JIP1_HUMAN
ID JIP1_HUMAN Reviewed; 711 AA.
AC Q9UQF2; D3DQP4; O43407;
DT 05-DEC-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 202.
DE RecName: Full=C-Jun-amino-terminal kinase-interacting protein 1;
DE Short=JIP-1;
DE Short=JNK-interacting protein 1;
DE AltName: Full=Islet-brain 1;
DE Short=IB-1;
DE AltName: Full=JNK MAP kinase scaffold protein 1;
DE AltName: Full=Mitogen-activated protein kinase 8-interacting protein 1;
GN Name=MAPK8IP1; Synonyms=IB1, JIP1, PRKM8IP;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Insulinoma;
RX PubMed=9933567; DOI=10.1006/geno.1998.5641;
RA Mooser V., Maillard A., Bonny C., Steinmann M., Shaw P., Yarnall D.P.,
RA Burns D.K., Schorderet D.F., Nicod P., Waeber G.;
RT "Genomic organization, fine-mapping, and expression of the human islet-
RT brain 1 (IB1)/C-jun-amino-terminal kinase interacting protein-1 (JIP-1)
RT gene.";
RL Genomics 55:202-208(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 468-711.
RC TISSUE=Brain;
RA Yu W., Sarginson J., Gibbs R.A.;
RL Submitted (JUN-1997) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP INTERACTION WITH ARHGEF28, AND SUBCELLULAR LOCATION.
RX PubMed=10574993; DOI=10.1074/jbc.274.49.35113;
RA Meyer D., Liu A., Margolis B.;
RT "Interaction of c-Jun amino-terminal kinase interacting protein-1 with p190
RT rhoGEF and its localization in differentiated neurons.";
RL J. Biol. Chem. 274:35113-35118(1999).
RN [5]
RP MUTAGENESIS, AND INTERACTION WITH KINESIN.
RX PubMed=11238452; DOI=10.1083/jcb.152.5.959;
RA Verhey K.J., Meyer D., Deehan R., Blenis J., Schnapp B.J., Rapoport T.A.,
RA Margolis B.;
RT "Cargo of kinesin identified as JIP scaffolding proteins and associated
RT signaling molecules.";
RL J. Cell Biol. 152:959-970(2001).
RN [6]
RP INTERACTION WITH MAP3K13.
RX PubMed=11726277; DOI=10.1093/oxfordjournals.jbchem.a003048;
RA Ikeda A., Hasegawa K., Masaki M., Moriguchi T., Nishida E., Kozutsumi Y.,
RA Oka S., Kawasaki T.;
RT "Mixed lineage kinase LZK forms a functional signaling complex with JIP-1,
RT a scaffold protein of the c-Jun NH(2)-terminal kinase pathway.";
RL J. Biochem. 130:773-781(2001).
RN [7]
RP INTERACTION WITH APP.
RX PubMed=11912189; DOI=10.1074/jbc.m108372200;
RA Taru H., Iijima K., Hase M., Kirino Y., Yagi Y., Suzuki T.;
RT "Interaction of Alzheimer's beta-amyloid precursor family proteins with
RT scaffold proteins of the JNK signaling cascade.";
RL J. Biol. Chem. 277:20070-20078(2002).
RN [8]
RP PHOSPHORYLATION AT THR-103 AND THR-205, AND MUTAGENESIS OF ARG-160 AND
RP PRO-161.
RX PubMed=12756254; DOI=10.1074/jbc.m304212200;
RA Nihalani D., Wong H.N., Holzman L.B.;
RT "Recruitment of JNK to JIP1 and JNK-dependent JIP1 phosphorylation
RT regulates JNK module dynamics and activation.";
RL J. Biol. Chem. 278:28694-28702(2003).
RN [9]
RP PEPTIDE INHIBITORS OF JNK.
RX PubMed=11147798; DOI=10.2337/diabetes.50.1.77;
RA Bonny C., Oberson A., Negri S., Sauser C., Schorderet D.F.;
RT "Cell-permeable peptide inhibitors of JNK: novel blockers of beta-cell
RT death.";
RL Diabetes 50:77-82(2001).
RN [10]
RP CALCIUM- AND PROTEASOME-DEPENDENT DEGRADATION.
