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Protein

SH2 domain-containing protein 3C

Gene

SH2D3C

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

Functioni

Eph receptor-binding protein which may be a positive regulator of TCR signaling. Binding to BCAR1 is required to induce membrane ruffling and promote EGF-dependent cell migration (By similarity).By similarity

GO - Molecular functioni

  • guanyl-nucleotide exchange factor activity Source: InterPro
  • SH3/SH2 adaptor activity Source: ProtInc

GO - Biological processi

  • JNK cascade Source: ProtInc
  • small GTPase mediated signal transduction Source: InterPro

Enzyme and pathway databases

SignaLinkiQ8N5H7

Names & Taxonomyi

Protein namesi
Recommended name:
SH2 domain-containing protein 3C
Alternative name(s):
Novel SH2-containing protein 3
SH2 domain-containing Eph receptor-binding protein 1
Short name:
SHEP1
Gene namesi
Name:SH2D3C
Synonyms:NSP3
ORF Names:UNQ272/PRO309/PRO34088
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 9

Organism-specific databases

EuPathDBiHostDB:ENSG00000095370.19
HGNCiHGNC:16884 SH2D3C
MIMi604722 gene
neXtProtiNX_Q8N5H7

Subcellular locationi

Keywords - Cellular componenti

Cytoplasm, Membrane

Pathology & Biotechi

Organism-specific databases

DisGeNETi10044
OpenTargetsiENSG00000095370
PharmGKBiPA38191

Polymorphism and mutation databases

BioMutaiSH2D3C
DMDMi74751027

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002288331 – 860SH2 domain-containing protein 3CAdd BLAST860

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei22PhosphoserineBy similarity1
Modified residuei278PhosphotyrosineBy similarity1
Modified residuei283PhosphotyrosineBy similarity1
Modified residuei359PhosphoserineBy similarity1
Modified residuei440PhosphoserineCombined sources1
Modified residuei793PhosphotyrosineBy similarity1

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ8N5H7
MaxQBiQ8N5H7
PaxDbiQ8N5H7
PeptideAtlasiQ8N5H7
PRIDEiQ8N5H7
ProteomicsDBi72054
72055 [Q8N5H7-2]
72056 [Q8N5H7-3]
72057 [Q8N5H7-4]
72058 [Q8N5H7-5]

PTM databases

iPTMnetiQ8N5H7
PhosphoSitePlusiQ8N5H7

Expressioni

Tissue specificityi

Ubiquitously expressed.1 Publication

Gene expression databases

BgeeiENSG00000095370
CleanExiHS_SH2D3C
ExpressionAtlasiQ8N5H7 baseline and differential
GenevisibleiQ8N5H7 HS

Organism-specific databases

HPAiHPA047586

Interactioni

Subunit structurei

Interacts with PTK2B. Interacts with NEDD9/HEF1 (By similarity). Interacts (via C-terminus) with BCAR1/CAS.By similarity1 Publication

Binary interactionsi

Show more details

GO - Molecular functioni

  • guanyl-nucleotide exchange factor activity Source: InterPro
  • SH3/SH2 adaptor activity Source: ProtInc

Protein-protein interaction databases

BioGridi115355, 6 interactors
DIPiDIP-59443N
IntActiQ8N5H7, 7 interactors
STRINGi9606.ENSP00000317817

Structurei

Secondary structure

1860
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi555 – 557Combined sources3
Beta strandi561 – 563Combined sources3
Helixi572 – 583Combined sources12
Helixi587 – 601Combined sources15
Beta strandi604 – 606Combined sources3
Helixi609 – 615Combined sources7
Beta strandi616 – 618Combined sources3
Helixi620 – 623Combined sources4
Helixi627 – 629Combined sources3
Helixi630 – 652Combined sources23
Helixi658 – 677Combined sources20
Helixi682 – 692Combined sources11
Helixi695 – 698Combined sources4
Helixi701 – 710Combined sources10
Helixi712 – 720Combined sources9
Helixi722 – 730Combined sources9
Helixi738 – 740Combined sources3
Helixi747 – 752Combined sources6
Helixi773 – 787Combined sources15
Helixi790 – 800Combined sources11
Turni801 – 803Combined sources3
Helixi808 – 813Combined sources6
Helixi816 – 824Combined sources9
Helixi828 – 830Combined sources3
Helixi833 – 851Combined sources19

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3T6GX-ray2.50A/C539-860[»]
ProteinModelPortaliQ8N5H7
SMRiQ8N5H7
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini220 – 319SH2PROSITE-ProRule annotationAdd BLAST100
Domaini586 – 854Ras-GEFPROSITE-ProRule annotationAdd BLAST269

Domaini

The C-terminal Cdc25-homology/Ras-GEF domain adopts a closed conformation rendering it incapable of carrying out canonical exchange factor function, this closed conformation is required for interaction with BCAR1.

