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Q8TEB7 (RN128_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 107. 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·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
E3 ubiquitin-protein ligase RNF128

EC=6.3.2.-
Alternative name(s):
Gene related to anergy in lymphocytes protein
Short name=GRAIL
RING finger protein 128
Gene names
Name:RNF128
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length428 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

E3 ubiquitin-protein ligase that catalyzes 'Lys-48'- and 'Lys-63'-linked polyubiquitin chains formation. Functions as an inhibitor of cytokine gene transcription. Inhibits IL2 and IL4 transcription, thereby playing an important role in the induction of the anergic phenotype, a long-term stable state of T-lymphocyte unresponsiveness to antigenic stimulation associated with the blockade of interleukin production. Ubiquitinates ARPC5 with 'Lys-48' linkages and COR1A with 'Lys-63' linkages leading to their degradation, down-regulation of these cytosleletal components results in impaired lamellipodium formation and reduced accumulation of F-actin at the immunological synapse. Functions in the patterning of the dorsal ectoderm; sensitizes ectoderm to respond to neural-inducing signals. Ref.1 Ref.5

Pathway

Protein modification; protein ubiquitination.

Subcellular location

Endomembrane system; Single-pass membrane protein By similarity. Cytoplasmcytoskeleton. Cytoplasmperinuclear region By similarity. Note: Localized in an asymmetric perinuclear punctate manner. Localizes to the internal pool of the transferrin recycling endosomal pathway. Partially colocalized with the endoplasmic reticulum resident HSPA5, with Golgi resident STX5, and with the late endosomal GTPase RAB7A By similarity. Ref.1 Ref.5

Induction

Induced under anergic conditions. Up-regulated during T-cell anergy induction following signaling through the T-cell antigen receptor. Ref.1

Domain

Binding to E2 ubiquitin-conjugating enzyme requires an intact RING finger domain.

Post-translational modification

Auto-ubiquitinated. Controls the development of T-cell clonal anergy by ubiquitination.

Sequence similarities

Contains 1 PA (protease associated) domain.

Contains 1 RING-type zinc finger.

Sequence caution

The sequence BAB15682.1 differs from that shown. Reason: Frameshift at position 291.

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q8TEB7-1)

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: Q8TEB7-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-161: MGPPPGAGVS...RNEVIPMSHP → MNQENRSSFF...GNQTIQMANF
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 3838 Potential
Chain39 – 428390E3 ubiquitin-protein ligase RNF128
PRO_0000261412

Regions

Transmembrane208 – 22821Helical; Potential
Domain75 – 183109PA
Zinc finger277 – 31842RING-type; atypical

Amino acid modifications

Glycosylation481N-linked (GlcNAc...) Potential
Glycosylation591N-linked (GlcNAc...) Potential
Glycosylation1011N-linked (GlcNAc...) Ref.6

Natural variations

Alternative sequence1 – 161161MGPPP…PMSHP → MNQENRSSFFWLLVIFTFLL KITASFSMSAYVTVTYYNET SNYTAIETCECGVYGLASPV ANAMGVVGIPKNNNYQACDH NTEFSNTKKPWIALIERGNC TFSEKIQTAGRRNADAVVIY NAPETGNQTIQMANF in isoform 2.
VSP_021685

Experimental info

Sequence conflict41P → L in AAK77554. Ref.1
Sequence conflict2141S → P in AAK77554. Ref.1
Sequence conflict2231V → G in AAK77554. Ref.1
Sequence conflict2551I → L in BAB15682. Ref.2
Sequence conflict2571R → G in AAH56677. Ref.4
Sequence conflict2611R → L in BAB15682. Ref.2
Sequence conflict3361V → A in BAB15682. Ref.2

Secondary structure

................... 428
Helix Strand Turn

Details...

Sequences

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

Last modified June 1, 2002. Version 1.
Checksum: 32F9CDB32BF208FA

FASTA42846,521
        10         20         30         40         50         60 
MGPPPGAGVS CRGGCGFSRL LAWCFLLALS PQAPGSRGAE AVWTAYLNVS WRVPHTGVNR 

        70         80         90        100        110        120 
TVWELSEEGV YGQDSPLEPV AGVLVPPDGP GALNACNPHT NFTVPTVWGS TVQVSWLALI 

       130        140        150        160        170        180 
QRGGGCTFAD KIHLAYERGA SGAVIFNFPG TRNEVIPMSH PGAVDIVAIM IGNLKGTKIL 

       190        200        210        220        230        240 
QSIQRGIQVT MVIEVGKKHG PWVNHYSIFF VSVSFFIITA ATVGYFIFYS ARRLRNARAQ 

       250        260        270        280        290        300 
SRKQRQLKAD AKKAIGRLQL RTLKQGDKEI GPDGDSCAVC IELYKPNDLV RILTCNHIFH 

       310        320        330        340        350        360 
KTCVDPWLLE HRTCPMCKCD ILKALGIEVD VEDGSVSLQV PVSNEISNSA SSHEEDNRSE 

       370        380        390        400        410        420 
TASSGYASVQ GTDEPPLEEH VQSTNESLQL VNHEANSVAV DVIPHVDNPT FEEDETPNQE 


TAVREIKS 

« Hide

Isoform 2 [UniParc].

