P98077 (SHC2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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 names

Name:	SHC2
Synonyms:	SCK, SHCB

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	582 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 By similarity.
Subunit structure	Interacts with the Trk receptors in a phosphotyrosine-dependent manner and MEGF12. Once activated, binds to GRB2. Ref.2 Ref.6 Ref.7
Tissue specificity	Expressed in brain. Expressed at high level in the hypothalamus and at low level in the caudate nucleus. Ref.2
Domain	The PID domain mediates binding to the TrkA receptor.
Post-translational modification	Phosphorylated on tyrosines by the Trk receptors. Ref.6
Miscellaneous	Ref.1 has shown that SHC2 is poorly phosphorylated by the Trk receptors, in opposite to Ref.6.
Sequence similarities	Contains 1 PID domain. Contains 1 SH2 domain.

Ontologies

Keywords
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 insulin receptor signaling pathway Traceable author statement. Source: Reactome nerve growth factor receptor signaling pathway Traceable author statement. Source: Reactome
Cellular_component	cytosol Traceable author statement. Source: Reactome
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 582	582	SHC-transforming protein 2		PRO_0000097732
Regions
	Domain	147 – 329	183	PID
	Domain	487 – 578	92	SH2
	Region	330 – 486	157	CH1
Amino acid modifications
	Modified residue	338	1	Phosphotyrosine Probable
	Modified residue	339	1	Phosphotyrosine Probable
	Modified residue	414	1	Phosphotyrosine Probable
Experimental info
	Sequence conflict	45 – 56	12	GRGPA…RAAGA → IRGSNAQKVVGASG in BAA25798. Ref.2
	Sequence conflict	61	1	D → G in BAA25798. Ref.2
	Sequence conflict	65	1	E → D in BAA25798. Ref.2
	Sequence conflict	96 – 125	30	LSRCR…AAAEW → MAFAGLASHVWWWRPSSQNR IWFRRGSPEF Ref.3
	Sequence conflict	114	1	A → P Ref.4
	Sequence conflict	188	1	E → I Ref.3
	Sequence conflict	226	1	I → T Ref.3
	Sequence conflict	272	1	I → E Ref.3
	Sequence conflict	440	1	Missing Ref.3

Sequences

	Sequence		Length	Mass (Da)
	P98077 [UniParc]. Last modified July 1, 2008. Version 4. Checksum: F640AC298DA37B68	FASTA	582	61,916
	10 20 30 40 50 60 MTQGPGGRAP PAPPAPPEPE APTTFCALLP RMPQWKFAAP GGFLGRGPAA ARAAGASGGA 70 80 90 100 110 120 DPQPEPAGPG GVPALAAAVL GACEPRCAAP CPLPALSRCR GAGSRGSRGG RGAAGSGDAA 130 140 150 160 170 180 AAAEWIRKGS FIHKPAHGWL HPDARVLGPG VSYVVRYMGC IEVLRSMRSL DFNTRTQVTR 190 200 210 220 230 240 EAINRLHEAV PGVRGSWKKK APNKALASVL GKSNLRFAGM SISIHISTDG LSLSVPATRQ 250 260 270 280 290 300 VIANHHMPSI SFASGGDTDM TDYVAYVAKD PINQRACHIL ECCEGLAQSI ISTVGQAFEL 310 320 330 340 350 360 RFKQYLHSPP KVALPPERLA GPEESAWGDE EDSLEHNYYN SIPGKEPPLG GLVDSRLALT 370 380 390 400 410 420 QPCALTALDQ GPSPSLRDAC SLPWDVGSTG TAPPGDGYVQ ADARGPPDHE EHLYVNTQGL 430 440 450 460 470 480 DAPEPEDSPK KDLFDMRPFE DALKLHECSV AAGVTAAPLP LEDQWPSPPT RRAPVAPTEE 490 500 510 520 530 540 QLRQEPWYHG RMSRRAAERM LRADGDFLVR DSVTNPGQYV LTGMHAGQPK HLLLVDPEGV 550 560 570 580 VRTKDVLFES ISHLIDHHLQ NGQPIVAAES ELHLRGVVSR EP

References

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

Cross-references

Sequence databases
EMBL GenBank DDBJ	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.
IPI	IPI00786975.
RefSeq	NP_036567.2. NM_012435.2.
UniGene	Hs.30965.
3D structure databases
ProteinModelPortal	P98077.
ModBase	Search...
Protein-protein interaction databases
MINT	MINT-127694.
STRING	9606.ENSP00000264554.
PTM databases
PhosphoSite	P98077.
Polymorphism databases
DMDM	193806386.
Proteomic databases
PaxDb	P98077.
PRIDE	P98077.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000264554; ENSP00000264554; ENSG00000129946.
GeneID	25759.
KEGG	hsa:25759.
UCSC	uc002loq.4. human.
Organism-specific databases
CTD	25759.
GeneCards	GC19M000369.
H-InvDB	HIX0027436.
HGNC	HGNC:29869. SHC2.
HPA	HPA006136.
MIM	605217. gene.
neXtProt	NX_P98077.
PharmGKB	PA134971076.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG315087.
HOGENOM	HOG000231974.
HOVERGEN	HBG050121.
InParanoid	P98077.
KO	K06279.
OMA	GACEPRC.
OrthoDB	EOG42NJ0D.
Enzyme and pathway databases
Pathway_Interaction_DB	trkrpathway. Neurotrophic factor-mediated Trk receptor signaling. vegfr1_2_pathway. Signaling events mediated by VEGFR1 and VEGFR2. vegfr1_pathway. VEGFR1 specific signals.
Reactome	REACT_111102. Signal Transduction.
Gene expression databases
Bgee	P98077.
CleanEx	HS_SHC2.
Genevestigator	P98077.
GermOnline	ENSG00000129946. 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
BindingDB	P98077.
ChEMBL	CHEMBL3299.
GenomeRNAi	25759.
NextBio	46868.
SOURCE	Search...

Entry information

Entry name

SHC2_HUMAN

Accession

Primary (citable) accession number: P98077
Secondary accession number(s): O60230, Q9NPL5, Q9UCX4

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1996
Last sequence update:	July 1, 2008
Last modified:	May 1, 2013
This is version 105 of the entry and version 4 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.