Q8TEB7 (RN128_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
E3 ubiquitin-protein ligase RNF128
EC=6.3.2.-

Alternative name(s):
Gene related to anergy in lymphocytes protein
RING finger protein 128

Gene names

Name:	RNF128
Synonyms:	GRAIL

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	428 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	E3 ubiquitin-protein ligase that catalyzes polyubiquitin chains. Functions as an inhibitor of cytokine gene transcription. Inhibits IL2 and IL4 transcription and this activity is likely to be mediated by E3 ligase activity. Plays an important role in the induction of the anergic phenotype. Functions in the patterning of the dorsal ectoderm; sensitizes ectoderm to respond to neural-inducing signals By similarity. Ref.1
Pathway	Protein modification; protein ubiquitination.
Subcellular location	Endomembrane system; Single-pass membrane protein By similarity. Cytoplasm › perinuclear 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
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.

Ontologies

Keywords
Biological process	Ubl conjugation pathway
Cellular component	Cytoplasm Membrane
Coding sequence diversity	Alternative splicing
Domain	Signal Transmembrane Transmembrane helix Zinc-finger
Ligand	Metal-binding Zinc
Molecular function	Ligase
PTM	Glycoprotein Ubl conjugation
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	negative regulation of cytokine biosynthetic process Inferred from electronic annotation. Source: Compara
Cellular_component	Golgi apparatus Inferred from electronic annotation. Source: Compara endomembrane system Inferred from electronic annotation. Source: UniProtKB-SubCell endoplasmic reticulum Inferred from electronic annotation. Source: Compara integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW late endosome Inferred from electronic annotation. Source: Compara perinuclear region of cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	ubiquitin-protein ligase activity Inferred from electronic annotation. Source: Compara zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

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 key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 38

38

Potential

Chain

39 – 428

390

E3 ubiquitin-protein ligase RNF128

PRO_0000261412

Regions

Transmembrane

208 – 228

21

Helical; Potential

Domain

75 – 183

109

PA

Zinc finger

277 – 318

42

RING-type; atypical

Amino acid modifications

Glycosylation

48

1

N-linked (GlcNAc...) Potential

Glycosylation

59

1

N-linked (GlcNAc...) Potential

Glycosylation

101

1

N-linked (GlcNAc...) Ref.5

Natural variations

Alternative sequence

1 – 161

161

MGPPP…PMSHP → MNQENRSSFFWLLVIFTFLL KITASFSMSAYVTVTYYNET SNYTAIETCECGVYGLASPV ANAMGVVGIPKNNNYQACDH NTEFSNTKKPWIALIERGNC TFSEKIQTAGRRNADAVVIY NAPETGNQTIQMANF in isoform 2.

VSP_021685

Experimental info

Sequence conflict

4

1

P → L in AAK77554. Ref.1

Sequence conflict

214

1

S → P in AAK77554. Ref.1

Sequence conflict

223

1

V → G in AAK77554. Ref.1

Sequence conflict

255

1

I → L in BAB15682. Ref.2

Sequence conflict

257

1

R → G in AAH56677. Ref.4

Sequence conflict

261

1

R → L in BAB15682. Ref.2

Sequence conflict

336

1

V → A in BAB15682. Ref.2

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

428

Helix Strand Turn

Details...

