P70451 (FER_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Tyrosine-protein kinase Fer
EC=2.7.10.2

Alternative name(s):
Proto-oncogene c-Fer
p94-Fer

Gene names

Name:	Fer
Synonyms:	Fert2

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	823 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Tyrosine-protein kinase that acts downstream of cell surface receptors for growth factors and plays a role in the regulation of the actin cytoskeleton, microtubule assembly, lamellipodia formation, cell adhesion, cell migration and chemotaxis. Acts downstream of EGFR, KIT, PDGFRA and PDGFRB. Acts downstream of EGFR to promote activation of NF-kappa-B and cell proliferation. May play a role in the regulation of the mitotic cell cycle. Plays a role in the insulin receptor signaling pathway and in activation of phosphatidylinositol 3-kinase. Acts downstream of the activated FCER1 receptor and plays a role in FCER1 (high affinity immunoglobulin epsilon receptor)-mediated signaling in mast cells. Plays a role in the regulation of mast cell degranulation. Plays a role in leukocyte recruitment and diapedesis in response to bacterial lipopolysaccharide (LPS). Phosphorylates CTTN, CTNND1, PTK2/FAK1, GAB1, PECAM1 and PTPN11. May phosphorylate JUP and PTPN1. Can phosphorylate STAT3 according to Ref.10 and Ref.24, but clearly plays a redundant role in STAT3 phosphorylation. According to Ref.12, cells where wild type FER has been replaced by a kinase-dead mutant show no reduction in STAT3 phosphorylation. Phosphorylates TMF1. Isoform 3 lacks kinase activity. Ref.3 Ref.6 Ref.7 Ref.10 Ref.14 Ref.17 Ref.19 Ref.20 Ref.21 Ref.23 Ref.24 Ref.26
Catalytic activity	ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate. Ref.9
Enzyme regulation	Activated by phosphatidic acid binding By similarity. Activated by hydrogen peroxide (in vitro). Activated by reactive oxygen species (ROS). Ref.20 Ref.23
Subunit structure	Homotrimer. Isoform 4 is a monomer, due to the absence of the N-terminal coiled coil domains. Interacts with CTNND1, EGFR, FLT3, PECAM1 and PDGFR. Interacts (via SH2 domain) with CTTN. Component of a complex that contains at least FER, CTTN and PTK2/FAK1 By similarity. Interacts with IRS1 and PIK3R1. Interacts with STAT3. Interacts with PPP1CA and regulates its phosphorylation at 'Thr-320'. Interacts with JAK1. Interacts with HSP90; this stabilizes phosphorylated FER and protects FER against proteasomal degradation. Interacts with ARHGDIA, NRP1, PLEC and TMF1. Ref.3 Ref.6 Ref.9 Ref.10 Ref.13 Ref.16 Ref.18 Ref.21 Ref.24 Ref.26
Subcellular location	Cytoplasm. Cytoplasm › cytoskeleton. Cell membrane; Peripheral membrane protein; Cytoplasmic side By similarity. Cell projection By similarity. Cell junction By similarity. Membrane; Peripheral membrane protein; Cytoplasmic side By similarity. Nucleus Ref.8 Ref.10 Ref.11 Ref.19. Cytoplasm › cell cortex By similarity. Note: Detected on microtubules in polarized and motile vascular endothelial cells. Colocalizes with F-actin at the cell cortex. Colocalizes with PECAM1 and CTNND1 at nascent cell-cell contacts By similarity. Not detected in the nucleus, but detected in the nuclear area surrounding the chromosomes after breakdown of the nuclear envelope during mitosis (Ref.11). Ref.8 Ref.10 Ref.11 Ref.19 Isoform 4: Nucleus Ref.8 Ref.10 Ref.11 Ref.19.
Tissue specificity	Detected in liver and testis. Isoform 4 is detected only in testis (at protein level). Widely expressed. Ref.2 Ref.9 Ref.12
Induction	Up-regulated by insulin in myogenic cells (in vitro). Ref.16 Ref.20 Ref.23
Domain	The coiled coil domains mediate homooligomerization and are required for location at microtubules By similarity. Ref.9 The N-terminal region including the first coiled coil domain mediates interaction with phosphoinositide-containing membranes By similarity. Ref.9
Post-translational modification	Autophosphorylated. Ref.2 Ref.3 Ref.6 Ref.7 Ref.8 Ref.9 Ref.10 Ref.19 Ref.20 Ref.24 Polyubiquitinated; this leads to proteasomal degradation.
Disruption phenotype	No visible phenotype, and the mice are fertile. Mice have reduced CTTN phosphorylation. Mice lacking both Fps/Fes and Fer activity are viable and fertile, but produce slightly fewer pups per litter than normal. They display elevated levels of circulating neutrophils, erythrocytes and platelets, while other cell counts are normal. Ref.12 Ref.15
Sequence similarities	Belongs to the protein kinase superfamily. Tyr protein kinase family. Fes/fps subfamily. Contains 1 FCH domain. Contains 1 protein kinase domain. Contains 1 SH2 domain.

