C-Jun-amino-terminal kinase-interacting protein 1


NameC-Jun-amino-terminal kinase-interacting protein 1
SynonymsIB-1 IB1 Islet-brain 1 JIP-1 JIP1 JNK MAP kinase scaffold protein 1 Mitogen-activated protein kinase 8-interacting protein 1 PRKM8IP
Gene NameMAPK8IP1
OrganismHuman
Amino acid sequence
>lcl|BSEQ0019471|C-Jun-amino-terminal kinase-interacting protein 1
MAERESGGLGGGAASPPAASPFLGLHIASPPNFRLTHDISLEEFEDEDLSEITDECGISL
QCKDTLSLRPPRAGLLSAGGGGAGSRLQAEMLQMDLIDATGDTPGAEDDEEDDDEERAAR
RPGAGPPKAESGQEPASRGQGQSQGQSQGPGSGDTYRPKRPTTLNLFPQVPRSQDTLNNN
SLGKKHSWQDRVSRSSSPLKTGEQTPPHEHICLSDELPPQSGPAPTTDRGTSTDSPCRRS
TATQMAPPGGPPAAPPGGRGHSHRDRIHYQADVRLEATEEIYLTPVQRPPDAAEPTSAFL
PPTESRMSVSSDPDPAAYPSTAGRPHPSISEEEEGFDCLSSPERAEPPGGGWRGSLGEPP
PPPRASLSSDTSALSYDSVKYTLVVDEHAQLELVSLRPCFGDYSDESDSATVYDNCASVS
SPYESAIGEEYEEAPRPQPPACLSEDSTPDEPDVHFSKKFLNVFMSGRSRSSSAESFGLF
SCIINGEEQEQTHRAIFRFVPRHEDELELEVDDPLLVELQAEDYWYEAYNMRTGARGVFP
AYYAIEVTKEPEHMAALAKNSDWVDQFRVKFLGSVQVPYHKGNDVLCAAMQKIATTRRLT
VHFNPPSSCVLEISVRGVKIGVKADDSQEAKGNKCSHFFQLKNISFCGYHPKNNKYFGFI
TKHPADHRFACHVFVSEDSTKALAESVGRAFQQFYKQFVEYTCPTEDIYLE
Number of residues711
Molecular Weight77523.56
Theoretical pI4.61
GO Classification
Functions
    protein kinase inhibitor activity
    kinesin binding
    MAP-kinase scaffold activity
Processes
    regulation of transcription, DNA-templated
    negative regulation of intrinsic apoptotic signaling pathway
    positive regulation of signal transduction
    regulation of JNK cascade
    vesicle-mediated transport
    negative regulation of cyclin-dependent protein kinase activity
    JUN phosphorylation
Components
    dentate gyrus mossy fiber
    dendrite
    synapse
    cytoplasm
    cell body
    nucleus
    endoplasmic reticulum membrane
    mitochondrial membrane
    cytosol
    perinuclear region of cytoplasm
General FunctionProtein kinase inhibitor activity
Specific FunctionThe JNK-interacting protein (JIP) group of scaffold proteins selectively mediates JNK signaling by aggregating specific components of the MAPK cascade to form a functional JNK signaling module. Required for JNK activation in response to excitotoxic stress. Cytoplasmic MAPK8IP1 causes inhibition of JNK-regulated activity by retaining JNK in the cytoplasm and inhibiting JNK phosphorylation of c-Jun. May also participate in ApoER2-specific reelin signaling. Directly, or indirectly, regulates GLUT2 gene expression and beta-cell function. Appears to have a role in cell signaling in mature and developing nerve terminals. May function as a regulator of vesicle transport, through interactions with the JNK-signaling components and motor proteins (By similarity). Functions as an anti-apoptotic protein and whose level seems to influence the beta-cell death or survival response.
