EKS-MUM-00431

Eukaryotic Protein Kinase & Protein Phosphatase Database

Tag

Content

EKPD ID

EKS-MUM-00431

Classification

Group/Family	Score	E-Value	Start	End	Domain Length
TK/Axl	551.3	8.5E-166	521	786	266

Status

Reviewed

Ensembl Protein

ENSMUSP00000083110

UniProt Accession

Q00993; Q80YQ3;

Protein Name

Tyrosine-protein kinase receptor UFO

Protein Synonyms/Alias

Adhesion-related kinase;

Gene Name

Axl

Gene Synonyms/Alias

Axl; Ark, Ufo;

Ensembl Information

Ensembl Gene ID	Ensembl Protein ID	Ensembl Transcript ID
ENSMUSG00000002602	ENSMUSP00000114907	ENSMUST00000132038
ENSMUSG00000002602	ENSMUSP00000083110	ENSMUST00000085948
ENSMUSG00000002602	ENSMUSP00000002677	ENSMUST00000002677

Organism

Mus musculus

Functional Description

Receptor tyrosine kinase that transduces signals fromthe extracellular matrix into the cytoplasm by binding growth factor GAS6 and which is thus regulating many physiological processes including cell survival, cell proliferation, migration and differentiation. Ligand binding at the cell surface induces dimerization and autophosphorylation of AXL. Following activation by ligand, ALX binds and induces tyrosine phosphorylation of PI3- kinase subunits PIK3R1, PIK3R2 and PIK3R3; but also GRB2, PLCG1, LCK and PTPN11. Other downstream substrate candidates for AXL are CBL, NCK2, SOCS1 and TENC1. Recruitment of GRB2 and phosphatidylinositol 3 kinase regulatory subunits by AXL leads to the downstream activation of the AKT kinase. GAS6/AXL signaling plays a role in various processes such as endothelial cell survival during acidification by preventing apoptosis, optimal cytokine signaling during human natural killer cell development, hepatic regeneration, gonadotropin-releasing hormone neuron survival and migration, platelet activation, or regulation of thrombotic responses. Plays also an important role in inhibition of Toll-like receptors (TLRs)-mediated innate immune response.

Protein Length

879

Protein Sequence
(FASTA)

MGRVPLAWWL ALCCWGCAAH KDTQTEAGSP FVGNPGNITG ARGLTGTLRC ELQVQGEPPE 60

VVWLRDGQIL ELADNTQTQV PLGEDWQDEW KVVSQLRISA LQLSDAGEYQ CMVHLEGRTF 120

VSQPGFVGLE GLPYFLEEPE DKAVPANTPF NLSCQAQGPP EPVTLLWLQD AVPLAPVTGH 180

SSQHSLQTPG LNKTSSFSCE AHNAKGVTTS RTATITVLPQ RPHHLHVVSR QPTELEVAWT 240

PGLSGIYPLT HCNLQAVLSD DGVGIWLGKS DPPEDPLTLQ VSVPPHQLRL EKLLPHTPYH 300

IRISCSSSQG PSPWTHWLPV ETTEGVPLGP PENVSAMRNG SQVLVRWQEP RVPLQGTLLG 360

YRLAYRGQDT PEVLMDIGLT REVTLELRGD RPVANLTVSV TAYTSAGDGP WSLPVPLEPW 420

RPVSEPPPRA FSWPWWYVLL GALVAAACVL ILALFLVHRR KKETRYGEVF EPTVERGELV 480

VRYRVRKSYS RRTTEATLNS LGISEELKEK LRDVMVDRHK VALGKTLGEG EFGAVMEGQL 540

NQDDSILKVA VKTMKIAICT RSELEDFLSE AVCMKEFDHP NVMRLIGVCF QGSDREGFPE 600

PVVILPFMKH GDLHSFLLYS RLGDQPVFLP TQMLVKFMAD IASGMEYLST KRFIHRDLAA 660

RNCMLNENMS VCVADFGLSK KIYNGDYYRQ GRIAKMPVKW IAIESLADRV YTSKSDVWSF 720

GVTMWEIATR GQTPYPGVEN SEIYDYLRQG NRLKQPVDCL DGLYALMSRC WELNPRDRPS 780

FAELREDLEN TLKALPPAQE PDEILYVNMD EGGSHLEPRG AAGGADPPTQ PDPKDSCSCL 840

TAADVHSAGR YVLCPSTAPG PTLSADRGCP APPGQEDGA 879

Nucleotide Sequence
(FASTA)

