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Protein

SHC-transforming protein 4

Gene

SHC4

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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

GO - Molecular functioni

  1. protein kinase binding Source: GO_Central
  2. receptor tyrosine kinase binding Source: GO_Central

GO - Biological processi

  1. apoptotic process Source: Ensembl
  2. intracellular signal transduction Source: InterPro
  3. positive regulation of cell proliferation Source: Ensembl
  4. regulation of gene expression Source: Ensembl
  5. stem cell differentiation Source: Ensembl
  6. transmembrane receptor protein tyrosine kinase signaling pathway Source: GO_Central
Complete GO annotation...

Enzyme and pathway databases

SignaLinkiQ6S5L8.

Names & Taxonomyi

Protein namesi
Recommended 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 namesi
Name:SHC4
Synonyms:SHCD
ORF Names:UNQ6438/PRO21364
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640 Componenti: Chromosome 15

Organism-specific databases

HGNCiHGNC:16743. SHC4.

Subcellular locationi

  1. Cell junctionsynapsepostsynaptic cell membrane

  2. Note: Colocalized with MUSK at the neuromuscular junction.By similarity

GO - Cellular componenti

  1. cell junction Source: UniProtKB-KW
  2. plasma membrane Source: GO_Central
  3. postsynaptic membrane Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Cell junction, Cell membrane, Membrane, Postsynaptic cell membrane, Synapse

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi315 – 3151R → Q: Phosphorylation is markedly decreased. Completely reduces the phosphorylation and interaction with MUSK; when associated with K-549. 1 Publication
Mutagenesisi374 – 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. 1 Publication
Mutagenesisi403 – 4031Y → F: Completely abolishes the phosphorylation in presence of MUSK; when associated with 374-F-F-375; F-413; F-424 and F-465. 1 Publication
Mutagenesisi413 – 4131Y → F: Completely abolishes the phosphorylation in presence of MUSK; when associated with 374-F-F-375; F-403; F-424 and F-465. 1 Publication
Mutagenesisi424 – 4241Y → 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. 1 Publication
Mutagenesisi465 – 4651Y → 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. 1 Publication
Mutagenesisi549 – 5491R → K: Completely reduces the phosphorylation and interaction with MUSK; when associated with Q-315. 1 Publication

Organism-specific databases

PharmGKBiPA142670917.

Polymorphism and mutation databases

BioMutaiSHC4.
DMDMi74722804.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 630630SHC-transforming protein 4PRO_0000337200Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei424 – 4241Phosphotyrosine1 Publication

Post-translational modificationi

Phosphorylated; the phosphorylation is enhanced by EGF. Phosphorylation at Tyr-424 is required for the interaction with GRB2.1 Publication

Keywords - PTMi

Phosphoprotein

Proteomic databases

MaxQBiQ6S5L8.
PaxDbiQ6S5L8.
PRIDEiQ6S5L8.

PTM databases

PhosphoSiteiQ6S5L8.

Expressioni

Tissue specificityi

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.1 Publication

Gene expression databases

BgeeiQ6S5L8.
CleanExiHS_SHC4.
ExpressionAtlasiQ6S5L8. baseline and differential.
GenevestigatoriQ6S5L8.

Interactioni

Subunit structurei

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.1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
ARP102753EBI-9453524,EBI-608057
EGFRP005332EBI-9453524,EBI-297353
METP085813EBI-9453524,EBI-1039152

Protein-protein interaction databases

BioGridi134386. 7 interactions.
IntActiQ6S5L8. 4 interactions.
STRINGi9606.ENSP00000329668.

Structurei

3D structure databases

ProteinModelPortaliQ6S5L8.
SMRiQ6S5L8. Positions 185-377, 520-619.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini186 – 369184PIDPROSITE-ProRule annotationAdd
BLAST
Domaini526 – 61792SH2PROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni1 – 185185CH2Add
BLAST
Regioni370 – 525156CH1Add
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.
InParanoidiQ6S5L8.
KOiK17449.
OMAiPRMASMK.
OrthoDBiEOG7MD4QK.
PhylomeDBiQ6S5L8.
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.
IPR029596. SHC4.
[Graphical view]
PANTHERiPTHR10337:SF12. PTHR10337:SF12. 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 1 (identifier: Q6S5L8-1) [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
MRERGQDSLA GLVLYVGLFG HPGMLHRAKY SRFRNESITS LDEGSSGGSV
60 70 80 90 100
GNKGSPQPPH PALAPHLPTE DATLPSQESP TPLCTLIPRM ASMKLANPAT
110 120 130 140 150
LLSLKNFCLG TKEVPRLKLQ ESRDPGSSGP SSPETSLSRS GTAPPPQQDL
160 170 180 190 200
VGHRATALTP DSCPLPGPGE PTLRSRQDRH FLQHLLGMGM NYCVRYMGCV
210 220 230 240 250
EVLQSMRSLD FGMRTQVTRE AISRLCEAVP GANGAIKKRK PPVKFLSTVL
260 270 280 290 300
GKSNLQFSGM NIKLTISTCS LTLMNLDNQQ IIANHHMQSI SFASGGDPDT
310 320 330 340 350
TDYVAYVAKD PVNQRACHIL ECHNGMAQDV ISTIGQAFEL RFKQYLKNPS
360 370 380 390 400
LNTSCESEEV HIDSHAEERE DHEYYNEIPG KQPPVGGVSD MRIKVQATEQ
410 420 430 440 450
MAYCPIQCEK LCYLPGNSKC SSVYENCLEQ SRAIGNVHPR GVQSQRDTSL
460 470 480 490 500
LKHTCRVDLF DDPCYINTQA LQSTPGSAGN QRSAQPLGSP WHCGKAPETV
510 520 530 540 550
QPGATAQPAS SHSLPHIKQQ LWSEECYHGK LSRKAAESLL VKDGDFLVRE
560 570 580 590 600
SATSPGQYVL SGLQGGQAKH LLLVDPEGKV RTKDHVFDNV GHLIRYHMDN
610 620 630
SLPIISSGSE VSLKQPVRKD NNPALLHSNK
Length:630
Mass (Da):68,785
Last modified:July 5, 2004 - v1
Checksum:i504F3FCB894E2C59
GO
Isoform 2 (identifier: Q6S5L8-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-243: Missing.
     244-280: KFLSTVLGKSNLQFSGMNIKLTISTCSLTLMNLDNQQ → MLPALEHWIPKFFSFRTRTGSPLSLACRQPIVGPCDH