Keywords - Domaini

SH2 domain

Phylogenomic databases

eggNOGiENOG410IFQG Eukaryota
ENOG410XTJR LUCA
GeneTreeiENSGT00390000008976
HOGENOMiHOG000231595
HOVERGENiHBG053174
InParanoidiQ8N5H7
OMAiNTTFPHI
OrthoDBiEOG091G01KG
PhylomeDBiQ8N5H7
TreeFamiTF323756

Family and domain databases

Gene3Di1.10.840.10, 1 hit
3.30.505.10, 1 hit
InterProiView protein in InterPro
IPR023578 Ras_GEF_dom_sf
IPR001895 RASGEF_cat_dom
IPR036964 RASGEF_cat_dom_sf
IPR000980 SH2
IPR036860 SH2_dom_sf
PfamiView protein in Pfam
PF00617 RasGEF, 1 hit
PF00017 SH2, 1 hit
SMARTiView protein in SMART
SM00147 RasGEF, 1 hit
SM00252 SH2, 1 hit
SUPFAMiSSF48366 SSF48366, 1 hit
SSF55550 SSF55550, 1 hit
PROSITEiView protein in PROSITE
PS50009 RASGEF_CAT, 1 hit
PS50001 SH2, 1 hit

Sequences (6)i

Sequence statusi: Complete.

This entry describes 6 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q8N5H7-1) [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
MTEGTKKTSK KFKFFKFKGF GSLSNLPRSF TLRRSSASIS RQSHLEPDTF
60 70 80 90 100
EATQDDMVTV PKSPPAYARS SDMYSHMGTM PRPSIKKAQN SQAARQAQEA
110 120 130 140 150
GPKPNLVPGG VPDPPGLEAA KEVMVKATGP LEDTPAMEPN PSAVEVDPIR
160 170 180 190 200
KPEVPTGDVE EERPPRDVHS ERAAGEPEAG SDYVKFSKEK YILDSSPEKL
210 220 230 240 250
HKELEEELKL SSTDLRSHAW YHGRIPREVS ETLVQRNGDF LIRDSLTSLG
260 270 280 290 300
DYVLTCRWRN QALHFKINKV VVKAGESYTH IQYLFEQESF DHVPALVRYH
310 320 330 340 350
VGSRKAVSEQ SGAIIYCPVN RTFPLRYLEA SYGLGQGSSK PASPVSPSGP
360 370 380 390 400
KGSHMKRRSV TMTDGLTADK VTRSDGCPTS TSLPRPRDSI RSCALSMDQI
410 420 430 440 450
PDLHSPMSPI SESPSSPAYS TVTRVHAAPA APSATALPAS PVARRSSEPQ
460 470 480 490 500
LCPGSAPKTH GESDKGPHTS PSHTLGKASP SPSLSSYSDP DSGHYCQLQP
510 520 530 540 550
PVRGSREWAA TETSSQQARS YGERLKELSE NGAPEGDWGK TFTVPIVEVT
560 570 580 590 600
SSFNPATFQS LLIPRDNRPL EVGLLRKVKE LLAEVDARTL ARHVTKVDCL
610 620 630 640 650
VARILGVTKE MQTLMGVRWG MELLTLPHGR QLRLDLLERF HTMSIMLAVD
660 670 680 690 700
ILGCTGSAEE RAALLHKTIQ LAAELRGTMG NMFSFAAVMG ALDMAQISRL
710 720 730 740 750
EQTWVTLRQR HTEGAILYEK KLKPFLKSLN EGKEGPPLSN TTFPHVLPLI
760 770 780 790 800
TLLECDSAPP EGPEPWGSTE HGVEVVLAHL EAARTVAHHG GLYHTNAEVK
810 820 830 840 850
LQGFQARPEL LEVFSTEFQM RLLWGSQGAS SSQARRYEKF DKVLTALSHK
860
LEPAVRSSEL
Length:860
Mass (Da):94,411
Last modified:October 1, 2002 - v1
Checksum:i62598F2F643147C5
GO
Isoform 2 (identifier: Q8N5H7-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-172: MTEGTKKTSK...RPPRDVHSER → MTAVGRRCPALGSRG

Show »
Length:703
Mass (Da):77,141
Checksum:i005B0EA32F7CA869
GO
Isoform 3 (identifier: Q8N5H7-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-354: Missing.

