Reviewed, UniProtKB/Swiss-Prot P98077 (SHC2_HUMAN)

Names and origin

Protein names

Recommended name:
    SHC-transforming protein 2
Alternative name(s):
    Src homology 2 domain-containing-transforming protein C2
      Short name=SH2 domain protein C2
    Protein Sck

Gene names

Name:	SHC2
Synonyms:	SCK, SHCB

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	582 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
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.
Tissue specificity	Expressed in brain. Expressed at high level in the hypothalamus and at low level in the caudate nucleus.
Domain	The PID domain mediates binding to the TrkA receptor.
Post-translational modification	Phosphorylated on tyrosines by the Trk receptors.
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
Gene Ontology (GO)
Biological process	Ras protein signal transduction Inferred from Experiment. Source: Reactome
Cellular component	cytoplasm Inferred from direct assay. Source: HPA
Molecular function	protein binding Ref.4 Traceable author statement. Source: UniProtKB
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)
	P98077-1 [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: 15057824] [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: 9507002] [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: 8760305] [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: 7527937] [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: 12006576] [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: 15851471] [Abstract] Cited for: INTERACTION WITH MEGF12. Tissue: Platelet.

Cross-references

Sequence databases
EMBLGenBankDDBJ	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.
RefSeq	NP_036567.2.
UniGene	Hs.30965
3D structure databases
HSSP	HSSP built from PDB template 1MIL based on UniProtKB P29353.
ModBase	Search...
PTM databases
PhosphoSite	P98077.
Genome annotation databases
Ensembl	ENSG00000129946. Homo sapiens. [Contig view]
GeneID	25759.
KEGG	hsa:25759.
Organism-specific databases
H-InvDB	HIX0027436.
HGNC	HGNC:29869. SHC2.
HPA	HPA006136.
MIM	605217. gene.
PharmGKB	PA134971076.
GenAtlas	Search...
GeneCards	Search...
Phylogenomic databases
HOGENOM	P98077.
HOVERGEN	P98077.
Gene expression databases
ArrayExpress	P98077.
CleanEx	HS_SHC2.
GermOnline	ENSG00000129946. Homo sapiens.
Family and domain databases
PRINTS	PR00401. SH2DOMAIN. PR00629. SHCPIDOMAIN.
ProDom	PD000093. SH2. 1 hit. [Graphical view] [Entries sharing at least one domain]
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 Resources
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:	November 25, 2008
This is version 65 of the entry and version 4 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)