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Protein

SH2 domain-containing protein 3C

Gene

Sh2d3c

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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.

GO - Molecular functioni

GO - Biological processi

  • signal transduction Source: MGI
  • small GTPase mediated signal transduction Source: InterPro
  • transmembrane receptor protein tyrosine kinase signaling pathway Source: GOC
Complete GO annotation...

Names & Taxonomyi

Protein namesi
Recommended name:
SH2 domain-containing protein 3C
Alternative name(s):
Cas/HEF1-associated signal transducer
SH2 domain-containing Eph receptor-binding protein 1
Gene namesi
Name:Sh2d3c
Synonyms:Chat, Shep1
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 2

Organism-specific databases

MGIiMGI:1351631. Sh2d3c.

Subcellular locationi

  • Cytoplasm 1 Publication
  • Membrane 1 Publication; Peripheral membrane protein 1 Publication

  • Note: Associated with the membrane when EGF-stimulated. Found at ruffling membranes.

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi787 – 7871Y → E: Disrupts binding to BCAR1 and inhibits EGF-induced tyrosine phosphorylation. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 854854SH2 domain-containing protein 3CPRO_0000228834Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei22 – 221PhosphoserineCombined sources
Modified residuei273 – 2731Phosphotyrosine1 Publication
Modified residuei278 – 2781Phosphotyrosine1 Publication
Modified residuei354 – 3541PhosphoserineCombined sources
Modified residuei435 – 4351PhosphoserineCombined sources
Modified residuei787 – 7871Phosphotyrosine1 Publication

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ9QZS8.
MaxQBiQ9QZS8.
PaxDbiQ9QZS8.
PRIDEiQ9QZS8.

PTM databases

iPTMnetiQ9QZS8.
PhosphoSiteiQ9QZS8.

Expressioni

Tissue specificityi

Isoform 2 is ubiquitously expressed. Isoform 1 is expressed in hematopoietic cells from spleen, lymph node and thymus.3 Publications

Gene expression databases

BgeeiQ9QZS8.
CleanExiMM_CHAT.
MM_SH2D3C.
GenevisibleiQ9QZS8. MM.

Interactioni

Subunit structurei

Interacts (via C-terminus) with BCAR1/CAS (By similarity). Interacts with PTK2B. Isoform 2 interacts with NEDD9/HEF1.By similarity2 Publications

GO - Molecular functioni

  • transmembrane receptor protein tyrosine kinase adaptor activity Source: MGI

Protein-protein interaction databases

DIPiDIP-42657N.
IntActiQ9QZS8. 1 interaction.
MINTiMINT-1503279.
STRINGi10090.ENSMUSP00000073866.

Structurei

3D structure databases

ProteinModelPortaliQ9QZS8.
SMRiQ9QZS8. Positions 209-295, 537-849.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini215 – 314100SH2PROSITE-ProRule annotationAdd
BLAST
Domaini580 – 848269Ras-GEFPROSITE-ProRule annotationAdd
BLAST

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.By similarity

Sequence similaritiesi

Contains 1 Ras-GEF domain.PROSITE-ProRule annotation
Contains 1 SH2 domain.PROSITE-ProRule annotation

Keywords - Domaini

SH2 domain

Phylogenomic databases

eggNOGiENOG410IFQG. Eukaryota.
ENOG410XTJR. LUCA.
GeneTreeiENSGT00390000008976.
HOGENOMiHOG000231595.
HOVERGENiHBG053174.
InParanoidiQ9QZS8.
OMAiKRRSITM.
OrthoDBiEOG77126R.
PhylomeDBiQ9QZS8.
TreeFamiTF323756.

Family and domain databases

Gene3Di1.10.840.10. 1 hit.
3.30.505.10. 1 hit.
InterProiIPR023578. Ras_GEF_dom.
IPR001895. RASGEF_cat_dom.
IPR000980. SH2.
[Graphical view]
PfamiPF00617. RasGEF. 1 hit.
PF00017. SH2. 1 hit.
[Graphical view]
SMARTiSM00147. RasGEF. 1 hit.
SM00252. SH2. 1 hit.
[Graphical view]
SUPFAMiSSF48366. SSF48366. 1 hit.
SSF55550. SSF55550. 1 hit.
PROSITEiPS50009. RASGEF_CAT. 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: Q9QZS8-1) [UniParc]FASTAAdd to basket

Also known as: Chat-H

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
MTEMPKKTGR KFKFFKFKGL GSLSNLPRSF SLRRSSASAS IRSCPEPDTF
60 70 80 90 100
EATQDDMVTL PKSPPAYARS SDMYSHMGTM PRPNIKKAQK QQAVQKAQEV
110 120 130 140 150
SRESHLVSRR LPEPPDLEAA KEAGEGTEAL LEDTAPSAVE VDPMRELEDL
160 170 180 190 200
TVDTEKEQVP GDVSPERTAA ELEAAGDYVK FSKEKYILDS SPEKLHKELE
210 220 230 240 250
EELKLSSTDL RSHAWYHGRI PREVSETLVQ RNGDFLIRDS LTSLGDYVLT
260 270 280 290 300
CRWHNQALHF KINKVVVKAG ESYTHIRYLF EQESFDHVPA LVRYHVGSRK
310 320 330 340 350
AVSEQSGAII YCPVNRTFPL RYLEASYGLS QGSSKTASPA SPSGSKGSHM
360 370 380 390 400
KRRSITMTDG LTTDKVTRSD GCPNSTSLPH PRDSIRNCAL SMDQIPDLHS
410 420 430 440 450
PLSPISESPS SPAYSTVTRV HAPSATPSTS AQPASPVARR SSEPQLCPGN
460 470 480 490 500
TPKPPGESDR APHASPSHTL CKASPSPSLS SYSDPDSGHY CQLQPPVRGS
510 520 530 540 550
REQAAGETPR KARGSGERQK ELLENGVSDG EWGKTFTVPV VEATSSFNLA
560 570 580 590 600
TFQSQLIPKE NRPLEVALLR KVKELLSEVD ARTLARHVTK VDCLVARILG
610 620 630 640 650
VTKEMQTLMG VRWGMELLTL PHGRQLRLDL LERFHTMSIM LAVDILGCTG
660 670 680 690 700
SAEERAALLH KTIQLAAELR GTMGNMFSFA AVMGALEMAQ ISRLEQTWMT
710 720 730 740 750
LRQRHTEGAI LYEKKLKPFL KSLNEGKEGP PLSNTTFPHV LPFITLLECD
760 770 780 790 800
SAPAEGPEPW GSTEHGVEVV LAHLEAARTV AHHGGLYHTN AEVKLQGFQA
810 820 830 840 850
RPELLEVFST EFQMRLLWGS QGANSSQAWR YEKFDKVLTA LSHKLEPAIR

SSEL
Length:854
Mass (Da):94,323
Last modified:May 1, 2000 - v1
Checksum:iFA8FC2FDEAE32FF5
GO
Isoform 2 (identifier: Q9QZS8-2) [UniParc]FASTAAdd to basket

Also known as: Chat

The sequence of this isoform differs from the canonical sequence as follows:
     1-166: MTEMPKKTGR...EQVPGDVSPE → MTAVGRRCSALEPR

Show »
Length:702
Mass (Da):77,488
Checksum:iB563FF3E9D3FBA59
GO

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 166166MTEMP…DVSPE → MTAVGRRCSALEPR in isoform 2. 2 PublicationsVSP_017709Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF168364 mRNA. Translation: AAF13305.1.
AB030442 mRNA. Translation: BAA90557.1.
AB043953 mRNA. Translation: BAA96361.1.
AK042709 mRNA. Translation: BAC31340.1.
AK155165 mRNA. Translation: BAE33088.1.
AL772271 Genomic DNA. Translation: CAM16622.1.
BC113203 mRNA. Translation: AAI13204.1.
CCDSiCCDS15928.1. [Q9QZS8-1]
CCDS57168.1. [Q9QZS8-2]
RefSeqiNP_001239476.1. NM_001252547.1. [Q9QZS8-2]
NP_038809.1. NM_013781.3. [Q9QZS8-1]
UniGeneiMm.474256.
Mm.9593.

Genome annotation databases

EnsembliENSMUST00000074248; ENSMUSP00000073866; ENSMUSG00000059013. [Q9QZS8-1]
ENSMUST00000113242; ENSMUSP00000108868; ENSMUSG00000059013. [Q9QZS8-2]
GeneIDi27387.
KEGGimmu:27387.
UCSCiuc008jgp.2. mouse. [Q9QZS8-1]
uc008jgr.2. mouse. [Q9QZS8-2]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF168364 mRNA. Translation: AAF13305.1.
AB030442 mRNA. Translation: BAA90557.1.
AB043953 mRNA. Translation: BAA96361.1.
AK042709 mRNA. Translation: BAC31340.1.
AK155165 mRNA. Translation: BAE33088.1.
AL772271 Genomic DNA. Translation: CAM16622.1.
BC113203 mRNA. Translation: AAI13204.1.
CCDSiCCDS15928.1. [Q9QZS8-1]
CCDS57168.1. [Q9QZS8-2]
RefSeqiNP_001239476.1. NM_001252547.1. [Q9QZS8-2]
NP_038809.1. NM_013781.3. [Q9QZS8-1]
UniGeneiMm.474256.
Mm.9593.

3D structure databases

ProteinModelPortaliQ9QZS8.
SMRiQ9QZS8. Positions 209-295, 537-849.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

DIPiDIP-42657N.
IntActiQ9QZS8. 1 interaction.
MINTiMINT-1503279.
STRINGi10090.ENSMUSP00000073866.

