EKS-RAN-00016

Eukaryotic Protein Kinase & Protein Phosphatase Database

Tag

Content

EKPD ID

EKS-RAN-00016

Classification

Group/Family	Score	E-Value	Start	End	Domain Length
TK/InsR	540.6	7.2E-163	1000	1267	268

Status

Reviewed

Ensembl Protein

ENSRNOP00000019267

UniProt Accession

P24062;

Protein Name

Insulin-like growth factor 1 receptor beta chain

Protein Synonyms/Alias

Insulin-like growth factor I receptor; IGF-I receptor;

Gene Name

Igf1r

Gene Synonyms/Alias

Igf1r;

Ensembl Information

Ensembl Gene ID	Ensembl Protein ID	Ensembl Transcript ID
ENSRNOG00000014187	ENSRNOP00000019267	ENSRNOT00000019267

Organism

Rattus norvegicus

Functional Description

Receptor tyrosine kinase which mediates actions ofinsulin-like growth factor 1 (IGF1). Binds IGF1 with high affinity and IGF2 and insulin (INS) with a lower affinity. The activated IGF1R is involved in cell growth and survival control. IGF1R is crucial for tumor transformation and survival of malignant cell. Ligand binding activates the receptor kinase, leading to receptor autophosphorylation, and tyrosines phosphorylation of multiple substrates, that function as signaling adapter proteins including, the insulin-receptor substrates (IRS1/2), Shc and 14-3-3 proteins. Phosphorylation of IRSs proteins lead to the activation of two main signaling pathways: the PI3K-AKT/PKB pathway and the Ras-MAPK pathway. The result of activating the MAPK pathway is increased cellular proliferation, whereas activating the PI3K pathway inhibits apoptosis and stimulates protein synthesis. Phosphorylated IRS1 can activate the 85 kDa regulatory subunit of PI3K (PIK3R1), leading to activation of several downstream substrates, including protein AKT/PKB. AKT phosphorylation, in turn, enhances protein synthesis through mTOR activation and triggers the antiapoptotic effects of IGFIR through phosphorylation and inactivation of BAD. In parallel to PI3K- driven signaling, recruitment of Grb2/SOS by phosphorylated IRS1 or Shc leads to recruitment of Ras and activation of the ras-MAPK pathway. In addition to these two main signaling pathways IGF1R signals also through the Janus kinase/signal transducer and activator of transcription pathway (JAK/STAT). Phosphorylation of JAK proteins can lead to phosphorylation/activation of signal transducers and activators of transcription (STAT) proteins. In particular activation of STAT3, may be essential for the transforming activity of IGF1R. The JAK/STAT pathway activates gene transcription and may be responsible for the transforming activity. JNK kinases can also be activated by the IGF1R. IGF1 exerts inhibiting activities on JNK activation via phosphorylation and inhibition of MAP3K5/ASK1, which is able to directly associate with the IGF1R (By similarity). When present in a hybrid receptor with INSR, binds IGF1 (By similarity).

Protein Length

1370

Protein Sequence
(FASTA)

