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Protein

E3 ubiquitin-protein ligase SH3RF1

Gene

Sh3rf1

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Has E3 ubiquitin-protein ligase activity. In the absence of an external substrate, it can catalyze self-ubiquitination. Stimulates ubiquitination of potassium channel KCNJ1, enhancing its dynamin-dependent and clathrin-independent endocytosis (By similarity). Acts as a scaffold protein that coordinates with MAPK8IP1/JIP1 in organizing different components of the JNK pathway, including RAC1 or RAC2, MAP3K11/MLK3 or MAP3K7/TAK1, MAP2K7/MKK7, MAPK8/JNK1 and/or MAPK9/JNK2 into a functional multiprotein complex to ensure the effective activation of the JNK signaling pathway. Regulates the differentiation of CD4+ and CD8+ T-cells and promotes T-helper 1 (Th1) cell differentiation. Regulates the activation of MAPK8/JNK1 and MAPK9/JNK2 in CD4+ T-cells and the activation of MAPK8/JNK1 in CD8+ T-cells (PubMed:23963642, PubMed:27084103, PubMed:9482736). Plays a crucial role in the migration of neocortical neurons in the developing brain. Controls proper cortical neuronal migration and the formation of proximal cytoplasmic dilation in the leading process (PCDLP) in migratory neocortical neurons by regulating the proper localization of activated RAC1 and F-actin assembly (PubMed:22959435).By similarity4 Publications

Catalytic activityi

S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-cysteine + N6-ubiquitinyl-[acceptor protein]-L-lysine.By similarity

Pathwayi: protein ubiquitination

This protein is involved in the pathway protein ubiquitination, which is part of Protein modification.
View all proteins of this organism that are known to be involved in the pathway protein ubiquitination and in Protein modification.

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri12 – 53RING-typePROSITE-ProRule annotationAdd BLAST42

GO - Molecular functioni

  • MAP-kinase scaffold activity Source: UniProtKB
  • metal ion binding Source: UniProtKB-KW
  • ubiquitin protein ligase activity Source: MGI

GO - Biological processi

Keywordsi

Molecular functionTransferase
Biological processUbl conjugation pathway
LigandMetal-binding, Zinc

Enzyme and pathway databases

UniPathwayi
UPA00143

Names & Taxonomyi

Protein namesi
Recommended name:
E3 ubiquitin-protein ligase SH3RF1 (EC:2.3.2.27By similarity)
Alternative name(s):
Plenty of SH3s
Short name:
Protein POSH2 Publications
RING-type E3 ubiquitin transferase SH3RF1Curated
SH3 domain-containing RING finger protein 1
SH3 multiple domains protein 2
Gene namesi
Name:Sh3rf1
Synonyms:Kiaa1494, Posh2 Publications, Posh1By similarity, Sh3md2
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Unplaced

Organism-specific databases

MGIiMGI:1913066 Sh3rf1

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cell projection, Cytoplasm, Golgi apparatus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi470E → Q: Loss of binding to AKT2. 1 Publication1
Mutagenesisi489W → A: Loss of binding to AKT2 and enhanced binding to MAP3K11. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00003341521 – 892E3 ubiquitin-protein ligase SH3RF1Add BLAST892

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei304PhosphoserineCombined sources1
Modified residuei539PhosphoserineBy similarity1
Modified residuei741PhosphoserineCombined sources1

Post-translational modificationi

Phosphorylated at Ser-304 by AKT1 and AKT2. When phosphorylated, it has reduced ability to bind Rac.By similarity
Autoubiquitinated. Ubiquitinated by SH3RF2, leading to proteasome-mediated degradation.By similarity

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

PaxDbiQ69ZI1
PRIDEiQ69ZI1

PTM databases

iPTMnetiQ69ZI1
PhosphoSitePlusiQ69ZI1

Expressioni

Tissue specificityi

Ubiquitously expressed.1 Publication

Developmental stagei

Expressed in the embryonic brain. Expressed strongly in the venricular zone (VZ), subventricular zone (SVZ), and lower intermediate zone (IZ) but weakly in the upper IZ and cortical plate (CP) at embryonic day 14.5 (E14.5). At E16.5, expression increases in the IZ and CP. At E18.5, it increases significantly in the CP but decreases in the IZ, SVZ, and VZ (at protein level).1 Publication

