ERBIN (erbb2 interacting protein)

Gene

• Entrez ID: 55914
• Gene name: Erbb2 interacting protein
• Gene symbol: ERBIN
• Synonyms (NCBI Gene): ERBB2IP, HEL-S-78, LAP2
• Chromosome: 5
• Chromosome location: 5q12.3
• Summary: This gene is a member of the leucine-rich repeat and PDZ domain (LAP) family. The encoded protein contains 17 leucine-rich repeats and one PDZ domain. It binds to the unphosphorylated form of the ERBB2 protein and regulates ERBB2 function and localization

miRNA

miRTarBase ID	miRNA	Experiments	Reference
MIRT703885	hsa-miR-183-5p	HITS-CLIP	23313552
MIRT703883	hsa-miR-6819-3p	HITS-CLIP	23313552
MIRT703882	hsa-miR-6877-3p	HITS-CLIP	23313552
MIRT703881	hsa-miR-6740-3p	HITS-CLIP	23313552
MIRT703880	hsa-miR-6843-3p	HITS-CLIP	23313552
MIRT703879	hsa-miR-6848-3p	HITS-CLIP	23313552
MIRT703878	hsa-miR-7159-3p	HITS-CLIP	23313552
MIRT573115	hsa-miR-4662a-3p	PAR-CLIP	20371350
MIRT573113	hsa-miR-1183	PAR-CLIP	20371350
MIRT573114	hsa-miR-5197-3p	PAR-CLIP	20371350
MIRT573112	hsa-miR-873-3p	PAR-CLIP	20371350
MIRT573111	hsa-miR-7154-5p	PAR-CLIP	20371350
MIRT573110	hsa-miR-433-3p	PAR-CLIP	20371350
MIRT573109	hsa-miR-3672	PAR-CLIP	20371350
MIRT573108	hsa-miR-6864-3p	PAR-CLIP	20371350
MIRT573107	hsa-miR-3977	PAR-CLIP	20371350
MIRT096901	hsa-miR-454-3p	PAR-CLIP	22012620
MIRT096904	hsa-miR-4295	PAR-CLIP	22012620
MIRT096902	hsa-miR-301b-3p	PAR-CLIP	22012620
MIRT096905	hsa-miR-3666	PAR-CLIP	22012620
MIRT096896	hsa-miR-301a-3p	PAR-CLIP	22012620
MIRT096894	hsa-miR-130a-3p	PAR-CLIP	22012620
MIRT096897	hsa-miR-130b-3p	PAR-CLIP	22012620
MIRT096893	hsa-miR-16-2-3p	PAR-CLIP	22012620
MIRT096895	hsa-miR-195-3p	PAR-CLIP	22012620
MIRT537663	hsa-miR-4635	PAR-CLIP	22012620
MIRT537662	hsa-miR-130a-5p	PAR-CLIP	22012620
MIRT537661	hsa-miR-23a-3p	PAR-CLIP	22012620
MIRT537660	hsa-miR-23b-3p	PAR-CLIP	22012620
MIRT537659	hsa-miR-23c	PAR-CLIP	22012620
MIRT537658	hsa-miR-488-3p	PAR-CLIP	22012620
MIRT096908	hsa-miR-8081	PAR-CLIP	22012620

Gene ontology (GO)

