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Q7Z7G1 (CLNK_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 76. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Cytokine-dependent hematopoietic cell linker
Alternative name(s):
Mast cell immunoreceptor signal transducer
Gene names
Name:CLNK
Synonyms:MIST
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length428 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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.

Subunit structure

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

Domain

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.

Post-translational modification

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.

Sequence similarities

Contains 1 SH2 domain.

Binary interactions

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q7Z7G1-1)

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.
Isoform 2 (identifier: Q7Z7G1-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-42: Missing.
     211-211: V → P
     212-428: Missing.
Isoform 3 (identifier: Q7Z7G1-3)

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

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 428428Cytokine-dependent hematopoietic cell linker
PRO_0000314597

Regions

Domain309 – 419111SH2
Region159 – 1646Mediates interaction with PLCG1 By similarity
Region178 – 1803Mediates interaction with LAT and GRB2 By similarity
Compositional bias159 – 18628Pro-rich
Compositional bias243 – 2464Poly-Ser

Amino acid modifications

Modified residue691Phosphotyrosine; by LYN By similarity
Modified residue961Phosphotyrosine; by LYN By similarity

Natural variations

Alternative sequence1 – 4242Missing in isoform 2.
VSP_030330
Alternative sequence147 – 18337Missing in isoform 3.
VSP_030331
Alternative sequence2111V → P in isoform 2.
VSP_030332
Alternative sequence212 – 428217Missing in isoform 2.
VSP_030333
Natural variant651S → G.
Corresponds to variant rs16869924 [ dbSNP | Ensembl ].
VAR_037984

Experimental info

Sequence conflict1401K → R in BAC76765. Ref.1
Sequence conflict1401K → R in BAA96241. Ref.3
Sequence conflict1981R → G in BAC76765. Ref.1
Sequence conflict1981R → G in BAA96241. Ref.3

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified January 15, 2008. Version 2.
Checksum: 98DEDD4378D395A7

FASTA42849,554
        10         20         30         40         50         60 
MNRQGNRKTT KEGSNDLKFQ NFSLPKNRSW PRINSATGQY QRMNKPLLDW ERNFAAVLDG 

        70         80         90        100        110        120 
AKGHSDDDYD DPELRMEETW QSIKILPARP IKESEYADTH YFKVAMDTPL PLDTRTSISI 

       130        140        150        160        170        180 
GQPTWNTQTR LERVDKPISK DVRSQNIKGD ASVRKNKIPL PPPRPLITLP KKYQPLPPEP 

       190        200        210        220        230        240 
ESSRPPLSQR HTFPEVQRMP SQISLRDLSE VLEAEKVPHN QRKPESTHLL ENQNTQEIPL 

       250        260        270        280        290        300 
AISSSSFTTS NHSVQNRDHR GGMQPCSPQR CQPPASCSPH ENILPYKYTS WRPPFPKRSD 

       310        320        330        340        350        360 
RKDVQHNEWY IGEYSRQAVE EAFMKENKDG SFLVRDCSTK SKEEPYVLAV FYENKVYNVK 

       370        380        390        400        410        420 
IRFLERNQQF ALGTGLRGDE KFDSVEDIIE HYKNFPIILI DGKDKTGVHR KQCHLTQPLP 


LTRHLLPL 

« Hide

Isoform 2 [UniParc].

Checksum: 94F30955424B92F0
Show »

FASTA16919,416
Isoform 3 [UniParc].

Checksum: 3B3D533514DBC45F
Show »

FASTA39145,469

References

« Hide 'large scale' references
[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. expand/collapse author list , 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).
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AB110420 mRNA. Translation: BAC76765.1.
AC005599 Genomic DNA. No translation available.
BC029887 mRNA. Translation: AAH29887.1.
AB032369 mRNA. Translation: BAA96241.1.
RefSeqNP_443196.2. NM_052964.2.
UniGeneHs.678910.

3D structure databases

ProteinModelPortalQ7Z7G1.
SMRQ7Z7G1. Positions 303-423.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid125512. 2 interactions.
IntActQ7Z7G1. 2 interactions.
MINTMINT-1493840.
STRING9606.ENSP00000226951.

PTM databases

PhosphoSiteQ7Z7G1.

Polymorphism databases

DMDM166217263.

Proteomic databases

PaxDbQ7Z7G1.
PRIDEQ7Z7G1.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000226951; ENSP00000226951; ENSG00000109684. [Q7Z7G1-1]
ENST00000442825; ENSP00000390744; ENSG00000109684. [Q7Z7G1-2]
ENST00000507719; ENSP00000427208; ENSG00000109684. [Q7Z7G1-2]
GeneID116449.
KEGGhsa:116449.
UCSCuc003gmo.4. human. [Q7Z7G1-1]
uc003gmp.3. human. [Q7Z7G1-2]

Organism-specific databases

CTD116449.
GeneCardsGC04M010491.
HGNCHGNC:17438. CLNK.
HPAHPA035671.
HPA035672.
MIM611434. gene.
neXtProtNX_Q7Z7G1.
PharmGKBPA164718067.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG77726.
HOGENOMHOG000111793.
InParanoidQ7Z7G1.
OMAQRHTFPE.
OrthoDBEOG7FJH09.
PhylomeDBQ7Z7G1.
TreeFamTF326567.

Enzyme and pathway databases

SignaLinkQ7Z7G1.

Gene expression databases

ArrayExpressQ7Z7G1.
BgeeQ7Z7G1.
GenevestigatorQ7Z7G1.

Family and domain databases

Gene3D3.30.505.10. 1 hit.
InterProIPR000980. SH2.
[Graphical view]
PfamPF00017. SH2. 1 hit.
[Graphical view]
PRINTSPR00401. SH2DOMAIN.
SMARTSM00252. SH2. 1 hit.
[Graphical view]
SUPFAMSSF55550. SSF55550. 1 hit.
PROSITEPS50001. SH2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GenomeRNAi116449.
NextBio79941.
PROQ7Z7G1.
SOURCESearch...

Entry information

Entry nameCLNK_HUMAN
AccessionPrimary (citable) accession number: Q7Z7G1
Secondary accession number(s): Q05C27, Q9P2U9
Entry history
Integrated into UniProtKB/Swiss-Prot: January 15, 2008
Last sequence update: January 15, 2008
Last modified: April 16, 2014
This is version 76 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 4

Human chromosome 4: entries, gene names and cross-references to MIM