SHKB1_HUMAN
ID SHKB1_HUMAN Reviewed; 707 AA.
AC Q8TBC3; Q8N2I6; Q8WY93; Q96IB8;
DT 23-OCT-2007, integrated into UniProtKB/Swiss-Prot.
DT 23-OCT-2007, sequence version 2.
DT 03-AUG-2022, entry version 162.
DE RecName: Full=SH3KBP1-binding protein 1;
DE AltName: Full=SETA-binding protein 1 {ECO:0000303|PubMed:16733801};
GN Name=SHKBP1; Synonyms=SB1 {ECO:0000303|PubMed:16733801}; ORFNames=PP203;
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 [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Ovary;
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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RX PubMed=15498874; DOI=10.1073/pnas.0404089101;
RA Wan D., Gong Y., Qin W., Zhang P., Li J., Wei L., Zhou X., Li H., Qiu X.,
RA Zhong F., He L., Yu J., Yao G., Jiang H., Qian L., Yu Y., Shu H., Chen X.,
RA Xu H., Guo M., Pan Z., Chen Y., Ge C., Yang S., Gu J.;
RT "Large-scale cDNA transfection screening for genes related to cancer
RT development and progression.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:15724-15729(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT LEU-507.
RC TISSUE=Brain, and Uterus;
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 [4]
RP INTERACTION WITH CTSB, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=16733801; DOI=10.1007/s11010-006-9214-7;
RA Liu J.P., Liu N.S., Yuan H.Y., Guo Q., Lu H., Li Y.Y.;
RT "Human homologue of SETA binding protein 1 interacts with cathepsin B and
RT participates in TNF-Induced apoptosis in ovarian cancer cells.";
RL Mol. Cell. Biochem. 292:189-195(2006).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-649, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [6]
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 [7]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-163; SER-647; SER-649 AND
RP THR-696, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and 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 [9]
RP X-RAY CRYSTALLOGRAPHY (1.72 ANGSTROMS) OF 18-120, AND SUBUNIT.
RX PubMed=28963344; DOI=10.1042/bcj20170527;
RA Pinkas D.M., Sanvitale C.E., Bufton J.C., Sorrell F.J., Solcan N.,
RA Chalk R., Doutch J., Bullock A.N.;
RT "Structural complexity in the KCTD family of Cullin3-dependent E3 ubiquitin
RT ligases.";
RL Biochem. J. 474:3747-3761(2017).
CC -!- FUNCTION: Inhibits CBL-SH3KBP1 complex mediated down-regulation of EGFR
CC signaling by sequestration of SH3KBP1. Binds to SH3KBP1 and prevents
CC its interaction with CBL and inhibits translocation of SH3KBP1 to EGFR
CC containing vesicles upon EGF stimulation.
CC {ECO:0000250|UniProtKB:Q6P7W2}.
CC -!- SUBUNIT: Monomer (PubMed:28963344). Interacts with CUL3; interaction is
CC direct and forms a 5:5 heterodecamer (PubMed:28963344). Interacts (via
CC PXXXPR motifs) with SH3KBP1 (via SH3 domains) (By similarity). Directly
CC interacts with cathepsin B/CTSB (PubMed:16733801).
CC {ECO:0000250|UniProtKB:Q6P7W2, ECO:0000269|PubMed:16733801,
CC ECO:0000269|PubMed:28963344}.
CC -!- INTERACTION:
CC Q8TBC3; Q13618: CUL3; NbExp=6; IntAct=EBI-724292, EBI-456129;
CC Q8TBC3; Q9BS40: LXN; NbExp=3; IntAct=EBI-724292, EBI-1044504;
CC Q8TBC3; O43395: PRPF3; NbExp=3; IntAct=EBI-724292, EBI-744322;
CC Q8TBC3; Q8TBC3: SHKBP1; NbExp=3; IntAct=EBI-724292, EBI-724292;
CC -!- SUBCELLULAR LOCATION: Lysosome {ECO:0000269|PubMed:16733801}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q8TBC3-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q8TBC3-2; Sequence=VSP_028873, VSP_028874;
CC -!- TISSUE SPECIFICITY: Widely expressed. {ECO:0000269|PubMed:16733801}.
CC -!- SIMILARITY: Belongs to the KCTD3 family. {ECO:0000305}.
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DR EMBL; AK075057; BAC11374.1; -; mRNA.
DR EMBL; AF258553; AAG23756.1; -; mRNA.
DR EMBL; BC007653; AAH07653.1; -; mRNA.
