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Protein

Cytokine-dependent hematopoietic cell linker

Gene

Clnk

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 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.3 Publications

GO - Biological processi

Complete GO annotation...

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
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 5

Organism-specific databases

MGIiMGI:1351468. Clnk.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi69Y → F: Loss of phosphorylation and loss of interaction with PLCG1, PLCG2 and VAV. 2 Publications1
Mutagenesisi96Y → F: Loss of phosphorylation and loss of interaction with PLCG1, PLCG2 and VAV. 2 Publications1
Mutagenesisi101Y → F: Loss of phosphorylation and loss of interaction with PLCG1, PLCG2 and VAV. 2 Publications1
Mutagenesisi153Y → F: Loss of phosphorylation and loss of interaction with PLCG1, PLCG2 and VAV. 2 Publications1
Mutagenesisi174Y → F: Loss of phosphorylation and loss of interaction with PLCG1, PLCG2 and VAV. 2 Publications1
Mutagenesisi188Y → F: Loss of phosphorylation and loss of interaction with PLCG1, PLCG2 and VAV. 2 Publications1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00003145981 – 435Cytokine-dependent hematopoietic cell linkerAdd BLAST435

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei69Phosphotyrosine; by LYNCombined sources1 Publication1
Modified residuei96Phosphotyrosine; by LYN1 Publication1

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-96.2 Publications

Keywords - PTMi

Phosphoprotein

Proteomic databases

PaxDbiQ9QZE2.
PRIDEiQ9QZE2.
TopDownProteomicsiQ9QZE2-1. [Q9QZE2-1]

PTM databases

iPTMnetiQ9QZE2.
PhosphoSitePlusiQ9QZE2.

Expressioni

Tissue specificityi

Expressed in mast cells of the skin (at protein level). Expressed in cytokine-stimulated hemopoietic cells.2 Publications

Inductioni

By cytokines such as interleukin (IL)-2 and IL-3.1 Publication

Gene expression databases

BgeeiENSMUSG00000039315.
CleanExiMM_CLNK.
ExpressionAtlasiQ9QZE2. baseline and differential.
GenevisibleiQ9QZE2. MM.

Interactioni

Subunit structurei

When phosphorylated, interacts with PLCG1, PLCG2, GRB2, VAV and LAT. Associated with a tyrosine-phosphorylated polypeptide (p92) in response to immunoreceptor stimulation.3 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
FgrP142343EBI-8040679,EBI-7587024

Protein-protein interaction databases

IntActiQ9QZE2. 1 interactor.
MINTiMINT-263696.
STRINGi10090.ENSMUSP00000128473.

Structurei

3D structure databases

ProteinModelPortaliQ9QZE2.
SMRiQ9QZE2.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini309 – 418SH2PROSITE-ProRule annotationAdd BLAST110

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni160 – 165Mediates interaction with PLCG1; essential for BCR signaling; involved in restoration of BCR-induced calcium response and ERK2 and JNK2 activation in BLNK-deficient cells expressing LAT1 Publication6
Regioni178 – 182Mediates interaction with LAT and GRB2; involved in translocation to the glycolipid-enriched microdomain and restoration of BCR-induced calcium response in BLNK-deficient DT40 cells expressing LAT1 Publication5

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi160 – 196Pro-richAdd BLAST37

Domaini

The N-terminal proline-rich region interacts with the SH3 domain of PLCG1.1 Publication
The SH2 domain is important for restoration of BCR-induced calcium response and JNK2 activation in BLNK-deficient DT40 cells expressing LAT.1 Publication

Sequence similaritiesi

Contains 1 SH2 domain.PROSITE-ProRule annotation

Keywords - Domaini

SH2 domain

Phylogenomic databases

eggNOGiENOG410IHD0. Eukaryota.
ENOG410Z0GE. LUCA.
GeneTreeiENSGT00530000063094.
HOGENOMiHOG000111793.
InParanoidiQ9QZE2.
OMAiRHTFPEV.
OrthoDBiEOG091G053I.
PhylomeDBiQ9QZE2.

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 (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q9QZE2-1) [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

