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Q7Z6J0 (SH3R1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 93. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | 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
RING finger protein 142
SH3 domain-containing RING finger protein 1
SH3 multiple domains protein 2
Gene names
Name:SH3RF1
Synonyms:KIAA1494, POSH, RNF142, SH3MD2
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length888 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. May be involved in targeting of HIV-1 GAG and GAG-POL polyproteins to the plasma membrane. Ref.6 Ref.11

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. Ref.6 Ref.11

Plays an essential role in the targeting of HIV-1 Gag to the plasma membrane, this function is dependent on it's RING domain, and hence it's E3 ligase activity. Ref.6 Ref.11

Pathway

Protein modification; protein ubiquitination.

Subunit structure

Interacts with Rac; in a GTP-dependent manner By similarity. 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. Interacts with HERP1. Probably part of a signaling complex that may contain SH3RF1, MAPK8IP, DLK1, MAP2K4, MAP2K7, MAPK8, MAPK9, AKT1 and AKT2. Ref.4 Ref.5 Ref.7 Ref.8 Ref.9 Ref.10

Subcellular location

Cytoplasmperinuclear region By similarity. Cell projectionlamellipodium. Cytoplasm. Golgi apparatustrans-Golgi network. Note: Colocalizes, with AKT2, in lamellipodia By similarity. Colocalizes, with HERP1, in trans-Golgi network. Ref.6 Ref.10

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. Ref.9

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 AAH33203.1 differs from that shown. Reason: Frameshift at position 182.

The sequence AAH33203.1 differs from that shown. Reason: Contaminating sequence. Potential poly-A sequence.

The sequence AAH53671.1 differs from that shown. Reason: Contaminating sequence. Sequence of unknown origin in the middle of the protein.

Binary interactions

With

Entry

#Exp.

IntAct

Notes

RAC1P630002EBI-311339,EBI-413628
SIAH2O432552EBI-311339,EBI-948141

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q7Z6J0-1)

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: Q7Z6J0-3)

The sequence of this isoform differs from the canonical sequence as follows:
     394-441: TLNPPLPPPP...AGSTDQIAHL → APPPLLLLLE...IHTLLGKRIN
     442-888: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 888888E3 ubiquitin-protein ligase SH3RF1
PRO_0000334151

Regions

Domain134 – 19360SH3 1
Domain196 – 25964SH3 2
Domain445 – 50662SH3 3
Domain829 – 88860SH3 4
Zinc finger12 – 5342RING-type
Region440 – 543104Interaction with AKT2 By similarity
Compositional bias397 – 4037Poly-Pro
Compositional bias417 – 4248Poly-Ala
Compositional bias657 – 6626Poly-Ala

Amino acid modifications

Modified residue3041Phosphoserine Ref.9 Ref.12

Natural variations

Alternative sequence394 – 44148TLNPP…QIAHL → APPPLLLLLEWDRGPWQDPL TRLHIYGRRLAPVCMLLYIH TLLGKRIN in isoform 2.
VSP_033622
Alternative sequence442 – 888447Missing in isoform 2.
VSP_033623
Natural variant6631P → S.
Corresponds to variant rs3811813 [ dbSNP | Ensembl ].
VAR_043342

Experimental info

Mutagenesis141V → A: Loss of Ubl activity. Ref.10
Mutagenesis3041S → A: Decreased level of phosphorylation and no change in the ability to induce apoptosis. Ref.9
Mutagenesis3041S → D: Decreased level of phosphorylation and Rac-binding ability and important loss of the ability to induce apoptosis. Ref.9
Mutagenesis3041S → E: Decreased Rac-binding ability. Ref.9

Sequences

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

Last modified July 22, 2008. Version 2.
Checksum: B3018000F03D0CF1

FASTA88893,129
        10         20         30         40         50         60 
MDESALLDLL ECPVCLERLD ASAKVLPCQH TFCKRCLLGI VGSRNELRCP ECRTLVGSGV 

