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Q9UKV5 (AMFR_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 120. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
E3 ubiquitin-protein ligase AMFR

EC=6.3.2.-
Alternative name(s):
Autocrine motility factor receptor
Short name=AMF receptor
RING finger protein 45
gp78
Gene names
Name:AMFR
Synonyms:RNF45
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length643 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

E3 ubiquitin-protein ligase that mediates the polyubiquitination of a number of proteins such as CD3D, CYP3A4, CFTR and APOB for proteasomal degradation. Component of a VCP/p97-AMFR/gp78 complex that participates in the final step of endoplasmic reticulum-associated degradation (ERAD). The VCP/p97-AMFR/gp78 complex is involved in the sterol-accelerated ERAD degradation of HMGCR through binding to the HMGCR-INSIG complex at the ER membrane and initiating ubiquitination of HMGCR. The ubiquitinated HMGCR is then released from the ER by the complex into the cytosol for subsequent destruction. Also acts as a scaffold protein to assemble a complex that couples ubiquitination, retranslocation and deglycosylation. Mediates tumor invasion and metastasis as a receptor for the GPI/autocrine motility factor. Ref.1 Ref.5 Ref.7 Ref.10

Pathway

Protein modification; protein ubiquitination.

Subunit structure

Interacts with RNF5. Also forms an ERAD complex containing VCP/p97, NGLY1; PSMC1; SAKS1 AND RAD23B required for coupling retrotranslocation, ubiquitination and deglycosylation By similarity. Interacts with DRL1. Interacts (through a region distinct from the RING finger) with UBE2G2/UBC7. Component of the VCP/p97-AMFR/gp78 complex that enhances VCP/p97 binding to polyubiquitinated proteins for their degradation by the endoplasmic reticulum-associated degradation (ERAD) pathway. Interacts (via the VIM) with VCP/p97. Interacts (via its membrane domain) with INSIG1; the interaction initiates the sterol-mediated ubiquitination and degradation of HMGCR by the ERAD pathway. Ref.5 Ref.7 Ref.8

Subcellular location

Endoplasmic reticulum membrane; Multi-pass membrane protein Ref.5.

Domain

The VCP/p97-interacting motif (VIM) is sufficient for binding VCP/p97 to form a complex capable of transferring VCP/p97 from the cytosol to microsomes.

Sequence similarities

Contains 1 CUE domain.

Contains 1 RING-type zinc finger.

Sequence caution

The sequence AAA36671.1 differs from that shown. Reason: Several sequencing errors.

The sequence AAA79362.1 differs from that shown. Reason: Frameshift at positions 355, 388, 411, 487, 537, 583 and 632.

Ontologies

Keywords
   Biological processUbl conjugation pathway
   Cellular componentEndoplasmic reticulum
Membrane
   Coding sequence diversityPolymorphism
   DomainTransmembrane
Transmembrane helix
Zinc-finger
   LigandMetal-binding
Zinc
   Molecular functionLigase
Receptor
   PTMPhosphoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processER-associated ubiquitin-dependent protein catabolic process

Inferred from direct assay Ref.5. Source: UniProtKB

aging

Inferred from electronic annotation. Source: Ensembl

cellular component movement

Traceable author statement Ref.4. Source: ProtInc

endoplasmic reticulum unfolded protein response

Inferred from mutant phenotype PubMed 17157811. Source: UniProtKB

learning or memory

Inferred from electronic annotation. Source: Ensembl

protein oligomerization

Inferred from direct assay PubMed 17310145. Source: UniProtKB

protein polyubiquitination

Inferred from direct assay PubMed 17310145Ref.10. Source: UniProtKB

signal transduction

Traceable author statement Ref.4. Source: ProtInc

ubiquitin-dependent protein catabolic process

Inferred from mutant phenotype Ref.7PubMed 17043353. Source: UniProtKB

   Cellular_componentdendrite

Inferred from electronic annotation. Source: Ensembl

growth cone

Inferred from electronic annotation. Source: Ensembl

integral component of endoplasmic reticulum membrane

Inferred from direct assay Ref.5. Source: UniProtKB

integral component of membrane

Non-traceable author statement Ref.4. Source: UniProtKB

neuronal cell body

Inferred from electronic annotation. Source: Ensembl

nucleus

Inferred from electronic annotation. Source: Ensembl

perinuclear region of cytoplasm

Inferred from direct assay PubMed 16275660. Source: ParkinsonsUK-UCL

protein complex

Inferred from direct assay PubMed 23382219. Source: MGI

   Molecular_functionprotein binding

Inferred from physical interaction Ref.5Ref.7PubMed 17681147. Source: UniProtKB

receptor activity

Inferred from physical interaction Ref.4. Source: UniProtKB

ubiquitin-protein transferase activity

Inferred from direct assay Ref.5PubMed 17681147Ref.10. Source: UniProtKB

zinc ion binding

Inferred from electronic annotation. Source: InterPro

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

VCPP550726EBI-1046367,EBI-355164

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 643643E3 ubiquitin-protein ligase AMFR
PRO_0000064579

