EKS-MUM-00338

Eukaryotic Protein Kinase & Protein Phosphatase Database

Tag

Content

EKPD ID

EKS-MUM-00338

Classification

Group/Family	Score	E-Value	Start	End	Domain Length
TK/Alk	534.2	1.4E-160	1120	1389	270

Status

Reviewed

Ensembl Protein

ENSMUSP00000083840

UniProt Accession

P97793; E9QKV3;

Protein Name

ALK tyrosine kinase receptor

Protein Synonyms/Alias

Anaplastic lymphoma kinase;

Gene Name

Alk

Gene Synonyms/Alias

Alk;

Ensembl Information

Ensembl Gene ID	Ensembl Protein ID	Ensembl Transcript ID
ENSMUSG00000055471	ENSMUSP00000083840	ENSMUST00000086639

Organism

Mus musculus

Functional Description

Neuronal orphan receptor tyrosine kinase that isessentially and transiently expressed in specific regions of the central and peripheral nervous systems and plays an important role in the genesis and differentiation of the nervous system. Transduces signals from ligands at the cell surface, through specific activation of the mitogen-activated protein kinase (MAPK) pathway. Phosphorylates almost exclusively at the first tyrosine of the Y-x-x-x-Y-Y motif. Following activation by ligand, ALK induces tyrosine phosphorylation of CBL, FRS2, IRS1 and SHC1, as well as of the MAP kinases MAPK1/ERK2 and MAPK3/ERK1. Acts as a receptor for ligands pleiotrophin (PTN), a secreted growth factor, and midkine (MDK), a PTN-related factor, thus participating in PTN and MDK signal transduction. PTN-binding induces MAPK pathway activation, which is important for the anti-apoptotic signaling of PTN and regulation of cell proliferation. MDK-binding induces phosphorylation of the ALK target insulin receptor substrate (IRS1), activates mitogen-activated protein kinases (MAPKs) and PI3-kinase, resulting also in cell proliferation induction. Drives NF-kappa-B activation, probably through IRS1 and the activation of the AKT serine/threonine kinase. Recruitment of IRS1 to activated ALK and the activation of NF-kappa-B are essential for the autocrine growth and survival signaling of MDK.

Protein Length

1621

Protein Sequence
(FASTA)