Show »
Length:506
Mass (Da):55,191
Checksum:i6A525DAC855CF389
GO
Isoform 4 (identifier: Q8N5H7-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-172: MTEGTKKTSK...RPPRDVHSER → MAPALPSPHK...GRCPLLLCGG

Note: No experimental confirmation available.
Show »
Length:792
Mass (Da):86,436
Checksum:iCF76362417FEC80E
GO
Isoform 5 (identifier: Q8N5H7-5) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-185: MTEGTKKTSK...EPEAGSDYVK → MTERCSLWSALSAAACCFYRGSFVQ
     186-186: F → VQF

Note: No experimental confirmation available.
Show »
Length:702
Mass (Da):77,349
Checksum:iF1B0521F92431081
GO
Isoform 6 (identifier: Q8N5H7-6) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-185: MTEGTKKTSK...EPEAGSDYVK → MTERCSLWSALSAAACCFYRGSFVQ

Note: No experimental confirmation available.
Show »
Length:700
Mass (Da):77,122
Checksum:i26650B429A943FF8
GO

Sequence cautioni

The sequence AAQ88456 differs from that shown. Reason: Erroneous initiation.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti445R → C in AAD28246 (PubMed:10187783).Curated1
Sequence conflicti445R → C in AAQ89948 (PubMed:12975309).Curated1
Sequence conflicti723K → E in BAF84082 (PubMed:14702039).Curated1
Isoform 3 (identifier: Q8N5H7-3)
Sequence conflicti29L → T in CAI46101 (PubMed:17974005).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_05135223L → F. Corresponds to variant dbSNP:rs10760500Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0177061 – 354Missing in isoform 3. 1 PublicationAdd BLAST354
Alternative sequenceiVSP_0445811 – 185MTEGT…SDYVK → MTERCSLWSALSAAACCFYR GSFVQ in isoform 5 and isoform 6. 1 PublicationAdd BLAST185
Alternative sequenceiVSP_0177071 – 172MTEGT…VHSER → MTAVGRRCPALGSRG in isoform 2. 3 PublicationsAdd BLAST172
Alternative sequenceiVSP_0177081 – 172MTEGT…VHSER → MAPALPSPHKAVARPELLLD TAAHSGKLRAPDGGEGAECA GHNGGPSWGVGQGQSQEPSR QGIPQAPWLVSWQRRGFPPS SFCPGPLRTEKLRAGRCPLL LCGG in isoform 4. 1 PublicationAdd BLAST172
Alternative sequenceiVSP_044582186F → VQF in isoform 5. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF124251 mRNA Translation: AAD28246.1
AY358089 Transcribed RNA Translation: AAQ88456.1 Different initiation.
AY358440 mRNA Translation: AAQ89948.1
AK056068 mRNA Translation: BAG51614.1
AK291393 mRNA Translation: BAF84082.1
BX647905 mRNA Translation: CAI46101.1
AL162586 Genomic DNA No translation available.
AL162426 Genomic DNA No translation available.
BC027962 mRNA Translation: AAH27962.1
BC032365 mRNA Translation: AAH32365.1
CCDSiCCDS48026.1 [Q8N5H7-5]
CCDS48027.1 [Q8N5H7-6]
CCDS48028.1 [Q8N5H7-3]
CCDS59145.1 [Q8N5H7-4]
CCDS6877.1 [Q8N5H7-1]
CCDS6878.1 [Q8N5H7-2]
RefSeqiNP_001136004.1, NM_001142532.1 [Q8N5H7-3]
NP_001136005.1, NM_001142533.1 [Q8N5H7-5]
NP_001136006.1, NM_001142534.1 [Q8N5H7-6]
NP_001239263.1, NM_001252334.1 [Q8N5H7-4]
NP_005480.2, NM_005489.3 [Q8N5H7-2]
NP_733745.1, NM_170600.2 [Q8N5H7-1]
XP_005251696.1, XM_005251639.1 [Q8N5H7-3]
XP_011516419.1, XM_011518117.2 [Q8N5H7-3]
XP_016869663.1, XM_017014174.1 [Q8N5H7-3]
UniGeneiHs.306412

Genome annotation databases

EnsembliENST00000314830; ENSP00000317817; ENSG00000095370 [Q8N5H7-1]
ENST00000373276; ENSP00000362373; ENSG00000095370 [Q8N5H7-4]
ENST00000373277; ENSP00000362374; ENSG00000095370 [Q8N5H7-2]
ENST00000420366; ENSP00000388536; ENSG00000095370 [Q8N5H7-5]
ENST00000429553; ENSP00000394632; ENSG00000095370 [Q8N5H7-3]
ENST00000629203; ENSP00000485866; ENSG00000095370 [Q8N5H7-6]
GeneIDi10044
KEGGihsa:10044
UCSCiuc004bry.4 human [Q8N5H7-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiSH2D3_HUMAN
AccessioniPrimary (citable) accession number: Q8N5H7
Secondary accession number(s): A8K5S8
, E9PG48, Q5HYE5, Q5JU31, Q6UY42, Q8N6X3, Q9Y2X5
Entry historyiIntegrated into UniProtKB/Swiss-Prot: March 21, 2006
Last sequence update: October 1, 2002
Last modified: June 20, 2018
This is version 138 of the entry and version 1 of the sequence. See 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

3D-structure, Complete proteome, Reference proteome

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