        10         20         30         40         50
MTSQGNKRTT KEGFGDLRFQ NVSLLKNRSW PSLSSAKGRC RAVLEPLPDH
60 70 80 90 100
RRNLAGVPGG EKCNSNNDYE DPEFQLLKAW PSMKILPARP IQESEYADTR
110 120 130 140 150
YFQDTMEAPL LLPPKASVST ERQTRDVRMT HLEEVDKPTF KDVRSQRFKG
160 170 180 190 200
FKYTKINKTP LPPPRPAITL PKKYQPLPPA PPEESSAYFA PKPTFPEVQR
210 220 230 240 250
GPRQRSAKDF SRVLGAEEES HHQTKPESSC PSSNQNTQKS PPAIASSSYM
260 270 280 290 300
PGKHSIQARD HTGSMQHCPA QRCQAAASHS PRMLPYENTN SEKPDPTKPD
310 320 330 340 350
EKDVWQNEWY IGEYSRQAVE DVLMKENKDG TFLVRDCSTK SKAEPYVLVV
360 370 380 390 400
FYGNKVYNVK IRFLESNQQF ALGTGLRGNE MFDSVEDIIE HYTYFPILLI
410 420 430
DGKDKAARRK QCYLTQPLPL ARLLLTQYSS QALHE
Length:435
Mass (Da):49,492
Last modified:May 1, 2000 - v1
Checksum:i5CD27EC971FC0EA5
GO
Isoform 2 (identifier: Q9QZE2-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     5-28: Missing.

Show »
Length:411
Mass (Da):46,731
Checksum:iB7AFC6B93275E448
GO

Sequence cautioni

The sequence BAC38640 differs from that shown. Reason: Erroneous initiation.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti105T → M in BAA96240 (PubMed:10744659).Curated1
Sequence conflicti105T → M in AAI25638 (PubMed:15489334).Curated1
Sequence conflicti131H → Q in BAA96240 (PubMed:10744659).Curated1
Sequence conflicti131H → Q in AAI25638 (PubMed:15489334).Curated1
Sequence conflicti337C → R in BAC38640 (PubMed:16141072).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0303345 – 28Missing in isoform 2. CuratedAdd BLAST24

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF187819 mRNA. Translation: AAF14299.1.
AB021220 mRNA. Translation: BAA96240.1.
BC125637 mRNA. Translation: AAI25638.1.
BC125639 mRNA. Translation: AAI25640.1.
AK082826 mRNA. Translation: BAC38640.2. Different initiation.
CCDSiCCDS51486.1. [Q9QZE2-1]
RefSeqiNP_038776.3. NM_013748.3. [Q9QZE2-1]
XP_006504037.1. XM_006503974.2. [Q9QZE2-1]
XP_011239036.1. XM_011240734.1. [Q9QZE2-2]
UniGeneiMm.440845.

Genome annotation databases

EnsembliENSMUST00000169819; ENSMUSP00000128473; ENSMUSG00000039315. [Q9QZE2-1]
GeneIDi27278.
KEGGimmu:27278.
UCSCiuc008xgv.2. mouse. [Q9QZE2-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF187819 mRNA. Translation: AAF14299.1.
AB021220 mRNA. Translation: BAA96240.1.
BC125637 mRNA. Translation: AAI25638.1.
BC125639 mRNA. Translation: AAI25640.1.
AK082826 mRNA. Translation: BAC38640.2. Different initiation.
CCDSiCCDS51486.1. [Q9QZE2-1]
RefSeqiNP_038776.3. NM_013748.3. [Q9QZE2-1]
XP_006504037.1. XM_006503974.2. [Q9QZE2-1]
XP_011239036.1. XM_011240734.1. [Q9QZE2-2]
UniGeneiMm.440845.

3D structure databases

ProteinModelPortaliQ9QZE2.
SMRiQ9QZE2.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiQ9QZE2. 1 interactor.
MINTiMINT-263696.
STRINGi10090.ENSMUSP00000128473.

PTM databases

iPTMnetiQ9QZE2.
PhosphoSitePlusiQ9QZE2.

Proteomic databases

PaxDbiQ9QZE2.
PRIDEiQ9QZE2.
TopDownProteomicsiQ9QZE2-1. [Q9QZE2-1]

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000169819; ENSMUSP00000128473; ENSMUSG00000039315. [Q9QZE2-1]
GeneIDi27278.
KEGGimmu:27278.
UCSCiuc008xgv.2. mouse. [Q9QZE2-1]

Organism-specific databases

CTDi116449.
MGIiMGI:1351468. Clnk.

Phylogenomic databases

eggNOGiENOG410IHD0. Eukaryota.
ENOG410Z0GE. LUCA.
GeneTreeiENSGT00530000063094.
HOGENOMiHOG000111793.
InParanoidiQ9QZE2.
OMAiRHTFPEV.
OrthoDBiEOG091G053I.
PhylomeDBiQ9QZE2.

Miscellaneous databases

PROiQ9QZE2.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000039315.
CleanExiMM_CLNK.
ExpressionAtlasiQ9QZE2. baseline and differential.
GenevisibleiQ9QZE2. MM.

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]
ProtoNetiSearch...

Entry informationi

Entry nameiCLNK_MOUSE
AccessioniPrimary (citable) accession number: Q9QZE2
Secondary accession number(s): Q8C479, Q9JMJ3
Entry historyi
Integrated into UniProtKB/Swiss-Prot: January 15, 2008
Last sequence update: May 1, 2000
Last modified: November 2, 2016
This is version 100 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.