ID HCLS1_HUMAN Reviewed; 486 AA. AC P14317; Q53Y93; Q6IBK9; Q9UDK0; DT 01-JAN-1990, integrated into UniProtKB/Swiss-Prot. DT 05-MAY-2009, sequence version 2. DT 05-OCT-2010, entry version 121. 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 VARIANT LEU-436. RX MEDLINE=90067934; 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 VARIANT 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 VARIANT 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 VARIANT 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], AND VARIANT THR-235. 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 VARIANT 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 MEDLINE=93234551; 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 MEDLINE=96311348; 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 INTERACTION WITH HAX1. RX MEDLINE=97211841; 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 [10] RP PHOSPHORYLATION AT TYR-222. RX MEDLINE=99167527; 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 [11] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-198, AND MASS RP SPECTROMETRY. RX MEDLINE=22426906; 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 [12] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-103 AND SER-275, AND RP MASS SPECTROMETRY. RC TISSUE=Leukemic T-cell; RX PubMed=16094384; DOI=10.1038/nmeth776; RA Tao W.A., Wollscheid B., O'Brien R., Eng J.K., Li X.-J., RA Bodenmiller B., Watts J.D., Hood L., Aebersold R.; RT "Quantitative phosphoproteome analysis using a dendrimer conjugation RT chemistry and tandem mass spectrometry."; RL Nat. Methods 2:591-598(2005). RN [13] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RA Colinge J., Superti-Furga G., Bennett K.L.; RL Submitted (OCT-2008) to UniProtKB. 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., Walther T., RA Olsen J.V., Mann M.; RT "Lysine acetylation targets protein complexes and co-regulates major RT cellular functions."; RL Science 325:834-840(2009). 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. 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 LYN; rapidly after cross-linking of surface CC IgM on B-cells. CC -!- SIMILARITY: Contains 4 cortactin repeats. CC -!- SIMILARITY: Contains 1 SH3 domain. CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution-NoDerivs License CC ----------------------------------------------------------------------- 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 IPI; IPI00026156; -. DR PIR; S07633; S07633. DR RefSeq; NP_005326.2; -. DR UniGene; Hs.14601; -. DR ProteinModelPortal; P14317; -. DR IntAct; P14317; 11. DR MINT; MINT-1343660; -. DR STRING; P14317; -. DR PhosphoSite; P14317; -. DR PRIDE; P14317; -. DR Ensembl; ENST00000314583; ENSP00000320176; ENSG00000180353. DR GeneID; 3059; -. DR KEGG; hsa:3059; -. DR CTD; 3059; -. DR GeneCards; GC03M121350; -. DR HGNC; HGNC:4844; HCLS1. DR HPA; HPA019143; -. DR MIM; 601306; gene. DR PharmGKB; PA29220; -. DR eggNOG; prNOG16686; -. DR HOGENOM; HBG446303; -. DR HOVERGEN; HBG005994; -. DR InParanoid; P14317; -. DR Pathway_Interaction_DB; fcer1pathway; Fc-epsilon receptor I signaling in mast cells. DR NextBio; 12103; -. DR PMAP-CutDB; P14317; -. DR ArrayExpress; P14317; -. DR Bgee; P14317; -. DR CleanEx; HS_HCLS1; -. DR Genevestigator; P14317; -. DR GermOnline; ENSG00000180353; Homo sapiens. DR GO; GO:0016020; C:membrane; IEA:UniProtKB-SubCell. DR GO; GO:0005739; C:mitochondrion; IEA:UniProtKB-SubCell. DR GO; GO:0005634; C:nucleus; ISS:UniProtKB. DR GO; GO:0003700; F:transcription factor activity; TAS:ProtInc. DR GO; GO:0030218; P:erythrocyte differentiation; ISS:UniProtKB. DR GO; GO:0023034; P:intracellular signaling pathway; TAS:ProtInc. DR GO; GO:0008284; P:positive regulation of cell proliferation; ISS:UniProtKB. DR GO; GO:0042531; P:positive regulation of tyrosine phosphoryla...; ISS:UniProtKB. DR GO; GO:0006355; P:regulation of transcription, DNA-dependent; TAS:ProtInc. DR GO; GO:0009725; P:response to hormone stimulus; ISS:UniProtKB. DR InterPro; IPR003134; Hs1_Cortactin. DR InterPro; IPR000108; p67phox. DR InterPro; IPR001452; SH3_domain. DR Pfam; PF02218; HS1_rep; 4. DR Pfam; PF00018; SH3_1; 1. DR PRINTS; PR00499; P67PHOX. DR PRINTS; PR00452; SH3DOMAIN. DR SMART; SM00326; SH3; 1. DR SUPFAM; SSF50044; SH3; 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; Repeat; KW 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. FT MOD_RES 241 241 N6-acetyllysine. FT MOD_RES 275 275 Phosphoserine. FT MOD_RES 308 308 Phosphothreonine. FT VARIANT 235 235 A -> T (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; 53984 MW; 61AE72A78CA33DF2 CRC64; MWKSVVGHDV SVSVETQGDD WDTDPDFVND ISEKEQRWGA KTIEGSGRTE HINIHQLRNK VSEEHDVLRK KEMESGPKAS HGYGGRFGVE RDRMDKSAVG HEYVAEVEKH SSQTDAAKGF GGKYGVERDR ADKSAVGFDY KGEVEKHTSQ KDYSRGFGGR YGVEKDKWDK AALGYDYKGE TEKHESQRDY AKGFGGQYGI QKDRVDKSAV GFNEMEAPTT AYKKTTPIEA ASSGARGLKA 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 //