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MSH2

mutS homolog 2, the group of MutS homologs

Basic information

Region (hg38): 2:47403066-47663146

Previous symbols: [ "COCA1" ]

Links

ENSG00000095002 ∙ NCBI:4436 ∙ OMIM:609309 ∙ HGNC:7325 ∙ Uniprot:P43246 ∙ AlphaFold ∙ GenCC ∙ jax ∙ Sfari ∙ GnomAD ∙ Pubmed ∙ ClinVar

Phenotypes

GenCC

Source: genCC

  • rhabdomyosarcoma (Moderate), mode of inheritance: AR
  • Lynch syndrome 1 (Strong), mode of inheritance: AD
  • ovarian cancer (Strong), mode of inheritance: AD
  • malignant pancreatic neoplasm (Moderate), mode of inheritance: AD
  • Muir-Torre syndrome (Strong), mode of inheritance: AD
  • Muir-Torre syndrome (Supportive), mode of inheritance: AD
  • Lynch syndrome (Supportive), mode of inheritance: AD
  • mismatch repair cancer syndrome 1 (Supportive), mode of inheritance: AR
  • mismatch repair cancer syndrome 2 (Strong), mode of inheritance: AR
  • prostate cancer (Moderate), mode of inheritance: AD
  • breast cancer (Disputed Evidence), mode of inheritance: AD
  • Lynch syndrome 1 (Definitive), mode of inheritance: AD
  • mismatch repair cancer syndrome 1 (Definitive), mode of inheritance: AR
  • Muir-Torre syndrome (Definitive), mode of inheritance: AD
  • Lynch syndrome 1 (Strong), mode of inheritance: AD
  • Lynch syndrome (Definitive), mode of inheritance: AD
  • mismatch repair cancer syndrome 1 (Definitive), mode of inheritance: AR
  • hereditary breast carcinoma (Refuted Evidence), mode of inheritance: AD

Clinical Genomic Database

Source: CGD

ConditionInheritanceIntervention CategoriesIntervention/Rationale Manifestation CategoriesReferences
Colorectal cancer, hereditary nonpolyposis, type 1 (Lynch syndrome 1); Endometrial cancer; Mismatch repair cancer syndrome 2; Muir-Torre syndromeAD/AROncologicIn HNPCC, For surveillance, colonoscopy with polyp removal is indicated starting at (whichever is earlier) age 20-25 years or 10 years prior to the earliest familial diagnosis; Prophylactic Hysterectomy with bilateral oophorectomy may be considered after childbearing is completed; For individuals with colon cancer, surgical treatment with full colectomy (and ileorectal anastomosis) is recommended; Cigarette smoking should be avoided; For other tumor types (individuals may be at risk for a number of cancer types), awareness of cancer risk may allow early diagnosis and treatment, which may reduce morbidity and mortality; Individuals with Mismatch repair cancer syndrome are at risk of multiple types of malignancy, and awareness may allow early detection and managementDermatologic; Oncologic6020987; 5684233; 4016686; 2029018; 8484121; 8252616; 8261515; 8484120; 8072530; 8931714; 9218993; 9593786; 9634524; 9843200; 10534628; 10190329; 10196371; 11600610; 11112663; 11809679; 12549480; 12650804; 14574010; 14994245; 15520370; 14871915; 15235030; 15872208; 15662714; 15937084; 16807412; 16372347; 16511680; 17539897; 17327285; 19419416; 20093870; 20301390; 20591884; 23612316; 23729658; 23891921; 23990280; 24434690
Homozygous/compound heterozygous variants have been described in individuals with severe disease; Variants in PMS1 thought to be associated with hereditary colon cancer were found to co-segregate in individuals with MSH2 variants; Variants may also contribute to cancer susceptibility, and individuals may be at risk for a number of cancer types

ClinVar

This is a list of variants' phenotypes submitted to ClinVar and linked to the MSH2 gene.

  • Hereditary cancer-predisposing syndrome (4232 variants)
  • Hereditary nonpolyposis colorectal neoplasms (3934 variants)
  • Lynch syndrome 1 (1509 variants)
  • not provided (1272 variants)
  • not specified (703 variants)
  • Lynch syndrome (703 variants)
  • Breast and/or ovarian cancer (94 variants)
  • Carcinoma of colon (82 variants)
  • Hereditary nonpolyposis colon cancer (81 variants)
  • Malignant tumor of breast (57 variants)
  • MSH2-related condition (39 variants)
  • Lynch-like syndrome (28 variants)
  • Lynch syndrome 1;Muir-Torré syndrome;Mismatch repair cancer syndrome 2 (18 variants)
  • Endometrial carcinoma (17 variants)
  • Breast carcinoma (16 variants)
  • Hereditary breast ovarian cancer syndrome (16 variants)
  • Gastric cancer (12 variants)
  • Inborn genetic diseases (12 variants)
  • Mismatch repair cancer syndrome 1;Muir-Torré syndrome;Lynch syndrome 1 (11 variants)
  • Lynch syndrome 1;Mismatch repair cancer syndrome 1;Muir-Torré syndrome (10 variants)
  • Mismatch repair cancer syndrome 1 (10 variants)
  • Colorectal cancer, non-polyposis (10 variants)
  • Ovarian cancer (9 variants)
  • Muir-Torré syndrome (9 variants)
  • Mismatch repair cancer syndrome 2 (5 variants)
  • Lynch syndrome 1;Mismatch repair cancer syndrome 2;Muir-Torré syndrome (5 variants)
  • Mismatch repair cancer syndrome 2;Lynch syndrome 1;Muir-Torré syndrome (4 variants)
  • Neoplasm of ovary (4 variants)
  • Muir-Torré syndrome;Lynch syndrome 1;Mismatch repair cancer syndrome 2 (4 variants)
  • Hereditary cancer (3 variants)
  • Muir-Torré syndrome;Mismatch repair cancer syndrome 2;Lynch syndrome 1 (3 variants)
  • Lynch syndrome;Mismatch repair cancer syndrome 2 (3 variants)
  • Muir-Torré syndrome;Lynch syndrome 1;Mismatch repair cancer syndrome 1 (3 variants)
  • MSH2-Related disorders (2 variants)
  • Lynch syndrome 1;Mismatch repair cancer syndrome 1 (2 variants)
  • Uterine corpus cancer (2 variants)
  • - (2 variants)
  • Colorectal cancer (2 variants)
  • Colon cancer (2 variants)
  • Familial cancer of breast (1 variants)
  • Polyp of colon (1 variants)
  • Hereditary nonpolyposis colorectal carcinoma (1 variants)
  • See cases (1 variants)
  • Ovarian cyst (1 variants)
  • MSH2-related disorder (1 variants)
  • Mismatch repair cancer syndrome 1;Lynch syndrome 1 (1 variants)
  • Muir-Torré syndrome;Lynch syndrome 1 (1 variants)
  • Bile duct cancer (1 variants)
  • Breast-ovarian cancer, familial, susceptibility to, 1 (1 variants)
  • Familial colorectal cancer (1 variants)
  • Rectal neoplasm (1 variants)
  • Papillary renal cell carcinoma type 1 (1 variants)
  • Glioblastoma (1 variants)
  • Rhabdomyosarcoma (1 variants)
  • Malignant tumor of ascending colon (1 variants)
  • Muir-Torré syndrome;Lynch syndrome (1 variants)
  • Hepatoblastoma (1 variants)
  • MSH2 POLYMORPHISM (1 variants)
  • Sarcoma (1 variants)
  • Mismatch repair cancer syndrome 2;Muir-Torré syndrome;Lynch syndrome 1 (1 variants)
  • Familial colorectal cancer;Lynch syndrome (1 variants)
  • Malignant tumor of breast;Ataxia-telangiectasia syndrome (1 variants)
  • Colonic diverticula (1 variants)
  • Sigmoid colon cancer (1 variants)
  • Mismatch repair cancer syndrome 2;Lynch syndrome (1 variants)
  • Ependymoma (1 variants)

Variants pathogenicity by type

Statistics on ClinVar variants can assist in determining whether a specific variant type in the MSH2 gene is commonly pathogenic or not.

In the table, we include only reliable ClinVar variants with their consequences to MANE Select, Mane Plus Clinical transcripts, or transcripts with TSL equals 1. Click the count to view the source variants.

Warning: slight differences between displayed counts and the number of variants in ClinVar may occur, primarily due to (1) the application of a different transcript and/or consequence by our variant effect predictor or (2) differences in clinical significance: we classify Benign/Likely benign variants as Likely benign and Pathogenic/Likely pathogenic variants as Likely pathogenic.

