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P16591

- FER_HUMAN

UniProt

P16591 - FER_HUMAN

Protein

Tyrosine-protein kinase Fer

Gene

FER

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 161 (01 Oct 2014)
      Sequence version 2 (16 May 2006)
      Previous versions | rss
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    Functioni

    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). Plays a role in synapse organization, trafficking of synaptic vesicles, the generation of excitatory postsynaptic currents and neuron-neuron synaptic transmission. Plays a role in neuronal cell death after brain damage. Phosphorylates CTTN, CTNND1, PTK2/FAK1, GAB1, PECAM1 and PTPN11. May phosphorylate JUP and PTPN1. Can phosphorylate STAT3, but the biological relevance of this depends on cell type and stimulus.10 Publications

    Catalytic activityi

    ATP + a [protein]-L-tyrosine = ADP + a [protein]-L-tyrosine phosphate.2 PublicationsPROSITE-ProRule annotation

    Enzyme regulationi

    Activated by phosphatidic acid binding. Activated by hydrogen peroxide (in vitro). Activated by reactive oxygen species (ROS).1 Publication

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei591 – 5911ATPPROSITE-ProRule annotation
    Active sitei684 – 6841Proton acceptorPROSITE-ProRule annotation

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi569 – 5779ATPPROSITE-ProRule annotation

    GO - Molecular functioni

    1. ATP binding Source: UniProtKB-KW
    2. epidermal growth factor receptor binding Source: UniProtKB
    3. lipid binding Source: UniProtKB
    4. non-membrane spanning protein tyrosine kinase activity Source: UniProtKB
    5. protein binding Source: IntAct
    6. protein tyrosine kinase activity Source: ProtInc

    GO - Biological processi

    1. actin cytoskeleton reorganization Source: UniProtKB
    2. cell-cell adhesion mediated by cadherin Source: UniProtKB
    3. cell proliferation Source: UniProtKB
    4. cellular response to insulin stimulus Source: UniProtKB
    5. cellular response to macrophage colony-stimulating factor stimulus Source: UniProtKB
    6. cellular response to reactive oxygen species Source: UniProtKB
    7. chemotaxis Source: Ensembl
    8. cytokine-mediated signaling pathway Source: UniProtKB
    9. diapedesis Source: UniProtKB
    10. extracellular matrix-cell signaling Source: UniProtKB
    11. Fc-epsilon receptor signaling pathway Source: UniProtKB
    12. insulin receptor signaling pathway via phosphatidylinositol 3-kinase Source: UniProtKB
    13. interleukin-6-mediated signaling pathway Source: UniProtKB
    14. intracellular signal transduction Source: ProtInc
    15. Kit signaling pathway Source: UniProtKB
    16. microtubule cytoskeleton organization Source: UniProtKB
    17. mitotic cell cycle Source: UniProtKB
    18. negative regulation of mast cell activation involved in immune response Source: UniProtKB
    19. peptidyl-tyrosine phosphorylation Source: UniProtKB
    20. platelet-derived growth factor receptor signaling pathway Source: UniProtKB
    21. positive regulation of actin filament polymerization Source: UniProtKB
    22. positive regulation of cell migration Source: UniProtKB
    23. positive regulation of cell proliferation Source: UniProtKB
    24. positive regulation of NF-kappaB transcription factor activity Source: UniProtKB
    25. protein autophosphorylation Source: UniProtKB
    26. protein phosphorylation Source: ProtInc
    27. regulation of epidermal growth factor receptor signaling pathway Source: UniProtKB
    28. regulation of fibroblast migration Source: Ensembl
    29. regulation of lamellipodium assembly Source: UniProtKB
    30. regulation of protein phosphorylation Source: UniProtKB
    31. response to lipopolysaccharide Source: UniProtKB
    32. response to platelet-derived growth factor Source: UniProtKB
    33. substrate adhesion-dependent cell spreading Source: UniProtKB
    34. tyrosine phosphorylation of Stat3 protein Source: UniProtKB

