Full text data of HCLS1
HCLS1
(HS1)
[Confidence: low (only semi-automatic identification from reviews)]
Hematopoietic lineage cell-specific protein (Hematopoietic cell-specific LYN substrate 1; LckBP1; p75)
Hematopoietic lineage cell-specific protein (Hematopoietic cell-specific LYN substrate 1; LckBP1; p75)
UniProt
P14317
ID HCLS1_HUMAN Reviewed; 486 AA.
AC P14317; Q53Y93; Q6IBK9; Q9UDK0;
DT 01-JAN-1990, integrated into UniProtKB/Swiss-Prot.
read moreDT 11-JAN-2011, sequence version 3.
DT 22-JAN-2014, entry version 151.
DE RecName: Full=Hematopoietic lineage cell-specific protein;
DE AltName: Full=Hematopoietic cell-specific LYN substrate 1;
DE AltName: Full=LckBP1;
DE AltName: Full=p75;
GN Name=HCLS1; Synonyms=HS1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANTS ALA-235 AND LEU-436.
RX PubMed=2587259;
RA Kitamura D., Kaneko H., Miyagoe Y., Ariyasu T., Watanabe T.;
RT "Isolation and characterization of a novel human gene expressed
RT specifically in the cells of hematopoietic lineage.";
RL Nucleic Acids Res. 17:9367-9379(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANTS ALA-235 AND
RP LEU-436.
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor
RT vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANTS ALA-235 AND
RP LEU-436.
RC TISSUE=Spleen;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANTS ALA-235 AND
RP LEU-436.
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16641997; DOI=10.1038/nature04728;
RA Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R.,
RA Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R.,
RA Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V.,
RA Hume J., Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R.,
RA Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Morgan M.B.,
RA Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Wei S.,
RA Wheeler D.A., Wright M.W., Worley K.C., Yuan Y., Zhang Z., Adams C.Q.,
RA Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z.,
RA Clendenning J., Clerc-Blankenburg K.P., Chen R., Chen Z., Davis C.,
RA Delgado O., Dinh H.H., Dong W., Draper H., Ernst S., Fu G.,
RA Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J., Hao B.,
RA Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W., Jackson L.R.,
RA Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B., Liu J.,
RA Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Palmeiri A.,
RA Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B.,
RA Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H.,
RA Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J.,
RA Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J.,
RA Zhang X., Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H.,
RA Reinhardt R., Naylor S.L., Yang H., Olson M., Weinstock G.,
RA Gibbs R.A.;
RT "The DNA sequence, annotation and analysis of human chromosome 3.";
RL Nature 440:1194-1198(2006).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANTS ALA-235 AND
RP LEU-436.
RC TISSUE=Lymph;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP PROTEIN SEQUENCE OF 4-26; 79-95; 134-146; 208-223 AND 274-289,
RP INTERACTION WITH LYN, SUBCELLULAR LOCATION, AND PHOSPHORYLATION.
RC TISSUE=B-cell lymphoma;
RX PubMed=7682714; DOI=10.1073/pnas.90.8.3631;
RA Yamanashi Y., Okada M., Semba T., Yamori T., Umemori H., Tsunasawa S.,
RA Toyoshima K., Kitamura D., Watanabe T., Yamamoto T.;
RT "Identification of HS1 protein as a major substrate of protein-
RT tyrosine kinase(s) upon B-cell antigen receptor-mediated signaling.";
RL Proc. Natl. Acad. Sci. U.S.A. 90:3631-3635(1993).
RN [8]
RP PROTEIN SEQUENCE OF 97-108; 193-201 AND 240-248.
RX PubMed=8713105; DOI=10.1006/bbrc.1996.1082;
RA Egerton M., Moritz R.L., Druker B., Kelso A., Simpson R.J.;
RT "Identification of the 70kD heat shock cognate protein (Hsc70) and
RT alpha-actinin-1 as novel phosphotyrosine-containing proteins in T
RT lymphocytes.";
RL Biochem. Biophys. Res. Commun. 224:666-674(1996).
RN [9]
RP PHOSPHORYLATION AT TYR-222 AND TYR-397, AND PHOSPHORYLATION BY SYK;
RP LYN; FYN AND FGR.
RX PubMed=8611520; DOI=10.1021/bi9528614;
RA Ruzzene M., Brunati A.M., Marin O., Donella-Deana A., Pinna L.A.;
RT "SH2 domains mediate the sequential phosphorylation of HS1 protein by
RT p72syk and Src-related protein tyrosine kinases.";
RL Biochemistry 35:5327-5332(1996).
RN [10]
RP INTERACTION WITH HAX1.
RX PubMed=9058808;
RA Suzuki Y., Demoliere C., Kitamura D., Takeshita H., Deuschle U.,
RA Watanabe T.;
RT "HAX-1, a novel intracellular protein, localized on mitochondria,
RT directly associates with HS1, a substrate of Src family tyrosine
RT kinases.";
RL J. Immunol. 158:2736-2744(1997).
RN [11]
RP PHOSPHORYLATION AT TYR-222 AND TYR-397, MASS SPECTROMETRY, AND
RP INTERACTION WITH FGR.
