P14317 (HCLS1_HUMAN) 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
p75

Gene names

Name:	HCLS1
Synonyms:	HS1

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	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.
Subunit structure	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 By similarity. Interacts (via SH2 domain) with FGR. Forms a multiprotein complex with LYN and ANKRD54 By similarity. Ref.7 Ref.10 Ref.11
Subcellular location	Membrane; Peripheral membrane protein. Cytoplasm. Mitochondrion Probable Ref.7.
Tissue specificity	Expressed only in tissues and cells of hematopoietic origin.
Developmental stage	Expressed in early stage of myeloid and erythroid differentiation.
Post-translational modification	Phosphorylated by FES By similarity. 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 or FES. Ref.7 Ref.9 Ref.11
Sequence similarities	Contains 4 cortactin repeats. Contains 1 SH3 domain.

Ontologies

Keywords
Cellular component	Cytoplasm Membrane Mitochondrion
Coding sequence diversity	Polymorphism
Domain	Repeat SH3 domain
PTM	Acetylation Phosphoprotein
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	cellular response to cytokine stimulus Inferred from mutant phenotype PubMed 23001182. Source: BHF-UCL erythrocyte differentiation Inferred from sequence or structural similarity. Source: UniProtKB intracellular signal transduction Traceable author statement PubMed 8978766. Source: ProtInc negative regulation of leukocyte apoptotic process Inferred from mutant phenotype PubMed 23001182. Source: BHF-UCL positive regulation of actin cytoskeleton reorganization Inferred by curator PubMed 23001182. Source: BHF-UCL positive regulation of cell proliferation Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of granulocyte differentiation Inferred from mutant phenotype PubMed 23001182. Source: BHF-UCL positive regulation of peptidyl-serine phosphorylation Inferred from mutant phenotype PubMed 23001182. Source: BHF-UCL positive regulation of phosphatidylinositol 3-kinase cascade Inferred from mutant phenotype PubMed 23001182. Source: BHF-UCL positive regulation of protein kinase B signaling cascade Inferred from mutant phenotype PubMed 23001182. Source: BHF-UCL positive regulation of transcription factor import into nucleus 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 sequence or structural similarity. Source: UniProtKB regulation of actin filament polymerization Inferred from mutant phenotype PubMed 23001182. Source: BHF-UCL response to hormone stimulus Inferred from sequence or structural similarity. Source: UniProtKB
Cellular_component	cytoplasm Inferred from sequence or structural similarity. Source: UniProtKB mitochondrion Inferred from electronic annotation. Source: UniProtKB-SubCell plasma membrane Inferred from direct assay. Source: HPA transcription factor complex Inferred from direct assay PubMed 23001182. Source: BHF-UCL
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
WIPF1	O43516	2	EBI-750369,EBI-346356

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_0000083921
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	428 – 486	59	SH3
	Region	27 – 66	40	Involved in HAX-1 binding
Amino acid modifications
	Modified residue	41	1	N6-acetyllysine Ref.15
	Modified residue	103	1	Phosphotyrosine
	Modified residue	123	1	N6-acetyllysine Ref.15
	Modified residue	140	1	Phosphotyrosine By similarity
	Modified residue	192	1	N6-acetyllysine Ref.15
	Modified residue	198	1	Phosphotyrosine Ref.12 Ref.13
	Modified residue	222	1	Phosphotyrosine; by FGR Ref.9 Ref.11
	Modified residue	241	1	N6-acetyllysine Ref.15
	Modified residue	275	1	Phosphoserine Ref.14
	Modified residue	308	1	Phosphothreonine Ref.14
	Modified residue	378	1	Phosphotyrosine; by SYK and FES By similarity
	Modified residue	397	1	Phosphotyrosine; by SYK and FES By similarity
Natural variations
	Natural variant	235	1	T → A. Ref.1 Ref.2 Ref.3 Ref.4 Ref.6 Corresponds to variant rs2070179 [ dbSNP | Ensembl ].		VAR_055006
	Natural variant	361	1	E → K. Corresponds to variant rs2070180 [ dbSNP | Ensembl ].		VAR_055007
	Natural variant	436	1	V → L. Ref.1 Ref.2 Ref.3 Ref.4 Ref.6 Corresponds to variant rs9869984 [ dbSNP | Ensembl ].		VAR_056910
Experimental info
	Sequence conflict	241 – 242	2	KF → FK AA sequence Ref.8
	Sequence conflict	486	1	E → D in CAG33075. Ref.4