        70         80         90        100        110        120 
EELPSNILLV RLLDGIKQRP WKPGPGGGSG TNCTNALRSQ SSTVANCSSK DLQSSQGGQQ 

       130        140        150        160        170        180 
PRVQSWSPPV RGIPQLPCAK ALYNYEGKEP GDLKFSKGDI IILRRQVDEN WYHGEVNGIH 

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

       250        260        270        280        290        300 
MLADKIGIFP ISYVEFNSAA KQLIEWDKPP VPGVDAGECS SAAAQSSTAP KHSDTKKNTK 

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

       370        380        390        400        410        420 
TTGLIVTPPP SSPVTTGPSF TFPSDVPYQA ALGTLNPPLP PPPLLAATVL ASTPPGATAA 

       430        440        450        460        470        480 
AAAAGMGPRP MAGSTDQIAH LRPQTRPSVY VAIYPYTPRK EDELELRKGE MFLVFERCQD 

       490        500        510        520        530        540 
GWFKGTSMHT SKIGVFPGNY VAPVTRAVTN ASQAKVPMST AGQTSRGVTM VSPSTAGGPA 

       550        560        570        580        590        600 
QKLQGNGVAG SPSVVPAAVV SAAHIQTSPQ AKVLLHMTGQ MTVNQARNAV RTVAAHNQER 

       610        620        630        640        650        660 
PTAAVTPIQV QNAAGLSPAS VGLSHHSLAS PQPAPLMPGS ATHTAAISIS RASAPLACAA 

       670        680        690        700        710        720 
AAPLTSPSIT SASLEAEPSG RIVTVLPGLP TSPDSASSAC GNSSATKPDK DSKKEKKGLL 

       730        740        750        760        770        780 
KLLSGASTKR KPRVSPPASP TLEVELGSAE LPLQGAVGPE LPPGGGHGRA GSCPVDGDGP 

       790        800        810        820        830        840 
VTTAVAGAAL AQDAFHRKAS SLDSAVPIAP PPRQACSSLG PVLNESRPVV CERHRVVVSY 

       850        860        870        880 
PPQSEAELEL KEGDIVFVHK KREDGWFKGT LQRNGKTGLF PGSFVENI 

« Hide

Isoform 2 [UniParc].

Checksum: 567606B80C58414A
Show »

