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P98077

- SHC2_HUMAN

UniProt

P98077 - SHC2_HUMAN

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Protein

SHC-transforming protein 2

Gene

SHC2

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli

Functioni

Signaling adapter that couples activated growth factor receptors to signaling pathway in neurons. Involved in the signal transduction pathways of neurotrophin-activated Trk receptors in cortical neurons (By similarity).By similarity

GO - Biological processi

  1. activation of MAPK activity Source: InterPro
  2. insulin receptor signaling pathway Source: Reactome
  3. neurotrophin TRK receptor signaling pathway Source: Reactome
  4. Ras protein signal transduction Source: Reactome
Complete GO annotation...

Enzyme and pathway databases

ReactomeiREACT_12033. Signalling to RAS.
REACT_508. Signal attenuation.
REACT_661. SHC-mediated signalling.
SignaLinkiP98077.

Names & Taxonomyi

Protein namesi
Recommended name:
SHC-transforming protein 2
Alternative name(s):
Protein Sck
SHC-transforming protein B
Src homology 2 domain-containing-transforming protein C2
Short name:
SH2 domain protein C2
Gene namesi
Name:SHC2
Synonyms:SCK, SHCB
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 19

Organism-specific databases

HGNCiHGNC:29869. SHC2.

Subcellular locationi

GO - Cellular componenti

  1. cytosol Source: Reactome
Complete GO annotation...

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA134971076.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 582582SHC-transforming protein 2PRO_0000097732Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei338 – 3381Phosphotyrosine1 Publication
Modified residuei339 – 3391Phosphotyrosine1 Publication
Modified residuei414 – 4141Phosphotyrosine1 Publication

Post-translational modificationi

Phosphorylated on tyrosines by the Trk receptors.1 Publication

Keywords - PTMi

Phosphoprotein

Proteomic databases

PaxDbiP98077.
PRIDEiP98077.

PTM databases

PhosphoSiteiP98077.

Expressioni

Tissue specificityi

Expressed in brain. Expressed at high level in the hypothalamus and at low level in the caudate nucleus.1 Publication

Gene expression databases

BgeeiP98077.
CleanExiHS_SHC2.
GenevestigatoriP98077.

Organism-specific databases

HPAiHPA006136.

Interactioni

Subunit structurei

Interacts with the Trk receptors in a phosphotyrosine-dependent manner and MEGF12. Once activated, binds to GRB2.3 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
EGFRP005333EBI-7256023,EBI-297353
ERBB2P046263EBI-7256023,EBI-641062
KITP107215EBI-7256023,EBI-1379503
METP085812EBI-7256023,EBI-1039152

Protein-protein interaction databases

BioGridi117302. 5 interactions.
IntActiP98077. 5 interactions.
MINTiMINT-127694.
STRINGi9606.ENSP00000264554.

Structurei

3D structure databases

ProteinModelPortaliP98077.
SMRiP98077. Positions 124-306, 480-581.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini147 – 329183PIDPROSITE-ProRule annotationAdd
BLAST
Domaini487 – 57892SH2PROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni330 – 486157CH1Add
BLAST

Domaini

The PID domain mediates binding to the TrkA receptor.

Sequence similaritiesi

Contains 1 PID domain.PROSITE-ProRule annotation
Contains 1 SH2 domain.PROSITE-ProRule annotation

Keywords - Domaini

SH2 domain

Phylogenomic databases

eggNOGiNOG315087.
GeneTreeiENSGT00390000018860.
HOGENOMiHOG000231974.
HOVERGENiHBG050121.
InParanoidiP98077.
KOiK17447.
OMAiGACEPRC.
OrthoDBiEOG7MD4QK.
PhylomeDBiP98077.
TreeFamiTF315807.

Family and domain databases

Gene3Di2.30.29.30. 1 hit.
3.30.505.10. 1 hit.
InterProiIPR011993. PH_like_dom.
IPR006019. PID_Shc-like.
IPR006020. PTB/PI_dom.
IPR000980. SH2.
IPR029591. SHC2.
[Graphical view]
PANTHERiPTHR10337:SF5. PTHR10337:SF5. 1 hit.
PfamiPF00640. PID. 1 hit.
PF00017. SH2. 1 hit.
[Graphical view]
PRINTSiPR00401. SH2DOMAIN.
PR00629. SHCPIDOMAIN.
SMARTiSM00462. PTB. 1 hit.
SM00252. SH2. 1 hit.
[Graphical view]
SUPFAMiSSF55550. SSF55550. 1 hit.
PROSITEiPS01179. PID. 1 hit.
PS50001. SH2. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

