MCRIP1

Summary

MCRIP1 (MAPK regulated corepressor interacting protein 1, HGNC:28007) is a protein-coding gene on chromosome 17q25.3, encoding Mapk-regulated corepressor-interacting protein 1 (C9JLW8). The phosphorylation status of MCRIP1 functions as a molecular switch to regulate epithelial-mesenchymal transition.

Involved in regulation of epithelial to mesenchymal transition. Located in cytoplasmic stress granule and nucleus.

Source: NCBI Gene 348262 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 9 total
• MANE Select transcript: NM_207368

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:28007
Approved symbol	MCRIP1
Name	MAPK regulated corepressor interacting protein 1
Location	17q25.3
Locus type	gene with protein product
Status	Approved
Aliases	GRAN2, MCRIP
Ensembl gene	ENSG00000225663
Ensembl biotype	protein_coding
OMIM	616514
Entrez	348262

Gene structure

Transcript identifiers

Ensembl transcripts: 34 — 33 protein_coding, 1 protein_coding_CDS_not_defined

ENST00000455127, ENST00000457257, ENST00000538396, ENST00000570507, ENST00000572645, ENST00000573478, ENST00000574190, ENST00000575061, ENST00000575090, ENST00000576431, ENST00000576679, ENST00000576730, ENST00000906142, ENST00000906143, ENST00000906144, ENST00000906145, ENST00000906146, ENST00000906147, ENST00000906148, ENST00000906149, ENST00000929061, ENST00000929062, ENST00000929063, ENST00000929064, ENST00000929065, ENST00000929066, ENST00000929067, ENST00000929068, ENST00000929069, ENST00000953590, ENST00000953591, ENST00000953592, ENST00000953593, ENST00000953594

RefSeq mRNA: 4 — MANE Select: NM_207368 NM_001093767, NM_001288798, NM_001288799, NM_207368

CCDS: CCDS45814, CCDS74178, CCDS74179

Canonical transcript exons

ENST00000455127 — 5 exons

Exon	Start	End
ENSE00001635655	81833238	81833291
ENSE00002635853	81822361	81823311
ENSE00003462755	81824499	81824554
ENSE00003753090	81824287	81824405
ENSE00003753357	81823412	81823513

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 98.47.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 32.2868 / max 206.6965, expressed in 1817 samples.

FANTOM5 promoters (1 alternative TSS)

Promoter ID	TPM avg	Samples expressed
168786	32.2868	1817

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right testis	UBERON:0004534	98.47	gold quality
left testis	UBERON:0004533	98.42	gold quality
prefrontal cortex	UBERON:0000451	98.41	gold quality
frontal cortex	UBERON:0001870	98.02	gold quality
temporal lobe	UBERON:0001871	97.98	gold quality
amygdala	UBERON:0001876	97.98	gold quality
apex of heart	UBERON:0002098	97.96	gold quality
anterior cingulate cortex	UBERON:0009835	97.85	gold quality
cerebral cortex	UBERON:0000956	97.80	gold quality
right frontal lobe	UBERON:0002810	97.74	gold quality
substantia nigra	UBERON:0002038	97.70	gold quality
Ammon’s horn	UBERON:0001954	97.67	gold quality
hypothalamus	UBERON:0001898	97.63	gold quality
Brodmann (1909) area 9	UBERON:0013540	97.63	gold quality
dorsolateral prefrontal cortex	UBERON:0009834	97.62	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	97.52	gold quality
ganglionic eminence	UBERON:0004023	97.37	gold quality
right coronary artery	UBERON:0001625	97.29	gold quality
primary visual cortex	UBERON:0002436	97.29	gold quality
testis	UBERON:0000473	97.26	gold quality
cortical plate	UBERON:0005343	97.16	gold quality
ascending aorta	UBERON:0001496	97.11	gold quality
popliteal artery	UBERON:0002250	97.11	gold quality
tibial artery	UBERON:0007610	97.11	gold quality
thoracic aorta	UBERON:0001515	97.08	gold quality
brain	UBERON:0000955	97.06	gold quality
lower esophagus muscularis layer	UBERON:0035833	97.05	gold quality
lower esophagus	UBERON:0013473	97.02	gold quality
left coronary artery	UBERON:0001626	96.98	gold quality
putamen	UBERON:0001874	96.92	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 2.