    Keywords - Molecular functioni

    Kinase, Transferase, Tyrosine-protein kinase

    Keywords - Ligandi

    ATP-binding, Lipid-binding, Nucleotide-binding

    Enzyme and pathway databases

    BRENDAi2.7.10.2. 2681.
    ReactomeiREACT_111040. Signaling by SCF-KIT.
    SignaLinkiP16591.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Tyrosine-protein kinase Fer (EC:2.7.10.2)
    Alternative name(s):
    Feline encephalitis virus-related kinase FER
    Fujinami poultry sarcoma/Feline sarcoma-related protein Fer
    Proto-oncogene c-Fer
    Tyrosine kinase 3
    p94-Fer
    Gene namesi
    Name:FER
    Synonyms:TYK3
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 5

    Organism-specific databases

    HGNCiHGNC:3655. FER.

    Subcellular locationi

    Cytoplasm. Cytoplasmcytoskeleton. Cell membrane; Peripheral membrane protein; Cytoplasmic side. Cell projection. Cell junction. Membrane; Peripheral membrane protein; Cytoplasmic side. Nucleus. Cytoplasmcell cortex
    Note: Associated with the chromatin. 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.

    GO - Cellular componenti

    1. cell cortex Source: UniProtKB-SubCell
    2. cell junction Source: UniProtKB-SubCell
    3. cell projection Source: UniProtKB-SubCell
    4. cytoplasm Source: UniProtKB
    5. cytoskeleton Source: UniProtKB-SubCell
    6. cytosol Source: Reactome
    7. extrinsic component of cytoplasmic side of plasma membrane Source: UniProtKB
    8. nucleus Source: UniProtKB

    Keywords - Cellular componenti

    Cell junction, Cell membrane, Cell projection, Cytoplasm, Cytoskeleton, Membrane, Nucleus

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi483 – 4831R → Q: Abolishes kinase activity. Abolishes location at microtubules. 1 Publication
    Mutagenesisi591 – 5911K → R: Abolishes kinase activity. 1 Publication

    Keywords - Diseasei

    Proto-oncogene

    Organism-specific databases

    PharmGKBiPA28095.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 822822Tyrosine-protein kinase FerPRO_0000088084Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei402 – 4021Phosphotyrosine2 Publications
    Modified residuei434 – 4341Phosphoserine2 Publications
    Modified residuei615 – 6151Phosphotyrosine; by autocatalysisBy similarity
    Modified residuei714 – 7141Phosphotyrosine; by autocatalysis

    Post-translational modificationi

    Autophosphorylated.4 Publications
    Polyubiquitinated; this leads to proteasomal degradation.By similarity

    Keywords - PTMi

    Phosphoprotein, Ubl conjugation

    Proteomic databases

    MaxQBiP16591.
    PaxDbiP16591.
    PeptideAtlasiP16591.
    PRIDEiP16591.

    PTM databases

    PhosphoSiteiP16591.

    Expressioni

    Tissue specificityi

    Isoform 1 is detected in normal colon and in fibroblasts (at protein level). Isoform 3 is detected in normal testis, in colon carcinoma-derived metastases in lung, liver and ovary, and in colon carcinoma and hepato carcinoma cell lines (at protein level). Isoform 3 is not detected in normal colon or in normal fibroblasts (at protein level). Widely expressed.3 Publications

    Gene expression databases

    ArrayExpressiP16591.
    BgeeiP16591.
    CleanExiHS_FER.
    GenevestigatoriP16591.

    Organism-specific databases

    HPAiCAB022464.
    HPA007641.

    Interactioni

    Subunit structurei

    Homotrimer. Interacts with ARHGDIA, IRS1, JAK1, NRP1, PIK3R1, PLEC and TMF1. Interacts with PPP1CA and regulates its phosphorylation at 'Thr-320' By similarity. Interacts with CTNND1, EGFR, FLT3, PECAM1, PDGFR and STAT3. Interacts (via SH2 domain) with CTTN. Interacts with HSP90; this stabilizes phosphorylated FER and protects FER against proteasomal degradation. Component of a complex that contains at least FER, CTTN and PTK2/FAK1.By similarity8 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    CDC37Q165432EBI-1380661,EBI-295634
    chBcatO424862EBI-1380661,EBI-972394From a different organism.