MKSGSGGGSP TSLWGLVFLS AALSLWPTSG EICGPGIDIR NDYQQLKRLE NCTVIEGFLH 60

ILLISKAEDY RSYRFPKLTV ITEYLLLFRV AGLESLGDLF PNLTVIRGWK LFYNYALVIF 120

EMTNLKDIGL YNLRNITRGA IRIEKNADLC YLSTIDWSLI LDAVSNNYIV GNKPPKECGD 180

LCPGTLEEKP MCEKTTINNE YNYRCWTTNR CQKMCPSVCG KRACTENNEC CHPECLGSCH 240

TPDDNTTCVA CRHYYYKGVC VPACPPGTYR FEGWRCVDRD FCANIPNAES SDSDGFVIHD 300

GECMQECPSG FIRNSTQSMY CIPCEGPCPK VCGDEEKKTK TIDSVTSAQM LQGCTILKGN 360

LLINIRRGNN IASELENFMG LIEVVTGYVK IRHSHALVSL SFLKNLRLIL GEEQLEGNYS 420

FYVLDNQNLQ QLWDWNHRNL TVRSGKMYFA FNPKLCVSEI YRMEEVTGTK GRQSKGDINT 480

RNNGERASCE SDVLRFTSTT TWKNRIIITW HRYRPPDYRD LISFTVYYKE APFKNVTEYD 540

GQDACGSNSW NMVDVDLPPN KEGEPGILLH GLKPWTQYAV YVKAVTLTMV ENDHIRGAKS 600

EILYIRTNAS VPSIPLDVLS ASNSSSQLIV KWNPPTLPNG NLSYYIVRWQ RQPQDGYLFR 660

HNYCSKDKIP IRKYADGTID VEEVTENPKT EVCGGDKGPC CACPKTEAEK QAEKEEAEYR 720

KVFENFLHNS IFVPRPERRR RDVLQVANTT MSSRSRNTTV ADTYNITDPE EFETEYPFFE 780

SRVDNKERTV ISNLRPFTLY RIDIHSCNHE AEKLGCSASN FVFARTMPAE GADDIPGPVT 840

WEPRPENSIF LKWPEPENPN GLILMYEIKY GSQVEDQREC VSRQEYRKYG GAKLNRLNPG 900

NYTARIQATS LSGNGSWTDP VFFYVPAKTT YENFMHLIIA LPVAILLIVG GLVIMLYVFH 960

RKRNNSRLGN GVLYASVNPE YFSAADVYVP DEWEVAREKI TMNRELGQGS FGMVYEGVAK 1020

GVVKDEPETR VAIKTVNEAA SMRERIEFLN EASVMKEFNC HHVVRLLGVV SQGQPTLVIM 1080

ELMTRGDLKS YLRSLRPEVE NNLVLIPPSL SKMIQMAGEI ADGMAYLNAN KFVHRDLAAR 1140

NCMVAEDFTV KIGDFGMTRD IYETDYYRKG GKGLLPVRWM SPESLKDGVF TTHSDVWSFG 1200

VVLWEIATLA EQPYQGLSNE QVLRFVMEGG LLDKPDNCPD MLFELMRMCW QYNPKMRPSF 1260

LEIIGSIKDE MEPSFQEVSF YYSEENKPPE PEELEMELEL EPENMESVPL DPSASSASLP 1320

LPERHSGHKA ENGPGVLVLR ASFDERQPYA HMNGGRANER ALPLPQSSTC 1370

Nucleotide Sequence
(FASTA)

