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Protein

E3 ubiquitin-protein ligase SH3RF1

Gene

SH3RF1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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.By similarity2 Publications
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.
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.

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.

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

GO - Biological processi

  • apoptotic process Source: InterPro
  • negative regulation of apoptotic process Source: UniProtKB
  • negative regulation of cysteine-type endopeptidase activity involved in apoptotic process Source: UniProtKB
  • negative regulation of extrinsic apoptotic signaling pathway Source: UniProtKB
  • protein ubiquitination Source: UniProtKB-UniPathway
  • regulation of JNK cascade Source: InterPro

Keywordsi

Molecular functionTransferase
Biological processUbl conjugation pathway
LigandMetal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-HSA-983168 Antigen processing: Ubiquitination & Proteasome degradation
SignaLinkiQ7Z6J0
SIGNORiQ7Z6J0
UniPathwayiUPA00143

Names & Taxonomyi

Protein namesi
Recommended name:
E3 ubiquitin-protein ligase SH3RF1 (EC:2.3.2.27)
Alternative name(s):
Plenty of SH3s
Short name:
Protein POSH
RING finger protein 142
RING-type E3 ubiquitin transferase SH3RF1Curated
SH3 domain-containing RING finger protein 1
SH3 multiple domains protein 2
Gene namesi
Name:SH3RF1
Synonyms:KIAA1494, POSH, RNF142, SH3MD2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 4

Organism-specific databases

EuPathDBiHostDB:ENSG00000154447.14
HGNCiHGNC:17650 SH3RF1
neXtProtiNX_Q7Z6J0

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
Mutagenesisi14V → A: Loss of Ubl activity. 1 Publication1
Mutagenesisi304S → A: Decreased level of phosphorylation and no change in the ability to induce apoptosis. 1 Publication1
Mutagenesisi304S → D: Decreased level of phosphorylation and Rac-binding ability and important loss of the ability to induce apoptosis. 1 Publication1
Mutagenesisi304S → E: Decreased Rac-binding ability. 1 Publication1

Organism-specific databases

DisGeNETi57630
OpenTargetsiENSG00000154447
PharmGKBiPA134915904

Polymorphism and mutation databases

BioMutaiSH3RF1
DMDMi205830834

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00003341511 – 888E3 ubiquitin-protein ligase SH3RF1Add BLAST888

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei304PhosphoserineCombined sources1 Publication1
Modified residuei532PhosphoserineCombined sources1
Modified residuei735PhosphoserineBy similarity1

Post-translational modificationi

Phosphorylated at Ser-304 by AKT1 and AKT2. When phosphorylated, it has reduced ability to bind Rac.1 Publication
Subject to ubiquitination and proteasomal degradation.By similarity

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ7Z6J0
MaxQBiQ7Z6J0
PaxDbiQ7Z6J0
PeptideAtlasiQ7Z6J0
PRIDEiQ7Z6J0

PTM databases

iPTMnetiQ7Z6J0
PhosphoSitePlusiQ7Z6J0

Expressioni

Gene expression databases

BgeeiENSG00000154447
CleanExiHS_SH3RF1
ExpressionAtlasiQ7Z6J0 baseline and differential
GenevisibleiQ7Z6J0 HS

Organism-specific databases

HPAiHPA074783

Interactioni

Subunit structurei

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.By similarity6 Publications

Binary interactionsi

Show more details

Protein-protein interaction databases

BioGridi121673, 21 interactors
CORUMiQ7Z6J0
DIPiDIP-31636N
ELMiQ7Z6J0
IntActiQ7Z6J0, 12 interactors
MINTiQ7Z6J0
STRINGi9606.ENSP00000284637

Structurei

3D structure databases

ProteinModelPortaliQ7Z6J0
SMRiQ7Z6J0
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini134 – 193SH3 1PROSITE-ProRule annotationAdd BLAST60
Domaini196 – 259SH3 2PROSITE-ProRule annotationAdd BLAST64
Domaini445 – 506SH3 3PROSITE-ProRule annotationAdd BLAST62
Domaini829 – 888SH3 4PROSITE-ProRule annotationAdd BLAST60

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni440 – 543Interaction with AKT2By similarityAdd BLAST104

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi397 – 403Poly-Pro7
Compositional biasi417 – 424Poly-Ala8
Compositional biasi657 – 662Poly-Ala6