GO ID	Ontology	Definition	Evidence	Reference
GO:0005102	Function	Signaling receptor binding	IPI	16203728
GO:0005176	Function	ErbB-2 class receptor binding	TAS	11375975
GO:0005200	Function	Structural constituent of cytoskeleton	NAS	11375975
GO:0005515	Function	Protein binding	IPI	11375975, 12047349, 16203728, 16714539, 24550280, 30833792
GO:0005604	Component	Basement membrane	TAS	10878805
GO:0005634	Component	Nucleus	IDA	11375975
GO:0005634	Component	Nucleus	IEA
GO:0005737	Component	Cytoplasm	IDA	11375975
GO:0005886	Component	Plasma membrane	IDA
GO:0005886	Component	Plasma membrane	IEA
GO:0005886	Component	Plasma membrane	TAS
GO:0006605	Process	Protein targeting	IEA
GO:0007155	Process	Cell adhesion	NAS	11375975
GO:0007165	Process	Signal transduction	TAS	10878805
GO:0007173	Process	Epidermal growth factor receptor signaling pathway	TAS	11375975
GO:0007229	Process	Integrin-mediated signaling pathway	NAS	11375975
GO:0009925	Component	Basal plasma membrane	NAS	11375975
GO:0010468	Process	Regulation of gene expression	IEA
GO:0016020	Component	Membrane	IEA
GO:0016323	Component	Basolateral plasma membrane	IDA	16203728
GO:0016323	Component	Basolateral plasma membrane	IEA
GO:0016607	Component	Nuclear speck	IDA
GO:0030054	Component	Cell junction	IDA
GO:0030054	Component	Cell junction	IEA
GO:0030056	Component	Hemidesmosome	IDA	11375975
GO:0030056	Component	Hemidesmosome	IEA
GO:0031594	Component	Neuromuscular junction	IEA
GO:0031965	Component	Nuclear membrane	IEA
GO:0032088	Process	Negative regulation of NF-kappaB transcription factor activity	IMP	16203728
GO:0032495	Process	Response to muramyl dipeptide	IMP	16203728
GO:0032496	Process	Response to lipopolysaccharide	IMP	16203728
GO:0035556	Process	Intracellular signal transduction	IBA
GO:0045104	Process	Intermediate filament cytoskeleton organization	NAS	11375975
GO:0045175	Process	Basal protein localization	NAS	11375975
GO:0045197	Process	Establishment or maintenance of epithelial cell apical/basal polarity	NAS	11375975
GO:0070161	Component	Anchoring junction	IEA
GO:0070433	Process	Negative regulation of nucleotide-binding oligomerization domain containing 2 signaling pathway	IBA
GO:0070433	Process	Negative regulation of nucleotide-binding oligomerization domain containing 2 signaling pathway	IEA
GO:0070433	Process	Negative regulation of nucleotide-binding oligomerization domain containing 2 signaling pathway	IMP	16203728
GO:0071356	Process	Cellular response to tumor necrosis factor	IMP	16203728
GO:0071638	Process	Negative regulation of monocyte chemotactic protein-1 production	IEA
GO:0098794	Component	Postsynapse	IEA
GO:0098978	Component	Glutamatergic synapse	IEA
GO:0099072	Process	Regulation of postsynaptic membrane neurotransmitter receptor levels	IEA
GO:0099572	Component	Postsynaptic specialization	IEA

Other IDs

• MIM: 606944
• HGNC: 15842
• e!Ensembl: ENSG00000112851

Protein

• UniProt ID: Q96RT1
• Protein name: Erbin (Densin-180-like protein) (Erbb2-interacting protein) (Protein LAP2)
• Protein function: Acts as an adapter for the receptor ERBB2, in epithelia. By binding the unphosphorylated 'Tyr-1248' of receptor ERBB2, it may contribute to stabilize this unphosphorylated state (PubMed:16203728). Inhibits NOD2-dependent NF-kappa-B signaling and
• PDB: 1MFG, 1MFL, 1N7T, 2H3L, 2QBW, 3CH8, 6Q0M, 6Q0N, 6Q0U, 6UBH, 7LUL
• Family and domains:

  Pfam

  Accession	ID	Position in sequence	Description	Type
  PF13855	LRR_8	46 → 104	Leucine rich repeat	Repeat
  PF13855	LRR_8	345 → 402	Leucine rich repeat	Repeat
  PF00595	PDZ	1321 → 1407	PDZ domain	Domain

• Tissue specificity: TISSUE SPECIFICITY: Highly expressed in brain, heart, kidney, muscle and stomach, followed by liver, spleen and intestine. {ECO:0000269|PubMed:10878805}.
• Sequence:

  MTTKRSLFVRLVPCRCLRGEEETVTTLDYSHCSLEQVPKEIFTFEKTLEELYLDANQIEE
  LPKQLFNCQSLHKLSLPDNDLTTLPASIANLINLRELDVSKNGIQEFPENIKNCKVLTIV
  EASVNPISKLPDGFSQLLNLTQLYLNDAFLEFLPANFGRLTKLQILELRENQLKMLPKTM
  NRLTQLERLDLGSNEFTEVPEVLEQLSGLKEFWMDANRLTFIPGFIGSLKQLTYLDVSKN
  NIEMVEEGISTCENLQDLLLSSNSLQQLPETIGSLKNITTLKIDENQLMYLPDSIGGLIS
  VEELDCSFNEVEALPSSIGQLTNLRTFAADHNYLQQLPPEIGSWKNITVLFLHSNKLETL
  PEEMGDMQKLKVINLSDNRLKNLPFSFTKLQQLTAMWLSDNQSKPLIPLQKETDSETQKM
  VLTNYMFPQQPRTEDVMFISDNESFNPSLWEEQRKQRAQVAFECDEDKDEREAPPREGNL
  KRYPTPYPDELKNMVKTVQTIVHRLKDEETNEDSGRDLKPHEDQQDINKDVGVKTSESTT
  TVKSKVDEREKYMIGNSVQKISEPEAEISPGSLPVTANMKASENLKHIVNHDDVFEESEE
  LSSDEEMKMAEMRPPLIETSINQPKVVALSNNKKDDTKETDSLSDEVTHNSNQNNSNCSS
  PSRMSDSVSLNTDSSQDTSLCSPVKQTHIDINSKIRQEDENFNSLLQNGDILNSSTEEKF
  KAHDKKDFNLPEYDLNVEERLVLIEKSVDSTATADDTHKLDHINMNLNKLITNDTFQPEI
  MERSKTQDIVLGTSFLSINSKEETEHLENGNKYPNLESVNKVNGHSEETSQSPNRTEPHD
  SDCSVDLGISKSTEDLSPQKSGPVGSVVKSHSITNMEIGGLKIYDILSDNGPQQPSTTVK
  ITSAVDGKNIVRSKSATLLYDQPLQVFTGSSSSSDLISGTKAIFKFDSNHNPEEPNIIRG
  PTSGPQSAPQIYGPPQYNIQYSSSAAVKDTLWHSKQNPQIDHASFPPQLLPRSESTENQS
  YAKHSANMNFSNHNNVRANTAYHLHQRLGPARHGEMWAISPNDRLIPAVTRSTIQRQSSV
  SSTASVNLGDPGSTRRAQIPEGDYLSYREFHSAGRTPPMMPGSQRPLSARTYSIDGPNAS
  RPQSARPSINEIPERTMSVSDFNYSRTSPSKRPNARVGSEHSLLDPPGKSKVPRDWREQV
  LRHIEAKKLEKKHPQTSSSGDPCQDGIFISGQQNYSSATLSHKDVPPDSLMKMPLSNGQM
  GQPLRPQANYSQIHHPPQASVARHPSREQLIDYLMLKVAHQPPYTQPHCSPRQGHELAKQ
  EIRVRVEKDPELGFSISGGVGGRGNPFRPDDDGIFVTRVQPEGPASKLLQPGDKIIQANG
  YSFINIEHGQAVSLLKTFQNTVELIIVREVSS

• Sequence length: 1412

Pathways

KEGG:

NOD-like receptor signaling pathway

Reactome:

Signaling by ERBB2
Downregulation of ERBB2 signaling
Constitutive Signaling by Overexpressed ERBB2
Drug-mediated inhibition of ERBB2 signaling
Signaling by ERBB2 KD Mutants
Resistance of ERBB2 KD mutants to trastuzumab
Resistance of ERBB2 KD mutants to sapitinib
Resistance of ERBB2 KD mutants to tesevatinib
Resistance of ERBB2 KD mutants to neratinib
Resistance of ERBB2 KD mutants to osimertinib
Resistance of ERBB2 KD mutants to afatinib
Resistance of ERBB2 KD mutants to AEE788
Resistance of ERBB2 KD mutants to lapatinib
Signaling by ERBB2 ECD mutants
Signaling by ERBB2 TMD/JMD mutants
Drug resistance in ERBB2 TMD/JMD mutants

Associated diseases

Evidence Score:

• ★☆☆☆☆  Gene-disease association found in Text Mining only
• ★★☆☆☆  Found in Text Mining and Unknown/Other Associations
• ★★★☆☆  Reported in Unknown/Other Associations across ≥2 Sources
• ★★★★☆  ClinVar: Pathogenic/Likely Pathogenic (<5 Variants)
• ★★★★★  ClinVar: Pathogenic/Likely Pathogenic (≥5 Variants)

Unknown / Other Associations
Phenotype Name	Clinical Significance	Source	Evidence Score
Acute myeloid leukemia	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Amelia cleft lip palate hydrocephalus iris coloboma	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
AUTOSOMAL DOMINANT COMBINED IMMUNODEFICIENCY DUE TO ERBIN DEFICIENCY	—	ClinGen, Disgenet, GWAS catalog, Orphanet ClinGen, Disgenet, GWAS catalog, Orphanet ClinGen, Disgenet, GWAS catalog, Orphanet	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
CARCINOMA, ADENOID CYSTIC	—	CTD	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Cervical cancer	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Colon adenocarcinoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
ERBIN-related disorder	Uncertain significance; Conflicting classifications of pathogenicity; Likely benign; Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Gastric cancer	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Hepatocellular carcinoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Lung cancer	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Malignant tumor of esophagus	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Malignant tumor of urinary bladder	Likely benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
NON-SMALL CELL LUNG CARCINOMA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Nonpapillary renal cell carcinoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Prostate cancer	Uncertain significance	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Sarcoma	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SCOLIOSIS	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SQUAMOUS CELL CARCINOMA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
SQUAMOUS CELL LUNG CARCINOMA	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Thyroid cancer, nonmedullary, 1	Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
Uterine corpus endometrial carcinoma	Uncertain significance; Benign	ClinVar	★★☆☆☆ Found in Text Mining + Unknown/Other Associations
UTERINE FIBROID	—	GWAS catalog	★★☆☆☆ Found in Text Mining + Unknown/Other Associations