Transmembrane Regions
GenBank Protein ID4426597
UniProtKB IDQ9UQF2
UniProtKB Entry NameJIP1_HUMAN
Cellular LocationCytoplasm
Gene sequence
>lcl|BSEQ0019472|C-Jun-amino-terminal kinase-interacting protein 1 (MAPK8IP1)
ATGGCGGAGCGAGAAAGCGGCGGCCTGGGAGGGGGGGCCGCGTCCCCGCCCGCCGCCTCC
CCGTTCCTGGGGCTGCACATCGCTTCGCCTCCCAATTTCAGGCTCACCCATGACATCAGC
CTGGAGGAGTTTGAGGATGAAGACCTCTCGGAGATCACTGATGAGTGTGGCATCAGCTTA
CAGTGCAAAGACACCCTGTCCTTACGGCCCCCGCGCGCCGGGCTGCTCTCTGCGGGCGGC
GGCGGCGCGGGGAGCCGGTTGCAGGCCGAGATGCTGCAGATGGACCTGATCGACGCGACG
GGGGACACTCCCGGGGCCGAGGACGACGAGGAGGACGACGACGAGGAGCGCGCGGCCCGG
CGGCCGGGAGCGGGGCCGCCCAAGGCCGAGTCCGGCCAGGAGCCGGCGTCCCGCGGCCAG
GGCCAGAGCCAAGGCCAGAGCCAGGGCCCGGGCAGCGGGGACACGTACCGGCCCAAGCGG
CCCACCACGCTCAACCTCTTTCCGCAGGTGCCGCGGTCTCAGGACACACTGAATAATAAT
TCTCTGGGCAAAAAGCACAGTTGGCAGGATCGGGTGTCTCGATCATCCTCACCCCTGAAG
ACAGGGGAGCAGACACCACCGCATGAACACATCTGCCTGAGCGATGAGCTGCCCCCCCAG
AGCGGCCCCGCCCCCACCACAGATCGAGGCACCTCCACCGACAGCCCTTGCCGCCGCAGC
ACAGCCACCCAGATGGCACCTCCGGGTGGTCCCCCTGCTGCCCCGCCTGGGGGTCGGGGC
CACTCGCATCGAGACCGAATCCACTACCAGGCCGATGTGCGACTAGAGGCCACTGAGGAG
ATCTACCTGACCCCAGTGCAGAGGCCCCCAGACGCTGCAGAGCCCACCTCCGCCTTCCTG
CCGCCCACTGAGAGCCGGATGTCAGTCAGCTCCGATCCAGACCCTGCCGCCTACCCCTCC
ACGGCAGGGCGGCCGCACCCCTCCATCAGTGAAGAGGAAGAGGGCTTCGACTGCCTGTCG
TCCCCAGAGCGGGCTGAGCCCCCAGGCGGAGGGTGGCGGGGGAGCCTGGGGGAGCCGCCG
CCACCTCCACGGGCCTCTCTGAGCTCGGACACCAGCGCCCTGTCCTATGACTCTGTCAAG
TACACGCTGGTGGTAGATGAGCATGCACAGCTGGAGCTGGTGAGCCTGCGGCCGTGCTTC
GGAGACTACAGTGACGAGAGTGACTCTGCCACCGTCTATGACAACTGTGCCTCCGTCTCC
TCGCCCTATGAGTCGGCCATCGGAGAGGAATATGAGGAGGCCCCGCGGCCCCAGCCCCCT
GCCTGCCTCTCCGAGGACTCCACGCCTGATGAACCCGACGTCCATTTCTCCAAGAAATTC
CTGAACGTCTTCATGAGTGGCCGCTCCCGCTCCTCCAGTGCTGAGTCCTTCGGGCTGTTC
TCCTGCATCATCAACGGGGAGGAGCAGGAGCAGACCCACCGGGCCATATTCAGGTTTGTG
CCTCGACACGAAGACGAACTTGAGCTGGAAGTGGATGACCCTCTGCTAGTGGAGCTCCAG
GCTGAAGACTACTGGTACGAGGCCTACAACATGCGCACTGGTGCCCGGGGTGTCTTTCCT
GCCTATTACGCCATCGAGGTCACCAAGGAGCCCGAGCACATGGCAGCCCTGGCCAAAAAC
AGTGACTGGGTGGACCAGTTCCGGGTGAAGTTCCTGGGCTCAGTCCAGGTTCCCTATCAC
AAGGGCAATGACGTCCTCTGTGCTGCTATGCAAAAGATTGCCACCACCCGCCGGCTCACC
GTGCACTTTAACCCGCCCTCCAGCTGTGTCCTGGAGATCAGCGTGCGGGGTGTGAAGATA
GGCGTCAAGGCCGATGACTCCCAGGAGGCCAAGGGGAATAAATGTAGCCACTTTTTCCAG
TTAAAAAACATCTCTTTCTGCGGATATCATCCAAAGAACAACAAGTACTTTGGGTTCATC
ACCAAGCACCCCGCCGACCACCGGTTTGCCTGCCACGTCTTTGTGTCTGAAGACTCCACC
AAAGCCCTGGCAGAGTCCGTGGGGAGAGCATTCCAGCAGTTCTACAAGCAGTTTGTGGAG
TACACCTGCCCCACAGAAGATATCTACCTGGAGTAG
GenBank Gene IDAF074091
GeneCard IDNone
GenAtlas ID
HGNC IDHGNC:6882
Chromosome Location11
Locus11p12-p11.2
References
  1. Mooser V, Maillard A, Bonny C, Steinmann M, Shaw P, Yarnall DP, Burns DK, Schorderet DF, Nicod P, Waeber G: Genomic organization, fine-mapping, and expression of the human islet-brain 1 (IB1)/c-Jun-amino-terminal kinase interacting protein-1 (JIP-1) gene. Genomics. 1999 Jan 15;55(2):202-8.[9933567 ]
