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Reviewed, UniProtKB/Swiss-Prot Q9UQF2 (JIP1_HUMAN)

Last modified January 19, 2010. Version 96. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents

Names and origin

Protein namesRecommended name:
    C-jun-amino-terminal kinase-interacting protein 1
      Short name=JNK-interacting protein 1
      Short name=JIP-1
Alternative name(s):
    JNK MAP kinase scaffold protein 1
    Islet-brain 1
      Short name=IB-1
    Mitogen-activated protein kinase 8-interacting protein 1
Gene names
Name: MAPK8IP1
Synonyms: IB1, JIP1, PRKM8IP
OrganismHomo sapiens (Human) [Complete proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length711 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level.

General annotation (Comments)

Function

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 By similarity. Functions as an anti-apoptotic protein and whose level seems to influence the beta-cell death or survival response.

Subunit structure

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 RGNEF. 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 By similarity. Ref.3 Ref.4 Ref.5 Ref.6

Subcellular location

Cytoplasm By similarity. Cytoplasmperinuclear region By similarity. Nucleus By similarity. Note: Accumulates in cell surface projections. Under certain stress conditions, translocates to the perinuclear region of neurons. In insulin-secreting cells, detected in both the cytoplasm and nucleus By similarity. Ref.3

Tissue specificity

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.

Domain

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.

Post-translational modification

Phosphorylated by MAPK8, MAPK9 and MAPK10. Phosphorylation on Thr-103 is also necessary for the dissociation and activation of MAP3K12. Ref.7

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. Ref.9

Involvement in disease

Defects in MAPK8IP1 are a cause of non-insulin-dependent diabetes mellitus (NIDDM) [MIM:125853]. NIDDM is characterized by an autosomal dominant mode of inheritance, onset during adulthood and insulin resistance. Ref.11

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.

Sequence similarities

Belongs to the JIP scaffold family.

Contains 1 PID domain.

Contains 1 SH3 domain.

Binary interactions

With

Entry

#Exp.

IntAct

Notes

APPP050673EBI-78404,EBI-77613
AppP120231EBI-78404,EBI-78814From a different organism.
AppP12023-21EBI-78404,EBI-286828From a different organism.
MAP3K7O433181EBI-78404,EBI-358684

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 711711C-jun-amino-terminal kinase-interacting protein 1
PRO_0000220628

Regions

Domain488 – 54962SH3
Domain561 – 700140PID
Region127 – 285159JNK-binding domain (JBD)
Region157 – 17620Minimal inhibitory domain (MID)
Motif353 – 3608D-box 1
Motif364 – 3729D-box 2
Compositional bias42 – 487Asp/Glu-rich (acidic)
Compositional bias79 – 846Poly-Gly
Compositional bias107 – 11610Asp/Glu-rich (acidic)
Compositional bias331 – 3344Poly-Glu
Compositional bias359 – 3635Poly-Pro

Amino acid modifications

Modified residue1031Phosphothreonine; by MAPK8, MAPK9 and MAPK10
Modified residue2051Phosphothreonine; by MAPK8, MAPK9 and MAPK10

Natural variations

Natural variant591S → N in NIDDM. Ref.11
VAR_012243
Natural variant3221A → V: dbSNP rs34420676.
VAR_049664
Natural variant3531R → Q: dbSNP rs12295161.
VAR_049665

Experimental info

Mutagenesis1601R → G: Abolishes MAPK9 interaction.
Mutagenesis1611P → G: Abolishes MAPK9 interaction.
Mutagenesis7041P → A: No effect on KNS2 binding.
Mutagenesis7091Y → A: Abolishes KNS2 binding.

Sequences

Sequence LengthMass (Da)Tools
Q9UQF2-1 [UniParc].

Last modified May 1, 2000. Version 1.
Checksum: 55EA53B30080A751

FASTA71177,524
        10         20         30         40         50         60 
MAERESGGLG GGAASPPAAS PFLGLHIASP PNFRLTHDIS LEEFEDEDLS EITDECGISL 

        70         80         90        100        110        120 
QCKDTLSLRP PRAGLLSAGG GGAGSRLQAE MLQMDLIDAT GDTPGAEDDE EDDDEERAAR 

       130        140        150        160        170        180 
RPGAGPPKAE SGQEPASRGQ GQSQGQSQGP GSGDTYRPKR PTTLNLFPQV PRSQDTLNNN 

