ID SHCH1_CAEEL Reviewed; 316 AA.
AC Q9TYT3; H2KZG0; H2KZG2;
DT 22-JUL-2015, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2002, sequence version 2.
DT 27-MAR-2024, entry version 154.
DE RecName: Full=SHC-transforming protein homolog 1 {ECO:0000250|UniProtKB:P29353};
DE AltName: Full=Src homology 2 domain adapter homolog 1 {ECO:0000305};
GN Name=shc-1 {ECO:0000312|WormBase:F54A5.3a};
GN ORFNames=F54A5.3 {ECO:0000312|WormBase:F54A5.3a};
OS Caenorhabditis elegans.
OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC Caenorhabditis.
OX NCBI_TaxID=6239 {ECO:0000312|Proteomes:UP000001940};
RN [1] {ECO:0000312|Proteomes:UP000001940}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Bristol N2 {ECO:0000312|Proteomes:UP000001940};
RX PubMed=9851916; DOI=10.1126/science.282.5396.2012;
RG The C. elegans sequencing consortium;
RT "Genome sequence of the nematode C. elegans: a platform for investigating
RT biology.";
RL Science 282:2012-2018(1998).
RN [2] {ECO:0000305}
RP FUNCTION, INTERACTION WITH DAF-2 AND MEK-1, SUBCELLULAR LOCATION, AND
RP TISSUE SPECIFICITY.
RX PubMed=18832074; DOI=10.1101/gad.478408;
RA Neumann-Haefelin E., Qi W., Finkbeiner E., Walz G., Baumeister R.,
RA Hertweck M.;
RT "SHC-1/p52Shc targets the insulin/IGF-1 and JNK signaling pathways to
RT modulate life span and stress response in C. elegans.";
RL Genes Dev. 22:2721-2735(2008).
RN [3] {ECO:0000305}
RP FUNCTION, INTERACTION WITH MEK-1 AND MLK-1, TISSUE SPECIFICITY, AND
RP MUTAGENESIS OF ARG-136 AND ARG-234.
RX PubMed=18809575; DOI=10.1128/mcb.00938-08;
RA Mizuno T., Fujiki K., Sasakawa A., Hisamoto N., Matsumoto K.;
RT "Role of the Caenorhabditis elegans Shc adaptor protein in the c-Jun N-
RT terminal kinase signaling pathway.";
RL Mol. Cell. Biol. 28:7041-7049(2008).
RN [4] {ECO:0000305}
RP FUNCTION, AND INTERACTION WITH MLK-1.
RX PubMed=23072806; DOI=10.1038/ncomms2136;
RA Pastuhov S.I., Fujiki K., Nix P., Kanao S., Bastiani M., Matsumoto K.,
RA Hisamoto N.;
RT "Endocannabinoid-Goalpha signalling inhibits axon regeneration in
RT Caenorhabditis elegans by antagonizing Gqalpha-PKC-JNK signalling.";
RL Nat. Commun. 3:1136-1136(2012).
RN [5]
RP FUNCTION.
RX PubMed=22916022; DOI=10.1371/journal.pgen.1002836;
RA Qi W., Huang X., Neumann-Haefelin E., Schulze E., Baumeister R.;
RT "Cell-nonautonomous signaling of FOXO/DAF-16 to the stem cells of
RT Caenorhabditis elegans.";
RL PLoS Genet. 8:e1002836-e1002836(2012).
RN [6]
RP FUNCTION.
RX PubMed=24746511; DOI=10.1016/j.exger.2014.04.002;
RA Wolf T., Qi W., Schindler V., Runkel E.D., Baumeister R.;
RT "Doxycyclin ameliorates a starvation-induced germline tumor in C. elegans
RT daf-18/PTEN mutant background.";
RL Exp. Gerontol. 56:114-122(2014).
RN [7]
RP FUNCTION, INTERACTION WITH SVH-2 AND SVH-4, AND MUTAGENESIS OF ARG-234.
RX PubMed=27984580; DOI=10.1371/journal.pgen.1006475;
RA Hisamoto N., Nagamori Y., Shimizu T., Pastuhov S.I., Matsumoto K.;
RT "The C. elegans discoidin domain receptor DDR-2 modulates the Met-like RTK-
RT JNK signaling pathway in axon regeneration.";
RL PLoS Genet. 12:E1006475-E1006475(2016).