Regions

Transmembrane82 – 10221Helical; Potential
Transmembrane122 – 14221Helical; Potential
Transmembrane145 – 16521Helical; Potential
Transmembrane186 – 20621Helical; Potential
Transmembrane215 – 23521Helical; Potential
Transmembrane276 – 29621Helical; Potential
Transmembrane429 – 44921Helical; Potential
Domain456 – 49843CUE
Zinc finger341 – 37939RING-type
Region614 – 64330VCP/p97-interacting motif (VIM)

Amino acid modifications

Modified residue5161Phosphoserine Ref.9
Modified residue5421Phosphoserine By similarity

Natural variations

Natural variant6051D → V in a breast cancer sample; somatic mutation. Ref.12
VAR_035790

Experimental info

Mutagenesis3561C → G: No degradation of HMGCR. Ref.7
Sequence conflict4061V → D in AAA79362. Ref.3
Sequence conflict4911D → V in AAA79362. Ref.3
Sequence conflict5001V → L in AAA79362. Ref.3
Sequence conflict6141S → L in AAD56722. Ref.1

Secondary structure

........................ 643
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q9UKV5 [UniParc].

Last modified June 1, 2003. Version 2.
Checksum: 8782324609C0E62A

FASTA64372,996
        10         20         30         40         50         60 
MPLLFLERFP WPSLRTYTGL SGLALLGTII SAYRALSQPE AGPGEPDQLT ASLQPEPPAP 

        70         80         90        100        110        120 
ARPSAGGPRA RDVAQYLLSD SLFVWVLVNT ACCVLMLVAK LIQCIVFGPL RVSERQHLKD 

       130        140        150        160        170        180 
KFWNFIFYKF IFIFGVLNVQ TVEEVVMWCL WFAGLVFLHL MVQLCKDRFE YLSFSPTTPM 

       190        200        210        220        230        240 
SSHGRVLSLL VAMLLSCCGL AAVCSITGYT HGMHTLAFMA AESLLVTVRT AHVILRYVIH 

       250        260        270        280        290        300 
LWDLNHEGTW EGKGTYVYYT DFVMELTLLS LDLMHHIHML LFGNIWLSMA SLVIFMQLRY 

       310        320        330        340        350        360 
LFHEVQRRIR RHKNYLRVVG NMEARFAVAT PEELAVNNDD CAICWDSMQA ARKLPCGHLF 

       370        380        390        400        410        420 
HNSCLRSWLE QDTSCPTCRM SLNIADNNRV REEHQGENLD ENLVPVAAAE GRPRLNQHNH 

       430        440        450        460        470        480 
FFHFDGSRIA SWLPSFSVEV MHTTNILGIT QASNSQLNAM AHQIQEMFPQ VPYHLVLQDL 

       490        500        510        520        530        540 
QLTRSVEITT DNILEGRIQV PFPTQRSDSI RPALNSPVER PSSDQEEGET SAQTERVPLD 

       550        560        570        580        590        600 
LSPRLEETLD FGEVEVEPSE VEDFEARGSR FSKSADERQR MLVQRKDELL QQARKRFLNK 

