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Q7Z7G1

- CLNK_HUMAN

UniProt

Q7Z7G1 - CLNK_HUMAN

Protein

Cytokine-dependent hematopoietic cell linker

Gene

CLNK

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 4 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 80 (01 Oct 2014)
      Sequence version 2 (15 Jan 2008)
      Previous versions | rss
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    Functioni

    Plays a role in the regulation of immunoreceptor signaling, including PLC-gamma-mediated B-cell antigen receptor (BCR) signaling and FC-epsilon R1-mediated mast cell degranulation. Involved in phosphorylation of LAT By similarity.By similarity

    GO - Molecular functioni

    1. protein binding Source: IntAct
    2. SH3/SH2 adaptor activity Source: UniProtKB

    GO - Biological processi

    1. immune response Source: UniProtKB
    2. intracellular signal transduction Source: UniProtKB
    3. positive regulation of signal transduction Source: GOC
    4. transmembrane receptor protein tyrosine kinase signaling pathway Source: Ensembl

    Enzyme and pathway databases

    SignaLinkiQ7Z7G1.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Cytokine-dependent hematopoietic cell linker
    Alternative name(s):
    Mast cell immunoreceptor signal transducer
    Gene namesi
    Name:CLNK
    Synonyms:MIST
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 4

    Organism-specific databases

    HGNCiHGNC:17438. CLNK.

    Subcellular locationi

    GO - Cellular componenti

    1. intracellular Source: UniProtKB

    Pathology & Biotechi

    Organism-specific databases

    PharmGKBiPA164718067.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 428428Cytokine-dependent hematopoietic cell linkerPRO_0000314597Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei69 – 691Phosphotyrosine; by LYNBy similarity
    Modified residuei96 – 961Phosphotyrosine; by LYNBy similarity

    Post-translational modificationi

    Tyrosine-phosphorylated upon BCR cross-linking. Tyrosine phosphorylation at both Tyr-69 and Tyr-96 are required for BCR-induced calcium response and are essential to restore PLCG2-mediated signaling in BLNK-deficient DT40 cells, but this phosphorylation is dispensable in cells expressing LAT. Interacts with the SH2 domain of PLCG1 via phosphorylated Tyr-96 By similarity.By similarity

    Keywords - PTMi

    Phosphoprotein

    Proteomic databases

    PaxDbiQ7Z7G1.
    PRIDEiQ7Z7G1.

    PTM databases

    PhosphoSiteiQ7Z7G1.

    Expressioni

    Gene expression databases

    ArrayExpressiQ7Z7G1.
    BgeeiQ7Z7G1.
    GenevestigatoriQ7Z7G1.

    Organism-specific databases

    HPAiHPA035671.
    HPA035672.

    Interactioni

    Subunit structurei

    When phosphorylated, interacts with PLCG1, PLCG2, GRB2, VAV and LAT.By similarity

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    EGFRP005332EBI-7878194,EBI-297353
    ERBB2P046262EBI-7878194,EBI-641062

    Protein-protein interaction databases

    BioGridi125512. 2 interactions.
    IntActiQ7Z7G1. 2 interactions.
    MINTiMINT-1493840.
    STRINGi9606.ENSP00000226951.

    Structurei

    3D structure databases

    ProteinModelPortaliQ7Z7G1.
    SMRiQ7Z7G1. Positions 309-406.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini309 – 419111SH2PROSITE-ProRule annotationAdd
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni159 – 1646Mediates interaction with PLCG1By similarity
    Regioni178 – 1803Mediates interaction with LAT and GRB2By similarity

    Compositional bias

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Compositional biasi159 – 18628Pro-richAdd
    BLAST
    Compositional biasi243 – 2464Poly-Ser

    Domaini

    The N-terminal proline-rich region interacts with the SH3 domain of PLCG1.By similarity
    The SH2 domain is important for restoration of BCR-induced calcium response and JNK2 activation in BLNK-deficient DT40 cells expressing LAT.By similarity

    Sequence similaritiesi

    Contains 1 SH2 domain.PROSITE-ProRule annotation

    Keywords - Domaini

    SH2 domain

    Phylogenomic databases

    eggNOGiNOG77726.
    HOGENOMiHOG000111793.
    InParanoidiQ7Z7G1.
    OMAiQRHTFPE.
    OrthoDBiEOG7FJH09.
    PhylomeDBiQ7Z7G1.
    TreeFamiTF326567.

