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Protein

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

Gene

MAPK8IP1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

The 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. Functions as an anti-apoptotic protein and whose level seems to influence the beta-cell death or survival response. Acts as a scaffold protein that coordinates with SH3RF1 in organizing different components of the JNK pathway, including RAC1 or RAC2, MAP3K11/MLK3 or MAP3K7/TAK1, MAP2K7/MKK7, MAPK8/JNK1 and/or MAPK9/JNK2 into a functional multiprotein complex to ensure the effective activation of the JNK signaling pathway. Regulates the activation of MAPK8/JNK1 and differentiation of CD8+ T-cells.By similarity

Miscellaneous

A chemically synthesized cell-permeable peptide of the minimal inhibitory domain decreases brain lesions in both transient and permanent ischemia. The level of protection is still high when administered 6 or 12 hours after ischemia.

GO - Molecular functioni

  • JUN kinase binding Source: Ensembl
  • kinesin binding Source: UniProtKB
  • MAP-kinase scaffold activity Source: UniProtKB
  • mitogen-activated protein kinase kinase binding Source: Ensembl
  • mitogen-activated protein kinase kinase kinase binding Source: Ensembl
  • protein kinase inhibitor activity Source: ProtInc

GO - Biological processi

Enzyme and pathway databases

SignaLinkiQ9UQF2
SIGNORiQ9UQF2

Names & Taxonomyi

Protein namesi
Recommended name:
C-Jun-amino-terminal kinase-interacting protein 1
Short name:
JIP-1
Short name:
JNK-interacting protein 1
Alternative name(s):
Islet-brain 1
Short name:
IB-1
JNK MAP kinase scaffold protein 1
Mitogen-activated protein kinase 8-interacting protein 1
Gene namesi
Name:MAPK8IP1
Synonyms:IB1, JIP1, PRKM8IP
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 11

Organism-specific databases

EuPathDBiHostDB:ENSG00000121653.11
HGNCiHGNC:6882 MAPK8IP1
MIMi604641 gene
neXtProtiNX_Q9UQF2

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Endoplasmic reticulum, Membrane, Mitochondrion, Nucleus

Pathology & Biotechi

Involvement in diseasei

Diabetes mellitus, non-insulin-dependent (NIDDM)1 Publication
The disease may be caused by mutations affecting the gene represented in this entry.
Disease descriptionA multifactorial disorder of glucose homeostasis caused by a lack of sensitivity to the body's own insulin. Affected individuals usually have an obese body habitus and manifestations of a metabolic syndrome characterized by diabetes, insulin resistance, hypertension and hypertriglyceridemia. The disease results in long-term complications that affect the eyes, kidneys, nerves, and blood vessels.
See also OMIM:125853
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_01224359S → N in NIDDM. 1 PublicationCorresponds to variant dbSNP:rs119489103EnsemblClinVar.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi160R → G: Abolishes MAPK9 interaction. 1 Publication1
Mutagenesisi161P → G: Abolishes MAPK9 interaction. 1 Publication1
Mutagenesisi704P → A: No effect on KNS2 binding. 1 Publication1
Mutagenesisi709Y → A: Abolishes KNS2 binding. 1 Publication1

Keywords - Diseasei

Diabetes mellitus, Disease mutation

Organism-specific databases

DisGeNETi9479
MalaCardsiMAPK8IP1
MIMi125853 phenotype
OpenTargetsiENSG00000121653
PharmGKBiPA30626

Polymorphism and mutation databases

BioMutaiMAPK8IP1
DMDMi17433093

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002206281 – 711C-Jun-amino-terminal kinase-interacting protein 1Add BLAST711

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei15PhosphoserineBy similarity1
Modified residuei29PhosphoserineBy similarity1
Modified residuei40Phosphoserine1 Publication1
Modified residuei103Phosphothreonine; by MAPK8, MAPK9 and MAPK101 Publication1
Modified residuei152Phosphoserine1 Publication1
Modified residuei181Phosphoserine1 Publication1
Modified residuei187Phosphoserine1 Publication1
Modified residuei193Phosphoserine1 Publication1
Modified residuei195Phosphoserine1 Publication1
Modified residuei196Phosphoserine1 Publication1
Modified residuei205Phosphothreonine; by MAPK8, MAPK9 and MAPK101 Publication1
Modified residuei214Phosphoserine1 Publication1
Modified residuei311Phosphoserine1 Publication1
Modified residuei328Phosphoserine1 Publication1
Modified residuei330Phosphoserine1 Publication1
Modified residuei340Phosphoserine1 Publication1
Modified residuei355Phosphoserine1 Publication1
Modified residuei366Phosphoserine1 Publication1
Modified residuei369Phosphoserine1 Publication1
Modified residuei407Phosphoserine1 Publication1
Modified residuei409Phosphoserine1 Publication1
Modified residuei411Phosphothreonine1 Publication1
Modified residuei444Phosphoserine1 Publication1
Modified residuei447Phosphoserine1 Publication1
Modified residuei448Phosphothreonine1 Publication1
Modified residuei469Phosphoserine1 Publication1
Modified residuei471Phosphoserine1 Publication1
Modified residuei472Phosphoserine1 Publication1
Modified residuei473Phosphoserine1 Publication1

Post-translational modificationi

Phosphorylated by MAPK8, MAPK9 and MAPK10. Phosphorylation on Thr-103 is also necessary for the dissociation and activation of MAP3K12. Phosphorylated by isoform 1 and isoform 2 of VRK2. Hyperphosphorylated during mitosis following activation of stress-activated and MAP kinases.1 Publication
Ubiquitinated. Two preliminary events are required to prime for ubiquitination; phosphorylation and an increased in intracellular calcium concentration. Then, the calcium influx initiates ubiquitination and degradation by the ubiquitin-proteasome pathway.

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ9UQF2
PaxDbiQ9UQF2
PeptideAtlasiQ9UQF2
PRIDEiQ9UQF2
ProteomicsDBi85551

PTM databases

iPTMnetiQ9UQF2
PhosphoSitePlusiQ9UQF2

Expressioni

Tissue specificityi

Highly expressed in brain. Expressed in neurons, localizing to neurite tips in differentiating cells. Also expressed in the pancreas, testis and prostate. Low levels in heart, ovary and small intestine. Decreased levels in pancreatic beta cells sensitize cells to IL-1-beta-induced apoptosis.

Gene expression databases

BgeeiENSG00000121653
CleanExiHS_MAPK8IP1
ExpressionAtlasiQ9UQF2 baseline and differential
GenevisibleiQ9UQF2 HS

Organism-specific databases

HPAiHPA058921
HPA070332

Interactioni

Subunit structurei

Forms homo- or heterooligomeric complexes. Binds specific components of the JNK signaling pathway namely, MAPK8, MAPK9, MAPK10, MAPKK7, MLK2, MLK3, MAP3K12 and MAP3K13. Also binds the proline-rich domain-containing splice variant of apolipoprotein E receptor 2 (ApoER2). Interacts, via the PID domain, with ARHGEF28. Binds the cytoplasmic tails of LRP1 and LRP2 (Megalin). Binds the TPR motif-containing C-terminal of KNS2, then the pre-assembled MAPK8IP1 scaffolding complexes are transported as a cargo of kinesin, to the required subcellular location. Interacts with the cytoplasmic domain of APP. Interacts with DCLK2 (By similarity). Interacts with MAP3K7. Interacts with isoform 1 and isoform 2 of VRK2. Found in a complex with SH3RF1, RAC1, MAP3K11/MLK3, MAP2K7/MKK7 and MAPK8/JNK1. Found in a complex with SH3RF1, RAC2, MAP3K7/TAK1, MAP2K7/MKK7, MAPK8/JNK1 and MAPK9/JNK2. Interacts with SH3RF2 (By similarity).By similarity6 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • JUN kinase binding Source: Ensembl
  • kinesin binding Source: UniProtKB
  • MAP-kinase scaffold activity Source: UniProtKB
  • mitogen-activated protein kinase kinase binding Source: Ensembl
  • mitogen-activated protein kinase kinase kinase binding Source: Ensembl

Protein-protein interaction databases

BioGridi114864, 36 interactors
CORUMiQ9UQF2
ELMiQ9UQF2
IntActiQ9UQF2, 15 interactors
MINTiQ9UQF2
STRINGi9606.ENSP00000241014

Structurei

3D structure databases

ProteinModelPortaliQ9UQF2
SMRiQ9UQF2
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ9UQF2

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini488 – 549SH3PROSITE-ProRule annotationAdd BLAST62
Domaini561 – 700PIDPROSITE-ProRule annotationAdd BLAST140

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni127 – 285JNK-binding domain (JBD)Add BLAST159
Regioni157 – 176Minimal inhibitory domain (MID)Add BLAST20
Regioni283 – 471Interaction with MAP3K71 PublicationAdd BLAST189
Regioni471 – 660Interaction with VRK21 PublicationAdd BLAST190

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi353 – 360D-box 18
Motifi364 – 372D-box 29

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi42 – 48Asp/Glu-rich (acidic)7
Compositional biasi79 – 84Poly-Gly6
Compositional biasi107 – 116Asp/Glu-rich (acidic)10
Compositional biasi331 – 334Poly-Glu4
Compositional biasi359 – 363Poly-Pro5

Domaini

The destruction boxes (D-box) may act as recognition signals for degradation via the ubiquitin-proteasome pathway.
A minimal inhibitory domain prevents pancreatic beta cell apoptosis in vitro, and prevents activation of c-jun by MAPK8, MAPK9 and MAPK10.
The SH3 domain mediates homodimerization.By similarity

