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Q8N5H7 (SH2D3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 111. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:SH2D3C
Synonyms:NSP3
ORF Names:UNQ272/PRO309/PRO34088
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length860 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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.

Subunit structure

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

Subcellular location

Cytoplasm By similarity. Membrane; Peripheral membrane protein By similarity. Note: Associated with the membrane when EGF-stimulated. Found at ruffling membranes By similarity.

Tissue specificity

Ubiquitously expressed. Ref.1

Domain

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.

Sequence similarities

Contains 1 Ras-GEF domain.

Contains 1 SH2 domain.

Sequence caution

The sequence AAQ88456.1 differs from that shown. Reason: Erroneous initiation.

Binary interactions

Alternative products

This entry describes 6 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q8N5H7-1)

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: Q8N5H7-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-172: MTEGTKKTSK...RPPRDVHSER → MTAVGRRCPALGSRG
Isoform 3 (identifier: Q8N5H7-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-354: Missing.
Isoform 4 (identifier: Q8N5H7-4)

The sequence of this isoform differs from the canonical sequence as follows:
     1-172: MTEGTKKTSK...RPPRDVHSER → MAPALPSPHK...GRCPLLLCGG
Note: No experimental confirmation available.
Isoform 5 (identifier: Q8N5H7-5)

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.
Isoform 6 (identifier: Q8N5H7-6)

The sequence of this isoform differs from the canonical sequence as follows:
     1-185: MTEGTKKTSK...EPEAGSDYVK → MTERCSLWSALSAAACCFYRGSFVQ
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 860860SH2 domain-containing protein 3C
PRO_0000228833

Regions

Domain220 – 319100SH2
Domain586 – 854269Ras-GEF

Amino acid modifications

Modified residue2781Phosphotyrosine By similarity
Modified residue2831Phosphotyrosine By similarity
Modified residue4401Phosphoserine By similarity
Modified residue7931Phosphotyrosine By similarity

Natural variations

Alternative sequence1 – 354354Missing in isoform 3.
VSP_017706
Alternative sequence1 – 185185MTEGT…SDYVK → MTERCSLWSALSAAACCFYR GSFVQ in isoform 5 and isoform 6.
VSP_044581
Alternative sequence1 – 172172MTEGT…VHSER → MTAVGRRCPALGSRG in isoform 2.
VSP_017707
Alternative sequence1 – 172172MTEGT…VHSER → MAPALPSPHKAVARPELLLD TAAHSGKLRAPDGGEGAECA GHNGGPSWGVGQGQSQEPSR QGIPQAPWLVSWQRRGFPPS SFCPGPLRTEKLRAGRCPLL LCGG in isoform 4.
VSP_017708
Alternative sequence1861F → VQF in isoform 5.
VSP_044582
Natural variant231L → F.
Corresponds to variant rs10760500 [ dbSNP | Ensembl ].
VAR_051352

Experimental info

Sequence conflict4451R → C in AAD28246. Ref.1
Sequence conflict4451R → C in AAQ89948. Ref.2
Sequence conflict7231K → E in BAF84082. Ref.3
Isoform 3:
Sequence conflict291L → T in CAI46101. Ref.4

Secondary structure

................................................ 860
Helix Strand Turn

Details...

Sequences

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

Last modified October 1, 2002. Version 1.
Checksum: 62598F2F643147C5

FASTA86094,411
        10         20         30         40         50         60 
MTEGTKKTSK KFKFFKFKGF GSLSNLPRSF TLRRSSASIS RQSHLEPDTF EATQDDMVTV 

        70         80         90        100        110        120 
PKSPPAYARS SDMYSHMGTM PRPSIKKAQN SQAARQAQEA GPKPNLVPGG VPDPPGLEAA 

       130        140        150        160        170        180 
KEVMVKATGP LEDTPAMEPN PSAVEVDPIR KPEVPTGDVE EERPPRDVHS ERAAGEPEAG 

       190        200        210        220        230        240 
SDYVKFSKEK YILDSSPEKL HKELEEELKL SSTDLRSHAW YHGRIPREVS ETLVQRNGDF 

       250        260        270        280        290        300 
LIRDSLTSLG DYVLTCRWRN QALHFKINKV VVKAGESYTH IQYLFEQESF DHVPALVRYH 

       310        320        330        340        350        360 
VGSRKAVSEQ SGAIIYCPVN RTFPLRYLEA SYGLGQGSSK PASPVSPSGP KGSHMKRRSV 

       370        380        390        400        410        420 
TMTDGLTADK VTRSDGCPTS TSLPRPRDSI RSCALSMDQI PDLHSPMSPI SESPSSPAYS 

       430        440        450        460        470        480 
TVTRVHAAPA APSATALPAS PVARRSSEPQ LCPGSAPKTH GESDKGPHTS PSHTLGKASP 

       490        500        510        520        530        540 
SPSLSSYSDP DSGHYCQLQP PVRGSREWAA TETSSQQARS YGERLKELSE NGAPEGDWGK 

       550        560        570        580        590        600 
TFTVPIVEVT SSFNPATFQS LLIPRDNRPL EVGLLRKVKE LLAEVDARTL ARHVTKVDCL 

       610        620        630        640        650        660 
VARILGVTKE MQTLMGVRWG MELLTLPHGR QLRLDLLERF HTMSIMLAVD ILGCTGSAEE 

       670        680        690        700        710        720 
RAALLHKTIQ LAAELRGTMG NMFSFAAVMG ALDMAQISRL EQTWVTLRQR HTEGAILYEK 

       730        740        750        760        770        780 
KLKPFLKSLN EGKEGPPLSN TTFPHVLPLI TLLECDSAPP EGPEPWGSTE HGVEVVLAHL 

       790        800        810        820        830        840 
EAARTVAHHG GLYHTNAEVK LQGFQARPEL LEVFSTEFQM RLLWGSQGAS SSQARRYEKF 

       850        860 
DKVLTALSHK LEPAVRSSEL 

« Hide

Isoform 2 [UniParc].

Checksum: 005B0EA32F7CA869
Show »

FASTA70377,141
Isoform 3 [UniParc].

Checksum: 6A525DAC855CF389
Show »

FASTA50655,191
Isoform 4 [UniParc].

Checksum: CF76362417FEC80E
Show »

FASTA79286,436
Isoform 5 [UniParc].

Checksum: F1B0521F92431081
Show »

FASTA70277,349
Isoform 6 [UniParc].

Checksum: 26650B429A943FF8
Show »

FASTA70077,122

References

« Hide 'large scale' references
[1]"NSP1 defines a novel family of adaptor proteins linking integrin and tyrosine kinase receptors to the c-Jun N-terminal kinase/stress-activated protein kinase signaling pathway."
Lu Y., Brush J., Stewart T.A.
J. Biol. Chem. 274:10047-10052(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), TISSUE SPECIFICITY.
Tissue: Placenta.
[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] (ISOFORMS 2 AND 3).
[3]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 5 AND 6).
Tissue: Brain.
[4]"The full-ORF clone resource of the German cDNA consortium."
Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I.
BMC Genomics 8:399-399(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 4).
Tissue: Cervix.
[5]"DNA sequence and analysis of human chromosome 9."
Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L., Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R., Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S., Bagguley C.L. expand/collapse author list , Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E., Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M., Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J., Frankish A., Frankland J.A., French L., Fricker D.G., Garner P., Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S., Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E., Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D., Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E., Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K., Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J., Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E., McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V., Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S., Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K., Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J., Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L., Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M., Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J., Dunham I.
Nature 429:369-374(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]"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] (ISOFORMS 1 AND 2).
Tissue: Pancreas and Testis.
[7]"NSP-Cas protein structures reveal a promiscuous interaction module in cell signaling."
Mace P.D., Wallez Y., Dobaczewska M.K., Lee J.J., Robinson H., Pasquale E.B., Riedl S.J.
Nat. Struct. Mol. Biol. 18:1381-1387(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 539-860 IN COMPLEX WITH BCAR1.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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, AL162426 Genomic DNA. Translation: CAI39761.1.
AL162586, AL162426 Genomic DNA. Translation: CAI39763.1.
AL162586, AL162426 Genomic DNA. Translation: CAI39766.1.
AL162426, AL162586 Genomic DNA. Translation: CAI41177.1.
AL162426, AL162586 Genomic DNA. Translation: CAI41179.1.
AL162426, AL162586 Genomic DNA. Translation: CAI41182.1.
BC027962 mRNA. Translation: AAH27962.1.
BC032365 mRNA. Translation: AAH32365.1.
CCDSCCDS48026.1. [Q8N5H7-5]
CCDS48027.1. [Q8N5H7-6]
CCDS48028.1. [Q8N5H7-3]
CCDS59145.1. [Q8N5H7-4]
CCDS6877.1. [Q8N5H7-1]
CCDS6878.1. [Q8N5H7-2]
RefSeqNP_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]
UniGeneHs.306412.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
3T6GX-ray2.50A/C539-860[»]
ProteinModelPortalQ8N5H7.
SMRQ8N5H7. Positions 219-300, 543-855.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid115355. 5 interactions.
DIPDIP-59443N.
IntActQ8N5H7. 4 interactions.
MINTMINT-1427552.
STRING9606.ENSP00000317817.

