Q7Z7G1 (CLNK_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Cytokine-dependent hematopoietic cell linker

Alternative name(s):
Mast cell immunoreceptor signal transducer

Gene names

Name:	CLNK
Synonyms:	MIST

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	428 AA.
Sequence status	Complete.
Protein existence	Evidence at transcript 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.

Ontologies

Keywords
Coding sequence diversity	Alternative splicing Polymorphism
Domain	SH2 domain
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	immune response Non-traceable author statement Ref.4. Source: UniProtKB intracellular signal transduction Inferred from direct assay Ref.4. Source: UniProtKB transmembrane receptor protein tyrosine kinase signaling pathway Inferred from electronic annotation. Source: Compara
Cellular_component	intracellular Non-traceable author statement Ref.4. Source: UniProtKB
Molecular_function	SH3/SH2 adaptor activity Non-traceable author statement Ref.4. Source: UniProtKB
Complete GO annotation...

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 key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 428	428	Cytokine-dependent hematopoietic cell linker		PRO_0000314597
Regions
	Domain	309 – 419	111	SH2
	Region	159 – 164	6	Mediates interaction with PLCG1 By similarity
	Region	178 – 180	3	Mediates interaction with LAT and GRB2 By similarity
	Compositional bias	159 – 186	28	Pro-rich
	Compositional bias	243 – 246	4	Poly-Ser
Amino acid modifications
	Modified residue	69	1	Phosphotyrosine; by LYN By similarity
	Modified residue	96	1	Phosphotyrosine; by LYN By similarity
Natural variations
	Alternative sequence	1 – 42	42	Missing in isoform 2.		VSP_030330
	Alternative sequence	147 – 183	37	Missing in isoform 3.		VSP_030331
	Alternative sequence	211	1	V → P in isoform 2.		VSP_030332
	Alternative sequence	212 – 428	217	Missing in isoform 2.		VSP_030333
	Natural variant	65	1	S → G. Corresponds to variant rs16869924 [ dbSNP | Ensembl ].		VAR_037984
Experimental info
	Sequence conflict	140	1	K → R in BAC76765. Ref.1
	Sequence conflict	140	1	K → R in BAA96241. Ref.3
	Sequence conflict	198	1	R → G in BAC76765. Ref.1
	Sequence conflict	198	1	R → G in BAA96241. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified January 15, 2008. Version 2. Checksum: 98DEDD4378D395A7	FASTA	428	49,554
	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
	Isoform 2 [UniParc]. Checksum: 94F30955424B92F0	FASTA	169	19,416
	10 20 30 40 50 60 MNKPLLDWER NFAAVLDGAK GHSDDDYDDP ELRMEETWQS IKILPARPIK ESEYADTHYF 70 80 90 100 110 120 KVAMDTPLPL DTRTSISIGQ PTWNTQTRLE RVDKPISKDV RSQNIKGDAS VRKNKIPLPP 130 140 150 160 PRPLITLPKK YQPLPPEPES SRPPLSQRHT FPEVQRMPSQ ISLRDLSEP
	Isoform 3 [UniParc]. Checksum: 3B3D533514DBC45F	FASTA	391	45,469
	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 DVRSQNRPPL SQRHTFPEVQ RMPSQISLRD LSEVLEAEKV 190 200 210 220 230 240 PHNQRKPEST HLLENQNTQE IPLAISSSSF TTSNHSVQNR DHRGGMQPCS PQRCQPPASC 250 260 270 280 290 300 SPHENILPYK YTSWRPPFPK RSDRKDVQHN EWYIGEYSRQ AVEEAFMKEN KDGSFLVRDC 310 320 330 340 350 360 STKSKEEPYV LAVFYENKVY NVKIRFLERN QQFALGTGLR GDEKFDSVED IIEHYKNFPI 370 380 390 ILIDGKDKTG VHRKQCHLTQ PLPLTRHLLP L

References

	« Hide 'large scale' referencesShow '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. , 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.
IPI	IPI00185667. IPI00877744. IPI00879489.
RefSeq	NP_443196.2. NM_052964.2.
UniGene	Hs.678910.
3D structure databases
HSSP	HSSP built from PDB template 2SHP based on UniProtKB Q06124.
ProteinModelPortal	Q7Z7G1.
ModBase	Search...
Protein-protein interaction databases
MINT	MINT-1493840.
STRING	9606.ENSP00000226951.
PTM databases
PhosphoSite	Q7Z7G1.
Polymorphism databases
DMDM	166217263.
Proteomic databases
PaxDb	Q7Z7G1.
PRIDE	Q7Z7G1.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000226951; ENSP00000226951; ENSG00000109684. ENST00000442825; ENSP00000390744; ENSG00000109684. ENST00000507719; ENSP00000427208; ENSG00000109684.
GeneID	116449.
KEGG	hsa:116449.
UCSC	uc003gmo.4. human. uc003gmp.3. human.
Organism-specific databases
CTD	116449.
GeneCards	GC04M010491.
HGNC	HGNC:17438. CLNK.
HPA	HPA035671. HPA035672.
MIM	611434. gene.
neXtProt	NX_Q7Z7G1.
PharmGKB	PA164718067.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG77726.
HOGENOM	HOG000111793.
InParanoid	Q7Z7G1.
OMA	QRHTFPE.
OrthoDB	EOG4QJRNB.
Gene expression databases
ArrayExpress	Q7Z7G1.
Bgee	Q7Z7G1.
Genevestigator	Q7Z7G1.
Family and domain databases
Gene3D	3.30.505.10. 1 hit.
InterPro	IPR000980. SH2. [Graphical view]
Pfam	PF00017. SH2. 1 hit. [Graphical view]
PRINTS	PR00401. SH2DOMAIN.
SMART	SM00252. SH2. 1 hit. [Graphical view]
PROSITE	PS50001. SH2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	116449.
NextBio	79941.
SOURCE	Search...

Entry information

Entry name

CLNK_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 68 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.