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Q9UKV5

- AMFR_HUMAN

UniProt

Q9UKV5 - AMFR_HUMAN

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Protein
E3 ubiquitin-protein ligase AMFR
Gene
AMFR, RNF45
Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5 - Experimental evidence at protein leveli

Functioni

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.4 Publications

Pathwayi

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Zinc fingeri341 – 37939RING-type
Add
BLAST

GO - Molecular functioni

  1. ligase activity Source: UniProtKB-KW
  2. protein binding Source: UniProtKB
  3. receptor activity Source: UniProtKB
  4. ubiquitin-protein transferase activity Source: UniProtKB
  5. zinc ion binding Source: InterPro
Complete GO annotation...

GO - Biological processi

  1. ER-associated ubiquitin-dependent protein catabolic process Source: UniProtKB
  2. aging Source: Ensembl
  3. cellular component movement Source: ProtInc
  4. endoplasmic reticulum unfolded protein response Source: UniProtKB
  5. learning or memory Source: Ensembl
  6. protein oligomerization Source: UniProtKB
  7. protein polyubiquitination Source: UniProtKB
  8. signal transduction Source: ProtInc
  9. ubiquitin-dependent protein catabolic process Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Ligase, Receptor

Keywords - Biological processi

Ubl conjugation pathway

Keywords - Ligandi

Metal-binding, Zinc

Enzyme and pathway databases

UniPathwayiUPA00143.

Names & Taxonomyi

Protein namesi
Recommended 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 namesi
Name:AMFR
Synonyms:RNF45
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 16

Organism-specific databases

HGNCiHGNC:463. AMFR.

Subcellular locationi

Endoplasmic reticulum membrane; Multi-pass membrane protein 1 Publication

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Transmembranei82 – 10221Helical; Reviewed prediction
Add
BLAST
Transmembranei122 – 14221Helical; Reviewed prediction
Add
BLAST
Transmembranei145 – 16521Helical; Reviewed prediction
Add
BLAST
Transmembranei186 – 20621Helical; Reviewed prediction
Add
BLAST
Transmembranei215 – 23521Helical; Reviewed prediction
Add
BLAST
Transmembranei276 – 29621Helical; Reviewed prediction
Add
BLAST
Transmembranei429 – 44921Helical; Reviewed prediction
Add
BLAST

GO - Cellular componenti

  1. Hrd1p ubiquitin ligase complex Source: UniProt
  2. dendrite Source: Ensembl
  3. endoplasmic reticulum membrane Source: UniProt
  4. growth cone Source: Ensembl
  5. integral component of endoplasmic reticulum membrane Source: UniProtKB
  6. integral component of membrane Source: UniProtKB
  7. neuronal cell body Source: Ensembl
  8. nucleus Source: Ensembl
  9. perinuclear region of cytoplasm Source: ParkinsonsUK-UCL
  10. protein complex Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Endoplasmic reticulum, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi356 – 3561C → G: No degradation of HMGCR. 1 Publication

Organism-specific databases

PharmGKBiPA24768.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 643643E3 ubiquitin-protein ligase AMFR
PRO_0000064579Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei516 – 5161Phosphoserine1 Publication
Modified residuei542 – 5421Phosphoserine By similarity

Keywords - PTMi

Phosphoprotein

Proteomic databases

MaxQBiQ9UKV5.
PeptideAtlasiQ9UKV5.
PRIDEiQ9UKV5.

PTM databases

PhosphoSiteiQ9UKV5.

Expressioni

Gene expression databases

ArrayExpressiQ9UKV5.
BgeeiQ9UKV5.
CleanExiHS_AMFR.
GenevestigatoriQ9UKV5.

Organism-specific databases

HPAiCAB026381.
HPA029018.

Interactioni

Subunit structurei

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.3 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
VCPP550726EBI-1046367,EBI-355164

Protein-protein interaction databases

BioGridi106764. 82 interactions.
DIPiDIP-29060N.
IntActiQ9UKV5. 16 interactions.
MINTiMINT-2821880.
STRINGi9606.ENSP00000290649.