RX PubMed=14507925; DOI=10.1074/jbc.m306745200;
RA Allaman-Pillet N., Storling J., Oberson A., Roduit R., Negri S., Sauser C.,
RA Nicod P., Beckmann J.S., Schorderet D.F., Mandrup-Poulsen T., Bonny C.;
RT "Calcium- and proteasome-dependent degradation of the JNK scaffold protein
RT islet-brain 1.";
RL J. Biol. Chem. 278:48720-48726(2003).
RN [11]
RP PROTECTION AGAINST EXCITOTOXICITY AND CEREBRAL ISCHEMIA.
RX PubMed=12937412; DOI=10.1038/nm911;
RA Borsello T., Clarke P.G., Hirt L., Vercelli A., Repici M., Schorderet D.F.,
RA Bogousslavsky J., Bonny C.;
RT "A peptide inhibitor of c-Jun N-terminal kinase protects against
RT excitotoxicity and cerebral ischemia.";
RL Nat. Med. 9:1180-1186(2003).
RN [12]
RP PHOSPHORYLATION AT SER-40; SER-152; SER-181; SER-187; SER-193; SER-195;
RP SER-196; SER-214; SER-311; SER-328; SER-330; SER-340; SER-355; SER-366;
RP SER-369; SER-407; SER-409; THR-411; SER-444; SER-447; THR-448; SER-469;
RP SER-471; SER-472 AND SER-473.
RX PubMed=16195223; DOI=10.1074/mcp.m500226-mcp200;
RA D'Ambrosio C., Arena S., Fulcoli G., Scheinfeld M.H., Zhou D., D'Adamio L.,
RA Scaloni A.;
RT "Hyperphosphorylation of JNK-interacting protein 1, a protein associated
RT with Alzheimer disease.";
RL Mol. Cell. Proteomics 5:97-113(2006).
RN [13]
RP INTERACTION WITH MAP3K7.
RX PubMed=17709393; DOI=10.1128/mcb.00025-07;
RA Blanco S., Santos C., Lazo P.A.;
RT "Vaccinia-related kinase 2 modulates the stress response to hypoxia
RT mediated by TAK1.";
RL Mol. Cell. Biol. 27:7273-7283(2007).
RN [14]
RP SUBCELLULAR LOCATION, INTERACTION WITH VRK2, AND PHOSPHORYLATION.
RX PubMed=18286207; DOI=10.1371/journal.pone.0001660;
RA Blanco S., Sanz-Garcia M., Santos C.R., Lazo P.A.;
RT "Modulation of interleukin-1 transcriptional response by the interaction
RT between VRK2 and the JIP1 scaffold protein.";
RL PLoS ONE 3:E1660-E1660(2008).
RN [15]
RP VARIANT NIDDM ASN-59.
RX PubMed=10700186; DOI=10.1038/73523;
RA Waeber G., Delplanque J., Bonny C., Mooser V., Steinmann M., Widmann C.,
RA Maillard A., Miklossy J., Dina C., Hani E.H., Vionnet N., Nicod P.,
RA Boutin P., Froguel P.;
RT "The gene, MAPK8IP1, encoding islet-brain-1, is a candidate for type 2
RT diabetes.";
RL Nat. Genet. 24:291-295(2000).
CC -!- FUNCTION: The JNK-interacting protein (JIP) group of scaffold proteins
CC selectively mediates JNK signaling by aggregating specific components
CC of the MAPK cascade to form a functional JNK signaling module. Required
CC for JNK activation in response to excitotoxic stress. Cytoplasmic
CC MAPK8IP1 causes inhibition of JNK-regulated activity by retaining JNK
CC in the cytoplasm and inhibiting JNK phosphorylation of c-Jun. May also
CC participate in ApoER2-specific reelin signaling. Directly, or
CC indirectly, regulates GLUT2 gene expression and beta-cell function.
CC Appears to have a role in cell signaling in mature and developing nerve
CC terminals. May function as a regulator of vesicle transport, through
CC interactions with the JNK-signaling components and motor proteins.
