P49710 (HCLS1_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Hematopoietic lineage cell-specific protein

Alternative name(s):
Hematopoietic cell-specific LYN substrate 1
LckBP1

Gene names

Name:	Hcls1
Synonyms:	Hs1

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	486 AA.
Sequence status	Complete.
Protein existence	Evidence 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 component	Mitochondrion
Domain	Repeat SH3 domain
PTM	Acetylation Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	erythrocyte differentiation Inferred from mutant phenotype PubMed 10713104. Source: UniProtKB 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 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 response to hormone stimulus Inferred from direct assay PubMed 10713104. Source: UniProtKB
Cellular_component	cytoplasm 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: Compara
Molecular_function	SH3 domain binding Inferred from direct assay PubMed 9126384. Source: MGI
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
Lyn	P25911	10	EBI-924601,EBI-643537

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 486	486	Hematopoietic lineage cell-specific protein		PRO_0000083922
Regions
	Repeat	79 – 115	37	Cortactin 1
	Repeat	116 – 152	37	Cortactin 2
	Repeat	153 – 189	37	Cortactin 3
	Repeat	190 – 212	23	Cortactin 4; truncated
	Domain	429 – 486	58	SH3
	Region	27 – 66	40	Involved in HAX-1 binding By similarity
Amino acid modifications
	Modified residue	41	1	N6-acetyllysine By similarity
	Modified residue	103	1	Phosphotyrosine By similarity
	Modified residue	123	1	N6-acetyllysine By similarity
	Modified residue	140	1	Phosphotyrosine Ref.6
	Modified residue	192	1	N6-acetyllysine By similarity
	Modified residue	198	1	Phosphotyrosine By similarity
	Modified residue	222	1	Phosphotyrosine; by FGR By similarity
	Modified residue	241	1	N6-acetyllysine By similarity
	Modified residue	275	1	Phosphoserine By similarity
	Modified residue	388	1	Phosphotyrosine; by SYK and FES Probable
	Modified residue	405	1	Phosphotyrosine; by SYK and FES Probable
Experimental info
	Mutagenesis	388	1	Y → F: Strongly reduces phosphorylation by FES. Abolishes phosphorylation by FES; when associated with F-405. Ref.8
	Mutagenesis	405	1	Y → F: Minor effect on phosphorylation by FES. Abolishes phosphorylation by FES; when associated with F-388. Ref.8
	Sequence conflict	86	1	R → Q in BAA07701. Ref.1
	Sequence conflict	86	1	R → Q in CAA59265. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	P49710 [UniParc]. Last modified July 27, 2011. Version 2. Checksum: 0EE14FEFA0A31412	FASTA	486	54,240
	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

References

	« Hide 'large scale' referencesShow '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, MASS SPECTROMETRY. 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.
IPI	IPI00117011.
PIR	I49760.
RefSeq	NP_032251.2. NM_008225.2.
UniGene	Mm.4091.
3D structure databases
ProteinModelPortal	P49710.
SMR	P49710. Positions 431-485.
ModBase	Search...
Protein-protein interaction databases
IntAct	P49710. 3 interactions.
MINT	MINT-84934.
PTM databases
PhosphoSite	P49710.
Proteomic databases
PaxDb	P49710.
PRIDE	P49710.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000023531; ENSMUSP00000023531; ENSMUSG00000022831.
GeneID	15163.
KEGG	mmu:15163.
Organism-specific databases
CTD	3059.
MGI	MGI:104568. Hcls1.
Phylogenomic databases
eggNOG	NOG123488.
GeneTree	ENSGT00530000062953.
HOGENOM	HOG000006523.
HOVERGEN	HBG005994.
InParanoid	Q922I8.
KO	K06106.
OMA	DRHEQED.
OrthoDB	EOG405S15.
Gene expression databases
ArrayExpress	P49710.
Bgee	P49710.
CleanEx	MM_HCLS1.
Genevestigator	P49710.
GermOnline	ENSMUSG00000022831. Mus musculus.
Family and domain databases
InterPro	IPR003134. Hs1_Cortactin. IPR000108. p67phox. IPR001452. SH3_domain. [Graphical view]
Pfam	PF02218. HS1_rep. 4 hits. PF00018. SH3_1. 1 hit. [Graphical view]
PRINTS	PR00499. P67PHOX. PR00452. SH3DOMAIN.
SMART	SM00326. SH3. 1 hit. [Graphical view]
SUPFAM	SSF50044. SH3. 1 hit.
PROSITE	PS51090. CORTACTIN. 4 hits. PS50002. SH3. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	287660.
PMAP-CutDB	P49710.
SOURCE	Search...

Entry information

Entry name

HCLS1_MOUSE

Accession

Primary (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:	April 3, 2013
This is version 109 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program