HCLS1_HUMAN
ID HCLS1_HUMAN Reviewed; 486 AA.
AC P14317; B4DQ69; Q53Y93; Q6IBK9; Q9UDK0;
DT 01-JAN-1990, integrated into UniProtKB/Swiss-Prot.
DT 11-JAN-2011, sequence version 3.
DT 03-AUG-2022, entry version 219.
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; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), 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] (ISOFORM 1), AND VARIANTS ALA-235
RP AND 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 vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), AND VARIANTS
RP ALA-235 AND 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., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., 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., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA 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] (ISOFORM 1), AND VARIANTS ALA-235
RP AND 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., Buhay C.J.,
RA Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P.,
RA Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A.,
RA Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L.,
RA Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G.,
RA Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W.,
RA Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M.,
RA Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P.,
RA Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H.,
RA Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J.,
RA Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W.,
RA Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B.,
RA Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O.,
RA Palmeiri A., 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., Zhang X.,
RA Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R.,
RA Naylor S.L., Yang H., Olson M., Weinstock G., 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] (ISOFORM 1), AND VARIANTS ALA-235
RP AND 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 project:
RT 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, INTERACTION
RP 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-tyrosine
RT 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 alpha-
RT actinin-1 as novel phosphotyrosine-containing proteins in T lymphocytes.";
RL Biochem. Biophys. Res. Commun. 224:666-674(1996).
RN [9]
RP PHOSPHORYLATION AT TYR-222 AND TYR-397, AND PHOSPHORYLATION BY SYK; LYN;
RP 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, directly
RT associates with HS1, a substrate of Src family tyrosine kinases.";
RL J. Immunol. 158:2736-2744(1997).
RN [11]
RP PHOSPHORYLATION AT TYR-222 AND TYR-397, IDENTIFICATION BY MASS
RP SPECTROMETRY, AND 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., Marin O.,
RA 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 IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=12522270; DOI=10.1073/pnas.2436191100;
RA Salomon A.R., Ficarro S.B., Brill L.M., Brinker A., Phung Q.T., Ericson C.,
RA Sauer K., Brock A., Horn D.M., Schultz P.G., Peters E.C.;
RT "Profiling of tyrosine phosphorylation pathways in human cells using mass
RT spectrometry.";
RL Proc. Natl. Acad. Sci. U.S.A. 100:443-448(2003).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-198, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
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 from
RT human T cells using immobilized metal affinity chromatography and tandem
RT mass spectrometry.";
RL Anal. Chem. 76:2763-2772(2004).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-275 AND THR-308, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
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 LYS-241,
RP AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C.,
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).
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., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-275 AND THR-308, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [18]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-275, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
CC -!- FUNCTION: Substrate of the antigen receptor-coupled tyrosine kinase.
CC Plays a role in antigen receptor signaling for both clonal expansion
CC and deletion in lymphoid cells. May also be involved in the regulation
CC of gene expression.
CC -!- SUBUNIT: Associates with the SH2 and SH3 domains of LCK. Binding to he
CC LCK SH3 domain occurs constitutively, while binding to the LCK SH2
CC domain occurs only upon TCR stimulation. A similar binding pattern was
CC observed with LYN, but not with FYN in which the FYN SH2 region
CC associates upon TCR stimulation but the FYN SH3 region does not
CC associate regardless of TCR stimulation. Directly associates with HAX1,
CC through binding to its C-terminal region. Interacts with HS1BP3.
CC Interacts with FES/FPS (By similarity). Interacts (via SH2 domain) with
CC FGR. Forms a multiprotein complex with LYN and ANKRD54 (By similarity).
CC {ECO:0000250}.
CC -!- INTERACTION:
CC P14317; Q9H788: SH2D4A; NbExp=8; IntAct=EBI-750369, EBI-747035;
CC P14317; P78314-3: SH3BP2; NbExp=3; IntAct=EBI-750369, EBI-12304031;
CC P14317; P54274: TERF1; NbExp=2; IntAct=EBI-750369, EBI-710997;
CC P14317; O43516: WIPF1; NbExp=2; IntAct=EBI-750369, EBI-346356;
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000269|PubMed:7682714}; Peripheral
CC membrane protein {ECO:0000269|PubMed:7682714}. Cytoplasm
CC {ECO:0000269|PubMed:7682714}. Mitochondrion
CC {ECO:0000305|PubMed:7682714}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P14317-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P14317-2; Sequence=VSP_056429, VSP_056430;
CC -!- TISSUE SPECIFICITY: Expressed only in tissues and cells of
CC hematopoietic origin.