Associations from Text Mining
Disease Name	Disease (Merged)	Source	PMID	Relationship Type	Evidence Score
Adenoid Cystic Carcinoma	Adenocarcinoma	CTD_human_DG	23685749		★☆☆☆☆ Found in Text Mining only
Barrett Esophagus	Barrett esophagus	Pubtator	35437997	Associate	★☆☆☆☆ Found in Text Mining only
Bile duct carcinoma	Bile duct carcinoma	BEFREE	22745766		★☆☆☆☆ Found in Text Mining only
Blister	Blister	Pubtator	16185268	Associate	★☆☆☆☆ Found in Text Mining only
Carcinoma Hepatocellular	Hepatocellular carcinoma	Pubtator	39778021	Associate	★☆☆☆☆ Found in Text Mining only
Carcinoma Squamous Cell	Squamous cell carcinoma	Pubtator	26908436	Associate	★☆☆☆☆ Found in Text Mining only
Cardiomyopathies	Cardiomyopathy	BEFREE	29912636		★☆☆☆☆ Found in Text Mining only
Cardiomyopathy, Dilated	Cardiomyopathy	BEFREE	16247757		★☆☆☆☆ Found in Text Mining only
Cardiomyopathy, Familial Idiopathic	Cardiomyopathy	BEFREE	16247757		★☆☆☆☆ Found in Text Mining only
Cholangiocarcinoma	Cholangiocarcinoma	BEFREE	24812403		★☆☆☆☆ Found in Text Mining only
Cholangiocarcinoma	Cholangiocarcinoma	Pubtator	24812403	Associate	★☆☆☆☆ Found in Text Mining only
Colonic Neoplasms	Colonic neoplasm	Pubtator	17164780	Associate	★☆☆☆☆ Found in Text Mining only
Congestive heart failure	Congestive Heart Failure	BEFREE	24711380, 26025865		★☆☆☆☆ Found in Text Mining only
Eosinophilic Esophagitis	Eosinophilia	Pubtator	35437997	Stimulate	★☆☆☆☆ Found in Text Mining only
Epidermolysis Bullosa	Epidermolysis Bullosa	BEFREE	16185268		★☆☆☆☆ Found in Text Mining only
Epidermolysis Bullosa	Epidermolysis bullosa	Pubtator	16185268	Associate	★☆☆☆☆ Found in Text Mining only
Epidermolysis Bullosa Dystrophica	Epidermolysis Bullosa	BEFREE	16185268		★☆☆☆☆ Found in Text Mining only
Esophageal carcinoma	Esophageal Carcinoma	BEFREE	24589738		★☆☆☆☆ Found in Text Mining only
Esophageal Neoplasms	Esophagus Neoplasm	BEFREE	24589738		★☆☆☆☆ Found in Text Mining only
Familial dilated cardiomyopathy	Cardiomyopathy	BEFREE	16247757		★☆☆☆☆ Found in Text Mining only
Heart failure	Heart Failure	BEFREE	24711380, 26025865		★☆☆☆☆ Found in Text Mining only
Leukemia Myeloid Acute	Myeloid leukemia	Pubtator	30799283	Associate	★☆☆☆☆ Found in Text Mining only
Liver carcinoma	Liver carcinoma	BEFREE	30103114, 30551364		★☆☆☆☆ Found in Text Mining only
Malignant neoplasm of esophagus	Esophagus Neoplasm	BEFREE	24589738		★☆☆☆☆ Found in Text Mining only
Malignant Neoplasms	Malignant Neoplasm	BEFREE	22745766, 24812403		★☆☆☆☆ Found in Text Mining only
Medullary carcinoma	Megalencephaly, Polymicrogyria, Polydactyly, Hydrocephalus Syndrome	BEFREE	26254781		★☆☆☆☆ Found in Text Mining only
Neoplasms	Neoplasms	BEFREE	12825852		★☆☆☆☆ Found in Text Mining only
Neuropathy	Neuropathy	BEFREE	15927533		★☆☆☆☆ Found in Text Mining only
Non-alcoholic Fatty Liver Disease	Non-Alcoholic Fatty Liver Disease	BEFREE	28902428		★☆☆☆☆ Found in Text Mining only
Prostatic Neoplasms	Prostatic neoplasm	Pubtator	25472581	Associate	★☆☆☆☆ Found in Text Mining only
Squamous cell carcinoma of skin	Skin carcinoma	BEFREE	26908436		★☆☆☆☆ Found in Text Mining only