RX PubMed=10066823; DOI=10.1074/jbc.274.11.7557;
RA Brunati A.M., Donella-Deana A., James P., Quadroni M., Contri A.,
RA Marin O., Pinna L.A.;
RT "Molecular features underlying the sequential phosphorylation of HS1
RT protein and its association with c-Fgr protein-tyrosine kinase.";
RL J. Biol. Chem. 274:7557-7564(1999).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-198, AND MASS
RP SPECTROMETRY.
RX PubMed=12522270; DOI=10.1073/pnas.2436191100;
RA Salomon A.R., Ficarro S.B., Brill L.M., Brinker A., Phung Q.T.,
RA Ericson C., Sauer K., Brock A., Horn D.M., Schultz P.G., Peters E.C.;
RT "Profiling of tyrosine phosphorylation pathways in human cells using
RT mass spectrometry.";
RL Proc. Natl. Acad. Sci. U.S.A. 100:443-448(2003).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-198, AND MASS
RP SPECTROMETRY.
RC TISSUE=Leukemic T-cell;
RX PubMed=15144186; DOI=10.1021/ac035352d;
RA Brill L.M., Salomon A.R., Ficarro S.B., Mukherji M., Stettler-Gill M.,
RA Peters E.C.;
RT "Robust phosphoproteomic profiling of tyrosine phosphorylation sites
RT from human T cells using immobilized metal affinity chromatography and
RT tandem mass spectrometry.";
RL Anal. Chem. 76:2763-2772(2004).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-275 AND THR-308, AND
RP MASS SPECTROMETRY.
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [15]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-41; LYS-123; LYS-192 AND
RP LYS-241, AND MASS SPECTROMETRY.
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M.,
RA Walther T.C., Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [16]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
CC -!- FUNCTION: Substrate of the antigen receptor-coupled tyrosine
CC kinase. Plays a role in antigen receptor signaling for both clonal
CC expansion and deletion in lymphoid cells. May also be involved in
CC the regulation of gene expression.
CC -!- SUBUNIT: Associates with the SH2 and SH3 domains of LCK. Binding
CC to he LCK SH3 domain occurs constitutively, while binding to the
CC LCK SH2 domain occurs only upon TCR stimulation. A similar binding
CC pattern was observed with LYN, but not with FYN in which the FYN
CC SH2 region associates upon TCR stimulation but the FYN SH3 region
CC does not associate regardless of TCR stimulation. Directly
CC associates with HAX1, through binding to its C-terminal region.
CC Interacts with HS1BP3. Interacts with FES/FPS (By similarity).
CC Interacts (via SH2 domain) with FGR. Forms a multiprotein complex
CC with LYN and ANKRD54 (By similarity).
CC -!- INTERACTION:
CC O43516:WIPF1; NbExp=2; IntAct=EBI-750369, EBI-346356;
CC -!- SUBCELLULAR LOCATION: Membrane; Peripheral membrane protein.
CC Cytoplasm. Mitochondrion (Probable).
CC -!- TISSUE SPECIFICITY: Expressed only in tissues and cells of
CC hematopoietic origin.
CC -!- DEVELOPMENTAL STAGE: Expressed in early stage of myeloid and
CC erythroid differentiation.
CC -!- PTM: Phosphorylated by FES (By similarity). Phosphorylated by LYN,
CC FYN and FGR after cross-linking of surface IgM on B-cells.
CC Phosphorylation by LYN, FYN and FGR requires prior phosphorylation
CC by SYK or FES.
CC -!- SIMILARITY: Contains 4 cortactin repeats.
CC -!- SIMILARITY: Contains 1 SH3 domain.
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DR EMBL; X16663; CAA34651.1; -; mRNA.
DR EMBL; BT006824; AAP35470.1; -; mRNA.
DR EMBL; AK312750; BAG35617.1; -; mRNA.
DR EMBL; CR456794; CAG33075.1; -; mRNA.
DR EMBL; AC133750; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC016758; AAH16758.1; -; mRNA.
DR PIR; S07633; S07633.
DR RefSeq; NP_005326.2; NM_005335.4.
DR UniGene; Hs.14601; -.
DR ProteinModelPortal; P14317; -.
DR SMR; P14317; 429-484.
DR IntAct; P14317; 12.
DR MINT; MINT-1343660; -.
DR STRING; 9606.ENSP00000320176; -.
DR PhosphoSite; P14317; -.
DR DMDM; 229462919; -.
DR PaxDb; P14317; -.
DR PRIDE; P14317; -.
DR DNASU; 3059; -.
DR Ensembl; ENST00000314583; ENSP00000320176; ENSG00000180353.
DR GeneID; 3059; -.
DR KEGG; hsa:3059; -.
DR UCSC; uc003eeh.4; human.
DR CTD; 3059; -.
DR GeneCards; GC03M121350; -.
DR HGNC; HGNC:4844; HCLS1.
DR HPA; HPA019143; -.
DR MIM; 601306; gene.
DR neXtProt; NX_P14317; -.
DR PharmGKB; PA29220; -.
DR eggNOG; NOG123488; -.
DR HOGENOM; HOG000006523; -.
DR HOVERGEN; HBG005994; -.