Checksum: CCE3A965DB2F4F2E
Show »

FASTA40244,617

References

« Hide 'large scale' references
[1]"GRAIL: an E3 ubiquitin ligase that inhibits cytokine gene transcription is expressed in anergic CD4+ T cells."
Anandasabapathy N., Ford G.S., Bloom D., Holness C., Paragas V., Seroogy C., Skrenta H., Hollenhorst M., Fathman C.G., Soares L.
Immunity 18:535-547(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, SUBCELLULAR LOCATION, INDUCTION, MUTAGENESIS.
[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] (ISOFORMS 1 AND 2).
Tissue: Hepatoma, Lung and Mammary gland.
[3]"The DNA sequence of the human X chromosome."
Ross M.T., Grafham D.V., Coffey A.J., Scherer S., McLay K., Muzny D., Platzer M., Howell G.R., Burrows C., Bird C.P., Frankish A., Lovell F.L., Howe K.L., Ashurst J.L., Fulton R.S., Sudbrak R., Wen G., Jones M.C. expand/collapse author list , Hurles M.E., Andrews T.D., Scott C.E., Searle S., Ramser J., Whittaker A., Deadman R., Carter N.P., Hunt S.E., Chen R., Cree A., Gunaratne P., Havlak P., Hodgson A., Metzker M.L., Richards S., Scott G., Steffen D., Sodergren E., Wheeler D.A., Worley K.C., Ainscough R., Ambrose K.D., Ansari-Lari M.A., Aradhya S., Ashwell R.I., Babbage A.K., Bagguley C.L., Ballabio A., Banerjee R., Barker G.E., Barlow K.F., Barrett I.P., Bates K.N., Beare D.M., Beasley H., Beasley O., Beck A., Bethel G., Blechschmidt K., Brady N., Bray-Allen S., Bridgeman A.M., Brown A.J., Brown M.J., Bonnin D., Bruford E.A., Buhay C., Burch P., Burford D., Burgess J., Burrill W., Burton J., Bye J.M., Carder C., Carrel L., Chako J., Chapman J.C., Chavez D., Chen E., Chen G., Chen Y., Chen Z., Chinault C., Ciccodicola A., Clark S.Y., Clarke G., Clee C.M., Clegg S., Clerc-Blankenburg K., Clifford K., Cobley V., Cole C.G., Conquer J.S., Corby N., Connor R.E., David R., Davies J., Davis C., Davis J., Delgado O., Deshazo D., Dhami P., Ding Y., Dinh H., Dodsworth S., Draper H., Dugan-Rocha S., Dunham A., Dunn M., Durbin K.J., Dutta I., Eades T., Ellwood M., Emery-Cohen A., Errington H., Evans K.L., Faulkner L., Francis F., Frankland J., Fraser A.E., Galgoczy P., Gilbert J., Gill R., Gloeckner G., Gregory S.G., Gribble S., Griffiths C., Grocock R., Gu Y., Gwilliam R., Hamilton C., Hart E.A., Hawes A., Heath P.D., Heitmann K., Hennig S., Hernandez J., Hinzmann B., Ho S., Hoffs M., Howden P.J., Huckle E.J., Hume J., Hunt P.J., Hunt A.R., Isherwood J., Jacob L., Johnson D., Jones S., de Jong P.J., Joseph S.S., Keenan S., Kelly S., Kershaw J.K., Khan Z., Kioschis P., Klages S., Knights A.J., Kosiura A., Kovar-Smith C., Laird G.K., Langford C., Lawlor S., Leversha M., Lewis L., Liu W., Lloyd C., Lloyd D.M., Loulseged H., Loveland J.E., Lovell J.D., Lozado R., Lu J., Lyne R., Ma J., Maheshwari M., Matthews L.H., McDowall J., McLaren S., McMurray A., Meidl P., Meitinger T., Milne S., Miner G., Mistry S.L., Morgan M., Morris S., Mueller I., Mullikin J.C., Nguyen N., Nordsiek G., Nyakatura G., O'dell C.N., Okwuonu G., Palmer S., Pandian R., Parker D., Parrish J., Pasternak S., Patel D., Pearce A.V., Pearson D.M., Pelan S.E., Perez L., Porter K.M., Ramsey Y., Reichwald K., Rhodes S., Ridler K.A., Schlessinger D., Schueler M.G., Sehra H.K., Shaw-Smith C., Shen H., Sheridan E.M., Shownkeen R., Skuce C.D., Smith M.L., Sotheran E.C., Steingruber H.E., Steward C.A., Storey R., Swann R.M., Swarbreck D., Tabor P.E., Taudien S., Taylor T., Teague B., Thomas K., Thorpe A., Timms K., Tracey A., Trevanion S., Tromans A.C., d'Urso M., Verduzco D., Villasana D., Waldron L., Wall M., Wang Q., Warren J., Warry G.L., Wei X., West A., Whitehead S.L., Whiteley M.N., Wilkinson J.E., Willey D.L., Williams G., Williams L., Williamson A., Williamson H., Wilming L., Woodmansey R.L., Wray P.W., Yen J., Zhang J., Zhou J., Zoghbi H., Zorilla S., Buck D., Reinhardt R., Poustka A., Rosenthal A., Lehrach H., Meindl A., Minx P.J., Hillier L.W., Willard H.F., Wilson R.K., Waterston R.H., Rice C.M., Vaudin M., Coulson A., Nelson D.L., Weinstock G., Sulston J.E., Durbin R.M., Hubbard T., Gibbs R.A., Beck S., Rogers J., Bentley D.R.
Nature 434:325-337(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[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 1).
Tissue: Brain.
[5]"GRAIL (gene related to anergy in lymphocytes) regulates cytoskeletal reorganization through ubiquitination and degradation of Arp2/3 subunit 5 and coronin 1A."
Ichikawa D., Mizuno M., Yamamura T., Miyake S.
J. Biol. Chem. 286:43465-43474(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION.
[6]"PA domain of the E3 ligase GRAIL."
Structural genomics consortium (SGC)
Submitted (OCT-2009) to the PDB data bank
Cited for: X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 38-204, GLYCOSYLATION AT ASN-101.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF394689 mRNA. Translation: AAK77554.1.
AK027169 mRNA. Translation: BAB15682.1. Frameshift.
AK074264 mRNA. Translation: BAB85033.1.
AK126553 mRNA. Translation: BAC86589.1.
AL391315 Genomic DNA. Translation: CAI39545.1.
AL391315, AL606833 Genomic DNA. Translation: CAI39546.1.
AL606833, AL391315 Genomic DNA. Translation: CAI41228.1.
BC030951 mRNA. Translation: AAH30951.1.
BC056677 mRNA. Translation: AAH56677.1.
BC063404 mRNA. Translation: AAH63404.1.
RefSeqNP_078815.3. NM_024539.3.
NP_919445.1. NM_194463.1.
UniGeneHs.496542.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
3ICUX-ray2.10A38-204[»]
ProteinModelPortalQ8TEB7.
SMRQ8TEB7. Positions 38-204, 277-320.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid122731. 12 interactions.
IntActQ8TEB7. 2 interactions.
STRING9606.ENSP00000255499.