MGAAGFLWLL PPLLLAAASY SGAATDQRAG SPASGPPLQP REPLSYSRLQ RKSLAVDFVV 60

PSLFRVYARD LLLPQPRSPS EPEAGGLEAR GSLALDCEPL LRLLGPLPGI SWADGASSPS 120

PEAGPTLSRV LKGGSVRKLR RAKQLVLELG EETILEGCIG PPEEVAAVGI LQFNLSELFS 180

WWILHGEGRL RIRLMPEKKA SEVGREGRLS SAIRASQPRL LFQIFGTGHS SMESPSETPS 240

PPGTFMWNLT WTMKDSFPFL SHRSRYGLEC SFDFPCELEY SPPLHNHGNQ SWSWRHVPSE 300

EASRMNLLDG PEAEHSQEMP RGSFLLLNTS ADSKHTILSP WMRSSSDHCT LAVSVHRHLQ 360

PSGRYVAQLL PHNEAGREIL LVPTPGKHGW TVLQGRVGRP ANPFRVALEY ISSGNRSLSA 420

VDFFALKNCS EGTSPGSKMA LQSSFTCWNG TVLQLGQACD FHQDCAQGED EGQLCSKLPA 480

GFYCNFENGF CGWTQSPLSP HMPRWQVRTL RDAHSQGHQG RALLLSTTDI LASEGATVTS 540

ATFPAPMKNS PCELRMSWLI RGVLRGNVSL VLVENKTGKE QSRTVWHVAT DEGLSLWQHT 600

VLSLLDVTDR FWLQIVTWWG PGSRATVGFD NISISLDCYL TISGEEKMSL NSVPKSRNLF 660

EKNPNKESKS WANISGPTPI FDPTVHWLFT TCGASGPHGP TQAQCNNAYQ NSNLSVVVGS 720

EGPLKGVQIW KVPATDTYSI SGYGAAGGKG GKNTMMRSHG VSVLGIFNLE KGDTLYILVG 780

QQGEDACPRA NQLIQKVCVG ENNVIEEEIR VNRSVHEWAG GGGGGGGATY VFKMKDGVPV 840

PLIIAAGGGG RAYGAKTETF HPERLESNSS VLGLNGNSGA AGGGGGWNDN TSLLWAGKSL 900

LEGAAGGHSC PQAMKKWGWE TRGGFGGGGG GCSSGGGGGG YIGGNAASNN DPEMDGEDGV 960

SFISPLGILY TPALKVMEGH GEVNIKHYLN CSHCEVDECH MDPESHKVIC FCDHGTVLAD 1020

DGVSCIVSPT PEPHLPLSLI LSVVTSALVA ALVLAFSGIM IVYRRKHQEL QAMQMELQSP 1080

EYKLSKLRTS TIMTDYNPNY CFAGKTSSIS DLKEVPRKNI TLIRGLGHGA FGEVYEGQVS 1140

GMPNDPSPLQ VAVKTLPEVC SEQDELDFLM EALIISKFNH QNIVRCIGVS LQALPRFILL 1200

ELMAGGDLKS FLRETRPRPN QPTSLAMLDL LHVARDIACG CQYLEENHFI HRDIAARNCL 1260

LTCPGAGRIA KIGDFGMARD IYRASYYRKG GCAMLPVKWM PPEAFMEGIF TSKTDTWSFG 1320

VLLWEIFSLG YMPYPSKSNQ EVLEFVTSGG RMDPPKNCPG PVYRIMTQCW QHQPEDRPNF 1380

AIILERIEYC TQDPDVINTA LPIEYGPVVE EEEKVPMRPK DPEGMPPLLV SPQPAKHEEA 1440

SAAPQPAALT APGPSVKKPP GAGAGAGAGA GAGPVPRGAA DRGHVNMAFS QPNPPPELHK 1500

GPGSRNKPTS LWNPTYGSWF TEKPAKKTHP PPGAEPQARA GAAEGGWTGP GAGPRRAEAA 1560

LLLEPSALSA TMKEVPLFRL RHFPCGNVNY GYQQQGLPLE ATAAPGDTML KSKNKVTQPG 1620

P 1621

Nucleotide Sequence
(FASTA)

