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 04-NOV-2026, entry version 238. 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; DOI=10.4049/jimmunol.158.6.2736; 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_001278970.2; NM_001292041.2. DR RefSeq; NP_005326.3; NM_005335.6. [P14317-1] DR AlphaFoldDB; P14317; -. DR SMR; P14317; -. DR BioGRID; 109309; 88. DR FunCoup; P14317; 721. DR IntAct; P14317; 35. DR MINT; P14317; -. DR NDEx; IQUERY-CP-HCLS1; 4 NDEx IQuery Curated Pathways. DR STRING; 9606.ENSP00000320176; -. DR BindingDB; P14317; -. DR ChEMBL; CHEMBL6066407; -. DR GlyCosmos; P14317; 3 sites, 2 glycans. 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 jPOST; P14317; -. DR MassIVE; P14317; -. DR PaxDb; 9606-ENSP00000320176; -. DR PeptideAtlas; P14317; -. DR ProteomicsDB; 4850; -. DR ProteomicsDB; 53045; -. [P14317-1] DR Pumba; P14317; -. DR Antibodypedia; 16699; 555 antibodies from 43 providers. DR DNASU; 3059; -. DR Ensembl; ENST00000314583.8; ENSP00000320176.3; ENSG00000180353.12. [P14317-1] DR Ensembl; ENST00000495491.5; ENSP00000418299.1; ENSG00000180353.12. [P14317-2] DR Ensembl; ENST00000909628.1; ENSP00000579687.1; ENSG00000180353.12. [P14317-1] 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 AGR; HGNC:4844; -. DR ClinPGx; PA29220; -. 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 OpenTargets; ENSG00000180353; -. DR VEuPathDB; HostDB:ENSG00000180353; -. DR eggNOG; ENOG502QS6C; Eukaryota. DR GeneTree; ENSGT00940000158997; -. DR HOGENOM; CLU_019379_2_0_1; -. DR InParanoid; P14317; -. DR OMA; ACDNDYE; -. DR OrthoDB; 5971719at2759; -. DR PAN-GO; P14317; 2 GO annotations based on evolutionary models. DR PhylomeDB; P14317; -. DR PathwayCommons; P14317; -. DR SignaLink; P14317; -. DR SIGNOR; P14317; -. DR Agora; ENSG00000180353; Agora Nominated Target for Alzheimer's Disease. DR BioGRID-ORCS; 3059; 16 hits in 1165 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 170 other cell types or tissues. DR ExpressionAtlas; P14317; baseline and differential. DR GO; GO:0005737; C:cytoplasm; IDA:BHF-UCL. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:0030139; C:endocytic vesicle; IBA:GO_Central. 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:0005667; C:transcription regulator complex; IDA:BHF-UCL. DR GO; GO:0051015; F:actin filament binding; TAS:BHF-UCL. 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:0035591; F:signaling adaptor activity; IMP:BHF-UCL. DR GO; GO:0007015; P:actin filament organization; 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:0038158; P:granulocyte colony-stimulating factor signaling pathway; IMP:BHF-UCL. 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:0051169; P:nuclear transport; IMP:BHF-UCL. DR GO; GO:0008284; P:positive regulation of cell population 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:0051897; P:positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction; IMP:BHF-UCL. DR GO; GO:0042307; P:positive regulation of protein import into nucleus; IMP:BHF-UCL. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IMP:BHF-UCL. DR GO; GO:0030833; P:regulation of actin filament polymerization; IMP:BHF-UCL. DR GO; GO:0006355; P:regulation of DNA-templated transcription; TAS:ProtInc. DR GO; GO:0009725; P:response to hormone; ISS:UniProtKB. DR GO; GO:0007165; P:signal transduction; IBA:GO_Central. DR CDD; cd12073; SH3_HS1; 1. DR FunFam; 2.30.30.40:FF:000139; Hematopoietic cell-specific Lyn substrate 1; 1. DR Gene3D; 2.30.30.40; SH3 Domains; 1. DR InterPro; IPR003134; Hs1_Cortactin. DR InterPro; IPR036028; SH3-like_dom_sf. DR InterPro; IPR001452; SH3_domain. DR PANTHER; PTHR10829; CORTACTIN AND DREBRIN; 1. DR PANTHER; PTHR10829:SF5; HEMATOPOIETIC LINEAGE CELL-SPECIFIC PROTEIN; 1. 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-domain; 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; Proteomics identification; KW Reference proteome; Repeat; 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..276 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 315..324 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 353..383 FT /note="Acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 390..405 FT /note="Acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 406..419 FT /note="Low complexity" 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 //