Ontologies

Keywords
Cellular component	Cell junction Cell membrane Cell projection Cytoplasm Cytoskeleton Membrane Nucleus
Coding sequence diversity	Alternative splicing
Disease	Proto-oncogene
Domain	Coiled coil SH2 domain
Ligand	ATP-binding Lipid-binding Nucleotide-binding
Molecular function	Kinase Transferase Tyrosine-protein kinase
PTM	Phosphoprotein Ubl conjugation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	Fc-epsilon receptor signaling pathway Inferred from mutant phenotype PubMed 12192036. Source: UniProtKB Kit signaling pathway Inferred from mutant phenotype PubMed 12192036. Source: UniProtKB actin cytoskeleton reorganization Inferred from mutant phenotype Ref.19. Source: UniProtKB cell proliferation Inferred from electronic annotation. Source: Compara cell-cell adhesion mediated by cadherin Inferred from mutant phenotype Ref.19. Source: UniProtKB cellular response to macrophage colony-stimulating factor stimulus Inferred from electronic annotation. Source: Compara cellular response to reactive oxygen species Inferred from mutant phenotype Ref.23. Source: UniProtKB chemotaxis Inferred from mutant phenotype PubMed 12192036. Source: MGI diapedesis Inferred from mutant phenotype PubMed 16009680. Source: UniProtKB extracellular matrix-cell signaling Inferred from mutant phenotype Ref.23. Source: UniProtKB insulin receptor signaling pathway via phosphatidylinositol 3-kinase cascade Inferred from direct assay Ref.3. Source: UniProtKB interleukin-6-mediated signaling pathway Inferred from electronic annotation. Source: Compara microtubule cytoskeleton organization Inferred from sequence or structural similarity. Source: UniProtKB mitotic cell cycle Inferred from electronic annotation. Source: Compara negative regulation of mast cell activation involved in immune response Inferred from mutant phenotype Ref.20. Source: UniProtKB peptidyl-tyrosine phosphorylation Inferred from sequence or structural similarity. Source: UniProtKB platelet-derived growth factor receptor signaling pathway Inferred from direct assay Ref.6. Source: UniProtKB positive regulation of NF-kappaB transcription factor activity Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of actin filament polymerization Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of cell migration Inferred from sequence or structural similarity. Source: UniProtKB protein autophosphorylation Inferred from direct assay PubMed 12192036. Source: MGI regulation of epidermal growth factor receptor signaling pathway Inferred from sequence or structural similarity. Source: UniProtKB regulation of fibroblast migration Inferred from mutant phenotype Ref.23. Source: UniProtKB regulation of lamellipodium assembly Inferred from sequence or structural similarity. Source: UniProtKB regulation of protein phosphorylation Inferred from mutant phenotype Ref.21. Source: UniProtKB response to lipopolysaccharide Inferred from mutant phenotype PubMed 16009680. Source: UniProtKB response to platelet-derived growth factor stimulus Inferred from direct assay Ref.6. Source: UniProtKB substrate adhesion-dependent cell spreading Inferred from mutant phenotype Ref.19. Source: UniProtKB tyrosine phosphorylation of Stat3 protein Inferred from electronic annotation. Source: Compara
Cellular_component	actin cytoskeleton Inferred from electronic annotation. Source: Compara cell cortex Inferred from electronic annotation. Source: UniProtKB-SubCell cell junction Inferred from electronic annotation. Source: UniProtKB-SubCell cytoplasm Inferred from sequence or structural similarity. Source: UniProtKB extrinsic to internal side of plasma membrane Inferred from sequence or structural similarity. Source: UniProtKB lamellipodium Inferred from electronic annotation. Source: Compara microtubule cytoskeleton Inferred from electronic annotation. Source: Compara nuclear chromatin Inferred from electronic annotation. Source: Compara
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW epidermal growth factor receptor binding Inferred from sequence or structural similarity. Source: UniProtKB lipid binding Inferred from sequence or structural similarity. Source: UniProtKB non-membrane spanning protein tyrosine kinase activity Inferred from sequence or structural similarity. Source: UniProtKB
Complete GO annotation...