PTM databases

PhosphoSiteQ8TEB7.

Polymorphism databases

DMDM74751443.

Proteomic databases

PaxDbQ8TEB7.
PRIDEQ8TEB7.

Protocols and materials databases

DNASU79589.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000255499; ENSP00000255499; ENSG00000133135. [Q8TEB7-1]
ENST00000324342; ENSP00000316127; ENSG00000133135. [Q8TEB7-2]
GeneID79589.
KEGGhsa:79589.
UCSCuc004emk.3. human. [Q8TEB7-2]
uc004eml.3. human. [Q8TEB7-1]

Organism-specific databases

CTD79589.
GeneCardsGC0XP105937.
HGNCHGNC:21153. RNF128.
HPAHPA019675.
MIM300439. gene.
neXtProtNX_Q8TEB7.
PharmGKBPA134868457.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG271676.
HOGENOMHOG000231432.
HOVERGENHBG057659.
InParanoidQ8TEB7.
KOK10629.
OMATVPGDWG.
PhylomeDBQ8TEB7.
TreeFamTF317486.

Enzyme and pathway databases

UniPathwayUPA00143.

Gene expression databases

ArrayExpressQ8TEB7.
BgeeQ8TEB7.
CleanExHS_RNF128.
GenevestigatorQ8TEB7.

Family and domain databases

Gene3D3.30.40.10. 1 hit.
InterProIPR003137. Protease-assoc_domain.
IPR001841. Znf_RING.
IPR013083. Znf_RING/FYVE/PHD.
[Graphical view]
PfamPF02225. PA. 1 hit.
PF13639. zf-RING_2. 1 hit.
[Graphical view]
SMARTSM00184. RING. 1 hit.
[Graphical view]
PROSITEPS50089. ZF_RING_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceQ8TEB7.
GeneWikiRNF128.
GenomeRNAi79589.
NextBio35460171.
PROQ8TEB7.
SOURCESearch...

Entry information

Entry nameRN128_HUMAN
AccessionPrimary (citable) accession number: Q8TEB7
Secondary accession number(s): A0PJI4 expand/collapse secondary AC list , Q6PH80, Q6ZTJ8, Q96RF3, Q9H5E4
Entry history
Integrated into UniProtKB/Swiss-Prot: November 28, 2006
Last sequence update: June 1, 2002
Last modified: April 16, 2014
This is version 107 of the entry and version 1 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

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

PATHWAY comments

Index of metabolic and biosynthesis pathways

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human chromosome X

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