ATGAAGTCTG GCTCCGGAGG AGGGTCCCCG ACCTCGCTGT GGGGGCTCGT GTTTCTCTCC 60

GCCGCGCTCT CGCTCTGGCC GACGAGTGGA GAAATTTGTG GGCCCGGCAT TGACATCCGC 120

AACGACTATC AGCAGCTGAA GCGCCTGGAA AACTGCACGG TGATCGAGGG CTTCCTCCAC 180

ATCCTGCTCA TCTCCAAGGC CGAGGACTAC CGAAGCTACC GCTTCCCCAA GCTCACGGTC 240

ATCACCGAGT ACTTGCTGCT GTTTCGAGTG GCCGGCCTCG AGAGCCTGGG AGACCTCTTC 300

CCGAACCTCA CAGTCATCCG TGGCTGGAAA CTCTTCTACA ATTACGCACT GGTCATCTTC 360

GAGATGACCA ATCTCAAGGA TATTGGGCTT TATAATCTGA GGAACATTAC TCGGGGGGCC 420

ATCAGGATTG AGAAAAACGC TGACCTCTGT TACCTCTCCA CCATAGACTG GTCTCTCATC 480

TTGGATGCGG TGTCCAATAA CTACATTGTG GGGAACAAGC CCCCAAAGGA ATGTGGGGAC 540

CTGTGTCCAG GGACCTTGGA GGAGAAGCCC ATGTGTGAGA AGACCACCAT CAACAATGAG 600

TACAACTACC GCTGCTGGAC CACAAATCGC TGCCAGAAAA TGTGCCCAAG TGTGTGTGGG 660

AAGCGAGCCT GCACCGAGAA CAATGAGTGC TGCCACCCGG AGTGCCTAGG CAGCTGCCAC 720

ACACCGGACG ACAACACAAC CTGCGTGGCC TGCCGACACT ACTACTACAA AGGCGTGTGC 780

GTGCCTGCCT GCCCGCCTGG CACCTACAGG TTCGAGGGCT GGCGCTGTGT GGACCGGGAT 840

TTCTGCGCCA ACATCCCCAA CGCCGAGAGC AGTGACTCAG ATGGCTTCGT CATCCACGAT 900

GGCGAGTGCA TGCAGGAGTG TCCATCAGGC TTCATCCGCA ACAGCACCCA GAGCATGTAC 960

TGTATCCCCT GTGAAGGCCC CTGCCCCAAG GTCTGCGGCG ATGAAGAAAA GAAAACGAAA 1020

ACCATCGATT CTGTGACGTC TGCCCAGATG CTCCAAGGGT GCACCATTTT GAAGGGCAAT 1080

CTGCTTATTA ACATCCGGCG AGGCAATAAC ATTGCCTCGG AATTGGAGAA CTTCATGGGG 1140

CTCATCGAGG TGGTGACTGG CTACGTGAAG ATCCGCCATT CCCATGCCTT GGTCTCCTTG 1200

TCCTTCCTGA AGAACCTTCG TCTCATCTTA GGAGAGGAGC AGCTAGAAGG GAACTACTCC 1260

TTCTATGTCC TGGACAACCA GAACTTGCAG CAGCTGTGGG ACTGGAACCA CCGGAACCTG 1320

ACCGTCAGGT CAGGGAAAAT GTACTTCGCT TTCAATCCCA AGCTGTGTGT CTCTGAAATT 1380

TACCGGATGG AGGAGGTGAC AGGAACAAAG GGACGGCAGA GCAAAGGAGA CATAAACACC 1440

AGGAACAACG GAGAGCGAGC TTCCTGTGAA AGTGATGTTC TCCGTTTCAC CTCCACCACC 1500

ACCTGGAAGA ACCGCATCAT CATAACGTGG CACCGGTACC GGCCGCCGGA CTACCGGGAT 1560

CTCATCAGTT TCACAGTCTA CTACAAGGAG GCACCCTTTA AAAACGTCAC GGAATACGAC 1620

GGGCAGGATG CCTGTGGCTC CAACAGCTGG AACATGGTGG ACGTGGACCT GCCTCCGAAC 1680

AAGGAGGGGG AGCCTGGCAT TTTGCTGCAT GGGCTGAAGC CCTGGACCCA GTATGCAGTC 1740

TATGTCAAGG CTGTGACCCT CACCATGGTG GAAAACGACC ACATCCGTGG GGCCAAAAGT 1800

GAAATCTTGT ACATTCGCAC CAACGCTTCA GTTCCTTCCA TTCCTCTAGA TGTCCTCTCG 1860

GCATCAAACT CCTCCTCTCA GCTGATCGTG AAGTGGAACC CCCCAACTCT GCCCAATGGT 1920

