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Protein

COMM domain-containing protein 1

Gene

COMMD1

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

Functioni

Proposed scaffold protein that is implicated in diverse physiological processes and whose function may be in part linked to its ability to regulate ubiquitination of specific cellular proteins. Can modulate activity of cullin-RING E3 ubiquitin ligase (CRL) complexes by displacing CAND1; in vitro promotes CRL E3 activity and dissociates CAND1 from CUL1 and CUL2 (PubMed:21778237). Promotes ubiquitination of NF-kappa-B subunit RELA and its subsequent proteasomal degradation. Down-regulates NF-kappa-B activity (PubMed:15799966, PubMed:17183367, PubMed:20048074). Involved in the regulation of membrane expression and ubiquitination of SLC12A2 (PubMed:23515529). Modulates Na+ transport in epithelial cells by regulation of apical cell surface expression of amiloride-sensitive sodium channel (ENaC) subunits and by promoting their ubiquitination presumably involving NEDD4L. Promotes the localization of SCNN1D to recycling endosomes (PubMed:14645214, PubMed:20237237, PubMed:21741370). Promotes CFTR cell surface expression through regulation of its ubiquitination (PubMed:21483833). Down-regulates SOD1 activity by interfering with its homodimerization (PubMed:20595380). Plays a role in copper ion homeostasis. Involved in copper-dependent ATP7A trafficking between the trans-Golgi network and vesicles in the cell periphery; the function is proposed to depend on its association within the CCC complex and cooperation with the WASH complex on early endosomes (PubMed:25355947). Can bind one copper ion per monomer (PubMed:17309234). May function to facilitate biliary copper excretion within hepatocytes. Binds to phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2) (PubMed:18940794). Involved in the regulation of HIF1A-mediated transcription; competes with ARNT/Hif-1-beta for binding to HIF1A resulting in decreased DNA binding and impaired transcriptional activation by HIF-1 (PubMed:20458141).15 Publications

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi101 – 1011CopperSequence analysis
Metal bindingi110 – 1101CopperSequence analysis
Metal bindingi134 – 1341CopperSequence analysis

GO - Molecular functioni

  • copper ion binding Source: UniProtKB
  • identical protein binding Source: IntAct
  • phosphatidic acid binding Source: UniProtKB
  • phosphatidylinositol-3,4,5-trisphosphate binding Source: UniProtKB
  • phosphatidylinositol-3,4-bisphosphate binding Source: UniProtKB
  • phosphatidylinositol-3,5-bisphosphate binding Source: UniProtKB
  • phosphatidylinositol-4,5-bisphosphate binding Source: UniProtKB
  • protein homodimerization activity Source: UniProtKB

GO - Biological processi

  • copper ion homeostasis Source: UniProtKB
  • Golgi to plasma membrane transport Source: UniProtKB
  • negative regulation of NF-kappaB transcription factor activity Source: UniProtKB
  • negative regulation of protein localization to cell surface Source: UniProtKB
  • negative regulation of sodium ion transmembrane transport Source: UniProtKB
  • plasma membrane to endosome transport Source: UniProtKB
  • positive regulation of protein ubiquitination Source: UniProtKB
  • protein transport Source: UniProtKB-KW
  • regulation of proteasomal ubiquitin-dependent protein catabolic process Source: UniProtKB
  • transcription, DNA-templated Source: UniProtKB-KW
Complete GO annotation...

Keywords - Biological processi

Protein transport, Transcription, Transcription regulation, Transport, Ubl conjugation pathway

Keywords - Ligandi

Copper, Lipid-binding, Metal-binding

Names & Taxonomyi

Protein namesi
Recommended name:
COMM domain-containing protein 1
Alternative name(s):
Protein Murr1
Gene namesi
Name:COMMD1
Synonyms:C2orf5, MURR1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 2

Organism-specific databases

HGNCiHGNC:23024. COMMD1.

Subcellular locationi

GO - Cellular componenti

  • Cul2-RING ubiquitin ligase complex Source: UniProtKB
  • cytoplasm Source: UniProtKB
  • cytoplasmic, membrane-bounded vesicle Source: UniProtKB-SubCell
  • early endosome Source: UniProtKB
  • endosome membrane Source: UniProtKB-SubCell
  • extracellular exosome Source: UniProtKB
  • nucleoplasm Source: HPA
  • nucleus Source: UniProtKB
  • recycling endosome Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Cytoplasmic vesicle, Endosome, Membrane, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi110 – 1101M → A: Reduces copper-induced fluorescence change. 1 Publication
Mutagenesisi134 – 1341H → A: Reduces copper-induced fluorescence change. 1 Publication

Organism-specific databases

PharmGKBiPA134891368.

Polymorphism and mutation databases

BioMutaiCOMMD1.
DMDMi51316026.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methionineiRemovedCombined sources
Chaini2 – 190189COMM domain-containing protein 1PRO_0000077384Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei2 – 21N-acetylalanineCombined sources

Post-translational modificationi

Acetylated by EP300 ina stimuli-specific manner; protecting it from XIAP-mediated proteasomal degradation and required for interaction with RElA in response to stress.1 Publication
Ubiquitinated; undergoes both 'Lys-63'- and 'Lys-48'-linked polyubiquitination. Ubiquitinated by XIAP, leading to its proteasomal degradation.3 Publications

Keywords - PTMi

Acetylation, Ubl conjugation

Proteomic databases

EPDiQ8N668.
MaxQBiQ8N668.
PaxDbiQ8N668.
PeptideAtlasiQ8N668.
PRIDEiQ8N668.

PTM databases

iPTMnetiQ8N668.
PhosphoSiteiQ8N668.

Expressioni

Tissue specificityi

Ubiquitous. Highest expression in the liver, with lower expression in brain, lung, placenta, pancreas, small intestine, heart, skeletal muscle, kidney and placenta. Down-regulated in cancer tissues.4 Publications

Gene expression databases

BgeeiENSG00000173163.
CleanExiHS_COMMD1.
ExpressionAtlasiQ8N668. baseline and differential.
GenevisibleiQ8N668. HS.

Organism-specific databases

HPAiHPA034633.
HPA049223.

Interactioni

Subunit structurei

Monomer, homodimer. Can form heterodimers with other COMM domain-containing proteins but only certain combinations may exist in vivo (PubMed:23563313). Interacts (via COMM domain) with COMMD2, COMMD3, COMMD4, COMMD5, COMMD6, COMMD7, COMMD8 and COMMD10 (via COMM domain). Identified in a complex with an E3 ubiquitin ligase complex composed of TCEB1/elongin C, CUL2, SOCS1 and RBX1; in the complex interacts directly with SOCS1 and CUL2. Interacts directly with ATP7B (via the N-terminal region). Interacts with CCS, CDKN2A, RELA, REL, RELB, NFKB1/p105, NFKB2/p100, NFKBIB, SCNN1D, SCNN1B, CFTR, CLU, SGK1, AKT1, CUL1, CUL2, CUL3, CUL4A, CUL4B, CUL5, CUL7, HIF1A. Identified in a complex with NF-kappa-B. Interacts directly with SLC12A2. Interacts with CCDC22, CCDC93 and C16orf62; proposed to be a component of the CCC (COMMD/CCDC22/CCDC93) complex which contains at least COMMD1 (and possibly other COMM domain-containing proteins), CCDC22, CCDC93 and C16orf62 (PubMed:25355947).2 Publications18 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
itself2EBI-1550112,EBI-1550112
CCDC22O6082614EBI-1550112,EBI-3943153
COMMD3Q9UBI14EBI-1550112,EBI-714979
COMMD4Q9H0A83EBI-1550112,EBI-1550064
COMMD6Q7Z4G112EBI-1550112,EBI-1550081
COMMD8Q9NX082EBI-1550112,EBI-725694
CUL2Q136176EBI-1550112,EBI-456179
NFKBIAP259633EBI-1550112,EBI-307386
RELQ048643EBI-1550112,EBI-307352
RELAQ042067EBI-1550112,EBI-73886
RELBQ012012EBI-1550112,EBI-357837
SCNN1DP511723EBI-1550112,EBI-2547114
SOCS1O155243EBI-1550112,EBI-968198
TCEB1Q153692EBI-1550112,EBI-301231

GO - Molecular functioni

  • identical protein binding Source: IntAct
  • protein homodimerization activity Source: UniProtKB

Protein-protein interaction databases

BioGridi127317. 74 interactions.
IntActiQ8N668. 30 interactions.
MINTiMINT-4140741.
STRINGi9606.ENSP00000308236.

Structurei

Secondary structure

1
190
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi3 – 53Combined sources
Helixi9 – 135Combined sources
Helixi15 – 184Combined sources
Beta strandi23 – 253Combined sources
Helixi32 – 398Combined sources
Beta strandi41 – 433Combined sources
Helixi48 – 525Combined sources
Turni53 – 553Combined sources
Helixi59 – 624Combined sources
Turni63 – 653Combined sources
Turni69 – 713Combined sources
Turni73 – 753Combined sources
Helixi76 – 794Combined sources
Beta strandi82 – 843Combined sources
Helixi88 – 947Combined sources
Turni95 – 1017Combined sources
Beta strandi102 – 1065Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2H2MNMR-A1-108[»]
ProteinModelPortaliQ8N668.
SMRiQ8N668. Positions 1-108.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ8N668.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini118 – 18669COMMPROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni2 – 123122Sufficient for interaction with SLC12A21 PublicationAdd
BLAST
Regioni125 – 19066Required for binding to PtdIns(4,5)P21 PublicationAdd
BLAST

Sequence similaritiesi

Contains 1 COMM domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiENOG410IWFF. Eukaryota.
ENOG4111IWI. LUCA.
GeneTreeiENSGT00390000012029.
HOGENOMiHOG000236295.
HOVERGENiHBG051067.
InParanoidiQ8N668.
OMAiGELEGCK.
OrthoDBiEOG091G0XWL.
PhylomeDBiQ8N668.
TreeFamiTF332823.

