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Protein

Tripartite motif-containing protein 2

Gene

TRIM2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

UBE2D1-dependent E3 ubiquitin-protein ligase that mediates the ubiquitination of NEFL and of phosphorylated BCL2L11. Plays a neuroprotective function. May play a role in neuronal rapid ischemic tolerance.By similarity

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 fingeri23 – 64RING-typePROSITE-ProRule annotationAdd BLAST42
Zinc fingeri113 – 154B box-typePROSITE-ProRule annotationAdd BLAST42

GO - Molecular functioni

  • ligase activity Source: UniProtKB-KW
  • ubiquitin-protein transferase activity Source: UniProtKB
  • zinc ion binding Source: UniProtKB

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Ligase

Keywords - Biological processi

Ubl conjugation pathway

Keywords - Ligandi

Metal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-HSA-877300. Interferon gamma signaling.
UniPathwayiUPA00143.

Names & Taxonomyi

Protein namesi
Recommended name:
Tripartite motif-containing protein 2 (EC:6.3.2.-)
Alternative name(s):
E3 ubiquitin-protein ligase TRIM2
RING finger protein 86
Gene namesi
Name:TRIM2
Synonyms:KIAA0517, RNF86
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 4

Organism-specific databases

HGNCiHGNC:15974. TRIM2.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Involvement in diseasei

Charcot-Marie-Tooth disease 2R (CMT2R)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn axonal form of Charcot-Marie-Tooth disease, a disorder of the peripheral nervous system, characterized by progressive weakness and atrophy, initially of the peroneal muscles and later of the distal muscles of the arms. Charcot-Marie-Tooth disease is classified in two main groups on the basis of electrophysiologic properties and histopathology: primary peripheral demyelinating neuropathies (designated CMT1 when they are dominantly inherited) and primary peripheral axonal neuropathies (CMT2). Neuropathies of the CMT2 group are characterized by signs of axonal degeneration in the absence of obvious myelin alterations, normal or slightly reduced nerve conduction velocities, and progressive distal muscle weakness and atrophy. Nerve conduction velocities are normal or slightly reduced.
See also OMIM:615490
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_070874227E → V in CMT2R; reduced stability of the mutant protein. 1 PublicationCorresponds to variant rs587777063dbSNPEnsembl.1

Keywords - Diseasei

Charcot-Marie-Tooth disease, Disease mutation, Neurodegeneration, Neuropathy

Organism-specific databases

DisGeNETi23321.
MalaCardsiTRIM2.
MIMi615490. phenotype.
OpenTargetsiENSG00000109654.
Orphaneti397968. Charcot-Marie-Tooth disease type 2R.
PharmGKBiPA38070.

Polymorphism and mutation databases

BioMutaiTRIM2.
DMDMi21363034.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000561951 – 744Tripartite motif-containing protein 2Add BLAST744

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei10PhosphoserineBy similarity1
Modified residuei371PhosphothreonineBy similarity1
Modified residuei375PhosphoserineBy similarity1
Modified residuei424PhosphoserineBy similarity1
Modified residuei428PhosphoserineBy similarity1

Post-translational modificationi

RING-type zinc finger-dependent and UBE2D1-dependent autoubiquitination.By similarity

Keywords - PTMi

Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ9C040.
MaxQBiQ9C040.
PaxDbiQ9C040.
PeptideAtlasiQ9C040.
PRIDEiQ9C040.

PTM databases

iPTMnetiQ9C040.
PhosphoSitePlusiQ9C040.

Expressioni

Gene expression databases

BgeeiENSG00000109654.
CleanExiHS_TRIM2.
ExpressionAtlasiQ9C040. baseline and differential.
GenevisibleiQ9C040. HS.

Organism-specific databases

HPAiHPA035853.
HPA035854.

Interactioni

Subunit structurei

Interacts with myosin V; myosin V may not be a substrate for ubiquitination (By similarity). Interacts with NEFL (By similarity). Interacts with phosphorylated BCL2L11.By similarity1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
CIB3Q96Q775EBI-749840,EBI-10292696
KCTD7Q96MP8-24EBI-749840,EBI-11954971
LRRC8EQ6NSJ53EBI-749840,EBI-8647013
TRIM3O753824EBI-749840,EBI-2129889
UBAC1Q9BSL16EBI-749840,EBI-749370

Protein-protein interaction databases

BioGridi116910. 30 interactors.
IntActiQ9C040. 23 interactors.
STRINGi9606.ENSP00000339659.