CC -!- FUNCTION: Scaffold protein which plays an important role in the
CC activation of the JNK pathway composed of mlk-1, mek-1 and kgb-1; by
CC bringing together mek-1 and mlk-1, promotes mlk-1-mediated
CC phosphorylation and activation of mek-1 which in turn phosphorylates
CC kgb-1 (PubMed:18832074, PubMed:18809575, PubMed:22916022). In addition,
CC negatively modulates the activation of the insulin/IGF-1-like signaling
CC (IIS) probably by inhibiting the insulin receptor daf-2
CC (PubMed:18832074, PubMed:22916022). Positively regulates the activity
CC of the transcription factor daf-16/FOXO by both inhibiting IIS and
CC activating the JNK pathway (PubMed:18832074, PubMed:22916022). Plays a
CC role in maintaining gonadal basement membrane integrity through
CC activation of the JNK pathway components mek-1 and jnk-1
CC (PubMed:22916022). Involved in the response to several environmental
CC stresses including heavy metal ions (Cu(2+) and Cd(2+)), heat,
CC oxidative and protein misfolding (ER) stresses (PubMed:18832074,
CC PubMed:18809575). Plays a role in gonad and germline development
CC following the L1 diapause (PubMed:24746511). Plays a role in life span
CC and egg laying (PubMed:18832074, PubMed:23072806). Plays a role in axon
CC regeneration after injury (PubMed:23072806, PubMed:27984580).
CC {ECO:0000269|PubMed:18809575, ECO:0000269|PubMed:18832074,
CC ECO:0000269|PubMed:22916022, ECO:0000269|PubMed:23072806,
CC ECO:0000269|PubMed:24746511, ECO:0000269|PubMed:27984580}.
CC -!- SUBUNIT: Interacts (via PID domain) with daf-2 (via cytoplasmic domain)
CC (PubMed:18832074). Interacts with mek-1; the interaction is independent
CC of mek-1 catalytic activity and is constitutive (PubMed:18832074,
CC PubMed:18809575). Interacts (via N-terminus) with mlk-1 (via NPQY motif
CC when phosphorylated on tyrosine residue) (PubMed:18809575,
CC PubMed:23072806). Does not interact with jkk-1 or sek-1
CC (PubMed:18809575). Interacts (via SH2 domain) with svh-2
CC (PubMed:27984580). Interacts with svh-4 (PubMed:27984580).
CC {ECO:0000269|PubMed:18809575, ECO:0000269|PubMed:18832074,
CC ECO:0000269|PubMed:23072806, ECO:0000269|PubMed:27984580}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:18832074}. Nucleus
CC {ECO:0000269|PubMed:18832074}. Cell membrane
CC {ECO:0000269|PubMed:18832074}; Peripheral membrane protein
CC {ECO:0000269|PubMed:18832074}. Note=In intestinal cells, enriched in
CC the nucleus. {ECO:0000269|PubMed:18832074}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=a {ECO:0000312|WormBase:F54A5.3a};
CC IsoId=Q9TYT3-1; Sequence=Displayed;
CC Name=b {ECO:0000312|WormBase:F54A5.3b};
CC IsoId=Q9TYT3-2; Sequence=VSP_061752;
CC -!- TISSUE SPECIFICITY: Expressed in hypodermis, intestine, head and tail
CC neurons, pharynx, gonads, vulva and body muscles.
CC {ECO:0000269|PubMed:18809575, ECO:0000269|PubMed:18832074}.
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DR EMBL; BX284601; CCD68061.1; -; Genomic_DNA.
DR EMBL; BX284601; CCD68062.2; -; Genomic_DNA.
DR PIR; T33836; T33836.
DR RefSeq; NP_490799.2; NM_058398.4. [Q9TYT3-1]
DR RefSeq; NP_490800.2; NM_058399.4.
DR AlphaFoldDB; Q9TYT3; -.
DR SMR; Q9TYT3; -.
DR DIP; DIP-25661N; -.
DR IntAct; Q9TYT3; 2.
DR STRING; 6239.F54A5.3a.1; -.
DR EPD; Q9TYT3; -.
DR PaxDb; 6239-F54A5-3a; -.
DR PeptideAtlas; Q9TYT3; -.
DR EnsemblMetazoa; F54A5.3a.1; F54A5.3a.1; WBGene00018788. [Q9TYT3-1]
DR EnsemblMetazoa; F54A5.3b.1; F54A5.3b.1; WBGene00018788. [Q9TYT3-2]
DR EnsemblMetazoa; F54A5.3b.2; F54A5.3b.2; WBGene00018788. [Q9TYT3-2]
DR EnsemblMetazoa; F54A5.3b.3; F54A5.3b.3; WBGene00018788. [Q9TYT3-2]
DR GeneID; 3565745; -.
DR KEGG; cel:CELE_F54A5.3; -.
DR UCSC; F54A5.3a; c. elegans. [Q9TYT3-1]
DR AGR; WB:WBGene00018788; -.
DR WormBase; F54A5.3a; CE30804; WBGene00018788; shc-1.
DR WormBase; F54A5.3b; CE50617; WBGene00018788; shc-1.
