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Q6S5L8 (SHC4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 91. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
SHC-transforming protein 4
Alternative name(s):
Rai-like protein
Short name=RaLP
SHC-transforming protein D
Short name=hShcD
Src homology 2 domain-containing-transforming protein C4
Short name=SH2 domain protein C4
Gene names
Name:SHC4
Synonyms:SHCD
ORF Names:UNQ6438/PRO21364
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length630 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Activates both Ras-dependent and Ras-independent migratory pathways in melanomas. Contributes to the early phases of agrin-induced tyrosine phosphorylation of CHRNB1. Ref.1

Subunit structure

Interacts (via PID domain) with phosphorylated MUSK (via NPXY motif); undergoes tyrosine phosphorylation downstream of activated MUSK. Interacts with GRB2; the interaction is dependent of Tyr-424 phosphorylation and increased by EGF. Ref.4

Subcellular location

Cell junctionsynapsepostsynaptic cell membrane. Note: Colocalized with MUSK at the neuromuscular junction By similarity.

Tissue specificity

Only expressed in melanomas. Weakly expressed in normal melanocytes and benign nevi. Highly expressed at the transition from radial growth phase to vertical growth phase and metastatic melanomas, when tumor cells acquire migratory competence and invasive potential. Ref.1

Post-translational modification

Phosphorylated; the phosphorylation is enhanced by EGF. Phosphorylation at Tyr-424 is required for the interaction with GRB2. Ref.4

Sequence similarities

Contains 1 PID domain.

Contains 1 SH2 domain.

Ontologies

Keywords
   Cellular componentCell junction
Cell membrane
Membrane
Postsynaptic cell membrane
Synapse
   Coding sequence diversityAlternative splicing
Polymorphism
   DomainSH2 domain
   PTMPhosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processintracellular signal transduction

Inferred from electronic annotation. Source: InterPro

   Cellular_componentcell junction

Inferred from electronic annotation. Source: UniProtKB-KW

postsynaptic membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q6S5L8-1)

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 2 (identifier: Q6S5L8-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-243: Missing.
     244-280: KFLSTVLGKSNLQFSGMNIKLTISTCSLTLMNLDNQQ → MLPALEHWIPKFFSFRTRTGSPLSLACRQPIVGPCDH
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 630630SHC-transforming protein 4
PRO_0000337200

Regions

Domain186 – 369184PID
Domain526 – 61792SH2
Region1 – 185185CH2
Region370 – 525156CH1

Amino acid modifications

Modified residue4241Phosphotyrosine

Natural variations

Alternative sequence1 – 243243Missing in isoform 2.
VSP_033965
Alternative sequence244 – 28037KFLST…LDNQQ → MLPALEHWIPKFFSFRTRTG SPLSLACRQPIVGPCDH in isoform 2.
VSP_033966
Natural variant521N → D. Ref.3
Corresponds to variant rs17856991 [ dbSNP | Ensembl ].
VAR_043672
Natural variant2441K → E. Ref.3
Corresponds to variant rs17856990 [ dbSNP | Ensembl ].
VAR_043673
Natural variant4001Q → H.
Corresponds to variant rs16961728 [ dbSNP | Ensembl ].
VAR_043674
Natural variant4471D → G. Ref.3
Corresponds to variant rs17856992 [ dbSNP | Ensembl ].
VAR_043675

Experimental info

Mutagenesis3151R → Q: Phosphorylation is markedly decreased. Completely reduces the phosphorylation and interaction with MUSK; when associated with K-549. Ref.4
Mutagenesis374 – 3752YY → F: Remains phosphorylated. Contains a residual phosphorylation; when associated with F-465. Retains the ability to bind MUSK. Reduced the phosphorylation in presence of MUSK; when associated with F-424 and F-465. Completely abolishes the phosphorylation in presence of MUSK; when associated with F-403; F-413; F-424 and F-465. Retains the ability to bind MUSK; when associated with F-465. Retains the ability to bind MUSK; when associated with F-424 and F-465. Retains the ability to bind MUSK; when associated with F-403; F-413; F-424 and F-465. Ref.4
Mutagenesis4031Y → F: Completely abolishes the phosphorylation in presence of MUSK; when associated with 374-F-F-375; F-413; F-424 and F-465. Ref.4
Mutagenesis4131Y → F: Completely abolishes the phosphorylation in presence of MUSK; when associated with 374-F-F-375; F-403; F-424 and F-465. Ref.4
Mutagenesis4241Y → F: Significantly decreased GRB2 interaction. Reduced the phosphorylation in presence of MUSK; when associated with 374-F-F-375 and F-465. Completely abolishes the phosphorylation in presence of MUSK; when associated with 374-F-F-375; F-403; F-413 and F-465. Ref.4
Mutagenesis4651Y → F: Remains phosphorylated. Contains a residual phosphorylation; when associated with 374-F-F-375. Reduced the phosphorylation in presence of MUSK; when associated with 374-F-F-375 and 424. Completely abolishes the phosphorylation in presence of MUSK; when associated with 374-F-F-375; F-403; F-413 and F-424. Retains the ability to bind MUSK. Retains the ability to bind MUSK; when associated with 374-F-F-375. Retains the ability to bind MUSK; when associated with 374-F-F-375 and F-424. Retains the ability to bind MUSK; when associated with 374-F-F-375; F-403; F-413 and F-424. Ref.4
Mutagenesis5491R → K: Completely reduces the phosphorylation and interaction with MUSK; when associated with Q-315. Ref.4

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified July 5, 2004. Version 1.
Checksum: 504F3FCB894E2C59

FASTA63068,785
        10         20         30         40         50         60 
MRERGQDSLA GLVLYVGLFG HPGMLHRAKY SRFRNESITS LDEGSSGGSV GNKGSPQPPH 

        70         80         90        100        110        120 
PALAPHLPTE DATLPSQESP TPLCTLIPRM ASMKLANPAT LLSLKNFCLG TKEVPRLKLQ 

       130        140        150        160        170        180 
ESRDPGSSGP SSPETSLSRS GTAPPPQQDL VGHRATALTP DSCPLPGPGE PTLRSRQDRH 

       190        200        210        220        230        240 
FLQHLLGMGM NYCVRYMGCV EVLQSMRSLD FGMRTQVTRE AISRLCEAVP GANGAIKKRK 

       250        260        270        280        290        300 
PPVKFLSTVL GKSNLQFSGM NIKLTISTCS LTLMNLDNQQ IIANHHMQSI SFASGGDPDT 

       310        320        330        340        350        360 
TDYVAYVAKD PVNQRACHIL ECHNGMAQDV ISTIGQAFEL RFKQYLKNPS LNTSCESEEV 

       370        380        390        400        410        420 
HIDSHAEERE DHEYYNEIPG KQPPVGGVSD MRIKVQATEQ MAYCPIQCEK LCYLPGNSKC 

       430        440        450        460        470        480 
SSVYENCLEQ SRAIGNVHPR GVQSQRDTSL LKHTCRVDLF DDPCYINTQA LQSTPGSAGN 

       490        500        510        520        530        540 
QRSAQPLGSP WHCGKAPETV QPGATAQPAS SHSLPHIKQQ LWSEECYHGK LSRKAAESLL 

       550        560        570        580        590        600 
VKDGDFLVRE SATSPGQYVL SGLQGGQAKH LLLVDPEGKV RTKDHVFDNV GHLIRYHMDN 

       610        620        630 
SLPIISSGSE VSLKQPVRKD NNPALLHSNK 

« Hide

Isoform 2 [UniParc].