Beta strand

42 – 52

11

Beta strand

61 – 71

11

Beta strand

80 – 85

6

Beta strand

116 – 122

7

Helix

128 – 137

10

Beta strand

141 – 146

6

Beta strand

165 – 171

7

Helix

173 – 184

12

Beta strand

189 – 199

11

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified June 1, 2002. Version 1. Checksum: 32F9CDB32BF208FA	FASTA	428	46,521
	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
	Isoform 2 [UniParc]. Checksum: CCE3A965DB2F4F2E	FASTA	402	44,617
	10 20 30 40 50 60 MNQENRSSFF WLLVIFTFLL KITASFSMSA YVTVTYYNET SNYTAIETCE CGVYGLASPV 70 80 90 100 110 120 ANAMGVVGIP KNNNYQACDH NTEFSNTKKP WIALIERGNC TFSEKIQTAG RRNADAVVIY 130 140 150 160 170 180 NAPETGNQTI QMANFGAVDI VAIMIGNLKG TKILQSIQRG IQVTMVIEVG KKHGPWVNHY 190 200 210 220 230 240 SIFFVSVSFF IITAATVGYF IFYSARRLRN ARAQSRKQRQ LKADAKKAIG RLQLRTLKQG 250 260 270 280 290 300 DKEIGPDGDS CAVCIELYKP NDLVRILTCN HIFHKTCVDP WLLEHRTCPM CKCDILKALG 310 320 330 340 350 360 IEVDVEDGSV SLQVPVSNEI SNSASSHEED NRSETASSGY ASVQGTDEPP LEEHVQSTNE 370 380 390 400 SLQLVNHEAN SVAVDVIPHV DNPTFEEDET PNQETAVREI KS

References

	« Hide 'large scale' referencesShow '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. , 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. , 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]	"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.
BC056677 mRNA. Translation: AAH56677.1.
BC063404 mRNA. Translation: AAH63404.1.

IPI

IPI00152698.
IPI00376602.

RefSeq

NP_078815.3. NM_024539.3.
NP_919445.1. NM_194463.1.

UniGene

Hs.496542.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3ICU	X-ray	2.10	A	38-204	[»]

ProteinModelPortal

Q8TEB7.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q8TEB7. 2 interactions.

STRING

9606.ENSP00000255499.

PTM databases

PhosphoSite

Q8TEB7.

Polymorphism databases

DMDM

74751443.

Proteomic databases

PaxDb

Q8TEB7.

PRIDE

Q8TEB7.

Protocols and materials databases

DNASU

79589.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000255499; ENSP00000255499; ENSG00000133135.
ENST00000324342; ENSP00000316127; ENSG00000133135.

GeneID

79589.

KEGG

hsa:79589.

UCSC

uc004emk.3. human.
uc004eml.3. human.

Organism-specific databases

CTD

79589.

GeneCards

GC0XP105937.

HGNC

HGNC:21153. RNF128.

HPA

HPA019675.

MIM

300439. gene.

neXtProt

NX_Q8TEB7.

PharmGKB

PA134868457.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG271676.

HOGENOM

HOG000231432.

HOVERGEN

HBG057659.

InParanoid

Q8TEB7.

KO

K10629.

OMA

HEASSMA.

PhylomeDB

Q8TEB7.

Enzyme and pathway databases

Pathway_Interaction_DB

nfat_tfpathway. Calcineurin-regulated NFAT-dependent transcription in lymphocytes.

UniPathway

UPA00143.

Gene expression databases

ArrayExpress

Q8TEB7.

Bgee

Q8TEB7.

CleanEx

HS_RNF128.

Genevestigator

Q8TEB7.

Family and domain databases

Gene3D

3.30.40.10. 1 hit.

InterPro

IPR003137. Protease-assoc_domain.
IPR001841. Znf_RING.
IPR013083. Znf_RING/FYVE/PHD.
[Graphical view]

Pfam

PF02225. PA. 1 hit.
PF13639. zf-RING_2. 1 hit.
[Graphical view]

SMART

SM00184. RING. 1 hit.
[Graphical view]

PROSITE

PS00518. ZF_RING_1. False negative.
PS50089. ZF_RING_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

Q8TEB7.

GenomeRNAi

79589.

NextBio

68594.

SOURCE

Search...

Entry information

Entry name

RN128_HUMAN

Accession

Primary (citable) accession number: Q8TEB7
Secondary accession number(s): Q6PH80 , Q6ZTJ8, Q96RF3, Q9H5E4

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 28, 2006
Last sequence update:	June 1, 2002
Last modified:	May 1, 2013
This is version 100 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.