DR eggNOG; KOG3697; Eukaryota.
DR GeneTree; ENSGT00950000182870; -.
DR HOGENOM; CLU_861198_0_0_1; -.
DR InParanoid; Q9TYT3; -.
DR OMA; VKECINM; -.
DR OrthoDB; 2903566at2759; -.
DR PhylomeDB; Q9TYT3; -.
DR SignaLink; Q9TYT3; -.
DR PRO; PR:Q9TYT3; -.
DR Proteomes; UP000001940; Chromosome I.
DR Bgee; WBGene00018788; Expressed in pharyngeal muscle cell (C elegans) and 4 other cell types or tissues.
DR GO; GO:0005737; C:cytoplasm; IDA:WormBase.
DR GO; GO:0005634; C:nucleus; IDA:WormBase.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005159; F:insulin-like growth factor receptor binding; IPI:WormBase.
DR GO; GO:0031434; F:mitogen-activated protein kinase kinase binding; IPI:WormBase.
DR GO; GO:0031435; F:mitogen-activated protein kinase kinase kinase binding; IPI:UniProtKB.
DR GO; GO:0048680; P:positive regulation of axon regeneration; IMP:UniProtKB.
DR GO; GO:0034976; P:response to endoplasmic reticulum stress; IMP:WormBase.
DR GO; GO:0010038; P:response to metal ion; IMP:WormBase.
DR CDD; cd00934; PTB; 1.
DR CDD; cd09925; SH2_SHC; 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; IPR006020; PTB/PI_dom.
DR InterPro; IPR000980; SH2.
DR InterPro; IPR036860; SH2_dom_sf.
DR InterPro; IPR035676; SHC_SH2.
DR PANTHER; PTHR19969:SF5; ADAPTER MOLECULE CRK; 1.
DR PANTHER; PTHR19969; SH2-SH3 ADAPTOR PROTEIN-RELATED; 1.
DR Pfam; PF00640; PID; 1.
DR Pfam; PF00017; SH2; 1.
DR PRINTS; PR00401; SH2DOMAIN.
DR SMART; SM00462; PTB; 1.
DR SMART; SM00252; SH2; 1.
DR SUPFAM; SSF50729; PH domain-like; 1.
DR SUPFAM; SSF55550; SH2 domain; 1.
DR PROSITE; PS01179; PID; 1.
DR PROSITE; PS50001; SH2; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell membrane; Cytoplasm; Membrane; Nucleus;
KW Reference proteome; SH2 domain; Stress response.
FT CHAIN 1..316
FT /note="SHC-transforming protein homolog 1"
FT /evidence="ECO:0000305"
FT /id="PRO_0000433512"
FT DOMAIN 16..158
FT /note="PID"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00148"
FT DOMAIN 211..307
FT /note="SH2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00191"
FT REGION 292..316
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT SITE 234
FT /note="Required for interaction with svh-2"
FT /evidence="ECO:0000269|PubMed:27984580"
FT VAR_SEQ 1..89
FT /note="Missing (in isoform b)"
FT /evidence="ECO:0000305"
FT /id="VSP_061752"
FT MUTAGEN 136
FT /note="R->K: Partial sensitivity to Cu(2+). May prevent
FT interaction with mlk-1 when phosphorylated at Tyr-209 which
FT in turn may prevent the interaction between mlk-1 and mek-
FT 1. No effect on the association with mek-1. Severe
FT sensitivity to Cu(2+) and no effect on the association with
FT mek-1; when associated with K-234."
FT /evidence="ECO:0000269|PubMed:18809575"
FT MUTAGEN 234
FT /note="R->K: Weak sensitivity to Cu(2+). Severe sensitivity
FT to Cu(2+) and no effect on the association with mek-1; when
FT associated with K-136. Abolishes interaction with svh-2."
FT /evidence="ECO:0000269|PubMed:18809575,
FT ECO:0000269|PubMed:27984580"
SQ SEQUENCE 316 AA; 35170 MW; D370FF4B941F97E1 CRC64;
MLNVEPSFAE ELRSSGVSLS ATYLGSVPVV ESINVMVSEM RVQVVSECIQ HVAATVGVTA
AREINPVVSR VIGEVKKENF PVDINISSKM IKIIKQSRLI QRHPFSFFSF GAQGQKGTDT
ELMFGYIAKN KDGTDRRCHV VFIEDVHKLI DVLTTAINVN TFDAQANAST SNDGFTVPAP
PMRHRSSLHR QSFVSNCRAP TVTEDVVGKV WYHGNLSRED AQALLKTEGD FLVRQSDHTP
GKYVLSGRTA ENEHKHLILL DNHNRVRTRD RTFSNISELI DYHVNNGMAV RSEGRDRETS
LNLIRPVPCP GSDDIE
//