Checksum: 558D4E2167B69AF7
Show »

FASTA38742,782

References

« Hide 'large scale' references
[1]"RaLP, a new member of the Src homology and collagen family, regulates cell migration and tumor growth of metastatic melanomas."
Fagiani E., Giardina G., Luzi L., Cesaroni M., Quarto M., Capra M., Germano G., Bono M., Capillo M., Pelicci P., Lanfrancone L.
Cancer Res. 67:3064-3073(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, TISSUE SPECIFICITY.
[2]"The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment."
Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J., Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P., Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E. expand/collapse author list , Heldens S., Huang A., Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D., Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L., Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C., Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J., Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.
Genome Res. 13:2265-2270(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
[3]"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 1), VARIANTS ASP-52; GLU-244 AND GLY-447.
Tissue: Testis.
[4]"Analysis of a Shc family adaptor protein, ShcD/Shc4, that associates with muscle-specific kinase."
Jones N., Hardy W.R., Friese M.B., Jorgensen C., Smith M.J., Woody N.M., Burden S.J., Pawson T.
Mol. Cell. Biol. 27:4759-4773(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH MUSK AND GRB2, PHOSPHORYLATION, MUTAGENESIS OF ARG-315; 374-TYR-TYR-375; TYR-403; TYR-413; TYR-424; TYR-465 AND ARG-549.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AY464565 mRNA. Translation: AAR19363.1.
AY358250 mRNA. Translation: AAQ88617.1.
BC033907 mRNA. Translation: AAH33907.1.
RefSeqNP_976224.3. NM_203349.3.
XP_005254433.1. XM_005254376.2.
UniGeneHs.642615.

3D structure databases

ProteinModelPortalQ6S5L8.
SMRQ6S5L8. Positions 185-347, 520-619.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid134386. 1 interaction.
STRING9606.ENSP00000329668.

PTM databases

PhosphoSiteQ6S5L8.

Polymorphism databases

DMDM74722804.

Proteomic databases

PaxDbQ6S5L8.
PRIDEQ6S5L8.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000332408; ENSP00000329668; ENSG00000185634. [Q6S5L8-1]
ENST00000396535; ENSP00000379786; ENSG00000185634. [Q6S5L8-2]
GeneID399694.
KEGGhsa:399694.
UCSCuc001zxb.1. human. [Q6S5L8-1]
uc010uey.1. human. [Q6S5L8-2]

Organism-specific databases

CTD399694.
GeneCardsGC15M049115.
H-InvDBHIX0202177.
HGNCHGNC:16743. SHC4.
neXtProtNX_Q6S5L8.
PharmGKBPA142670917.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG315087.
HOGENOMHOG000231974.
HOVERGENHBG050121.
InParanoidQ6S5L8.
KOK17449.
OMAISTCSLT.
OrthoDBEOG7MD4QK.
PhylomeDBQ6S5L8.
TreeFamTF315807.

Enzyme and pathway databases

SignaLinkQ6S5L8.

Gene expression databases

ArrayExpressQ6S5L8.
BgeeQ6S5L8.
CleanExHS_SHC4.
GenevestigatorQ6S5L8.

Family and domain databases

Gene3D2.30.29.30. 1 hit.
3.30.505.10. 1 hit.
InterProIPR011993. PH_like_dom.
IPR006019. PID_Shc-like.
IPR006020. PTB/PI_dom.
IPR000980. SH2.
[Graphical view]
PfamPF00640. PID. 1 hit.
PF00017. SH2. 1 hit.
[Graphical view]
PRINTSPR00401. SH2DOMAIN.
PR00629. SHCPIDOMAIN.
SMARTSM00462. PTB. 1 hit.
SM00252. SH2. 1 hit.
[Graphical view]
SUPFAMSSF55550. SSF55550. 1 hit.
PROSITEPS01179. PID. 1 hit.
PS50001. SH2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSSHC4. human.
GenomeRNAi399694.
NextBio105503.
PROQ6S5L8.

Entry information

Entry nameSHC4_HUMAN
AccessionPrimary (citable) accession number: Q6S5L8
Secondary accession number(s): Q6UXQ3, Q8IYW3
Entry history
Integrated into UniProtKB/Swiss-Prot: May 20, 2008
Last sequence update: July 5, 2004
Last modified: April 16, 2014
This is version 91 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 15

Human chromosome 15: entries, gene names and cross-references to MIM