CC Functions as an anti-apoptotic protein and whose level seems to
CC influence the beta-cell death or survival response. Acts as a scaffold
CC protein that coordinates with SH3RF1 in organizing different components
CC of the JNK pathway, including RAC1 or RAC2, MAP3K11/MLK3 or
CC MAP3K7/TAK1, MAP2K7/MKK7, MAPK8/JNK1 and/or MAPK9/JNK2 into a
CC functional multiprotein complex to ensure the effective activation of
CC the JNK signaling pathway. Regulates the activation of MAPK8/JNK1 and
CC differentiation of CD8(+) T-cells. {ECO:0000250|UniProtKB:Q9WVI9}.
CC -!- SUBUNIT: Forms homo- or heterooligomeric complexes. Binds specific
CC components of the JNK signaling pathway namely, MAPK8/JNK1, MAPK9/JNK2,
CC MAPK10/JNK3, MAP2K7/MKK7, MAP3K11/MLK3 and DLK1. Also binds the
CC proline-rich domain-containing splice variant of apolipoprotein E
CC receptor 2 (ApoER2). Interacts, via the PID domain, with ARHGEF28.
CC Binds the cytoplasmic tails of LRP1 and LRP2 (Megalin). Binds the TPR
CC motif-containing C-terminal of KNS2, then the pre-assembled MAPK8IP1
CC scaffolding complexes are transported as a cargo of kinesin, to the
CC required subcellular location. Interacts with the cytoplasmic domain of
CC APP. Interacts with DCLK2 (By similarity). Interacts with MAP3K7/TAK1.
CC Interacts with isoform 1 and isoform 2 of VRK2. Found in a complex with
CC SH3RF1, RAC1, MAP3K11/MLK3, MAP2K7/MKK7 and MAPK8/JNK1. Found in a
CC complex with SH3RF1, RAC2, MAP3K7/TAK1, MAP2K7/MKK7, MAPK8/JNK1 and
CC MAPK9/JNK2. Interacts with SH3RF2 (By similarity).
CC {ECO:0000250|UniProtKB:Q9R237, ECO:0000250|UniProtKB:Q9WVI9,
CC ECO:0000269|PubMed:10574993, ECO:0000269|PubMed:11238452,
CC ECO:0000269|PubMed:11726277, ECO:0000269|PubMed:11912189,
CC ECO:0000269|PubMed:17709393, ECO:0000269|PubMed:18286207}.
CC -!- INTERACTION:
CC Q9UQF2; P00533: EGFR; NbExp=3; IntAct=EBI-78404, EBI-297353;
CC Q9UQF2; P04626: ERBB2; NbExp=4; IntAct=EBI-78404, EBI-641062;
CC Q9UQF2; O14733: MAP2K7; NbExp=5; IntAct=EBI-78404, EBI-492605;
CC Q9UQF2; O43318: MAP3K7; NbExp=11; IntAct=EBI-78404, EBI-358684;
CC Q9UQF2; P45983: MAPK8; NbExp=7; IntAct=EBI-78404, EBI-286483;
CC Q9UQF2; P12023: App; Xeno; NbExp=2; IntAct=EBI-78404, EBI-78814;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Cytoplasm, perinuclear
CC region {ECO:0000250}. Nucleus {ECO:0000250}. Endoplasmic reticulum
CC membrane. Mitochondrion membrane. Note=Accumulates in cell surface
CC projections. Under certain stress conditions, translocates to the
CC perinuclear region of neurons. In insulin-secreting cells, detected in
CC both the cytoplasm and nucleus (By similarity). {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Highly expressed in brain. Expressed in neurons,
CC localizing to neurite tips in differentiating cells. Also expressed in
CC the pancreas, testis and prostate. Low levels in heart, ovary and small
CC intestine. Decreased levels in pancreatic beta cells sensitize cells to
CC IL-1-beta-induced apoptosis.
CC -!- DOMAIN: The destruction boxes (D-box) may act as recognition signals
CC for degradation via the ubiquitin-proteasome pathway.
CC -!- DOMAIN: A minimal inhibitory domain prevents pancreatic beta cell
CC apoptosis in vitro, and prevents activation of c-jun by MAPK8, MAPK9
CC and MAPK10.
CC -!- DOMAIN: The SH3 domain mediates homodimerization. {ECO:0000250}.
CC -!- PTM: Phosphorylated by MAPK8, MAPK9 and MAPK10. Phosphorylation on Thr-
CC 103 is also necessary for the dissociation and activation of MAP3K12.
CC Phosphorylated by isoform 1 and isoform 2 of VRK2. Hyperphosphorylated
CC during mitosis following activation of stress-activated and MAP
CC kinases. {ECO:0000269|PubMed:12756254}.
CC -!- PTM: Ubiquitinated. Two preliminary events are required to prime for
CC ubiquitination; phosphorylation and an increased in intracellular
CC calcium concentration. Then, the calcium influx initiates
CC ubiquitination and degradation by the ubiquitin-proteasome pathway.
CC -!- DISEASE: Diabetes mellitus, non-insulin-dependent (NIDDM) [MIM:125853]:
CC A multifactorial disorder of glucose homeostasis caused by a lack of
CC sensitivity to the body's own insulin. Affected individuals usually
CC have an obese body habitus and manifestations of a metabolic syndrome
CC characterized by diabetes, insulin resistance, hypertension and
CC hypertriglyceridemia. The disease results in long-term complications
CC that affect the eyes, kidneys, nerves, and blood vessels.
CC {ECO:0000269|PubMed:10700186}. Note=The disease may be caused by
CC variants affecting the gene represented in this entry.
CC -!- MISCELLANEOUS: A chemically synthesized cell-permeable peptide of the
CC minimal inhibitory domain decreases brain lesions in both transient and
CC permanent ischemia. The level of protection is still high when
CC administered 6 or 12 hours after ischemia.
CC -!- SIMILARITY: Belongs to the JIP scaffold family. {ECO:0000305}.
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DR EMBL; AF074091; AAD20443.1; -; mRNA.
DR EMBL; CH471064; EAW68027.1; -; Genomic_DNA.
DR EMBL; CH471064; EAW68028.1; -; Genomic_DNA.
DR EMBL; AF007134; AAC19150.1; -; mRNA.
DR CCDS; CCDS7916.1; -.
DR RefSeq; NP_005447.1; NM_005456.3.
DR PDB; 2G01; X-ray; 3.50 A; F/G=157-167.
DR PDB; 2GMX; X-ray; 3.50 A; F/G=157-167.
DR PDB; 2H96; X-ray; 3.00 A; F/G=157-167.
DR PDB; 3OXI; X-ray; 2.20 A; J=158-167.
DR PDB; 3PTG; X-ray; 2.43 A; J=157-167.
DR PDB; 3VUD; X-ray; 3.50 A; F=157-167.
DR PDB; 3VUG; X-ray; 3.24 A; F=157-167.
DR PDB; 3VUH; X-ray; 2.70 A; F=157-167.
DR PDB; 3VUI; X-ray; 2.80 A; F=157-167.
DR PDB; 3VUK; X-ray; 2.95 A; F=157-167.
DR PDB; 3VUL; X-ray; 2.81 A; F=157-167.
DR PDB; 3VUM; X-ray; 2.69 A; F=157-167.
DR PDB; 4E73; X-ray; 2.27 A; B=158-167.
DR PDB; 4G1W; X-ray; 2.45 A; B=157-167.
DR PDB; 4H39; X-ray; 1.99 A; B=158-167.
DR PDB; 4HYS; X-ray; 2.42 A; B=157-167.
DR PDB; 4HYU; X-ray; 2.15 A; B=157-167.
DR PDB; 4IZY; X-ray; 2.30 A; B=157-167.
DR PDB; 5LW1; X-ray; 3.20 A; C/F/I=157-167.
DR PDB; 6FUZ; X-ray; 2.70 A; A=701-711.
DR PDB; 7NYK; X-ray; 1.45 A; AAA/BBB/CCC/DDD=490-549.
DR PDB; 7NYL; X-ray; 1.95 A; AAA/BBB=490-549.
DR PDB; 7NYM; X-ray; 1.61 A; AAA/BBB/CCC/DDD=490-549.
DR PDB; 7NYN; X-ray; 1.54 A; AAA/BBB/CCC/DDD/EEE/FFF/GGG/HHH/III/JJJ/KKK/LLL=490-549.
DR PDB; 7NYO; X-ray; 1.40 A; AAA/BBB/CCC/DDD=490-549.
DR PDB; 7NZB; X-ray; 1.96 A; AAA/BBB/CCC/DDD/EEE/FFF/GGG/HHH/III/JJJ/KKK/LLL=490-549.
DR PDBsum; 2G01; -.
DR PDBsum; 2GMX; -.
DR PDBsum; 2H96; -.