Alternative products

This entry describes 5 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P70451-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: P70451-2)

The sequence of this isoform differs from the canonical sequence as follows:
     70-127: Missing.

Note: No experimental confirmation available.

Isoform 3 (identifier: P70451-3)

Also known as: iFer;

The sequence of this isoform differs from the canonical sequence as follows:
     491-542: GEYVLSVYSD...FNTKQVITKK → ESVSIRGHRV...GGSAQPHPKG
     543-823: Missing.

Isoform 4 (identifier: P70451-4)

Also known as: FerT; p51FerT;

The sequence of this isoform differs from the canonical sequence as follows:
     1-369: Missing.
     370-412: LRCTEAKCAA...EEDARSVTSM → MDKSMECPHC...PSSSEILRYK
     444-444: Missing.

Isoform 5 (identifier: P70451-5)

The sequence of this isoform differs from the canonical sequence as follows:
     444-444: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 823	823	Tyrosine-protein kinase Fer		PRO_0000260825
Regions
	Domain	1 – 58	58	FCH
	Domain	461 – 551	91	SH2
	Domain	564 – 817	254	Protein kinase
	Nucleotide binding	570 – 578	9	ATP By similarity
	Region	1 – 300	300	Important for interaction with membranes containing phosphoinositides By similarity
	Coiled coil	123 – 185	63	Potential
	Coiled coil	301 – 381	81	Potential
Sites
	Active site	685	1	Proton acceptor By similarity
	Binding site	592	1	ATP By similarity
Amino acid modifications
	Modified residue	402	1	Phosphotyrosine Ref.22 Ref.25
	Modified residue	434	1	Phosphoserine By similarity
	Modified residue	616	1	Phosphotyrosine; by autocatalysis Ref.24
	Modified residue	715	1	Phosphotyrosine; by autocatalysis By similarity
Natural variations
	Alternative sequence	1 – 369	369	Missing in isoform 4.		VSP_041766
	Alternative sequence	70 – 127	58	Missing in isoform 2.		VSP_021634
	Alternative sequence	370 – 412	43	LRCTE…SVTSM → MDKSMECPHCEGVLEPESDP QFSKKCSIPLSPGPSSSEIL RYK in isoform 4.		VSP_041767
	Alternative sequence	444	1	Missing in isoform 4 and isoform 5.		VSP_041768
	Alternative sequence	491 – 542	52	GEYVL…VITKK → ESVSIRGHRVFKHSPAYRSP LQYKASHHQEVWGGSAQPHP KG in isoform 3.		VSP_041769
	Alternative sequence	543 – 823	281	Missing in isoform 3.		VSP_041770
Experimental info
	Mutagenesis	135 – 136	2	KL → RP: Abolishes homooligomerization.
	Mutagenesis	322 – 323	2	ML → RP: Abolishes homooligomerization.
	Mutagenesis	571	1	G → R: Abolishes kinase activity. Ref.7
	Mutagenesis	592	1	K → R: Abolishes kinase activity. Ref.9
	Mutagenesis	606	1	F → A: Abolishes interaction with PPP1CA. Ref.21
	Mutagenesis	616	1	Y → F: Abolishes autophosphorylation. Ref.24
	Mutagenesis	715	1	Y → F: Abolishes autophosphorylation. Ref.8
	Mutagenesis	743	1	D → R: Abolishes kinase activity. Ref.9
	Sequence conflict	328	1	A → G in BAC38626. Ref.5