FASTA44148,108

References

« Hide 'large scale' references
[1]"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), NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 140-888 (ISOFORM 2).
Tissue: Eye and Ovary.
[2]"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] OF 1-712 (ISOFORM 1).
Tissue: Embryo.
[3]"Prediction of the coding sequences of unidentified human genes. XVII. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro."
Nagase T., Kikuno R., Ishikawa K., Hirosawa M., Ohara O.
DNA Res. 7:143-150(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 251-888 (ISOFORM 1).
Tissue: Brain.
[4]"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.
[5]"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 AKT1 AND AKT2.
[6]"The trans-Golgi network-associated human ubiquitin-protein ligase POSH is essential for HIV type 1 production."
Alroy I., Tuvia S., Greener T., Gordon D., Barr H.M., Taglicht D., Mandil-Levin R., Ben-Avraham D., Konforty D., Nir A., Levius O., Bicoviski V., Dori M., Cohen S., Yaar L., Erez O., Propheta-Meiran O., Koskas M. expand/collapse author list , Caspi-Bachar E., Alchanati I., Sela-Brown A., Moskowitz H., Tessmer U., Schubert U., Reiss Y.
Proc. Natl. Acad. Sci. U.S.A. 102:1478-1483(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION AS AN E3 UBIQUITIN-PROTEIN LIGASE, FUNCTION IN HIV-1 PLASMA MEMBRANE TARGETING, SUBCELLULAR LOCATION, SELF-UBIQUITINATION.
[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.
[9]"Regulation of the pro-apoptotic scaffolding protein POSH by Akt."
Lyons T.R., Thorburn J., Ryan P.W., Thorburn A., Anderson S.M., Kassenbrock C.K.
J. Biol. Chem. 282:21987-21997(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH AKT1 AND AKT2, PHOSPHORYLATION AT SER-304, MUTAGENESIS OF SER-304, IDENTIFICATION BY MASS SPECTROMETRY.
[10]"The ubiquitin E3 ligase POSH regulates calcium homeostasis through spatial control of Herp."
Tuvia S., Taglicht D., Erez O., Alroy I., Alchanati I., Bicoviski V., Dori-Bachash M., Ben-Avraham D., Reiss Y.
J. Cell Biol. 177:51-61(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH HERP1, SUBCELLULAR LOCATION, MUTAGENESIS OF VAL-14.
[11]"POSH stimulates the ubiquitination and the clathrin-independent endocytosis of ROMK1 channels."
Lin D.H., Yue P., Pan C.Y., Sun P., Zhang X., Han Z., Roos M., Caplan M., Giebisch G., Wang W.H.
J. Biol. Chem. 284:29614-29624(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION AS AN E3 UBIQUITIN-PROTEIN LIGASE.
[12]"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis."
Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.
Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-304, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
BC033203 mRNA. Translation: AAH33203.1. Sequence problems.
BC041023 mRNA. Translation: AAH41023.1.
BC053671 mRNA. Translation: AAH53671.1. Sequence problems.
AK021429 mRNA. Translation: BAB13822.1.
AB040927 mRNA. Translation: BAA96018.1.
RefSeqNP_065921.2. NM_020870.3.
UniGeneHs.301804.

3D structure databases

ProteinModelPortalQ7Z6J0.
SMRQ7Z6J0. Positions 137-255, 450-505, 835-888.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid121673. 16 interactions.
IntActQ7Z6J0. 11 interactions.
MINTMINT-2792302.
STRING9606.ENSP00000284637.

PTM databases

PhosphoSiteQ7Z6J0.

Polymorphism databases

DMDM205830834.

Proteomic databases

PaxDbQ7Z6J0.
PRIDEQ7Z6J0.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000284637; ENSP00000284637; ENSG00000154447. [Q7Z6J0-1]
GeneID57630.
KEGGhsa:57630.
UCSCuc003isa.1. human. [Q7Z6J0-1]

Organism-specific databases

CTD57630.
GeneCardsGC04M170015.
HGNCHGNC:17650. SH3RF1.
neXtProtNX_Q7Z6J0.
PharmGKBPA134915904.
HUGESearch...
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG314495.
HOGENOMHOG000045564.
HOVERGENHBG069552.
InParanoidQ7Z6J0.
KOK12171.
OMAPKHSDTK.
OrthoDBEOG7HMS0X.
PhylomeDBQ7Z6J0.
TreeFamTF105571.

Enzyme and pathway databases

SignaLinkQ7Z6J0.
UniPathwayUPA00143.

Gene expression databases

ArrayExpressQ7Z6J0.
BgeeQ7Z6J0.
CleanExHS_SH3RF1.
GenevestigatorQ7Z6J0.

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.
PfamPF00097. 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

ChiTaRSSH3RF1. human.
GeneWikiSH3RF1.
GenomeRNAi57630.
NextBio64333.
PROQ7Z6J0.

Entry information

Entry nameSH3R1_HUMAN
AccessionPrimary (citable) accession number: Q7Z6J0
Secondary accession number(s): Q05BT2 expand/collapse secondary AC list , Q8IW46, Q9HAM2, Q9P234
Entry history
Integrated into UniProtKB/Swiss-Prot: May 20, 2008
Last sequence update: July 22, 2008
Last modified: April 16, 2014
This is version 93 of the entry and version 2 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

PATHWAY comments

Index of metabolic and biosynthesis pathways

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 4

Human chromosome 4: entries, gene names and cross-references to MIM