    Family and domain databases

    Gene3Di3.30.505.10. 1 hit.
    InterProiIPR000980. SH2.
    [Graphical view]
    PfamiPF00017. SH2. 1 hit.
    [Graphical view]
    PRINTSiPR00401. SH2DOMAIN.
    SMARTiSM00252. SH2. 1 hit.
    [Graphical view]
    SUPFAMiSSF55550. SSF55550. 1 hit.
    PROSITEiPS50001. SH2. 1 hit.
    [Graphical view]

    Sequences (3)i

    Sequence statusi: Complete.

    This entry describes 3 isoformsi produced by alternative splicing. Align

    Isoform 1 (identifier: Q7Z7G1-1) [UniParc]FASTAAdd to Basket

    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

    MNRQGNRKTT KEGSNDLKFQ NFSLPKNRSW PRINSATGQY QRMNKPLLDW    50
    ERNFAAVLDG AKGHSDDDYD DPELRMEETW QSIKILPARP IKESEYADTH 100
    YFKVAMDTPL PLDTRTSISI GQPTWNTQTR LERVDKPISK DVRSQNIKGD 150
    ASVRKNKIPL PPPRPLITLP KKYQPLPPEP ESSRPPLSQR HTFPEVQRMP 200
    SQISLRDLSE VLEAEKVPHN QRKPESTHLL ENQNTQEIPL AISSSSFTTS 250
    NHSVQNRDHR GGMQPCSPQR CQPPASCSPH ENILPYKYTS WRPPFPKRSD 300
    RKDVQHNEWY IGEYSRQAVE EAFMKENKDG SFLVRDCSTK SKEEPYVLAV 350
    FYENKVYNVK IRFLERNQQF ALGTGLRGDE KFDSVEDIIE HYKNFPIILI 400
    DGKDKTGVHR KQCHLTQPLP LTRHLLPL 428
    Length:428
    Mass (Da):49,554
    Last modified:January 15, 2008 - v2
    Checksum:i98DEDD4378D395A7
    GO
    Isoform 2 (identifier: Q7Z7G1-2) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         1-42: Missing.
         211-211: V → P
         212-428: Missing.

    Show »
    Length:169
    Mass (Da):19,416
    Checksum:i94F30955424B92F0
    GO
    Isoform 3 (identifier: Q7Z7G1-3) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         147-183: Missing.

    Show »
    Length:391
    Mass (Da):45,469
    Checksum:i3B3D533514DBC45F
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti140 – 1401K → R in BAC76765. 1 PublicationCurated
    Sequence conflicti140 – 1401K → R in BAA96241. (PubMed:15489334)Curated
    Sequence conflicti198 – 1981R → G in BAC76765. 1 PublicationCurated
    Sequence conflicti198 – 1981R → G in BAA96241. (PubMed:15489334)Curated

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti65 – 651S → G.
    Corresponds to variant rs16869924 [ dbSNP | Ensembl ].
    VAR_037984

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei1 – 4242Missing in isoform 2. 1 PublicationVSP_030330Add
    BLAST
    Alternative sequencei147 – 18337Missing in isoform 3. CuratedVSP_030331Add
    BLAST
    Alternative sequencei211 – 2111V → P in isoform 2. 1 PublicationVSP_030332
    Alternative sequencei212 – 428217Missing in isoform 2. 1 PublicationVSP_030333Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AB110420 mRNA. Translation: BAC76765.1.
    AC005599 Genomic DNA. No translation available.
    BC029887 mRNA. Translation: AAH29887.1.
    AB032369 mRNA. Translation: BAA96241.1.
    CCDSiCCDS47024.1. [Q7Z7G1-1]
    RefSeqiNP_443196.2. NM_052964.2. [Q7Z7G1-1]
    UniGeneiHs.678910.

    Genome annotation databases

    EnsembliENST00000226951; ENSP00000226951; ENSG00000109684. [Q7Z7G1-1]
    ENST00000442825; ENSP00000390744; ENSG00000109684. [Q7Z7G1-2]
    ENST00000507719; ENSP00000427208; ENSG00000109684. [Q7Z7G1-2]
    GeneIDi116449.
    KEGGihsa:116449.
    UCSCiuc003gmo.4. human. [Q7Z7G1-1]
    uc003gmp.3. human. [Q7Z7G1-2]

    Polymorphism databases

    DMDMi166217263.

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AB110420 mRNA. Translation: BAC76765.1 .
    AC005599 Genomic DNA. No translation available.
    BC029887 mRNA. Translation: AAH29887.1 .
    AB032369 mRNA. Translation: BAA96241.1 .
    CCDSi CCDS47024.1. [Q7Z7G1-1 ]
    RefSeqi NP_443196.2. NM_052964.2. [Q7Z7G1-1 ]
    UniGenei Hs.678910.

    3D structure databases

    ProteinModelPortali Q7Z7G1.
    SMRi Q7Z7G1. Positions 309-406.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 125512. 2 interactions.
    IntActi Q7Z7G1. 2 interactions.
    MINTi MINT-1493840.
    STRINGi 9606.ENSP00000226951.

    PTM databases

    PhosphoSitei Q7Z7G1.

    Polymorphism databases

    DMDMi 166217263.

    Proteomic databases

    PaxDbi Q7Z7G1.
    PRIDEi Q7Z7G1.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000226951 ; ENSP00000226951 ; ENSG00000109684 . [Q7Z7G1-1 ]
    ENST00000442825 ; ENSP00000390744 ; ENSG00000109684 . [Q7Z7G1-2 ]
    ENST00000507719 ; ENSP00000427208 ; ENSG00000109684 . [Q7Z7G1-2 ]
    GeneIDi 116449.
    KEGGi hsa:116449.
    UCSCi uc003gmo.4. human. [Q7Z7G1-1 ]
    uc003gmp.3. human. [Q7Z7G1-2 ]

    Organism-specific databases

    CTDi 116449.
    GeneCardsi GC04M010491.
    HGNCi HGNC:17438. CLNK.
    HPAi HPA035671.
    HPA035672.
    MIMi 611434. gene.
    neXtProti NX_Q7Z7G1.
    PharmGKBi PA164718067.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG77726.
    HOGENOMi HOG000111793.
    InParanoidi Q7Z7G1.
    OMAi QRHTFPE.
    OrthoDBi EOG7FJH09.
    PhylomeDBi Q7Z7G1.
    TreeFami TF326567.

    Enzyme and pathway databases

    SignaLinki Q7Z7G1.

    Miscellaneous databases

    GenomeRNAii 116449.
    NextBioi 79941.
    PROi Q7Z7G1.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi Q7Z7G1.
    Bgeei Q7Z7G1.
    Genevestigatori Q7Z7G1.

    Family and domain databases

    Gene3Di 3.30.505.10. 1 hit.
    InterProi IPR000980. SH2.
    [Graphical view ]
    Pfami PF00017. SH2. 1 hit.
    [Graphical view ]
    PRINTSi PR00401. SH2DOMAIN.
    SMARTi SM00252. SH2. 1 hit.
    [Graphical view ]
    SUPFAMi SSF55550. SSF55550. 1 hit.
    PROSITEi PS50001. SH2. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Genomic organization of human MIST gene."
      Goitsuka R.
      Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
    2. "Generation and annotation of the DNA sequences of human chromosomes 2 and 4."
      Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H.
      , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K.
      Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    3. "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).
      Tissue: Brain.
    4. "A BASH/SLP-76-related adaptor protein MIST/Clnk involved in IgE receptor-mediated mast cell degranulation."
      Goitsuka R., Kanazashi H., Sasanuma H., Fujimura Y.-C., Hidaka Y., Tatsuno A., Ra C., Hayashi K., Kitamura D.
      Int. Immunol. 12:573-580(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 19-394 (ISOFORM 1), IDENTIFICATION (ISOFORM 3).

    Entry informationi

    Entry nameiCLNK_HUMAN
    AccessioniPrimary (citable) accession number: Q7Z7G1
    Secondary accession number(s): Q05C27, Q9P2U9
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: January 15, 2008
    Last sequence update: January 15, 2008
    Last modified: October 1, 2014
    This is version 80 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

    Complete proteome, Reference proteome

    Documents

    1. Human chromosome 4
      Human chromosome 4: 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. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3