Experiment	Marker?	Max mean expression
E-MTAB-6819	yes	116.81
E-ANND-3	yes	8.31

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

17 targeting MCRIP1, 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-4476	100.00	68.18	2030
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-15A-5P	99.90	72.80	2787
HSA-MIR-15B-5P	99.90	72.78	2798
HSA-MIR-16-5P	99.90	72.80	2780
HSA-MIR-195-5P	99.90	72.81	2805
HSA-MIR-424-5P	99.89	71.90	2641
HSA-MIR-6838-5P	99.89	71.94	2690
HSA-MIR-3065-3P	99.87	70.25	1407
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-4755-3P	98.77	65.59	1915
HSA-MIR-4635	98.74	67.63	1339
HSA-MIR-3652	97.71	65.43	1890
HSA-MIR-4430	97.47	65.61	1813
HSA-MIR-3616-3P	96.96	65.45	983
HSA-MIR-12128	96.67	66.98	1471

Literature-anchored findings (GeneRIF, showing 1)

• MCRIP1, an ERK substrate, mediates ERK-induced gene silencing during epithelial-mesenchymal transition by regulating the co-repressor CtBP. (PMID:25728771)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	mcrip1	ENSDARG00000078383
mus_musculus	Mcrip1	ENSMUSG00000061111
rattus_norvegicus	Mcrip1	ENSRNOG00000036691
rattus_norvegicus		ENSRNOG00000090268

Paralogs (2): FGFRL1 (ENSG00000127418), MCRIP2 (ENSG00000172366)

Protein

Protein identifiers

Mapk-regulated corepressor-interacting protein 1 — C9JLW8 (reviewed: C9JLW8)

Alternative names: Granulin-2, Protein FAM195B

All UniProt accessions (6): C9JLW8, I3L2L5, I3L317, I3L3A7, I3L3C1, I3L4Q0

UniProt curated annotations — full annotation on UniProt →

Function. The phosphorylation status of MCRIP1 functions as a molecular switch to regulate epithelial-mesenchymal transition. Unphosphorylated MCRIP1 binds to and inhibits the transcriptional corepressor CTBP(s). When phosphorylated by MAPK/ERK, MCRIP1 releases CTBP(s) resulting in transcriptional silencing of the E-cadherin gene and induction of epithelial-mesenchymal transition.

Subunit / interactions. Interacts (unphosphorylated form, via the PXDLS motif) with CTBP1, competitively inhibiting CTBP-ZEB1 interaction. Interacts with CTBP2. Interacts with MCRIP2. Interacts with DDX6.

Subcellular location. Nucleus. Cytoplasm. Stress granule.

Post-translational modifications. Phosphorylation by MAPK3/1 (ERK1/2) regulates MCRIP1 binding to CTBP(s).

Similarity. Belongs to the MCRIP family.

RefSeq proteins (4): NP_001087236, NP_001275727, NP_001275728, NP_997251* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR029428	MCRIP	Family

Pfam: PF14799

UniProt features (8 total): modified residue 5, chain 1, region of interest 1, short sequence motif 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-C9JLW8-F1	76.48	0.25

Functional residue map

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

Post-translational modifications (5): 21, 24, 30, 41, 79

Function

Pathways and Gene Ontology

Reactome pathways

1 pathways

ID	Pathway
R-HSA-9764725	Negative Regulation of CDH1 Gene Transcription

MSigDB gene sets: 69 (showing top): REACTOME_ADHERENS_JUNCTIONS_INTERACTIONS, GOBP_NEGATIVE_REGULATION_OF_GENE_EXPRESSION_EPIGENETIC, GOBP_MESENCHYMAL_CELL_DIFFERENTIATION, GOBP_MESENCHYME_DEVELOPMENT, GCM_NF2, GOBP_CHROMATIN_REMODELING, GOBP_EPIGENETIC_REGULATION_OF_GENE_EXPRESSION, GOBP_REGULATION_OF_EPITHELIAL_TO_MESENCHYMAL_TRANSITION, GOCC_CYTOPLASMIC_STRESS_GRANULE, GOCC_RIBONUCLEOPROTEIN_GRANULE, REACTOME_CELL_JUNCTION_ORGANIZATION, GOCC_SUPRAMOLECULAR_COMPLEX, DACH1_TARGET_GENES, FOXN3_TARGET_GENES, NFKBIA_TARGET_GENES

GO Biological Process (3): gene expression (GO:0010467), regulation of epithelial to mesenchymal transition (GO:0010717), negative regulation of gene expression, epigenetic (GO:0045814)

GO Molecular Function (1): protein binding (GO:0005515)

GO Cellular Component (4): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytoplasmic stress granule (GO:0010494)

Reactome top-level categories

Rollup of top-1 pathways:

Category	Pathways
Regulation of CDH1 Gene Transcription	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
macromolecule biosynthetic process	1
epithelial to mesenchymal transition	1
regulation of cell differentiation	1
negative regulation of gene expression	1
epigenetic regulation of gene expression	1
binding	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular anatomical structure	1
cytoplasmic ribonucleoprotein granule	1

Protein interactions and networks

STRING

508 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
MCRIP1	SAYSD1	Q9NPB0	617
MCRIP1	DHRS7C	A6NNS2	607
MCRIP1	NUTM2G	Q5VZR2	514
MCRIP1	DNAH8	Q96JB1	473
MCRIP1	ILF2	Q12905	444
MCRIP1	KHSRP	Q92945	435
MCRIP1	KRTAP9-1	A8MXZ3	435
MCRIP1	CCDC134	Q9H6E4	433
MCRIP1	MROH8	Q9H579	419
MCRIP1	RCVRN	P35243	413
MCRIP1	ERICH6	Q7L0X2	396
MCRIP1	LRRC57	Q8N9N7	386
MCRIP1	CCDC116	Q8IYX3	381
MCRIP1	TAPT1	Q6NXT6	374
MCRIP1	CLUL1	Q15846	373

IntAct

40 interactions, top by confidence:

A	B	Type	Score
YWHAG	BLTP3B	psi-mi:“MI:0914”(association)	0.640
YWHAH	BLTP3B	psi-mi:“MI:0914”(association)	0.570
DDX6	MCRIP1	psi-mi:“MI:0914”(association)	0.510
MCRIP1	DDX6	psi-mi:“MI:0403”(colocalization)	0.510
MCRIP1	DDX6	psi-mi:“MI:0914”(association)	0.510
TNFAIP3	LRRIQ3	psi-mi:“MI:0914”(association)	0.420
TNFAIP3	LRRIQ3	psi-mi:“MI:2364”(proximity)	0.420
EIF4ENIF1	MCRIP1	psi-mi:“MI:0915”(physical association)	0.400
MCRIP1	DNMT1	psi-mi:“MI:0915”(physical association)	0.370
	MCRIP1	psi-mi:“MI:0914”(association)	0.350
E4	MCRIP1	psi-mi:“MI:0914”(association)	0.350
PPP1R16B	MCRIP1	psi-mi:“MI:0914”(association)	0.350
PTPRH	MCRIP1	psi-mi:“MI:0914”(association)	0.350
ECH1	MCRIP1	psi-mi:“MI:0914”(association)	0.350
P2RY6	ESYT2	psi-mi:“MI:0914”(association)	0.350
TNFRSF10A	NAP1L4	psi-mi:“MI:0914”(association)	0.350
P2RY6		psi-mi:“MI:0914”(association)	0.350
ARHGAP27	MCRIP1	psi-mi:“MI:0914”(association)	0.350
YWHAQ	MCRIP1	psi-mi:“MI:0914”(association)	0.350
MAPT	SHTN1	psi-mi:“MI:0914”(association)	0.350
CEP135	MCRIP1	psi-mi:“MI:0914”(association)	0.350

BioGRID (83): FAM195B (Affinity Capture-MS), FAM195B (Affinity Capture-MS), FAM195B (Affinity Capture-MS), FAM195B (Affinity Capture-MS), FAM195B (Affinity Capture-MS), FAM195B (Proximity Label-MS), FAM195B (Affinity Capture-MS), FAM195B (Affinity Capture-MS), FAM195B (Affinity Capture-MS), FAM195B (Affinity Capture-MS), FAM195B (Proximity Label-MS), FAM195B (Proximity Label-MS), FAM195B (Proximity Label-MS), FAM195B (Proximity Label-MS), FAM195B (Proximity Label-MS)

ESM2 similar proteins: A0A7P0TBJ1, A4IG66, A8E4M4, A8E4X8, A9JSQ8, B0BN72, C9JLW8, O75182, P97578, Q02225, Q0P4B9, Q0P5A7, Q13541, Q1JPG0, Q3MHI4, Q3UGS4, Q3ULM0, Q4QQM5, Q4V8E4, Q504E7, Q5BLE2, Q5DTY9, Q5U465, Q5XJS0, Q5ZIU1, Q5ZKK0, Q60876, Q62141, Q62622, Q63068, Q68DU8, Q6GR21, Q6IEG0, Q6PCG6, Q6TYB5, Q7L4E1, Q7Z3D4, Q8AVJ1, Q8BK03, Q8C6E0

Diamond homologs: A8E4M4, A9JSQ8, B0BN72, C9JLW8, Q0II70, Q0P4B9, Q3UGS4, Q5ZIU1, Q9BUT9, Q9CQB2

SIGNOR signaling

7 interactions.