	Sequence conflict	373	1	T → S in AAB18988. Ref.1
	Sequence conflict	373	1	T → S in AAG40730. Ref.3
	Sequence conflict	730	1	P → A in AAA37617. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified November 28, 2006. Version 2. Checksum: F4C22E1E63721663	FASTA	823	94,579
	10 20 30 40 50 60 MGFGSDLKNS QEAVLKLQDW ELRLLETVKK FMALRIKSDK EYAYTLQNLC NQVDKESTVQ 70 80 90 100 110 120 VNYVSNVSKS WLLMIQQTEQ LSRIMKTHAE DLNSGPLHRL TMMIKDKQQV KKSYVGIHQQ 130 140 150 160 170 180 IEAEMIKVTK TELEKLKSSY RQLIKEMNSA KEKYKEALAK GKETEKAKER YDKATMKLHM 190 200 210 220 230 240 LHNQYVLALK GAQLHQSQYY DTTLPLLLDS VQKMQEEMIK ALKGIFDDYS QITSLVTEEI 250 260 270 280 290 300 VNVHKEIQMS VEQIDPSTEY NNFIDVHRTT AAKEQEIEFD TSLLEENENL QANEIMWNNL 310 320 330 340 350 360 TADSLQVMLK TLAEELTQTQ QMLLHKEAAV LELEKRIEES FETCEKKSDI VLLLGQKQAL 370 380 390 400 410 420 EELKQSVQQL RCTEAKCAAQ KALLEQKVQE NDGKEPPPVV NYEEDARSVT SMERKERLSK 430 440 450 460 470 480 FESIRHSIAG IIKSPKSVLG SSTQVCDVIS VGERPLAEHD WYHGAIPRIE AQELLKQQGD 490 500 510 520 530 540 FLVRESHGKP GEYVLSVYSD GQRRHFIIQF VDNLYRFEGT GFSNIPQLID HHFNTKQVIT 550 560 570 580 590 600 KKSGVVLLNP IPKDKKWVLN HEDVSLGELL GKGNFGEVYK GTLKDKTPVA IKTCKEDLPQ 610 620 630 640 650 660 ELKIKFLQEA KILKQYDHPN IVKLIGVCTQ RQPVYIIMEL VPGGDFLTFL RKRKDELKLK 670 680 690 700 710 720 QLVRFSLDVA AGMLYLESKN CIHRDLAARN CLVGENNTLK ISDFGMSRQE DGGVYSSSGL 730 740 750 760 770 780 KQIPIKWTAP EALNYGRYSS ESDVWSFGIL LWETFSLGVC PYPGMTNQQA REQVERGYRM 790 800 810 820 SAPQNCPEEV FTIMMKCWDY KPENRPKFND LHKELTVIKK MIT
	Isoform 2 [UniParc]. Checksum: 91FCCCAAFEF1C283	FASTA	765	87,762
	10 20 30 40 50 60 MGFGSDLKNS QEAVLKLQDW ELRLLETVKK FMALRIKSDK EYAYTLQNLC NQVDKESTVQ 70 80 90 100 110 120 VNYVSNVSKV TKTELEKLKS SYRQLIKEMN SAKEKYKEAL AKGKETEKAK ERYDKATMKL 130 140 150 160 170 180 HMLHNQYVLA LKGAQLHQSQ YYDTTLPLLL DSVQKMQEEM IKALKGIFDD YSQITSLVTE 190 200 210 220 230 240 EIVNVHKEIQ MSVEQIDPST EYNNFIDVHR TTAAKEQEIE FDTSLLEENE NLQANEIMWN 250 260 270 280 290 300 NLTADSLQVM LKTLAEELTQ TQQMLLHKEA AVLELEKRIE ESFETCEKKS DIVLLLGQKQ 310 320 330 340 350 360 ALEELKQSVQ QLRCTEAKCA AQKALLEQKV QENDGKEPPP VVNYEEDARS VTSMERKERL 370 380 390 400 410 420 SKFESIRHSI AGIIKSPKSV LGSSTQVCDV ISVGERPLAE HDWYHGAIPR IEAQELLKQQ 430 440 450 460 470 480 GDFLVRESHG KPGEYVLSVY SDGQRRHFII QFVDNLYRFE GTGFSNIPQL IDHHFNTKQV 490 500 510 520 530 540 ITKKSGVVLL NPIPKDKKWV LNHEDVSLGE LLGKGNFGEV YKGTLKDKTP VAIKTCKEDL 550 560 570 580 590 600 PQELKIKFLQ EAKILKQYDH PNIVKLIGVC TQRQPVYIIM ELVPGGDFLT FLRKRKDELK 610 620 630 640 650 660 LKQLVRFSLD VAAGMLYLES KNCIHRDLAA RNCLVGENNT LKISDFGMSR QEDGGVYSSS 670 680 690 700 710 720 GLKQIPIKWT APEALNYGRY SSESDVWSFG ILLWETFSLG VCPYPGMTNQ QAREQVERGY 730 740 750 760 RMSAPQNCPE EVFTIMMKCW DYKPENRPKF NDLHKELTVI KKMIT
	Isoform 3 (iFer) [UniParc]. Checksum: 7468E01E9EB6F6E2	FASTA	532	61,094