DR EMBL; BC022855; AAH22855.1; -; mRNA.
DR CCDS; CCDS12560.1; -. [Q8TBC3-1]
DR RefSeq; NP_612401.2; NM_138392.3. [Q8TBC3-1]
DR PDB; 4CRH; X-ray; 1.72 A; A=18-120.
DR PDBsum; 4CRH; -.
DR AlphaFoldDB; Q8TBC3; -.
DR SMR; Q8TBC3; -.
DR BioGRID; 124979; 124.
DR IntAct; Q8TBC3; 40.
DR MINT; Q8TBC3; -.
DR STRING; 9606.ENSP00000291842; -.
DR iPTMnet; Q8TBC3; -.
DR MetOSite; Q8TBC3; -.
DR PhosphoSitePlus; Q8TBC3; -.
DR BioMuta; SHKBP1; -.
DR DMDM; 160185660; -.
DR EPD; Q8TBC3; -.
DR jPOST; Q8TBC3; -.
DR MassIVE; Q8TBC3; -.
DR MaxQB; Q8TBC3; -.
DR PaxDb; Q8TBC3; -.
DR PeptideAtlas; Q8TBC3; -.
DR PRIDE; Q8TBC3; -.
DR ProteomicsDB; 73989; -. [Q8TBC3-1]
DR ProteomicsDB; 73990; -. [Q8TBC3-2]
DR Antibodypedia; 45190; 69 antibodies from 20 providers.
DR DNASU; 92799; -.
DR Ensembl; ENST00000291842.10; ENSP00000291842.4; ENSG00000160410.15. [Q8TBC3-1]
DR GeneID; 92799; -.
DR KEGG; hsa:92799; -.
DR MANE-Select; ENST00000291842.10; ENSP00000291842.4; NM_138392.4; NP_612401.2.
DR UCSC; uc002oob.4; human. [Q8TBC3-1]
DR CTD; 92799; -.
DR DisGeNET; 92799; -.
DR GeneCards; SHKBP1; -.
DR HGNC; HGNC:19214; SHKBP1.
DR HPA; ENSG00000160410; Tissue enhanced (lymphoid).
DR MIM; 617322; gene.
DR neXtProt; NX_Q8TBC3; -.
DR OpenTargets; ENSG00000160410; -.
DR PharmGKB; PA134954640; -.
DR VEuPathDB; HostDB:ENSG00000160410; -.
DR eggNOG; KOG2714; Eukaryota.
DR GeneTree; ENSGT00940000153881; -.
DR HOGENOM; CLU_012214_0_1_1; -.
DR InParanoid; Q8TBC3; -.
DR OMA; NWLEIAY; -.
DR OrthoDB; 351369at2759; -.
DR PhylomeDB; Q8TBC3; -.
DR TreeFam; TF313754; -.
DR PathwayCommons; Q8TBC3; -.
DR Reactome; R-HSA-9013148; CDC42 GTPase cycle.
DR SignaLink; Q8TBC3; -.
DR BioGRID-ORCS; 92799; 12 hits in 1115 CRISPR screens.
DR ChiTaRS; SHKBP1; human.
DR GenomeRNAi; 92799; -.
DR Pharos; Q8TBC3; Tbio.
DR PRO; PR:Q8TBC3; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; Q8TBC3; protein.
DR Bgee; ENSG00000160410; Expressed in granulocyte and 138 other tissues.
DR ExpressionAtlas; Q8TBC3; baseline and differential.
DR Genevisible; Q8TBC3; HS.
DR GO; GO:0005764; C:lysosome; IEA:UniProtKB-SubCell.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0045742; P:positive regulation of epidermal growth factor receptor signaling pathway; ISS:UniProtKB.
DR GO; GO:0051260; P:protein homooligomerization; IEA:InterPro.
DR Gene3D; 2.130.10.10; -; 1.
DR Gene3D; 3.30.710.10; -; 1.
DR InterPro; IPR000210; BTB/POZ_dom.
DR InterPro; IPR011333; SKP1/BTB/POZ_sf.
DR InterPro; IPR003131; T1-type_BTB.
DR InterPro; IPR015943; WD40/YVTN_repeat-like_dom_sf.
DR InterPro; IPR001680; WD40_repeat.
DR InterPro; IPR036322; WD40_repeat_dom_sf.
DR Pfam; PF02214; BTB_2; 1.
DR SMART; SM00225; BTB; 1.
DR SMART; SM00320; WD40; 3.
DR SUPFAM; SSF50978; SSF50978; 1.
