SHC3_HUMAN
ID SHC3_HUMAN Reviewed; 594 AA.
AC Q92529; Q5T7I7; Q8TAP2; Q9UCX5;
DT 29-MAR-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1997, sequence version 1.
DT 03-AUG-2022, entry version 176.
DE RecName: Full=SHC-transforming protein 3;
DE AltName: Full=Neuronal Shc;
DE Short=N-Shc;
DE AltName: Full=Protein Rai;
DE AltName: Full=SHC-transforming protein C;
DE AltName: Full=Src homology 2 domain-containing-transforming protein C3;
DE Short=SH2 domain protein C3;
GN Name=SHC3; Synonyms=NSHC, SHCC;
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] (ISOFORMS P64 AND P52), AND TISSUE SPECIFICITY.
RC TISSUE=Brain;
RX PubMed=8808684;
RA Nakamura T., Sanokawa R., Sasaki Y., Ayusawa D., Oishi M., Mori N.;
RT "N-Shc: a neural-specific adapter molecule that mediates signaling from
RT neurotrophin/Trk to Ras/MAPK pathway.";
RL Oncogene 13:1111-1121(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM P52).
RC TISSUE=Fetal brain;
RX PubMed=8760305;
RA Pelicci G., Dente L., De Giuseppe A., Verducci-Galletti B., Giuli S.,
RA Mele S., Vetriani C., Giorgio M., Pandolfi P.P., Cesareni G.,
RA Pelicci P.-G.;
RT "A family of Shc related proteins with conserved PTB, CH1 and SH2
RT regions.";
RL Oncogene 13:633-641(1996).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164053; DOI=10.1038/nature02465;
RA Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L.,
RA Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R.,
RA Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S.,
RA Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K.,
RA Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C.,
RA Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E.,
RA Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M.,
RA Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J.,
RA Frankish A., Frankland J.A., French L., Fricker D.G., Garner P.,
RA Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S.,
RA Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E.,
RA Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D.,
RA Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E.,
RA Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K.,
RA Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S.,
RA Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J.,
RA Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E.,
RA McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V.,
RA Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S.,
RA Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K.,
RA Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J.,
RA Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M.,
RA West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L.,
RA Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M.,
RA Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J.,
RA Dunham I.;
RT "DNA sequence and analysis of human chromosome 9.";
RL Nature 429:369-374(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM P64).
RC TISSUE=Brain;
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 PHOSPHORYLATION, AND INTERACTION WITH THE TRK RECEPTORS.
RX PubMed=12006576; DOI=10.1074/jbc.m111659200;
RA Liu H.Y., Meakin S.O.;
RT "ShcB and ShcC activation by the Trk family of receptor tyrosine kinases.";
RL J. Biol. Chem. 277:26046-26056(2002).
CC -!- FUNCTION: Signaling adapter that couples activated growth factor
CC receptors to signaling pathway in neurons. Involved in the signal
CC transduction pathways of neurotrophin-activated Trk receptors in
CC cortical neurons.
CC -!- SUBUNIT: Interacts with the Trk receptors in a phosphotyrosine-
CC dependent manner. Once activated, binds to GRB2. Interacts with
CC activated EGF receptors. {ECO:0000269|PubMed:12006576}.