DR InParanoid; P14317; -.
DR KO; K06106; -.
DR OMA; EMDRHEQ; -.
DR OrthoDB; EOG7V49ZC; -.
DR PhylomeDB; P14317; -.
DR ChiTaRS; HCLS1; human.
DR GeneWiki; HCLS1; -.
DR GenomeRNAi; 3059; -.
DR NextBio; 12103; -.
DR PMAP-CutDB; P14317; -.
DR PRO; PR:P14317; -.
DR ArrayExpress; P14317; -.
DR Bgee; P14317; -.
DR CleanEx; HS_HCLS1; -.
DR Genevestigator; P14317; -.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:HPA.
DR GO; GO:0005667; C:transcription factor complex; IDA:BHF-UCL.
DR GO; GO:0071345; P:cellular response to cytokine stimulus; IMP:BHF-UCL.
DR GO; GO:0030218; P:erythrocyte differentiation; ISS:UniProtKB.
DR GO; GO:0035556; P:intracellular signal transduction; TAS:ProtInc.
DR GO; GO:2000107; P:negative regulation of leukocyte apoptotic process; IMP:BHF-UCL.
DR GO; GO:0000122; P:negative regulation of transcription from RNA polymerase II promoter; IEA:Ensembl.
DR GO; GO:2000251; P:positive regulation of actin cytoskeleton reorganization; IC:BHF-UCL.
DR GO; GO:0008284; P:positive regulation of cell proliferation; ISS:UniProtKB.
DR GO; GO:0030854; P:positive regulation of granulocyte differentiation; IMP:BHF-UCL.
DR GO; GO:0045651; P:positive regulation of macrophage differentiation; IEA:Ensembl.
DR GO; GO:0033138; P:positive regulation of peptidyl-serine phosphorylation; IMP:BHF-UCL.
DR GO; GO:0014068; P:positive regulation of phosphatidylinositol 3-kinase cascade; IMP:BHF-UCL.
DR GO; GO:0051897; P:positive regulation of protein kinase B signaling cascade; IMP:BHF-UCL.
DR GO; GO:0042993; P:positive regulation of transcription factor import into nucleus; IMP:BHF-UCL.
DR GO; GO:0045944; P:positive regulation of transcription from RNA polymerase II promoter; IMP:BHF-UCL.
DR GO; GO:0042531; P:positive regulation of tyrosine phosphorylation of STAT protein; ISS:UniProtKB.
DR GO; GO:0030833; P:regulation of actin filament polymerization; IMP:BHF-UCL.
DR GO; GO:0009725; P:response to hormone stimulus; ISS:UniProtKB.
DR InterPro; IPR028534; HS1.
DR InterPro; IPR003134; Hs1_Cortactin.
DR InterPro; IPR001452; SH3_domain.
DR PANTHER; PTHR10829:SF5; PTHR10829:SF5; 1.
DR Pfam; PF02218; HS1_rep; 4.
DR Pfam; PF00018; SH3_1; 1.
DR PRINTS; PR00452; SH3DOMAIN.
DR SMART; SM00326; SH3; 1.
DR SUPFAM; SSF50044; SSF50044; 1.
DR PROSITE; PS51090; CORTACTIN; 4.
DR PROSITE; PS50002; SH3; 1.
PE 1: Evidence at protein level;
KW Acetylation; Complete proteome; Cytoplasm; Direct protein sequencing;
KW Membrane; Mitochondrion; Phosphoprotein; Polymorphism;
KW Reference proteome; Repeat; SH3 domain.
FT CHAIN 1 486 Hematopoietic lineage cell-specific
FT protein.
FT /FTId=PRO_0000083921.
FT REPEAT 79 115 Cortactin 1.
FT REPEAT 116 152 Cortactin 2.
FT REPEAT 153 189 Cortactin 3.
FT REPEAT 190 212 Cortactin 4; truncated.
FT DOMAIN 428 486 SH3.
FT REGION 27 66 Involved in HAX-1 binding.
FT MOD_RES 41 41 N6-acetyllysine.
FT MOD_RES 103 103 Phosphotyrosine.
FT MOD_RES 123 123 N6-acetyllysine.
FT MOD_RES 140 140 Phosphotyrosine (By similarity).
FT MOD_RES 192 192 N6-acetyllysine.
FT MOD_RES 198 198 Phosphotyrosine.
FT MOD_RES 222 222 Phosphotyrosine; by FGR.
FT MOD_RES 241 241 N6-acetyllysine.
FT MOD_RES 275 275 Phosphoserine.
FT MOD_RES 308 308 Phosphothreonine.
FT MOD_RES 378 378 Phosphotyrosine; by SYK and FES (By
FT similarity).
FT MOD_RES 397 397 Phosphotyrosine; by SYK and FES (By
FT similarity).
FT VARIANT 235 235 T -> A (in dbSNP:rs2070179).
FT /FTId=VAR_055006.
FT VARIANT 361 361 E -> K (in dbSNP:rs2070180).
FT /FTId=VAR_055007.
FT VARIANT 436 436 V -> L (in dbSNP:rs9869984).
FT /FTId=VAR_056910.