    Protein-protein interaction databases

    BioGridi108532. 13 interactions.
    IntActiP16591. 12 interactions.
    MINTiMINT-261636.
    STRINGi9606.ENSP00000281092.

    Structurei

    Secondary structure

    1
    822
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Turni455 – 4573
    Beta strandi461 – 4644
    Helixi467 – 4726
    Beta strandi480 – 4845
    Beta strandi492 – 4987
    Beta strandi501 – 51010
    Beta strandi513 – 5186
    Beta strandi520 – 5223
    Helixi524 – 53310
    Turni540 – 5423

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    2KK6NMR-A453-557[»]
    ProteinModelPortaliP16591.
    SMRiP16591. Positions 1-400, 452-820.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP16591.

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini1 – 5858FCHPROSITE-ProRule annotationAdd
    BLAST
    Domaini460 – 55091SH2PROSITE-ProRule annotationAdd
    BLAST
    Domaini563 – 816254Protein kinasePROSITE-ProRule annotationAdd
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni1 – 300300Important for interaction with membranes containing phosphoinositidesAdd
    BLAST

    Coiled coil

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Coiled coili123 – 18563Sequence AnalysisAdd
    BLAST
    Coiled coili301 – 39090Sequence AnalysisAdd
    BLAST

    Domaini

    The coiled coil domains mediate homooligomerization and are required for location at microtubules.
    The N-terminal region including the first coiled coil domain mediates interaction with phosphoinositide-containing membranes.

    Sequence similaritiesi

    Belongs to the protein kinase superfamily. Tyr protein kinase family. Fes/fps subfamily.PROSITE-ProRule annotation
    Contains 1 FCH domain.PROSITE-ProRule annotation
    Contains 1 protein kinase domain.PROSITE-ProRule annotation
    Contains 1 SH2 domain.PROSITE-ProRule annotation

    Keywords - Domaini

    Coiled coil, SH2 domain

    Phylogenomic databases

    eggNOGiCOG0515.
    HOGENOMiHOG000059550.
    HOVERGENiHBG005655.
    InParanoidiP16591.
    KOiK08889.
    OMAiFVDNLYR.
    OrthoDBiEOG708VXW.
    PhylomeDBiP16591.
    TreeFamiTF315363.

    Family and domain databases

    Gene3Di3.30.505.10. 1 hit.
    InterProiIPR001060. FCH_dom.
    IPR028539. Fer.
    IPR011009. Kinase-like_dom.
    IPR000719. Prot_kinase_dom.
    IPR017441. Protein_kinase_ATP_BS.
    IPR001245. Ser-Thr/Tyr_kinase_cat_dom.
    IPR000980. SH2.
    IPR016250. Tyr-prot_kinase_Fes/Fps.
    IPR008266. Tyr_kinase_AS.
    IPR020635. Tyr_kinase_cat_dom.
    [Graphical view]
    PANTHERiPTHR24418:SF227. PTHR24418:SF227. 1 hit.
    PfamiPF00611. FCH. 1 hit.
    PF07714. Pkinase_Tyr. 1 hit.
    PF00017. SH2. 1 hit.
    [Graphical view]
    PIRSFiPIRSF000632. TyrPK_fps. 1 hit.
    PRINTSiPR00401. SH2DOMAIN.
    PR00109. TYRKINASE.
    SMARTiSM00055. FCH. 1 hit.
    SM00252. SH2. 1 hit.
    SM00219. TyrKc. 1 hit.
    [Graphical view]
    SUPFAMiSSF55550. SSF55550. 1 hit.
    SSF56112. SSF56112. 1 hit.
    PROSITEiPS50133. 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]

    Sequences (3)i

    Sequence statusi: Complete.

    This entry describes 3 isoformsi produced by alternative promoter usage and alternative splicing. Align

    Isoform 1 (identifier: P16591-1) [UniParc]FASTAAdd to Basket

    Also known as: p94

    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.