ATGGGCAGGG TCCCGCTGGC CTGGTGGTTG GCGCTGTGCT GCTGGGGGTG TGCAGCCCAT 60

AAGGACACAC AGACCGAGGC TGGCAGCCCG TTTGTGGGGA ACCCAGGGAA TATCACAGGT 120

GCCAGAGGAC TCACGGGGAC ACTTCGGTGT GAGCTCCAGG TTCAGGGGGA ACCCCCTGAG 180

GTGGTGTGGC TTCGAGATGG ACAGATCCTA GAACTGGCTG ATAACACCCA GACCCAGGTG 240

CCTCTGGGCG AAGACTGGCA AGATGAATGG AAAGTTGTCA GTCAGCTCAG AATCTCAGCC 300

CTGCAACTTT CAGATGCAGG GGAGTACCAG TGTATGGTGC ATCTAGAAGG ACGGACCTTT 360

GTGTCTCAGC CGGGCTTTGT AGGGCTGGAA GGTCTCCCGT ACTTCCTGGA GGAGCCTGAG 420

GACAAAGCTG TGCCTGCCAA CACCCCTTTC AACCTAAGCT GCCAGGCCCA GGGACCCCCG 480

GAACCCGTGA CCCTACTCTG GCTTCAAGAT GCTGTCCCCC TGGCCCCAGT CACAGGACAC 540

AGCTCCCAGC ACAGTCTGCA AACTCCAGGC CTGAACAAGA CATCTTCTTT CTCATGTGAA 600

GCCCACAATG CCAAGGGAGT CACCACCTCC CGCACAGCCA CCATCACAGT GCTCCCCCAG 660

AGGCCTCACC ATCTCCACGT GGTTTCCAGA CAACCTACGG AGCTAGAGGT AGCTTGGACC 720

CCTGGCCTGA GTGGCATCTA CCCGCTCACC CACTGCAACC TGCAGGCCGT GCTGTCAGAC 780

GATGGGGTGG GTATCTGGCT GGGAAAGTCA GATCCTCCTG AAGACCCCCT CACCTTGCAA 840

GTATCAGTGC CCCCCCACCA GCTTCGGCTG GAAAAGCTCC TTCCTCACAC CCCGTATCAC 900

ATCCGGATAT CCTGCAGCAG CAGCCAGGGC CCCTCACCTT GGACCCACTG GCTTCCTGTG 960

GAGACCACAG AGGGAGTGCC CTTGGGTCCC CCTGAGAACG TTAGCGCCAT GCGGAATGGG 1020

AGCCAGGTCC TCGTGCGTTG GCAGGAGCCA AGGGTGCCCC TGCAAGGCAC CCTGTTAGGG 1080

TACCGGCTGG CATATCGAGG CCAGGACACC CCCGAGGTAC TTATGGATAT AGGGCTAACT 1140

CGAGAGGTGA CCTTGGAACT GCGGGGGGAC AGGCCTGTGG CTAACCTGAC TGTGTCTGTG 1200

ACAGCCTATA CCTCGGCTGG GGATGGGCCC TGGAGCCTTC CTGTGCCCCT AGAGCCCTGG 1260

CGCCCAGTGA GTGAACCCCC ACCTCGCGCC TTCTCGTGGC CTTGGTGGTA TGTACTGCTG 1320

GGAGCACTTG TGGCTGCCGC CTGCGTCCTC ATCTTGGCCC TGTTCCTTGT CCATCGGAGG 1380

AAGAAGGAGA CTCGATATGG GGAGGTGTTT GAGCCAACCG TGGAAAGAGG TGAACTGGTA 1440

GTCAGGTACC GTGTCCGAAA GTCCTACAGC CGGCGGACCA CTGAAGCCAC CTTGAACAGT 1500

CTGGGCATCA GTGAAGAGCT GAAGGAGAAA CTACGAGACG TCATGGTAGA TCGGCATAAG 1560

GTGGCCTTGG GGAAGACCCT GGGAGAAGGA GAATTTGGCG CTGTGATGGA AGGTCAGCTC 1620

AATCAGGATG ACTCCATCCT CAAGGTCGCT GTGAAGACCA TGAAAATTGC CATCTGCACA 1680

AGATCAGAGC TGGAGGATTT CCTGAGTGAA GCTGTCTGCA TGAAGGAATT TGACCACCCC 1740

AACGTCATGA GGCTCATTGG CGTCTGTTTT CAGGGCTCTG ACAGAGAGGG TTTCCCAGAA 1800

CCTGTGGTCA TCTTGCCTTT CATGAAACAC GGAGACCTAC ACAGTTTCCT CCTGTACTCC 1860

CGGCTCGGGG ACCAGCCAGT GTTCCTGCCC ACTCAGATGC TAGTGAAGTT CATGGCCGAC 1920

ATTGCCAGTG GTATGGAGTA CCTGAGTACC AAGAGATTCA TACATCGGGA CCTGGCTGCC 1980

AGGAACTGCA TGCTGAATGA GAACATGTCC GTGTGTGTGG CAGACTTCGG GCTCTCCAAG 2040

AAGATCTACA ACGGGGATTA CTACCGCCAA GGGCGCATTG CCAAGATGCC AGTCAAGTGG 2100

ATTGCTATTG AGAGTCTGGC AGATCGGGTC TACACCAGCA AGAGCGATGT GTGGTCCTTC 2160

GGTGTGACAA TGTGGGAGAT CGCCACCCGA GGCCAAACTC CCTATCCAGG GGTGGAGAAC 2220

AGTGAGATTT ACGACTACCT GCGTCAAGGA AATCGGCTGA AACAGCCTGT GGACTGTCTG 2280

GACGGCCTGT ATGCCCTGAT GTCTCGGTGC TGGGAACTGA ACCCTCGAGA CCGGCCAAGT 2340

TTTGCGGAGC TCCGGGAAGA CTTGGAGAAC ACACTGAAGG CTCTGCCCCC TGCTCAGGAG 2400

CCAGATGAAA TCCTCTATGT CAACATGGAT GAGGGCGGAA GCCACCTTGA ACCCCGTGGG 2460

GCTGCTGGAG GAGCTGACCC CCCAACCCAA CCTGATCCTA AGGATTCCTG TAGCTGTCTC 2520

ACTGCAGCTG ACGTCCACTC AGCTGGACGC TATGTCCTTT GTCCTTCTAC AGCCCCAGGA 2580

CCCACTCTGT CTGCTGACAG AGGCTGCCCA GCACCTCCAG GGCAGGAGGA CGGAGCCTGA 2640

Domain Profile

S: 1     lvlgkvlgegefgsvmegqlkqedgsilkvavktlkldiiarseieeflseaacmkefdh  60

         ++lgk+lgegefg+vmegql+q+d silkvavkt+k++i++rse+e+flsea+cmkefdh

Q: 521   VALGKTLGEGEFGAVMEGQLNQDD-SILKVAVKTMKIAICTRSELEDFLSEAVCMKEFDH  579

         68**********************.***********************************

S: 61    pnvirlvgvslessekgrlpkpvvilpfmkygdlhafllysrlgenpvylplqtlvkfmv  120

         pnv+rl+gv++++s+++ +p+pvvilpfmk+gdlh+fllysrlg++pv+lp+q+lvkfm+

Q: 580   PNVMRLIGVCFQGSDREGFPEPVVILPFMKHGDLHSFLLYSRLGDQPVFLPTQMLVKFMA  639

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

S: 121   diasgmeylssrnfihrdlaarncmlaedmtvcvadfglskkiysgdyyrqgriaklpvk  180

         diasgmeyls+++fihrdlaarncml+e+m+vcvadfglskkiy+gdyyrqgriak+pvk

Q: 640   DIASGMEYLSTKRFIHRDLAARNCMLNENMSVCVADFGLSKKIYNGDYYRQGRIAKMPVK  699

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

S: 181   wiaiesladrvytsksdvwafgvtmweiatrgqtpyagvenaeiydyllqgnrlkqpedc  240

         wiaiesladrvytsksdvw+fgvtmweiatrgqtpy+gven+eiydyl+qgnrlkqp+dc

Q: 700   WIAIESLADRVYTSKSDVWSFGVTMWEIATRGQTPYPGVENSEIYDYLRQGNRLKQPVDC  759

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

S: 241   ldelydlmyrcweadpkdrpsfsvlre  267

         ld+ly+lm+rcwe++p+drpsf++lre

Q: 760   LDGLYALMSRCWELNPRDRPSFAELRE  786

         *************************96

Domain Sequence
(FASTA)

VALGKTLGEG EFGAVMEGQL NQDDSILKVA VKTMKIAICT RSELEDFLSE AVCMKEFDHP 60

NVMRLIGVCF QGSDREGFPE PVVILPFMKH GDLHSFLLYS RLGDQPVFLP TQMLVKFMAD 120

IASGMEYLST KRFIHRDLAA RNCMLNENMS VCVADFGLSK KIYNGDYYRQ GRIAKMPVKW 180

IAIESLADRV YTSKSDVWSF GVTMWEIATR GQTPYPGVEN SEIYDYLRQG NRLKQPVDCL 240

DGLYALMSRC WELNPRDRPS FAELRE 266

Keyword

ATP-binding; Cell membrane; Complete proteome; Differentiation; Disulfide bond; Glycoprotein; Immunity; Immunoglobulin domain; Innate immunity; Kinase; Membrane; Nucleotide-binding; Oncogene; Phosphoprotein; Receptor; Reference proteome; Repeat; Signal; Transferase; Transmembrane; Transmembrane helix; Tyrosine-protein kinase; Ubl conjugation.