CC -!- DEVELOPMENTAL STAGE: Expressed in early stage of myeloid and erythroid
CC differentiation.
CC -!- PTM: Phosphorylated by FES (By similarity). Phosphorylated by LYN, FYN
CC and FGR after cross-linking of surface IgM on B-cells. Phosphorylation
CC by LYN, FYN and FGR requires prior phosphorylation by SYK or FES.
CC {ECO:0000250, ECO:0000269|PubMed:10066823, ECO:0000269|PubMed:7682714,
CC ECO:0000269|PubMed:8611520}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; X16663; CAA34651.1; -; mRNA.
DR EMBL; BT006824; AAP35470.1; -; mRNA.
DR EMBL; AK298663; BAG60831.1; -; 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 CCDS; CCDS3003.1; -. [P14317-1]
DR PIR; S07633; S07633.
DR RefSeq; NP_001278970.1; NM_001292041.1.
DR RefSeq; NP_005326.2; NM_005335.5. [P14317-1]
DR AlphaFoldDB; P14317; -.
DR SMR; P14317; -.
DR BioGRID; 109309; 37.
DR IntAct; P14317; 30.
DR MINT; P14317; -.
DR STRING; 9606.ENSP00000320176; -.
DR GlyGen; P14317; 3 sites, 2 O-linked glycans (3 sites).
DR iPTMnet; P14317; -.
DR MetOSite; P14317; -.
DR PhosphoSitePlus; P14317; -.
DR BioMuta; HCLS1; -.
DR DMDM; 317373440; -.
DR EPD; P14317; -.
DR jPOST; P14317; -.
DR MassIVE; P14317; -.
DR MaxQB; P14317; -.
DR PaxDb; P14317; -.
DR PeptideAtlas; P14317; -.
DR PRIDE; P14317; -.
DR ProteomicsDB; 4850; -.
DR ProteomicsDB; 53045; -. [P14317-1]
DR Antibodypedia; 16699; 501 antibodies from 39 providers.
DR DNASU; 3059; -.
DR Ensembl; ENST00000314583.8; ENSP00000320176.3; ENSG00000180353.11. [P14317-1]
DR Ensembl; ENST00000495491.5; ENSP00000418299.1; ENSG00000180353.11. [P14317-2]
DR GeneID; 3059; -.
DR KEGG; hsa:3059; -.
DR MANE-Select; ENST00000314583.8; ENSP00000320176.3; NM_005335.6; NP_005326.3.
DR UCSC; uc003eeh.5; human. [P14317-1]
DR CTD; 3059; -.
DR DisGeNET; 3059; -.
DR GeneCards; HCLS1; -.
DR HGNC; HGNC:4844; HCLS1.
DR HPA; ENSG00000180353; Tissue enhanced (bone marrow, lymphoid tissue).
DR MIM; 601306; gene.
DR neXtProt; NX_P14317; -.
DR OpenTargets; ENSG00000180353; -.
DR PharmGKB; PA29220; -.
DR VEuPathDB; HostDB:ENSG00000180353; -.
DR eggNOG; ENOG502QS6C; Eukaryota.
DR GeneTree; ENSGT00940000158997; -.
DR HOGENOM; CLU_019379_2_0_1; -.
DR InParanoid; P14317; -.
DR OMA; RCRGHFG; -.
DR OrthoDB; 1243441at2759; -.
DR PhylomeDB; P14317; -.
DR TreeFam; TF318935; -.
DR PathwayCommons; P14317; -.
DR SignaLink; P14317; -.
DR SIGNOR; P14317; -.
DR BioGRID-ORCS; 3059; 15 hits in 1087 CRISPR screens.
DR ChiTaRS; HCLS1; human.
DR GenomeRNAi; 3059; -.
DR Pharos; P14317; Tbio.
DR PRO; PR:P14317; -.
DR Proteomes; UP000005640; Chromosome 3.
DR RNAct; P14317; protein.
DR Bgee; ENSG00000180353; Expressed in monocyte and 168 other tissues.
DR ExpressionAtlas; P14317; baseline and differential.
DR Genevisible; P14317; HS.
DR GO; GO:0030864; C:cortical actin cytoskeleton; IBA:GO_Central.
DR GO; GO:0005737; C:cytoplasm; IDA:BHF-UCL.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0005739; C:mitochondrion; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; IDA:BHF-UCL.
DR GO; GO:0005886; C:plasma membrane; IDA:HPA.
DR GO; GO:0030427; C:site of polarized growth; IBA:GO_Central.
DR GO; GO:0005667; C:transcription regulator complex; IDA:BHF-UCL.
DR GO; GO:0051015; F:actin filament binding; IBA:GO_Central.
DR GO; GO:0019901; F:protein kinase binding; IPI:BHF-UCL.
DR GO; GO:0061629; F:RNA polymerase II-specific DNA-binding transcription factor binding; IPI:BHF-UCL.
DR GO; GO:0017124; F:SH3 domain binding; IEA:Ensembl.
DR GO; GO:0030041; P:actin filament polymerization; IEA:InterPro.
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 by RNA polymerase II; 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 population proliferation; ISS:UniProtKB.
DR GO; GO:0051091; P:positive regulation of DNA-binding transcription factor activity; IMP:BHF-UCL.
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:0050731; P:positive regulation of peptidyl-tyrosine phosphorylation; IMP:BHF-UCL.
DR GO; GO:0014068; P:positive regulation of phosphatidylinositol 3-kinase signaling; IMP:BHF-UCL.
DR GO; GO:0042307; P:positive regulation of protein import into nucleus; IMP:BHF-UCL.
DR GO; GO:0051897; P:positive regulation of protein kinase B signaling; IMP:BHF-UCL.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; 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:0006355; P:regulation of transcription, DNA-templated; TAS:ProtInc.
DR GO; GO:0009725; P:response to hormone; ISS:UniProtKB.
DR InterPro; IPR028534; HS1.
DR InterPro; IPR003134; Hs1_Cortactin.
DR InterPro; IPR036028; SH3-like_dom_sf.
DR InterPro; IPR001452; SH3_domain.
DR PANTHER; PTHR10829:SF5; PTHR10829:SF5; 2.
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; Alternative splicing; Cytoplasm; Direct protein sequencing;
KW Membrane; Mitochondrion; Phosphoprotein; Reference proteome; Repeat;
KW SH3 domain.
FT CHAIN 1..486
FT /note="Hematopoietic lineage cell-specific protein"
FT /id="PRO_0000083921"
FT REPEAT 79..115
FT /note="Cortactin 1"
FT REPEAT 116..152
FT /note="Cortactin 2"
FT REPEAT 153..189
FT /note="Cortactin 3"
FT REPEAT 190..212
FT /note="Cortactin 4; truncated"
FT DOMAIN 428..486
FT /note="SH3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192"
FT REGION 27..66
FT /note="Involved in HAX-1 binding"
FT REGION 243..419
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 243..274
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 356..403
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 41
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 123
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 140
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P49710"
FT MOD_RES 192
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 198
FT /note="Phosphotyrosine"
FT /evidence="ECO:0007744|PubMed:12522270,
FT ECO:0007744|PubMed:15144186"
FT MOD_RES 222
FT /note="Phosphotyrosine; by FGR"
FT /evidence="ECO:0000269|PubMed:10066823,
FT ECO:0000269|PubMed:8611520"
FT MOD_RES 241
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 275
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19690332,
FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569"
FT MOD_RES 308
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:19690332,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 378
FT /note="Phosphotyrosine; by SYK and FES"
FT /evidence="ECO:0000250|UniProtKB:P49710"
FT MOD_RES 397
FT /note="Phosphotyrosine; by SYK and FES"
FT /evidence="ECO:0000250|UniProtKB:P49710"
FT VAR_SEQ 134..209
FT /note="SAVGFDYKGEVEKHTSQKDYSRGFGGRYGVEKDKWDKAALGYDYKGETEKHE
FT SQRDYAKGFGGQYGIQKDRVDKSA -> ITLVALVAGTGWRRINGTKQLWDMTTRERRR
FT NTSPREIMPRALVASMESRRTEWIRALSASMKWRPRPQLIRRRRP (in isoform
FT 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_056429"
FT VAR_SEQ 210..486
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_056430"
FT VARIANT 235
FT /note="T -> A (in dbSNP:rs2070179)"
FT /evidence="ECO:0000269|PubMed:14702039,
FT ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:2587259,
FT ECO:0000269|Ref.2, ECO:0000269|Ref.4"
FT /id="VAR_055006"
FT VARIANT 361
FT /note="E -> K (in dbSNP:rs2070180)"
FT /id="VAR_055007"
FT VARIANT 436
FT /note="V -> L (in dbSNP:rs9869984)"
FT /evidence="ECO:0000269|PubMed:14702039,
FT ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:2587259,
FT ECO:0000269|Ref.2, ECO:0000269|Ref.4"
FT /id="VAR_056910"
FT CONFLICT 241..242
FT /note="KF -> FK (in Ref. 8; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 486
FT /note="E -> D (in Ref. 4; CAG33075)"
FT /evidence="ECO:0000305"
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