Interactioni

Subunit structurei

Interacts with HERP1 (By similarity). Interacts with RAC1; in a GTP-dependent manner (PubMed:22959435, PubMed:9482736). Interacts with MAP3K10/MLK2 and MAP3K11/MLK3. Interacts with MAPK8IP; this interaction leads to the PJAC complex (POSH-JIP or SH3RF1/MAPK8IP1 apoptotic complex) with a 1:1 ratio. Interacts with SIAH1. Probably part of a signaling complex that may contain SH3RF1, MAPK8IP, DLK1, MAP2K4/MKK4, MAP2K7/MKK7, MAPK8/JNK1, MAPK9/JNK2, AKT1 and AKT2 (PubMed:12514131, PubMed:14504284, PubMed:16230351, PubMed:16571722, PubMed:23963642). Found in a complex with RAC2, MAP3K7/TAK1, MAP2K7/MKK7, MAPK8IP1/JIP1, MAPK8/JNK1 and MAPK9/JNK2 (PubMed:27084103). Found in a complex with RAC1, MAP3K11/MLK3, MAP2K7/MKK7, MAPK8IP1/JIP1 and MAPK8/JNK1 (PubMed:23963642). Interacts with SH3RF2 (By similarity).By similarity8 Publications

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi208480, 2 interactors
IntActiQ69ZI1, 6 interactors
STRINGi10090.ENSMUSP00000034060

Structurei

3D structure databases

ProteinModelPortaliQ69ZI1
SMRiQ69ZI1
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini134 – 193SH3 1PROSITE-ProRule annotationAdd BLAST60
Domaini196 – 259SH3 2PROSITE-ProRule annotationAdd BLAST64
Domaini452 – 513SH3 3PROSITE-ProRule annotationAdd BLAST62
Domaini833 – 892SH3 4PROSITE-ProRule annotationAdd BLAST60

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni292 – 362Interaction with RAC1By similarityAdd BLAST71
Regioni447 – 550Interaction with AKT21 PublicationAdd BLAST104

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi84 – 90Poly-Gly7
Compositional biasi397 – 403Poly-Pro7
Compositional biasi406 – 431Ala-richAdd BLAST26

Domaini

The RING finger domain is required for ubiquitin ligase activity and autoubiquitination.By similarity

Sequence similaritiesi

Belongs to the SH3RF family.Curated

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri12 – 53RING-typePROSITE-ProRule annotationAdd BLAST42

Keywords - Domaini

Repeat, SH3 domain, Zinc-finger

Phylogenomic databases

eggNOGiENOG410ITG6 Eukaryota
ENOG410XS5R LUCA
HOGENOMiHOG000045564
HOVERGENiHBG069552
InParanoidiQ69ZI1
KOiK12171
PhylomeDBiQ69ZI1

Family and domain databases

CDDicd11930 SH3_SH3RF1_2, 1 hit
cd11785 SH3_SH3RF_C, 1 hit
Gene3Di3.30.40.10, 1 hit
InterProiView protein in InterPro
IPR036028 SH3-like_dom_sf
IPR001452 SH3_domain
IPR028502 SH3RF1
IPR035816 SH3RF1/SH3RF3_SH3_4
IPR035795 SH3RF1_SH3_2
IPR018957 Znf_C3HC4_RING-type
IPR001841 Znf_RING
IPR013083 Znf_RING/FYVE/PHD
IPR017907 Znf_RING_CS
PANTHERiPTHR44208:SF2 PTHR44208:SF2, 1 hit
PfamiView protein in Pfam
PF00018 SH3_1, 1 hit
PF14604 SH3_9, 3 hits
PF00097 zf-C3HC4, 1 hit
PRINTSiPR00452 SH3DOMAIN
SMARTiView protein in SMART
SM00184 RING, 1 hit
SM00326 SH3, 4 hits
SUPFAMiSSF50044 SSF50044, 4 hits
PROSITEiView protein in PROSITE
PS50002 SH3, 4 hits
PS00518 ZF_RING_1, 1 hit
PS50089 ZF_RING_2, 1 hit

Sequences (4+)i

Sequence statusi: Complete.

This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 4 described isoforms and 2 potential isoforms that are computationally mapped.Show allAlign All

Isoform 1 (identifier: Q69ZI1-1) [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
MDESALLDLL ECPVCLERLD ASAKVLPCQH TFCKRCLLGI VGSRNELRCP
60 70 80 90 100
ECRTLVGSGV DELPSNILLV RLLDGIKQRP WKPGPGGGGG TTCTNTLRAQ
110 120 130 140 150
GSTVVNCGSK DLQSSQCGQQ PRVQAWSPPV RGIPQLPCAK ALYNYEGKEP
160 170 180 190 200
GDLKFSKGDI IILRRQVDEN WYHGEVSGVH GFFPTNFVQI IKPLPQPPPQ
210 220 230 240 250
CKALYDFEVK DKEADKDCLP FAKDDVLTVI RRVDENWAEG MLADKIGIFP
260 270 280 290 300
ISYVEFNSAA KQLIEWDKPP VPGVDTAECP SATAQSTSAS KHPDTKKNTR
310 320 330 340 350
KRHSFTSLTM ANKSSQGSQN RHSMEISPPV LISSSNPTAA ARISELSGLS
360 370 380 390 400
CSAPSQVHIS TTGLIVTPPP SSPVTTGPAF TFPSDVPYQA ALGSMNPPLP
410 420 430 440 450
PPPLLAATVL ASTPSGATAA VAAAAAAAAA AGMGPRPVMG SSEQIAHLRP
460 470 480 490 500
QTRPSVYVAI YPYTPRKEDE LELRKGEMFL VFERCQDGWY KGTSMHTSKI
510 520 530 540 550
GVFPGNYVAP VTRAVTNASQ AKVSMSTAGQ ASRGVTMVSP STAGGPTQKP
560 570 580 590 600
QGNGVAGNPS VVPTAVVSAA HIQTSPQAKV LLHMSGQMTV NQARNAVRTV
610 620 630 640 650
AAHSQERPTA AVTPIQVQNA ACLGPASVGL PHHSLASQPL PPMAGPAAHG
660 670 680 690 700
AAVSISRTNA PMACAAGASL ASPNMTSAML ETEPSGRTVT ILPGLPTSPE
710 720 730 740 750
SAASACGNSS AGKPDKDSKK EKKGLLKLLS GASTKRKPRV SPPASPTLDV
760 770 780 790 800
ELGAGEAPLQ GAVGPELPLG GSHGRVGSCP TDGDGPVAAG TAALAQDAFH
810 820 830 840 850
RKTSSLDSAV PIAPPPRQAC SSLGPVMNEA RPVVCERHRV VVSYPPQSEA
860 870 880 890
ELELKEGDIV FVHKKREDGW FKGTLQRNGK TGLFPGSFVE NI
Length:892
Mass (Da):93,447
Last modified:May 20, 2008 - v2
Checksum:iD92071116F4D6EBE
GO
Isoform 2 (identifier: Q69ZI1-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     160-189: Missing.

Note: No experimental confirmation available.
Show »
Length:862
Mass (Da):89,906
Checksum:iD2B2F85D18812B47
GO
Isoform 3 (identifier: Q69ZI1-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     788-828: AAGTAALAQD...ACSSLGPVMN → DRWNSSPSPG...GLLLPGPSHE
     829-892: Missing.

Note: No experimental confirmation available.
Show »
Length:828
Mass (Da):86,342
Checksum:iC670E8A5CF0EB1D4
GO
Isoform 4 (identifier: Q69ZI1-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     345-381: ELSGLSCSAPSQVHISTTGLIVTPPPSSPVTTGPAFT → APSQVQGRGQLPKRGLLTSGKILAASFIFALVTSSLL
     382-892: Missing.

Note: No experimental confirmation available.
Show »
Length:381
Mass (Da):41,433
Checksum:i991E47F760D876CB
GO

Computationally mapped potential isoform sequencesi

There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
E9QQ33E9QQ33_MOUSE
E3 ubiquitin-protein ligase SH3RF1
Sh3rf1
891Annotation score:
A0A1B0GSY0A0A1B0GSY0_MOUSE
E3 ubiquitin-protein ligase SH3RF1
Sh3rf1
836Annotation score:

Sequence cautioni

The sequence BAD32463 differs from that shown. Reason: Erroneous initiation.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti160I → T in AAC40070 (PubMed:9482736).Curated1
Sequence conflicti321R → S in BAE28367 (PubMed:16141072).Curated1
Sequence conflicti342R → G in BAE28367 (PubMed:16141072).Curated1
Sequence conflicti431Missing in BAC32385 (PubMed:16141072).Curated1
Sequence conflicti431Missing in AAH60113 (PubMed:15489334).Curated1
Sequence conflicti431Missing in AAH60696 (PubMed:15489334).Curated1
Sequence conflicti630L → M in BAE28367 (PubMed:16141072).Curated1
Sequence conflicti679M → V in BAC32385 (PubMed:16141072).Curated1
Sequence conflicti679M → V in AAH60113 (PubMed:15489334).Curated1
Sequence conflicti679M → V in AAH60696 (PubMed:15489334).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_033624160 – 189Missing in isoform 2. 1 PublicationAdd BLAST30
Alternative sequenceiVSP_033625345 – 381ELSGL…GPAFT → APSQVQGRGQLPKRGLLTSG KILAASFIFALVTSSLL in isoform 4. 1 PublicationAdd BLAST37
Alternative sequenceiVSP_033626382 – 892Missing in isoform 4. 1 PublicationAdd BLAST511
Alternative sequenceiVSP_033627788 – 828AAGTA…GPVMN → DRWNSSPSPGCLPPQDKLPG LRSAHCSTTSPGLLLPGPSH E in isoform 3. 1 PublicationAdd BLAST41
Alternative sequenceiVSP_033628829 – 892Missing in isoform 3. 1 PublicationAdd BLAST64

