Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Basket 0
(max 400 entries)x

Your basket is currently empty.

Select item(s) and click on "Add to basket" to create your own collection here
(400 entries max)

P46109

- CRKL_HUMAN

UniProt

P46109 - CRKL_HUMAN

Protein

Crk-like protein

Gene

CRKL

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
    • BLAST
    • Align
    • Format
    • Add to basket
    • History
      Entry version 146 (01 Oct 2014)
      Sequence version 1 (01 Nov 1995)
      Previous versions | rss
    • Help video
    • Feedback
    • Comment

    Functioni

    May mediate the transduction of intracellular signals.

    GO - Molecular functioni

    1. poly(A) RNA binding Source: UniProtKB
    2. protein binding Source: IntAct
    3. SH3/SH2 adaptor activity Source: ProtInc
    4. signal transducer activity Source: ProtInc

    GO - Biological processi

    1. activation of MAPKK activity Source: Reactome
    2. anterior/posterior pattern specification Source: Ensembl
    3. blood vessel development Source: Ensembl
    4. heart development Source: Ensembl
    5. intracellular signal transduction Source: ProtInc
    6. JNK cascade Source: ProtInc
    7. neurotrophin TRK receptor signaling pathway Source: Reactome
    8. organ morphogenesis Source: Ensembl
    9. parathyroid gland development Source: Ensembl
    10. positive regulation of signal transduction Source: GOC
    11. Ras protein signal transduction Source: ProtInc
    12. thymus development Source: Ensembl

    Enzyme and pathway databases

    ReactomeiREACT_12076. Frs2-mediated activation.
    REACT_17025. Downstream signal transduction.
    REACT_23787. Regulation of signaling by CBL.
    SignaLinkiP46109.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Crk-like protein
    Gene namesi
    Name:CRKL
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 22

    Organism-specific databases

    HGNCiHGNC:2363. CRKL.

    Subcellular locationi

    GO - Cellular componenti

    1. cytosol Source: Reactome
    2. endosome Source: Reactome
    3. extracellular vesicular exosome Source: UniProt

    Pathology & Biotechi

    Organism-specific databases

    Orphaneti261330. Distal 22q11.2 microdeletion syndrome.
    PharmGKBiPA26881.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 303303Crk-like proteinPRO_0000079347Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei127 – 1271Phosphotyrosine1 Publication
    Modified residuei207 – 2071Phosphotyrosine1 Publication

    Keywords - PTMi

    Phosphoprotein

    Proteomic databases

    MaxQBiP46109.
    PaxDbiP46109.
    PeptideAtlasiP46109.
    PRIDEiP46109.

    2D gel databases

    OGPiP46109.

    PTM databases

    PhosphoSiteiP46109.

    Expressioni

    Gene expression databases

    BgeeiP46109.
    CleanExiHS_CRKL.
    GenevestigatoriP46109.

    Organism-specific databases

    HPAiHPA001100.

    Interactioni

    Subunit structurei

    Interacts with INPP5D/SHIP1. Interacts with DOCK2 and EPOR. Interacts with phosphorylated CBLB and IRS4.4 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    ABL1P005192EBI-910,EBI-375543
    CBLP226812EBI-910,EBI-518228
    DCBLD2Q96PD23EBI-910,EBI-8536103
    EGFRP005332EBI-910,EBI-297353
    ERBB2P046262EBI-910,EBI-641062
    ERBB3P218603EBI-910,EBI-720706
    FLT1P179489EBI-910,EBI-1026718
    GAB1Q134804EBI-910,EBI-517684
    Kcnma1Q084605EBI-910,EBI-1633915From a different organism.
    Kidins220Q9EQG62EBI-910,EBI-976654From a different organism.
    MAP4K1Q929185EBI-910,EBI-881
    PDGFRAP162343EBI-910,EBI-2861522
    PIK3R1P279862EBI-910,EBI-79464
    PTK2Q053972EBI-910,EBI-702142
    RAPGEF1Q139052EBI-910,EBI-976876
    SOS1Q078892EBI-910,EBI-297487

    Protein-protein interaction databases

    BioGridi107789. 66 interactions.
    DIPiDIP-29165N.
    IntActiP46109. 56 interactions.
    MINTiMINT-137265.
    STRINGi9606.ENSP00000346300.

    Structurei

    Secondary structure

    1
    303
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Helixi11 – 144
    Beta strandi15 – 184
    Helixi21 – 288
    Beta strandi29 – 313
    Beta strandi36 – 405
    Beta strandi42 – 465
    Beta strandi48 – 547
    Beta strandi57 – 6610
    Turni67 – 693
    Beta strandi70 – 734
    Beta strandi78 – 803
    Helixi81 – 888
    Beta strandi93 – 964
    Beta strandi105 – 1073
    Beta strandi119 – 13214
    Beta strandi138 – 1414
    Beta strandi146 – 1549
    Beta strandi157 – 1648
    Beta strandi170 – 1745
    Helixi175 – 1773
    Beta strandi178 – 1825
    Helixi190 – 1923
    Helixi203 – 2053
    Beta strandi238 – 2425
    Beta strandi248 – 2514
    Beta strandi253 – 2553
    Beta strandi263 – 2697
    Beta strandi271 – 2799
    Beta strandi282 – 2876
    Helixi288 – 2903
    Beta strandi291 – 2933
    Beta strandi296 – 2994

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    2BZXX-ray2.80A237-303[»]
    2BZYX-ray2.50A/B237-303[»]
    2DBKNMR-A229-303[»]
    2EO3NMR-A1-104[»]
    2LQNNMR-A1-303[»]
    2LQWNMR-A1-303[»]
    ProteinModelPortaliP46109.
    SMRiP46109. Positions 1-303.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP46109.

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini14 – 10289SH2PROSITE-ProRule annotationAdd
    BLAST
    Domaini123 – 18361SH3 1PROSITE-ProRule annotationAdd
    BLAST
    Domaini235 – 29662SH3 2PROSITE-ProRule annotationAdd
    BLAST

    Sequence similaritiesi

    Belongs to the CRK family.Curated
    Contains 1 SH2 domain.PROSITE-ProRule annotation
    Contains 2 SH3 domains.PROSITE-ProRule annotation

    Keywords - Domaini

    Repeat, SH2 domain, SH3 domain

    Phylogenomic databases

    eggNOGiNOG292767.
    HOGENOMiHOG000236288.
    HOVERGENiHBG105616.
    InParanoidiP46109.
    KOiK04438.
    OMAiRTLYDFT.
    OrthoDBiEOG7NW69P.
    PhylomeDBiP46109.
    TreeFamiTF321436.

    Family and domain databases

    Gene3Di3.30.505.10. 1 hit.
    InterProiIPR000980. SH2.
    IPR011511. SH3_2.
    IPR001452. SH3_domain.
    [Graphical view]
    PfamiPF00017. SH2. 1 hit.
    PF00018. SH3_1. 1 hit.
    PF07653. SH3_2. 1 hit.
    [Graphical view]
    PRINTSiPR00401. SH2DOMAIN.
    PR00452. SH3DOMAIN.
    SMARTiSM00252. SH2. 1 hit.
    SM00326. SH3. 2 hits.
    [Graphical view]
    SUPFAMiSSF50044. SSF50044. 2 hits.
    SSF55550. SSF55550. 2 hits.
    PROSITEiPS50001. SH2. 1 hit.
    PS50002. SH3. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    P46109-1 [UniParc]FASTAAdd to Basket

    « Hide

    MSSARFDSSD RSAWYMGPVS RQEAQTRLQG QRHGMFLVRD SSTCPGDYVL    50
    SVSENSRVSH YIINSLPNRR FKIGDQEFDH LPALLEFYKI HYLDTTTLIE 100
    PAPRYPSPPM GSVSAPNLPT AEDNLEYVRT LYDFPGNDAE DLPFKKGEIL 150
    VIIEKPEEQW WSARNKDGRV GMIPVPYVEK LVRSSPHGKH GNRNSNSYGI 200
    PEPAHAYAQP QTTTPLPAVS GSPGAAITPL PSTQNGPVFA KAIQKRVPCA 250
    YDKTALALEV GDIVKVTRMN INGQWEGEVN GRKGLFPFTH VKIFDPQNPD 300
    ENE 303
    Length:303
    Mass (Da):33,777
    Last modified:November 1, 1995 - v1
    Checksum:i294CF1EE2CD44B81
    GO

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    X59656 mRNA. Translation: CAA42199.1.
    CR456423 mRNA. Translation: CAG30309.1.
    AK292909 mRNA. Translation: BAF85598.1.
    CH471176 Genomic DNA. Translation: EAX02932.1.
    CH471176 Genomic DNA. Translation: EAX02933.1.
    CH471176 Genomic DNA. Translation: EAX02934.1.
    BC043500 mRNA. Translation: AAH43500.1.
    CCDSiCCDS13785.1.
    PIRiS41754.
    RefSeqiNP_005198.1. NM_005207.3.
    UniGeneiHs.5613.

    Genome annotation databases

    EnsembliENST00000354336; ENSP00000346300; ENSG00000099942.
    ENST00000411769; ENSP00000396646; ENSG00000099942.
    GeneIDi1399.
    KEGGihsa:1399.
    UCSCiuc002ztf.2. human.

    Polymorphism databases

    DMDMi1169094.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    X59656 mRNA. Translation: CAA42199.1 .
    CR456423 mRNA. Translation: CAG30309.1 .
    AK292909 mRNA. Translation: BAF85598.1 .
    CH471176 Genomic DNA. Translation: EAX02932.1 .
    CH471176 Genomic DNA. Translation: EAX02933.1 .
    CH471176 Genomic DNA. Translation: EAX02934.1 .
    BC043500 mRNA. Translation: AAH43500.1 .
    CCDSi CCDS13785.1.
    PIRi S41754.
    RefSeqi NP_005198.1. NM_005207.3.
    UniGenei Hs.5613.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    2BZX X-ray 2.80 A 237-303 [» ]
    2BZY X-ray 2.50 A/B 237-303 [» ]
    2DBK NMR - A 229-303 [» ]
    2EO3 NMR - A 1-104 [» ]
    2LQN NMR - A 1-303 [» ]
    2LQW NMR - A 1-303 [» ]
    ProteinModelPortali P46109.
    SMRi P46109. Positions 1-303.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 107789. 66 interactions.
    DIPi DIP-29165N.
    IntActi P46109. 56 interactions.
    MINTi MINT-137265.
    STRINGi 9606.ENSP00000346300.

    PTM databases

    PhosphoSitei P46109.

    Polymorphism databases

    DMDMi 1169094.

    2D gel databases

    OGPi P46109.

    Proteomic databases

    MaxQBi P46109.
    PaxDbi P46109.
    PeptideAtlasi P46109.
    PRIDEi P46109.

    Protocols and materials databases

    DNASUi 1399.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000354336 ; ENSP00000346300 ; ENSG00000099942 .
    ENST00000411769 ; ENSP00000396646 ; ENSG00000099942 .
    GeneIDi 1399.
    KEGGi hsa:1399.
    UCSCi uc002ztf.2. human.

    Organism-specific databases

    CTDi 1399.
    GeneCardsi GC22P021272.
    HGNCi HGNC:2363. CRKL.
    HPAi HPA001100.
    MIMi 602007. gene.
    neXtProti NX_P46109.
    Orphaneti 261330. Distal 22q11.2 microdeletion syndrome.
    PharmGKBi PA26881.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG292767.
    HOGENOMi HOG000236288.
    HOVERGENi HBG105616.
    InParanoidi P46109.
    KOi K04438.
    OMAi RTLYDFT.
    OrthoDBi EOG7NW69P.
    PhylomeDBi P46109.
    TreeFami TF321436.

    Enzyme and pathway databases

    Reactomei REACT_12076. Frs2-mediated activation.
    REACT_17025. Downstream signal transduction.
    REACT_23787. Regulation of signaling by CBL.
    SignaLinki P46109.

    Miscellaneous databases

    ChiTaRSi CRKL. human.
    EvolutionaryTracei P46109.
    GeneWikii CRKL.
    GenomeRNAii 1399.
    NextBioi 5727.
    PROi P46109.
    SOURCEi Search...

    Gene expression databases

    Bgeei P46109.
    CleanExi HS_CRKL.
    Genevestigatori P46109.

    Family and domain databases

    Gene3Di 3.30.505.10. 1 hit.
    InterProi IPR000980. SH2.
    IPR011511. SH3_2.
    IPR001452. SH3_domain.
    [Graphical view ]
    Pfami PF00017. SH2. 1 hit.
    PF00018. SH3_1. 1 hit.
    PF07653. SH3_2. 1 hit.
    [Graphical view ]
    PRINTSi PR00401. SH2DOMAIN.
    PR00452. SH3DOMAIN.
    SMARTi SM00252. SH2. 1 hit.
    SM00326. SH3. 2 hits.
    [Graphical view ]
    SUPFAMi SSF50044. SSF50044. 2 hits.
    SSF55550. SSF55550. 2 hits.
    PROSITEi PS50001. SH2. 1 hit.
    PS50002. SH3. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Isolation and chromosomal localization of CRKL, a human crk-like gene."
      ten Hoeve J., Morris C., Heisterkamp N., Groffen J.
      Oncogene 8:2469-2474(1993) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
      Tissue: Spleen.
    2. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    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].
      Tissue: Trachea.
    4. 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].
      Tissue: Skin.
    6. "Interplay of the proto-oncogene proteins CrkL and CrkII in insulin-like growth factor-I receptor-mediated signal transduction."
      Koval A.P., Karas M., Zick Y., LeRoith D.
      J. Biol. Chem. 273:14780-14787(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH IRS4.
    7. "Tyrosine phosphorylation and complex formation of Cbl-b upon T cell receptor stimulation."
      Elly C., Witte S., Zhang Z., Rosnet O., Lipkowitz S., Altman A., Liu Y.-C.
      Oncogene 18:1147-1156(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH CBLB.
    8. "DOCK2 associates with CrkL and regulates Rac1 in human leukemia cell lines."
      Nishihara H., Maeda M., Oda A., Tsuda M., Sawa H., Nagashima K., Tanaka S.
      Blood 100:3968-3974(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH DOCK2.
    9. "CrkL is recruited through its SH2 domain to the erythropoietin receptor and plays a role in Lyn-mediated receptor signaling."
      Arai A., Kanda E., Nosaka Y., Miyasaka N., Miura O.
      J. Biol. Chem. 276:33282-33290(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH EPOR.
    10. "Immunoaffinity profiling of tyrosine phosphorylation in cancer cells."
      Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H., Zha X.-M., Polakiewicz R.D., Comb M.J.
      Nat. Biotechnol. 23:94-101(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-207, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    11. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Cervix carcinoma.
    12. "Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions."
      Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K.
      Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-127, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Leukemic T-cell.
    13. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    14. "Solution structures of the SH3 domain of human CRK-like protein."
      RIKEN structural genomics initiative (RSGI)
      Submitted (DEC-2006) to the PDB data bank
      Cited for: STRUCTURE BY NMR OF 220-303.

    Entry informationi

    Entry nameiCRKL_HUMAN
    AccessioniPrimary (citable) accession number: P46109
    Secondary accession number(s): A8KA44, D3DX35
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: November 1, 1995
    Last sequence update: November 1, 1995
    Last modified: October 1, 2014
    This is version 146 of the entry and version 1 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 22
      Human chromosome 22: entries, gene names and cross-references to MIM
    2. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    3. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    4. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3