Human Gene AXL (uc010ehj.3) Description and Page Index
  Description: Homo sapiens AXL receptor tyrosine kinase (AXL), transcript variant 1, mRNA.
RefSeq Summary (NM_021913): The protein encoded by this gene is a member of the Tyro3-Axl-Mer (TAM) receptor tyrosine kinase subfamily. The encoded protein possesses an extracellular domain which is composed of two immunoglobulin-like motifs at the N-terminal, followed by two fibronectin type-III motifs. It transduces signals from the extracellular matrix into the cytoplasm by binding to the vitamin K-dependent protein growth arrest-specific 6 (Gas6). This gene may be involved in several cellular functions including growth, migration, aggregation and anti-inflammation in multiple cell types. Alternative splicing results in multiple transcript variants of this gene. [provided by RefSeq, Jul 2013].
Transcript (Including UTRs)
   Position: hg19 chr19:41,725,108-41,767,671 Size: 42,564 Total Exon Count: 20 Strand: +
Coding Region
   Position: hg19 chr19:41,725,298-41,765,809 Size: 40,512 Coding Exon Count: 20 

Page IndexSequence and LinksUniProtKB CommentsGenetic AssociationsMalaCardsCTD
Gene AllelesRNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther Species
GO AnnotationsmRNA DescriptionsPathwaysOther NamesGeneReviewsModel Information
Methods
Data last updated: 2013-06-14

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr19:41,725,108-41,767,671)mRNA (may differ from genome)Protein (894 aa)
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neXtProtOMIMPubMedReactomeStanford SOURCETreefam
UniProtKBWikipedia

-  Comments and Description Text from UniProtKB
  ID: UFO_HUMAN
DESCRIPTION: RecName: Full=Tyrosine-protein kinase receptor UFO; EC=2.7.10.1; AltName: Full=AXL oncogene; Flags: Precursor;
FUNCTION: Receptor tyrosine kinase that transduces signals from the 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. In case of filovirus infection, seems to function as a cell entry factor.
CATALYTIC ACTIVITY: ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.
ENZYME REGULATION: Activated by GAS6-binding and subsequent autophosphorylation.
SUBUNIT: Heterodimer and heterotetramer with ligand GAS6. Interacts with CBL, GRB2, LCK, NCK2, PIK3R1, PIK3R2, PIK3R3, PLCG1, SOCS1 and TENC1. Part of a complex including AXL, TNK2 and GRB2, in which GRB2 promotes AXL recruitment by TNK2.
SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane protein.
TISSUE SPECIFICITY: Highly expressed in metastatic colon tumors. Expressed in primary colon tumors. Weakly expressed in normal colon tissue.
PTM: Monoubiquitinated upon GAS6-binding. A very small proportion of the receptor could be subjected to polyubiquitination in a very transient fashion.
PTM: Phosphorylated at tyrosine residues by autocatalysis, which activates kinase activity.
DISEASE: Note=AXL and its ligand GAS6 are highly expressed in thyroid carcinoma tissues, and might thus be involved in thiroid tumorigenesis. Overexpression of AXL and its ligand was also detected in many other cancers such as myeloptoliferative disorders, prostatic carcinoma cells, or breast cancer.
SIMILARITY: Belongs to the protein kinase superfamily. Tyr protein kinase family. AXL/UFO subfamily.
SIMILARITY: Contains 2 fibronectin type-III domains.
SIMILARITY: Contains 2 Ig-like C2-type (immunoglobulin-like) domains.
SIMILARITY: Contains 1 protein kinase domain.

-  Genetic Association Studies of Complex Diseases and Disorders
  Genetic Association Database (archive): AXL
CDC HuGE Published Literature: AXL

-  MalaCards Disease Associations
  MalaCards Gene Search: AXL
Diseases sorted by gene-association score: zika virus infection (18), lymphocytic choriomeningitis (16), femoral neuropathy (9), mesangial proliferative glomerulonephritis (8), breast cancer (6), lassa fever (6), borna disease (5), la crosse encephalitis (5), lung cancer (2)

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

+  Common Gene Haplotype Alleles
  Press "+" in the title bar above to open this section.