Structurei

Secondary structure

Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi332 – 3376
Beta strandi342 – 3443
Beta strandi351 – 3533
Beta strandi355 – 3573
Beta strandi359 – 3613
Helixi362 – 3698
Beta strandi376 – 3783
Helixi456 – 46712
Helixi473 – 48311
Helixi486 – 4949
Helixi575 – 59925
Helixi625 – 63713

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
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[»]
ProteinModelPortaliQ9UKV5.
SMRiQ9UKV5. Positions 327-384, 453-504, 574-599.

Miscellaneous databases

EvolutionaryTraceiQ9UKV5.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini456 – 49843CUE
Add
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni614 – 64330VCP/p97-interacting motif (VIM)
Add
BLAST

Domaini

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 similaritiesi

Contains 1 CUE domain.

Keywords - Domaini

Transmembrane, Transmembrane helix, Zinc-finger

Phylogenomic databases

eggNOGiCOG5243.
HOGENOMiHOG000037436.
HOVERGENiHBG044694.
InParanoidiQ9UKV5.
KOiK10636.
OMAiNTACCFL.
OrthoDBiEOG7QRQT8.
PhylomeDBiQ9UKV5.
TreeFamiTF320052.

Family and domain databases

Gene3Di3.30.40.10. 1 hit.
InterProiIPR003892. CUE.
IPR001841. Znf_RING.
IPR013083. Znf_RING/FYVE/PHD.
[Graphical view]
PfamiPF02845. CUE. 1 hit.
PF13639. zf-RING_2. 1 hit.
[Graphical view]
SMARTiSM00546. CUE. 1 hit.
SM00184. RING. 1 hit.
[Graphical view]
PROSITEiPS51140. CUE. 1 hit.
PS50089. ZF_RING_2. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q9UKV5-1 [UniParc]FASTAAdd to Basket

« Hide

MPLLFLERFP WPSLRTYTGL SGLALLGTII SAYRALSQPE AGPGEPDQLT    50
ASLQPEPPAP ARPSAGGPRA RDVAQYLLSD SLFVWVLVNT ACCVLMLVAK 100
LIQCIVFGPL RVSERQHLKD KFWNFIFYKF IFIFGVLNVQ TVEEVVMWCL 150
WFAGLVFLHL MVQLCKDRFE YLSFSPTTPM SSHGRVLSLL VAMLLSCCGL 200
AAVCSITGYT HGMHTLAFMA AESLLVTVRT AHVILRYVIH LWDLNHEGTW 250
EGKGTYVYYT DFVMELTLLS LDLMHHIHML LFGNIWLSMA SLVIFMQLRY 300
LFHEVQRRIR RHKNYLRVVG NMEARFAVAT PEELAVNNDD CAICWDSMQA 350
ARKLPCGHLF HNSCLRSWLE QDTSCPTCRM SLNIADNNRV REEHQGENLD 400
ENLVPVAAAE GRPRLNQHNH FFHFDGSRIA SWLPSFSVEV MHTTNILGIT 450
QASNSQLNAM AHQIQEMFPQ VPYHLVLQDL QLTRSVEITT DNILEGRIQV 500
PFPTQRSDSI RPALNSPVER PSSDQEEGET SAQTERVPLD LSPRLEETLD 550
FGEVEVEPSE VEDFEARGSR FSKSADERQR MLVQRKDELL QQARKRFLNK 600
SSEDDAASES FLPSEGASSD PVTLRRRMLA AAAERRLQKQ QTS 643
Length:643
Mass (Da):72,996
Last modified:June 1, 2003 - v2
Checksum:i8782324609C0E62A
GO

Sequence cautioni

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.

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti605 – 6051D → V in a breast cancer sample; somatic mutation. 1 Publication
VAR_035790

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti406 – 4061V → D in AAA79362. 1 Publication
Sequence conflicti491 – 4911D → V in AAA79362. 1 Publication
Sequence conflicti500 – 5001V → L in AAA79362. 1 Publication
Sequence conflicti614 – 6141S → L in AAD56722. 1 Publication

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
AF124145 mRNA. Translation: AAD56722.1.
BC069197 mRNA. Translation: AAH69197.1.
L35233 mRNA. Translation: AAA79362.1. Frameshift.
M63175 mRNA. Translation: AAA36671.1. Sequence problems.
CCDSiCCDS10758.1.
PIRiA39877.
RefSeqiNP_001135.3. NM_001144.5.
UniGeneiHs.295137.

