Q92529 (SHC3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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 names

Name:	SHC3
Synonyms:	NSHC, SHCC

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	594 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	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.
Subunit structure	Interacts with the Trk receptors in a phosphotyrosine-dependent manner. Once activated, binds to GRB2. Interacts with activated EGF receptors. Ref.5
Tissue specificity	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. Ref.1
Post-translational modification	Tyrosine phosphorylated. Ref.5
Sequence similarities	Contains 1 PID domain. Contains 1 SH2 domain.

Ontologies

Keywords
Coding sequence diversity	Alternative splicing
Domain	SH2 domain
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	Ras protein signal transduction Traceable author statement. Source: Reactome central nervous system development Traceable author statement Ref.1. Source: ProtInc epidermal growth factor receptor signaling pathway Traceable author statement Ref.1. Source: ProtInc insulin receptor signaling pathway Traceable author statement. Source: Reactome learning or memory Inferred from electronic annotation. Source: Compara nerve growth factor receptor signaling pathway Traceable author statement. Source: Reactome synaptic transmission, glutamatergic Inferred from electronic annotation. Source: Compara
Cellular_component	cytosol Traceable author statement. Source: Reactome
Molecular_function	signal transducer activity Traceable author statement Ref.1. Source: ProtInc
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
APP	P05067	2	EBI-79084,EBI-77613

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform p64 (identifier: Q92529-1)

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.

Isoform p52 (identifier: Q92529-2)

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

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 594	594	SHC-transforming protein 3		PRO_0000097734
Regions
	Domain	149 – 334	186	PID
	Domain	499 – 590	92	SH2
	Region	335 – 498	164	CH1
Natural variations
	Alternative sequence	1 – 155	155	MLPRT…PGVTY → MHARAAASVMDICRIRLLIR LTIGLERPPGQV in isoform p52.		VSP_009805
Experimental info
	Sequence conflict	58	1	D → V in AAH26314. Ref.4
	Sequence conflict	201	1	K → R Ref.2
	Sequence conflict	271	1	A → T in AAH26314. Ref.4
	Sequence conflict	553	1	I → E Ref.2
	Sequence conflict	554	1	R → Q in AAH26314. Ref.4
	Sequence conflict	593 – 594	2	KQ → NE Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Isoform p64 [UniParc]. Last modified February 1, 1997. Version 1. Checksum: 047A9D08002E41BF	FASTA	594	64,056
	10 20 30 40 50 60 MLPRTKYNRF RNDSVTSVDD LLHSLSVSGG GGKVSAARAT PAAAPYLVSG EALRKAPDDG 70 80 90 100 110 120 PGSLGHLLHK VSHLKLSSSG LRGLSSAARE RAGARLSGSC SAPSLAAPDG SAPSAPRAPA 130 140 150 160 170 180 MSAARKGRPG DEPLPRPPRG APHASDQVLG PGVTYVVKYL GCIEVLRSMR SLDFSTRTQI 190 200 210 220 230 240 TREAISRVCE AVPGAKGAFK KRKPPSKMLS SILGKSNLQF AGMSISLTIS TASLNLRTPD 250 260 270 280 290 300 SKQIIANHHM RSISFASGGD PDTTDYVAYV AKDPVNRRAC HILECCDGLA QDVIGSIGQA 310 320 330 340 350 360 FELRFKQYLQ CPTKIPALHD RMQSLDEPWT EEEGDGSDHP YYNSIPSKMP PPGGFLDTRL 370 380 390 400 410 420 KPRPHAPDTA QFAGKEQTYY QGRHLGDTFG EDWQQTPLRQ GSSDIYSTPE GKLHVAPTGE 430 440 450 460 470 480 APTYVNTQQI PPQAWPAAVS SAESSPRKDL FDMKPFEDAL KNQPLGPVLS KAASVECISP 490 500 510 520 530 540 VSPRAPDAKM LEELQAETWY QGEMSRKEAE GLLEKDGDFL VRKSTTNPGS FVLTGMHNGQ 550 560 570 580 590 AKHLLLVDPE GTIRTKDRVF DSISHLINHH LESSLPIVSA GSELCLQQPV ERKQ
	Isoform p52 [UniParc]. Checksum: BE74C85B97AF30CE	FASTA	471	51,939
	10 20 30 40 50 60 MHARAAASVM DICRIRLLIR LTIGLERPPG QVVVKYLGCI EVLRSMRSLD FSTRTQITRE 70 80 90 100 110 120 AISRVCEAVP GAKGAFKKRK PPSKMLSSIL GKSNLQFAGM SISLTISTAS LNLRTPDSKQ 130 140 150 160 170 180 IIANHHMRSI SFASGGDPDT TDYVAYVAKD PVNRRACHIL ECCDGLAQDV IGSIGQAFEL 190 200 210 220 230 240 RFKQYLQCPT KIPALHDRMQ SLDEPWTEEE GDGSDHPYYN SIPSKMPPPG GFLDTRLKPR 250 260 270 280 290 300 PHAPDTAQFA GKEQTYYQGR HLGDTFGEDW QQTPLRQGSS DIYSTPEGKL HVAPTGEAPT 310 320 330 340 350 360 YVNTQQIPPQ AWPAAVSSAE SSPRKDLFDM KPFEDALKNQ PLGPVLSKAA SVECISPVSP 370 380 390 400 410 420 RAPDAKMLEE LQAETWYQGE MSRKEAEGLL EKDGDFLVRK STTNPGSFVL TGMHNGQAKH 430 440 450 460 470 LLLVDPEGTI RTKDRVFDSI SHLINHHLES SLPIVSAGSE LCLQQPVERK Q

References

	« Hide 'large scale' referencesShow 'large scale' references »
[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.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	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.
IPI	IPI00409679. IPI00410340.
RefSeq	NP_058544.3. NM_016848.5.
UniGene	Hs.292737.
3D structure databases
ProteinModelPortal	Q92529.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q92529. 1 interaction.
MINT	MINT-1492377.
STRING	9606.ENSP00000364995.
PTM databases
PhosphoSite	Q92529.
Polymorphism databases
DMDM	48474922.
Proteomic databases
PaxDb	Q92529.
PRIDE	Q92529.
Protocols and materials databases
DNASU	53358.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000375835; ENSP00000364995; ENSG00000148082.
GeneID	53358.
KEGG	hsa:53358.
UCSC	uc004aqf.2. human.
Organism-specific databases
CTD	53358.
GeneCards	GC09M091628.
HGNC	HGNC:18181. SHC3.
HPA	HPA046656.
MIM	605263. gene.
neXtProt	NX_Q92529.
PharmGKB	PA134913435.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG315087.
HOGENOM	HOG000231974.
HOVERGEN	HBG050121.
InParanoid	Q92529.
KO	K06279.
OMA	GSDHPYY.
OrthoDB	EOG4SF960.
PhylomeDB	Q92529.
Enzyme and pathway databases
Pathway_Interaction_DB	trkrpathway. Neurotrophic factor-mediated Trk receptor signaling.
Reactome	REACT_111102. Signal Transduction.
Gene expression databases
ArrayExpress	Q92529.
Bgee	Q92529.
CleanEx	HS_SHC3.
Genevestigator	Q92529.
GermOnline	ENSG00000148082. Homo sapiens.
Family and domain databases
Gene3D	2.30.29.30. 1 hit. 3.30.505.10. 1 hit.
InterPro	IPR011993. PH_like_dom. IPR006019. PID_domain. IPR006020. PTyr_interaction_dom. IPR000980. SH2. [Graphical view]
Pfam	PF00640. PID. 1 hit. PF00017. SH2. 1 hit. [Graphical view]
PRINTS	PR00401. SH2DOMAIN. PR00629. SHCPIDOMAIN.
SMART	SM00462. PTB. 1 hit. SM00252. SH2. 1 hit. [Graphical view]
PROSITE	PS01179. PID. 1 hit. PS50001. SH2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	53358.
NextBio	56022.
SOURCE	Search...

Entry information

Entry name

SHC3_HUMAN

Accession

Primary (citable) accession number: Q92529
Secondary accession number(s): Q5T7I7, Q8TAP2, Q9UCX5

Entry history

Integrated into UniProtKB/Swiss-Prot:	March 29, 2004
Last sequence update:	February 1, 1997
Last modified:	May 1, 2013
This is version 104 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.