P98077-1 [UniParc]FASTAAdd to Basket

« Hide

        10         20         30         40         50
MTQGPGGRAP PAPPAPPEPE APTTFCALLP RMPQWKFAAP GGFLGRGPAA
60 70 80 90 100
ARAAGASGGA DPQPEPAGPG GVPALAAAVL GACEPRCAAP CPLPALSRCR
110 120 130 140 150
GAGSRGSRGG RGAAGSGDAA AAAEWIRKGS FIHKPAHGWL HPDARVLGPG
160 170 180 190 200
VSYVVRYMGC IEVLRSMRSL DFNTRTQVTR EAINRLHEAV PGVRGSWKKK
210 220 230 240 250
APNKALASVL GKSNLRFAGM SISIHISTDG LSLSVPATRQ VIANHHMPSI
260 270 280 290 300
SFASGGDTDM TDYVAYVAKD PINQRACHIL ECCEGLAQSI ISTVGQAFEL
310 320 330 340 350
RFKQYLHSPP KVALPPERLA GPEESAWGDE EDSLEHNYYN SIPGKEPPLG
360 370 380 390 400
GLVDSRLALT QPCALTALDQ GPSPSLRDAC SLPWDVGSTG TAPPGDGYVQ
410 420 430 440 450
ADARGPPDHE EHLYVNTQGL DAPEPEDSPK KDLFDMRPFE DALKLHECSV
460 470 480 490 500
AAGVTAAPLP LEDQWPSPPT RRAPVAPTEE QLRQEPWYHG RMSRRAAERM
510 520 530 540 550
LRADGDFLVR DSVTNPGQYV LTGMHAGQPK HLLLVDPEGV VRTKDVLFES
560 570 580
ISHLIDHHLQ NGQPIVAAES ELHLRGVVSR EP
Length:582
Mass (Da):61,916
Last modified:July 1, 2008 - v4
Checksum:iF640AC298DA37B68
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti45 – 5612GRGPA…RAAGA → IRGSNAQKVVGASG in BAA25798. (PubMed:9507002)CuratedAdd
BLAST
Sequence conflicti61 – 611D → G in BAA25798. (PubMed:9507002)Curated
Sequence conflicti65 – 651E → D in BAA25798. (PubMed:9507002)Curated
Sequence conflicti96 – 12530LSRCR…AAAEW → MAFAGLASHVWWWRPSSQNR IWFRRGSPEF(PubMed:8760305)CuratedAdd
BLAST
Sequence conflicti114 – 1141A → P(PubMed:7527937)Curated
Sequence conflicti188 – 1881E → I(PubMed:8760305)Curated
Sequence conflicti226 – 2261I → T(PubMed:8760305)Curated
Sequence conflicti272 – 2721I → E(PubMed:8760305)Curated
Sequence conflicti440 – 4401Missing(PubMed:8760305)Curated

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
AC008988 Genomic DNA. No translation available.
AC138433 Genomic DNA. No translation available.
AC006124 Genomic DNA. No translation available.
AB001451 mRNA. Translation: BAA25798.1.
AL360254 mRNA. Translation: CAB96175.1.
CCDSiCCDS45891.1.
RefSeqiNP_036567.2. NM_012435.2.
UniGeneiHs.30965.

Genome annotation databases

EnsembliENST00000264554; ENSP00000264554; ENSG00000129946.
GeneIDi25759.
KEGGihsa:25759.
UCSCiuc002loq.4. human.

Polymorphism databases

DMDMi193806386.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
AC008988 Genomic DNA. No translation available.
AC138433 Genomic DNA. No translation available.
AC006124 Genomic DNA. No translation available.
AB001451 mRNA. Translation: BAA25798.1 .
AL360254 mRNA. Translation: CAB96175.1 .
CCDSi CCDS45891.1.
RefSeqi NP_036567.2. NM_012435.2.
UniGenei Hs.30965.

3D structure databases

ProteinModelPortali P98077.
SMRi P98077. Positions 124-306, 480-581.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 117302. 5 interactions.
IntActi P98077. 5 interactions.
MINTi MINT-127694.
STRINGi 9606.ENSP00000264554.

Chemistry

BindingDBi P98077.
ChEMBLi CHEMBL3299.

PTM databases

PhosphoSitei P98077.

Polymorphism databases

DMDMi 193806386.

Proteomic databases

PaxDbi P98077.
PRIDEi P98077.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000264554 ; ENSP00000264554 ; ENSG00000129946 .
GeneIDi 25759.
KEGGi hsa:25759.
UCSCi uc002loq.4. human.