Family and domain databases

InterProiIPR017920. COMM.
[Graphical view]
PfamiPF07258. HCaRG. 1 hit.
[Graphical view]
PROSITEiPS51269. COMM. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

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

Isoform 1 (identifier: Q8N668-1) [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
MAAGELEGGK PLSGLLNALA QDTFHGYPGI TEELLRSQLY PEVPPEEFRP
60 70 80 90 100
FLAKMRGILK SIASADMDFN QLEAFLTAQT KKQGGITSDQ AAVISKFWKS
110 120 130 140 150
HKTKIRESLM NQSRWNSGLR GLSWRVDGKS QSRHSAQIHT PVAIIELELG
160 170 180 190
KYGQESEFLC LEFDEVKVNQ ILKTLSEVEE SISTLISQPN
Length:190
Mass (Da):21,178
Last modified:October 1, 2002 - v1
Checksum:i9C810AECA67011DC
GO
Isoform 2 (identifier: Q8N668-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     155-190: ESEFLCLEFDEVKVNQILKTLSEVEESISTLISQPN → VHCNQ

Note: No experimental confirmation available.
Show »
Length:159
Mass (Da):17,665
Checksum:i3914BE73CBDD80F8
GO

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei155 – 19036ESEFL…ISQPN → VHCNQ in isoform 2. 1 PublicationVSP_055532Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB178811 mRNA. Translation: BAD18972.1.
AK294203 mRNA. Translation: BAG57515.1.
AC018462 Genomic DNA. No translation available.
AC107081 Genomic DNA. No translation available.
AC116652 Genomic DNA. No translation available.
BC009266 mRNA. Translation: AAH09266.2.
BC022046 mRNA. Translation: AAH22046.1.
CCDSiCCDS1869.1. [Q8N668-1]
RefSeqiNP_689729.1. NM_152516.3. [Q8N668-1]
UniGeneiHs.468702.

Genome annotation databases

EnsembliENST00000311832; ENSP00000308236; ENSG00000173163. [Q8N668-1]
GeneIDi150684.
KEGGihsa:150684.
UCSCiuc002sbp.4. human. [Q8N668-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB178811 mRNA. Translation: BAD18972.1.
AK294203 mRNA. Translation: BAG57515.1.
AC018462 Genomic DNA. No translation available.
AC107081 Genomic DNA. No translation available.
AC116652 Genomic DNA. No translation available.
BC009266 mRNA. Translation: AAH09266.2.
BC022046 mRNA. Translation: AAH22046.1.
CCDSiCCDS1869.1. [Q8N668-1]
RefSeqiNP_689729.1. NM_152516.3. [Q8N668-1]
UniGeneiHs.468702.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2H2MNMR-A1-108[»]
ProteinModelPortaliQ8N668.
SMRiQ8N668. Positions 1-108.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi127317. 74 interactions.
IntActiQ8N668. 30 interactions.
MINTiMINT-4140741.
STRINGi9606.ENSP00000308236.

PTM databases

iPTMnetiQ8N668.
PhosphoSiteiQ8N668.

Polymorphism and mutation databases

BioMutaiCOMMD1.
DMDMi51316026.

Proteomic databases

EPDiQ8N668.
MaxQBiQ8N668.
PaxDbiQ8N668.
PeptideAtlasiQ8N668.
PRIDEiQ8N668.

Protocols and materials databases

DNASUi150684.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000311832; ENSP00000308236; ENSG00000173163. [Q8N668-1]
GeneIDi150684.
KEGGihsa:150684.
UCSCiuc002sbp.4. human. [Q8N668-1]

Organism-specific databases

CTDi150684.
GeneCardsiCOMMD1.
HGNCiHGNC:23024. COMMD1.
HPAiHPA034633.
HPA049223.
MIMi607238. gene.
neXtProtiNX_Q8N668.
PharmGKBiPA134891368.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IWFF. Eukaryota.
ENOG4111IWI. LUCA.
GeneTreeiENSGT00390000012029.
HOGENOMiHOG000236295.
HOVERGENiHBG051067.
InParanoidiQ8N668.
OMAiGELEGCK.
OrthoDBiEOG091G0XWL.
PhylomeDBiQ8N668.
TreeFamiTF332823.

Miscellaneous databases

ChiTaRSiCOMMD1. human.
EvolutionaryTraceiQ8N668.
GeneWikiiCOMMD1.
GenomeRNAii150684.
PROiQ8N668.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000173163.
CleanExiHS_COMMD1.
ExpressionAtlasiQ8N668. baseline and differential.
GenevisibleiQ8N668. HS.

Family and domain databases

InterProiIPR017920. COMM.
[Graphical view]
PfamiPF07258. HCaRG. 1 hit.
[Graphical view]
PROSITEiPS51269. COMM. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiCOMD1_HUMAN
AccessioniPrimary (citable) accession number: Q8N668
Secondary accession number(s): B4DFQ4, Q96GS0
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 16, 2004
Last sequence update: October 1, 2002
Last modified: September 7, 2016
This is version 116 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

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 2
    Human chromosome 2: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. 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.