Note: No experimental confirmation available.

Show »
Length:387
Mass (Da):42,782
Checksum:i558D4E2167B69AF7
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti52 – 521N → D.1 Publication
Corresponds to variant rs17856991 [ dbSNP | Ensembl ].
VAR_043672
Natural varianti244 – 2441K → E.1 Publication
Corresponds to variant rs17856990 [ dbSNP | Ensembl ].
VAR_043673
Natural varianti400 – 4001Q → H.
Corresponds to variant rs16961728 [ dbSNP | Ensembl ].
VAR_043674
Natural varianti447 – 4471D → G.1 Publication
Corresponds to variant rs17856992 [ dbSNP | Ensembl ].
VAR_043675

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 243243Missing in isoform 2. 1 PublicationVSP_033965Add
BLAST
Alternative sequencei244 – 28037KFLST…LDNQQ → MLPALEHWIPKFFSFRTRTG SPLSLACRQPIVGPCDH in isoform 2. 1 PublicationVSP_033966Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY464565 mRNA. Translation: AAR19363.1.
AY358250 mRNA. Translation: AAQ88617.1.
BC033907 mRNA. Translation: AAH33907.1.
CCDSiCCDS10130.1. [Q6S5L8-1]
RefSeqiNP_976224.3. NM_203349.3. [Q6S5L8-1]
UniGeneiHs.642615.

Genome annotation databases

EnsembliENST00000332408; ENSP00000329668; ENSG00000185634. [Q6S5L8-1]
ENST00000396535; ENSP00000379786; ENSG00000185634. [Q6S5L8-2]
GeneIDi399694.
KEGGihsa:399694.
UCSCiuc001zxb.1. human. [Q6S5L8-1]
uc010uey.1. human. [Q6S5L8-2]

Polymorphism and mutation databases

BioMutaiSHC4.

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY464565 mRNA. Translation: AAR19363.1.
AY358250 mRNA. Translation: AAQ88617.1.
BC033907 mRNA. Translation: AAH33907.1.
CCDSiCCDS10130.1. [Q6S5L8-1]
RefSeqiNP_976224.3. NM_203349.3. [Q6S5L8-1]
UniGeneiHs.642615.

3D structure databases

ProteinModelPortaliQ6S5L8.
SMRiQ6S5L8. Positions 185-377, 520-619.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi134386. 7 interactions.
IntActiQ6S5L8. 4 interactions.
STRINGi9606.ENSP00000329668.

PTM databases

PhosphoSiteiQ6S5L8.

Polymorphism and mutation databases

BioMutaiSHC4.
DMDMi74722804.

Proteomic databases

MaxQBiQ6S5L8.
PaxDbiQ6S5L8.
PRIDEiQ6S5L8.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000332408; ENSP00000329668; ENSG00000185634. [Q6S5L8-1]
ENST00000396535; ENSP00000379786; ENSG00000185634. [Q6S5L8-2]
GeneIDi399694.
KEGGihsa:399694.
UCSCiuc001zxb.1. human. [Q6S5L8-1]
uc010uey.1. human. [Q6S5L8-2]

Organism-specific databases

CTDi399694.
GeneCardsiGC15M049115.
H-InvDBHIX0202177.
HGNCiHGNC:16743. SHC4.
neXtProtiNX_Q6S5L8.
PharmGKBiPA142670917.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG315087.
GeneTreeiENSGT00390000018860.
HOGENOMiHOG000231974.
HOVERGENiHBG050121.
InParanoidiQ6S5L8.
KOiK17449.
OMAiPRMASMK.
OrthoDBiEOG7MD4QK.
PhylomeDBiQ6S5L8.
TreeFamiTF315807.

Enzyme and pathway databases

SignaLinkiQ6S5L8.

Miscellaneous databases

ChiTaRSiSHC4. human.
GenomeRNAii399694.
NextBioi105503.
PROiQ6S5L8.

Gene expression databases

BgeeiQ6S5L8.
CleanExiHS_SHC4.
ExpressionAtlasiQ6S5L8. baseline and differential.
GenevestigatoriQ6S5L8.

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.
IPR029596. SHC4.
[Graphical view]
PANTHERiPTHR10337:SF12. PTHR10337:SF12. 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. "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. 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 AT TYR-424, MUTAGENESIS OF ARG-315; 374-TYR-TYR-375; TYR-403; TYR-413; TYR-424; TYR-465 AND ARG-549.

Entry informationi

Entry nameiSHC4_HUMAN
AccessioniPrimary (citable) accession number: Q6S5L8
Secondary accession number(s): Q6UXQ3, Q8IYW3
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 20, 2008
Last sequence update: July 5, 2004
Last modified: April 29, 2015
This is version 100 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 15
    Human chromosome 15: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. 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.