	10 20 30 40 50 60 MGFGSDLKNS QEAVLKLQDW ELRLLETVKK FMALRIKSDK EYAYTLQNLC NQVDKESTVQ 70 80 90 100 110 120 VNYVSNVSKS WLLMIQQTEQ LSRIMKTHAE DLNSGPLHRL TMMIKDKQQV KKSYVGIHQQ 130 140 150 160 170 180 IEAEMIKVTK TELEKLKSSY RQLIKEMNSA KEKYKEALAK GKETEKAKER YDKATMKLHM 190 200 210 220 230 240 LHNQYVLALK GAQLHQSQYY DTTLPLLLDS VQKMQEEMIK ALKGIFDDYS QITSLVTEEI 250 260 270 280 290 300 VNVHKEIQMS VEQIDPSTEY NNFIDVHRTT AAKEQEIEFD TSLLEENENL QANEIMWNNL 310 320 330 340 350 360 TADSLQVMLK TLAEELTQTQ QMLLHKEAAV LELEKRIEES FETCEKKSDI VLLLGQKQAL 370 380 390 400 410 420 EELKQSVQQL RCTEAKCAAQ KALLEQKVQE NDGKEPPPVV NYEEDARSVT SMERKERLSK 430 440 450 460 470 480 FESIRHSIAG IIKSPKSVLG SSTQVCDVIS VGERPLAEHD WYHGAIPRIE AQELLKQQGD 490 500 510 520 530 FLVRESHGKP ESVSIRGHRV FKHSPAYRSP LQYKASHHQE VWGGSAQPHP KG
	Isoform 4 (FerT) (p51FerT) [UniParc]. Checksum: 1CDAA93ED40B6A1D	FASTA	453	51,601
	10 20 30 40 50 60 MDKSMECPHC EGVLEPESDP QFSKKCSIPL SPGPSSSEIL RYKERKERLS KFESIRHSIA 70 80 90 100 110 120 GIIKSPKSVL GSSTVCDVIS VGERPLAEHD WYHGAIPRIE AQELLKQQGD FLVRESHGKP 130 140 150 160 170 180 GEYVLSVYSD GQRRHFIIQF VDNLYRFEGT GFSNIPQLID HHFNTKQVIT KKSGVVLLNP 190 200 210 220 230 240 IPKDKKWVLN HEDVSLGELL GKGNFGEVYK GTLKDKTPVA IKTCKEDLPQ ELKIKFLQEA 250 260 270 280 290 300 KILKQYDHPN IVKLIGVCTQ RQPVYIIMEL VPGGDFLTFL RKRKDELKLK QLVRFSLDVA 310 320 330 340 350 360 AGMLYLESKN CIHRDLAARN CLVGENNTLK ISDFGMSRQE DGGVYSSSGL KQIPIKWTAP 370 380 390 400 410 420 EALNYGRYSS ESDVWSFGIL LWETFSLGVC PYPGMTNQQA REQVERGYRM SAPQNCPEEV 430 440 450 FTIMMKCWDY KPENRPKFND LHKELTVIKK MIT
	Isoform 5 [UniParc]. Checksum: F08F6BB10161D738	FASTA	822	94,451
	10 20 30 40 50 60 MGFGSDLKNS QEAVLKLQDW ELRLLETVKK FMALRIKSDK EYAYTLQNLC NQVDKESTVQ 70 80 90 100 110 120 VNYVSNVSKS WLLMIQQTEQ LSRIMKTHAE DLNSGPLHRL TMMIKDKQQV KKSYVGIHQQ 130 140 150 160 170 180 IEAEMIKVTK TELEKLKSSY RQLIKEMNSA KEKYKEALAK GKETEKAKER YDKATMKLHM 190 200 210 220 230 240 LHNQYVLALK GAQLHQSQYY DTTLPLLLDS VQKMQEEMIK ALKGIFDDYS QITSLVTEEI 250 260 270 280 290 300 VNVHKEIQMS VEQIDPSTEY NNFIDVHRTT AAKEQEIEFD TSLLEENENL QANEIMWNNL 310 320 330 340 350 360 TADSLQVMLK TLAEELTQTQ QMLLHKEAAV LELEKRIEES FETCEKKSDI VLLLGQKQAL 370 380 390 400 410 420 EELKQSVQQL RCTEAKCAAQ KALLEQKVQE NDGKEPPPVV NYEEDARSVT SMERKERLSK 430 440 450 460 470 480 FESIRHSIAG IIKSPKSVLG SSTVCDVISV GERPLAEHDW YHGAIPRIEA QELLKQQGDF 490 500 510 520 530 540 LVRESHGKPG EYVLSVYSDG QRRHFIIQFV DNLYRFEGTG FSNIPQLIDH HFNTKQVITK 550 560 570 580 590 600 KSGVVLLNPI PKDKKWVLNH EDVSLGELLG KGNFGEVYKG TLKDKTPVAI KTCKEDLPQE 610 620 630 640 650 660 LKIKFLQEAK ILKQYDHPNI VKLIGVCTQR QPVYIIMELV PGGDFLTFLR KRKDELKLKQ 670 680 690 700 710 720 LVRFSLDVAA GMLYLESKNC IHRDLAARNC LVGENNTLKI SDFGMSRQED GGVYSSSGLK 730 740 750 760 770 780 QIPIKWTAPE ALNYGRYSSE SDVWSFGILL WETFSLGVCP YPGMTNQQAR EQVERGYRMS 790 800 810 820 APQNCPEEVF TIMMKCWDYK PENRPKFNDL HKELTVIKKM IT