       190        200        210        220        230        240 
SLGKKHSWQD RVSRSSSPLK TGEQTPPHEH ICLSDELPPQ SGPAPTTDRG TSTDSPCRRS 

       250        260        270        280        290        300 
TATQMAPPGG PPAAPPGGRG HSHRDRIHYQ ADVRLEATEE IYLTPVQRPP DAAEPTSAFL 

       310        320        330        340        350        360 
PPTESRMSVS SDPDPAAYPS TAGRPHPSIS EEEEGFDCLS SPERAEPPGG GWRGSLGEPP 

       370        380        390        400        410        420 
PPPRASLSSD TSALSYDSVK YTLVVDEHAQ LELVSLRPCF GDYSDESDSA TVYDNCASVS 

       430        440        450        460        470        480 
SPYESAIGEE YEEAPRPQPP ACLSEDSTPD EPDVHFSKKF LNVFMSGRSR SSSAESFGLF 

       490        500        510        520        530        540 
SCIINGEEQE QTHRAIFRFV PRHEDELELE VDDPLLVELQ AEDYWYEAYN MRTGARGVFP 

       550        560        570        580        590        600 
AYYAIEVTKE PEHMAALAKN SDWVDQFRVK FLGSVQVPYH KGNDVLCAAM QKIATTRRLT 

       610        620        630        640        650        660 
VHFNPPSSCV LEISVRGVKI GVKADDSQEA KGNKCSHFFQ LKNISFCGYH PKNNKYFGFI 

       670        680        690        700        710 
TKHPADHRFA CHVFVSEDST KALAESVGRA FQQFYKQFVE YTCPTEDIYL E 

« Hide

References

« Hide 'large scale' references
[1]"Genomic organization, fine-mapping, and expression of the human islet-brain 1 (IB1)/C-jun-amino-terminal kinase interacting protein-1 (JIP-1) gene."
Mooser V., Maillard A., Bonny C., Steinmann M., Shaw P., Yarnall D.P., Burns D.K., Schorderet D.F., Nicod P., Waeber G.
Genomics 55:202-208(1999) [PubMed: 9933567] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Insulinoma.
[2]Yu W., Sarginson J., Gibbs R.A.
Submitted (JUN-1997) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 468-711.
Tissue: Brain.
[3]"Interaction of c-Jun amino-terminal kinase interacting protein-1 with p190 rhoGEF and its localization in differentiated neurons."
Meyer D., Liu A., Margolis B.
J. Biol. Chem. 274:35113-35118(1999) [PubMed: 10574993] [Abstract]
Cited for: INTERACTION WITH RGNEF, SUBCELLULAR LOCATION.
[4]"Cargo of kinesin identified as JIP scaffolding proteins and associated signaling molecules."
Verhey K.J., Meyer D., Deehan R., Blenis J., Schnapp B.J., Rapoport T.A., Margolis B.
J. Cell Biol. 152:959-970(2001) [PubMed: 11238452] [Abstract]
Cited for: MUTAGENESIS, INTERACTION WITH KINESIN.
[5]"Mixed lineage kinase LZK forms a functional signaling complex with JIP-1, a scaffold protein of the c-Jun NH(2)-terminal kinase pathway."
Ikeda A., Hasegawa K., Masaki M., Moriguchi T., Nishida E., Kozutsumi Y., Oka S., Kawasaki T.
J. Biochem. 130:773-781(2001) [PubMed: 11726277] [Abstract]
Cited for: INTERACTION WITH MAP3K13.
[6]"Interaction of Alzheimer's beta-amyloid precursor family proteins with scaffold proteins of the JNK signaling cascade."
Taru H., Iijima K., Hase M., Kirino Y., Yagi Y., Suzuki T.
J. Biol. Chem. 277:20070-20078(2002) [PubMed: 11912189] [Abstract]
Cited for: INTERACTION WITH APP.
[7]"Recruitment of JNK to JIP1 and JNK-dependent JIP1 phosphorylation regulates JNK module dynamics and activation."
Nihalani D., Wong H.N., Holzman L.B.
J. Biol. Chem. 278:28694-28702(2003) [PubMed: 12756254] [Abstract]
Cited for: PHOSPHORYLATION BY JNK, MUTAGENESIS.
[8]"Cell-permeable peptide inhibitors of JNK: novel blockers of beta-cell death."
Bonny C., Oberson A., Negri S., Sauser C., Schorderet D.F.
Diabetes 50:77-82(2001) [PubMed: 11147798] [Abstract]
Cited for: PEPTIDE INHIBITORS OF JNK.
[9]"Calcium- and proteasome-dependent degradation of the JNK scaffold protein islet-brain 1."
Allaman-Pillet N., Storling J., Oberson A., Roduit R., Negri S., Sauser C., Nicod P., Beckmann J.S., Schorderet D.F., Mandrup-Poulsen T., Bonny C.
J. Biol. Chem. 278:48720-48726(2003) [PubMed: 14507925] [Abstract]
Cited for: CALCIUM- AND PROTEASOME-DEPENDENT DEGRADATION.
[10]"A peptide inhibitor of c-Jun N-terminal kinase protects against excitotoxicity and cerebral ischemia."
Borsello T., Clarke P.G., Hirt L., Vercelli A., Repici M., Schorderet D.F., Bogousslavsky J., Bonny C.
Nat. Med. 9:1180-1186(2003) [PubMed: 12937412] [Abstract]
Cited for: PROTECTION AGAINST EXCITOTOXICITY AND CEREBRAL ISCHEMIA.
[11]"The gene, MAPK8IP1, encoding islet-brain-1, is a candidate for type 2 diabetes."
Waeber G., Delplanque J., Bonny C., Mooser V., Steinmann M., Widmann C., Maillard A., Miklossy J., Dina C., Hani E.H., Vionnet N., Nicod P., Boutin P., Froguel P.
Nat. Genet. 24:291-295(2000) [PubMed: 10700186] [Abstract]
Cited for: VARIANT NIDDM ASN-59.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF074091 mRNA. Translation: AAD20443.1.
AF007134 mRNA. Translation: AAC19150.1.
IPIIPI00023133.
RefSeqNP_005447.1.
UniGeneHs.234249