CC -!- INTERACTION:
CC Q92529; Q9NXR5-2: ANKRD10; NbExp=3; IntAct=EBI-79084, EBI-12102070;
CC Q92529; P05067: APP; NbExp=5; IntAct=EBI-79084, EBI-77613;
CC Q92529; Q86U10: ASPG; NbExp=3; IntAct=EBI-79084, EBI-19946665;
CC Q92529; Q96LC9: BMF; NbExp=3; IntAct=EBI-79084, EBI-3919268;
CC Q92529; P24863: CCNC; NbExp=3; IntAct=EBI-79084, EBI-395261;
CC Q92529; Q9BXL8: CDCA4; NbExp=3; IntAct=EBI-79084, EBI-1773949;
CC Q92529; P40199: CEACAM6; NbExp=3; IntAct=EBI-79084, EBI-4314501;
CC Q92529; Q7L5N1: COPS6; NbExp=3; IntAct=EBI-79084, EBI-486838;
CC Q92529; Q8WUE5: CT55; NbExp=3; IntAct=EBI-79084, EBI-6873363;
CC Q92529; Q7L591-3: DOK3; NbExp=3; IntAct=EBI-79084, EBI-10694655;
CC Q92529; P04626: ERBB2; NbExp=2; IntAct=EBI-79084, EBI-641062;
CC Q92529; P21860: ERBB3; NbExp=2; IntAct=EBI-79084, EBI-720706;
CC Q92529; Q9C0B1-2: FTO; NbExp=3; IntAct=EBI-79084, EBI-18138793;
CC Q92529; Q08379: GOLGA2; NbExp=3; IntAct=EBI-79084, EBI-618309;
CC Q92529; A6NEM1: GOLGA6L9; NbExp=3; IntAct=EBI-79084, EBI-5916454;
CC Q92529; P10721: KIT; NbExp=3; IntAct=EBI-79084, EBI-1379503;
CC Q92529; Q15323: KRT31; NbExp=6; IntAct=EBI-79084, EBI-948001;
CC Q92529; Q14525: KRT33B; NbExp=3; IntAct=EBI-79084, EBI-1049638;
CC Q92529; O76011: KRT34; NbExp=3; IntAct=EBI-79084, EBI-1047093;
CC Q92529; Q92764: KRT35; NbExp=3; IntAct=EBI-79084, EBI-1058674;
CC Q92529; Q6A163: KRT39; NbExp=3; IntAct=EBI-79084, EBI-11958242;
CC Q92529; Q6A162: KRT40; NbExp=6; IntAct=EBI-79084, EBI-10171697;
CC Q92529; O43790: KRT86; NbExp=3; IntAct=EBI-79084, EBI-9996498;
CC Q92529; Q6P1K2: PMF1; NbExp=3; IntAct=EBI-79084, EBI-713832;
CC Q92529; Q8ND90: PNMA1; NbExp=3; IntAct=EBI-79084, EBI-302345;
CC Q92529; Q96T49: PPP1R16B; NbExp=3; IntAct=EBI-79084, EBI-10293968;
CC Q92529; P31321: PRKAR1B; NbExp=3; IntAct=EBI-79084, EBI-2805516;
CC Q92529; P48556: PSMD8; NbExp=3; IntAct=EBI-79084, EBI-359304;
CC Q92529; Q04864-2: REL; NbExp=3; IntAct=EBI-79084, EBI-10829018;
CC Q92529; Q9H7B4: SMYD3; NbExp=3; IntAct=EBI-79084, EBI-347919;
CC Q92529; O75558: STX11; NbExp=3; IntAct=EBI-79084, EBI-714135;
CC Q92529; Q13077: TRAF1; NbExp=3; IntAct=EBI-79084, EBI-359224;
CC Q92529; Q12933: TRAF2; NbExp=3; IntAct=EBI-79084, EBI-355744;
CC Q92529; Q9UPQ4-2: TRIM35; NbExp=3; IntAct=EBI-79084, EBI-17716262;
CC Q92529; Q9BYV2: TRIM54; NbExp=3; IntAct=EBI-79084, EBI-2130429;
CC Q92529; Q86WV8: TSC1; NbExp=5; IntAct=EBI-79084, EBI-12806590;
CC Q92529; Q5T6F2: UBAP2; NbExp=3; IntAct=EBI-79084, EBI-2514383;
CC Q92529; Q8N6Y0: USHBP1; NbExp=3; IntAct=EBI-79084, EBI-739895;
CC Q92529; Q70EL1-9: USP54; NbExp=3; IntAct=EBI-79084, EBI-11975223;
CC Q92529; Q9UK41-2: VPS28; NbExp=3; IntAct=EBI-79084, EBI-12146727;
CC Q92529; Q9NZC7-5: WWOX; NbExp=5; IntAct=EBI-79084, EBI-12040603;
CC Q92529; P62699: YPEL5; NbExp=3; IntAct=EBI-79084, EBI-11721624;
CC Q92529; Q9H0C1: ZMYND12; NbExp=3; IntAct=EBI-79084, EBI-12030590;
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=p64;
CC IsoId=Q92529-1; Sequence=Displayed;
CC Name=p52;
CC IsoId=Q92529-2; Sequence=VSP_009805;
CC -!- TISSUE SPECIFICITY: Mainly expressed in brain. Hardly detectable in
CC other tissues, except in pancreas. Highly expressed in the cerebral
CC cortex, frontal and temporal lobes, occipital pole, hippocampus,
CC caudate nucleus and amygdala. Expressed at low level in the cerebellum,
CC medulla and spinal cord. {ECO:0000269|PubMed:8808684}.
CC -!- PTM: Tyrosine phosphorylated. {ECO:0000269|PubMed:12006576}.