References

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[1]	"Murine Fer." Letwin K., Pawson T. Submitted (OCT-1996) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]	"A murine fer testis-specific transcript (ferT) encodes a truncated Fer protein." Fischman K., Edman J.C., Shackleford G.M., Turner J.A., Rutter W.J., Nir U. Mol. Cell. Biol. 10:146-153(1990) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 4), AUTOPHOSPHORYLATION, TISSUE SPECIFICITY.
[3]	"The protein-tyrosine kinase fer associates with signaling complexes containing insulin receptor substrate-1 and phosphatidylinositol 3-kinase." Iwanishi M., Czech M.P., Cherniack A.D. J. Biol. Chem. 275:38995-39000(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), FUNCTION, AUTOPHOSPHORYLATION, INTERACTION WITH IRS1 AND PIK3R1, SUBUNIT.
[4]	"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] (ISOFORM 2). Strain: C57BL/6 and FVB/N-3. Tissue: Brain and Mammary tumor.
[5]	"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] OF 125-823 (ISOFORM 5). Strain: C57BL/6J.
[6]	"The cytoplasmic tyrosine kinase FER is associated with the catenin-like substrate pp120 and is activated by growth factors." Kim L., Wong T.W. Mol. Cell. Biol. 15:4553-4561(1995) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN PHOSPHORYLATION OF CTNND1, AUTOPHOSPHORYLATION, INTERACTION WITH CTNND1 AND PDGFR.
[7]	"Tyrosine phosphorylation of the TATA element modulatory factor by the FER nuclear tyrosine kinases." Schwartz Y., Ben-Dor I., Navon A., Motro B., Nir U. FEBS Lett. 434:339-345(1998) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN PHOSPHORYLATION OF TMF1, AUTOPHOSPHORYLATION, MUTAGENESIS OF GLY-571, CHARACTERIZATION OF ISOFORM 4.
[8]	"Cell cycle-dependent nuclear accumulation of the p94fer tyrosine kinase is regulated by its NH2 terminus and is affected by kinase domain integrity and ATP binding." Ben-Dor I., Bern O., Tennenbaum T., Nir U. Cell Growth Differ. 10:113-129(1999) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION, PHOSPHORYLATION AT TYR-715, MUTAGENESIS OF TYR-715.
[9]	"Disruption of coiled-coil domains in Fer protein-tyrosine kinase abolishes trimerization but not kinase activation." Craig A.W., Zirngibl R., Greer P. J. Biol. Chem. 274:19934-19942(1999) [PubMed] [Europe PMC] [Abstract] Cited for: CATALYTIC ACTIVITY, SUBUNIT, DOMAIN, MUTAGENESIS OF 135-LYS-LEU-136; 322-MET-LEU-323; LYS-592 AND ASP-743, AUTOPHOSPHORYLATION, TISSUE SPECIFICITY.
[10]	"FER kinase activation of Stat3 is determined by the N-terminal sequence." Priel-Halachmi S., Ben-Dor I., Shpungin S., Tennenbaum T., Molavani H., Bachrach M., Salzberg S., Nir U. J. Biol. Chem. 275:28902-28910(2000) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN PHOSPHORYLATION OF STAT3, INTERACTION WITH STAT3, AUTOPHOSPHORYLATION, SUBCELLULAR LOCATION.
[11]	"Subcellular localization analysis of the closely related Fps/Fes and Fer protein-tyrosine kinases suggests a distinct role for Fps/Fes in vesicular trafficking." Zirngibl R., Schulze D., Mirski S.E., Cole S.P., Greer P.A. Exp. Cell Res. 266:87-94(2001) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION.
[12]	"Mice devoid of fer protein-tyrosine kinase activity are viable and fertile but display reduced cortactin phosphorylation." Craig A.W., Zirngibl R., Williams K., Cole L.A., Greer P.A. Mol. Cell. Biol. 21:603-613(2001) [PubMed] [Europe PMC] [Abstract] Cited for: DISRUPTION PHENOTYPE, ALTERNATIVE SPLICING, TISSUE SPECIFICITY.
