Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

P49710 (HCLS1_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 121. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Hematopoietic lineage cell-specific protein
Alternative name(s):
Hematopoietic cell-specific LYN substrate 1
LckBP1
Gene names
Name:Hcls1
Synonyms:Hs1
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length486 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Substrate of the antigen receptor-coupled tyrosine kinase. Plays a role in antigen receptor signaling for both clonal expansion and deletion in lymphoid cells. May also be involved in the regulation of gene expression By similarity.

Subunit structure

Interacts (via SH2 domain) with FGR By similarity. Associates with the SH2 and SH3 domains of LCK. Binding to he LCK SH3 domain occurs constitutively, while binding to the LCK SH2 domain occurs only upon TCR stimulation. A similar binding pattern was observed with LYN, but not with FYN in which the FYN SH2 region associates upon TCR stimulation but the FYN SH3 region does not associate regardless of TCR stimulation. Directly associates with HAX1, through binding to its C-terminal region. Interacts with HS1BP3. Interacts with FES/FPS. Forms a multiprotein complex with LYN and ANKRD54. Ref.4 Ref.5 Ref.7 Ref.8

Subcellular location

Mitochondrion By similarity.

Tissue specificity

Expressed only in tissues and cells of hematopoietic origin.

Post-translational modification

Phosphorylated by LYN, FYN and FGR after cross-linking of surface IgM on B-cells. Phosphorylation by LYN, FYN and FGR requires prior phosphorylation by SYK By similarity. Binds to LCK in vivo, and is tyrosine phosphorylated upon TCR stimulation. Phosphorylated by FES. Ref.8

Sequence similarities

Contains 4 cortactin repeats.

Contains 1 SH3 domain.

Ontologies

Keywords
   Cellular componentMitochondrion
   DomainRepeat
SH3 domain
   PTMAcetylation
Phosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processactin filament polymerization

Inferred from electronic annotation. Source: InterPro

cellular response to cytokine stimulus

Inferred from electronic annotation. Source: Ensembl

erythrocyte differentiation

Inferred from mutant phenotype PubMed 10713104. Source: UniProtKB

negative regulation of leukocyte apoptotic process

Inferred from electronic annotation. Source: Ensembl

negative regulation of transcription from RNA polymerase II promoter

Inferred from mutant phenotype PubMed 23001182. Source: BHF-UCL

positive regulation of cell proliferation

Inferred from mutant phenotype PubMed 10713104. Source: UniProtKB

positive regulation of granulocyte differentiation

Inferred from mutant phenotype PubMed 23001182. Source: BHF-UCL

positive regulation of macrophage differentiation

Inferred from mutant phenotype PubMed 23001182. Source: BHF-UCL

positive regulation of peptidyl-serine phosphorylation

Inferred from electronic annotation. Source: Ensembl

positive regulation of phosphatidylinositol 3-kinase signaling

Inferred from electronic annotation. Source: Ensembl

positive regulation of protein kinase B signaling

Inferred from electronic annotation. Source: Ensembl

positive regulation of transcription factor import into nucleus

Inferred from electronic annotation. Source: Ensembl

positive regulation of transcription from RNA polymerase II promoter

Inferred from mutant phenotype PubMed 23001182. Source: BHF-UCL

positive regulation of tyrosine phosphorylation of STAT protein

Inferred from mutant phenotype PubMed 10713104. Source: UniProtKB

regulation of actin filament polymerization

Inferred from electronic annotation. Source: Ensembl

response to hormone

Inferred from direct assay PubMed 10713104. Source: UniProtKB

   Cellular_componentcytoplasm

Inferred from direct assay PubMed 10713104. Source: UniProtKB

mitochondrion

Inferred from electronic annotation. Source: UniProtKB-SubCell

nucleus

Inferred from direct assay PubMed 10713104. Source: UniProtKB

plasma membrane

Inferred from electronic annotation. Source: Ensembl

transcription factor complex

Inferred from electronic annotation. Source: Ensembl

   Molecular_functionSH3 domain binding

Inferred from direct assay PubMed 9126384. Source: MGI

protein binding

Inferred from physical interaction PubMed 10713104. Source: UniProtKB

protein complex binding

Inferred from physical interaction Ref.7. Source: MGI

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

LynP2591110EBI-924601,EBI-643537

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 486486Hematopoietic lineage cell-specific protein
PRO_0000083922