Organism-specific databases

CTDi 25759.
GeneCardsi GC19M000420.
H-InvDB HIX0027436.
HGNCi HGNC:29869. SHC2.
HPAi HPA006136.
MIMi 605217. gene.
neXtProti NX_P98077.
PharmGKBi PA134971076.
GenAtlasi Search...

Phylogenomic databases

eggNOGi NOG315087.
GeneTreei ENSGT00390000018860.
HOGENOMi HOG000231974.
HOVERGENi HBG050121.
InParanoidi P98077.
KOi K17447.
OMAi GACEPRC.
OrthoDBi EOG7MD4QK.
PhylomeDBi P98077.
TreeFami TF315807.

Enzyme and pathway databases

Reactomei REACT_12033. Signalling to RAS.
REACT_508. Signal attenuation.
REACT_661. SHC-mediated signalling.
SignaLinki P98077.

Miscellaneous databases

GeneWikii SHC2.
GenomeRNAii 25759.
NextBioi 46868.
PROi P98077.
SOURCEi Search...

Gene expression databases

Bgeei P98077.
CleanExi HS_SHC2.
Genevestigatori P98077.

Family and domain databases

Gene3Di 2.30.29.30. 1 hit.
3.30.505.10. 1 hit.
InterProi IPR011993. PH_like_dom.
IPR006019. PID_Shc-like.
IPR006020. PTB/PI_dom.
IPR000980. SH2.
IPR029591. SHC2.
[Graphical view ]
PANTHERi PTHR10337:SF5. PTHR10337:SF5. 1 hit.
Pfami PF00640. PID. 1 hit.
PF00017. SH2. 1 hit.
[Graphical view ]
PRINTSi PR00401. SH2DOMAIN.
PR00629. SHCPIDOMAIN.
SMARTi SM00462. PTB. 1 hit.
SM00252. SH2. 1 hit.
[Graphical view ]
SUPFAMi SSF55550. SSF55550. 1 hit.
PROSITEi PS01179. PID. 1 hit.
PS50001. SH2. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  1. "The DNA sequence and biology of human chromosome 19."
    Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E., Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A., Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S., Carrano A.V.
    , Caoile C., Chan Y.M., Christensen M., Cleland C.A., Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J., Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M., Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W., Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V., Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D., McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I., Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L., Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E., Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M., Rubin E.M., Lucas S.M.
    Nature 428:529-535(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  2. "N-Shc and Sck, two neuronally expressed Shc adapter homologs. Their differential regional expression in the brain and roles in neurotrophin and Src signaling."
    Nakamura T., Muraoka S., Sanokawa R., Mori N.
    J. Biol. Chem. 273:6960-6967(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 45-582, INTERACTION WITH THE TRK RECEPTORS, TISSUE SPECIFICITY.
  3. "A family of Shc related proteins with conserved PTB, CH1 and SH2 regions."
    Pelicci G., Dente L., De Giuseppe A., Verducci-Galletti B., Giuli S., Mele S., Vetriani C., Giorgio M., Pandolfi P.P., Cesareni G., Pelicci P.-G.
    Oncogene 13:633-641(1996) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 96-582.
    Tissue: Fetal brain.
  4. "An alternative to SH2 domains for binding tyrosine-phosphorylated proteins."
    Kavanaugh W.M., Williams L.T.
    Science 266:1862-1865(1994) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 114-541.
  5. The European IMAGE consortium
    Submitted (JUL-2000) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 191-582.
  6. "ShcB and ShcC activation by the Trk family of receptor tyrosine kinases."
    Liu H.Y., Meakin S.O.
    J. Biol. Chem. 277:26046-26056(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION, INTERACTION WITH THE TRK RECEPTORS.
  7. "Platelet endothelial aggregation receptor 1 (PEAR1), a novel epidermal growth factor repeat-containing transmembrane receptor, participates in platelet contact-induced activation."
    Nanda N., Bao M., Lin H., Clauser K., Komuves L., Quertermous T., Conley P.B., Phillips D.R., Hart M.J.
    J. Biol. Chem. 280:24680-24689(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH MEGF12.
    Tissue: Platelet.

Entry informationi

Entry nameiSHC2_HUMAN
AccessioniPrimary (citable) accession number: P98077
Secondary accession number(s): O60230, Q9NPL5, Q9UCX4
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 1, 1996
Last sequence update: July 1, 2008
Last modified: October 29, 2014
This is version 120 of the entry and version 4 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Miscellaneous

PubMed:15057824 has shown that SHC2 is poorly phosphorylated by the Trk receptors, in opposite to PubMed:12006576.

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 19
    Human chromosome 19: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3