MARCHF11

Summary

MARCHF11 (membrane associated ring-CH-type finger 11, HGNC:33609) is a protein-coding gene on chromosome 5p15.1, encoding E3 ubiquitin-protein ligase MARCHF11 (A6NNE9). E3 ubiquitin-protein ligase that mediates polyubiquitination of CD4.

MARCH11 is a member of the MARCH family of membrane-bound E3 ubiquitin ligases (EC 6.3.2.19). These enzymes add ubiquitin (see MIM 191339) to target lysines in substrate proteins, thereby signaling their intracellular transport. March11 appears to have a role in ubiquitin-mediated protein sorting in the trans-Golgi network (TGN)-multivesicular body (MVB) transport pathway (Morokuma et al., 2007 [PubMed 17604280]).

Source: NCBI Gene 441061 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 76 total
• MANE Select transcript: NM_001102562

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:33609
Approved symbol	MARCHF11
Name	membrane associated ring-CH-type finger 11
Location	5p15.1
Locus type	gene with protein product
Status	Approved
Aliases	MARCH-XI, RNF226
Ensembl gene	ENSG00000183654
Ensembl biotype	protein_coding
OMIM	613338
Entrez	441061

Gene structure

Transcript identifiers

Ensembl transcripts: 3 — 2 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000332432, ENST00000505509, ENST00000507111

RefSeq mRNA: 1 — MANE Select: NM_001102562 NM_001102562

CCDS: CCDS47192

Canonical transcript exons

ENST00000332432 — 4 exons

Exon	Start	End
ENSE00001330612	16090889	16091081
ENSE00001491690	16179039	16179791
ENSE00002064922	16067139	16067793
ENSE00003527275	16177726	16177881

Expression profiles

Bgee: expression breadth ubiquitous, 135 present calls, max score 97.58.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.6709 / max 202.6135, expressed in 132 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
60992	0.3824	101
60991	0.1680	49
60995	0.0427	12
60990	0.0291	8
60993	0.0271	9
60994	0.0124	4
60996	0.0091	3

Top tissues by expression

237 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
sperm	CL:0000019	97.58	gold quality
left testis	UBERON:0004533	97.44	gold quality
right testis	UBERON:0004534	97.01	gold quality
testis	UBERON:0000473	95.08	gold quality
adult organism	UBERON:0007023	88.67	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	87.76	gold quality
endothelial cell	CL:0000115	85.65	gold quality
pituitary gland	UBERON:0000007	79.63	gold quality
adenohypophysis	UBERON:0002196	78.95	gold quality
prefrontal cortex	UBERON:0000451	78.02	gold quality
Brodmann (1909) area 23	UBERON:0013554	77.17	gold quality
left ventricle myocardium	UBERON:0006566	76.86	gold quality
secondary oocyte	CL:0000655	76.84	gold quality
right hemisphere of cerebellum	UBERON:0014890	76.64	gold quality
right frontal lobe	UBERON:0002810	76.51	gold quality
primary visual cortex	UBERON:0002436	76.19	gold quality
anterior cingulate cortex	UBERON:0009835	75.54	gold quality
Brodmann (1909) area 9	UBERON:0013540	75.50	gold quality
cerebellar cortex	UBERON:0002129	75.32	gold quality
cerebellar hemisphere	UBERON:0002245	75.24	gold quality
middle temporal gyrus	UBERON:0002771	75.00	gold quality
cerebellum	UBERON:0002037	74.75	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	74.74	gold quality
frontal cortex	UBERON:0001870	74.60	gold quality
myocardium	UBERON:0002349	74.47	silver quality
apex of heart	UBERON:0002098	74.46	gold quality
neocortex	UBERON:0001950	74.21	gold quality
hypothalamus	UBERON:0001898	73.53	gold quality
heart left ventricle	UBERON:0002084	72.98	gold quality
cardiac ventricle	UBERON:0002082	72.79	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.12