    « Hide

    MGFGSDLKNS HEAVLKLQDW ELRLLETVKK FMALRIKSDK EYASTLQNLC    50
    NQVDKESTVQ MNYVSNVSKS WLLMIQQTEQ LSRIMKTHAE DLNSGPLHRL 100
    TMMIKDKQQV KKSYIGVHQQ IEAEMIKVTK TELEKLKCSY RQLIKEMNSA 150
    KEKYKEALAK GKETEKAKER YDKATMKLHM LHNQYVLALK GAQLHQNQYY 200
    DITLPLLLDS LQKMQEEMIK ALKGIFDEYS QITSLVTEEI VNVHKEIQMS 250
    VEQIDPSTEY NNFIDVHRTT AAKEQEIEFD TSLLEENENL QANEIMWNNL 300
    TAESLQVMLK TLAEELMQTQ QMLLNKEEAV LELEKRIEES SETCEKKSDI 350
    VLLLSQKQAL EELKQSVQQL RCTEAKFSAQ KELLEQKVQE NDGKEPPPVV 400
    NYEEDARSVT SMERKERLSK FESIRHSIAG IIRSPKSALG SSALSDMISI 450
    SEKPLAEQDW YHGAIPRIEA QELLKKQGDF LVRESHGKPG EYVLSVYSDG 500
    QRRHFIIQYV DNMYRFEGTG FSNIPQLIDH HYTTKQVITK KSGVVLLNPI 550
    PKDKKWILSH EDVILGELLG KGNFGEVYKG TLKDKTSVAV KTCKEDLPQE 600
    LKIKFLQEAK ILKQYDHPNI VKLIGVCTQR QPVYIIMELV SGGDFLTFLR 650
    RKKDELKLKQ LVKFSLDAAA GMLYLESKNC IHRDLAARNC LVGENNVLKI 700
    SDFGMSRQED GGVYSSSGLK QIPIKWTAPE ALNYGRYSSE SDVWSFGILL 750
    WETFSLGVCP YPGMTNQQAR EQVERGYRMS APQHCPEDIS KIMMKCWDYK 800
    PENRPKFSEL QKELTIIKRK LT 822
    Length:822
    Mass (Da):94,638
    Last modified:May 16, 2006 - v2
    Checksum:iBD42DF6C03419C76
    GO
    Isoform 2 (identifier: P16591-2) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         1-175: Missing.

    Show »
    Length:647
    Mass (Da):74,266
    Checksum:iF05F6497716D7D36
    GO
    Isoform 3 (identifier: P16591-3) [UniParc]FASTAAdd to Basket

    Also known as: FerT, p47

    The sequence of this isoform differs from the canonical sequence as follows:
         1-369: Missing.
         370-412: LRCTEAKFSA...EEDARSVTSM → MEQKMKCPHC...PSTSEVHRDQ

    Note: Produced by alternative promoter usage.

    Show »
    Length:453
    Mass (Da):51,643
    Checksum:iE9B8AD1A2DD0A7DC
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti219 – 2191I → L in BAG61714. (PubMed:14702039)Curated
    Sequence conflicti234 – 2341S → N in BAG61714. (PubMed:14702039)Curated
    Sequence conflicti426 – 4261H → Q in BAG61714. (PubMed:14702039)Curated
    Sequence conflicti447 – 4471M → L in AEY69041. (PubMed:22223638)Curated
    Sequence conflicti485 – 4851S → G in AEY69041. (PubMed:22223638)Curated
    Sequence conflicti492 – 4921Y → H in AEY69041. (PubMed:22223638)Curated
    Sequence conflicti505 – 5051F → L in BAG61714. (PubMed:14702039)Curated
    Sequence conflicti558 – 5581L → F in AEY69041. (PubMed:22223638)Curated
    Sequence conflicti730 – 7301E → G in BAG61714. (PubMed:14702039)Curated