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF030131 mRNA Translation: AAC40070.1
AK173185 mRNA Translation: BAD32463.1 Different initiation.
BC060113 mRNA Translation: AAH60113.1
BC060696 mRNA Translation: AAH60696.1
AK088003 mRNA Translation: BAC40088.1
AK045470 mRNA Translation: BAC32385.1
AK148137 mRNA Translation: BAE28367.1
PIRiT09071
RefSeqiNP_067481.2, NM_021506.2
UniGeneiMm.27949

Genome annotation databases

GeneIDi59009
KEGGimmu:59009

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF030131 mRNA Translation: AAC40070.1
AK173185 mRNA Translation: BAD32463.1 Different initiation.
BC060113 mRNA Translation: AAH60113.1
BC060696 mRNA Translation: AAH60696.1
AK088003 mRNA Translation: BAC40088.1
AK045470 mRNA Translation: BAC32385.1
AK148137 mRNA Translation: BAE28367.1
PIRiT09071
RefSeqiNP_067481.2, NM_021506.2
UniGeneiMm.27949

3D structure databases

ProteinModelPortaliQ69ZI1
SMRiQ69ZI1
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi208480, 2 interactors
IntActiQ69ZI1, 6 interactors
STRINGi10090.ENSMUSP00000034060

PTM databases

iPTMnetiQ69ZI1
PhosphoSitePlusiQ69ZI1

Proteomic databases

PaxDbiQ69ZI1
PRIDEiQ69ZI1

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi59009
KEGGimmu:59009

Organism-specific databases

CTDi57630
MGIiMGI:1913066 Sh3rf1
RougeiSearch...

Phylogenomic databases

eggNOGiENOG410ITG6 Eukaryota
ENOG410XS5R LUCA
HOGENOMiHOG000045564
HOVERGENiHBG069552
InParanoidiQ69ZI1
KOiK12171
PhylomeDBiQ69ZI1

Enzyme and pathway databases

UniPathwayi
UPA00143

Miscellaneous databases

ChiTaRSiSh3rf1 mouse
PROiPR:Q69ZI1
SOURCEiSearch...

Family and domain databases

CDDicd11930 SH3_SH3RF1_2, 1 hit
cd11785 SH3_SH3RF_C, 1 hit
Gene3Di3.30.40.10, 1 hit
InterProiView protein in InterPro
IPR036028 SH3-like_dom_sf
IPR001452 SH3_domain
IPR028502 SH3RF1
IPR035816 SH3RF1/SH3RF3_SH3_4
IPR035795 SH3RF1_SH3_2
IPR018957 Znf_C3HC4_RING-type
IPR001841 Znf_RING
IPR013083 Znf_RING/FYVE/PHD
IPR017907 Znf_RING_CS
PANTHERiPTHR44208:SF2 PTHR44208:SF2, 1 hit
PfamiView protein in Pfam
PF00018 SH3_1, 1 hit
PF14604 SH3_9, 3 hits
PF00097 zf-C3HC4, 1 hit
PRINTSiPR00452 SH3DOMAIN
SMARTiView protein in SMART
SM00184 RING, 1 hit
SM00326 SH3, 4 hits
SUPFAMiSSF50044 SSF50044, 4 hits
PROSITEiView protein in PROSITE
PS50002 SH3, 4 hits
PS00518 ZF_RING_1, 1 hit
PS50089 ZF_RING_2, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiSH3R1_MOUSE
AccessioniPrimary (citable) accession number: Q69ZI1
Secondary accession number(s): O70254
, Q3UG42, Q6P9M8, Q8BR66, Q8C2T5
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 20, 2008
Last sequence update: May 20, 2008
Last modified: October 10, 2018
This is version 107 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  3. PATHWAY comments
    Index of metabolic and biosynthesis pathways
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Main funding by: National Institutes of Health

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