Reviewed, UniProtKB/Swiss-Prot Q7Z6J0 (SH3R1_HUMAN)

Names and origin

Protein names

Recommended name:
    Putative E3 ubiquitin-protein ligase SH3RF1
    EC=6.3.2.-
Alternative name(s):
    SH3 domain-containing RING finger protein 1
    Plenty of SH3s
      Short name=Protein POSH
    SH3 multiple domains protein 2
    RING finger protein 142

Gene names

Name:	SH3RF1
Synonyms:	KIAA1494, POSH, RNF142, SH3MD2

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	888 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence 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 menbrane. 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.
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.
Subcellular location	Cytoplasm › perinuclear regionBy similarity. Cell projection › lamellipodium. Cytoplasm. Golgi apparatus › trans-Golgi network. Note= Colocalizes, with AKT2, in lamellipodia By similarity. Colocalizes, with HERP1, in trans-Golgi network.
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. 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: Miscellaneous discrepancy. Contaminating sequence. Potential poly-A sequence. The sequence AAH53671.1 differs from that shown. Reason: Miscellaneous discrepancy. Contaminating sequence. Sequence of unknown origin in the middle of the protein.

Ontologies

Keywords
Cellular component	Cell projection Cytoplasm Golgi apparatus
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Repeat SH3 domain Zinc-finger
Ligand	Metal-binding Zinc
Molecular function	Ligase
PTM	Phosphoprotein Ubl conjugation
Gene Ontology (GO)
Cellular component	Golgi apparatus Inferred from electronic annotation. Source: UniProtKB-KW cell projection Inferred from electronic annotation. Source: UniProtKB-KW
Molecular function	ligase activity Inferred from electronic annotation. Source: UniProtKB-KW protein binding Ref.9 Inferred from physical interaction. Source: IntAct zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
AKT1	P31749	1	EBI-311339,EBI-296087
AKT2	P31751	1	EBI-311339,EBI-296058

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.

Notes: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 888	888	Putative E3 ubiquitin-protein ligase SH3RF1		PRO_0000334151
Regions
	Domain	134 – 193	60	SH3 1
	Domain	196 – 259	64	SH3 2
	Domain	445 – 506	62	SH3 3
	Domain	829 – 888	60	SH3 4
	Zinc finger	12 – 53	42	RING-type
	Region	440 – 543	104	Interaction with AKT2 By similarity
	Compositional bias	397 – 403	7	Poly-Pro
	Compositional bias	417 – 424	8	Poly-Ala
	Compositional bias	657 – 662	6	Poly-Ala
Amino acid modifications
	Modified residue	304	1	Phosphoserine
Natural variations
	Alternative sequence	394 – 441	48	TLNPP…QIAHL → APPPLLLLLEWDRGPWQDPL TRLHIYGRRLAPVCMLLYIH TLLGKRIN in isoform 2.		VSP_033622
	Alternative sequence	442 – 888	447	Missing in isoform 2.		VSP_033623
	Natural variant	663	1	P → S: dbSNP rs3811813.		VAR_043342
Experimental info
	Mutagenesis	14	1	V → A: Loss of Ubl activity
	Mutagenesis	304	1	S → A: Decreased level of phosphorylation and no change in the ability to induce apoptosis
	Mutagenesis	304	1	S → D: Decreased level of phosphorylation and Rac-binding ability and important loss of the ability to induce apoptosis
	Mutagenesis	304	1	S → E: Decreased Rac-binding ability

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified July 22, 2008. Version 2. Checksum: B3018000F03D0CF1	FASTA	888	93,129
	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
	Isoform 2 [UniParc]. Checksum: 567606B80C58414A		441	48,108
	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 ALGAPPPLLL LLEWDRGPWQ DPLTRLHIYG 430 440 RRLAPVCMLL YIHTLLGKRI N

References

	« Hide 'large scale' referencesShow '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: 15489334] [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. , 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: 14702039] [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: 10819331] [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: 12514131] [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: 14504284] [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. , 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: 15659549] [Abstract] Cited for: FUNCTION, 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: 16230351] [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: 16571722] [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: 17535800] [Abstract] Cited for: INTERACTION WITH AKT1 AND AKT2, PHOSPHORYLATION AT SER-304, MUTAGENESIS OF SER-304, 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: 17420289] [Abstract] Cited for: INTERACTION WITH HERP1, SUBCELLULAR LOCATION, MUTAGENESIS OF VAL-14.

Cross-references

Sequence databases
EMBLGenBankDDBJ	BC033203 mRNA. Translation: AAH33203.1. Sequence problems. BC041023 mRNA. Translation: AAH41023.1. BC053671 mRNA. Translation: AAH53671.1. AK021429 mRNA. Translation: BAB13822.1. AB040927 mRNA. Translation: BAA96018.1.
RefSeq	NP_065921.2.
UniGene	Hs.301804
3D structure databases
HSSP	HSSP built from PDB template 1K4U based on UniProtKB P19878.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q7Z6J0.
PTM databases
PhosphoSite	Q7Z6J0.
Genome annotation databases
Ensembl	ENSG00000154447. Homo sapiens. [Contig view]
GeneID	57630.
KEGG	hsa:57630.
Organism-specific databases
HGNC	HGNC:17650. SH3RF1.
HUGE	Search...
GenAtlas	Search...
GeneCards	Search...
Phylogenomic databases
HOVERGEN	Q7Z6J0.
Gene expression databases
CleanEx	HS_SH3RF1.
Family and domain databases
InterPro	IPR000108. Neu_cyt_fact_2. IPR001452. SH3. IPR001841. Znf_RING. IPR013083. Znf_RING/FYVE/PHD. [Graphical view]
Gene3D	G3DSA:3.30.40.10. Znf_RING/FYVE/PHD. 1 hit.
Pfam	PF00018. SH3_1. 6 hits. PF00097. zf-C3HC4. 1 hit. [Graphical view]
PRINTS	PR00499. P67PHOX. PR00452. SH3DOMAIN.
ProDom	PD000066. SH3. 6 hits. [Graphical view] [Entries sharing at least one domain]
SMART	SM00184. RING. 1 hit. SM00326. SH3. 6 hits. [Graphical view]
PROSITE	PS50002. SH3. 4 hits. PS00518. ZF_RING_1. 1 hit. PS50089. ZF_RING_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
LinkHub	Q7Z6J0.
NextBio	64333.

Entry information

Entry name

SH3R1_HUMAN

Accession

Primary (citable) accession number: Q7Z6J0
Secondary accession number(s): Q05BT2 , Q8IW46, Q9HAM2, Q9P234

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 20, 2008
Last sequence update:	July 22, 2008
Last modified:	November 25, 2008
This is version 38 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)