       610        620        630        640 
SSEDDAASES FLPSEGASSD PVTLRRRMLA AAAERRLQKQ QTS 

« Hide

References

« Hide 'large scale' references
[1]"The autocrine motility factor receptor gene encodes a novel type of seven transmembrane protein."
Shimizu K., Tani M., Watanabe H., Nagamachi Y., Niinaka Y., Shiroishi T., Ohwada S., Raz A., Yokota J.
FEBS Lett. 456:295-300(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION.
[2]"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].
Tissue: Ovary.
[3]"Identification of an upstream region that controls the transcription of the human autocrine motility factor receptor."
Huang B., Xie Y., Raz A.
Biochem. Biophys. Res. Commun. 212:727-742(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 358-643.
Tissue: Placenta.
[4]"Purification of human tumor cell autocrine motility factor and molecular cloning of its receptor."
Watanabe H., Carmi P., Hogan V., Raz T., Silletti S., Nabi I.R., Raz A.
J. Biol. Chem. 266:13442-13448(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 520-643.
[5]"The tumor autocrine motility factor receptor, gp78, is a ubiquitin protein ligase implicated in degradation from the endoplasmic reticulum."
Fang S., Ferrone M., Yang C., Jensen J.P., Tiwari S., Weissman A.M.
Proc. Natl. Acad. Sci. U.S.A. 98:14422-14427(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION AS A UBIQUITIN LIGASE, SUBCELLULAR LOCATION, INTERACTION WITH UBE2G2.
[6]"Overexpression of the tumor autocrine motility factor receptor, gp78, a ubiquitin protein ligase (E3), results in increased ubiquitinylation and decreased secretion of apolipoprotein B100 in Hep G2 cells."
Liang J.S., Kim T., Fang S., Yamaguchi J., Weissman A.M., Fisher E.A., Ginsberg H.N.
J. Biol. Chem. 278:23984-23988(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: UBIQUITINATION OF APOB.
[7]"Gp78, a membrane-anchored ubiquitin ligase, associates with Insig-1 and couples sterol-regulated ubiquitination to degradation of HMG CoA reductase."
Song B.L., Sever N., DeBose-Boyd R.A.
Mol. Cell 19:829-840(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH INSIG1 AND VCP, FUNCTION, MUTAGENESIS OF CYS-356.
[8]"Recruitment of the p97 ATPase and ubiquitin ligases to the site of retrotranslocation at the endoplasmic reticulum membrane."
Ye Y., Shibata Y., Kikkert M., van Voorden S., Wiertz E., Rapoport T.A.
Proc. Natl. Acad. Sci. U.S.A. 102:14132-14138(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH DERL1 AND VCP.
[9]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-516, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[10]"CYP3A4 ubiquitination by gp78 (the tumor autocrine motility factor receptor, AMFR) and CHIP E3 ligases."
Pabarcus M.K., Hoe N., Sadeghi S., Patterson C., Wiertz E., Correia M.A.
Arch. Biochem. Biophys. 483:66-74(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[11]"Solution structure of RSGI RUH-076, a human CUE domain."
RIKEN structural genomics initiative (RSGI)
Submitted (SEP-2007) to the PDB data bank
Cited for: STRUCTURE BY NMR OF 452-502.
[12]"The consensus coding sequences of human breast and colorectal cancers."
Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. expand/collapse author list , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E.
Science 314:268-274(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT [LARGE SCALE ANALYSIS] VAL-605.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF124145 mRNA. Translation: AAD56722.1.
BC069197 mRNA. Translation: AAH69197.1.
L35233 mRNA. Translation: AAA79362.1. Frameshift.
M63175 mRNA. Translation: AAA36671.1. Sequence problems.
CCDSCCDS10758.1.
PIRA39877.
RefSeqNP_001135.3. NM_001144.5.
UniGeneHs.295137.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2EJSNMR-A452-502[»]
2LVNNMR-C453-504[»]
2LVONMR-C453-504[»]
2LVPNMR-C453-504[»]
2LVQNMR-D453-504[»]
2LXHNMR-C313-393[»]
2LXPNMR-B574-600[»]
C327-384[»]
3FSHX-ray2.76C574-601[»]
3H8KX-ray1.80B573-600[»]
3TIWX-ray1.80C/D622-640[»]
4G3OX-ray1.60A456-498[»]
4LADX-ray2.30B313-393[»]
B574-600[»]
ProteinModelPortalQ9UKV5.
SMRQ9UKV5. Positions 327-384, 453-504, 574-599.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid106764. 81 interactions.
DIPDIP-29060N.
IntActQ9UKV5. 15 interactions.
MINTMINT-2821880.
STRING9606.ENSP00000290649.

PTM databases

PhosphoSiteQ9UKV5.

Polymorphism databases

DMDM34922250.

Proteomic databases

MaxQBQ9UKV5.
PeptideAtlasQ9UKV5.
PRIDEQ9UKV5.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000290649; ENSP00000290649; ENSG00000159461.
GeneID267.
KEGGhsa:267.
UCSCuc002eiy.4. human.

Organism-specific databases

CTD267.
GeneCardsGC16M056395.
HGNCHGNC:463. AMFR.
HPACAB026381.
HPA029018.
MIM603243. gene.
neXtProtNX_Q9UKV5.
PharmGKBPA24768.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG5243.
HOGENOMHOG000037436.
HOVERGENHBG044694.
InParanoidQ9UKV5.
KOK10636.
OMANTACCFL.
OrthoDBEOG7QRQT8.
PhylomeDBQ9UKV5.
TreeFamTF320052.

Enzyme and pathway databases

UniPathwayUPA00143.

Gene expression databases

ArrayExpressQ9UKV5.
BgeeQ9UKV5.
CleanExHS_AMFR.
GenevestigatorQ9UKV5.

Family and domain databases

Gene3D3.30.40.10. 1 hit.
InterProIPR003892. CUE.
IPR001841. Znf_RING.
IPR013083. Znf_RING/FYVE/PHD.
[Graphical view]
PfamPF02845. CUE. 1 hit.
PF13639. zf-RING_2. 1 hit.
[Graphical view]
SMARTSM00546. CUE. 1 hit.
SM00184. RING. 1 hit.
[Graphical view]
PROSITEPS51140. CUE. 1 hit.
PS50089. ZF_RING_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSAMFR. human.
EvolutionaryTraceQ9UKV5.
GeneWikiAMFR.
GenomeRNAi267.
NextBio1049.
PROQ9UKV5.
SOURCESearch...

Entry information

Entry nameAMFR_HUMAN
AccessionPrimary (citable) accession number: Q9UKV5
Secondary accession number(s): P26442, Q8IZ70
Entry history
Integrated into UniProtKB/Swiss-Prot: September 19, 2003
Last sequence update: June 1, 2003
Last modified: July 9, 2014
This is version 120 of the entry and version 2 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 polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 16

Human chromosome 16: entries, gene names and cross-references to MIM