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F1LM10 (F1LM10_RAT) Unreviewed, UniProtKB/TrEMBL

Last modified April 16, 2014. Version 28. Feed History...

Clusters with 100%, 90%, 50% identity | Third-party data text xml rdf/xml gff fasta
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Names and origin

Protein attributes

Sequence length707 AA.
Sequence statusComplete.
Protein existenceInferred from homology

General annotation (Comments)

Function

Calcium-independent, phospholipid- and diacylglycerol (DAG)-dependent serine/threonine-protein kinase that mediates non-redundant functions in T-cell receptor (TCR) signaling, including T-cells activation, proliferation, differentiation and survival, by mediating activation of multiple transcription factors such as NF-kappa-B, JUN, NFATC1 and NFATC2. In TCR-CD3/CD28-co-stimulated T-cells, is required for the activation of NF-kappa-B and JUN, which in turn are essential for IL2 production, and participates to the calcium-dependent NFATC1 and NFATC2 transactivation. Mediates the activation of the canonical NF-kappa-B pathway (NFKB1) by direct phosphorylation of CARD11 on several serine residues, inducing CARD11 association with lipid rafts and recruitment of the BCL10-MALT1 complex, which then activates IKK complex, resulting in nuclear translocation and activation of NFKB1. May also play an indirect role in activation of the non-canonical NF-kappa-B (NFKB2) pathway. In the signaling pathway leading to JUN activation, acts by phosphorylating the mediator STK39/SPAK and may not act through MAP kinases signaling. Plays a critical role in TCR/CD28-induced NFATC1 and NFATC2 transactivation by participating in the regulation of reduced inositol 1,4,5-trisphosphate generation and intracellular calcium mobilization. After costimulation of T-cells through CD28 can phosphorylate CBLB and is required for the ubiquitination and subsequent degradation of CBLB, which is a prerequisite for the activation of TCR. During T-cells differentiation, plays an important role in the development of T-helper 2 (Th2) cells following immune and inflammatory responses, and, in the development of inflammatory autoimmune diseases, is necessary for the activation of IL17-producing Th17 cells. May play a minor role in Th1 response. Upon TCR stimulation, mediates T-cell protective survival signal by phosphorylating BAD, thus protecting T-cells from BAD-induced apoptosis, and by up-regulating BCL-X(L)/BCL2L1 levels through NF-kappa-B and JUN pathways. In platelets, regulates signal transduction downstream of the ITGA2B, CD36/GP4, F2R/PAR1 and F2RL3/PAR4 receptors, playing a positive role in 'outside-in' signaling and granule secretion signal transduction. May relay signals from the activated ITGA2B receptor by regulating the uncoupling of WASP and WIPF1, thereby permitting the regulation of actin filament nucleation and branching activity of the Arp2/3 complex. May mediate inhibitory effects of free fatty acids on insulin signaling by phosphorylating IRS1, which in turn blocks IRS1 tyrosine phosphorylation and downstream activation of the PI3K/AKT pathway. Phosphorylates MSN (moesin) in the presence of phosphatidylglycerol or phosphatidylinositol. Phosphorylates PDPK1 at 'Ser-504' and 'Ser-532' and negatively regulates its ability to phosphorylate PKB/AKT1 By similarity. PIRNR PIRNR000551

Catalytic activity

ATP + a protein = ADP + a phosphoprotein. PIRNR PIRNR000551 SAAS SAAS000961

Cofactor

Magnesium By similarity. PIRNR PIRNR000551

Enzyme regulation

Novel PKCs (PRKCD, PRKCE, PRKCH and PRKCQ) are calcium-insensitive, but activated by diacylglycerol (DAG) and phosphatidylserine. Three specific sites; Thr-538 (activation loop of the kinase domain), Ser-676 (turn motif) and Ser-695 (hydrophobic region), need to be phosphorylated for its full activation By similarity. PIRNR PIRNR000551

Subunit structure

Interacts with GLRX3 (via N-terminus). Interacts with ECT2 By similarity. PIRNR PIRNR000551

Subcellular location

Cytoplasm. Cell membrane; Peripheral membrane protein. Note: In resting T-cells, mostly localized in cytoplasm. In response to TCR stimulation, associates with lipid rafts and then localizes in the immunological synapse By similarity. PIRNR PIRNR000551

Sequence similarities

Belongs to the protein kinase superfamily. AGC Ser/Thr protein kinase family. PKC subfamily. PIRNR PIRNR000551

Contains 1 protein kinase domain.