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2G01X-ray3.50F/G157-167[»]
2GMXX-ray3.50F/G157-167[»]
2H96X-ray3.00F/G157-167[»]
SMRQ9UQF2. Positions 490-549, 565-700.
ModBaseSearch...

Protein-protein interaction databases

IntActQ9UQF2. 17 interactions.
STRINGQ9UQF2.

PTM databases

PhosphoSiteQ9UQF2.

Proteomic databases

PRIDEQ9UQF2.

Genome annotation databases

EnsemblENST00000241014; ENSP00000241014; ENSG00000121653; Homo sapiens. [Genome view]
GeneID9479.
KEGGhsa:9479.
UCSCuc001nbr.1. human.

Organism-specific databases

CTD9479.
GeneCardsGC11P045863.
H-InvDBHIX0035850.
HIX0059692.
HGNCHGNC:6882. MAPK8IP1.
HPACAB013289.
MIM125853. phenotype.
604641. gene.
PharmGKBPA30626.
GenAtlasSearch...

Phylogenomic databases

eggNOGprNOG08481.
HOGENOMHBG717444.
HOVERGENQ9UQF2.
InParanoidQ9UQF2.
OMAGRGHSHR.
OrthoDBEOG9GQSQT.
PhylomeDBQ9UQF2.

Gene expression databases

ArrayExpressQ9UQF2.
BgeeQ9UQF2.
CleanExHS_MAPK8IP1.
GenevestigatorQ9UQF2.
GermOnlineENSG00000121653. Homo sapiens.

Family and domain databases

InterProIPR011993. PH_type.
IPR006020. PTyr_interaction_dom.
IPR001452. SH3_domain.
[Graphical view]
Gene3DG3DSA:2.30.29.30. PH_type. 1 hit.
PfamPF00640. PID. 1 hit.
PF00018. SH3_1. 1 hit.
[Graphical view]
SMARTSM00462. PTB. 1 hit.
SM00326. SH3. 1 hit.
[Graphical view]
PROSITEPS01179. PID. 1 hit.
PS50002. SH3. 1 hit.
[Graphical view]
ProtoNetSearch...

Other Resources

NextBio35528.
SOURCESearch...

Entry information

Entry nameJIP1_HUMAN
AccessionPrimary (citable) accession number: Q9UQF2
Secondary accession number(s): O43407
Entry history
Integrated into UniProtKB/Swiss-Prot: December 5, 2001
Last sequence update: May 1, 2000
Last modified: January 19, 2010
This is version 96 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)
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.

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Human chromosome 11: entries, gene names and cross-references to MIM

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List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

SIMILARITY comments

Index of protein domains and families

Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents