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Protein

Cytokine-dependent hematopoietic cell linker

Gene

CLNK

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

GO - Molecular functioni

  1. 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 Componenti: 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.

Polymorphism and mutation databases

BioMutaiCLNK.
DMDMi166217263.

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

BgeeiQ7Z7G1.
ExpressionAtlasiQ7Z7G1. baseline and differential.
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.
GeneTreeiENSGT00530000063094.
HOGENOMiHOG000111793.
InParanoidiQ7Z7G1.
OMAiSVQNRDH.
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. 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)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti140 – 1401K → R in BAC76765 (Ref. 1) Curated
Sequence conflicti140 – 1401K → R in BAA96241 (PubMed:15489334).Curated
Sequence conflicti198 – 1981R → G in BAC76765 (Ref. 1) Curated
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:
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_052964.2. [Q7Z7G1-1]
UniGeneiHs.678910.

Genome annotation databases

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

Polymorphism and mutation databases

BioMutaiCLNK.

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

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_052964.2. [Q7Z7G1-1]
UniGeneiHs.678910.

3D structure databases

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

Protein-protein interaction databases

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

PTM databases

PhosphoSiteiQ7Z7G1.

Polymorphism and mutation databases

BioMutaiCLNK.
DMDMi166217263.

Proteomic databases

PaxDbiQ7Z7G1.
PRIDEiQ7Z7G1.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi116449.
GeneCardsiGC04M010491.
HGNCiHGNC:17438. CLNK.
HPAiHPA035671.
HPA035672.
MIMi611434. gene.
neXtProtiNX_Q7Z7G1.
PharmGKBiPA164718067.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG77726.
GeneTreeiENSGT00530000063094.
HOGENOMiHOG000111793.
InParanoidiQ7Z7G1.
OMAiSVQNRDH.
OrthoDBiEOG7FJH09.
PhylomeDBiQ7Z7G1.
TreeFamiTF326567.

Enzyme and pathway databases

SignaLinkiQ7Z7G1.

Miscellaneous databases

ChiTaRSiCLNK. human.
GenomeRNAii116449.
NextBioi79941.
PROiQ7Z7G1.
SOURCEiSearch...

Gene expression databases

BgeeiQ7Z7G1.
ExpressionAtlasiQ7Z7G1. baseline and differential.
GenevestigatoriQ7Z7G1.

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...

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: April 29, 2015
This is version 84 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

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 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.