Contains AGC-kinase C-terminal domain. SAAS SAAS000961

Contains protein kinase domain. SAAS SAAS000961

Caution

The sequence shown here is derived from an Ensembl automatic analysis pipeline and should be considered as preliminary data. Ensembl ENSRNOP00000025902

Ontologies

Keywords
   Biological processInflammatory response PIRNR PIRNR000551
   Cellular componentCell membrane PIRNR PIRNR000551
Cytoplasm PIRNR PIRNR000551
Membrane
   DomainZinc-finger SAAS SAAS000961
   LigandATP-binding PIRNR PIRNR000551 SAAS SAAS000961 RuleBase RU000304
Magnesium PIRNR PIRNR000551
Metal-binding
Nucleotide-binding
Zinc
   Molecular functionKinase
Serine/threonine-protein kinase PIRNR PIRNR000551 SAAS SAAS000961
Transferase
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processinflammatory response

Inferred from electronic annotation. Source: UniProtKB-KW

intracellular signal transduction

Inferred from electronic annotation. Source: Ensembl

membrane protein ectodomain proteolysis

Inferred from electronic annotation. Source: Ensembl

negative regulation of T cell apoptotic process

Inferred from electronic annotation. Source: Ensembl

negative regulation of insulin receptor signaling pathway

Inferred from electronic annotation. Source: Ensembl

positive regulation of NF-kappaB transcription factor activity

Inferred from electronic annotation. Source: Ensembl

positive regulation of T cell proliferation

Inferred from electronic annotation. Source: Ensembl

positive regulation of T-helper 17 type immune response

Inferred from electronic annotation. Source: Ensembl

positive regulation of T-helper 2 cell activation

Inferred from electronic annotation. Source: Ensembl

positive regulation of interleukin-17 production

Inferred from electronic annotation. Source: Ensembl

positive regulation of interleukin-2 biosynthetic process

Inferred from electronic annotation. Source: Ensembl

positive regulation of interleukin-4 production

Inferred from electronic annotation. Source: Ensembl

regulation of platelet aggregation

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentcytoplasm

Inferred from electronic annotation. Source: UniProtKB-SubCell

immunological synapse

Inferred from electronic annotation. Source: Ensembl

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

metal ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

protein kinase C activity

Inferred from electronic annotation. Source: UniProtKB-EC

Complete GO annotation...

Sequences

Sequence LengthMass (Da)Tools
F1LM10 [UniParc].

Last modified May 3, 2011. Version 1.
Checksum: 7F81E6A3371B99A7

FASTA70781,777
        10         20         30         40         50         60 
MSPFLRIGLS NFDCGTCQAC QGEAVNPYCA VLVKEYVESE NGQMYIQKKP TMYPPWDSTF 

        70         80         90        100        110        120 
DAHINKGRVM QIIVKGKNVD LISETTVELY SLAERCRKNN GRTEIWLELK PQGRMLMNAR 

       130        140        150        160        170        180 
YFLEMSDTKD MSEFENEGFF ALHHRRGAIK QAKVHHVKCH EFTATFFPQP TFCSVCHEFV 

       190        200        210        220        230        240 
WGLNKQGYQC RQCNAAIHKK CIDKVIAKCT GSAINSRETM FHKERFKIDM PHRFKVYNYK 

       250        260        270        280        290        300 
SPTFCEHCGT LLWGLARQGL KCDACGMNVH HRCQTKVANL CGINQKLMAE ALAMIESTQQ 

       310        320        330        340        350        360 
ARTLRDSEHI FREGPIEISF PRSIKSETRP PCVPTPGKKE PQGICWESPL DGADKTAQPP 

       370        380        390        400        410        420 
EPEVNLQRAS LQLKLKIDDF ILHKMLGKGS FGKVFLAEFK RTKQFFAIKA LKKDVVLMDD 

       430        440        450        460        470        480 
DVECTMVEKR VLSLAWEHPF LTHMFCTFQT KENLFFVMEY LNGGDLMYHI QSCHKFDLSR 