DR PDBsum; 3OXI; -.
DR PDBsum; 3PTG; -.
DR PDBsum; 3VUD; -.
DR PDBsum; 3VUG; -.
DR PDBsum; 3VUH; -.
DR PDBsum; 3VUI; -.
DR PDBsum; 3VUK; -.
DR PDBsum; 3VUL; -.
DR PDBsum; 3VUM; -.
DR PDBsum; 4E73; -.
DR PDBsum; 4G1W; -.
DR PDBsum; 4H39; -.
DR PDBsum; 4HYS; -.
DR PDBsum; 4HYU; -.
DR PDBsum; 4IZY; -.
DR PDBsum; 5LW1; -.
DR PDBsum; 6FUZ; -.
DR PDBsum; 7NYK; -.
DR PDBsum; 7NYL; -.
DR PDBsum; 7NYM; -.
DR PDBsum; 7NYN; -.
DR PDBsum; 7NYO; -.
DR PDBsum; 7NZB; -.
DR AlphaFoldDB; Q9UQF2; -.
DR SMR; Q9UQF2; -.
DR BioGRID; 114864; 53.
DR CORUM; Q9UQF2; -.
DR ELM; Q9UQF2; -.
DR IntAct; Q9UQF2; 26.
DR MINT; Q9UQF2; -.
DR STRING; 9606.ENSP00000241014; -.
DR DrugBank; DB07276; 5-CYANO-N-(2,5-DIMETHOXYBENZYL)-6-ETHOXYPYRIDINE-2-CARBOXAMIDE.
DR DrugBank; DB07218; 6-CHLORO-9-HYDROXY-1,3-DIMETHYL-1,9-DIHYDRO-4H-PYRAZOLO[3,4-B]QUINOLIN-4-ONE.
DR DrugBank; DB11157; Anthralin.
DR DrugBank; DB07272; N-(4-AMINO-5-CYANO-6-ETHOXYPYRIDIN-2-YL)-2-(4-BROMO-2,5-DIMETHOXYPHENYL)ACETAMIDE.
DR DrugBank; DB01782; Pyrazolanthrone.
DR GlyGen; Q9UQF2; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q9UQF2; -.
DR PhosphoSitePlus; Q9UQF2; -.
DR BioMuta; MAPK8IP1; -.
DR DMDM; 17433093; -.
DR MassIVE; Q9UQF2; -.
DR PaxDb; Q9UQF2; -.
DR PeptideAtlas; Q9UQF2; -.
DR PRIDE; Q9UQF2; -.
DR ProteomicsDB; 85551; -.
DR Antibodypedia; 26197; 291 antibodies from 33 providers.
DR DNASU; 9479; -.
DR Ensembl; ENST00000241014.6; ENSP00000241014.2; ENSG00000121653.11.
DR GeneID; 9479; -.
DR KEGG; hsa:9479; -.
DR MANE-Select; ENST00000241014.6; ENSP00000241014.2; NM_005456.4; NP_005447.1.
DR UCSC; uc001nbr.4; human.
DR CTD; 9479; -.
DR DisGeNET; 9479; -.
DR GeneCards; MAPK8IP1; -.
DR HGNC; HGNC:6882; MAPK8IP1.
DR HPA; ENSG00000121653; Tissue enhanced (brain, pituitary gland).
DR MalaCards; MAPK8IP1; -.
DR MIM; 125853; phenotype.
DR MIM; 604641; gene.
DR neXtProt; NX_Q9UQF2; -.
DR OpenTargets; ENSG00000121653; -.
DR PharmGKB; PA30626; -.
DR VEuPathDB; HostDB:ENSG00000121653; -.
DR eggNOG; KOG3775; Eukaryota.
DR GeneTree; ENSGT00940000157089; -.
DR HOGENOM; CLU_006711_1_1_1; -.
DR InParanoid; Q9UQF2; -.
DR OMA; GHHRERI; -.
DR OrthoDB; 372907at2759; -.
DR PhylomeDB; Q9UQF2; -.
DR TreeFam; TF325073; -.
DR PathwayCommons; Q9UQF2; -.
DR SignaLink; Q9UQF2; -.
DR SIGNOR; Q9UQF2; -.
DR BioGRID-ORCS; 9479; 17 hits in 1085 CRISPR screens.
