Menkes Syndrome- Copper-transporting ATPase 1

Just a quick review: Menkes Syndrome is a recessively inherited X chromosomal gene which disrupts copper metabolism and decreases a cells' ability to absorb copper. Research suggests that this disease is caused by

a mutation in the gene encoding Cu(2+)-transporting ATPase, alpha polypeptide

(OMIM #309400).

Uniprot Characterization:

Function: May supply copper to copper-requiring proteins within the secretory pathway, when localized in the trans-Golgi network. Under conditions of elevated extracellular copper, it relocalized to the plasma membrane where it functions in the efflux of copper from cells.

Catalytic Activity: ATP + H2O + Cu2+(In) = ADP + phosphate + Cu2+(Out).

Subunit: Monomer

Subcellular Location: Integral membrane protein. Cycles constitutively between the trans-Golgi network (TGN) and the plasma membrane. Predominantly found in the TGN and relocalized to the plasma membrane in response to elevated copper levels. Isoform 3 may be cytosolic. Isoform 5 is located in the endoplasmic reticulum.

Psort- Results of the k-NN Prediction
k = 9/23
82.6 %: plasma membrane
17.4 %: endoplasmic reticulum
>> prediction for QUERY is pla (k=23)

Domain: The C-terminal di-leucine, 1487-Leu-Leu-1488, is an endocytic targeting signal which functions in retrieving recycling from the plasma membrane to the TGN. Mutation of the di-leucine signal results in the accumulation of the protein in the plasma membrane.

metal binding domain


Secondary Structure
COILS:

Searched for repeats using REP, no repeats found
Visual structure of metal binding domains- simliar

SOSUI- SHOW!!
This amino acid sequence is of a MEMBRANE PROTEIN which have 9 transmembrane helices.

Average of hydrophobicity : 0.097200

Using TopPred2...



Characterization:
Glycosylation sites (NetOGlyc):


Phosphorylation Sites predicted (NetPhoa 2.0):
Serine: 61
Threonine: 17
Tyrosine: 8



Sulfinator: no hits

Human Protein Reference Database Link

ProtParam Info:

amino acid sequence:
1 MDPSMGVNSV TISVEGMTCN SCVWTIEQQI GKVNGVHHIK VSLEEKNATI IYDPKLQTPK 60
61 TLQEAIDDMG FDAVIHNPDP LPVLTDTLFL TVTASLTLPW DHIQSTLLKT KGVTDIKIYP 120
121 QKRTVAVTII PSIVNANQIK ELVPELSLDT GTLEKKSGAC EDHSMAQAGE VVLKMKVEGM 180
181 TCHSCTSTIE GKIGKLQGVQ RIKVSLDNQE ATIVYQPHLI SVEEMKKQIE AMGFPAFVKK 240
241 QPKYLKLGAI DVERLKNTPV KSSEGSQQRS PSYTNDSTAT FIIDGMHCKS CVSNIESTLS 300
301 ALQYVSSIVV SLENRSAIVK YNASSVTPES LRKAIEAVSP GLYRVSITSE VESTSNSPSS 360
361 SSLQKIPLNV VSQPLTQETV INIDGMTCNS CVQSIEGVIS KKPGVKSIRV SLANSNGTVE 420
421 YDPLLTSPET LRGAIEDMGF DATLSDTNEP LVVIAQPSSE MPLLTSTNEF YTKGMTPVQD 480
481 KEEGKNSSKC YIQVTGMTCA SCVANIERNL RREEGIYSIL VALMAGKAEV RYNPAVIQPP 540
541 MIAEFIRELG FGATVIENAD EGDGVLELVV RGMTCASCVH KIESSLTKHR GILYCSVALA 600
601 TNKAHIKYDP EIIGPRDIIH TIESLGFEAS LVKKDRSASH LDHKREIRQW RRSFLVSLFF 660
661 CIPVMGLMIY MMVMDHHFAT LHHNQNMSKE EMINLHSSMF LERQILPGLS VMNLLSFLLC 720
721 VPVQFFGGWY FYIQAYKALK HKTANMDVLI VLATTIAFAY SLIILLVAMY ERAKVNPITF 780
781 FDTPPMLFVF IALGRWLEHI AKGKTSEALA KLISLQATEA TIVTLDSDNI LLSEEQVDVE 840
841 LVQRGDIIKV VPGGKFPVDG RVIEGHSMVD ESLITGEAMP VAKKPGSTVI AGSINQNGSL 900
901 LICATHVGAD TTLSQIVKLV EEAQTSKAPI QQFADKLSGY FVPFIVFVSI ATLLVWIVIG 960
961 FLNFEIVETY FPGYNRSISR TETIIRFAFQ ASITVLCIAC PCSLGLATPT AVMVGTGVGA 1020
1021 QNGILIKGGE PLEMAHKVKV VVFDKTGTIT HGTPVVNQVK VLTESNRISH HKILAIVGTA 1080
1081 ESNSEHPLGT AITKYCKQEL DTETLGTCID FQVVPGCGIS CKVTNIEGLL HKNNWNIEDN 1140
1141 NIKNASLVQI DASNEQSSTS SSMIIDAQIS NALNAQQYKV LIGNREWMIR NGLVINNDVN 1200
1201 DFMTEHERKG RTAVLVAVDD ELCGLIAIAD TVKPEAELAI HILKSMGLEV VLMTGDNSKT 1260
1261 ARSIASQVGI TKVFAEVLPS HKVAKVKQLQ EEGKRVAMVG DGINDSPALA MANVGIAIGT 1320
1321 GTDVAIEAAD VVLIRNDLLD VVASIDLSRE TVKRIRINFV FALIYNLVGI PIAAGVFMPI 1380
1381 GLVLQPWMGS AAMAASSVSV VLSSLFLKLY RKPTYESYEL PARSQIGQKS PSEISVHVGI 1440
1441 DDTSRNSPKL GLLDRIVNYS RASINSLLSD KRSLNSVVTS EPDKHSLLVG DFREDDDTAL

Number of amino acids: 1500
Molecular weight: 163373.7
Theoretical pI: 5.85

Atomic composition:
Carbon C 7246
Hydrogen H 11739
Nitrogen N 1929
Oxygen O 2203
Sulfur S 70

Formula: C7246H11739N1929O2203S70
Total number of atoms: 23187

Extinction coefficient at 280nm: 92450 M-1 cm-1