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Q69ZI1 (SH3R1_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified June 11, 2014. Version 81. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | 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:
E3 ubiquitin-protein ligase SH3RF1

EC=6.3.2.-
Alternative name(s):
Plenty of SH3s
Short name=Protein POSH
SH3 domain-containing RING finger protein 1
SH3 multiple domains protein 2
Gene names
Name:Sh3rf1
Synonyms:Kiaa1494, Posh, Sh3md2
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length892 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Acts as a scaffold protein, contributes to Rac-induced signal transduction such as JNKs (MAPK8 and MAPK9) activation and induces apoptosis. Within a signaling complex, it probably recruits protein kinases such as MAP3K10 or MAP3K11 which are in turn activated leading to the sequential activation of MAP2K4, MAP2K7 and JNKs (MAPK8 and MAPK9) By similarity. In fibroblasts, induces apoptosis. Ref.1

Might act as an E3 ubiquitin-protein ligase, or as part of E3 complex, which accepts ubiquitin from specific E2 ubiquitin-conjugating enzymes such as UBE2D1 or UBE2N and then transfers it to substrates. In the absence of an external substrate, it can catalyze self-ubiquitination. Stimulates ubiquitination of potassium channel KCNJ1, enhancing it's dynamin-dependent and clathrin-independent endocytosis By similarity. Ref.1

Pathway

Protein modification; protein ubiquitination.

Subunit structure

Interacts with HERP1 By similarity. Interacts with Rac; in a GTP-dependent manner. Interacts with MAP3K10 and MAP3K11. Interacts with MAPK8IP; this interaction leads to the PJAC complex (POSH-JIP or SH3RF1/MAPK8IP apoptotic complex) with a 1:1 ratio. Interacts with SIAH1. Probably part of a signaling complex that may contain SH3RF1, MAPK8IP, DLK1, MAP2K4, MAP2K7, MAPK8, MAPK9, AKT1 and AKT2. Ref.1 Ref.5 Ref.6 Ref.7 Ref.8

Subcellular location

Cytoplasmperinuclear region By similarity. Cell projectionlamellipodium. Golgi apparatustrans-Golgi network. Note: Colocalizes, with AKT2, in lamellipodia By similarity. Colocalizes, with HERP1, in trans-Golgi network By similarity. Ref.6

Tissue specificity

Ubiquitously expressed. Ref.1

Domain

The RING finger domain is responsible of ubiquitination and proteasomal degradation.

Post-translational modification

Phosphorylated at Ser-304 by AKT1 and AKT2. When phosphorylated, it has reduced ability to bind Rac By similarity.

Subject to ubiquitination and proteasomal degradation By similarity.

Sequence similarities

Belongs to the SH3RF family.

Contains 1 RING-type zinc finger.

Contains 4 SH3 domains.

Sequence caution

The sequence BAD32463.1 differs from that shown. Reason: Erroneous initiation.

Binary interactions

With

Entry

#Exp.

IntAct

Notes

Bnip3lQ9Z2F74EBI-957380,EBI-1774669
SIAH1Q8IUQ45EBI-957380,EBI-747107From a different organism.

Alternative products

This entry describes 4 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q69ZI1-1)

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: Q69ZI1-2)

The sequence of this isoform differs from the canonical sequence as follows:
     160-189: Missing.
Note: No experimental confirmation available.
Isoform 3 (identifier: Q69ZI1-3)

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.
Isoform 4 (identifier: Q69ZI1-4)

The sequence of this isoform differs from the canonical sequence as follows:
     345-381: ELSGLSCSAPSQVHISTTGLIVTPPPSSPVTTGPAFT → APSQVQGRGQLPKRGLLTSGKILAASFIFALVTSSLL
     382-892: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 892892E3 ubiquitin-protein ligase SH3RF1
PRO_0000334152

Regions

Domain134 – 19360SH3 1
Domain196 – 25964SH3 2
Domain452 – 51362SH3 3
Domain833 – 89260SH3 4
Zinc finger12 – 5342RING-type
Region447 – 550104Interaction with AKT2
Compositional bias84 – 907Poly-Gly
Compositional bias397 – 4037Poly-Pro
Compositional bias406 – 43126Ala-rich

Amino acid modifications

Modified residue3041Phosphoserine By similarity

Natural variations

Alternative sequence160 – 18930Missing in isoform 2.
VSP_033624
Alternative sequence345 – 38137ELSGL…GPAFT → APSQVQGRGQLPKRGLLTSG KILAASFIFALVTSSLL in isoform 4.
VSP_033625
Alternative sequence382 – 892511Missing in isoform 4.
VSP_033626
Alternative sequence788 – 82841AAGTA…GPVMN → DRWNSSPSPGCLPPQDKLPG LRSAHCSTTSPGLLLPGPSH E in isoform 3.
VSP_033627
Alternative sequence829 – 89264Missing in isoform 3.
VSP_033628