FT CONFLICT 241 242 KF -> FK (in Ref. 8; AA sequence).
FT CONFLICT 486 486 E -> D (in Ref. 4; CAG33075).
SQ SEQUENCE 486 AA; 54014 MW; 20AE72A28DA33DFB CRC64;
MWKSVVGHDV SVSVETQGDD WDTDPDFVND ISEKEQRWGA KTIEGSGRTE HINIHQLRNK
VSEEHDVLRK KEMESGPKAS HGYGGRFGVE RDRMDKSAVG HEYVAEVEKH SSQTDAAKGF
GGKYGVERDR ADKSAVGFDY KGEVEKHTSQ KDYSRGFGGR YGVEKDKWDK AALGYDYKGE
TEKHESQRDY AKGFGGQYGI QKDRVDKSAV GFNEMEAPTT AYKKTTPIEA ASSGTRGLKA
KFESMAEEKR KREEEEKAQQ VARRQQERKA VTKRSPEAPQ PVIAMEEPAV PAPLPKKISS
EAWPPVGTPP SSESEPVRTS REHPVPLLPI RQTLPEDNEE PPALPPRTLE GLQVEEEPVY
EAEPEPEPEP EPEPENDYED VEEMDRHEQE DEPEGDYEEV LEPEDSSFSS ALAGSSGCPA
GAGAGAVALG ISAVAVYDYQ GEGSDELSFD PDDVITDIEM VDEGWWRGRC HGHFGLFPAN
YVKLLE
//
ID HCLS1_HUMAN Reviewed; 486 AA.
AC P14317; Q53Y93; Q6IBK9; Q9UDK0;
DT 01-JAN-1990, integrated into UniProtKB/Swiss-Prot.
read moreDT 11-JAN-2011, sequence version 3.
DT 22-JAN-2014, entry version 151.
DE RecName: Full=Hematopoietic lineage cell-specific protein;
DE AltName: Full=Hematopoietic cell-specific LYN substrate 1;
DE AltName: Full=LckBP1;
DE AltName: Full=p75;
GN Name=HCLS1; Synonyms=HS1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANTS ALA-235 AND LEU-436.
RX PubMed=2587259;
RA Kitamura D., Kaneko H., Miyagoe Y., Ariyasu T., Watanabe T.;
RT "Isolation and characterization of a novel human gene expressed
RT specifically in the cells of hematopoietic lineage.";
RL Nucleic Acids Res. 17:9367-9379(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANTS ALA-235 AND
RP LEU-436.
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor
RT vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANTS ALA-235 AND
RP LEU-436.
RC TISSUE=Spleen;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANTS ALA-235 AND
RP LEU-436.
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16641997; DOI=10.1038/nature04728;
RA Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R.,
RA Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R.,
RA Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V.,
RA Hume J., Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R.,
RA Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Morgan M.B.,
RA Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Wei S.,
RA Wheeler D.A., Wright M.W., Worley K.C., Yuan Y., Zhang Z., Adams C.Q.,
RA Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z.,
RA Clendenning J., Clerc-Blankenburg K.P., Chen R., Chen Z., Davis C.,
RA Delgado O., Dinh H.H., Dong W., Draper H., Ernst S., Fu G.,
RA Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J., Hao B.,
RA Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W., Jackson L.R.,
RA Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B., Liu J.,
RA Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Palmeiri A.,
RA Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B.,
RA Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H.,
RA Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J.,
RA Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J.,
RA Zhang X., Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H.,
RA Reinhardt R., Naylor S.L., Yang H., Olson M., Weinstock G.,
RA Gibbs R.A.;
RT "The DNA sequence, annotation and analysis of human chromosome 3.";
RL Nature 440:1194-1198(2006).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANTS ALA-235 AND
RP LEU-436.
RC TISSUE=Lymph;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP PROTEIN SEQUENCE OF 4-26; 79-95; 134-146; 208-223 AND 274-289,
RP INTERACTION WITH LYN, SUBCELLULAR LOCATION, AND PHOSPHORYLATION.
RC TISSUE=B-cell lymphoma;
RX PubMed=7682714; DOI=10.1073/pnas.90.8.3631;
RA Yamanashi Y., Okada M., Semba T., Yamori T., Umemori H., Tsunasawa S.,
RA Toyoshima K., Kitamura D., Watanabe T., Yamamoto T.;
RT "Identification of HS1 protein as a major substrate of protein-
RT tyrosine kinase(s) upon B-cell antigen receptor-mediated signaling.";
RL Proc. Natl. Acad. Sci. U.S.A. 90:3631-3635(1993).
RN [8]
RP PROTEIN SEQUENCE OF 97-108; 193-201 AND 240-248.
RX PubMed=8713105; DOI=10.1006/bbrc.1996.1082;
RA Egerton M., Moritz R.L., Druker B., Kelso A., Simpson R.J.;
RT "Identification of the 70kD heat shock cognate protein (Hsc70) and
RT alpha-actinin-1 as novel phosphotyrosine-containing proteins in T
RT lymphocytes.";
RL Biochem. Biophys. Res. Commun. 224:666-674(1996).
RN [9]
RP PHOSPHORYLATION AT TYR-222 AND TYR-397, AND PHOSPHORYLATION BY SYK;
RP LYN; FYN AND FGR.
RX PubMed=8611520; DOI=10.1021/bi9528614;
RA Ruzzene M., Brunati A.M., Marin O., Donella-Deana A., Pinna L.A.;
RT "SH2 domains mediate the sequential phosphorylation of HS1 protein by
RT p72syk and Src-related protein tyrosine kinases.";
RL Biochemistry 35:5327-5332(1996).
RN [10]
RP INTERACTION WITH HAX1.
RX PubMed=9058808;
RA Suzuki Y., Demoliere C., Kitamura D., Takeshita H., Deuschle U.,
RA Watanabe T.;
RT "HAX-1, a novel intracellular protein, localized on mitochondria,
RT directly associates with HS1, a substrate of Src family tyrosine
RT kinases.";
RL J. Immunol. 158:2736-2744(1997).
RN [11]
RP PHOSPHORYLATION AT TYR-222 AND TYR-397, MASS SPECTROMETRY, AND
RP INTERACTION WITH FGR.
RX PubMed=10066823; DOI=10.1074/jbc.274.11.7557;
RA Brunati A.M., Donella-Deana A., James P., Quadroni M., Contri A.,
RA Marin O., Pinna L.A.;
RT "Molecular features underlying the sequential phosphorylation of HS1
RT protein and its association with c-Fgr protein-tyrosine kinase.";
RL J. Biol. Chem. 274:7557-7564(1999).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-198, AND MASS
RP SPECTROMETRY.
RX PubMed=12522270; DOI=10.1073/pnas.2436191100;
RA Salomon A.R., Ficarro S.B., Brill L.M., Brinker A., Phung Q.T.,
RA Ericson C., Sauer K., Brock A., Horn D.M., Schultz P.G., Peters E.C.;
RT "Profiling of tyrosine phosphorylation pathways in human cells using
RT mass spectrometry.";
RL Proc. Natl. Acad. Sci. U.S.A. 100:443-448(2003).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-198, AND MASS
RP SPECTROMETRY.
RC TISSUE=Leukemic T-cell;
RX PubMed=15144186; DOI=10.1021/ac035352d;
RA Brill L.M., Salomon A.R., Ficarro S.B., Mukherji M., Stettler-Gill M.,
RA Peters E.C.;
RT "Robust phosphoproteomic profiling of tyrosine phosphorylation sites
RT from human T cells using immobilized metal affinity chromatography and
RT tandem mass spectrometry.";
RL Anal. Chem. 76:2763-2772(2004).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-275 AND THR-308, AND
RP MASS SPECTROMETRY.
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [15]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-41; LYS-123; LYS-192 AND
RP LYS-241, AND MASS SPECTROMETRY.
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M.,
RA Walther T.C., Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [16]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
CC -!- FUNCTION: Substrate of the antigen receptor-coupled tyrosine
CC kinase. Plays a role in antigen receptor signaling for both clonal
CC expansion and deletion in lymphoid cells. May also be involved in
CC the regulation of gene expression.
CC -!- SUBUNIT: Associates with the SH2 and SH3 domains of LCK. Binding
CC to he LCK SH3 domain occurs constitutively, while binding to the
CC LCK SH2 domain occurs only upon TCR stimulation. A similar binding
CC pattern was observed with LYN, but not with FYN in which the FYN
CC SH2 region associates upon TCR stimulation but the FYN SH3 region
CC does not associate regardless of TCR stimulation. Directly
CC associates with HAX1, through binding to its C-terminal region.
CC Interacts with HS1BP3. Interacts with FES/FPS (By similarity).
CC Interacts (via SH2 domain) with FGR. Forms a multiprotein complex
CC with LYN and ANKRD54 (By similarity).
CC -!- INTERACTION:
CC O43516:WIPF1; NbExp=2; IntAct=EBI-750369, EBI-346356;
CC -!- SUBCELLULAR LOCATION: Membrane; Peripheral membrane protein.
CC Cytoplasm. Mitochondrion (Probable).
CC -!- TISSUE SPECIFICITY: Expressed only in tissues and cells of
CC hematopoietic origin.
CC -!- DEVELOPMENTAL STAGE: Expressed in early stage of myeloid and
CC erythroid differentiation.
CC -!- PTM: Phosphorylated by FES (By similarity). Phosphorylated by LYN,
CC FYN and FGR after cross-linking of surface IgM on B-cells.
CC Phosphorylation by LYN, FYN and FGR requires prior phosphorylation
CC by SYK or FES.
CC -!- SIMILARITY: Contains 4 cortactin repeats.
CC -!- SIMILARITY: Contains 1 SH3 domain.
CC -----------------------------------------------------------------------
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DR EMBL; X16663; CAA34651.1; -; mRNA.
DR EMBL; BT006824; AAP35470.1; -; mRNA.
DR EMBL; AK312750; BAG35617.1; -; mRNA.
DR EMBL; CR456794; CAG33075.1; -; mRNA.
DR EMBL; AC133750; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC016758; AAH16758.1; -; mRNA.
DR PIR; S07633; S07633.
DR RefSeq; NP_005326.2; NM_005335.4.
DR UniGene; Hs.14601; -.
DR ProteinModelPortal; P14317; -.
DR SMR; P14317; 429-484.
DR IntAct; P14317; 12.
DR MINT; MINT-1343660; -.
DR STRING; 9606.ENSP00000320176; -.
DR PhosphoSite; P14317; -.
DR DMDM; 229462919; -.
DR PaxDb; P14317; -.
DR PRIDE; P14317; -.
DR DNASU; 3059; -.
DR Ensembl; ENST00000314583; ENSP00000320176; ENSG00000180353.
DR GeneID; 3059; -.
DR KEGG; hsa:3059; -.
DR UCSC; uc003eeh.4; human.
DR CTD; 3059; -.
DR GeneCards; GC03M121350; -.
DR HGNC; HGNC:4844; HCLS1.
DR HPA; HPA019143; -.
DR MIM; 601306; gene.
DR neXtProt; NX_P14317; -.
DR PharmGKB; PA29220; -.
DR eggNOG; NOG123488; -.
DR HOGENOM; HOG000006523; -.
DR HOVERGEN; HBG005994; -.
DR InParanoid; P14317; -.
DR KO; K06106; -.
DR OMA; EMDRHEQ; -.
DR OrthoDB; EOG7V49ZC; -.
DR PhylomeDB; P14317; -.
DR ChiTaRS; HCLS1; human.
DR GeneWiki; HCLS1; -.
DR GenomeRNAi; 3059; -.
DR NextBio; 12103; -.
DR PMAP-CutDB; P14317; -.
DR PRO; PR:P14317; -.
DR ArrayExpress; P14317; -.
DR Bgee; P14317; -.
DR CleanEx; HS_HCLS1; -.
DR Genevestigator; P14317; -.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005739; C:mitochondrion; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IDA:HPA.
DR GO; GO:0005667; C:transcription factor complex; IDA:BHF-UCL.
DR GO; GO:0071345; P:cellular response to cytokine stimulus; IMP:BHF-UCL.
DR GO; GO:0030218; P:erythrocyte differentiation; ISS:UniProtKB.
DR GO; GO:0035556; P:intracellular signal transduction; TAS:ProtInc.
DR GO; GO:2000107; P:negative regulation of leukocyte apoptotic process; IMP:BHF-UCL.
DR GO; GO:0000122; P:negative regulation of transcription from RNA polymerase II promoter; IEA:Ensembl.
DR GO; GO:2000251; P:positive regulation of actin cytoskeleton reorganization; IC:BHF-UCL.
DR GO; GO:0008284; P:positive regulation of cell proliferation; ISS:UniProtKB.
DR GO; GO:0030854; P:positive regulation of granulocyte differentiation; IMP:BHF-UCL.
DR GO; GO:0045651; P:positive regulation of macrophage differentiation; IEA:Ensembl.
DR GO; GO:0033138; P:positive regulation of peptidyl-serine phosphorylation; IMP:BHF-UCL.
DR GO; GO:0014068; P:positive regulation of phosphatidylinositol 3-kinase cascade; IMP:BHF-UCL.
DR GO; GO:0051897; P:positive regulation of protein kinase B signaling cascade; IMP:BHF-UCL.
DR GO; GO:0042993; P:positive regulation of transcription factor import into nucleus; IMP:BHF-UCL.
DR GO; GO:0045944; P:positive regulation of transcription from RNA polymerase II promoter; IMP:BHF-UCL.
DR GO; GO:0042531; P:positive regulation of tyrosine phosphorylation of STAT protein; ISS:UniProtKB.
DR GO; GO:0030833; P:regulation of actin filament polymerization; IMP:BHF-UCL.
DR GO; GO:0009725; P:response to hormone stimulus; ISS:UniProtKB.
DR InterPro; IPR028534; HS1.
DR InterPro; IPR003134; Hs1_Cortactin.
DR InterPro; IPR001452; SH3_domain.
DR PANTHER; PTHR10829:SF5; PTHR10829:SF5; 1.
DR Pfam; PF02218; HS1_rep; 4.
DR Pfam; PF00018; SH3_1; 1.
DR PRINTS; PR00452; SH3DOMAIN.
DR SMART; SM00326; SH3; 1.
DR SUPFAM; SSF50044; SSF50044; 1.
DR PROSITE; PS51090; CORTACTIN; 4.
DR PROSITE; PS50002; SH3; 1.
PE 1: Evidence at protein level;
KW Acetylation; Complete proteome; Cytoplasm; Direct protein sequencing;
KW Membrane; Mitochondrion; Phosphoprotein; Polymorphism;
KW Reference proteome; Repeat; SH3 domain.
FT CHAIN 1 486 Hematopoietic lineage cell-specific
FT protein.
FT /FTId=PRO_0000083921.
FT REPEAT 79 115 Cortactin 1.
FT REPEAT 116 152 Cortactin 2.
FT REPEAT 153 189 Cortactin 3.
FT REPEAT 190 212 Cortactin 4; truncated.
FT DOMAIN 428 486 SH3.
FT REGION 27 66 Involved in HAX-1 binding.
FT MOD_RES 41 41 N6-acetyllysine.
FT MOD_RES 103 103 Phosphotyrosine.
FT MOD_RES 123 123 N6-acetyllysine.
FT MOD_RES 140 140 Phosphotyrosine (By similarity).
FT MOD_RES 192 192 N6-acetyllysine.
FT MOD_RES 198 198 Phosphotyrosine.
FT MOD_RES 222 222 Phosphotyrosine; by FGR.
FT MOD_RES 241 241 N6-acetyllysine.
FT MOD_RES 275 275 Phosphoserine.
FT MOD_RES 308 308 Phosphothreonine.
FT MOD_RES 378 378 Phosphotyrosine; by SYK and FES (By
FT similarity).
FT MOD_RES 397 397 Phosphotyrosine; by SYK and FES (By
FT similarity).
FT VARIANT 235 235 T -> A (in dbSNP:rs2070179).
FT /FTId=VAR_055006.
FT VARIANT 361 361 E -> K (in dbSNP:rs2070180).
FT /FTId=VAR_055007.
FT VARIANT 436 436 V -> L (in dbSNP:rs9869984).
FT /FTId=VAR_056910.
FT CONFLICT 241 242 KF -> FK (in Ref. 8; AA sequence).
FT CONFLICT 486 486 E -> D (in Ref. 4; CAG33075).
SQ SEQUENCE 486 AA; 54014 MW; 20AE72A28DA33DFB CRC64;
MWKSVVGHDV SVSVETQGDD WDTDPDFVND ISEKEQRWGA KTIEGSGRTE HINIHQLRNK
VSEEHDVLRK KEMESGPKAS HGYGGRFGVE RDRMDKSAVG HEYVAEVEKH SSQTDAAKGF
GGKYGVERDR ADKSAVGFDY KGEVEKHTSQ KDYSRGFGGR YGVEKDKWDK AALGYDYKGE
TEKHESQRDY AKGFGGQYGI QKDRVDKSAV GFNEMEAPTT AYKKTTPIEA ASSGTRGLKA
KFESMAEEKR KREEEEKAQQ VARRQQERKA VTKRSPEAPQ PVIAMEEPAV PAPLPKKISS
EAWPPVGTPP SSESEPVRTS REHPVPLLPI RQTLPEDNEE PPALPPRTLE GLQVEEEPVY
EAEPEPEPEP EPEPENDYED VEEMDRHEQE DEPEGDYEEV LEPEDSSFSS ALAGSSGCPA
GAGAGAVALG ISAVAVYDYQ GEGSDELSFD PDDVITDIEM VDEGWWRGRC HGHFGLFPAN
YVKLLE
//
MIM
601306
*RECORD*
*FIELD* NO
601306
*FIELD* TI
*601306 HEMATOPOIETIC CELL-SPECIFIC LYN SUBSTRATE 1; HCLS1
;;HS1
*FIELD* TX
CLONING
read more
By screening a hybridoma cDNA library with a probe to the
transactivating region of adenovirus-2 E1A, Kitamura et al. (1989)
obtained a cDNA encoding HCLS1, which they called HS1. Sequence analysis
predicted that the 486-amino acid hydrophilic protein lacks a signal
peptide, N-glycosylation sites, and a transmembrane region, but contains
several potential phosphorylation sites. HCLS1 has an N-terminal series
of at least three 37-amino acid repeats, each of which includes 2 alpha
helices, that are called HS1 repeats and are also found in contactin
(CNTN1; 600016). In addition, HCLS1 has a central region homologous to
the adenovirus E1A probe and a C-terminal SH3 domain. Northern blot
analysis revealed expression of a 2.0-kb HCLS1 transcript restricted to
hemopoietic tissues and cell lines. Western blot analysis showed
expression of a 75-kD protein, considerably larger than the predicted 54
kD. Kitamura et al. (1989) concluded that HCLS1 should be a good marker
for cells of hematopoietic origin.
GENE FUNCTION
The human HCLS1 gene encodes a 75-kD intracellular protein whose
expression is limited to hematopoietic cell lineages. Egashira et al.
(1996) noted that the protein is a major substrate of protein-tyrosine
kinases. It is an intracellular protein involved in the signal
transduction pathways that initiate at the antigen receptors of both B
and T lymphocytes. The protein is associated with LYN kinase (165120),
and is rapidly tyrosine-phosphorylated after crosslinking of surface IgM
on B cells.
Scielzo et al. (2005) analyzed 40 patients with chronic lymphocytic
leukemia (CLL; 151400) and found that those with predominantly
phosphorylated HS1 had a significantly shorter median survival time.
Scielzo et al. (2005) studied the expression pattern of HS1 after B-cell
receptor engagement and found that normal mature B cells stimulated by
anti-IgM shifted the non- or less-phosphorylated form of HS1 toward the
more-phosphorylated form, naive B cells showed both HS1 forms, and
memory B cells expressed mainly the phosphorylated fraction. Scielzo et
al. (2005) concluded that antigen stimulation plays a central role in
CLL.
MAPPING
Using fluorescence in situ hybridization, Egashira et al. (1996) mapped
HCLS1 to chromosome 3q13.