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DR EMBL; D84361; BAA12322.1; -; mRNA.
DR EMBL; D84361; BAA12323.1; -; mRNA.
DR EMBL; AL160054; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL353150; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC026314; AAH26314.1; -; mRNA.
DR CCDS; CCDS6681.1; -. [Q92529-1]
DR RefSeq; NP_058544.3; NM_016848.5. [Q92529-1]
DR AlphaFoldDB; Q92529; -.
DR SMR; Q92529; -.
DR BioGRID; 119752; 60.
DR CORUM; Q92529; -.
DR IntAct; Q92529; 49.
DR MINT; Q92529; -.
DR STRING; 9606.ENSP00000364995; -.
DR GlyGen; Q92529; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q92529; -.
DR PhosphoSitePlus; Q92529; -.
DR BioMuta; SHC3; -.
DR DMDM; 48474922; -.
DR jPOST; Q92529; -.
DR MassIVE; Q92529; -.
DR MaxQB; Q92529; -.
DR PaxDb; Q92529; -.
DR PeptideAtlas; Q92529; -.
DR PRIDE; Q92529; -.
DR ProteomicsDB; 75289; -. [Q92529-1]
DR ProteomicsDB; 75290; -. [Q92529-2]
DR Antibodypedia; 27964; 225 antibodies from 29 providers.
DR DNASU; 53358; -.
DR Ensembl; ENST00000375835.9; ENSP00000364995.4; ENSG00000148082.10. [Q92529-1]
DR GeneID; 53358; -.
DR KEGG; hsa:53358; -.
DR MANE-Select; ENST00000375835.9; ENSP00000364995.4; NM_016848.6; NP_058544.3.
DR UCSC; uc004aqf.2; human. [Q92529-1]
DR CTD; 53358; -.
DR DisGeNET; 53358; -.
DR GeneCards; SHC3; -.
DR HGNC; HGNC:18181; SHC3.
DR HPA; ENSG00000148082; Tissue enhanced (brain).
DR MIM; 605263; gene.
DR neXtProt; NX_Q92529; -.
DR OpenTargets; ENSG00000148082; -.
DR PharmGKB; PA134913435; -.
DR VEuPathDB; HostDB:ENSG00000148082; -.
DR eggNOG; KOG3697; Eukaryota.
DR GeneTree; ENSGT00950000182870; -.
DR HOGENOM; CLU_029532_2_1_1; -.
DR InParanoid; Q92529; -.
DR OMA; DGLDQTY; -.
DR OrthoDB; 1351843at2759; -.
DR PhylomeDB; Q92529; -.
DR TreeFam; TF315807; -.
DR PathwayCommons; Q92529; -.
DR Reactome; R-HSA-167044; Signalling to RAS.
DR Reactome; R-HSA-5673001; RAF/MAP kinase cascade.
DR Reactome; R-HSA-8853659; RET signaling.
DR SignaLink; Q92529; -.
DR SIGNOR; Q92529; -.
DR BioGRID-ORCS; 53358; 15 hits in 1073 CRISPR screens.
DR ChiTaRS; SHC3; human.
DR GeneWiki; SHC3; -.
DR GenomeRNAi; 53358; -.
DR Pharos; Q92529; Tbio.
DR PRO; PR:Q92529; -.
DR Proteomes; UP000005640; Chromosome 9.
DR RNAct; Q92529; protein.
DR Bgee; ENSG00000148082; Expressed in Brodmann (1909) area 23 and 155 other tissues.
DR ExpressionAtlas; Q92529; baseline and differential.
DR Genevisible; Q92529; HS.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
DR GO; GO:0001784; F:phosphotyrosine residue binding; IPI:CAFA.
DR GO; GO:0019901; F:protein kinase binding; IBA:GO_Central.
DR GO; GO:0030971; F:receptor tyrosine kinase binding; IBA:GO_Central.
DR GO; GO:0007417; P:central nervous system development; TAS:ProtInc.
DR GO; GO:0007173; P:epidermal growth factor receptor signaling pathway; TAS:ProtInc.
DR GO; GO:0035556; P:intracellular signal transduction; IEA:InterPro.
DR GO; GO:0007169; P:transmembrane receptor protein tyrosine kinase signaling pathway; IBA:GO_Central.
DR CDD; cd01209; PTB_Shc; 1.
DR CDD; cd09925; SH2_SHC; 1.
DR Gene3D; 2.30.29.30; -; 1.