Sequence similaritiesi

Belongs to the JIP scaffold family.Curated

Keywords - Domaini

Repeat, SH3 domain

Phylogenomic databases

eggNOGiKOG3775 Eukaryota
ENOG410ZFRJ LUCA
GeneTreeiENSGT00390000003908
HOGENOMiHOG000231470
HOVERGENiHBG018568
InParanoidiQ9UQF2
KOiK04434
OMAiKQCYSGY
OrthoDBiEOG091G0T9G
PhylomeDBiQ9UQF2
TreeFamiTF325073

Family and domain databases

CDDicd11943 SH3_JIP1, 1 hit
Gene3Di2.30.29.30, 1 hit
InterProiView protein in InterPro
IPR035638 JIP1_SH3
IPR011993 PH-like_dom_sf
IPR006020 PTB/PI_dom
IPR036028 SH3-like_dom_sf
IPR001452 SH3_domain
PfamiView protein in Pfam
PF00640 PID, 1 hit
PF14604 SH3_9, 1 hit
SMARTiView protein in SMART
SM00462 PTB, 1 hit
SM00326 SH3, 1 hit
SUPFAMiSSF50044 SSF50044, 2 hits
PROSITEiView protein in PROSITE
PS01179 PID, 1 hit
PS50002 SH3, 1 hit

Sequencei

Sequence statusi: Complete.

Q9UQF2-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MAERESGGLG GGAASPPAAS PFLGLHIASP PNFRLTHDIS LEEFEDEDLS
60 70 80 90 100
EITDECGISL QCKDTLSLRP PRAGLLSAGG GGAGSRLQAE MLQMDLIDAT
110 120 130 140 150
GDTPGAEDDE EDDDEERAAR RPGAGPPKAE SGQEPASRGQ GQSQGQSQGP
160 170 180 190 200
GSGDTYRPKR PTTLNLFPQV PRSQDTLNNN SLGKKHSWQD RVSRSSSPLK
210 220 230 240 250
TGEQTPPHEH ICLSDELPPQ SGPAPTTDRG TSTDSPCRRS TATQMAPPGG
260 270 280 290 300
PPAAPPGGRG HSHRDRIHYQ ADVRLEATEE IYLTPVQRPP DAAEPTSAFL
310 320 330 340 350
PPTESRMSVS SDPDPAAYPS TAGRPHPSIS EEEEGFDCLS SPERAEPPGG
360 370 380 390 400
GWRGSLGEPP PPPRASLSSD TSALSYDSVK YTLVVDEHAQ LELVSLRPCF
410 420 430 440 450
GDYSDESDSA TVYDNCASVS SPYESAIGEE YEEAPRPQPP ACLSEDSTPD
460 470 480 490 500
EPDVHFSKKF LNVFMSGRSR SSSAESFGLF SCIINGEEQE QTHRAIFRFV
510 520 530 540 550
PRHEDELELE VDDPLLVELQ AEDYWYEAYN MRTGARGVFP AYYAIEVTKE
560 570 580 590 600
PEHMAALAKN SDWVDQFRVK FLGSVQVPYH KGNDVLCAAM QKIATTRRLT
610 620 630 640 650
VHFNPPSSCV LEISVRGVKI GVKADDSQEA KGNKCSHFFQ LKNISFCGYH
660 670 680 690 700
PKNNKYFGFI TKHPADHRFA CHVFVSEDST KALAESVGRA FQQFYKQFVE
710
YTCPTEDIYL E
Length:711
Mass (Da):77,524
Last modified:May 1, 2000 - v1
Checksum:i55EA53B30080A751
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_01224359S → N in NIDDM. 1 PublicationCorresponds to variant dbSNP:rs119489103EnsemblClinVar.1
Natural variantiVAR_049664322A → V. Corresponds to variant dbSNP:rs34420676Ensembl.1
Natural variantiVAR_049665353R → Q. Corresponds to variant dbSNP:rs12295161Ensembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF074091 mRNA Translation: AAD20443.1
CH471064 Genomic DNA Translation: EAW68027.1
CH471064 Genomic DNA Translation: EAW68028.1
AF007134 mRNA Translation: AAC19150.1
CCDSiCCDS7916.1
RefSeqiNP_005447.1, NM_005456.3
UniGeneiHs.234249

Genome annotation databases

EnsembliENST00000241014; ENSP00000241014; ENSG00000121653
GeneIDi9479
KEGGihsa:9479
UCSCiuc001nbr.4 human

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Entry informationi

Entry nameiJIP1_HUMAN
AccessioniPrimary (citable) accession number: Q9UQF2
Secondary accession number(s): D3DQP4, O43407
Entry historyiIntegrated into UniProtKB/Swiss-Prot: December 5, 2001
Last sequence update: May 1, 2000
Last modified: July 18, 2018
This is version 177 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 11
    Human chromosome 11: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

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