A	Effect	B	Mechanism
MAPK3	“down-regulates activity”	MCRIP1	phosphorylation
MAPK1	“down-regulates activity”	MCRIP1	phosphorylation
MCRIP1	“down-regulates activity”	CTBP1	binding
Gbeta	“down-regulates activity”	MCRIP1	phosphorylation
ERK1/2	“down-regulates activity”	MCRIP1	phosphorylation

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	2
Likely benign	1
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1021 predictions. Top by Δscore:

Variant	Effect	Δscore
17:81823255:T:TA	donor_gain	1.0000
17:81823312:C:CC	acceptor_gain	1.0000
17:81823316:C:CT	acceptor_gain	1.0000
17:81823410:A:AC	donor_gain	1.0000
17:81823411:C:CT	donor_gain	1.0000
17:81823411:CT:C	donor_gain	1.0000
17:81823411:CTCTT:C	donor_gain	1.0000
17:81823514:C:CC	acceptor_gain	1.0000
17:81824283:CCAC:C	donor_loss	1.0000
17:81824284:CACC:C	donor_loss	1.0000
17:81824285:ACCTT:A	donor_loss	1.0000
17:81823217:T:TA	donor_gain	0.9900
17:81823307:GAAGG:G	acceptor_gain	0.9900
17:81823309:AGG:A	acceptor_gain	0.9900
17:81823310:GG:G	acceptor_gain	0.9900
17:81823311:GC:G	acceptor_loss	0.9900
17:81823312:C:A	acceptor_loss	0.9900
17:81823313:T:G	acceptor_loss	0.9900
17:81823316:C:T	acceptor_gain	0.9900
17:81823317:A:T	acceptor_gain	0.9900
17:81823407:CT:C	donor_loss	0.9900
17:81823408:TCACT:T	donor_loss	0.9900
17:81823409:CACT:C	donor_loss	0.9900
17:81823410:A:C	donor_loss	0.9900
17:81823410:ACT:A	donor_gain	0.9900
17:81823411:CTC:C	donor_gain	0.9900
17:81823447:TCCTC:T	donor_gain	0.9900
17:81823448:CCTCC:C	donor_gain	0.9900
17:81823509:CCAGG:C	acceptor_gain	0.9900
17:81823510:CAGG:C	acceptor_gain	0.9900

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000001219 (17:81831512 G>A), RS1000269938 (17:81829120 G>A), RS1000404663 (17:81825216 G>A,C), RS1000434018 (17:81825395 C>T), RS1000452669 (17:81834405 G>A,T), RS1000772179 (17:81824584 C>T), RS1000978140 (17:81829733 T>C), RS1001062430 (17:81825173 G>A), RS1001304174 (17:81829448 C>T), RS1001673175 (17:81825979 G>A), RS1001836629 (17:81828518 G>A), RS1001975523 (17:81828197 G>A,T), RS1002083981 (17:81833378 C>G,T), RS1002189621 (17:81823173 A>G), RS1002229909 (17:81824814 G>A,T)

Disease associations

OMIM: gene MIM:616514 | 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

29 total (human), top 29 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	increases expression, decreases expression	2
Cadmium Chloride	increases abundance, increases expression	2
aristolochic acid I	decreases expression	1
FR900359	decreases phosphorylation	1
triphenyl phosphate	affects expression	1
bisphenol A	increases expression	1
perfluorooctanoic acid	decreases expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
perfluoro-n-nonanoic acid	decreases expression	1
perfluorohexanesulfonic acid	decreases expression	1
ICG 001	affects expression	1
abrine	decreases expression	1
jinfukang	increases expression	1
(+)-JQ1 compound	increases expression	1
MT19c compound	decreases expression	1
4-(4-((5-(4,5-dimethyl-2-nitrophenyl)-2-furanyl)methylene)-4,5-dihydro-3-methyl-5-oxo-1H-pyrazol-1-yl)benzoic acid	decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Acetaminophen	increases expression	1
Benzo(a)pyrene	affects methylation	1
Cadmium	increases abundance, increases expression	1
Doxorubicin	increases expression	1
Ivermectin	decreases expression	1
Plant Extracts	affects cotreatment, decreases expression	1
Smoke	decreases expression	1
Thiram	increases expression	1
Tunicamycin	decreases expression	1
Valproic Acid	decreases expression, increases methylation	1
Thapsigargin	decreases expression	1

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_SM94	HAP1 FAM195B (-) 1	Cancer cell line	Male
CVCL_SM95	HAP1 FAM195B (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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