DR Gene3D; 3.30.505.10; -; 1.
DR InterPro; IPR011993; PH-like_dom_sf.
DR InterPro; IPR006019; PID_Shc-like.
DR InterPro; IPR006020; PTB/PI_dom.
DR InterPro; IPR000980; SH2.
DR InterPro; IPR036860; SH2_dom_sf.
DR InterPro; IPR029593; Shc3/ShcC/N-Shc.
DR InterPro; IPR035676; SHC_SH2.
DR PANTHER; PTHR10337:SF4; PTHR10337:SF4; 1.
DR Pfam; PF00640; PID; 1.
DR Pfam; PF00017; SH2; 1.
DR PRINTS; PR00401; SH2DOMAIN.
DR PRINTS; PR00629; SHCPIDOMAIN.
DR SMART; SM00462; PTB; 1.
DR SMART; SM00252; SH2; 1.
DR SUPFAM; SSF55550; SSF55550; 1.
DR PROSITE; PS01179; PID; 1.
DR PROSITE; PS50001; SH2; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Phosphoprotein; Reference proteome; SH2 domain.
FT CHAIN 1..594
FT /note="SHC-transforming protein 3"
FT /id="PRO_0000097734"
FT DOMAIN 149..334
FT /note="PID"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00148"
FT DOMAIN 499..590
FT /note="SH2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00191"
FT REGION 98..147
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 335..498
FT /note="CH1"
FT REGION 351..373
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 386..405
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 402
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q61120"
FT VAR_SEQ 1..155
FT /note="MLPRTKYNRFRNDSVTSVDDLLHSLSVSGGGGKVSAARATPAAAPYLVSGEA
FT LRKAPDDGPGSLGHLLHKVSHLKLSSSGLRGLSSAARERAGARLSGSCSAPSLAAPDGS
FT APSAPRAPAMSAARKGRPGDEPLPRPPRGAPHASDQVLGPGVTY -> MHARAAASVMD
FT ICRIRLLIRLTIGLERPPGQV (in isoform p52)"
FT /evidence="ECO:0000303|PubMed:8760305,
FT ECO:0000303|PubMed:8808684"
FT /id="VSP_009805"
FT CONFLICT 58
FT /note="D -> V (in Ref. 4; AAH26314)"
FT /evidence="ECO:0000305"
FT CONFLICT 201
FT /note="K -> R (in Ref. 2)"
FT /evidence="ECO:0000305"
FT CONFLICT 271
FT /note="A -> T (in Ref. 4; AAH26314)"
FT /evidence="ECO:0000305"
FT CONFLICT 553
FT /note="I -> E (in Ref. 2)"
FT /evidence="ECO:0000305"
FT CONFLICT 554
FT /note="R -> Q (in Ref. 4; AAH26314)"
FT /evidence="ECO:0000305"
FT CONFLICT 593..594
FT /note="KQ -> NE (in Ref. 2)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 594 AA; 64056 MW; 047A9D08002E41BF CRC64;
MLPRTKYNRF RNDSVTSVDD LLHSLSVSGG GGKVSAARAT PAAAPYLVSG EALRKAPDDG
PGSLGHLLHK VSHLKLSSSG LRGLSSAARE RAGARLSGSC SAPSLAAPDG SAPSAPRAPA
MSAARKGRPG DEPLPRPPRG APHASDQVLG PGVTYVVKYL GCIEVLRSMR SLDFSTRTQI
TREAISRVCE AVPGAKGAFK KRKPPSKMLS SILGKSNLQF AGMSISLTIS TASLNLRTPD
SKQIIANHHM RSISFASGGD PDTTDYVAYV AKDPVNRRAC HILECCDGLA QDVIGSIGQA
FELRFKQYLQ CPTKIPALHD RMQSLDEPWT EEEGDGSDHP YYNSIPSKMP PPGGFLDTRL
KPRPHAPDTA QFAGKEQTYY QGRHLGDTFG EDWQQTPLRQ GSSDIYSTPE GKLHVAPTGE
APTYVNTQQI PPQAWPAAVS SAESSPRKDL FDMKPFEDAL KNQPLGPVLS KAASVECISP
VSPRAPDAKM LEELQAETWY QGEMSRKEAE GLLEKDGDFL VRKSTTNPGS FVLTGMHNGQ
AKHLLLVDPE GTIRTKDRVF DSISHLINHH LESSLPIVSA GSELCLQQPV ERKQ