Sequences

	Sequence		Length	Mass (Da)
	P14317 [UniParc]. Last modified January 11, 2011. Version 3. Checksum: 20AE72A28DA33DFB	FASTA	486	54,014
	10 20 30 40 50 60 MWKSVVGHDV SVSVETQGDD WDTDPDFVND ISEKEQRWGA KTIEGSGRTE HINIHQLRNK 70 80 90 100 110 120 VSEEHDVLRK KEMESGPKAS HGYGGRFGVE RDRMDKSAVG HEYVAEVEKH SSQTDAAKGF 130 140 150 160 170 180 GGKYGVERDR ADKSAVGFDY KGEVEKHTSQ KDYSRGFGGR YGVEKDKWDK AALGYDYKGE 190 200 210 220 230 240 TEKHESQRDY AKGFGGQYGI QKDRVDKSAV GFNEMEAPTT AYKKTTPIEA ASSGTRGLKA 250 260 270 280 290 300 KFESMAEEKR KREEEEKAQQ VARRQQERKA VTKRSPEAPQ PVIAMEEPAV PAPLPKKISS 310 320 330 340 350 360 EAWPPVGTPP SSESEPVRTS REHPVPLLPI RQTLPEDNEE PPALPPRTLE GLQVEEEPVY 370 380 390 400 410 420 EAEPEPEPEP EPEPENDYED VEEMDRHEQE DEPEGDYEEV LEPEDSSFSS ALAGSSGCPA 430 440 450 460 470 480 GAGAGAVALG ISAVAVYDYQ GEGSDELSFD PDDVITDIEM VDEGWWRGRC HGHFGLFPAN YVKLLE