[13]	"Direct binding of plectin to Fer kinase and negative regulation of its catalytic activity." Lunter P.C., Wiche G. Biochem. Biophys. Res. Commun. 296:904-910(2002) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH PLEC.
[14]	"Absence of Fer protein-tyrosine kinase exacerbates leukocyte recruitment in response to endotoxin." McCafferty D.M., Craig A.W., Senis Y.A., Greer P.A. J. Immunol. 168:4930-4935(2002) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN RESPONSE TO LIPOPOLYSACCHARIDE AND LEUKOCYTE DIAPEDESIS.
[15]	"Fps/Fes and Fer protein-tyrosine kinases play redundant roles in regulating hematopoiesis." Senis Y.A., Craig A.W., Greer P.A. Exp. Hematol. 31:673-681(2003) [PubMed] [Europe PMC] [Abstract] Cited for: DISRUPTION PHENOTYPE.
[16]	"Fer is a downstream effector of insulin and mediates the activation of signal transducer and activator of transcription 3 in myogenic cells." Taler M., Shpungin S., Salem Y., Malovani H., Pasder O., Nir U. Mol. Endocrinol. 17:1580-1592(2003) [PubMed] [Europe PMC] [Abstract] Cited for: INDUCTION BY INSULIN, INTERACTION WITH STAT3 AND JAK1.
[17]	"Continuous association of cadherin with beta-catenin requires the non-receptor tyrosine-kinase Fer." Xu G., Craig A.W., Greer P., Miller M., Anastasiadis P.Z., Lilien J., Balsamo J. J. Cell Sci. 117:3207-3219(2004) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN PHOSPHORYLATION OF PTPN1.
[18]	"TMF/ARA160 is a BC-box-containing protein that mediates the degradation of Stat3." Perry E., Tsruya R., Levitsky P., Pomp O., Taller M., Weisberg S., Parris W., Kulkarni S., Malovani H., Pawson T., Shpungin S., Nir U. Oncogene 23:8908-8919(2004) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH TMF1.
[19]	"Phosphorylation of N-cadherin-associated cortactin by Fer kinase regulates N-cadherin mobility and intercellular adhesion strength." El Sayegh T.Y., Arora P.D., Fan L., Laschinger C.A., Greer P.A., McCulloch C.A., Kapus A. Mol. Biol. Cell 16:5514-5527(2005) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN PHOSPHORYLATION OF CTTN, PHOSPHORYLATION, SUBCELLULAR LOCATION.
[20]	"Fer and Fps/Fes participate in a Lyn-dependent pathway from FcepsilonRI to platelet-endothelial cell adhesion molecule 1 to limit mast cell activation." Udell C.M., Samayawardhena L.A., Kawakami Y., Kawakami T., Craig A.W. J. Biol. Chem. 281:20949-20957(2006) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN MAST CELL ACTIVATION, FUNCTION IN PHOSPHORYLATION OF PECAM1, PHOSPHORYLATION, ENZYME REGULATION.
[21]	"Downregulation of Fer induces PP1 activation and cell-cycle arrest in malignant cells." Pasder O., Shpungin S., Salem Y., Makovsky A., Vilchick S., Michaeli S., Malovani H., Nir U. Oncogene 25:4194-4206(2006) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, MUTAGENESIS OF PHE-606, INTERACTION WITH PPP1CA.
[22]	"Quantitative time-resolved phosphoproteomic analysis of mast cell signaling." Cao L., Yu K., Banh C., Nguyen V., Ritz A., Raphael B.J., Kawakami Y., Kawakami T., Salomon A.R. J. Immunol. 179:5864-5876(2007) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-402, MASS SPECTROMETRY. Tissue: Mast cell.
[23]	"Fer-mediated cortactin phosphorylation is associated with efficient fibroblast migration and is dependent on reactive oxygen species generation during integrin-mediated cell adhesion." Sangrar W., Gao Y., Scott M., Truesdell P., Greer P.A. Mol. Cell. Biol. 27:6140-6152(2007) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, ENZYME REGULATION.