PTM databases

iPTMnetiQ9QZS8.
PhosphoSiteiQ9QZS8.

Proteomic databases

EPDiQ9QZS8.
MaxQBiQ9QZS8.
PaxDbiQ9QZS8.
PRIDEiQ9QZS8.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000074248; ENSMUSP00000073866; ENSMUSG00000059013. [Q9QZS8-1]
ENSMUST00000113242; ENSMUSP00000108868; ENSMUSG00000059013. [Q9QZS8-2]
GeneIDi27387.
KEGGimmu:27387.
UCSCiuc008jgp.2. mouse. [Q9QZS8-1]
uc008jgr.2. mouse. [Q9QZS8-2]

Organism-specific databases

CTDi10044.
MGIiMGI:1351631. Sh2d3c.

Phylogenomic databases

eggNOGiENOG410IFQG. Eukaryota.
ENOG410XTJR. LUCA.
GeneTreeiENSGT00390000008976.
HOGENOMiHOG000231595.
HOVERGENiHBG053174.
InParanoidiQ9QZS8.
OMAiKRRSITM.
OrthoDBiEOG77126R.
PhylomeDBiQ9QZS8.
TreeFamiTF323756.

Miscellaneous databases

NextBioi305340.
PROiQ9QZS8.
SOURCEiSearch...

Gene expression databases

BgeeiQ9QZS8.
CleanExiMM_CHAT.
MM_SH2D3C.
GenevisibleiQ9QZS8. MM.

Family and domain databases

Gene3Di1.10.840.10. 1 hit.
3.30.505.10. 1 hit.
InterProiIPR023578. Ras_GEF_dom.
IPR001895. RASGEF_cat_dom.
IPR000980. SH2.
[Graphical view]
PfamiPF00617. RasGEF. 1 hit.
PF00017. SH2. 1 hit.
[Graphical view]
SMARTiSM00147. RasGEF. 1 hit.
SM00252. SH2. 1 hit.
[Graphical view]
SUPFAMiSSF48366. SSF48366. 1 hit.
SSF55550. SSF55550. 1 hit.
PROSITEiPS50009. RASGEF_CAT. 1 hit.
PS50001. SH2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "A novel signaling intermediate, SHEP1, directly couples Eph receptors to R-Ras and Rap1A."
    Dodelet V.C., Pazzagli C., Zisch A.H., Hauser C.A., Pasquale E.B.
    J. Biol. Chem. 274:31941-31946(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, PHOSPHORYLATION.
  2. "Chat, a Cas/HEF1-associated adaptor protein that integrates multiple signaling pathways."
    Sakakibara A., Hattori S.
    J. Biol. Chem. 275:6404-6410(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), INTERACTION WITH BCAR1 AND NEDD9, TISSUE SPECIFICITY, SUBCELLULAR LOCATION.
  3. "A novel hematopoietic adaptor protein, Chat-H, positively regulates T cell receptor-mediated interleukin-2 production by Jurkat cells."
    Sakakibara A., Hattori S., Nakamura S., Katagiri T.
    J. Biol. Chem. 278:6012-6017(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), INTERACTION WITH BCAR1; NEDD9 AND PTK2B, TISSUE SPECIFICITY, PHOSPHORYLATION.
    Tissue: Spleen.
  4. "The transcriptional landscape of the mammalian genome."
    Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.
    , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
    Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
    Strain: C57BL/6J and NOD.
    Tissue: Cerebellum.
  5. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    Strain: C57BL/6J.
  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] (ISOFORM 1).
  7. "SHEP1 function in cell migration is impaired by a single amino acid mutation that disrupts association with the scaffolding protein cas but not with Ras GTPases."
    Dail M., Kalo M.S., Seddon J.A., Cote J.-F., Vuori K., Pasquale E.B.
    J. Biol. Chem. 279:41892-41902(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION AT TYR-273; TYR-278 AND TYR-787, IDENTIFICATION BY MASS SPECTROMETRY, MUTAGENESIS OF TYR-787.
  8. "The phagosomal proteome in interferon-gamma-activated macrophages."
    Trost M., English L., Lemieux S., Courcelles M., Desjardins M., Thibault P.
    Immunity 30:143-154(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-435, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  9. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-22; SER-354 AND SER-435, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Kidney, Lung and Spleen.

Entry informationi

Entry nameiSH2D3_MOUSE
AccessioniPrimary (citable) accession number: Q9QZS8
Secondary accession number(s): A2AK84, Q9JME1
Entry historyi
Integrated into UniProtKB/Swiss-Prot: March 21, 2006
Last sequence update: May 1, 2000
Last modified: March 16, 2016
This is version 118 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

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 one 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.