Sequence Source

Ensembl

Orthology

Ortholog group

Ailuropoda melanoleuca"; ?>Anolis carolinensis"; ?>Bos taurus"; ?>Callithrix jacchus"; ?>Cavia porcellus"; ?>Ciona intestinalis"; ?>Equus caballus"; ?>Gasterosteus aculeatus"; ?>Gorilla gorilla"; ?>Homo sapiens"; ?>Ictidomys tridecemlineatus"; ?>Latimeria chalumnae"; ?>Loxodonta africana"; ?>Macaca mulatta"; ?>Monodelphis domestica"; ?>Mustela putorius furo"; ?>Myotis lucifugus"; ?>Oreochromis niloticus"; ?>Oryctolagus cuniculus"; ?>Oryzias latipes"; ?>Otolemur garnettii"; ?>Pan troglodytes"; ?>Petromyzon marinus"; ?>Pongo abelii"; ?>Rattus norvegicus"; ?>Sarcophilus harrisii"; ?>Takifugu rubripes"; ?>Tetraodon nigroviridis"; ?>Xenopus tropicalis"; ?>Xiphophorus maculatus"; ?>

Gene Ontology

GO:0009986	; C:cell surface
GO:0005615	; C:extracellular space
GO:0016021	; C:integral to membrane
GO:0005886	; C:plasma membrane
GO:0005524	; F:ATP binding
GO:0001786	; F:phosphatidylserine binding
GO:0004714	; F:transmembrane receptor protein tyrosine kinase activity
GO:0043277	; P:apoptotic cell clearance
GO:0001974	; P:blood vessel remodeling
GO:0048469	; P:cell maturation
GO:0031668	; P:cellular response to extracellular stimulus
GO:0035457	; P:cellular response to interferon-alpha
GO:0071222	; P:cellular response to lipopolysaccharide
GO:0097028	; P:dendritic cell differentiation
GO:0007167	; P:enzyme linked receptor protein signaling pathway
GO:0034101	; P:erythrocyte homeostasis
GO:0021885	; P:forebrain cell migration
GO:0006954	; P:inflammatory response
GO:0045087	; P:innate immune response
GO:0001779	; P:natural killer cell differentiation
GO:2000669	; P:negative regulation of dendritic cell apoptotic process
GO:0032689	; P:negative regulation of interferon-gamma production
GO:0051250	; P:negative regulation of lymphocyte activation
GO:0043524	; P:negative regulation of neuron apoptotic process
GO:0032720	; P:negative regulation of tumor necrosis factor production
GO:0001764	; P:neuron migration
GO:0042698	; P:ovulation cycle
GO:0030168	; P:platelet activation
GO:0001961	; P:positive regulation of cytokine-mediated signaling pathway
GO:0032825	; P:positive regulation of natural killer cell differentiation
GO:0051897	; P:positive regulation of protein kinase B signaling cascade
GO:0043491	; P:protein kinase B signaling cascade
GO:0032940	; P:secretion by cell
GO:0007283	; P:spermatogenesis
GO:0034446	; P:substrate adhesion-dependent cell spreading
GO:0060068	; P:vagina development

KEGG

mmu:26362

;

InterPros

IPR003961	; Fibronectin_type3.
IPR007110	; Ig-like.
IPR013783	; Ig-like_fold.
IPR003599	; Ig_sub.
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.

Pfam

PF00041	; fn3; 2.
PF07714	; Pkinase_Tyr; 1.

SMARTs

SM00060	; FN3; 2.
SM00409	; IG; 2.
SM00219	; TyrKc; 1.

Prosites

PS50853	; FN3; 2.
PS50835	; IG_LIKE; 2.
PS00107	; PROTEIN_KINASE_ATP; 1.
PS50011	; PROTEIN_KINASE_DOM; 1.
PS00109	; PROTEIN_KINASE_TYR; 1.

Prints

PR00109

; TYRKINASE.

Created Date

20-Feb-2013