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Q00993 (UFO_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 146. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Tyrosine-protein kinase receptor UFO

EC=2.7.10.1
Alternative name(s):
Adhesion-related kinase
Gene names
Name:Axl
Synonyms:Ark, Ufo
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length888 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

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. Ref.7 Ref.8

Catalytic activity

ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.

Enzyme regulation

Activated by GAS6-binding and subsequent autophosphorylation By similarity.

Subunit structure

Heterodimer and heterotetramer with ligand GAS6 By similarity. 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 By similarity. Ref.6

Subcellular location

Cell membrane; Single-pass type I membrane protein By similarity.

Tissue specificity

In distinct substructures of a broad spectrum of developing tissues (in the late embryogenesis). In cells forming organ capsules as well as in connective tissue structures (in adult).

Post-translational modification

Monoubiquitinated upon GAS6-binding. A very small proportion of the receptor could be subjected to polyubiquitination in a very transient fashion By similarity.

Phosphorylated at tyrosine residues by autocatalysis, which activates kinase activity By similarity.

Sequence similarities

Belongs to the protein kinase superfamily. Tyr protein kinase family. AXL/UFO subfamily.

Contains 2 fibronectin type-III domains.

Contains 2 Ig-like C2-type (immunoglobulin-like) domains.

Contains 1 protein kinase domain.

Ontologies

Keywords
   Biological processDifferentiation
Immunity
Innate immunity
   Cellular componentCell membrane
Membrane
   DiseaseOncogene
   DomainImmunoglobulin domain
Repeat
Signal
Transmembrane
Transmembrane helix
   LigandATP-binding
Nucleotide-binding
   Molecular functionKinase
Receptor
Transferase
Tyrosine-protein kinase
   PTMDisulfide bond
Glycoprotein
Phosphoprotein
Ubl conjugation
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processapoptotic cell clearance

Inferred from genetic interaction PubMed 18159085. Source: UniProtKB

blood vessel remodeling

Inferred from mutant phenotype PubMed 16627783. Source: MGI

cell maturation

Inferred from electronic annotation. Source: Ensembl

cellular response to extracellular stimulus

Inferred from direct assay PubMed 10322635. Source: MGI

cellular response to hydrogen peroxide

Inferred from electronic annotation. Source: Ensembl

cellular response to interferon-alpha

Inferred from electronic annotation. Source: Ensembl

cellular response to lipopolysaccharide

Inferred from electronic annotation. Source: Ensembl

dendritic cell differentiation

Inferred from electronic annotation. Source: Ensembl

enzyme linked receptor protein signaling pathway

Inferred from genetic interaction PubMed 9395235. Source: MGI

erythrocyte homeostasis

Inferred from mutant phenotype PubMed 18188450. Source: MGI

forebrain cell migration

Inferred from genetic interaction PubMed 18787040. Source: MGI

inflammatory response

Inferred from mutant phenotype PubMed 16627783. Source: MGI

innate immune response

Inferred from electronic annotation. Source: UniProtKB-KW

natural killer cell differentiation

Inferred from genetic interaction PubMed 16751775. Source: MGI

negative regulation of apoptotic process

Inferred from mutant phenotype PubMed 16723520. Source: UniProtKB

negative regulation of dendritic cell apoptotic process

Inferred from electronic annotation. Source: Ensembl

negative regulation of interferon-gamma production

Inferred from electronic annotation. Source: Ensembl

negative regulation of lymphocyte activation

Inferred from genetic interaction PubMed 11452127. Source: MGI

negative regulation of neuron apoptotic process

Inferred from mutant phenotype PubMed 18787040. Source: MGI

negative regulation of tumor necrosis factor production

Inferred from genetic interaction PubMed 16831897. Source: MGI

neuron migration

Inferred from mutant phenotype PubMed 19463168. Source: MGI

organ regeneration

Inferred from electronic annotation. Source: Ensembl

ovulation cycle

Inferred from genetic interaction PubMed 18787040. Source: MGI

phagocytosis

Inferred from genetic interaction PubMed 19602523. Source: MGI

platelet activation

Inferred from mutant phenotype PubMed 15650770. Source: MGI

positive regulation of cytokine-mediated signaling pathway

Inferred from electronic annotation. Source: Ensembl

positive regulation of natural killer cell differentiation

Inferred from electronic annotation. Source: Ensembl

positive regulation of protein kinase B signaling

Inferred from mutant phenotype PubMed 16723520. Source: UniProtKB

protein kinase B signaling

Inferred from mutant phenotype PubMed 16627783. Source: MGI

secretion by cell

Inferred from mutant phenotype PubMed 15650770. Source: MGI

spermatogenesis

Inferred from genetic interaction PubMed 10227296PubMed 19602523. Source: MGI

substrate adhesion-dependent cell spreading

Inferred from mutant phenotype PubMed 15650770. Source: MGI

vagina development

Inferred from genetic interaction PubMed 18393392. Source: MGI

   Cellular_componentcell surface

Inferred from electronic annotation. Source: Ensembl

extracellular space

Inferred from electronic annotation. Source: Ensembl

integral component of membrane

Inferred from electronic annotation. Source: UniProtKB-KW

plasma membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

phosphatidylserine binding

Inferred from electronic annotation. Source: Ensembl

protein heterodimerization activity

Inferred from physical interaction PubMed 18787040. Source: MGI

transmembrane receptor protein tyrosine kinase activity

Inferred from electronic annotation. Source: UniProtKB-EC

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 1818 Potential
Chain19 – 888870Tyrosine-protein kinase receptor UFO
PRO_0000024482