*FIELD* RF
1. Egashira, M.; Kitamura, D.; Watanabe, T.; Niikawa, N.: The human
HCLS1 gene maps to chromosome 3q13 by fluorescence in situ hybridization. Cytogenet.
Cell Genet. 72: 175-176, 1996.
2. Kitamura, D.; Kaneko, H.; Miyagoe, Y.; Ariyasu, T.; Watanabe, T.
: Isolation and characterization of a novel human gene expressed specifically
in the cells of hematopoietic lineage. Nucleic Acids Res. 17: 9367-9379,
1989.
3. Scielzo, C.; Ghia, P.; Conti, A.; Bachi, A.; Guida, G.; Geuna,
M.; Alessio, M.; Caligaris-Cappio, F.: HS1 protein is differentially
expressed in chronic lymphocytic leukemia patient subsets with good
or poor prognoses. J. Clin. Invest. 115: 1644-1650, 2005.
*FIELD* CN
Marla J. F. O'Neill - updated: 7/8/2005
Paul J. Converse - updated: 11/19/2001
*FIELD* CD
Victor A. McKusick: 6/11/1996
*FIELD* ED
wwang: 07/19/2005
wwang: 7/14/2005
terry: 7/8/2005
mgross: 12/5/2001
terry: 11/19/2001
mgross: 6/11/2001
mark: 6/11/1996
*RECORD*
*FIELD* NO
601306
*FIELD* TI
*601306 HEMATOPOIETIC CELL-SPECIFIC LYN SUBSTRATE 1; HCLS1
;;HS1
*FIELD* TX
CLONING
read more
By screening a hybridoma cDNA library with a probe to the
transactivating region of adenovirus-2 E1A, Kitamura et al. (1989)
obtained a cDNA encoding HCLS1, which they called HS1. Sequence analysis
predicted that the 486-amino acid hydrophilic protein lacks a signal
peptide, N-glycosylation sites, and a transmembrane region, but contains
several potential phosphorylation sites. HCLS1 has an N-terminal series
of at least three 37-amino acid repeats, each of which includes 2 alpha
helices, that are called HS1 repeats and are also found in contactin
(CNTN1; 600016). In addition, HCLS1 has a central region homologous to
the adenovirus E1A probe and a C-terminal SH3 domain. Northern blot
analysis revealed expression of a 2.0-kb HCLS1 transcript restricted to
hemopoietic tissues and cell lines. Western blot analysis showed
expression of a 75-kD protein, considerably larger than the predicted 54
kD. Kitamura et al. (1989) concluded that HCLS1 should be a good marker
for cells of hematopoietic origin.
GENE FUNCTION
The human HCLS1 gene encodes a 75-kD intracellular protein whose
expression is limited to hematopoietic cell lineages. Egashira et al.
(1996) noted that the protein is a major substrate of protein-tyrosine
kinases. It is an intracellular protein involved in the signal
transduction pathways that initiate at the antigen receptors of both B
and T lymphocytes. The protein is associated with LYN kinase (165120),
and is rapidly tyrosine-phosphorylated after crosslinking of surface IgM
on B cells.
Scielzo et al. (2005) analyzed 40 patients with chronic lymphocytic
leukemia (CLL; 151400) and found that those with predominantly
phosphorylated HS1 had a significantly shorter median survival time.
Scielzo et al. (2005) studied the expression pattern of HS1 after B-cell
receptor engagement and found that normal mature B cells stimulated by
anti-IgM shifted the non- or less-phosphorylated form of HS1 toward the
more-phosphorylated form, naive B cells showed both HS1 forms, and
memory B cells expressed mainly the phosphorylated fraction. Scielzo et
al. (2005) concluded that antigen stimulation plays a central role in
CLL.
MAPPING
Using fluorescence in situ hybridization, Egashira et al. (1996) mapped
HCLS1 to chromosome 3q13.
*FIELD* RF
1. Egashira, M.; Kitamura, D.; Watanabe, T.; Niikawa, N.: The human
HCLS1 gene maps to chromosome 3q13 by fluorescence in situ hybridization. Cytogenet.
Cell Genet. 72: 175-176, 1996.
2. Kitamura, D.; Kaneko, H.; Miyagoe, Y.; Ariyasu, T.; Watanabe, T.
: Isolation and characterization of a novel human gene expressed specifically
in the cells of hematopoietic lineage. Nucleic Acids Res. 17: 9367-9379,
1989.
3. Scielzo, C.; Ghia, P.; Conti, A.; Bachi, A.; Guida, G.; Geuna,
M.; Alessio, M.; Caligaris-Cappio, F.: HS1 protein is differentially
expressed in chronic lymphocytic leukemia patient subsets with good
or poor prognoses. J. Clin. Invest. 115: 1644-1650, 2005.
*FIELD* CN
Marla J. F. O'Neill - updated: 7/8/2005
Paul J. Converse - updated: 11/19/2001
*FIELD* CD
Victor A. McKusick: 6/11/1996
*FIELD* ED
wwang: 07/19/2005
wwang: 7/14/2005
terry: 7/8/2005
mgross: 12/5/2001
terry: 11/19/2001
mgross: 6/11/2001
mark: 6/11/1996