ID STAP2_HUMAN Reviewed; 403 AA. AC Q9UGK3; A6NKK3; Q9NXI2; DT 12-APR-2005, integrated into UniProtKB/Swiss-Prot. DT 05-MAY-2009, sequence version 2. DT 27-MAR-2024, entry version 170. DE RecName: Full=Signal-transducing adaptor protein 2; DE Short=STAP-2; DE AltName: Full=Breast tumor kinase substrate; DE Short=BRK substrate; GN Name=STAP2; Synonyms=BKS; 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), FUNCTION, INTERACTION WITH PTK6, RP SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND VARIANT ASN-93. RC TISSUE=Mammary gland; RX PubMed=10980601; DOI=10.1038/sj.onc.1203775; RA Mitchell P.J., Sara E.A., Crompton M.R.; RT "A novel adaptor-like protein which is a substrate for the non-receptor RT tyrosine kinase, BRK."; RL Oncogene 19:4273-4282(2000). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND VARIANT ASN-93. RC TISSUE=Colon mucosa; 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 [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15057824; DOI=10.1038/nature02399; RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E., RA Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A., RA Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S., RA Carrano A.V., Caoile C., Chan Y.M., Christensen M., Cleland C.A., RA Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J., RA Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M., RA Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W., RA Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V., RA Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D., RA McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I., RA Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L., RA Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., RA She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., RA Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., RA Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E., RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M., RA Rubin E.M., Lucas S.M.; RT "The DNA sequence and biology of human chromosome 19."; RL Nature 428:529-535(2004). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT ASN-93. RC TISSUE=Placenta; 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 [5] RP TISSUE SPECIFICITY, PHOSPHORYLATION AT TYR-22; TYR-250; TYR-310 AND RP TYR-322, AND MUTAGENESIS OF TYR-22; TYR-250; TYR-310 AND TYR-322. RX PubMed=12540842; DOI=10.1074/jbc.m211230200; RA Minoguchi M., Minoguchi S., Aki D., Joo A., Yamamoto T., Yumioka T., RA Matsuda T., Yoshimura A.; RT "STAP-2/BKS, an adaptor/docking protein, modulates STAT3 activation in RT acute-phase response through its YXXQ motif."; RL J. Biol. Chem. 278:11182-11189(2003). RN [6] RP PHOSPHORYLATION AT TYR-250 BY PTK6, AND INTERACTION WITH PTK6. RX PubMed=19393627; DOI=10.1016/j.bbrc.2009.04.076; RA Ikeda O., Miyasaka Y., Sekine Y., Mizushima A., Muromoto R., Nanbo A., RA Yoshimura A., Matsuda T.; RT "STAP-2 is phosphorylated at tyrosine-250 by Brk and modulates Brk-mediated RT STAT3 activation."; RL Biochem. Biophys. Res. Commun. 384:71-75(2009). RN [7] RP STRUCTURE BY NMR OF 137-247. RG RIKEN structural genomics initiative (RSGI); RT "Solution structure of the human STAP2 SH2 domain."; RL Submitted (OCT-2007) to the PDB data bank. CC -!- FUNCTION: Substrate of protein kinase PTK6. May play a regulatory role CC in the acute-phase response in systemic inflammation and may modulate CC STAT3 activity. {ECO:0000269|PubMed:10980601}. CC -!- SUBUNIT: Interacts with PTK6 and CSF1R. {ECO:0000269|PubMed:10980601, CC ECO:0000269|PubMed:19393627}. CC -!- INTERACTION: CC Q9UGK3; P51451: BLK; NbExp=3; IntAct=EBI-1553984, EBI-2105445; CC Q9UGK3; O14920: IKBKB; NbExp=7; IntAct=EBI-1553984, EBI-81266; CC Q9UGK3; Q14145: KEAP1; NbExp=3; IntAct=EBI-1553984, EBI-751001; CC Q9UGK3; Q99836: MYD88; NbExp=3; IntAct=EBI-1553984, EBI-447677; CC Q9UGK3; P42681: TXK; NbExp=3; IntAct=EBI-1553984, EBI-7877438; CC Q9UGK3; P07947: YES1; NbExp=3; IntAct=EBI-1553984, EBI-515331; CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:10980601}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=Q9UGK3-1; Sequence=Displayed; CC Name=2; CC IsoId=Q9UGK3-2; Sequence=VSP_041403; CC -!- TISSUE SPECIFICITY: Widely expressed. {ECO:0000269|PubMed:10980601, CC ECO:0000269|PubMed:12540842}. CC -!- PTM: Phosphorylated on tyrosine. Tyr-250 may be important for CC interaction with kinases. Phosphorylated by PTK6 at Tyr-250 modulates CC PTK6-mediated STAT3 activation. Tyr-22 and Tyr-322 appears to be CC phosphorylated by SRC. {ECO:0000269|PubMed:12540842, CC ECO:0000269|PubMed:19393627}. CC -!- MISCELLANEOUS: [Isoform 2]: Alu insert from position 358 to 403. CC {ECO:0000305}. 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; AJ245719; CAB65105.1; -; mRNA. DR EMBL; AK000241; BAA91028.1; -; mRNA. DR EMBL; AC008616; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC000795; AAH00795.1; -; mRNA. DR CCDS; CCDS12128.1; -. [Q9UGK3-2] DR CCDS; CCDS45926.1; -. [Q9UGK3-1] DR RefSeq; NP_001013863.1; NM_001013841.1. [Q9UGK3-1] DR RefSeq; NP_060190.2; NM_017720.2. [Q9UGK3-2] DR PDB; 2EL8; NMR; -; A=137-247. DR PDBsum; 2EL8; -. DR AlphaFoldDB; Q9UGK3; -. DR SMR; Q9UGK3; -. DR BioGRID; 120759; 22. DR IntAct; Q9UGK3; 97. DR MINT; Q9UGK3; -. DR STRING; 9606.ENSP00000468927; -. DR GlyGen; Q9UGK3; 2 sites, 1 O-linked glycan (2 sites). DR iPTMnet; Q9UGK3; -. DR PhosphoSitePlus; Q9UGK3; -. DR BioMuta; STAP2; -. DR DMDM; 229462752; -. DR EPD; Q9UGK3; -. DR jPOST; Q9UGK3; -. DR MassIVE; Q9UGK3; -. DR MaxQB; Q9UGK3; -. DR PeptideAtlas; Q9UGK3; -. DR ProteomicsDB; 84227; -. [Q9UGK3-1] DR ProteomicsDB; 84228; -. [Q9UGK3-2] DR Antibodypedia; 1197; 337 antibodies from 35 providers. DR DNASU; 55620; -. DR Ensembl; ENST00000594605.6; ENSP00000471052.1; ENSG00000178078.12. [Q9UGK3-1] DR Ensembl; ENST00000600324.5; ENSP00000468927.1; ENSG00000178078.12. [Q9UGK3-2] DR GeneID; 55620; -. DR KEGG; hsa:55620; -. DR MANE-Select; ENST00000594605.6; ENSP00000471052.1; NM_001013841.2; NP_001013863.1. DR UCSC; uc060rvu.1; human. [Q9UGK3-1] DR AGR; HGNC:30430; -. DR CTD; 55620; -. DR DisGeNET; 55620; -. DR GeneCards; STAP2; -. DR HGNC; HGNC:30430; STAP2. DR HPA; ENSG00000178078; Tissue enhanced (esophagus). DR MIM; 607881; gene. DR neXtProt; NX_Q9UGK3; -. DR OpenTargets; ENSG00000178078; -. DR PharmGKB; PA162404971; -. DR VEuPathDB; HostDB:ENSG00000178078; -. DR GeneTree; ENSGT00530000063841; -. DR HOGENOM; CLU_043957_0_0_1; -. DR InParanoid; Q9UGK3; -. DR OMA; SQLPPCY; -. DR OrthoDB; 4259410at2759; -. DR PhylomeDB; Q9UGK3; -. DR TreeFam; TF332087; -. DR PathwayCommons; Q9UGK3; -. DR Reactome; R-HSA-8849474; PTK6 Activates STAT3. DR Reactome; R-HSA-9707564; Cytoprotection by HMOX1. DR SignaLink; Q9UGK3; -. DR SIGNOR; Q9UGK3; -. DR BioGRID-ORCS; 55620; 9 hits in 1155 CRISPR screens. DR ChiTaRS; STAP2; human. DR EvolutionaryTrace; Q9UGK3; -. DR GeneWiki; STAP2; -. DR GenomeRNAi; 55620; -. DR Pharos; Q9UGK3; Tbio. DR PRO; PR:Q9UGK3; -. DR Proteomes; UP000005640; Chromosome 19. DR RNAct; Q9UGK3; Protein. DR Bgee; ENSG00000178078; Expressed in mucosa of transverse colon and 138 other cell types or tissues. DR ExpressionAtlas; Q9UGK3; baseline and differential. DR GO; GO:0005829; C:cytosol; TAS:Reactome. DR GO; GO:0005886; C:plasma membrane; TAS:Reactome. DR GO; GO:0035591; F:signaling adaptor activity; IEA:InterPro. DR CDD; cd13268; PH_Brdg1; 1. DR CDD; cd10404; SH2_STAP2; 1. DR Gene3D; 2.30.29.30; Pleckstrin-homology domain (PH domain)/Phosphotyrosine-binding domain (PTB); 1. DR Gene3D; 3.30.505.10; SH2 domain; 1. DR InterPro; IPR011993; PH-like_dom_sf. DR InterPro; IPR000980; SH2. DR InterPro; IPR036860; SH2_dom_sf. DR InterPro; IPR039111; STAP1/STAP2. DR InterPro; IPR035878; STAP2_SH2. DR PANTHER; PTHR16186:SF11; SIGNAL-TRANSDUCING ADAPTOR PROTEIN 2; 1. DR PANTHER; PTHR16186; SIGNAL-TRANSDUCING ADAPTOR PROTEIN-RELATED; 1. DR SUPFAM; SSF50729; PH domain-like; 1. DR SUPFAM; SSF55550; SH2 domain; 1. DR PROSITE; PS50001; SH2; 1. DR Genevisible; Q9UGK3; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Coiled coil; Cytoplasm; Phosphoprotein; KW Reference proteome; SH2 domain. FT CHAIN 1..403 FT /note="Signal-transducing adaptor protein 2" FT /id="PRO_0000072239" FT DOMAIN 18..130 FT /note="PH" FT DOMAIN 133..248 FT /note="SH2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00191" FT REGION 270..308 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 331..374 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COILED 382..402 FT /evidence="ECO:0000255" FT COMPBIAS 292..306 FT /note="Pro residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 338..358 FT /note="Pro residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 22 FT /note="Phosphotyrosine; by SRC" FT /evidence="ECO:0000305|PubMed:12540842" FT MOD_RES 250 FT /note="Phosphotyrosine; by PTK6" FT /evidence="ECO:0000269|PubMed:12540842, FT ECO:0000269|PubMed:19393627" FT MOD_RES 310 FT /note="Phosphotyrosine" FT /evidence="ECO:0000305|PubMed:12540842" FT MOD_RES 322 FT /note="Phosphotyrosine; by SRC" FT /evidence="ECO:0000305|PubMed:12540842" FT VAR_SEQ 356 FT /note="K -> KPVEKGFHHVAQAGLELLTSSDPPTSASQSAGITGVSHHTWPHLSSL FT (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_041403" FT VARIANT 93 FT /note="D -> N (in dbSNP:rs7247504)" FT /evidence="ECO:0000269|PubMed:10980601, FT ECO:0000269|PubMed:14702039, ECO:0000269|PubMed:15489334" FT /id="VAR_055239" FT MUTAGEN 22 FT /note="Y->F: Small decrease in tyrosine phosphorylation." FT /evidence="ECO:0000269|PubMed:12540842" FT MUTAGEN 250 FT /note="Y->F: Loss of tyrosine phosphorylation." FT /evidence="ECO:0000269|PubMed:12540842" FT MUTAGEN 310 FT /note="Y->F: Decrease in tyrosine phosphorylation." FT /evidence="ECO:0000269|PubMed:12540842" FT MUTAGEN 322 FT /note="Y->F: Decrease in tyrosine phosphorylation." FT /evidence="ECO:0000269|PubMed:12540842" FT STRAND 148..150 FT /evidence="ECO:0007829|PDB:2EL8" FT HELIX 159..168 FT /evidence="ECO:0007829|PDB:2EL8" FT STRAND 174..179 FT /evidence="ECO:0007829|PDB:2EL8" FT STRAND 182..191 FT /evidence="ECO:0007829|PDB:2EL8" FT STRAND 202..204 FT /evidence="ECO:0007829|PDB:2EL8" FT STRAND 215..219 FT /evidence="ECO:0007829|PDB:2EL8" FT HELIX 226..236 FT /evidence="ECO:0007829|PDB:2EL8" FT STRAND 237..239 FT /evidence="ECO:0007829|PDB:2EL8" SQ SEQUENCE 403 AA; 44894 MW; A5E809B3F233EFD0 CRC64; MASALRPPRV PKPKGVLPSH YYESFLEKKG PCDRDYKKFW AGLQGLTIYF YNSNRDFQHV EKLNLGAFEK LTDEIPWGSS RDPGTHFSLI LRDQEIKFKV ETLECREMWK GFILTVVELR VPTDLTLLPG HLYMMSEVLA KEEARRALET PSCFLKVSRL EAQLLLERYP ECGNLLLRPS GDGADGVSVT TRQMHNGTHV VRHYKVKREG PKYVIDVEQP FSCTSLDAVV NYFVSHTKKA LVPFLLDEDY EKVLGYVEAD KENGENVWVA PSAPGPGPAP CTGGPKPLSP ASSQDKLPPL PPLPNQEENY VTPIGDGPAV DYENQDVASS SWPVILKPKK LPKPPAKLPK PPVGPKPEPK VFNGGLGRKL PVSSAQPLFP TAGLADMTAE LQKKLEKRRA LEH //