ATGGGAGCTG CTGGGTTCCT GTGGCTGCTG CCTCCACTGC TTTTGGCAGC AGCCTCGTAC 60

TCCGGAGCTG CAACCGATCA GCGCGCGGGT TCCCCAGCCT CAGGGCCTCC TCTGCAGCCC 120

CGGGAGCCGC TCAGTTATTC GCGCCTGCAG AGGAAGAGTC TGGCAGTGGA CTTCGTTGTA 180

CCCTCGCTCT TCCGCGTCTA TGCCCGAGAC CTGCTGCTAC CGCAGCCACG GTCCCCCTCG 240

GAGCCCGAGG CTGGCGGGCT GGAGGCGCGG GGATCACTGG CCCTGGATTG TGAGCCTCTG 300

CTCAGGCTGC TGGGGCCACT GCCTGGAATC TCCTGGGCAG ATGGAGCCAG TTCTCCTAGT 360

CCCGAGGCGG GTCCGACGCT GTCCAGGGTG CTGAAGGGAG GCTCGGTGCG CAAGCTCAGG 420

CGTGCCAAAC AGCTGGTGCT GGAGCTGGGC GAGGAGACGA TTCTTGAAGG CTGTATTGGT 480

CCCCCAGAGG AGGTAGCGGC TGTGGGGATA CTCCAGTTCA ACCTCAGCGA GCTGTTCAGC 540

TGGTGGATTC TCCACGGCGA AGGGAGGCTG AGGATCCGCC TGATGCCTGA GAAGAAGGCA 600

TCGGAAGTGG GCAGGGAGGG AAGGCTATCC AGTGCGATCC GAGCCTCCCA GCCCCGCCTT 660

CTCTTCCAGA TCTTCGGGAC GGGACACAGC TCCATGGAGT CACCCTCAGA AACGCCTTCT 720

CCTCCTGGTA CCTTCATGTG GAATCTGACC TGGACGATGA AAGACTCCTT CCCTTTCCTT 780

TCCCACCGCA GTCGATATGG TCTGGAGTGC AGCTTTGACT TCCCCTGTGA GCTGGAATAT 840

TCTCCTCCCC TGCACAACCA CGGGAATCAG AGCTGGTCCT GGCGCCATGT GCCCTCCGAG 900

GAGGCCTCGA GGATGAACTT GCTGGATGGG CCAGAGGCAG AGCATTCTCA AGAGATGCCC 960

AGAGGCTCCT TCCTCCTCCT GAACACCTCT GCAGATTCCA AGCATACCAT TCTGAGCCCA 1020

TGGATGAGGA GCAGTAGTGA TCACTGCACA CTGGCTGTCT CCGTGCACAG ACATCTACAG 1080

CCTTCGGGGA GATATGTTGC CCAGCTCCTA CCCCACAACG AAGCTGGAAG AGAGATTCTT 1140

TTGGTGCCCA CCCCAGGGAA GCATGGCTGG ACAGTGCTGC AGGGGAGAGT CGGGCGCCCA 1200

GCAAACCCAT TTCGAGTGGC TCTGGAATAC ATCTCCAGTG GCAACCGGAG CTTGTCGGCG 1260

GTGGATTTCT TTGCCCTGAA GAACTGCAGT GAAGGGACAT CCCCAGGCTC CAAGATGGCA 1320

TTGCAGAGTT CCTTCACTTG TTGGAATGGG ACCGTCCTCC AGCTCGGGCA AGCCTGTGAT 1380

TTCCACCAGG ACTGTGCCCA AGGAGAAGAT GAGGGCCAGC TGTGCAGTAA ACTTCCTGCT 1440

GGATTTTACT GTAACTTTGA AAATGGCTTC TGTGGCTGGA CCCAAAGTCC ACTCTCACCC 1500

CATATGCCCC GGTGGCAAGT GAGGACCCTA AGAGATGCCC ATTCCCAGGG CCACCAAGGC 1560

CGTGCCCTGT TGCTCAGCAC CACTGACATC CTCGCTTCTG AAGGTGCAAC AGTGACCAGT 1620

GCCACCTTCC CTGCACCAAT GAAAAATTCT CCTTGTGAGC TCCGCATGTC CTGGCTCATC 1680

CGCGGGGTTT TGAGAGGAAA CGTATCTCTG GTGCTGGTGG AGAACAAAAC CGGAAAGGAG 1740

CAAAGCCGGA CTGTCTGGCA TGTCGCCACT GACGAAGGCT TAAGCCTGTG GCAGCATACA 1800

GTGCTGTCCC TCCTCGATGT GACTGACAGG TTCTGGCTGC AGATAGTCAC ATGGTGGGGT 1860

CCAGGATCCA GGGCAACCGT GGGATTTGAC AACATTTCCA TCAGCCTCGA CTGCTACCTT 1920

ACCATCAGTG GAGAGGAGAA AATGTCCCTG AATTCAGTAC CCAAATCTAG AAATCTGTTT 1980