AACTTGAGTT ACTACATTGT GAGGTGGCAG CGGCAGCCGC AGGATGGCTA TCTGTTCCGG 1980

CACAACTACT GCTCCAAAGA CAAAATACCC ATCAGAAAGT ACGCCGATGG TACCATCGAT 2040

GTGGAGGAGG TGACAGAAAA TCCCAAGACA GAAGTGTGCG GTGGTGATAA AGGGCCGTGC 2100

TGTGCCTGTC CTAAAACCGA AGCTGAGAAG CAGGCTGAGA AGGAGGAGGC TGAGTACCGT 2160

AAAGTCTTTG AGAATTTCCT TCACAACTCC ATCTTTGTGC CCAGACCTGA GAGGAGGCGG 2220

AGAGATGTCC TGCAGGTGGC TAACACCACC ATGTCCAGCC GAAGCAGGAA CACCACGGTA 2280

GCTGACACCT ACAATATCAC AGACCCGGAA GAGTTCGAGA CAGAATACCC TTTCTTTGAG 2340

AGCAGAGTGG ATAACAAGGA GAGGACTGTC ATTTCCAACC TCCGGCCTTT CACTCTGTAC 2400

CGTATCGATA TCCACAGCTG CAACCACGAG GCTGAGAAGC TGGGCTGCAG CGCCTCCAAC 2460

TTTGTCTTTG CAAGAACCAT GCCAGCAGAA GGAGCAGATG ACATTCCTGG CCCAGTGACC 2520

TGGGAGCCAA GACCTGAAAA CTCCATCTTT TTAAAGTGGC CAGAACCCGA GAACCCCAAC 2580

GGATTGATTC TAATGTATGA AATAAAATAC GGATCGCAAG TCGAGGATCA GCGGGAATGT 2640

GTGTCCAGAC AGGAGTACAG GAAGTATGGA GGGGCCAAAC TTAACCGTCT AAACCCAGGG 2700

AACTATACGG CCCGGATTCA GGCTACCTCC CTCTCTGGGA ATGGGTCGTG GACAGATCCT 2760

GTGTTCTTCT ATGTCCCAGC CAAAACAACG TATGAGAATT TCATGCATCT GATCATTGCT 2820

CTGCCGGTTG CCATCCTGCT GATTGTGGGG GGCCTGGTAA TCATGCTGTA TGTCTTCCAT 2880

AGAAAGAGGA ATAACAGCAG ATTGGGCAAC GGGGTGCTGT ACGCCTCTGT GAACCCCGAG 2940

TATTTCAGCG CAGCTGATGT GTACGTGCCT GATGAATGGG AGGTAGCTCG GGAGAAGATC 3000

ACCATGAACC GGGAGCTCGG ACAAGGGTCC TTCGGGATGG TCTATGAAGG AGTGGCCAAG 3060

GGCGTGGTCA AGGACGAGCC TGAAACCAGA GTGGCCATCA AGACAGTGAA TGAGGCTGCA 3120

AGTATGCGTG AGAGAATTGA GTTTCTCAAC GAGGCCTCAG TGATGAAGGA GTTCAACTGT 3180

CACCATGTGG TCCGGTTGCT GGGTGTAGTA TCCCAAGGCC AGCCCACCCT GGTCATCATG 3240

GAACTAATGA CACGTGGCGA TCTCAAAAGT TATCTCCGGT CTCTAAGGCC AGAGGTGGAG 3300

AATAATCTAG TCCTGATTCC TCCGAGCTTA AGCAAGATGA TCCAGATGGC TGGAGAGATT 3360

GCAGATGGCA TGGCCTACCT CAATGCCAAC AAGTTCGTCC ACAGAGACCT GGCTGCTCGG 3420

AACTGCATGG TAGCTGAAGA TTTCACAGTC AAAATTGGAG ATTTTGGTAT GACACGAGAC 3480

ATCTACGAGA CGGACTACTA CCGGAAAGGC GGGAAGGGCT TGCTGCCTGT GCGCTGGATG 3540

TCTCCCGAGT CCCTCAAGGA TGGCGTCTTC ACCACTCATT CCGATGTCTG GTCCTTTGGG 3600

GTCGTCCTCT GGGAGATCGC CACTCTGGCT GAGCAGCCGT ACCAGGGCCT GTCCAACGAG 3660

CAAGTTCTTC GTTTCGTCAT GGAGGGCGGC CTTCTGGACA AGCCGGATAA CTGCCCCGAT 3720

ATGCTGTTTG AACTTATGCG CATGTGCTGG CAGTACAACC CCAAGATGCG GCCCTCCTTC 3780

CTGGAGATCA TCGGAAGCAT CAAGGATGAG ATGGAGCCCA GTTTCCAGGA GGTCTCCTTC 3840

TACTACAGCG AGGAGAACAA GCCTCCAGAG CCGGAGGAGC TGGAGATGGA GCTGGAGCTG 3900