       490        500        510        520        530        540 
ATFYAAEIIL GLQFLHSKGI VYRDLKLDNI LLDRDGHIKI ADFGMCKENM LGDAKTNTFC 

       550        560        570        580        590        600 
GTPDYIAPEI LLGQKYNHSV DWWSFGVLLY EMLIGQSPFH GQDEEELFHS IRMDNPFYPR 

       610        620        630        640        650        660 
WLEREAKDLL VKLFVREPEK RLGVRGDIRQ HPLFREINWE ELERKEIDPP FRPKVKSPYD 

       670        680        690        700 
CSNFDKEFLS EKPRLSFADR ALINSMDQNM FSNFSFINPG METLICS 

« Hide

References

« Hide 'large scale' references
[1]"Genome sequence of the Brown Norway rat yields insights into mammalian evolution."
Rat Genome Sequencing Project Consortium
Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J., Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G., Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G., Morgan M. expand/collapse author list , Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G., Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S., Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T., Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D., Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L., Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D., Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M., Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C., Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J., Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H., Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X., Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q., Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P., Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A., Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C., Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J., Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J., Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F., Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A., Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A., Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J., Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E., Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M., Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C., Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L., Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W., Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y., Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V., Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M., Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S., Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B., Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R., Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J., Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D., Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S., Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S., Mockrin S., Collins F.S.
Nature 428:493-521(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Strain: Brown Norway Ensembl ENSRNOP00000025902.
[2]Ensembl
Submitted (JUL-2011) to UniProtKB
Cited for: IDENTIFICATION.
Strain: Brown Norway Ensembl ENSRNOP00000025902.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AABR06092751 Genomic DNA. No translation available.
AABR06092752 Genomic DNA. No translation available.
AABR06092753 Genomic DNA. No translation available.
AABR06092754 Genomic DNA. No translation available.
AABR06092755 Genomic DNA. No translation available.
AABR06092756 Genomic DNA. No translation available.
AABR06092757 Genomic DNA. No translation available.
AABR06092758 Genomic DNA. No translation available.
AABR06092759 Genomic DNA. No translation available.
RefSeqNP_001263650.1. NM_001276721.1.
UniGeneRn.8227.

3D structure databases

ProteinModelPortalF1LM10.
ModBaseSearch...
MobiDBSearch...

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSRNOT00000025901; ENSRNOP00000025902; ENSRNOG00000019057.
GeneID85420.
KEGGrno:85420.

Organism-specific databases

CTD5588.
RGD620968. Prkcq.

Phylogenomic databases

GeneTreeENSGT00750000117339.
KOK18052.
OMAREPQGIS.
OrthoDBEOG77M8QM.
TreeFamTF102004.

Family and domain databases

Gene3D2.60.40.150. 1 hit.
InterProIPR000961. AGC-kinase_C.
IPR000008. C2_dom.
IPR020454. DAG/PE-bd.
IPR011009. Kinase-like_dom.
IPR027264. PKC_theta.
IPR017892. Pkinase_C.
IPR014376. Prot_kin_PKC_delta.
IPR002219. Prot_Kinase_C-like_PE/DAG-bd.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR002290. Ser/Thr_dual-sp_kinase_dom.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamPF00130. C1_1. 2 hits.
PF00069. Pkinase. 1 hit.
PF00433. Pkinase_C. 1 hit.
[Graphical view]
PIRSFPIRSF000551. PKC_delta. 1 hit.
PIRSF501105. Protein_kin_C_theta. 1 hit.
PRINTSPR00008. DAGPEDOMAIN.
SMARTSM00109. C1. 2 hits.
SM00133. S_TK_X. 1 hit.
SM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMSSF49562. SSF49562. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEPS51285. AGC_KINASE_CTER. 1 hit.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
PS00479. ZF_DAG_PE_1. 2 hits.
PS50081. ZF_DAG_PE_2. 2 hits.
[Graphical view]
ProtoNetSearch...

Other

NextBio617498.

Entry information

Entry nameF1LM10_RAT
AccessionPrimary (citable) accession number: F1LM10
Entry history
Integrated into UniProtKB/TrEMBL: May 3, 2011
Last sequence update: May 3, 2011
Last modified: April 16, 2014
This is version 28 of the entry and version 1 of the sequence. [Complete history]
Entry statusUnreviewed (UniProtKB/TrEMBL)