Experimental info

Mutagenesis4701E → Q: Loss of binding to AKT2. Ref.6
Mutagenesis4891W → A: Loss of binding to AKT2 and enhanced binding to MAP3K11. Ref.6
Sequence conflict1601I → T in AAC40070. Ref.1
Sequence conflict3211R → S in BAE28367. Ref.3
Sequence conflict3421R → G in BAE28367. Ref.3
Sequence conflict4311Missing in BAC32385. Ref.3
Sequence conflict4311Missing in AAH60113. Ref.4
Sequence conflict4311Missing in AAH60696. Ref.4
Sequence conflict6301L → M in BAE28367. Ref.3
Sequence conflict6791M → V in BAC32385. Ref.3
Sequence conflict6791M → V in AAH60113. Ref.4
Sequence conflict6791M → V in AAH60696. Ref.4

Sequences

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

Last modified May 20, 2008. Version 2.
Checksum: D92071116F4D6EBE

FASTA89293,447
        10         20         30         40         50         60 
MDESALLDLL ECPVCLERLD ASAKVLPCQH TFCKRCLLGI VGSRNELRCP ECRTLVGSGV 

        70         80         90        100        110        120 
DELPSNILLV RLLDGIKQRP WKPGPGGGGG TTCTNTLRAQ GSTVVNCGSK DLQSSQCGQQ 

       130        140        150        160        170        180 
PRVQAWSPPV RGIPQLPCAK ALYNYEGKEP GDLKFSKGDI IILRRQVDEN WYHGEVSGVH 

       190        200        210        220        230        240 
GFFPTNFVQI IKPLPQPPPQ CKALYDFEVK DKEADKDCLP FAKDDVLTVI RRVDENWAEG 

       250        260        270        280        290        300 
MLADKIGIFP ISYVEFNSAA KQLIEWDKPP VPGVDTAECP SATAQSTSAS KHPDTKKNTR 

       310        320        330        340        350        360 
KRHSFTSLTM ANKSSQGSQN RHSMEISPPV LISSSNPTAA ARISELSGLS CSAPSQVHIS 

       370        380        390        400        410        420 
TTGLIVTPPP SSPVTTGPAF TFPSDVPYQA ALGSMNPPLP PPPLLAATVL ASTPSGATAA 

       430        440        450        460        470        480 
VAAAAAAAAA AGMGPRPVMG SSEQIAHLRP QTRPSVYVAI YPYTPRKEDE LELRKGEMFL 

       490        500        510        520        530        540 
VFERCQDGWY KGTSMHTSKI GVFPGNYVAP VTRAVTNASQ AKVSMSTAGQ ASRGVTMVSP 

       550        560        570        580        590        600 
STAGGPTQKP QGNGVAGNPS VVPTAVVSAA HIQTSPQAKV LLHMSGQMTV NQARNAVRTV 

       610        620        630        640        650        660 
AAHSQERPTA AVTPIQVQNA ACLGPASVGL PHHSLASQPL PPMAGPAAHG AAVSISRTNA 

       670        680        690        700        710        720 
PMACAAGASL ASPNMTSAML ETEPSGRTVT ILPGLPTSPE SAASACGNSS AGKPDKDSKK 

       730        740        750        760        770        780 
EKKGLLKLLS GASTKRKPRV SPPASPTLDV ELGAGEAPLQ GAVGPELPLG GSHGRVGSCP 

       790        800        810        820        830        840 
TDGDGPVAAG TAALAQDAFH RKTSSLDSAV PIAPPPRQAC SSLGPVMNEA RPVVCERHRV 

       850        860        870        880        890 
VVSYPPQSEA ELELKEGDIV FVHKKREDGW FKGTLQRNGK TGLFPGSFVE NI 

« Hide

Isoform 2 [UniParc].

Checksum: D2B2F85D18812B47
Show »

FASTA86289,906
Isoform 3 [UniParc].

Checksum: C670E8A5CF0EB1D4
Show »

FASTA82886,342
Isoform 4 [UniParc].