  2. Meyer D, Liu A, Margolis B: Interaction of c-Jun amino-terminal kinase interacting protein-1 with p190 rhoGEF and its localization in differentiated neurons. J Biol Chem. 1999 Dec 3;274(49):35113-8.[10574993 ]
  3. Verhey KJ, Meyer D, Deehan R, Blenis J, Schnapp BJ, Rapoport TA, Margolis B: Cargo of kinesin identified as JIP scaffolding proteins and associated signaling molecules. J Cell Biol. 2001 Mar 5;152(5):959-70.[11238452 ]
  4. Ikeda A, Hasegawa K, Masaki M, Moriguchi T, Nishida E, Kozutsumi Y, Oka S, Kawasaki T: Mixed lineage kinase LZK forms a functional signaling complex with JIP-1, a scaffold protein of the c-Jun NH(2)-terminal kinase pathway. J Biochem. 2001 Dec;130(6):773-81.[11726277 ]
  5. Taru H, Iijima K, Hase M, Kirino Y, Yagi Y, Suzuki T: Interaction of Alzheimer's beta -amyloid precursor family proteins with scaffold proteins of the JNK signaling cascade. J Biol Chem. 2002 May 31;277(22):20070-8. Epub 2002 Mar 22.[11912189 ]
  6. Nihalani D, Wong HN, Holzman LB: Recruitment of JNK to JIP1 and JNK-dependent JIP1 phosphorylation regulates JNK module dynamics and activation. J Biol Chem. 2003 Aug 1;278(31):28694-702. Epub 2003 May 19.[12756254 ]
  7. Bonny C, Oberson A, Negri S, Sauser C, Schorderet DF: Cell-permeable peptide inhibitors of JNK: novel blockers of beta-cell death. Diabetes. 2001 Jan;50(1):77-82.[11147798 ]
  8. Allaman-Pillet N, Storling J, Oberson A, Roduit R, Negri S, Sauser C, Nicod P, Beckmann JS, Schorderet DF, Mandrup-Poulsen T, Bonny C: Calcium- and proteasome-dependent degradation of the JNK scaffold protein islet-brain 1. J Biol Chem. 2003 Dec 5;278(49):48720-6. Epub 2003 Sep 24.[14507925 ]
  9. Borsello T, Clarke PG, Hirt L, Vercelli A, Repici M, Schorderet DF, Bogousslavsky J, Bonny C: A peptide inhibitor of c-Jun N-terminal kinase protects against excitotoxicity and cerebral ischemia. Nat Med. 2003 Sep;9(9):1180-6. Epub 2003 Aug 24.[12937412 ]
  10. D'Ambrosio C, Arena S, Fulcoli G, Scheinfeld MH, Zhou D, D'Adamio L, Scaloni A: Hyperphosphorylation of JNK-interacting protein 1, a protein associated with Alzheimer disease. Mol Cell Proteomics. 2006 Jan;5(1):97-113. Epub 2005 Sep 29.[16195223 ]
  11. Blanco S, Santos C, Lazo PA: Vaccinia-related kinase 2 modulates the stress response to hypoxia mediated by TAK1. Mol Cell Biol. 2007 Oct;27(20):7273-83. Epub 2007 Aug 20.[17709393 ]
  12. Blanco S, Sanz-Garcia M, Santos CR, Lazo PA: Modulation of interleukin-1 transcriptional response by the interaction between VRK2 and the JIP1 scaffold protein. PLoS One. 2008 Feb 20;3(2):e1660. doi: 10.1371/journal.pone.0001660.[18286207 ]
  13. Waeber G, Delplanque J, Bonny C, Mooser V, Steinmann M, Widmann C, Maillard A, Miklossy J, Dina C, Hani EH, Vionnet N, Nicod P, Boutin P, Froguel P: The gene MAPK8IP1, encoding islet-brain-1, is a candidate for type 2 diabetes. Nat Genet. 2000 Mar;24(3):291-5.[10700186 ]

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