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

23 targeting MARCHF11, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4776-3P	100.00	68.73	1340
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-302E	99.96	70.74	2669
HSA-MIR-1468-3P	99.96	72.74	3797
HSA-MIR-302C-3P	99.89	71.20	1778
HSA-MIR-302D-3P	99.89	71.25	1777
HSA-MIR-302A-3P	99.89	71.23	1777
HSA-MIR-302B-3P	99.89	71.23	1777
HSA-MIR-520E-3P	99.84	70.55	1698
HSA-MIR-373-3P	99.84	70.68	1668
HSA-MIR-372-3P	99.83	70.58	1691
HSA-MIR-520A-3P	99.83	70.59	1687
HSA-MIR-520B-3P	99.83	70.56	1699
HSA-MIR-520C-3P	99.83	70.56	1699
HSA-MIR-520D-3P	99.83	70.78	1676
HSA-MIR-376A-3P	99.06	69.17	1128
HSA-MIR-376B-3P	99.06	69.17	1128
HSA-MIR-143-5P	98.98	68.87	946
HSA-MIR-3944-5P	98.50	67.55	997
HSA-MIR-653-3P	98.31	67.71	1542
HSA-MIR-4275	97.96	68.42	1549
HSA-MIR-576-3P	96.14	65.63	773
HSA-MIR-31-3P	95.17	69.82	575

Literature-anchored findings (GeneRIF, showing 1)

• Anaplastic Lymphoma Kinase signaling stabilizes SLC3A2 expression via MARCH11 to promote neuroblastoma cell growth. (PMID:38858548)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	marchf11	ENSDARG00000075212
mus_musculus	Marchf11	ENSMUSG00000022269
rattus_norvegicus	Marchf11	ENSRNOG00000024461

Paralogs (6): MARCHF2 (ENSG00000099785), MARCHF9 (ENSG00000139266), MARCHF4 (ENSG00000144583), MARCHF1 (ENSG00000145416), MARCHF8 (ENSG00000165406), MARCHF3 (ENSG00000173926)

Protein

Protein identifiers

E3 ubiquitin-protein ligase MARCHF11 — A6NNE9 (reviewed: A6NNE9)

Alternative names: Membrane-associated RING finger protein 11, Membrane-associated RING-CH protein XI, RING-type E3 ubiquitin transferase MARCHF11

All UniProt accessions (2): A6NNE9, H0Y9K6

UniProt curated annotations — full annotation on UniProt →

Function. E3 ubiquitin-protein ligase that mediates polyubiquitination of CD4. E3 ubiquitin ligases accept ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and then directly transfer the ubiquitin to targeted substrates. May play a role in ubuquitin-dependent protein sorting in developmenting spermatids.

Subunit / interactions. Interacts (YXXL motif) with AP1M1. Interacts (via PDZ-binding motif) with LIN7A. Interacts with unidentified fucose glycoproteins.

Subcellular location. Cytoplasmic vesicle membrane.

Domain organisation. The RING-CH-type zinc finger domain is required for E3 ligase activity.

Pathway. Protein modification; protein ubiquitination.

Isoforms (2)

UniProt ID	Names	Canonical?
A6NNE9-1	1	yes
A6NNE9-2	2

RefSeq proteins (1): NP_001096032* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR011016	Znf_RING-CH	Domain
IPR013083	Znf_RING/FYVE/PHD	Homologous_superfamily
IPR046356	MARCHF4/9/11	Family
IPR047906	MARCHF11_RING_CH-C4HC3	Domain

Pfam: PF12906

UniProt features (19 total): binding site 8, compositionally biased region 3, transmembrane region 2, short sequence motif 2, chain 1, splice variant 1, zinc finger region 1, region of interest 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-A6NNE9-F1	63.87	0.18

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Ligand- & substrate-binding residues (8): 170; 173; 186; 188; 196; 199; 212; 215

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 37 (showing top): GOBP_POST_TRANSLATIONAL_PROTEIN_MODIFICATION, GOMF_ACYLTRANSFERASE_ACTIVITY, GOMF_AMINOACYLTRANSFERASE_ACTIVITY, GOMF_UBIQUITIN_LIKE_PROTEIN_LIGASE_ACTIVITY, GSE13762_CTRL_VS_125_VITAMIND_DAY5_DC_DN, MEISSNER_NPC_HCP_WITH_H3K4ME2, MIR302E, MIR302A_3P_MIR302B_3P_MIR302C_3P_MIR302D_3P, MIR520A_3P, MIR372_3P, MIR520D_3P, MIR520B_3P_MIR520C_3P_MIR520E_3P, MIR373_3P, MIR4275, MIR4776_3P

GO Biological Process (1): protein ubiquitination (GO:0016567)

GO Molecular Function (5): ubiquitin-protein transferase activity (GO:0004842), zinc ion binding (GO:0008270), ubiquitin protein ligase activity (GO:0061630), transferase activity (GO:0016740), metal ion binding (GO:0046872)

GO Cellular Component (3): cytoplasmic vesicle membrane (GO:0030659), membrane (GO:0016020), cytoplasmic vesicle (GO:0031410)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein modification by small protein conjugation	1
ubiquitin-like protein transferase activity	1
transition metal ion binding	1
ubiquitin-protein transferase activity	1
ubiquitin-like protein ligase activity	1
catalytic activity	1
cation binding	1
vesicle membrane	1
cytoplasmic vesicle	1
cellular anatomical structure	1
cytoplasm	1
intracellular vesicle	1

Protein interactions and networks

STRING

526 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MARCHF11	LIN7C	Q9NUP9	839
MARCHF11	AP1M1	Q9BXS5	761
MARCHF11	MARCHF10	Q8NA82	742
MARCHF11	AP1G1	O43747	639
MARCHF11	MARCHF7	Q9H992	616
MARCHF11	GSTM1	P09488	563
MARCHF11	UNCX	A6NJT0	544
MARCHF11	AJAP1	Q9UKB5	542
MARCHF11	FBXL7	Q9UJT9	465
MARCHF11	PCDHGB6	Q9Y5F9	418
MARCHF11	ZNF622	Q969S3	411
MARCHF11	CDO1	P78513	400
MARCHF11	OTULINL	Q9NUU6	376
MARCHF11	RAVER1	Q8IY67	350
MARCHF11	PTGDR	Q13258	329

IntAct

0 interactions, top by confidence:

BioGRID (1): MARCH11 (Affinity Capture-Western)

ESM2 similar proteins: A6NKL6, A6NNE9, A6P320, D3YYI7, E9Q0B3, F5H4A9, O60346, P0C1G7, P0C7U0, P0DPB3, P39881, P53349, Q0P496, Q13233, Q147X3, Q2TBI2, Q3TZ87, Q49LS4, Q52L14, Q5GH59, Q5GH67, Q5GH76, Q5VV17, Q62925, Q66JB6, Q6NS60, Q80TE3, Q86VE0, Q86YJ5, Q8BGW2, Q8CBH7, Q8R554, Q8TC41, Q8TE49, Q8TF61, Q96EP1, Q96SQ7, Q99MX7, Q99NA2, Q9BXQ6

Diamond homologs: A0JN69, A6NNE9, A6P320, F4JKK0, O60103, O60337, P40318, P90489, P90495, Q0IH10, Q0P496, Q0VD59, Q1LVZ2, Q28EX7, Q32L65, Q3TZ87, Q5I0I2, Q5PQ35, Q5R9W1, Q5T0T0, Q5XIE5, Q5XIV2, Q68FA7, Q6NZQ8, Q6ZQ89, Q80TE3, Q86UD3, Q86YJ5, Q8BRX9, Q8CBH7, Q8TCQ1, Q99M02, Q9DBD2, Q9P0N8, Q9P2E8, Q0X0A5, Q28IK8, Q3KNM2, Q3ZC24, Q5R9W2

SIGNOR signaling

1 interactions.

A	Effect	B	Mechanism
Ub:E2	“up-regulates activity”	MARCHF11	ubiquitination

Disease & clinical

Clinical variants and AI predictions

ClinVar

76 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	74
Likely benign	2
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

943 predictions. Top by Δscore:

Variant	Effect	Δscore
5:16177721:CTTA:C	donor_loss	1.0000
5:16177722:TTA:T	donor_loss	1.0000
5:16177723:TACCT:T	donor_loss	1.0000
5:16177724:A:T	donor_loss	1.0000
5:16177725:C:CA	donor_loss	1.0000
5:16177720:GCTTA:G	donor_loss	0.9900
5:16177878:CACC:C	acceptor_gain	0.9900
5:16177880:CC:C	acceptor_gain	0.9900
5:16177881:CC:C	acceptor_gain	0.9900
5:16177882:C:T	acceptor_gain	0.9900
5:16179033:CCTTA:C	donor_loss	0.9900
5:16179034:CTTA:C	donor_loss	0.9900
5:16179035:TTA:T	donor_loss	0.9900
5:16179036:TACCT:T	donor_loss	0.9900
5:16179037:ACC:A	donor_loss	0.9900
5:16179038:C:A	donor_loss	0.9900
5:16179038:CCTG:C	donor_gain	0.9900
5:16067792:ACC:A	acceptor_loss	0.9800
5:16067801:T:C	acceptor_gain	0.9800
5:16091079:CCACT:C	acceptor_gain	0.9800
5:16177155:T:TA	donor_gain	0.9800
5:16177724:A:AC	donor_gain	0.9800
5:16177725:C:CC	donor_gain	0.9800
5:16177882:C:CC	acceptor_gain	0.9800
5:16179037:A:AC	donor_gain	0.9800
5:16179038:C:CC	donor_gain	0.9800
5:16067794:C:CC	acceptor_gain	0.9700
5:16091078:GCCAC:G	acceptor_gain	0.9700
5:16091082:C:CC	acceptor_gain	0.9700
5:16150108:A:C	acceptor_gain	0.9700

AlphaMissense

2593 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:16067725:A:G	W319R	1.000
5:16067725:A:T	W319R	1.000
5:16067790:A:G	L297P	1.000
5:16067790:A:T	L297H	1.000
5:16090893:G:C	C294W	1.000
5:16090894:C:T	C294Y	1.000
5:16090895:A:G	C294R	1.000
5:16090904:C:G	D291H	1.000
5:16090905:C:A	M290I	1.000
5:16090905:C:G	M290I	1.000
5:16090905:C:T	M290I	1.000
5:16090906:A:T	M290K	1.000
5:16090912:C:T	G288D	1.000
5:16090916:A:G	Y287H	1.000
5:16090926:G:C	C283W	1.000
5:16090927:C:T	C283Y	1.000
5:16090928:A:G	C283R	1.000
5:16090935:A:C	F280L	1.000
5:16090935:A:T	F280L	1.000
5:16090937:A:G	F280L	1.000
5:16090985:A:G	W264R	1.000
5:16090985:A:T	W264R	1.000
5:16090990:A:G	L262P	1.000
5:16090994:A:G	W261R	1.000
5:16090994:A:T	W261R	1.000
5:16091001:A:C	S258R	1.000
5:16091001:A:T	S258R	1.000
5:16091002:C:A	S258I	1.000
5:16091003:T:G	S258R	1.000
5:16091013:G:C	F254L	1.000

dbSNP variants (sampled 300 via entrez): RS1000034561 (5:16179705 G>A,C), RS1000042274 (5:16129621 T>C,G), RS1000092540 (5:16157371 C>A), RS1000124422 (5:16139182 G>A,T), RS1000125145 (5:16130602 A>T), RS1000143739 (5:16142415 C>T), RS1000146866 (5:16106147 G>T), RS1000168610 (5:16102462 C>G), RS1000175964 (5:16181693 G>A,T), RS1000202559 (5:16095612 G>A), RS1000204847 (5:16092113 C>T), RS1000205266 (5:16143846 T>C), RS1000284411 (5:16110118 C>T), RS1000332221 (5:16149753 G>A), RS1000334600 (5:16145111 C>T)

Disease associations

OMIM: gene MIM:613338 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

9 total (human), top 9 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
entinostat	decreases expression	1
Sunitinib	increases expression	1
Calcitriol	increases expression, affects cotreatment	1
Testosterone	affects cotreatment, increases expression	1
Tretinoin	decreases expression	1
Valproic Acid	increases methylation	1
Antirheumatic Agents	increases expression	1
Okadaic Acid	decreases expression	1
Particulate Matter	increases methylation	1

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.