GAGCCCGAGA ACATGGAGAG CGTCCCGCTG GACCCTTCGG CCTCCTCAGC CTCCCTGCCT 3960

CTGCCTGAAA GACACTCAGG ACACAAGGCT GAGAACGGCC CTGGCGTGCT GGTTCTCCGT 4020

GCCAGTTTTG ATGAGAGACA GCCTTACGCT CACATGAATG GGGGACGCGC CAACGAGAGG 4080

GCCTTGCCTC TGCCCCAGTC CTCAACCTGC TGA 4113

Domain Profile

S: 1     ivllrelGqGsfGmvyeGvakdvvkgeeetrvaiktvneaassrerieflkeasvmkefk  60

         i+++relGqGsfGmvyeGvak+vvk+e etrvaiktvneaas+reriefl+easvmkef+

Q: 1000  ITMNRELGQGSFGMVYEGVAKGVVKDEPETRVAIKTVNEAASMRERIEFLNEASVMKEFN  1059

         799*********************************************************

S: 61    thhvvrllGvvskgqpalvvmelmkkGdlksylrslrpeeeneaalappaldkliqmaae  120

         +hhvvrllGvvs+gqp+lv+melm++Gdlksylrslrpe+en+ +l pp+l+k+iqma+e

Q: 1060  CHHVVRLLGVVSQGQPTLVIMELMTRGDLKSYLRSLRPEVENNLVLIPPSLSKMIQMAGE  1119

         ************************************************************

S: 121   iadGmayleakkfvhrdlaarncmvaedltvkiGdfGmtrdiyetdyyrkggkgllpvrw  180

         iadGmayl+a+kfvhrdlaarncmvaed+tvkiGdfGmtrdiyetdyyrkggkgllpvrw

Q: 1120  IADGMAYLNANKFVHRDLAARNCMVAEDFTVKIGDFGMTRDIYETDYYRKGGKGLLPVRW  1179

         ************************************************************

S: 181   mspeslkdGvftsksdvwsfGvvlweivtlaeqpyqGlsneqvlkfvldggvlekpencp  240

         mspeslkdGvft++sdvwsfGvvlwei+tlaeqpyqGlsneqvl+fv++gg+l+kp+ncp

Q: 1180  MSPESLKDGVFTTHSDVWSFGVVLWEIATLAEQPYQGLSNEQVLRFVMEGGLLDKPDNCP  1239

         ************************************************************

S: 241   elltelmrlcwqynpklrpsfleivell  268

         ++l+elmr+cwqynpk+rpsflei+ ++

Q: 1240  DMLFELMRMCWQYNPKMRPSFLEIIGSI  1267

         ************************9875

Domain Sequence
(FASTA)

ITMNRELGQG SFGMVYEGVA KGVVKDEPET RVAIKTVNEA ASMRERIEFL NEASVMKEFN 60

CHHVVRLLGV VSQGQPTLVI MELMTRGDLK SYLRSLRPEV ENNLVLIPPS LSKMIQMAGE 120

IADGMAYLNA NKFVHRDLAA RNCMVAEDFT VKIGDFGMTR DIYETDYYRK GGKGLLPVRW 180

MSPESLKDGV FTTHSDVWSF GVVLWEIATL AEQPYQGLSN EQVLRFVMEG GLLDKPDNCP 240

DMLFELMRMC WQYNPKMRPS FLEIIGSI 268

Keyword

ATP-binding; Cleavage on pair of basic residues; Complete proteome; Disulfide bond; Glycoprotein; Isopeptide bond; Kinase; Membrane; Nucleotide-binding; Phosphoprotein; Receptor; Reference proteome; Repeat; Signal; Transferase; Transmembrane; Transmembrane helix; Tyrosine-protein kinase; Ubl conjugation.