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti128 – 1281V → F.1 Publication
    Corresponds to variant rs35150210 [ dbSNP | Ensembl ].
    VAR_041691
    Natural varianti404 – 4041E → Q in an ovarian Endometrioid carcinoma sample; somatic mutation. 1 Publication
    VAR_041692
    Natural varianti412 – 4121M → V.1 Publication
    Corresponds to variant rs33940843 [ dbSNP | Ensembl ].
    VAR_041693
    Natural varianti439 – 4391L → V.3 Publications
    Corresponds to variant rs34499946 [ dbSNP | Ensembl ].
    VAR_006282
    Natural varianti443 – 4431A → P.1 Publication
    Corresponds to variant rs34259824 [ dbSNP | Ensembl ].
    VAR_041694
    Natural varianti460 – 4601W → C in a lung small cell carcinoma sample; somatic mutation. 1 Publication
    VAR_041695
    Natural varianti507 – 5071I → T.
    Corresponds to variant rs34204308 [ dbSNP | Ensembl ].
    VAR_051695
    Natural varianti813 – 8131E → Q.1 Publication
    Corresponds to variant rs56097357 [ dbSNP | Ensembl ].
    VAR_041696

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei1 – 369369Missing in isoform 3. 1 PublicationVSP_043846Add
    BLAST
    Alternative sequencei1 – 175175Missing in isoform 2. 1 PublicationVSP_041765Add
    BLAST
    Alternative sequencei370 – 41243LRCTE…SVTSM → MEQKMKCPHCKDQLESGFGS QSCKTCALMFSSEPSTSEVH RDQ in isoform 3. 1 PublicationVSP_043847Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    J03358 mRNA. Translation: AAA61190.1.
    JQ412173 mRNA. Translation: AEY69041.1.
    AK299855 mRNA. Translation: BAG61714.1.
    AK315234 mRNA. Translation: BAG37661.1.
    AC034207 Genomic DNA. No translation available.
    AC008871 Genomic DNA. No translation available.
    AC109481 Genomic DNA. No translation available.
    AC008955 Genomic DNA. No translation available.
    AC010228 Genomic DNA. No translation available.
    AC011421 Genomic DNA. No translation available.
    AC116428 Genomic DNA. No translation available.
    CH471086 Genomic DNA. Translation: EAW49055.1.
    CCDSiCCDS4098.1. [P16591-1]
    PIRiA31943. TVHUFE.
    RefSeqiNP_005237.2. NM_005246.2. [P16591-1]
    XP_006714635.1. XM_006714572.1. [P16591-1]
    XP_006714636.1. XM_006714573.1. [P16591-1]
    UniGeneiHs.221472.

    Genome annotation databases

    EnsembliENST00000281092; ENSP00000281092; ENSG00000151422. [P16591-1]
    ENST00000438717; ENSP00000394297; ENSG00000151422. [P16591-2]
    GeneIDi2241.
    KEGGihsa:2241.
    UCSCiuc003kop.1. human. [P16591-1]
    uc031skp.1. human. [P16591-3]

    Polymorphism databases

    DMDMi97536202.

    Keywords - Coding sequence diversityi

    Alternative promoter usage, Alternative splicing, Polymorphism

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    J03358 mRNA. Translation: AAA61190.1 .
    JQ412173 mRNA. Translation: AEY69041.1 .
    AK299855 mRNA. Translation: BAG61714.1 .
    AK315234 mRNA. Translation: BAG37661.1 .
    AC034207 Genomic DNA. No translation available.
    AC008871 Genomic DNA. No translation available.
    AC109481 Genomic DNA. No translation available.
    AC008955 Genomic DNA. No translation available.
    AC010228 Genomic DNA. No translation available.
    AC011421 Genomic DNA. No translation available.
    AC116428 Genomic DNA. No translation available.
    CH471086 Genomic DNA. Translation: EAW49055.1 .
    CCDSi CCDS4098.1. [P16591-1 ]
    PIRi A31943. TVHUFE.
    RefSeqi NP_005237.2. NM_005246.2. [P16591-1 ]
    XP_006714635.1. XM_006714572.1. [P16591-1 ]
    XP_006714636.1. XM_006714573.1. [P16591-1 ]
    UniGenei Hs.221472.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    2KK6 NMR - A 453-557 [» ]
    ProteinModelPortali P16591.
    SMRi P16591. Positions 1-400, 452-820.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 108532. 13 interactions.
    IntActi P16591. 12 interactions.
    MINTi MINT-261636.
    STRINGi 9606.ENSP00000281092.