DR ChiTaRS; MAPK8IP1; human.
DR EvolutionaryTrace; Q9UQF2; -.
DR GeneWiki; MAPK8IP1; -.
DR GenomeRNAi; 9479; -.
DR Pharos; Q9UQF2; Tbio.
DR PRO; PR:Q9UQF2; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; Q9UQF2; protein.
DR Bgee; ENSG00000121653; Expressed in C1 segment of cervical spinal cord and 107 other tissues.
DR ExpressionAtlas; Q9UQF2; baseline and differential.
DR Genevisible; Q9UQF2; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IEA:Ensembl.
DR GO; GO:0030425; C:dendrite; IEA:Ensembl.
DR GO; GO:0044302; C:dentate gyrus mossy fiber; IEA:Ensembl.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0031966; C:mitochondrial membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0043025; C:neuronal cell body; IEA:Ensembl.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; IDA:HPA.
DR GO; GO:0045202; C:synapse; IEA:Ensembl.
DR GO; GO:0019894; F:kinesin binding; IPI:UniProtKB.
DR GO; GO:0005078; F:MAP-kinase scaffold activity; IPI:UniProtKB.
DR GO; GO:0019901; F:protein kinase binding; IEA:Ensembl.
DR GO; GO:0004860; F:protein kinase inhibitor activity; TAS:ProtInc.
DR GO; GO:0007258; P:JUN phosphorylation; IEA:Ensembl.
DR GO; GO:2001243; P:negative regulation of intrinsic apoptotic signaling pathway; IEA:Ensembl.
DR GO; GO:0043508; P:negative regulation of JUN kinase activity; ISS:UniProtKB.
DR GO; GO:0046330; P:positive regulation of JNK cascade; ISS:UniProtKB.
DR GO; GO:2000564; P:regulation of CD8-positive, alpha-beta T cell proliferation; ISS:UniProtKB.
DR GO; GO:0046328; P:regulation of JNK cascade; ISS:UniProtKB.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; IEA:Ensembl.
DR GO; GO:0016192; P:vesicle-mediated transport; ISS:UniProtKB.
DR CDD; cd11943; SH3_JIP1; 1.
DR Gene3D; 2.30.29.30; -; 1.
DR IDEAL; IID00227; -.
DR InterPro; IPR035638; JIP1_SH3.
DR InterPro; IPR011993; PH-like_dom_sf.
DR InterPro; IPR006020; PTB/PI_dom.
DR InterPro; IPR036028; SH3-like_dom_sf.
DR InterPro; IPR001452; SH3_domain.
DR Pfam; PF00640; PID; 1.
DR Pfam; PF14604; SH3_9; 1.
DR SMART; SM00462; PTB; 1.
DR SMART; SM00326; SH3; 1.
DR SUPFAM; SSF50044; SSF50044; 1.
DR PROSITE; PS01179; PID; 1.
DR PROSITE; PS50002; SH3; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cytoplasm; Diabetes mellitus; Disease variant;
KW Endoplasmic reticulum; Membrane; Mitochondrion; Nucleus; Phosphoprotein;
KW Reference proteome; Repeat; SH3 domain; Ubl conjugation.