Structurei

3D structure databases

ProteinModelPortaliQ9C040.
SMRiQ9C040.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Repeati320 – 421FilaminAdd BLAST102
Repeati473 – 516NHL 1Add BLAST44
Repeati520 – 563NHL 2Add BLAST44
Repeati564 – 605NHL 3Add BLAST42
Repeati609 – 652NHL 4Add BLAST44
Repeati656 – 699NHL 5Add BLAST44
Repeati700 – 743NHL 6Add BLAST44

Domaini

The interaction with myosin V is dependent upon its NHL repeats, which form a beta-propeller (NHL) domain containing six blades.By similarity

Sequence similaritiesi

Belongs to the TRIM/RBCC family.Curated
Contains 1 B box-type zinc finger.PROSITE-ProRule annotation
Contains 1 filamin repeat.PROSITE-ProRule annotation
Contains 6 NHL repeats.PROSITE-ProRule annotation
Contains 1 RING-type zinc finger.PROSITE-ProRule annotation

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri23 – 64RING-typePROSITE-ProRule annotationAdd BLAST42
Zinc fingeri113 – 154B box-typePROSITE-ProRule annotationAdd BLAST42

Keywords - Domaini

Repeat, Zinc-finger

Phylogenomic databases

eggNOGiENOG410ITFR. Eukaryota.
ENOG410XQSU. LUCA.
GeneTreeiENSGT00550000074377.
HOGENOMiHOG000220817.
HOVERGENiHBG054843.
InParanoidiQ9C040.
KOiK11997.
OMAiCKSGNAY.
OrthoDBiEOG091G06IK.
PhylomeDBiQ9C040.
TreeFamiTF331018.

Family and domain databases

Gene3Di2.120.10.30. 1 hit.
2.60.40.10. 1 hit.
3.30.40.10. 1 hit.
4.10.45.10. 1 hit.
InterProiIPR011042. 6-blade_b-propeller_TolB-like.
IPR003649. Bbox_C.
IPR017868. Filamin/ABP280_repeat-like.
IPR001298. Filamin/ABP280_rpt.
IPR013783. Ig-like_fold.
IPR014756. Ig_E-set.
IPR001258. NHL_repeat.
IPR013017. NHL_repeat_subgr.
IPR027370. Znf-RING_LisH.
IPR000315. Znf_B-box.
IPR001841. Znf_RING.
IPR013083. Znf_RING/FYVE/PHD.
IPR017907. Znf_RING_CS.
[Graphical view]
PfamiPF00630. Filamin. 1 hit.
PF01436. NHL. 6 hits.
PF00643. zf-B_box. 1 hit.
PF13445. zf-RING_UBOX. 1 hit.
[Graphical view]
SMARTiSM00502. BBC. 1 hit.
SM00336. BBOX. 1 hit.
SM00557. IG_FLMN. 1 hit.
SM00184. RING. 1 hit.
[Graphical view]
SUPFAMiSSF81296. SSF81296. 1 hit.
PROSITEiPS50194. FILAMIN_REPEAT. 1 hit.
PS51125. NHL. 6 hits.
PS50119. ZF_BBOX. 1 hit.
PS00518. ZF_RING_1. 1 hit.
PS50089. ZF_RING_2. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

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

Isoform 1 (identifier: Q9C040-1) [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
MASEGTNIPS PVVRQIDKQF LICSICLERY KNPKVLPCLH TFCERCLQNY
60 70 80 90 100
IPAHSLTLSC PVCRQTSILP EKGVAALQNN FFITNLMDVL QRTPGSNAEE
110 120 130 140 150
SSILETVTAV AAGKPLSCPN HDGNVMEFYC QSCETAMCRE CTEGEHAEHP
160 170 180 190 200
TVPLKDVVEQ HKASLQVQLD AVNKRLPEID SALQFISEII HQLTNQKASI
210 220 230 240 250
VDDIHSTFDE LQKTLNVRKS VLLMELEVNY GLKHKVLQSQ LDTLLQGQES
260 270 280 290 300
IKSCSNFTAQ ALNHGTETEV LLVKKQMSEK LNELADQDFP LHPRENDQLD
310 320 330 340 350
FIVETEGLKK SIHNLGTILT TNAVASETVA TGEGLRQTII GQPMSVTITT
360 370 380 390 400
KDKDGELCKT GNAYLTAELS TPDGSVADGE ILDNKNGTYE FLYTVQKEGD
410 420 430 440 450
FTLSLRLYDQ HIRGSPFKLK VIRSADVSPT TEGVKRRVKS PGSGHVKQKA
460 470 480 490 500
VKRPASMYST GKRKENPIED DLIFRVGTKG RNKGEFTNLQ GVAASTNGKI
510 520 530 540 550
LIADSNNQCV QIFSNDGQFK SRFGIRGRSP GQLQRPTGVA VHPSGDIIIA
560 570 580 590 600
DYDNKWVSIF SSDGKFKTKI GSGKLMGPKG VSVDRNGHII VVDNKACCVF
610 620 630 640 650
IFQPNGKIVT RFGSRGNGDR QFAGPHFAAV NSNNEIIITD FHNHSVKVFN
660 670 680 690 700
QEGEFMLKFG SNGEGNGQFN APTGVAVDSN GNIIVADWGN SRIQVFDGSG
710 720 730 740
SFLSYINTSA DPLYGPQGLA LTSDGHVVVA DSGNHCFKVY RYLQ
Length:744
Mass (Da):81,530
Last modified:June 1, 2001 - v1
Checksum:iB69A5876188B1A27
GO
Isoform 2 (identifier: Q9C040-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-1: M → MHRSGRYGTQQQRAGSKTAGPPCQWSRM

Show »
Length:771
Mass (Da):84,545
Checksum:i7037A4D0FAA0770F
GO

Sequence cautioni

The sequence AAG53472 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
The sequence BAA25443 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti737 – 744FKVYRYLQ → LILIYSRHLFFYESKC in AAH05016 (PubMed:15489334).Curated8

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_070874227E → V in CMT2R; reduced stability of the mutant protein. 1 PublicationCorresponds to variant rs587777063dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0469231M → MHRSGRYGTQQQRAGSKTAG PPCQWSRM in isoform 2. 2 Publications1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF220018 mRNA. Translation: AAG53472.1. Different initiation.
AB011089 mRNA. Translation: BAA25443.1. Different initiation.
AC013477 Genomic DNA. No translation available.
AC114791 Genomic DNA. No translation available.
CH471056 Genomic DNA. Translation: EAX04960.1.
CH471056 Genomic DNA. Translation: EAX04962.1.
BC005016 mRNA. Translation: AAH05016.1.
BC011052 mRNA. Translation: AAH11052.1.
AL110234 mRNA. Translation: CAB53687.2.
CCDSiCCDS3781.2. [Q9C040-2]
CCDS47147.1. [Q9C040-1]
PIRiT00082.
RefSeqiNP_001123539.1. NM_001130067.1. [Q9C040-1]
NP_056086.2. NM_015271.4. [Q9C040-2]
XP_016863433.1. XM_017007944.1. [Q9C040-1]
XP_016863434.1. XM_017007945.1. [Q9C040-1]
XP_016863437.1. XM_017007948.1. [Q9C040-1]
XP_016863438.1. XM_017007949.1. [Q9C040-1]
XP_016863439.1. XM_017007950.1. [Q9C040-1]
XP_016863440.1. XM_017007951.1. [Q9C040-1]
XP_016863441.1. XM_017007952.1. [Q9C040-1]
UniGeneiHs.435711.

Genome annotation databases

EnsembliENST00000338700; ENSP00000339659; ENSG00000109654. [Q9C040-2]
ENST00000437508; ENSP00000415812; ENSG00000109654. [Q9C040-1]
GeneIDi23321.
KEGGihsa:23321.
UCSCiuc003ing.3. human. [Q9C040-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF220018 mRNA. Translation: AAG53472.1. Different initiation.
AB011089 mRNA. Translation: BAA25443.1. Different initiation.
AC013477 Genomic DNA. No translation available.
AC114791 Genomic DNA. No translation available.
CH471056 Genomic DNA. Translation: EAX04960.1.
CH471056 Genomic DNA. Translation: EAX04962.1.
BC005016 mRNA. Translation: AAH05016.1.
BC011052 mRNA. Translation: AAH11052.1.
AL110234 mRNA. Translation: CAB53687.2.
CCDSiCCDS3781.2. [Q9C040-2]
CCDS47147.1. [Q9C040-1]
PIRiT00082.
RefSeqiNP_001123539.1. NM_001130067.1. [Q9C040-1]
NP_056086.2. NM_015271.4. [Q9C040-2]
XP_016863433.1. XM_017007944.1. [Q9C040-1]
XP_016863434.1. XM_017007945.1. [Q9C040-1]
XP_016863437.1. XM_017007948.1. [Q9C040-1]
XP_016863438.1. XM_017007949.1. [Q9C040-1]
XP_016863439.1. XM_017007950.1. [Q9C040-1]
XP_016863440.1. XM_017007951.1. [Q9C040-1]
XP_016863441.1. XM_017007952.1. [Q9C040-1]
UniGeneiHs.435711.

3D structure databases

ProteinModelPortaliQ9C040.
SMRiQ9C040.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi116910. 30 interactors.
IntActiQ9C040. 23 interactors.
STRINGi9606.ENSP00000339659.

PTM databases

iPTMnetiQ9C040.
PhosphoSitePlusiQ9C040.

Polymorphism and mutation databases

BioMutaiTRIM2.
DMDMi21363034.

Proteomic databases

EPDiQ9C040.
MaxQBiQ9C040.
PaxDbiQ9C040.
PeptideAtlasiQ9C040.
PRIDEiQ9C040.

Protocols and materials databases

DNASUi23321.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000338700; ENSP00000339659; ENSG00000109654. [Q9C040-2]
ENST00000437508; ENSP00000415812; ENSG00000109654. [Q9C040-1]
GeneIDi23321.
KEGGihsa:23321.
UCSCiuc003ing.3. human. [Q9C040-1]

Organism-specific databases

CTDi23321.
DisGeNETi23321.
GeneCardsiTRIM2.
HGNCiHGNC:15974. TRIM2.
HPAiHPA035853.
HPA035854.
MalaCardsiTRIM2.
MIMi614141. gene.
615490. phenotype.
neXtProtiNX_Q9C040.
OpenTargetsiENSG00000109654.
Orphaneti397968. Charcot-Marie-Tooth disease type 2R.
PharmGKBiPA38070.
HUGEiSearch...
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410ITFR. Eukaryota.
ENOG410XQSU. LUCA.
GeneTreeiENSGT00550000074377.
HOGENOMiHOG000220817.
HOVERGENiHBG054843.
InParanoidiQ9C040.
KOiK11997.
OMAiCKSGNAY.
OrthoDBiEOG091G06IK.
PhylomeDBiQ9C040.
TreeFamiTF331018.

Enzyme and pathway databases

UniPathwayiUPA00143.
ReactomeiR-HSA-877300. Interferon gamma signaling.

Miscellaneous databases

ChiTaRSiTRIM2. human.
GenomeRNAii23321.
PROiQ9C040.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000109654.
CleanExiHS_TRIM2.
ExpressionAtlasiQ9C040. baseline and differential.
GenevisibleiQ9C040. HS.

Family and domain databases

Gene3Di2.120.10.30. 1 hit.
2.60.40.10. 1 hit.
3.30.40.10. 1 hit.
4.10.45.10. 1 hit.
InterProiIPR011042. 6-blade_b-propeller_TolB-like.
IPR003649. Bbox_C.
IPR017868. Filamin/ABP280_repeat-like.
IPR001298. Filamin/ABP280_rpt.
IPR013783. Ig-like_fold.
IPR014756. Ig_E-set.
IPR001258. NHL_repeat.
IPR013017. NHL_repeat_subgr.
IPR027370. Znf-RING_LisH.
IPR000315. Znf_B-box.
IPR001841. Znf_RING.
IPR013083. Znf_RING/FYVE/PHD.
IPR017907. Znf_RING_CS.
[Graphical view]
PfamiPF00630. Filamin. 1 hit.
PF01436. NHL. 6 hits.
PF00643. zf-B_box. 1 hit.
PF13445. zf-RING_UBOX. 1 hit.
[Graphical view]
SMARTiSM00502. BBC. 1 hit.
SM00336. BBOX. 1 hit.
SM00557. IG_FLMN. 1 hit.
SM00184. RING. 1 hit.
[Graphical view]
SUPFAMiSSF81296. SSF81296. 1 hit.
PROSITEiPS50194. FILAMIN_REPEAT. 1 hit.
PS51125. NHL. 6 hits.
PS50119. ZF_BBOX. 1 hit.
PS00518. ZF_RING_1. 1 hit.
PS50089. ZF_RING_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiTRIM2_HUMAN
AccessioniPrimary (citable) accession number: Q9C040
Secondary accession number(s): D3DP09
, O60272, Q9BSI9, Q9UFZ1
Entry historyi
Integrated into UniProtKB/Swiss-Prot: June 6, 2002
Last sequence update: June 1, 2001
Last modified: November 30, 2016
This is version 142 of the entry and version 1 of the sequence. [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

Documents

  1. Human chromosome 4
    Human chromosome 4: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.