Sequence Source

Ensembl

Orthology

Ortholog group

Anolis carolinensis"; ?>Bos taurus"; ?>Callithrix jacchus"; ?>Canis familiaris"; ?>Cavia porcellus"; ?>Ciona intestinalis"; ?>Danio rerio"; ?>Drosophila melanogaster"; ?>Equus caballus"; ?>Felis catus"; ?>Gallus gallus"; ?>Gasterosteus aculeatus"; ?>Homo sapiens"; ?>Loxodonta africana"; ?>Macaca mulatta"; ?>Meleagris gallopavo"; ?>Monodelphis domestica"; ?>Mus musculus"; ?>Mustela putorius furo"; ?>Myotis lucifugus"; ?>Oreochromis niloticus"; ?>Oryctolagus cuniculus"; ?>Oryzias latipes"; ?>Otolemur garnettii"; ?>Pan troglodytes"; ?>Pelodiscus sinensis"; ?>Petromyzon marinus"; ?>Pongo abelii"; ?>Sarcophilus harrisii"; ?>Sus scrofa"; ?>Taeniopygia guttata"; ?>Takifugu rubripes"; ?>Tetraodon nigroviridis"; ?>Tursiops truncatus"; ?>Xenopus tropicalis"; ?>Xiphophorus maculatus"; ?>

Gene Ontology

GO:0005901	; C:caveola
GO:0016021	; C:integral to membrane
GO:0043005	; C:neuron projection
GO:0005524	; F:ATP binding
GO:0043559	; F:insulin binding
GO:0043560	; F:insulin receptor substrate binding
GO:0005520	; F:insulin-like growth factor binding
GO:0005010	; F:insulin-like growth factor-activated receptor activity
GO:0043548	; F:phosphatidylinositol 3-kinase binding
GO:0007409	; P:axonogenesis
GO:0007420	; P:brain development
GO:0030010	; P:establishment of cell polarity
GO:0031017	; P:exocrine pancreas development
GO:0006955	; P:immune response
GO:0051389	; P:inactivation of MAPKK activity
GO:0030238	; P:male sex determination
GO:0030879	; P:mammary gland development
GO:0010656	; P:negative regulation of muscle cell apoptotic process
GO:0051898	; P:negative regulation of protein kinase B signaling cascade
GO:0048015	; P:phosphatidylinositol-mediated signaling
GO:0030335	; P:positive regulation of cell migration
GO:0032467	; P:positive regulation of cytokinesis
GO:0051054	; P:positive regulation of DNA metabolic process
GO:0045740	; P:positive regulation of DNA replication
GO:0043410	; P:positive regulation of MAPK cascade
GO:0051897	; P:positive regulation of protein kinase B signaling cascade
GO:0090031	; P:positive regulation of steroid hormone biosynthetic process
GO:0060740	; P:prostate gland epithelium morphogenesis
GO:0046777	; P:protein autophosphorylation
GO:0051291	; P:protein heterooligomerization
GO:0051262	; P:protein tetramerization
GO:0046328	; P:regulation of JNK cascade
GO:0033197	; P:response to vitamin E

KEGG

rno:25718

;

InterPros

IPR000494	; EGF_rcpt_L.
IPR003961	; Fibronectin_type3.
IPR006211	; Furin-like_Cys-rich_dom.
IPR006212	; Furin_repeat.
IPR009030	; Growth_fac_rcpt.
IPR013783	; Ig-like_fold.
IPR011009	; Kinase-like_dom.
IPR000719	; Prot_kinase_cat_dom.
IPR017441	; Protein_kinase_ATP_BS.
IPR001245	; Ser-Thr/Tyr_kinase_cat_dom.
IPR008266	; Tyr_kinase_AS.
IPR020635	; Tyr_kinase_cat_dom.
IPR016246	; Tyr_kinase_insulin-like_rcpt.
IPR002011	; Tyr_kinase_rcpt_2_CS.

Pfam

PF00041	; fn3; 1.
PF00757	; Furin-like; 1.
PF07714	; Pkinase_Tyr; 1.
PF01030	; Recep_L_domain; 2.

SMARTs

SM00060	; FN3; 3.
SM00261	; FU; 1.
SM00219	; TyrKc; 1.

Prosites

PS50853	; FN3; 3.
PS00107	; PROTEIN_KINASE_ATP; 1.
PS50011	; PROTEIN_KINASE_DOM; 1.
PS00109	; PROTEIN_KINASE_TYR; 1.
PS00239	; RECEPTOR_TYR_KIN_II; 1.

Prints

PR00109

; TYRKINASE.

Created Date

20-Feb-2013