLHVVIVIDQKVQKNLRVREMALKDVQKVADTLNVNLTRIDFDKLDFGETETLDLFYNADVALVDVTVTHQQPSLCYHIGVRESMGQSYNMILTYWSPDPEYHIMDALKKTHAHLPMIVYIHHQDSNQLQSYDKNNNDDDSKPPFARTNVPAKTITFQHRMKQVLKSVQVEASAHSREKFMSDLRKAREITDGDQKNDYLDKMRTRLDNPDVLHPDTVSLMMLSYRDNQNYGGMIRLVDDLKRIPDCLKVVDTPVIRYQYAFALNRRNKDGDRDLALNTVLSLVEGTTENEEKNGPLSPDVVCLAGRIYKDKFIASNYEDRESLNSAIEWYRRAFEMSPLEYSGINLTTLLRASGEHFENNLEMQQIAVVLNSLLGRKGALQNLMEYWDVATYFEVSVLAENYQKACEAALMMVKLKPPVWYLKSTMENIKLINRCAATISPIEKEKQQFLFWSEFFMEATEADTDISCPRYPVLILELNKEFTPSYLTLNNEEGTVILSHVLENSQQKKIHQSELRGIHRWHFARNNIKAVTESKRDDRQLFLYVHENSDDFNLLFPTKAHCKKAYDDMKSMADVADGNYQGRVLSNPDNEKIRFEYELSNSNERVVLGKGTYGTVYAARDMDTQRQIVVKEIEVKYDEEVQPLMEEISLHSTLCHANIVQYLGCDLVGKDGSNDHFLIFMEHVPGGSLSSLLRSKWGPMNENAMNYYGKQILEGLKYLHELKIVHRDIKGDNVLVNTYSGVCKISDFGTCKRLAGLNPVTETFTGTLQYMAPEVIDHGQRGYGAPADIWSFGCTMVEMATGRPPFVEMQNPQAAMFRVGMFKTHPPIPTEITEKCRNFIKSCFLPEACDRPSAKDLLQDPFIYHNHHSISRTRSGSINKKPATKIELNHDKEKKEKSKNQREMLRSTSHIGGMGVVERSPPTPEPMSATLTAGFSHVHSQTVSNALSTAREEKKLHLKIDHARNRTFSSSSPVPDGQSSAGTNMSHPGFQLSQPSSPIVDDTNHPHLIVSPISLNTMGSPLSSAALLNRTISDESSNSSSRFFMLQKDSERRRSLGQFMQDYKDLIIDSWSTLLIKQSDTELVVTVYMLEMLLDGMRDFLLKKDNTKMQKMIDDIRGLLDYDTAKIGQINLALYHFSDSIQPVLRRLDIKPHWMFALSNLITSAVQCAISILSPDLSLLLHAQDNLPSTSSIVAIRNSSLSEGEALIESRPPSREERVREDRKELRTLQEENEILIERLLQVERELNAQLKSGITRANRFRDFAMYRNTYPPFRTPPVAHAPPTPPFSASCGAQPSGTFTNQPPSFASIKPIAQKIIMPPGTENNYQVTRVQEELVSWLRGLEIDERSIALIASEAYTKSDMMDFVTRDELLSIGVGGGSSCRIMRAIGEVRERQRRQPVFLSPMRSRDDSLDDYHSSSADDMYTGAAAETSSGN