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 59.95 RPKM in Cells - Transformed fibroblasts
Total median expression: 820.81 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -104.80190-0.552 Picture PostScript Text
3' UTR -537.081862-0.288 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR003961 - Fibronectin_type3
IPR007110 - Ig-like
IPR013783 - Ig-like_fold
IPR003599 - Ig_sub
IPR013106 - Ig_V-set
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 Domains:
PF00041 - Fibronectin type III domain
PF00069 - Protein kinase domain
PF07679 - Immunoglobulin I-set domain
PF07714 - Protein tyrosine kinase
PF13927 - Immunoglobulin domain

SCOP Domains:
48726 - Immunoglobulin
49265 - Fibronectin type III
56112 - Protein kinase-like (PK-like)

Protein Data Bank (PDB) 3-D Structure
MuPIT help

2C5D
- X-ray MuPIT


ModBase Predicted Comparative 3D Structure on P30530
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The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
No orthologGenome BrowserNo orthologNo orthologNo orthologNo ortholog
Gene DetailsGene Details    
Gene SorterGene Sorter    
 RGD    
 Protein Sequence    
 Alignment    

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0000166 nucleotide binding
GO:0001618 virus receptor activity
GO:0001786 phosphatidylserine binding
GO:0004672 protein kinase activity
GO:0004713 protein tyrosine kinase activity
GO:0004714 transmembrane receptor protein tyrosine kinase activity
GO:0005515 protein binding
GO:0005524 ATP binding
GO:0016301 kinase activity
GO:0016740 transferase activity
GO:0032036 myosin heavy chain binding
GO:0043548 phosphatidylinositol 3-kinase binding
GO:0046982 protein heterodimerization activity

Biological Process:
GO:0001764 neuron migration
GO:0001779 natural killer cell differentiation
GO:0001818 negative regulation of cytokine production
GO:0001961 positive regulation of cytokine-mediated signaling pathway
GO:0001974 blood vessel remodeling
GO:0002376 immune system process
GO:0006468 protein phosphorylation
GO:0006909 phagocytosis
GO:0006954 inflammatory response
GO:0007165 signal transduction
GO:0007167 enzyme linked receptor protein signaling pathway
GO:0007283 spermatogenesis
GO:0016032 viral process
GO:0016310 phosphorylation
GO:0018108 peptidyl-tyrosine phosphorylation
GO:0021885 forebrain cell migration
GO:0030154 cell differentiation
GO:0030168 platelet activation
GO:0031100 animal organ regeneration
GO:0031668 cellular response to extracellular stimulus
GO:0032689 negative regulation of interferon-gamma production
GO:0032720 negative regulation of tumor necrosis factor production
GO:0032825 positive regulation of natural killer cell differentiation
GO:0032940 secretion by cell
GO:0034101 erythrocyte homeostasis
GO:0034446 substrate adhesion-dependent cell spreading
GO:0035457 cellular response to interferon-alpha
GO:0042698 ovulation cycle
GO:0043066 negative regulation of apoptotic process
GO:0043277 apoptotic cell clearance
GO:0043491 protein kinase B signaling
GO:0043524 negative regulation of neuron apoptotic process
GO:0045087 innate immune response
GO:0046718 viral entry into host cell
GO:0048010 vascular endothelial growth factor receptor signaling pathway
GO:0048469 cell maturation
GO:0048549 positive regulation of pinocytosis
GO:0051250 negative regulation of lymphocyte activation
GO:0051897 positive regulation of protein kinase B signaling
GO:0060068 vagina development
GO:0070301 cellular response to hydrogen peroxide
GO:0071222 cellular response to lipopolysaccharide
GO:0097028 dendritic cell differentiation
GO:0097350 neutrophil clearance
GO:2000669 negative regulation of dendritic cell apoptotic process

Cellular Component:
GO:0005615 extracellular space
GO:0005622 intracellular
GO:0005886 plasma membrane
GO:0005887 integral component of plasma membrane
GO:0009986 cell surface
GO:0016020 membrane
GO:0016021 integral component of membrane
GO:0044228 host cell surface
GO:0070062 extracellular exosome