[24]	"Hsp90 and a tyrosine embedded in the Hsp90 recognition loop are required for the Fer tyrosine kinase activity." Hikri E., Shpungin S., Nir U. Cell. Signal. 21:588-596(2009) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN STAT3 PHOSPHORYLATION, INTERACTION WITH HSP90, AUTOPHOSPHORYLATION AT TYR-616, MUTAGENESIS OF TYR-616, UBIQUITINATION, PROTEASOMAL DEGRADATION.
[25]	"Large scale localization of protein phosphorylation by use of electron capture dissociation mass spectrometry." Sweet S.M., Bailey C.M., Cunningham D.L., Heath J.K., Cooper H.J. Mol. Cell. Proteomics 8:904-912(2009) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-402, MASS SPECTROMETRY. Tissue: Embryonic fibroblast.
[26]	"Neuropilin 1 directly interacts with Fer kinase to mediate semaphorin 3A-induced death of cortical neurons." Jiang S.X., Whitehead S., Aylsworth A., Slinn J., Zurakowski B., Chan K., Li J., Hou S.T. J. Biol. Chem. 285:9908-9918(2010) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN NEURONAL CELL DEATH AFTER BRAIN DAMAGE, INTERACTION WITH NRP1.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	U76762 mRNA. Translation: AAB18988.1. M32054 mRNA. Translation: AAA37617.1. AF286537 mRNA. Translation: AAG40730.1. BC051249 mRNA. Translation: AAH51249.1. BC058100 mRNA. Translation: AAH58100.1. AK082799 mRNA. Translation: BAC38626.1.
IPI	IPI00109334. IPI00122458. IPI00808015. IPI01026841. IPI01027660.
PIR	I49663.
RefSeq	NP_001033086.2. NM_001037997.2. NP_032026.2. NM_008000.2.
UniGene	Mm.23039.
3D structure databases
HSSP	HSSP built from PDB template 1WQU based on UniProtKB P07332.
ProteinModelPortal	P70451.
SMR	P70451. Positions 1-400, 453-820.
ModBase	Search...
Protein-protein interaction databases
STRING	10090.ENSMUSP00000000129.
PTM databases
PhosphoSite	P70451.
Proteomic databases
PaxDb	P70451.
PRIDE	P70451.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000000129; ENSMUSP00000000129; ENSMUSG00000000127. ENSMUST00000038080; ENSMUSP00000037418; ENSMUSG00000000127.
GeneID	14158.
KEGG	mmu:14158.
UCSC	uc008dfo.2. mouse. uc008dfq.2. mouse.
Organism-specific databases
CTD	14158.
MGI	MGI:105917. Fer.
Phylogenomic databases
eggNOG	COG0515.
GeneTree	ENSGT00600000084126.
HOGENOM	HOG000233858.
HOVERGEN	HBG005655.
InParanoid	Q9EQ77.
KO	K08889.
OMA	QYRFEGT.
OrthoDB	EOG4JM7P1.
Gene expression databases
ArrayExpress	P70451.
Bgee	P70451.
Genevestigator	P70451.
GermOnline	ENSMUSG00000000127. Mus musculus.
Family and domain databases
Gene3D	3.30.505.10. 1 hit.
InterPro	IPR001060. FCH_dom. IPR011009. Kinase-like_dom. IPR000719. Prot_kinase_cat_dom. IPR017441. Protein_kinase_ATP_BS. IPR001245. Ser-Thr/Tyr_kinase_cat_dom. IPR000980. SH2. IPR008266. Tyr_kinase_AS. IPR020635. Tyr_kinase_cat_dom. IPR016250. Tyr_kinase_non-rcpt_Fes_subgr. [Graphical view]
Pfam	PF00611. FCH. 1 hit. PF07714. Pkinase_Tyr. 1 hit. PF00017. SH2. 1 hit. [Graphical view]
PIRSF	PIRSF000632. TyrPK_fps. 1 hit.
PRINTS	PR00401. SH2DOMAIN. PR00109. TYRKINASE.
SMART	SM00055. FCH. 1 hit. SM00252. SH2. 1 hit. SM00219. TyrKc. 1 hit. [Graphical view]
SUPFAM	SSF56112. Kinase_like. 1 hit.
PROSITE	PS50133. FCH. 1 hit. PS00107. PROTEIN_KINASE_ATP. 1 hit. PS50011. PROTEIN_KINASE_DOM. 1 hit. PS00109. PROTEIN_KINASE_TYR. 1 hit. PS50001. SH2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	285280.
SOURCE	Search...

Entry information

Entry name

FER_MOUSE

Accession

Primary (citable) accession number: P70451
Secondary accession number(s): Q61561 , Q6PEE5, Q80UI3, Q8C481, Q9EQ77

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 28, 2006
Last sequence update:	November 28, 2006
Last modified:	May 1, 2013
This is version 107 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program