Regions

Repeat79 – 11537Cortactin 1
Repeat116 – 15237Cortactin 2
Repeat153 – 18937Cortactin 3
Repeat190 – 21223Cortactin 4; truncated
Domain429 – 48658SH3
Region27 – 6640Involved in HAX-1 binding By similarity

Amino acid modifications

Modified residue411N6-acetyllysine By similarity
Modified residue1031Phosphotyrosine By similarity
Modified residue1231N6-acetyllysine By similarity
Modified residue1401Phosphotyrosine Ref.6
Modified residue1921N6-acetyllysine By similarity
Modified residue1981Phosphotyrosine By similarity
Modified residue2221Phosphotyrosine; by FGR By similarity
Modified residue2411N6-acetyllysine By similarity
Modified residue2751Phosphoserine By similarity
Modified residue3881Phosphotyrosine; by SYK and FES Probable
Modified residue4051Phosphotyrosine; by SYK and FES Probable

Experimental info

Mutagenesis3881Y → F: Strongly reduces phosphorylation by FES. Abolishes phosphorylation by FES; when associated with F-405. Ref.8
Mutagenesis4051Y → F: Minor effect on phosphorylation by FES. Abolishes phosphorylation by FES; when associated with F-388. Ref.8
Sequence conflict861R → Q in BAA07701. Ref.1
Sequence conflict861R → Q in CAA59265. Ref.2

Sequences

Sequence LengthMass (Da)Tools
P49710 [UniParc].

Last modified July 27, 2011. Version 2.
Checksum: 0EE14FEFA0A31412

FASTA48654,240
        10         20         30         40         50         60 
MWKSVVGHDV SVSVETQGDD WDTDPDFVND ISEKEQRWGA KTIEGSGRTE HINIHQLRNK 

        70         80         90        100        110        120 
VSEEHDILKK KELESGPKAS HGYGGRFGVE RDRMDKSAVG HEYVADVEKH SSQTDAARGF 

       130        140        150        160        170        180 
GGKYGVERDR ADKSAVGFDY KGEVEKHASQ KDYSHGFGGR YGVEKDKRDK AALGYDYKGE 

       190        200        210        220        230        240 
TEKHESQRDY AKGFGGQYGI QKDRVDKSAV GFNEMEAPTT AYKKTTPIEA ASSGARGLKA 

       250        260        270        280        290        300 
KFESLAEEKR KREEEEKAQQ MARQQQERKA VVKMSREVQQ PSMPVEEPAA PAQLPKKISS 

       310        320        330        340        350        360 
EVWPPAESHL PPESQPVRSR REYPVPSLPT RQSPLQNHLE DNEEPPALPP RTPEGLQVVE 

       370        380        390        400        410        420 
EPVYEAAPEL EPEPEPDYEP EPETEPDYED VGELDRQDED AEGDYEDVLE PEDTPSLSYQ 

       430        440        450        460        470        480 
AGPSAGAGGA GISAIALYDY QGEGSDELSF DPDDIITDIE MVDEGWWRGQ CRGHFGLFPA 