Checksum: 991E47F760D876CB
Show »

FASTA38141,433

References

« Hide 'large scale' references
[1]"A new rac target POSH is an SH3-containing scaffold protein involved in the JNK and NF-kappaB signalling pathways."
Tapon N., Nagata K., Lamarche N., Hall A.
EMBO J. 17:1395-1404(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, TISSUE SPECIFICITY, INTERACTION WITH RAC.
[2]"Prediction of the coding sequences of mouse homologues of KIAA gene: IV. The complete nucleotide sequences of 500 mouse KIAA-homologous cDNAs identified by screening of terminal sequences of cDNA clones randomly sampled from size-fractionated libraries."
Okazaki N., Kikuno R., Ohara R., Inamoto S., Koseki H., Hiraoka S., Saga Y., Seino S., Nishimura M., Kaisho T., Hoshino K., Kitamura H., Nagase T., Ohara O., Koga H.
DNA Res. 11:205-218(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Embryonic tail.
[3]"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. expand/collapse author list , 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 3 AND 4), NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 200-892 (ISOFORM 1).
Strain: C57BL/6J and NOD.
Tissue: Corpora quadrigemina and Thymus.
[4]"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 2).
Strain: C57BL/6.
Tissue: Brain.
[5]"POSH acts as a scaffold for a multiprotein complex that mediates JNK activation in apoptosis."
Xu Z., Kukekov N.V., Greene L.A.
EMBO J. 22:252-261(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH MAP3K10; MAP3K11; DLK1; MAP2K4; MAP2K7; MAPK8 AND MAPK9.
[6]"Akt2 negatively regulates assembly of the POSH-MLK-JNK signaling complex."
Figueroa C., Tarras S., Taylor J., Vojtek A.B.
J. Biol. Chem. 278:47922-47927(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH AKT2, MUTAGENESIS OF GLU-470 AND TRP-489, SUBCELLULAR LOCATION.
[7]"Siah1 interacts with the scaffold protein POSH to promote JNK activation and apoptosis."
Xu Z., Sproul A., Wang W., Kukekov N., Greene L.A.
J. Biol. Chem. 281:303-312(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH SIAH1.
[8]"Direct interaction of the molecular scaffolds POSH and JIP is required for apoptotic activation of JNKs."
Kukekov N.V., Xu Z., Greene L.A.
J. Biol. Chem. 281:15517-15524(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH MAPK8IP.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
PIRT09071.
RefSeqNP_067481.2. NM_021506.2.
UniGeneMm.27949.

3D structure databases

ProteinModelPortalQ69ZI1.
SMRQ69ZI1. Positions 3-59, 137-255, 457-512, 839-892.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid208480. 1 interaction.
IntActQ69ZI1. 5 interactions.

PTM databases

PhosphoSiteQ69ZI1.

Proteomic databases

PaxDbQ69ZI1.
PRIDEQ69ZI1.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

GeneID59009.
KEGGmmu:59009.

Organism-specific databases

CTD57630.
MGIMGI:1913066. Sh3rf1.
RougeSearch...

Phylogenomic databases

eggNOGNOG314495.
HOGENOMHOG000045564.
HOVERGENHBG069552.
InParanoidQ69ZI1.
KOK12171.
PhylomeDBQ69ZI1.

Enzyme and pathway databases

UniPathwayUPA00143.

Gene expression databases

GenevestigatorQ69ZI1.

Family and domain databases

Gene3D3.30.40.10. 1 hit.
InterProIPR028502. POSH1.
IPR001452. SH3_domain.
IPR018957. Znf_C3HC4_RING-type.
IPR001841. Znf_RING.
IPR013083. Znf_RING/FYVE/PHD.
IPR017907. Znf_RING_CS.
[Graphical view]
PANTHERPTHR10661:SF8. PTHR10661:SF8. 1 hit.
PfamPF14604. SH3_9. 4 hits.
PF00097. zf-C3HC4. 1 hit.
[Graphical view]
PRINTSPR00452. SH3DOMAIN.
SMARTSM00184. RING. 1 hit.
SM00326. SH3. 4 hits.
[Graphical view]
SUPFAMSSF50044. SSF50044. 4 hits.
PROSITEPS50002. SH3. 4 hits.
PS00518. ZF_RING_1. 1 hit.
PS50089. ZF_RING_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio314548.
PROQ69ZI1.
SOURCESearch...

Entry information

Entry nameSH3R1_MOUSE
AccessionPrimary (citable) accession number: Q69ZI1
Secondary accession number(s): O70254 expand/collapse secondary AC list , Q3UG42, Q6P9M8, Q8BR66, Q8C2T5
Entry history
Integrated into UniProtKB/Swiss-Prot: May 20, 2008
Last sequence update: May 20, 2008
Last modified: June 11, 2014
This is version 81 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PATHWAY comments

Index of metabolic and biosynthesis pathways

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot