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Protein

Cytokine-dependent hematopoietic cell linker

Gene

CLNK

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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).By similarity

GO - Molecular functioni

  • SH3/SH2 adaptor activity Source: UniProtKB

GO - Biological processi

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
Proteomesi
  • UP000005640 Componenti: Chromosome 4

Organism-specific databases

EuPathDBiHostDB:ENSG00000109684.14
HGNCiHGNC:17438 CLNK
MIMi611434 gene
neXtProtiNX_Q7Z7G1

Subcellular locationi

Pathology & Biotechi

Organism-specific databases

DisGeNETi116449
OpenTargetsiENSG00000109684
PharmGKBiPA164718067

Polymorphism and mutation databases

BioMutaiCLNK
DMDMi166217263

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00003145971 – 428Cytokine-dependent hematopoietic cell linkerAdd BLAST428

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei69Phosphotyrosine; by LYNBy similarity1
Modified residuei96Phosphotyrosine; by LYNBy similarity1

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
PeptideAtlasiQ7Z7G1
PRIDEiQ7Z7G1
ProteomicsDBi69537
69538 [Q7Z7G1-2]
69539 [Q7Z7G1-3]

PTM databases

iPTMnetiQ7Z7G1
PhosphoSitePlusiQ7Z7G1

Expressioni

Gene expression databases

BgeeiENSG00000109684
ExpressionAtlasiQ7Z7G1 baseline and differential
GenevisibleiQ7Z7G1 HS

Organism-specific databases

HPAiHPA035671
HPA035672

Interactioni

Subunit structurei

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

Binary interactionsi

Show more details

GO - Molecular functioni

  • SH3/SH2 adaptor activity Source: UniProtKB

Protein-protein interaction databases

BioGridi125512, 28 interactors
IntActiQ7Z7G1, 27 interactors
MINTiQ7Z7G1
STRINGi9606.ENSP00000226951

Structurei

3D structure databases

ProteinModelPortaliQ7Z7G1
SMRiQ7Z7G1
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini309 – 419SH2PROSITE-ProRule annotationAdd BLAST111

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni159 – 164Mediates interaction with PLCG1By similarity6
Regioni178 – 180Mediates interaction with LAT and GRB2By similarity3

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi159 – 186Pro-richAdd BLAST28
Compositional biasi243 – 246Poly-Ser4

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

Keywords - Domaini

SH2 domain

Phylogenomic databases

eggNOGiENOG410IHD0 Eukaryota
ENOG410Z0GE LUCA
GeneTreeiENSGT00530000063094
HOGENOMiHOG000111793
InParanoidiQ7Z7G1
PhylomeDBiQ7Z7G1
TreeFamiTF326567

Family and domain databases

Gene3Di3.30.505.10, 1 hit
InterProiView protein in InterPro
IPR000980 SH2
IPR036860 SH2_dom_sf
PfamiView protein in Pfam
PF00017 SH2, 1 hit
PRINTSiPR00401 SH2DOMAIN
SMARTiView protein in SMART
SM00252 SH2, 1 hit
SUPFAMiSSF55550 SSF55550, 1 hit
PROSITEiView protein in PROSITE
PS50001 SH2, 1 hit

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

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

        10         20         30         40         50
MNRQGNRKTT KEGSNDLKFQ NFSLPKNRSW PRINSATGQY QRMNKPLLDW
60 70 80 90 100
ERNFAAVLDG AKGHSDDDYD DPELRMEETW QSIKILPARP IKESEYADTH
110 120 130 140 150
YFKVAMDTPL PLDTRTSISI GQPTWNTQTR LERVDKPISK DVRSQNIKGD
160 170 180 190 200
ASVRKNKIPL PPPRPLITLP KKYQPLPPEP ESSRPPLSQR HTFPEVQRMP
210 220 230 240 250
SQISLRDLSE VLEAEKVPHN QRKPESTHLL ENQNTQEIPL AISSSSFTTS
260 270 280 290 300
NHSVQNRDHR GGMQPCSPQR CQPPASCSPH ENILPYKYTS WRPPFPKRSD
310 320 330 340 350
RKDVQHNEWY IGEYSRQAVE EAFMKENKDG SFLVRDCSTK SKEEPYVLAV
360 370 380 390 400
FYENKVYNVK IRFLERNQQF ALGTGLRGDE KFDSVEDIIE HYKNFPIILI
410 420
DGKDKTGVHR KQCHLTQPLP LTRHLLPL
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)DescriptionActionsGraphical viewLength
Sequence conflicti140K → R in BAC76765 (Ref. 1) Curated1
Sequence conflicti140K → R in BAA96241 (PubMed:15489334).Curated1
Sequence conflicti198R → G in BAC76765 (Ref. 1) Curated1
Sequence conflicti198R → G in BAA96241 (PubMed:15489334).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_03798465S → G. Corresponds to variant dbSNP:rs16869924Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0303301 – 42Missing in isoform 2. 1 PublicationAdd BLAST42
Alternative sequenceiVSP_030331147 – 183Missing in isoform 3. CuratedAdd BLAST37
Alternative sequenceiVSP_030332211V → P in isoform 2. 1 Publication1
Alternative sequenceiVSP_030333212 – 428Missing in isoform 2. 1 PublicationAdd BLAST217

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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_052964.3 [Q7Z7G1-1]
UniGeneiHs.62772
Hs.678910

Genome annotation databases

EnsembliENST00000226951; ENSP00000226951; ENSG00000109684 [Q7Z7G1-1]
ENST00000507719; ENSP00000427208; ENSG00000109684 [Q7Z7G1-2]
GeneIDi116449
KEGGihsa:116449
UCSCiuc003gmo.5 human [Q7Z7G1-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiCLNK_HUMAN
AccessioniPrimary (citable) accession number: Q7Z7G1
Secondary accession number(s): Q05C27, Q9P2U9
Entry historyiIntegrated into UniProtKB/Swiss-Prot: January 15, 2008
Last sequence update: January 15, 2008
Last modified: June 20, 2018
This is version 106 of the entry and version 2 of the sequence. See 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

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