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Isolation and characterization of a novel human gene expressed specifically in the cells of hematopoietic lineage." Kitamura D., Kaneko H., Miyagoe Y., Ariyasu T., Watanabe T. Nucleic Acids Res. 17:9367-9379(1989) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANTS ALA-235 AND LEU-436.
[2]	"Cloning of human full-length CDSs in BD Creator(TM) system donor vector." Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A. Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANTS ALA-235 AND LEU-436.
[3]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANTS ALA-235 AND LEU-436. Tissue: Spleen.
[4]	"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)." Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B. Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANTS ALA-235 AND LEU-436.
[5]	"The DNA sequence, annotation and analysis of human chromosome 3." Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J. , Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W., Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P., Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H., Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J., Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W., Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B., Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H., Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J., Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X., Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R., Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A. Nature 440:1194-1198(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"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], VARIANTS ALA-235 AND LEU-436. Tissue: Lymph.
[7]	"Identification of HS1 protein as a major substrate of protein-tyrosine kinase(s) upon B-cell antigen receptor-mediated signaling." Yamanashi Y., Okada M., Semba T., Yamori T., Umemori H., Tsunasawa S., Toyoshima K., Kitamura D., Watanabe T., Yamamoto T. Proc. Natl. Acad. Sci. U.S.A. 90:3631-3635(1993) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 4-26; 79-95; 134-146; 208-223 AND 274-289, INTERACTION WITH LYN, SUBCELLULAR LOCATION, PHOSPHORYLATION. Tissue: B-cell lymphoma.
[8]	"Identification of the 70kD heat shock cognate protein (Hsc70) and alpha-actinin-1 as novel phosphotyrosine-containing proteins in T lymphocytes." Egerton M., Moritz R.L., Druker B., Kelso A., Simpson R.J. Biochem. Biophys. Res. Commun. 224:666-674(1996) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 97-108; 193-201 AND 240-248.
[9]	"SH2 domains mediate the sequential phosphorylation of HS1 protein by p72syk and Src-related protein tyrosine kinases." Ruzzene M., Brunati A.M., Marin O., Donella-Deana A., Pinna L.A. Biochemistry 35:5327-5332(1996) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION AT TYR-222 AND TYR-397, PHOSPHORYLATION BY SYK; LYN; FYN AND FGR.
[10]	"HAX-1, a novel intracellular protein, localized on mitochondria, directly associates with HS1, a substrate of Src family tyrosine kinases." Suzuki Y., Demoliere C., Kitamura D., Takeshita H., Deuschle U., Watanabe T. J. Immunol. 158:2736-2744(1997) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH HAX1.
[11]	"Molecular features underlying the sequential phosphorylation of HS1 protein and its association with c-Fgr protein-tyrosine kinase." Brunati A.M., Donella-Deana A., James P., Quadroni M., Contri A., Marin O., Pinna L.A. J. Biol. Chem. 274:7557-7564(1999) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION AT TYR-222 AND TYR-397, MASS SPECTROMETRY, INTERACTION WITH FGR.
[12]	"Profiling of tyrosine phosphorylation pathways in human cells using mass spectrometry." Salomon A.R., Ficarro S.B., Brill L.M., Brinker A., Phung Q.T., Ericson C., Sauer K., Brock A., Horn D.M., Schultz P.G., Peters E.C. Proc. Natl. Acad. Sci. U.S.A. 100:443-448(2003) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-198, MASS SPECTROMETRY.
[13]	"Robust phosphoproteomic profiling of tyrosine phosphorylation sites from human T cells using immobilized metal affinity chromatography and tandem mass spectrometry." Brill L.M., Salomon A.R., Ficarro S.B., Mukherji M., Stettler-Gill M., Peters E.C. Anal. Chem. 76:2763-2772(2004) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-198, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[14]	"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions." Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K. Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-275 AND THR-308, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[15]	"Lysine acetylation targets protein complexes and co-regulates major cellular functions." Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., Olsen J.V., Mann M. Science 325:834-840(2009) [PubMed] [Europe PMC] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-41; LYS-123; LYS-192 AND LYS-241, MASS SPECTROMETRY.
[16]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	X16663 mRNA. Translation: CAA34651.1. BT006824 mRNA. Translation: AAP35470.1. AK312750 mRNA. Translation: BAG35617.1. CR456794 mRNA. Translation: CAG33075.1. AC133750 Genomic DNA. No translation available. BC016758 mRNA. Translation: AAH16758.1.
IPI	IPI00026156.
PIR	S07633.
RefSeq	NP_005326.2. NM_005335.4.
UniGene	Hs.14601.
3D structure databases
ProteinModelPortal	P14317.
SMR	P14317. Positions 429-484.
ModBase	Search...
Protein-protein interaction databases
IntAct	P14317. 9 interactions.
MINT	MINT-1343660.
STRING	9606.ENSP00000320176.
PTM databases
PhosphoSite	P14317.
Polymorphism databases
DMDM	229462919.
Proteomic databases
PaxDb	P14317.
PRIDE	P14317.
Protocols and materials databases
DNASU	3059.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000314583; ENSP00000320176; ENSG00000180353.
GeneID	3059.
KEGG	hsa:3059.
UCSC	uc003eeh.4. human.
Organism-specific databases
CTD	3059.
GeneCards	GC03M121350.
HGNC	HGNC:4844. HCLS1.
HPA	HPA019143.
MIM	601306. gene.
neXtProt	NX_P14317.
PharmGKB	PA29220.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG123488.
HOGENOM	HOG000006523.
HOVERGEN	HBG005994.
InParanoid	P14317.
KO	K06106.
OMA	DRHEQED.
OrthoDB	EOG405S15.
PhylomeDB	P14317.
Enzyme and pathway databases
Pathway_Interaction_DB	fcer1pathway. Fc-epsilon receptor I signaling in mast cells.
Gene expression databases
ArrayExpress	P14317.
Bgee	P14317.
CleanEx	HS_HCLS1.
Genevestigator	P14317.
GermOnline	ENSG00000180353. Homo sapiens.
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
ChiTaRS	HCLS1. human.
GenomeRNAi	3059.
NextBio	12103.
PMAP-CutDB	P14317.
SOURCE	Search...

Entry information

Entry name

HCLS1_HUMAN

Accession

Primary (citable) accession number: P14317
Secondary accession number(s): Q53Y93, Q6IBK9, Q9UDK0

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 1, 1990
Last sequence update:	January 11, 2011
Last modified:	April 3, 2013
This is version 146 of the entry and version 3 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.