KCMF1 (potassium channel modulatory factor 1)

2009-07-01 Roshan Mandrawalia , Ranjan Tamuli Affiliation

Department of Biotechnology, Indian Institute of Technology Guwahati, Guwahati-781 039, Assam, India

Identity

HGNC

KCMF1

LOCATION

2p11.2

LOCUSID

56888

ALIAS

DEBT91,FIGC,PCMF,ZZZ1

FUSION GENES

Show Gene Fusions

DNA/RNA

Description

DNA size 87.29 kb, mRNA size 7555 bp, 7 exons.

Proteins

Description

381 amino acids; 41.945 kDa protein.
KCMF1 protein contains ring finger (Zinc finger, ZZ-type) 3-50 (48), zinc finger (C2H2-type) 78-101 (23), nuclear localization signal (NLS) 152-168 (17), and a coiled coil domain 225-257 (33).

Isoforms:
Two isoforms that predicted to encode proteins containing the zinc finger domain have been identified; other isoforms are relatively shorter and not well defined.

Isoform bApr07: This partial mRNA is 625 bp long. It is reconstructed from a myeloma cDNA clone. The pre-messenger RNA has 5 exons and covers 74.08 kb. The predicted partial protein has 208 aa (22.9 kDa, pI 5.8) and a very good coding score (7). It contains one Zinc finger, ZZ-type domain, one zinc finger, C2H2-type domain.

Isoform dApr07: The dApr07 mRNA variant is 431 bp long. It is reconstructed from a testis cDNA clone. The pre-mRNA has 4 exons and covers 12.72 kb. The predicted partial protein has 143 aa (15.7 kDa, pI 7.2) and a very good coding score (5). It contains one zinc finger, C2H2-type domain.

Expression

Ubiquitously expressed. High level of expression is in pharynx, thyroid, respiratory tract and larynx; less expressed in female system, uterus and cervix.

Localisation

Nuclear.

Function

KCMF1 is a transcription factor. Basic functions of the KCMF1 gene are (i) early gene up-regulation during growth factor-induced branching tubulogenesis, (ii) ubiquitination through intrinsic E3 ubiquitin ligase activity, and (iii) a possible role in ion channel activity.

Homology

The percent identity below represents identity of KCMF1 over an aligned region in UniGene.
Pan troglodytes: 97 (Percentage Identity)
Canis lupas familiaris: 91
Bos Taurus: 90
Mus musculus: 96
Gallus gallus: 93
Danio rerio: 85.

Implicated in

Entity name

Ewings sarcoma family of tumors (ESFT)

Note

KCMF1 is down regulated by high constitutive CD99 (a cell surface glycoprotein) expression in ESFT. KCMF1 expression is inversely correlated with CD99 expression, as seen in a series of 22 primary ESFT. High CD99 expression levels contribute to the malignant properties of ESFT by promoting growth and migration of tumor cells.

Entity name

Gastric cancer

Note

KCMF1 (also known as FIGC) encode a RING finger protein, has intrinsic E3 ubiquitin ligase activity and promotes ubiquitination. KCMF1 contains a novel C6H2-type RING finger domain at the NH2-terminal region, consensus sequence CX2C(7-11) CX2CXA5CX2CX(5-9) HX (1-3) H (XA: acidic residues). Using differential display approach with basic fibroblast growth factor (b-FGF) inducible genes in gastric cancer cells, it was observed that FIGC upregulation in response to bFGF in gastric cancer. This suggests that FIGC might be implicated in gastric carcinogenesis through dysregulation of growth modulator.

Bibliography

Pubmed ID	Last Year	Title	Authors
15581609	2004	FIGC, a novel FGF-induced ubiquitin-protein ligase in gastric cancers.	Jang JH et al
16314831	2006	Suppression of KCMF1 by constitutive high CD99 expression is involved in the migratory ability of Ewing's sarcoma cells.	Kreppel M et al
12810064	2003	Debt91, a putative zinc finger protein differentially expressed during epithelial morphogenesis.	Li Z et al

Other Information

Locus ID:

NCBI: 56888
MIM: 614719
HGNC: 20589
Ensembl: ENSG00000176407

Variants:

dbSNP: 56888
ClinVar: 56888
TCGA: ENSG00000176407
COSMIC: KCMF1

RNA/Proteins

Gene ID	Transcript ID	Uniprot
ENSG00000176407	ENST00000409785	Q9P0J7
ENSG00000176407	ENST00000428691	C9JSW5
ENSG00000176407	ENST00000453448	C9J3I2
ENSG00000176407	ENST00000456682	A0A1D5RMQ3

Expression (GTEx)

Adipose - Subcutaneous

Adipose - Visceral

Adrenal Gland

Artery - Aorta

Artery - Tibial

Bladder

Brain - Amygdala

Brain - Anterior cingulate cortex

Brain - Caudate

Brain - Cerebellar Hemisphere

Brain - Cerebellum

Brain - Cortex

Brain - Frontal Cortex

Brain - Hippocampus

Brain - Hypothalamus

Brain - Nucleus accumbens

Brain - Putamen

Brain - Spinal cord

Brain - Substantia nigra

Breast - Mammary Tissue

Cells - Cultured fibroblasts

Cells - EBV - transformed lymphocytes

Cervix - Ectocervix

Cervix - Endocervix

Colon - Sigmoid

Colon - Transverse

Esophagus - Gastroesophageal Junction

Esophagus - Mucosa

Esophagus - Muscularis

Fallopian Tube

Heart - Atrial Appendage

Heart - Left Ventricle

Kidney - Cortex

Kidney - Medulla

Liver

Lung

Minor Salivary Gland

Muscle - Skeletal

Nerve - Tibial

Ovary

Pancreas

Pituitary

Prostate

Skin - Not Sun Exposed

Skin - Sun Exposed

Small Intestine - Terminal Ileum

Spleen

Stomach

Testis

Thyroid

Uterus

Vagina

Whole Blood

Pathways

Pathway	Source	External ID
Immune System	REACTOME	R-HSA-168256
Innate Immune System	REACTOME	R-HSA-168249
Neutrophil degranulation	REACTOME	R-HSA-6798695

Protein levels (Protein atlas)

Not detected

Low

Medium

High

References

Pubmed ID	Year	Title	Citations
24980667	2014	MicroRNA-210 contributes to preeclampsia by downregulating potassium channel modulatory factor 1.	23
16314831	2006	Suppression of KCMF1 by constitutive high CD99 expression is involved in the migratory ability of Ewing's sarcoma cells.	18
15581609	2004	FIGC, a novel FGF-induced ubiquitin-protein ligase in gastric cancers.	15
25582440	2015	KCMF1 (potassium channel modulatory factor 1) Links RAD6 to UBR4 (ubiquitin N-recognin domain-containing E3 ligase 4) and lysosome-mediated degradation.	10

Citation

Roshan Mandrawalia ; Ranjan Tamuli

KCMF1 (potassium channel modulatory factor 1)

Atlas Genet Cytogenet Oncol Haematol. 2009-07-01

Online version: http://atlasgeneticsoncology.org/gene/46364/kcmf1