    Chemistry

    BindingDBi P16591.
    ChEMBLi CHEMBL3982.
    GuidetoPHARMACOLOGYi 2022.

    PTM databases

    PhosphoSitei P16591.

    Polymorphism databases

    DMDMi 97536202.

    Proteomic databases

    MaxQBi P16591.
    PaxDbi P16591.
    PeptideAtlasi P16591.
    PRIDEi P16591.

    Protocols and materials databases

    DNASUi 2241.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000281092 ; ENSP00000281092 ; ENSG00000151422 . [P16591-1 ]
    ENST00000438717 ; ENSP00000394297 ; ENSG00000151422 . [P16591-2 ]
    GeneIDi 2241.
    KEGGi hsa:2241.
    UCSCi uc003kop.1. human. [P16591-1 ]
    uc031skp.1. human. [P16591-3 ]

    Organism-specific databases

    CTDi 2241.
    GeneCardsi GC05P108111.
    HGNCi HGNC:3655. FER.
    HPAi CAB022464.
    HPA007641.
    MIMi 176942. gene.
    neXtProti NX_P16591.
    PharmGKBi PA28095.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi COG0515.
    HOGENOMi HOG000059550.
    HOVERGENi HBG005655.
    InParanoidi P16591.
    KOi K08889.
    OMAi FVDNLYR.
    OrthoDBi EOG708VXW.
    PhylomeDBi P16591.
    TreeFami TF315363.

    Enzyme and pathway databases

    BRENDAi 2.7.10.2. 2681.
    Reactomei REACT_111040. Signaling by SCF-KIT.
    SignaLinki P16591.

    Miscellaneous databases

    EvolutionaryTracei P16591.
    GeneWikii FER_(gene).
    GenomeRNAii 2241.
    NextBioi 9065.
    PROi P16591.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi P16591.
    Bgeei P16591.
    CleanExi HS_FER.
    Genevestigatori P16591.

    Family and domain databases

    Gene3Di 3.30.505.10. 1 hit.
    InterProi IPR001060. FCH_dom.
    IPR028539. Fer.
    IPR011009. Kinase-like_dom.
    IPR000719. Prot_kinase_dom.
    IPR017441. Protein_kinase_ATP_BS.
    IPR001245. Ser-Thr/Tyr_kinase_cat_dom.
    IPR000980. SH2.
    IPR016250. Tyr-prot_kinase_Fes/Fps.
    IPR008266. Tyr_kinase_AS.
    IPR020635. Tyr_kinase_cat_dom.
    [Graphical view ]
    PANTHERi PTHR24418:SF227. PTHR24418:SF227. 1 hit.
    Pfami PF00611. FCH. 1 hit.
    PF07714. Pkinase_Tyr. 1 hit.
    PF00017. SH2. 1 hit.
    [Graphical view ]
    PIRSFi PIRSF000632. TyrPK_fps. 1 hit.
    PRINTSi PR00401. SH2DOMAIN.
    PR00109. TYRKINASE.
    SMARTi SM00055. FCH. 1 hit.
    SM00252. SH2. 1 hit.
    SM00219. TyrKc. 1 hit.
    [Graphical view ]
    SUPFAMi SSF55550. SSF55550. 1 hit.
    SSF56112. SSF56112. 1 hit.
    PROSITEi 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 ]
    ProtoNeti Search...

    Publicationsi

    1. "Isolation and sequence analysis of a novel human tyrosine kinase gene."
      Hao Q.-L., Heisterkamp N., Groffen J.
      Mol. Cell. Biol. 9:1587-1593(1989) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT VAL-439.
    2. "Intronic promoter drives the BORIS-regulated expression of FerT in colon carcinoma cells."
      Makovski A., Yaffe E., Shpungin S., Nir U.
      J. Biol. Chem. 287:6100-6112(2012) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), ALTERNATIVE PROMOTER USAGE, FUNCTION, IDENTIFICATION BY MASS SPECTROMETRY, TISSUE SPECIFICITY.
      Tissue: Testis.
    3. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
      Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
      , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
      Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
      Tissue: Brain.
    4. "The DNA sequence and comparative analysis of human chromosome 5."
      Schmutz J., Martin J., Terry A., Couronne O., Grimwood J., Lowry S., Gordon L.A., Scott D., Xie G., Huang W., Hellsten U., Tran-Gyamfi M., She X., Prabhakar S., Aerts A., Altherr M., Bajorek E., Black S.
      , Branscomb E., Caoile C., Challacombe J.F., Chan Y.M., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Glavina T., Gomez M., Gonzales E., Goodstein D., Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Lopez F., Lou Y., Martinez D., Medina C., Morgan J., Nandkeshwar R., Noonan J.P., Pitluck S., Pollard M., Predki P., Priest J., Ramirez L., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wheeler J., Wu K., Yang J., Dickson M., Cheng J.-F., Eichler E.E., Olsen A., Pennacchio L.A., Rokhsar D.S., Richardson P., Lucas S.M., Myers R.M., Rubin E.M.
      Nature 431:268-274(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    5. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    6. "A survey of protein tyrosine kinase mRNAs expressed in normal human melanocytes."
      Lee S.-T., Strunk K.M., Spritz R.A.
      Oncogene 8:3403-3410(1993) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 686-741.
    7. "Identification and chromosomal mapping of new human tyrosine kinase genes."
      Krolewski J.J., Lee R., Eddy R., Shows T.B., Dalla-Favera R.
      Oncogene 5:277-282(1990) [PubMed] [Europe PMC] [Abstract]
      Cited for: TISSUE SPECIFICITY.
    8. "Nuclear and cytoplasmic location of the FER tyrosine kinase."
      Hao Q.-L., Ferris D.K., White G., Heisterkamp N., Groffen J.
      Mol. Cell. Biol. 11:1180-1183(1991) [PubMed] [Europe PMC] [Abstract]
      Cited for: SUBCELLULAR LOCATION.
    9. "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, SUBUNIT, INTERACTION WITH CTNND1.
    10. "Growth factor-dependent phosphorylation of the actin-binding protein cortactin is mediated by the cytoplasmic tyrosine kinase FER."
      Kim L., Wong T.W.
      J. Biol. Chem. 273:23542-23548(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN PHOSPHORYLATION OF CTTN, INTERACTION WITH CTTN; CTNND1 AND PDGFR, MUTAGENESIS OF LYS-591, SUBCELLULAR LOCATION.
    11. "Identification of Fer tyrosine kinase localized on microtubules as a platelet endothelial cell adhesion molecule-1 phosphorylating kinase in vascular endothelial cells."
      Kogata N., Masuda M., Kamioka Y., Yamagishi A., Endo A., Okada M., Mochizuki N.
      Mol. Biol. Cell 14:3553-3564(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN PHOSPHORYLATION OF PECAM1; PTPN11 AND GAB1, SUBCELLULAR LOCATION, CATALYTIC ACTIVITY, MUTAGENESIS OF ARG-483, INTERACTION WITH PECAM1.
    12. "Tyrosine phosphorylation of plakoglobin causes contrary effects on its association with desmosomes and adherens junction components and modulates beta-catenin-mediated transcription."
      Miravet S., Piedra J., Castano J., Raurell I., Franci C., Dunach M., Garcia de Herreros A.
      Mol. Cell. Biol. 23:7391-7402(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN PHOSPHORYLATION OF JUP AND IN REGULATION OF PROTEIN PHOSPHORYLATION.
    13. "Coordination between the actin cytoskeleton and membrane deformation by a novel membrane tubulation domain of PCH proteins is involved in endocytosis."
      Tsujita K., Suetsugu S., Sasaki N., Furutani M., Oikawa T., Takenawa T.
      J. Cell Biol. 172:269-279(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: SUBCELLULAR LOCATION, LIPID-BINDING, DOMAIN.
    14. "Expression of Fer testis (FerT) tyrosine kinase transcript variants and distribution sites of FerT during the development of the acrosome-acroplaxome-manchette complex in rat spermatids."
      Kierszenbaum A.L., Rivkin E., Tres L.L.
      Dev. Dyn. 237:3882-3891(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: IDENTIFICATION OF ISOFORM 3, TISSUE SPECIFICITY.
    15. "Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle."
      Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M.
      Mol. Cell 31:438-448(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-402 AND SER-434, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Cervix carcinoma.
    16. "Specific tyrosine phosphorylation of focal adhesion kinase mediated by Fer tyrosine kinase in suspended hepatocytes."
      Oh M.A., Choi S., Lee M.J., Choi M.C., Lee S.A., Ko W., Cance W.G., Oh E.S., Buday L., Kim S.H., Lee J.W.
      Biochim. Biophys. Acta 1793:781-791(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN PHOSPHORYLATION OF PTK2/FAK1, FUNCTION IN REGULATION OF ACTIN CYTOSKELETON, SUBUNIT, IDENTIFICATION IN A COMPLEX WITH CTTN AND PTK2/FAK1.
    17. "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: INTERACTION WITH HSP90.
    18. "The Fer tyrosine kinase cooperates with interleukin-6 to activate signal transducer and activator of transcription 3 and promote human prostate cancer cell growth."
      Zoubeidi A., Rocha J., Zouanat F.Z., Hamel L., Scarlata E., Aprikian A.G., Chevalier S.
      Mol. Cancer Res. 7:142-155(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN IL6 SIGNALING PATHWAY; CELL PROLIFERATION AND IN PHOSPHORYLATION OF STAT3, INTERACTION WITH STAT3.
    19. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-402 AND SER-434, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    20. "The tyrosine kinase Fer is a downstream target of the PLD-PA pathway that regulates cell migration."
      Itoh T., Hasegawa J., Tsujita K., Kanaho Y., Takenawa T.
      Sci. Signal. 2:RA52-RA52(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN REGULATION OF ACTIN CYTOSKELETON AND CELL MIGRATION, CATALYTIC ACTIVITY, DOMAIN, LIPID-BINDING, ENZYME REGULATION.
    21. Cited for: FUNCTION IN CELL PROLIFERATION, PHOSPHORYLATION, INTERACTION WITH FLT3.
    22. "FER tyrosine kinase (FER) overexpression mediates resistance to quinacrine through EGF-dependent activation of NF-kappaB."
      Guo C., Stark G.R.
      Proc. Natl. Acad. Sci. U.S.A. 108:7968-7973(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION IN ACTIVATION OF NF-KAPPA-B DOWNSTREAM OF EGFR AND CELL PROLIFERATION, INTERACTION WITH EGFR, PHOSPHORYLATION.
    23. "Solution structure of SH2 domain of proto-oncogene tyrosine-protein kinase FER from Homo sapiens, Northeast structural genomics consortium (NESG) target HR3461D."
      Northeast structural genomics consortium (NESG)
      Submitted (AUG-2009) to the PDB data bank
      Cited for: STRUCTURE BY NMR OF 453-557.
    24. "Closing in on the biological functions of Fps/Fes and Fer."
      Greer P.
      Nat. Rev. Mol. Cell Biol. 3:278-289(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: REVIEW.
    25. Cited for: VARIANT VAL-439.
    26. "Patterns of somatic mutation in human cancer genomes."
      Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G.
      , Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R.
      Nature 446:153-158(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANTS [LARGE SCALE ANALYSIS] PHE-128; GLN-404; VAL-412; VAL-439; PRO-443; CYS-460 AND GLN-813.

    Entry informationi

    Entry nameiFER_HUMAN
    AccessioniPrimary (citable) accession number: P16591
    Secondary accession number(s): B2RCR4, B4DSQ2, H2FLB8
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: August 1, 1990
    Last sequence update: May 16, 2006
    Last modified: October 1, 2014
    This is version 161 of the entry and version 2 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Reference proteome

    Documents

    1. Human chromosome 5
      Human chromosome 5: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    6. Human and mouse protein kinases
      Human and mouse protein kinases: classification and index
    7. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3