Genome annotation databases

EnsembliENST00000290649; ENSP00000290649; ENSG00000159461.
GeneIDi267.
KEGGihsa:267.
UCSCiuc002eiy.4. human.

Polymorphism databases

DMDMi34922250.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
AF124145 mRNA. Translation: AAD56722.1 .
BC069197 mRNA. Translation: AAH69197.1 .
L35233 mRNA. Translation: AAA79362.1 . Frameshift.
M63175 mRNA. Translation: AAA36671.1 . Sequence problems.
CCDSi CCDS10758.1.
PIRi A39877.
RefSeqi NP_001135.3. NM_001144.5.
UniGenei Hs.295137.

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
2EJS NMR - A 452-502 [» ]
2LVN NMR - C 453-504 [» ]
2LVO NMR - C 453-504 [» ]
2LVP NMR - C 453-504 [» ]
2LVQ NMR - D 453-504 [» ]
2LXH NMR - C 313-393 [» ]
2LXP NMR - B 574-600 [» ]
C 327-384 [» ]
3FSH X-ray 2.76 C 574-601 [» ]
3H8K X-ray 1.80 B 573-600 [» ]
3TIW X-ray 1.80 C/D 622-640 [» ]
4G3O X-ray 1.60 A 456-498 [» ]
4LAD X-ray 2.30 B 313-393 [» ]
B 574-600 [» ]
ProteinModelPortali Q9UKV5.
SMRi Q9UKV5. Positions 327-384, 453-504, 574-599.
ModBasei Search...

Protein-protein interaction databases

BioGridi 106764. 82 interactions.
DIPi DIP-29060N.
IntActi Q9UKV5. 16 interactions.
MINTi MINT-2821880.
STRINGi 9606.ENSP00000290649.

PTM databases

PhosphoSitei Q9UKV5.

Polymorphism databases

DMDMi 34922250.

Proteomic databases

MaxQBi Q9UKV5.
PeptideAtlasi Q9UKV5.
PRIDEi Q9UKV5.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000290649 ; ENSP00000290649 ; ENSG00000159461 .
GeneIDi 267.
KEGGi hsa:267.
UCSCi uc002eiy.4. human.

Organism-specific databases

CTDi 267.
GeneCardsi GC16M056395.
HGNCi HGNC:463. AMFR.
HPAi CAB026381.
HPA029018.
MIMi 603243. gene.
neXtProti NX_Q9UKV5.
PharmGKBi PA24768.
GenAtlasi Search...

Phylogenomic databases

eggNOGi COG5243.
HOGENOMi HOG000037436.
HOVERGENi HBG044694.
InParanoidi Q9UKV5.
KOi K10636.
OMAi NTACCFL.
OrthoDBi EOG7QRQT8.
PhylomeDBi Q9UKV5.
TreeFami TF320052.

Enzyme and pathway databases

UniPathwayi UPA00143 .

Miscellaneous databases

ChiTaRSi AMFR. human.
EvolutionaryTracei Q9UKV5.
GeneWikii AMFR.
GenomeRNAii 267.
NextBioi 1049.
PROi Q9UKV5.
SOURCEi Search...

Gene expression databases

ArrayExpressi Q9UKV5.
Bgeei Q9UKV5.
CleanExi HS_AMFR.
Genevestigatori Q9UKV5.

Family and domain databases

Gene3Di 3.30.40.10. 1 hit.
InterProi IPR003892. CUE.
IPR001841. Znf_RING.
IPR013083. Znf_RING/FYVE/PHD.
[Graphical view ]
Pfami PF02845. CUE. 1 hit.
PF13639. zf-RING_2. 1 hit.
[Graphical view ]
SMARTi SM00546. CUE. 1 hit.
SM00184. RING. 1 hit.
[Graphical view ]
PROSITEi PS51140. CUE. 1 hit.
PS50089. ZF_RING_2. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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. 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. Cited for: VARIANT [LARGE SCALE ANALYSIS] VAL-605.

Entry informationi

Entry nameiAMFR_HUMAN
AccessioniPrimary (citable) accession number: Q9UKV5
Secondary accession number(s): P26442, Q8IZ70
Entry historyi
Integrated into UniProtKB/Swiss-Prot: September 19, 2003
Last sequence update: June 1, 2003
Last modified: September 3, 2014
This is version 121 of the entry and version 2 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 16
    Human chromosome 16: 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. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  7. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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