Regions

Topological domain19 – 445427Extracellular Potential
Transmembrane446 – 46621Helical; Potential
Topological domain467 – 888422Cytoplasmic Potential
Domain30 – 12293Ig-like C2-type 1
Domain133 – 21684Ig-like C2-type 2
Domain221 – 325105Fibronectin type-III 1
Domain330 – 42293Fibronectin type-III 2
Domain530 – 801272Protein kinase
Nucleotide binding536 – 5449ATP By similarity
Region19 – 8668Interaction with GAS6 By similarity

Sites

Active site6661Proton acceptor By similarity
Binding site5611ATP By similarity

Amino acid modifications

Modified residue6971Phosphotyrosine; by autocatalysis By similarity
Modified residue7731Phosphotyrosine; by autocatalysis By similarity
Modified residue8151Phosphotyrosine; by autocatalysis By similarity
Modified residue8601Phosphotyrosine; by autocatalysis By similarity
Glycosylation371N-linked (GlcNAc...) Potential
Glycosylation1511N-linked (GlcNAc...) Potential
Glycosylation1921N-linked (GlcNAc...) Potential
Glycosylation3331N-linked (GlcNAc...) Potential
Glycosylation3391N-linked (GlcNAc...) Potential
Glycosylation3951N-linked (GlcNAc...) Potential
Disulfide bond50 ↔ 111 By similarity
Disulfide bond154 ↔ 199 By similarity

Experimental info

Sequence conflict3941A → R in CAA42158. Ref.2
Sequence conflict4861G → P in CAA42158. Ref.2
Sequence conflict5661A → V in CAA42158. Ref.2
Sequence conflict7681C → F in CAA45097. Ref.1
Sequence conflict7741A → S in CAA45097. Ref.1

Sequences

Sequence LengthMass (Da)Tools
Q00993 [UniParc].

Last modified July 27, 2011. Version 2.
Checksum: C5350E3A8995E975

FASTA88898,191
        10         20         30         40         50         60 
MGRVPLAWWL ALCCWGCAAH KDTQTEAGSP FVGNPGNITG ARGLTGTLRC ELQVQGEPPE 

        70         80         90        100        110        120 
VVWLRDGQIL ELADNTQTQV PLGEDWQDEW KVVSQLRISA LQLSDAGEYQ CMVHLEGRTF 

       130        140        150        160        170        180 
VSQPGFVGLE GLPYFLEEPE DKAVPANTPF NLSCQAQGPP EPVTLLWLQD AVPLAPVTGH 

       190        200        210        220        230        240 
SSQHSLQTPG LNKTSSFSCE AHNAKGVTTS RTATITVLPQ RPHHLHVVSR QPTELEVAWT 

       250        260        270        280        290        300 
PGLSGIYPLT HCNLQAVLSD DGVGIWLGKS DPPEDPLTLQ VSVPPHQLRL EKLLPHTPYH 

       310        320        330        340        350        360 
IRISCSSSQG PSPWTHWLPV ETTEGVPLGP PENVSAMRNG SQVLVRWQEP RVPLQGTLLG 

       370        380        390        400        410        420 
YRLAYRGQDT PEVLMDIGLT REVTLELRGD RPVANLTVSV TAYTSAGDGP WSLPVPLEPW 

       430        440        450        460        470        480 
RPGQGQPLHH LVSEPPPRAF SWPWWYVLLG ALVAAACVLI LALFLVHRRK KETRYGEVFE 

       490        500        510        520        530        540 
PTVERGELVV RYRVRKSYSR RTTEATLNSL GISEELKEKL RDVMVDRHKV ALGKTLGEGE 

       550        560        570        580        590        600 
FGAVMEGQLN QDDSILKVAV KTMKIAICTR SELEDFLSEA VCMKEFDHPN VMRLIGVCFQ 

       610        620        630        640        650        660 
GSDREGFPEP VVILPFMKHG DLHSFLLYSR LGDQPVFLPT QMLVKFMADI ASGMEYLSTK 

       670        680        690        700        710        720 
RFIHRDLAAR NCMLNENMSV CVADFGLSKK IYNGDYYRQG RIAKMPVKWI AIESLADRVY 

       730        740        750        760        770        780 
TSKSDVWSFG VTMWEIATRG QTPYPGVENS EIYDYLRQGN RLKQPVDCLD GLYALMSRCW 

       790        800        810        820        830        840 
ELNPRDRPSF AELREDLENT LKALPPAQEP DEILYVNMDE GGSHLEPRGA AGGADPPTQP 