Domaini

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

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
GeneTreeiENSGT00760000119190
HOGENOMiHOG000045564
HOVERGENiHBG069552
InParanoidiQ7Z6J0
KOiK12171
OMAiGWYKGTH
OrthoDBiEOG091G09B6
PhylomeDBiQ7Z6J0
TreeFamiTF105571

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 (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q7Z6J0-1) [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 EELPSNILLV RLLDGIKQRP WKPGPGGGSG TNCTNALRSQ
110 120 130 140 150
SSTVANCSSK DLQSSQGGQQ PRVQSWSPPV RGIPQLPCAK ALYNYEGKEP
160 170 180 190 200
GDLKFSKGDI IILRRQVDEN WYHGEVNGIH GFFPTNFVQI IKPLPQPPPQ
210 220 230 240 250
CKALYDFEVK DKEADKDCLP FAKDDVLTVI RRVDENWAEG MLADKIGIFP
260 270 280 290 300
ISYVEFNSAA KQLIEWDKPP VPGVDAGECS SAAAQSSTAP KHSDTKKNTK
310 320 330 340 350
KRHSFTSLTM ANKSSQASQN RHSMEISPPV LISSSNPTAA ARISELSGLS
360 370 380 390 400
CSAPSQVHIS TTGLIVTPPP SSPVTTGPSF TFPSDVPYQA ALGTLNPPLP
410 420 430 440 450
PPPLLAATVL ASTPPGATAA AAAAGMGPRP MAGSTDQIAH LRPQTRPSVY
460 470 480 490 500
VAIYPYTPRK EDELELRKGE MFLVFERCQD GWFKGTSMHT SKIGVFPGNY
510 520 530 540 550
VAPVTRAVTN ASQAKVPMST AGQTSRGVTM VSPSTAGGPA QKLQGNGVAG
560 570 580 590 600
SPSVVPAAVV SAAHIQTSPQ AKVLLHMTGQ MTVNQARNAV RTVAAHNQER
610 620 630 640 650
PTAAVTPIQV QNAAGLSPAS VGLSHHSLAS PQPAPLMPGS ATHTAAISIS
660 670 680 690 700
RASAPLACAA AAPLTSPSIT SASLEAEPSG RIVTVLPGLP TSPDSASSAC
710 720 730 740 750
GNSSATKPDK DSKKEKKGLL KLLSGASTKR KPRVSPPASP TLEVELGSAE
760 770 780 790 800
LPLQGAVGPE LPPGGGHGRA GSCPVDGDGP VTTAVAGAAL AQDAFHRKAS
810 820 830 840 850
SLDSAVPIAP PPRQACSSLG PVLNESRPVV CERHRVVVSY PPQSEAELEL
860 870 880
KEGDIVFVHK KREDGWFKGT LQRNGKTGLF PGSFVENI
Length:888
Mass (Da):93,129
Last modified:July 22, 2008 - v2
Checksum:iB3018000F03D0CF1
GO
Isoform 2 (identifier: Q7Z6J0-3) [UniParc]FASTAAdd to basket

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.
Show »
Length:441
Mass (Da):48,108
Checksum:i567606B80C58414A
GO

Sequence cautioni

The sequence AAH33203 differs from that shown. Contaminating sequence. Potential poly-A sequence.Curated
The sequence AAH33203 differs from that shown. Reason: Frameshift at position 182.Curated
The sequence AAH53671 differs from that shown. Contaminating sequence. Sequence of unknown origin in the middle of the protein.Curated

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_043342663P → S. Corresponds to variant dbSNP:rs3811813Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_033622394 – 441TLNPP…QIAHL → APPPLLLLLEWDRGPWQDPL TRLHIYGRRLAPVCMLLYIH TLLGKRIN in isoform 2. 1 PublicationAdd BLAST48
Alternative sequenceiVSP_033623442 – 888Missing in isoform 2. 1 PublicationAdd BLAST447

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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
CCDSiCCDS34099.1 [Q7Z6J0-1]
RefSeqiNP_065921.2, NM_020870.3 [Q7Z6J0-1]
UniGeneiHs.301804

Genome annotation databases

EnsembliENST00000284637; ENSP00000284637; ENSG00000154447 [Q7Z6J0-1]
GeneIDi57630
KEGGihsa:57630
UCSCiuc003isa.2 human [Q7Z6J0-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiSH3R1_HUMAN
AccessioniPrimary (citable) accession number: Q7Z6J0
Secondary accession number(s): Q05BT2
, Q8IW46, Q9HAM2, Q9P234
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 20, 2008
Last sequence update: July 22, 2008
Last modified: March 28, 2018
This is version 126 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health