GAGAAAAACC CAAACAAGGA GTCAAAATCC TGGGCAAACA TATCAGGACC AACTCCCATC 2040

TTCGACCCTA CAGTTCACTG GCTGTTCACC ACGTGTGGGG CCAGTGGACC TCATGGCCCC 2100

ACCCAGGCAC AGTGCAACAA CGCCTACCAG AATTCCAACT TGAGCGTGGT GGTGGGAAGT 2160

GAAGGGCCCT TGAAGGGAGT CCAGATTTGG AAAGTGCCAG CTACTGACAC CTACAGTATC 2220

TCGGGCTACG GAGCAGCTGG CGGGAAAGGT GGGAAAAACA CCATGATGCG GTCCCATGGC 2280

GTGTCTGTCC TGGGCATCTT CAATCTGGAG AAAGGTGACA CACTCTACAT CCTTGTCGGT 2340

CAGCAAGGGG AGGATGCCTG TCCCAGGGCA AACCAACTAA TCCAGAAAGT CTGTGTGGGT 2400

GAGAACAATG TCATAGAAGA AGAGATCCGA GTGAACAGAA GCGTGCACGA GTGGGCAGGA 2460

GGAGGAGGAG GTGGGGGTGG AGCCACCTAC GTGTTTAAGA TGAAAGATGG CGTGCCTGTA 2520

CCCCTGATCA TTGCAGCTGG TGGTGGTGGC AGGGCCTATG GGGCCAAGAC AGAAACGTTC 2580

CACCCAGAGA GACTGGAGAG TAACTCCTCG GTTCTAGGGC TGAACGGCAA TTCCGGAGCC 2640

GCAGGTGGTG GAGGCGGCTG GAATGATAAC ACTTCCTTGC TCTGGGCCGG AAAGTCTTTG 2700

CTGGAGGGTG CCGCCGGAGG ACATTCCTGC CCCCAGGCCA TGAAGAAGTG GGGGTGGGAG 2760

ACAAGAGGGG GTTTCGGAGG GGGTGGAGGG GGGTGCTCCT CAGGTGGAGG AGGCGGAGGA 2820

TATATAGGTG GCAACGCAGC ATCAAACAAT GACCCCGAAA TGGATGGGGA AGATGGGGTT 2880

TCCTTCATCA GTCCATTGGG TATCCTGTAC ACCCCGGCCT TAAAAGTGAT GGAGGGCCAC 2940

GGGGAAGTGA ATATCAAGCA TTATCTAAAC TGCAGTCACT GCGAGGTAGA CGAATGTCAC 3000

ATGGACCCCG AGAGCCACAA AGTCATCTGC TTCTGTGATC ATGGGACCGT GCTGGCTGAT 3060

GATGGTGTCT CCTGCATTGT GTCACCCACC CCGGAGCCCC ACCTGCCGCT CTCATTGATC 3120

CTCTCCGTCG TGACCTCTGC CCTGGTGGCT GCCCTTGTTC TGGCATTCTC CGGCATCATG 3180

ATTGTGTACC GTCGGAAGCA CCAGGAGTTG CAGGCTATGC AGATGGAACT GCAGAGCCCC 3240

GAGTATAAGC TGAGCAAGCT ACGGACCTCG ACCATCATGA CCGACTACAA CCCCAACTAC 3300

TGCTTCGCTG GCAAGACTTC CTCCATCAGT GACCTGAAAG AAGTGCCACG GAAAAACATC 3360

ACACTCATCC GGGGCCTAGG CCATGGCGCA TTTGGGGAGG TGTATGAAGG CCAGGTGTCT 3420

GGAATGCCCA ATGACCCAAG CCCTCTACAA GTGGCTGTAA AGACGCTGCC AGAAGTGTGT 3480

TCAGAACAAG ATGAGCTGGA CTTTCTCATG GAAGCTCTGA TCATCAGCAA ATTCAACCAC 3540

CAGAATATTG TTCGCTGCAT CGGGGTGAGT CTACAAGCCC TGCCCCGCTT CATCCTGCTG 3600

GAACTCATGG CTGGCGGAGA CCTCAAGTCC TTCCTCAGGG AGACACGCCC TCGCCCGAAC 3660

CAACCCACCT CCCTGGCCAT GCTGGACCTT CTGCATGTGG CTCGGGACAT TGCCTGTGGC 3720

TGTCAGTACC TAGAGGAGAA TCACTTTATC CACCGGGATA TTGCTGCTAG AAACTGTCTG 3780

TTGACCTGCC CAGGAGCTGG AAGAATAGCA AAGATTGGAG ACTTTGGGAT GGCCCGAGAT 3840

ATCTACAGGG CCAGCTACTA CCGAAAGGGA GGCTGCGCCA TGCTGCCGGT CAAGTGGATG 3900

CCCCCTGAAG CCTTCATGGA AGGGATATTT ACCTCTAAAA CAGACACATG GTCTTTTGGA 3960

GTGTTGCTAT GGGAAATATT TTCTCTTGGA TATATGCCGT ACCCCAGCAA GAGCAACCAG 4020

GAAGTTCTGG AGTTTGTCAC CAGCGGAGGA CGGATGGACC CGCCTAAGAA CTGCCCCGGG 4080

CCTGTATACC GGATAATGAC GCAGTGCTGG CAGCATCAGC CTGAAGACAG ACCCAACTTC 4140

GCCATCATTT TGGAGAGGAT CGAATACTGC ACCCAGGACC CCGATGTGAT CAACACAGCT 4200

CTGCCCATCG AATACGGTCC AGTAGTAGAA GAGGAGGAGA AAGTGCCCAT GCGCCCCAAA 4260

GACCCCGAGG GGATGCCACC TTTGCTGGTG TCTCCCCAGC CTGCGAAGCA CGAGGAGGCG 4320

TCCGCAGCTC CCCAGCCCGC AGCCCTGACG GCACCAGGCC CATCGGTGAA GAAGCCCCCG 4380

GGTGCGGGTG CGGGCGCGGG CGCGGGTGCG GGTGCCGGCC CGGTGCCCCG AGGTGCGGCC 4440

GATCGGGGCC ACGTGAACAT GGCTTTCTCT CAGCCCAACC CTCCCCCGGA GCTGCACAAA 4500

GGCCCGGGAT CCAGAAACAA GCCGACCAGC CTGTGGAACC CCACCTACGG CTCGTGGTTC 4560

ACCGAGAAGC CTGCCAAAAA GACCCATCCT CCGCCAGGCG CCGAGCCGCA GGCGCGGGCA 4620

GGAGCGGCCG AGGGTGGCTG GACCGGGCCG GGCGCGGGGC CCCGCAGAGC CGAGGCAGCG 4680

CTGCTGCTAG AGCCATCGGC GCTGAGCGCC ACCATGAAGG AGGTGCCGCT GTTCAGGCTG 4740

CGCCACTTCC CCTGCGGCAA TGTCAACTAT GGTTACCAGC AACAGGGTCT CCCCTTGGAA 4800

GCCACAGCCG CGCCAGGGGA CACCATGCTG AAAAGCAAGA ATAAGGTCAC CCAGCCGGGG 4860

CCCTGA 4866

Domain Profile

S: 1     ielvralGkGafGevyeglvsglpgdasklavavktlpesaseqdeldflkealiiskfn  60

         i+l+r+lG+GafGevyeg+vsg+p+d+s+l+vavktlpe++seqdeldfl+ealiiskfn

Q: 1120  ITLIRGLGHGAFGEVYEGQVSGMPNDPSPLQVAVKTLPEVCSEQDELDFLMEALIISKFN  1179

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

S: 61    henivrliGvsleklprlillellaGGdlksflresrpkpeqlsslamkdllkvaldvak  120

         h+nivr+iGvsl++lpr+illel+aGGdlksflre+rp+p+q++slam dll+va+d+a+

Q: 1180  HQNIVRCIGVSLQALPRFILLELMAGGDLKSFLRETRPRPNQPTSLAMLDLLHVARDIAC  1239

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

S: 121   GckyleenkfihrdiaarnillsskGpsrvakiadfGmardiyraeyyrkggrallpvkw  180

         Gc+yleen+fihrdiaarn+ll+++G++r+aki+dfGmardiyra+yyrkgg+a+lpvkw

Q: 1240  GCQYLEENHFIHRDIAARNCLLTCPGAGRIAKIGDFGMARDIYRASYYRKGGCAMLPVKW  1299

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

S: 181   mppeafleGiftsktdvwsfGvllwevfslGvvpypgksnqevlelvveGgrldspkeip  240

         mppeaf+eGiftsktd+wsfGvllwe+fslG++pyp+ksnqevle+v++Ggr+d+pk++p

Q: 1300  MPPEAFMEGIFTSKTDTWSFGVLLWEIFSLGYMPYPSKSNQEVLEFVTSGGRMDPPKNCP  1359

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

S: 241   gsvyrimtdcwkhepedrpkfvsilerlqa  270

         g+vyrimt+cw+h+pedrp+f++iler+++

Q: 1360  GPVYRIMTQCWQHQPEDRPNFAIILERIEY  1389

         ***************************986

Domain Sequence
(FASTA)

