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 24-JAN-2024, entry version 210. 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 T2D 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; P05067: APP; NbExp=3; IntAct=EBI-78404, EBI-77613; 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: Type 2 diabetes mellitus (T2D) [MIM:125853]: A multifactorial CC disorder of glucose homeostasis caused by a lack of sensitivity to the CC body's own insulin. Affected individuals usually have an obese body CC habitus and manifestations of a metabolic syndrome characterized by CC diabetes, insulin resistance, hypertension and hypertriglyceridemia. CC The disease results in long-term complications that affect the eyes, CC kidneys, nerves, and blood vessels. {ECO:0000269|PubMed:10700186}. CC Note=Disease susceptibility may be associated with variants affecting CC 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}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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; 28. 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 GlyCosmos; Q9UQF2; 1 site, 1 glycan. 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; 9606-ENSP00000241014; -. DR PeptideAtlas; Q9UQF2; -. DR ProteomicsDB; 85551; -. DR Antibodypedia; 26197; 328 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 AGR; HGNC:6882; -. DR CTD; 9479; -. DR DisGeNET; 9479; -. DR GeneCards; MAPK8IP1; -. DR HGNC; HGNC:6882; MAPK8IP1. DR HPA; ENSG00000121653; Group enriched (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; 2904222at2759; -. DR PhylomeDB; Q9UQF2; -. DR TreeFam; TF325073; -. DR PathwayCommons; Q9UQF2; -. DR SignaLink; Q9UQF2; -. DR SIGNOR; Q9UQF2; -. DR BioGRID-ORCS; 9479; 23 hits in 1163 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 109 other cell types or tissues. DR ExpressionAtlas; Q9UQF2; baseline and differential. 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:0008432; F:JUN kinase binding; IBA:GO_Central. DR GO; GO:0019894; F:kinesin binding; IPI:UniProtKB. DR GO; GO:0005078; F:MAP-kinase scaffold activity; IPI:UniProtKB. DR GO; GO:0004860; F:protein kinase inhibitor activity; TAS:ProtInc. DR GO; GO:0007254; P:JNK cascade; IBA:GO_Central. 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:0006355; P:regulation of DNA-templated transcription; IEA:Ensembl. DR GO; GO:0046328; P:regulation of JNK cascade; ISS:UniProtKB. DR GO; GO:0016192; P:vesicle-mediated transport; ISS:UniProtKB. DR CDD; cd01212; PTB_JIP; 1. DR CDD; cd11943; SH3_JIP1; 1. DR Gene3D; 2.30.29.30; Pleckstrin-homology domain (PH domain)/Phosphotyrosine-binding domain (PTB); 1. DR Gene3D; 2.30.30.40; SH3 Domains; 1. DR IDEAL; IID00227; -. DR InterPro; IPR047178; JIP1_scaffold. 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 PANTHER; PTHR47437:SF3; C-JUN-AMINO-TERMINAL KINASE-INTERACTING PROTEIN 1; 1. DR PANTHER; PTHR47437; JNK-INTERACTING PROTEIN 1-LIKE PROTEIN; 1. DR Pfam; PF00640; PID; 1. DR Pfam; PF14604; SH3_9; 1. DR SMART; SM00462; PTB; 1. DR SMART; SM00326; SH3; 1. DR SUPFAM; SSF50729; PH domain-like; 1. DR SUPFAM; SSF50044; SH3-domain; 1. DR PROSITE; PS01179; PID; 1. DR PROSITE; PS50002; SH3; 1. DR Genevisible; Q9UQF2; HS. 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 T2D; risk factor; 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 //