-  Descriptions from all associated GenBank mRNAs
  JD080453 - Sequence 61477 from Patent EP1572962.
JD445378 - Sequence 426402 from Patent EP1572962.
JD342814 - Sequence 323838 from Patent EP1572962.
JD214635 - Sequence 195659 from Patent EP1572962.
JD179183 - Sequence 160207 from Patent EP1572962.
JD062681 - Sequence 43705 from Patent EP1572962.
BC032229 - Homo sapiens AXL receptor tyrosine kinase, mRNA (cDNA clone MGC:34202 IMAGE:5205825), complete cds.
M76125 - Human tyrosine kinase receptor (axl) mRNA, complete cds.
JD476922 - Sequence 457946 from Patent EP1572962.
S65125 - UFO=proto-oncogene [human, NIH3T3 cell, mRNA, 3116 nt].
X57019 - H.sapiens mRNA for tyrosine kinase receptor.
AK310881 - Homo sapiens cDNA, FLJ17923.
AB385214 - Synthetic construct DNA, clone: pF1KB9417, Homo sapiens AXL gene for AXL receptor tyrosine kinase, complete cds, without stop codon, in Flexi system.
DQ894117 - Synthetic construct Homo sapiens clone IMAGE:100008577; FLH167929.01L; RZPDo839H0589D AXL receptor tyrosine kinase (AXL) gene, encodes complete protein.
AK309139 - Homo sapiens cDNA, FLJ99180.
JD123899 - Sequence 104923 from Patent EP1572962.
JD452798 - Sequence 433822 from Patent EP1572962.
JD410667 - Sequence 391691 from Patent EP1572962.
JD555372 - Sequence 536396 from Patent EP1572962.
JD318528 - Sequence 299552 from Patent EP1572962.
X66029 - H.sapiens mRNA for tyrosine kinase receptor.
JD279887 - Sequence 260911 from Patent EP1572962.
JD510588 - Sequence 491612 from Patent EP1572962.
JD233933 - Sequence 214957 from Patent EP1572962.
JD145690 - Sequence 126714 from Patent EP1572962.
JD352866 - Sequence 333890 from Patent EP1572962.
JD526142 - Sequence 507166 from Patent EP1572962.
JD523253 - Sequence 504277 from Patent EP1572962.
JD406256 - Sequence 387280 from Patent EP1572962.
JD459843 - Sequence 440867 from Patent EP1572962.
JD246399 - Sequence 227423 from Patent EP1572962.
JD239923 - Sequence 220947 from Patent EP1572962.
JD128234 - Sequence 109258 from Patent EP1572962.
JD499762 - Sequence 480786 from Patent EP1572962.
JD342090 - Sequence 323114 from Patent EP1572962.
JD218498 - Sequence 199522 from Patent EP1572962.
JD466732 - Sequence 447756 from Patent EP1572962.
JD106923 - Sequence 87947 from Patent EP1572962.
JD377505 - Sequence 358529 from Patent EP1572962.
JD088203 - Sequence 69227 from Patent EP1572962.
JD367555 - Sequence 348579 from Patent EP1572962.
JD428943 - Sequence 409967 from Patent EP1572962.
JD446901 - Sequence 427925 from Patent EP1572962.
JD268191 - Sequence 249215 from Patent EP1572962.
JD240982 - Sequence 222006 from Patent EP1572962.
JD258082 - Sequence 239106 from Patent EP1572962.
JD232623 - Sequence 213647 from Patent EP1572962.
JD057998 - Sequence 39022 from Patent EP1572962.
JD183587 - Sequence 164611 from Patent EP1572962.
JD410674 - Sequence 391698 from Patent EP1572962.
JD166495 - Sequence 147519 from Patent EP1572962.
JD489729 - Sequence 470753 from Patent EP1572962.
JD501061 - Sequence 482085 from Patent EP1572962.
JD167451 - Sequence 148475 from Patent EP1572962.
JD559407 - Sequence 540431 from Patent EP1572962.
JD188300 - Sequence 169324 from Patent EP1572962.
JD089632 - Sequence 70656 from Patent EP1572962.
JD218864 - Sequence 199888 from Patent EP1572962.
JD291423 - Sequence 272447 from Patent EP1572962.
JD282103 - Sequence 263127 from Patent EP1572962.

-  Biochemical and Signaling Pathways
  Reactome (by CSHL, EBI, and GO)

Protein P30530 (Reactome details) participates in the following event(s):

R-HSA-5357432 AXL binds SRC-1
R-HSA-5357429 AXL autophosphorylates on Y772 and Y814
R-HSA-5357479 p-AXL binds PI3K
R-HSA-5218819 VEGFA dimer:p-6Y-VEGFR2 dimer:PI3K phosphorylates PIP2 to PIP3
R-HSA-4420097 VEGFA-VEGFR2 Pathway
R-HSA-194138 Signaling by VEGF
R-HSA-9006934 Signaling by Receptor Tyrosine Kinases
R-HSA-162582 Signal Transduction

-  Other Names for This Gene
  Alternate Gene Symbols: NM_021913, NP_068713, P30530, Q8N5L2, Q9UD27, UFO, UFO_HUMAN
UCSC ID: uc010ehj.3
RefSeq Accession: NM_021913
Protein: P30530 (aka UFO_HUMAN)
CCDS: CCDS12574.1, CCDS12575.1

-  GeneReviews for This Gene
  GeneReviews article(s) related to gene AXL:
kms (Isolated Gonadotropin-Releasing Hormone (GnRH) Deficiency)

-  Gene Model Information
 
category: coding nonsense-mediated-decay: no RNA accession: NM_021913.3
exon count: 20CDS single in 3' UTR: no RNA size: 4743
ORF size: 2685CDS single in intron: no Alignment % ID: 99.98
txCdsPredict score: 4714.00frame shift in genome: no % Coverage: 99.87
has start codon: yes stop codon in genome: no # of Alignments: 1
has end codon: yes retained intron: no # AT/AC introns 0
selenocysteine: no end bleed into intron: 0# strange splices: 0
Click here for a detailed description of the fields of the table above.

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.