Protein
Mitogen-activated protein kinase kinase kinase 5
Function
Serine/threonine kinase which acts as an essential component of the MAP kinase signal transduction pathway. Plays an important role in the cascades of cellular responses evoked by changes in the environment. Mediates signaling for determination of cell fate such as differentiation and survival. Plays a crucial role in the apoptosis signal transduction pathway through mitochondria-dependent caspase activation. MAP3K5/ASK1 is required for the innate immune response, which is essential for host defense against a wide range of pathogens. Mediates signal transduction of various stressors like oxidative stress as well as by receptor-mediated inflammatory signals, such as the tumor necrosis factor (TNF) or lipopolysaccharide (LPS). Once activated, acts as an upstream activator of the MKK/JNK signal transduction cascade and the p38 MAPK signal transduction cascade through the phosphorylation and activation of several MAP kinase kinases like MAP2K4/SEK1, MAP2K3/MKK3, MAP2K6/MKK6 and MAP2K7/MKK7. These MAP2Ks in turn activate p38 MAPKs and c-jun N-terminal kinases (JNKs). Both p38 MAPK and JNKs control the transcription factors activator protein-1 (AP-1).
Similarity
Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. MAP kinase kinase kinase subfamily.
Sequence
MGTEAGEGITFSVPPFASVGFCTIPEGGSCRRGGGAATAAEGEPSLQPLLVPPPPPPPGSFWNVESAAAPGTSCPTTAPGSSATRGRGNSGSGGGRRTTVAYVINEASQGQLVVAESEALQSLREACEAVGATLETLHFGKLDFGETAVLDRFYNADIAVVEMSDAFRQPSLFYHLGVRESFSMANNIILYCDTNSDSLQSLKEIICQKNTVCTGNYTFIPYMVTPHNKVYCCDSSFMKGLTELMQPNFELLLGPICLPLVDRFVQLLKVAQASSSQYFRESILSDIRKARNLYTGKELAAELARIRQRVDNIEVLTADIVINLLLSYRDIQDYDSIVKLVETLEKLPTFDLASHHHVKFHYAFALNRRNLPGDRAKALDIMIPMVQSEEQVASDMYCLVGRIYKDMFLDSNFTDTESRDHGASWFKKAFESEPTLQSGINYAVLLLAAGHQFESSFELRKVGVKLSSLLGKKGNLEKLQSYWEVGFFLGASVLANDHLRVIQASEKLFRLKTPAWYLKSIVETILIYKHFVKLTTEQPSAKQELVDFWMDFLVEATKTDVTVVRFPVLILEPTKIYQPSYLSINNEVEEKTISIWHVLPDDKKGIHEWNFGASSVRGVSISKFEERCCFLYVLHNSDDFQIYFCTELHCKRFFEMVNTITEEKGRGAEDGDCEGDSLEYDYEYDENGDRVVLGKGTYGIVYAGRDLSNQVRIAIKEIPERDSRYSQPLHEEIALHKHLKHKNIVQYLGSFSENGFIKIFMEQVPGGSLSALLRSKWGPLKDNEQTIGFYTKQILEGLKYLHDNQIVHRDIKGDNVLINTYSGVLKISDFGTSKRLAGINPCTETFTGTLQYMAPEIIDKGPRGYGKAADIWSLGCTIIEMATGKPPFYELGEPQAAMFKVGMFKVHPEIPESMSAEAKAFILKCFEPDPDKRACANDLLIDEFLKVSSKKKKTQPKLSALSTGSNEYLRSISLPVPVLVEDTSSSSEYGSVSPDTELKADPFSFKARAKSCGEKDGKGIRTLFLGIPDENFEDHSAPPSPEEKDSGFFMLRKDSERRATLHRILTEDQDKVVRNLMESLAQGAEEPKLKWEHITTLISSLREFVRSTDRKIIATTLSKLKLELDFDSHGISQVQVVLFGFQDAVNKVLRNHNIKPHWMFALDSIIRKAVQTAITILVPELRPHFSLASESDTADPEDLDVEDEHEELSSNQTVRRPQAITEDAVATSGVSTLSSTVSHDSQNAHRSLNVQLGRMKIETNRLLEELVRKERELQALLHQAIEEKDQEIRHLKLKSQPIDIPGFPVCHLNSPGTTTEDSELPGWLRENGADEDTISRFLAEDYTLVDVLYYVTRDDLKCLRLRGGMLCTLWKAIIDFRNKC