ITLIRGLGHG AFGEVYEGQV SGMPNDPSPL QVAVKTLPEV CSEQDELDFL MEALIISKFN 60

HQNIVRCIGV SLQALPRFIL LELMAGGDLK SFLRETRPRP NQPTSLAMLD LLHVARDIAC 120

GCQYLEENHF IHRDIAARNC LLTCPGAGRI AKIGDFGMAR DIYRASYYRK GGCAMLPVKW 180

MPPEAFMEGI FTSKTDTWSF GVLLWEIFSL GYMPYPSKSN QEVLEFVTSG GRMDPPKNCP 240

GPVYRIMTQC WQHQPEDRPN FAIILERIEY 270

Keyword

ATP-binding; Cell membrane; Complete proteome; Glycoprotein; Kinase; Membrane; Nucleotide-binding; Phosphoprotein; Receptor; Reference proteome; Repeat; Signal; Transferase; Transmembrane; Transmembrane helix; Tyrosine-protein kinase.

Sequence Source

Ensembl

Orthology

Ortholog group

Anolis carolinensis"; ?>Bos taurus"; ?>Caenorhabditis elegans"; ?>Callithrix jacchus"; ?>Canis familiaris"; ?>Cavia porcellus"; ?>Danio rerio"; ?>Drosophila melanogaster"; ?>Equus caballus"; ?>Felis catus"; ?>Gallus gallus"; ?>Gasterosteus aculeatus"; ?>Gorilla gorilla"; ?>Homo sapiens"; ?>Ictidomys tridecemlineatus"; ?>Latimeria chalumnae"; ?>Loxodonta africana"; ?>Macaca mulatta"; ?>Macropus eugenii"; ?>Meleagris gallopavo"; ?>Monodelphis domestica"; ?>Mustela putorius furo"; ?>Myotis lucifugus"; ?>Nomascus leucogenys"; ?>Oreochromis niloticus"; ?>Ornithorhynchus anatinus"; ?>Oryctolagus cuniculus"; ?>Oryzias latipes"; ?>Otolemur garnettii"; ?>Pelodiscus sinensis"; ?>Petromyzon marinus"; ?>Pongo abelii"; ?>Rattus norvegicus"; ?>Sarcophilus harrisii"; ?>Sus scrofa"; ?>Taeniopygia guttata"; ?>Takifugu rubripes"; ?>Tetraodon nigroviridis"; ?>Xenopus tropicalis"; ?>Xiphophorus maculatus"; ?>

Gene Ontology

GO:0005887	; C:integral to plasma membrane
GO:0005524	; F:ATP binding
GO:0004714	; F:transmembrane receptor protein tyrosine kinase activity
GO:0000187	; P:activation of MAPK activity
GO:0048666	; P:neuron development
GO:0007169	; P:transmembrane receptor protein tyrosine kinase signaling pathway

KEGG

mmu:11682

;

InterPros

IPR026830	; ALK.
IPR008985	; ConA-like_lec_gl_sf.
IPR011009	; Kinase-like_dom.
IPR002172	; LDrepeatLR_classA_rpt.
IPR000998	; MAM_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.
IPR002011	; Tyr_kinase_rcpt_2_CS.

Pfam

PF00629	; MAM; 2.
PF07714	; Pkinase_Tyr; 1.

SMARTs

SM00192	; LDLa; 1.
SM00219	; TyrKc; 1.

Prosites

PS01209	; LDLRA_1; FALSE_NEG.
PS50068	; LDLRA_2; FALSE_NEG.
PS00740	; MAM_1; FALSE_NEG.
PS50060	; MAM_2; 2.
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