FT CHAIN 1..711
FT /note="C-Jun-amino-terminal kinase-interacting protein 1"
FT /id="PRO_0000220628"
FT DOMAIN 488..549
FT /note="SH3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192"
FT DOMAIN 561..700
FT /note="PID"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00148"
FT REGION 1..27
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 78..371
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 127..285
FT /note="JNK-binding domain (JBD)"
FT REGION 157..176
FT /note="Minimal inhibitory domain (MID)"
FT REGION 283..471
FT /note="Interaction with MAP3K7"
FT /evidence="ECO:0000269|PubMed:17709393"
FT REGION 429..451
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 471..660
FT /note="Interaction with VRK2"
FT /evidence="ECO:0000269|PubMed:18286207"
FT MOTIF 353..360
FT /note="D-box 1"
FT MOTIF 364..372
FT /note="D-box 2"
FT COMPBIAS 135..153
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 166..203
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 220..242
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 259..275
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 15
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9WVI9"
FT MOD_RES 29
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9WVI9"
FT MOD_RES 40
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:16195223"
FT MOD_RES 103
FT /note="Phosphothreonine; by MAPK8, MAPK9 and MAPK10"
FT /evidence="ECO:0000269|PubMed:12756254"
FT MOD_RES 152
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:16195223"
FT MOD_RES 181
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:16195223"
FT MOD_RES 187
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:16195223"
FT MOD_RES 193
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:16195223"
FT MOD_RES 195
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:16195223"
FT MOD_RES 196
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:16195223"
FT MOD_RES 205
FT /note="Phosphothreonine; by MAPK8, MAPK9 and MAPK10"
FT /evidence="ECO:0000269|PubMed:12756254"
FT MOD_RES 214
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:16195223"
FT MOD_RES 311
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:16195223"
FT MOD_RES 328
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:16195223"
FT MOD_RES 330
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:16195223"
FT MOD_RES 340
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:16195223"
FT MOD_RES 355
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:16195223"
FT MOD_RES 366
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:16195223"
FT MOD_RES 369
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:16195223"
FT MOD_RES 407
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:16195223"
FT MOD_RES 409
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:16195223"
FT MOD_RES 411
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:16195223"
FT MOD_RES 444
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:16195223"
FT MOD_RES 447
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:16195223"
FT MOD_RES 448
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:16195223"
FT MOD_RES 469
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:16195223"
FT MOD_RES 471
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:16195223"
FT MOD_RES 472
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:16195223"
FT MOD_RES 473
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:16195223"
FT VARIANT 59
FT /note="S -> N (in NIDDM; dbSNP:rs119489103)"
FT /evidence="ECO:0000269|PubMed:10700186"
FT /id="VAR_012243"
FT VARIANT 322
FT /note="A -> V (in dbSNP:rs34420676)"
FT /id="VAR_049664"
FT VARIANT 353
FT /note="R -> Q (in dbSNP:rs12295161)"
FT /id="VAR_049665"
FT MUTAGEN 160
FT /note="R->G: Abolishes MAPK9 interaction."
FT /evidence="ECO:0000269|PubMed:12756254"
FT MUTAGEN 161
FT /note="P->G: Abolishes MAPK9 interaction."
FT /evidence="ECO:0000269|PubMed:12756254"
FT MUTAGEN 704
FT /note="P->A: No effect on KNS2 binding."
FT /evidence="ECO:0000269|PubMed:11238452"
FT MUTAGEN 709
FT /note="Y->A: Abolishes KNS2 binding."
FT /evidence="ECO:0000269|PubMed:11238452"
SQ SEQUENCE 711 AA; 77524 MW; 55EA53B30080A751 CRC64;
MAERESGGLG GGAASPPAAS PFLGLHIASP PNFRLTHDIS LEEFEDEDLS EITDECGISL
QCKDTLSLRP PRAGLLSAGG GGAGSRLQAE MLQMDLIDAT GDTPGAEDDE EDDDEERAAR
RPGAGPPKAE SGQEPASRGQ GQSQGQSQGP GSGDTYRPKR PTTLNLFPQV PRSQDTLNNN
SLGKKHSWQD RVSRSSSPLK TGEQTPPHEH ICLSDELPPQ SGPAPTTDRG TSTDSPCRRS
TATQMAPPGG PPAAPPGGRG HSHRDRIHYQ ADVRLEATEE IYLTPVQRPP DAAEPTSAFL
PPTESRMSVS SDPDPAAYPS TAGRPHPSIS EEEEGFDCLS SPERAEPPGG GWRGSLGEPP
PPPRASLSSD TSALSYDSVK YTLVVDEHAQ LELVSLRPCF GDYSDESDSA TVYDNCASVS
SPYESAIGEE YEEAPRPQPP ACLSEDSTPD EPDVHFSKKF LNVFMSGRSR SSSAESFGLF
SCIINGEEQE QTHRAIFRFV PRHEDELELE VDDPLLVELQ AEDYWYEAYN MRTGARGVFP
AYYAIEVTKE PEHMAALAKN SDWVDQFRVK FLGSVQVPYH KGNDVLCAAM QKIATTRRLT
VHFNPPSSCV LEISVRGVKI GVKADDSQEA KGNKCSHFFQ LKNISFCGYH PKNNKYFGFI
TKHPADHRFA CHVFVSEDST KALAESVGRA FQQFYKQFVE YTCPTEDIYL E