       850        860        870        880 
DPKDSCSCLT AADVHSAGRY VLCPSTAPGP TLSADRGCPA PPGQEDGA 

« Hide

References

« Hide 'large scale' references
[1]"The murine ufo receptor: molecular cloning, chromosomal localization and in situ expression analysis."
Faust M., Ebensperger C., Schulz A.S., Schleithoff L., Hameister H., Bartram C.R., Janssen J.W.G.
Oncogene 7:1287-1293(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Strain: CD-1.
Tissue: Heart.
[2]"A putative receptor tyrosine kinase with unique structural topology."
Rescigno J., Mansukhani A., Basilico C.
Oncogene 6:1909-1913(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]"The transcriptional landscape of the mammalian genome."
Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. expand/collapse author list , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Strain: NOD.
Tissue: Dendritic cell.
[4]Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Strain: C57BL/6.
Tissue: Brain and Eye.
[6]"The anticoagulation factor protein S and its relative, Gas6, are ligands for the Tyro 3/Axl family of receptor tyrosine kinases."
Stitt T.N., Conn G., Gore M., Lai C., Bruno J., Radziejewski C., Mattsson K., Fisher J., Gies D.R., Jones P.F., Masiakowski P., Ryan T.E., Tobkes N.J., Chen D.H., DiStefano P.S., Long G.L., Basilico C., Goldfarb M.P. expand/collapse author list , Lemke G., Glass D.J., Yancopoulos G.D.
Cell 80:661-670(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH LIGAND GAS6.
[7]"TAM receptors are pleiotropic inhibitors of the innate immune response."
Rothlin C.V., Ghosh S., Zuniga E.I., Oldstone M.B., Lemke G.
Cell 131:1124-1136(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN INNATE IMMUNE RESPONSE INHIBITION.
[8]"Sertoli cell-initiated testicular innate immune response through toll-like receptor-3 activation is negatively regulated by Tyro3, Axl, and mer receptors."
Sun B., Qi N., Shang T., Wu H., Deng T., Han D.
Endocrinology 151:2886-2897(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN INNATE IMMUNE RESPONSE INHIBITION.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X63535 mRNA. Translation: CAA45097.1.
X59560 Genomic DNA. Translation: CAA42158.1.
AK155567 mRNA. Translation: BAE33327.1.
CH466593 Genomic DNA. Translation: EDL24236.1.
BC046618 mRNA. Translation: AAH46618.1.
BC050914 mRNA. Translation: AAH50914.1.
CCDSCCDS20996.1.
PIRS23065.
S23251.
RefSeqNP_033491.2. NM_009465.4.
XP_006540052.1. XM_006539989.1.
XP_006540053.1. XM_006539990.1.
UniGeneMm.4128.

3D structure databases

ProteinModelPortalQ00993.
SMRQ00993. Positions 29-417, 485-836.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid204922. 1 interaction.
IntActQ00993. 2 interactions.
STRING10090.ENSMUSP00000002677.

Protein family/group databases

MEROPSI43.001.

PTM databases

PhosphoSiteQ00993.

Proteomic databases

PaxDbQ00993.
PRIDEQ00993.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000002677; ENSMUSP00000002677; ENSMUSG00000002602.
GeneID26362.
KEGGmmu:26362.
UCSCuc009ftx.2. mouse.

Organism-specific databases

CTD558.
MGIMGI:1347244. Axl.

Phylogenomic databases

eggNOGCOG0515.
GeneTreeENSGT00720000108377.
HOGENOMHOG000231685.
HOVERGENHBG006346.
InParanoidQ80YQ3.
KOK05115.
OMAQVQGEPP.
OrthoDBEOG77DJ5C.
TreeFamTF317402.

Enzyme and pathway databases

BRENDA2.7.10.1. 3474.

Gene expression databases

ArrayExpressQ00993.
BgeeQ00993.
CleanExMM_AXL.
GenevestigatorQ00993.

Family and domain databases

Gene3D2.60.40.10. 4 hits.
InterProIPR003961. Fibronectin_type3.
IPR007110. Ig-like_dom.
IPR013783. Ig-like_fold.
IPR003599. Ig_sub.
IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR001245. Ser-Thr/Tyr_kinase_cat_dom.
IPR008266. Tyr_kinase_AS.
IPR020635. Tyr_kinase_cat_dom.
[Graphical view]
PfamPF00041. fn3. 2 hits.
PF07714. Pkinase_Tyr. 1 hit.
[Graphical view]
PRINTSPR00109. TYRKINASE.
SMARTSM00060. FN3. 2 hits.
SM00409. IG. 2 hits.
SM00219. TyrKc. 1 hit.
[Graphical view]
SUPFAMSSF49265. SSF49265. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEPS50853. FN3. 2 hits.
PS50835. IG_LIKE. 2 hits.
PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00109. PROTEIN_KINASE_TYR. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSAXL. mouse.
NextBio304223.
PMAP-CutDBQ80YQ3.
PROQ00993.
SOURCESearch...

Entry information

Entry nameUFO_MOUSE
AccessionPrimary (citable) accession number: Q00993
Secondary accession number(s): Q80YQ3
Entry history
Integrated into UniProtKB/Swiss-Prot: April 1, 1993
Last sequence update: July 27, 2011
Last modified: July 9, 2014
This is version 146 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot