Q00993 (UFO_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Tyrosine-protein kinase receptor UFO
EC=2.7.10.1

Alternative name(s):
Adhesion-related kinase

Gene names

Name:	Axl
Synonyms:	Ark, Ufo

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	888 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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 process	Differentiation Immunity Innate immunity
Cellular component	Cell membrane Membrane
Disease	Oncogene
Domain	Immunoglobulin domain Repeat Signal Transmembrane Transmembrane helix
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Receptor Transferase Tyrosine-protein kinase
PTM	Disulfide bond Glycoprotein Phosphoprotein Ubl conjugation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	apoptotic 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: Compara cellular response to extracellular stimulus Inferred from direct assay PubMed 10322635. Source: MGI cellular response to interferon-alpha Inferred from electronic annotation. Source: Compara cellular response to lipopolysaccharide Inferred from electronic annotation. Source: Compara dendritic cell differentiation Inferred from electronic annotation. Source: Compara 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 dendritic cell apoptotic process Inferred from electronic annotation. Source: Compara negative regulation of interferon-gamma production Inferred from electronic annotation. Source: Compara 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 ovulation cycle Inferred from genetic interaction PubMed 18787040. Source: MGI platelet activation Inferred from mutant phenotype PubMed 15650770. Source: MGI positive regulation of cytokine-mediated signaling pathway Inferred from electronic annotation. Source: Compara positive regulation of natural killer cell differentiation Inferred from electronic annotation. Source: Compara positive regulation of protein kinase B signaling cascade Inferred from mutant phenotype PubMed 16723520. Source: UniProtKB protein kinase B signaling cascade 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_component	cell surface Inferred from electronic annotation. Source: Compara extracellular space Inferred from electronic annotation. Source: Compara integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW plasma membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW phosphatidylserine binding Inferred from electronic annotation. Source: Compara transmembrane receptor protein tyrosine kinase activity Inferred from electronic annotation. Source: EC
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 18	18	Potential
	Chain	19 – 888	870	Tyrosine-protein kinase receptor UFO		PRO_0000024482
Regions
	Topological domain	19 – 445	427	Extracellular Potential
	Transmembrane	446 – 466	21	Helical; Potential
	Topological domain	467 – 888	422	Cytoplasmic Potential
	Domain	30 – 122	93	Ig-like C2-type 1
	Domain	133 – 216	84	Ig-like C2-type 2
	Domain	219 – 326	108	Fibronectin type-III 1
	Domain	327 – 419	93	Fibronectin type-III 2
	Domain	530 – 801	272	Protein kinase
	Nucleotide binding	536 – 544	9	ATP By similarity
	Region	19 – 86	68	Interaction with GAS6 By similarity
Sites
	Active site	666	1	Proton acceptor By similarity
	Binding site	561	1	ATP By similarity
Amino acid modifications
	Modified residue	697	1	Phosphotyrosine; by autocatalysis By similarity
	Modified residue	773	1	Phosphotyrosine; by autocatalysis By similarity
	Modified residue	815	1	Phosphotyrosine; by autocatalysis By similarity
	Modified residue	860	1	Phosphotyrosine; by autocatalysis By similarity
	Glycosylation	37	1	N-linked (GlcNAc...) Potential
	Glycosylation	151	1	N-linked (GlcNAc...) Potential
	Glycosylation	192	1	N-linked (GlcNAc...) Potential
	Glycosylation	333	1	N-linked (GlcNAc...) Potential
	Glycosylation	339	1	N-linked (GlcNAc...) Potential
	Glycosylation	395	1	N-linked (GlcNAc...) Potential
	Disulfide bond	50 ↔ 111		By similarity
	Disulfide bond	154 ↔ 199		By similarity
Experimental info
	Sequence conflict	394	1	A → R in CAA42158. Ref.2
	Sequence conflict	486	1	G → P in CAA42158. Ref.2
	Sequence conflict	566	1	A → V in CAA42158. Ref.2
	Sequence conflict	768	1	C → F in CAA45097. Ref.1
	Sequence conflict	774	1	A → S in CAA45097. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Q00993 [UniParc]. Last modified July 27, 2011. Version 2. Checksum: C5350E3A8995E975	FASTA	888	98,191
	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

References

	« Hide 'large scale' referencesShow '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. , 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. , 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.
IPI	IPI00312509.
PIR	S23065. S23251.
RefSeq	NP_033491.2. NM_009465.4.
UniGene	Mm.4128.
3D structure databases
ProteinModelPortal	Q00993.
SMR	Q00993. Positions 29-417, 485-836.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q00993. 1 interaction.
STRING	10090.ENSMUSP00000002677.
Protein family/group databases
MEROPS	I43.001.
PTM databases
PhosphoSite	Q00993.
Proteomic databases
PaxDb	Q00993.
PRIDE	Q00993.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000002677; ENSMUSP00000002677; ENSMUSG00000002602.
GeneID	26362.
KEGG	mmu:26362.
UCSC	uc009ftx.2. mouse.
Organism-specific databases
CTD	558.
MGI	MGI:1347244. Axl.
Phylogenomic databases
eggNOG	COG0515.
GeneTree	ENSGT00550000074361.
HOGENOM	HOG000231685.
HOVERGEN	HBG006346.
InParanoid	Q80YQ3.
KO	K05115.
OMA	WQEPRAP.
OrthoDB	EOG44BB1N.
Enzyme and pathway databases
BRENDA	2.7.10.1. 3474.
Gene expression databases
ArrayExpress	Q00993.
Bgee	Q00993.
CleanEx	MM_AXL.
Genevestigator	Q00993.
GermOnline	ENSMUSG00000002602. Mus musculus.
Family and domain databases
Gene3D	2.60.40.10. 4 hits.
InterPro	IPR003961. Fibronectin_type3. IPR007110. Ig-like_dom. 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. [Graphical view]
Pfam	PF00041. fn3. 2 hits. PF07714. Pkinase_Tyr. 1 hit. [Graphical view]
PRINTS	PR00109. TYRKINASE.
SMART	SM00060. FN3. 2 hits. SM00409. IG. 2 hits. SM00219. TyrKc. 1 hit. [Graphical view]
SUPFAM	SSF49265. FN_III-like. 2 hits. SSF56112. Kinase_like. 1 hit.
PROSITE	PS50853. 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]
ProtoNet	Search...
Other
ChiTaRS	AXL. mouse.
NextBio	304223.
PMAP-CutDB	Q80YQ3.
SOURCE	Search...

Entry information

Entry name

UFO_MOUSE

Accession

Primary (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:	May 29, 2013
This is version 136 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program