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Q7Z7G1

- CLNK_HUMAN

UniProt

Q7Z7G1 - CLNK_HUMAN

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Protein

Cytokine-dependent hematopoietic cell linker

Gene
CLNK, MIST
Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 4 out of 5 - Experimental evidence at protein leveli

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.

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
Complete GO annotation...

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
Complete GO annotation...

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 LYN By similarity
Modified residuei96 – 961Phosphotyrosine; by LYN By 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.

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.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini309 – 419111SH2Add
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni159 – 1646Mediates interaction with PLCG1 By similarity
Regioni178 – 1803Mediates interaction with LAT and GRB2 By 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.

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

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. VSP_030330Add
BLAST
Alternative sequencei147 – 18337Missing in isoform 3. VSP_030331Add
BLAST
Alternative sequencei211 – 2111V → P in isoform 2. VSP_030332
Alternative sequencei212 – 428217Missing in isoform 2. VSP_030333Add
BLAST

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti140 – 1401K → R in BAC76765. 1 Publication
Sequence conflicti140 – 1401K → R in BAA96241. 1 Publication
Sequence conflicti198 – 1981R → G in BAC76765. 1 Publication
Sequence conflicti198 – 1981R → G in BAA96241. 1 Publication

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

« Hide 'large scale' publications
  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: July 9, 2014
This is version 79 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

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