PTM databases

PhosphoSiteQ8N5H7.

Polymorphism databases

DMDM74751027.

Proteomic databases

MaxQBQ8N5H7.
PaxDbQ8N5H7.
PeptideAtlasQ8N5H7.
PRIDEQ8N5H7.

Protocols and materials databases

DNASU10044.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000314830; ENSP00000317817; ENSG00000095370. [Q8N5H7-1]
ENST00000373274; ENSP00000362371; ENSG00000095370. [Q8N5H7-6]
ENST00000373277; ENSP00000362374; ENSG00000095370. [Q8N5H7-2]
ENST00000420366; ENSP00000388536; ENSG00000095370. [Q8N5H7-5]
ENST00000429553; ENSP00000394632; ENSG00000095370. [Q8N5H7-3]
GeneID10044.
KEGGhsa:10044.
UCSCuc004bry.3. human. [Q8N5H7-5]
uc004brz.4. human. [Q8N5H7-1]
uc004bsa.3. human. [Q8N5H7-2]

Organism-specific databases

CTD10044.
GeneCardsGC09M130501.
HGNCHGNC:16884. SH2D3C.
HPAHPA047586.
MIM604722. gene.
neXtProtNX_Q8N5H7.
PharmGKBPA38191.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG149796.
HOGENOMHOG000231595.
HOVERGENHBG053174.
InParanoidQ8N5H7.
OrthoDBEOG77126R.
PhylomeDBQ8N5H7.
TreeFamTF323756.

Enzyme and pathway databases

SignaLinkQ8N5H7.

Gene expression databases

ArrayExpressQ8N5H7.
BgeeQ8N5H7.
CleanExHS_SH2D3C.
GenevestigatorQ8N5H7.

Family and domain databases

Gene3D1.10.840.10. 1 hit.
3.30.505.10. 1 hit.
InterProIPR023578. Ras_GEF_dom.
IPR001895. RasGRF_CDC25.
IPR000980. SH2.
[Graphical view]
PfamPF00617. RasGEF. 1 hit.
PF00017. SH2. 1 hit.
[Graphical view]
SMARTSM00147. RasGEF. 1 hit.
SM00252. SH2. 1 hit.
[Graphical view]
SUPFAMSSF48366. SSF48366. 1 hit.
SSF55550. SSF55550. 1 hit.
PROSITEPS50009. RASGEF_CAT. 1 hit.
PS50001. SH2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiSH2D3C.
GenomeRNAi10044.
NextBio37937.
PROQ8N5H7.
SOURCESearch...

Entry information

Entry nameSH2D3_HUMAN
AccessionPrimary (citable) accession number: Q8N5H7
Secondary accession number(s): A8K5S8 expand/collapse secondary AC list , E9PG48, Q5HYE5, Q5JU31, Q6UY42, Q8N6X3, Q9Y2X5
Entry history
Integrated into UniProtKB/Swiss-Prot: March 21, 2006
Last sequence update: October 1, 2002
Last modified: July 9, 2014
This is version 111 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

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

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 9

Human chromosome 9: entries, gene names and cross-references to MIM