DR SUPFAM; SSF54695; SSF54695; 1.
DR PROSITE; PS50097; BTB; 1.
DR PROSITE; PS00678; WD_REPEATS_1; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Lysosome; Phosphoprotein;
KW Reference proteome; Repeat; WD repeat.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0007744|PubMed:22814378"
FT CHAIN 2..707
FT /note="SH3KBP1-binding protein 1"
FT /id="PRO_0000307932"
FT DOMAIN 19..88
FT /note="BTB"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00037"
FT REPEAT 185..225
FT /note="WD 1"
FT REPEAT 226..278
FT /note="WD 2"
FT REPEAT 279..318
FT /note="WD 3"
FT REPEAT 319..362
FT /note="WD 4"
FT REPEAT 363..420
FT /note="WD 5"
FT REPEAT 421..466
FT /note="WD 6"
FT REPEAT 467..518
FT /note="WD 7"
FT REPEAT 519..577
FT /note="WD 8"
FT REGION 145..165
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 628..707
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 621..626
FT /note="PXXXPR"
FT /evidence="ECO:0000305"
FT MOTIF 681..686
FT /note="PXXXPW"
FT /evidence="ECO:0000305"
FT COMPBIAS 628..647
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 678..692
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0007744|PubMed:22814378"
FT MOD_RES 163
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 647
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 649
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 696
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT VAR_SEQ 283..305
FT /note="VFHLGVPVEALFFVGNQLIATSH -> AHRGVECRHQALAGPGGAAHHQL
FT (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_028873"
FT VAR_SEQ 306..707
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_028874"
FT VARIANT 507
FT /note="Q -> L (in dbSNP:rs17855499)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_036714"
FT CONFLICT 58
FT /note="D -> G (in Ref. 1; BAC11374)"
FT /evidence="ECO:0000305"
FT CONFLICT 153
FT /note="G -> R (in Ref. 1; BAC11374)"
FT /evidence="ECO:0000305"
FT STRAND 20..25
FT /evidence="ECO:0007829|PDB:4CRH"
FT STRAND 28..33
FT /evidence="ECO:0007829|PDB:4CRH"
FT HELIX 34..38
FT /evidence="ECO:0007829|PDB:4CRH"
FT HELIX 44..48
FT /evidence="ECO:0007829|PDB:4CRH"
FT STRAND 63..65
FT /evidence="ECO:0007829|PDB:4CRH"
FT HELIX 72..81
FT /evidence="ECO:0007829|PDB:4CRH"
FT HELIX 93..101
FT /evidence="ECO:0007829|PDB:4CRH"
FT HELIX 104..117
FT /evidence="ECO:0007829|PDB:4CRH"
SQ SEQUENCE 707 AA; 76344 MW; 1E38F2FA5B84332F CRC64;
MAAAATAAEG VPSRGPPGEV IHLNVGGKRF STSRQTLTWI PDSFFSSLLS GRISTLKDET
GAIFIDRDPT VFAPILNFLR TKELDPRGVH GSSLLHEAQF YGLTPLVRRL QLREELDRSS
CGNVLFNGYL PPPVFPVKRR NRHSLVGPQQ LGGRPAPVRR SNTMPPNLGN AGLLGRMLDE
KTPPSPSGQP EEPGMVRLVC GHHNWIAVAY TQFLVCYRLK EASGWQLVFS SPRLDWPIER
LALTARVHGG ALGEHDKMVA AATGSEILLW ALQAEGGGSE IGVFHLGVPV EALFFVGNQL
IATSHTGRIG VWNAVTKHWQ VQEVQPITSY DAAGSFLLLG CNNGSIYYVD VQKFPLRMKD
NDLLVSELYR DPAEDGVTAL SVYLTPKTSD SGNWIEIAYG TSSGGVRVIV QHPETVGSGP
QLFQTFTVHR SPVTKIMLSE KHLISVCADN NHVRTWSVTR FRGMISTQPG STPLASFKIL
ALESADGHGG CSAGNDIGPY GERDDQQVFI QKVVPSASQL FVRLSSTGQR VCSVRSVDGS
PTTAFTVLEC EGSRRLGSRP RRYLLTGQAN GSLAMWDLTT AMDGLGQAPA GGLTEQELME
QLEHCELAPP APSAPSWGCL PSPSPRISLT SLHSASSNTS LSGHRGSPSP PQAEARRRGG
GSFVERCQEL VRSGPDLRRP PTPAPWPSSG LGTPLTPPKM KLNETSF
