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Protein

SHC-transforming protein 3

Gene

SHC3

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: 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.

GO - Molecular functioni

  • protein kinase binding Source: GO_Central
  • receptor tyrosine kinase binding Source: GO_Central
  • signal transducer activity Source: ProtInc

GO - Biological processi

Complete GO annotation...

Enzyme and pathway databases

ReactomeiREACT_12033. Signalling to RAS.
REACT_508. Signal attenuation.
REACT_661. SHC-mediated signalling.
SignaLinkiQ92529.

Names & Taxonomyi

Protein namesi
Recommended name:
SHC-transforming protein 3
Alternative name(s):
Neuronal Shc
Short name:
N-Shc
Protein Rai
SHC-transforming protein C
Src homology 2 domain-containing-transforming protein C3
Short name:
SH2 domain protein C3
Gene namesi
Name:SHC3
Synonyms:NSHC, SHCC
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640 Componenti: Chromosome 9

Organism-specific databases

HGNCiHGNC:18181. SHC3.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA134913435.

Polymorphism and mutation databases

BioMutaiSHC3.
DMDMi48474922.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 594594SHC-transforming protein 3PRO_0000097734Add
BLAST

Post-translational modificationi

Tyrosine phosphorylated.1 Publication

Keywords - PTMi

Phosphoprotein

Proteomic databases

PaxDbiQ92529.
PRIDEiQ92529.

PTM databases

PhosphoSiteiQ92529.

Expressioni

Tissue specificityi

Mainly expressed in brain. Hardly detectable in other tissues, except in pancreas. Highly expressed in the cerebral cortex, frontal and temporal lobes, occipital pole, hippocampus, caudate nucleus and amygdala. Expressed at low level in the cerebellum, medulla and spinal cord.1 Publication

Gene expression databases

BgeeiQ92529.
CleanExiHS_SHC3.
ExpressionAtlasiQ92529. baseline and differential.
GenevisibleiQ92529. HS.

Organism-specific databases

HPAiHPA046656.

Interactioni

Subunit structurei

Interacts with the Trk receptors in a phosphotyrosine-dependent manner. Once activated, binds to GRB2. Interacts with activated EGF receptors.1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
APPP050672EBI-79084,EBI-77613
ERBB2P046262EBI-79084,EBI-641062
ERBB3P218602EBI-79084,EBI-720706
GOLGA2Q083793EBI-79084,EBI-618309
KITP107213EBI-79084,EBI-1379503
KRT31Q153233EBI-79084,EBI-948001
KRT40Q6A1623EBI-79084,EBI-10171697

Protein-protein interaction databases

BioGridi119752. 12 interactions.
IntActiQ92529. 12 interactions.
MINTiMINT-1492377.
STRINGi9606.ENSP00000364995.

Structurei

3D structure databases

ProteinModelPortaliQ92529.
SMRiQ92529. Positions 136-310, 492-593.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini149 – 334186PIDPROSITE-ProRule annotationAdd
BLAST
Domaini499 – 59092SH2PROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni335 – 498164CH1Add
BLAST

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.
InParanoidiQ92529.
KOiK17448.
OMAiGSDHPYY.
OrthoDBiEOG7MD4QK.
PhylomeDBiQ92529.
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.
IPR029593. Shc3/ShcC/N-Shc.
[Graphical view]
PANTHERiPTHR10337:SF4. PTHR10337:SF4. 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]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform p64 (identifier: Q92529-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MLPRTKYNRF RNDSVTSVDD LLHSLSVSGG GGKVSAARAT PAAAPYLVSG
60 70 80 90 100
EALRKAPDDG PGSLGHLLHK VSHLKLSSSG LRGLSSAARE RAGARLSGSC
110 120 130 140 150
SAPSLAAPDG SAPSAPRAPA MSAARKGRPG DEPLPRPPRG APHASDQVLG
160 170 180 190 200
PGVTYVVKYL GCIEVLRSMR SLDFSTRTQI TREAISRVCE AVPGAKGAFK
210 220 230 240 250
KRKPPSKMLS SILGKSNLQF AGMSISLTIS TASLNLRTPD SKQIIANHHM
260 270 280 290 300
RSISFASGGD PDTTDYVAYV AKDPVNRRAC HILECCDGLA QDVIGSIGQA
310 320 330 340 350
FELRFKQYLQ CPTKIPALHD RMQSLDEPWT EEEGDGSDHP YYNSIPSKMP
360 370 380 390 400
PPGGFLDTRL KPRPHAPDTA QFAGKEQTYY QGRHLGDTFG EDWQQTPLRQ
410 420 430 440 450
GSSDIYSTPE GKLHVAPTGE APTYVNTQQI PPQAWPAAVS SAESSPRKDL
460 470 480 490 500
FDMKPFEDAL KNQPLGPVLS KAASVECISP VSPRAPDAKM LEELQAETWY
510 520 530 540 550
QGEMSRKEAE GLLEKDGDFL VRKSTTNPGS FVLTGMHNGQ AKHLLLVDPE
560 570 580 590
GTIRTKDRVF DSISHLINHH LESSLPIVSA GSELCLQQPV ERKQ
Length:594
Mass (Da):64,056
Last modified:February 1, 1997 - v1
Checksum:i047A9D08002E41BF
GO
Isoform p52 (identifier: Q92529-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-155: MLPRTKYNRF...DQVLGPGVTY → MHARAAASVMDICRIRLLIRLTIGLERPPGQV

Show »
Length:471
Mass (Da):51,939
Checksum:iBE74C85B97AF30CE
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti58 – 581D → V in AAH26314 (PubMed:15489334).Curated
Sequence conflicti201 – 2011K → R (PubMed:8760305).Curated
Sequence conflicti271 – 2711A → T in AAH26314 (PubMed:15489334).Curated
Sequence conflicti553 – 5531I → E (PubMed:8760305).Curated
Sequence conflicti554 – 5541R → Q in AAH26314 (PubMed:15489334).Curated
Sequence conflicti593 – 5942KQ → NE (PubMed:8760305).Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 155155MLPRT…PGVTY → MHARAAASVMDICRIRLLIR LTIGLERPPGQV in isoform p52. 2 PublicationsVSP_009805Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D84361 mRNA. Translation: BAA12322.1.
D84361 mRNA. Translation: BAA12323.1.
AL353150, AL160054 Genomic DNA. Translation: CAI16865.1.
AL160054, AL353150 Genomic DNA. Translation: CAI41366.1.
BC026314 mRNA. Translation: AAH26314.1.
CCDSiCCDS6681.1. [Q92529-1]
RefSeqiNP_058544.3. NM_016848.5. [Q92529-1]
UniGeneiHs.292737.

Genome annotation databases

EnsembliENST00000375835; ENSP00000364995; ENSG00000148082.
GeneIDi53358.
KEGGihsa:53358.
UCSCiuc004aqf.2. human. [Q92529-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D84361 mRNA. Translation: BAA12322.1.
D84361 mRNA. Translation: BAA12323.1.
AL353150, AL160054 Genomic DNA. Translation: CAI16865.1.
AL160054, AL353150 Genomic DNA. Translation: CAI41366.1.
BC026314 mRNA. Translation: AAH26314.1.
CCDSiCCDS6681.1. [Q92529-1]
RefSeqiNP_058544.3. NM_016848.5. [Q92529-1]
UniGeneiHs.292737.

3D structure databases

ProteinModelPortaliQ92529.
SMRiQ92529. Positions 136-310, 492-593.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi119752. 12 interactions.
IntActiQ92529. 12 interactions.
MINTiMINT-1492377.
STRINGi9606.ENSP00000364995.

PTM databases

PhosphoSiteiQ92529.

Polymorphism and mutation databases

BioMutaiSHC3.
DMDMi48474922.

Proteomic databases

PaxDbiQ92529.
PRIDEiQ92529.

Protocols and materials databases

DNASUi53358.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000375835; ENSP00000364995; ENSG00000148082.
GeneIDi53358.
KEGGihsa:53358.
UCSCiuc004aqf.2. human. [Q92529-1]

Organism-specific databases

CTDi53358.
GeneCardsiGC09M091628.
HGNCiHGNC:18181. SHC3.
HPAiHPA046656.
MIMi605263. gene.
neXtProtiNX_Q92529.
PharmGKBiPA134913435.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG315087.
GeneTreeiENSGT00390000018860.
HOGENOMiHOG000231974.
HOVERGENiHBG050121.
InParanoidiQ92529.
KOiK17448.
OMAiGSDHPYY.
OrthoDBiEOG7MD4QK.
PhylomeDBiQ92529.
TreeFamiTF315807.

Enzyme and pathway databases

ReactomeiREACT_12033. Signalling to RAS.
REACT_508. Signal attenuation.
REACT_661. SHC-mediated signalling.
SignaLinkiQ92529.

Miscellaneous databases

ChiTaRSiSHC3. human.
GeneWikiiSHC3.
GenomeRNAii53358.
NextBioi56022.
PROiQ92529.
SOURCEiSearch...

Gene expression databases

BgeeiQ92529.
CleanExiHS_SHC3.
ExpressionAtlasiQ92529. baseline and differential.
GenevisibleiQ92529. HS.

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.
IPR029593. Shc3/ShcC/N-Shc.
[Graphical view]
PANTHERiPTHR10337:SF4. PTHR10337:SF4. 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]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "N-Shc: a neural-specific adapter molecule that mediates signaling from neurotrophin/Trk to Ras/MAPK pathway."
    Nakamura T., Sanokawa R., Sasaki Y., Ayusawa D., Oishi M., Mori N.
    Oncogene 13:1111-1121(1996) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS P64 AND P52), TISSUE SPECIFICITY.
    Tissue: Brain.
  2. "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] (ISOFORM P52).
    Tissue: Fetal brain.
  3. "DNA sequence and analysis of human chromosome 9."
    Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L., Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R., Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S., Bagguley C.L.
    , Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E., Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M., Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J., Frankish A., Frankland J.A., French L., Fricker D.G., Garner P., Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S., Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E., Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D., Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E., Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K., Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J., Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E., McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V., Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S., Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K., Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J., Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L., Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M., Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J., Dunham I.
    Nature 429:369-374(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  4. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM P64).
    Tissue: Brain.
  5. "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.

Entry informationi

Entry nameiSHC3_HUMAN
AccessioniPrimary (citable) accession number: Q92529
Secondary accession number(s): Q5T7I7, Q8TAP2, Q9UCX5
Entry historyi
Integrated into UniProtKB/Swiss-Prot: March 29, 2004
Last sequence update: February 1, 1997
Last modified: July 22, 2015
This is version 125 of the entry and version 1 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

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 9
    Human chromosome 9: 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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.