NYVKLL 

« Hide

References

« Hide 'large scale' references
[1]"Molecular cloning and characterization of mouse HS1."
Kitamura D., Kaneko H., Taniuchi I., Yamamura K., Watanabe T.
Biochem. Biophys. Res. Commun. 208:1137-1146(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]"LckBP1, a proline-rich protein expressed in haematopoietic lineage cells, directly associates with the SH3 domain of protein tyrosine kinase p56(lck)."
Takemoto Y., Furuta M., Li X.-K., Strong-Sparks W.J., Hashimoto Y.
EMBO J. 14:3403-3414(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Thymocyte.
[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].
Strain: FVB/N.
Tissue: Mammary tumor.
[4]"Distinct binding patterns of HS1 to the Src SH2 and SH3 domains reflect possible mechanisms of recruitment and activation of downstream molecules."
Takemoto Y., Sato M., Furuta M., Hashimoto Y.
Int. Immunol. 8:1699-1705(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH LCK, BINDING PATTERN OF SERVERAL SRC KINASES.
Strain: BALB/c.
[5]"Isolation and characterization of a novel HS1 SH3 domain binding protein, HS1BP3."
Takemoto Y., Furuta M., Sato M., Kubo M., Hashimoto Y.
Int. Immunol. 11:1957-1964(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH HS1BP3.
[6]"Quantitative time-resolved phosphoproteomic analysis of mast cell signaling."
Cao L., Yu K., Banh C., Nguyen V., Ritz A., Raphael B.J., Kawakami Y., Kawakami T., Salomon A.R.
J. Immunol. 179:5864-5876(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-140, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Mast cell.
[7]"Liar, a novel Lyn-binding nuclear/cytoplasmic shuttling protein that influences erythropoietin-induced differentiation."
Samuels A.L., Klinken S.P., Ingley E.
Blood 113:3845-3856(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH ANKRD54.
[8]"Contributions of F-BAR and SH2 domains of Fes protein tyrosine kinase for coupling to the FcepsilonRI pathway in mast cells."
McPherson V.A., Everingham S., Karisch R., Smith J.A., Udell C.M., Zheng J., Jia Z., Craig A.W.
Mol. Cell. Biol. 29:389-401(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH FES/FPS, PHOSPHORYLATION AT TYR-388 AND TYR-405, MUTAGENESIS OF TYR-388 AND TYR-405.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
D42120 mRNA. Translation: BAA07701.1.
X84797 mRNA. Translation: CAA59265.1.
BC007469 mRNA. Translation: AAH07469.1.
CCDSCCDS37336.1.
PIRI49760.
RefSeqNP_032251.2. NM_008225.2.
UniGeneMm.4091.

3D structure databases

ProteinModelPortalP49710.
SMRP49710. Positions 431-485.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid200250. 2 interactions.
IntActP49710. 4 interactions.
MINTMINT-84934.

PTM databases

PhosphoSiteP49710.

Proteomic databases

MaxQBP49710.
PaxDbP49710.
PRIDEP49710.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000023531; ENSMUSP00000023531; ENSMUSG00000022831.
GeneID15163.
KEGGmmu:15163.
UCSCuc007zdi.2. mouse.

Organism-specific databases

CTD3059.
MGIMGI:104568. Hcls1.

Phylogenomic databases

eggNOGNOG123488.
GeneTreeENSGT00530000062953.
HOGENOMHOG000006523.
HOVERGENHBG005994.
InParanoidQ922I8.
KOK06106.
OMAEMDRHEQ.
OrthoDBEOG7V49ZC.
TreeFamTF318935.

Gene expression databases

ArrayExpressP49710.
BgeeP49710.
CleanExMM_HCLS1.
GenevestigatorP49710.

Family and domain databases

InterProIPR028534. HS1.
IPR003134. Hs1_Cortactin.
IPR001452. SH3_domain.
[Graphical view]
PANTHERPTHR10829:SF5. PTHR10829:SF5. 1 hit.
PfamPF02218. HS1_rep. 4 hits.
PF00018. SH3_1. 1 hit.
[Graphical view]
PRINTSPR00452. SH3DOMAIN.
SMARTSM00326. SH3. 1 hit.
[Graphical view]
SUPFAMSSF50044. SSF50044. 1 hit.
PROSITEPS51090. CORTACTIN. 4 hits.
PS50002. SH3. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio287660.
PMAP-CutDBP49710.
PROP49710.
SOURCESearch...

Entry information

Entry nameHCLS1_MOUSE
AccessionPrimary (citable) accession number: P49710
Secondary accession number(s): Q922I8
Entry history
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: July 27, 2011
Last modified: July 9, 2014
This is version 121 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot