STAP2_HUMAN
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 03-AUG-2022, entry version 161.
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}.
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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; 17.
DR IntAct; Q9UGK3; 98.
DR MINT; Q9UGK3; -.
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 PRIDE; Q9UGK3; -.
DR ProteomicsDB; 84227; -. [Q9UGK3-1]
DR ProteomicsDB; 84228; -. [Q9UGK3-2]
DR Antibodypedia; 1197; 312 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 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; 680358at2759; -.
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 1077 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 137 other tissues.
DR ExpressionAtlas; Q9UGK3; baseline and differential.
DR Genevisible; Q9UGK3; HS.
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; cd10404; SH2_STAP2; 1.
DR Gene3D; 2.30.29.30; -; 1.
DR Gene3D; 3.30.505.10; -; 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; PTHR16186; 1.
DR SUPFAM; SSF55550; SSF55550; 1.
DR PROSITE; PS50001; SH2; 1.
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