Variant type Pathogenic Likely pathogenic VUS Likely benign Benign Sum
synonymous
21
clinvar
775
clinvar
6
clinvar
 802
missense
41
clinvar
89
clinvar
1629
clinvar
195
clinvar
23
clinvar
 1977
nonsense
318
clinvar
26
clinvar
11
clinvar
1
clinvar
 356
start loss
1
clinvar
2
clinvar
7
clinvar
 10
frameshift
1033
clinvar
66
clinvar
13
clinvar
 1112
inframe indel
5
clinvar
5
clinvar
69
clinvar
1
clinvar
 80
splice donor/acceptor (+/-2bp)
50
clinvar
164
clinvar
6
clinvar
 220
splice region
?
    Intron variants in splice region, excluding donor/acceptor (+/-2bp)
5
6
109
97
5
 222
non coding
?
    UTR, intron and other, non coding variants
3
clinvar
6
clinvar
95
clinvar
437
clinvar
105
clinvar
 646
Total 1451 358 1851 1407 136

Highest pathogenic variant AF is 0.000697

Variants in MSH2

This is a list of pathogenic ClinVar variants found in the MSH2 region.

You can filter this list by clicking the number of variants in the Variants pathogenicity by type table.

Position Type Phenotype Significance ClinVar
2-47403071-T-A Hereditary cancer-predisposing syndrome Uncertain significance (Apr 22, 2019)1752835
2-47403074-T-C Lynch syndrome • Hereditary cancer-predisposing syndrome • not specified • Lynch syndrome 1 • Hereditary nonpolyposis colorectal neoplasms Benign (Sep 05, 2013)90485
2-47403074-T-G Hereditary cancer-predisposing syndrome Uncertain significance (Sep 19, 2018)1744639
2-47403074-TTG-CTT Hereditary cancer-predisposing syndrome Uncertain significance (Aug 07, 2019)1741970
2-47403076-G-T Hereditary cancer-predisposing syndrome • Lynch syndrome 1 Conflicting classifications of pathogenicity (Sep 10, 2021)142876
2-47403078-G-A Hereditary cancer-predisposing syndrome Uncertain significance (Nov 24, 2017)186689
2-47403080-G-A Hereditary cancer-predisposing syndrome Uncertain significance (Oct 26, 2018)234153
2-47403082-G-A Hereditary cancer-predisposing syndrome Uncertain significance (Apr 20, 2016)1794821
2-47403083-G-A Hereditary cancer-predisposing syndrome Uncertain significance (Jul 27, 2018)1791832
2-47403085-C-A Hereditary cancer-predisposing syndrome • not specified Conflicting classifications of pathogenicity (Nov 19, 2021)142695
2-47403085-C-T Hereditary cancer-predisposing syndrome Uncertain significance (Dec 15, 2019)1786012
2-47403086-G-A Hereditary cancer-predisposing syndrome Uncertain significance (Apr 30, 2019)1783064
2-47403086-G-C Hereditary cancer-predisposing syndrome • not specified Uncertain significance (Feb 11, 2020)186353
2-47403088-C-A Hereditary cancer-predisposing syndrome Uncertain significance (Sep 06, 2018)1776556
2-47403088-C-T Hereditary cancer-predisposing syndrome Uncertain significance (Apr 08, 2019)1776647
2-47403089-G-A Hereditary cancer-predisposing syndrome Uncertain significance (May 22, 2019)1773756
2-47403089-G-T Hereditary cancer-predisposing syndrome Uncertain significance (Jan 14, 2019)1773802
2-47403090-T-A Hereditary cancer-predisposing syndrome Uncertain significance (May 31, 2018)1770889
2-47403090-T-C Hereditary cancer-predisposing syndrome Conflicting classifications of pathogenicity (Oct 23, 2019)184385
2-47403091-G-C Hereditary cancer-predisposing syndrome Uncertain significance (Jan 27, 2015)230360
2-47403092-G-A Hereditary cancer-predisposing syndrome Uncertain significance (Mar 23, 2020)232695
2-47403092-G-C Hereditary cancer-predisposing syndrome Uncertain significance (Feb 22, 2019)1797968
2-47403092-G-T Hereditary cancer-predisposing syndrome Uncertain significance (Jul 03, 2017)1798331
2-47403093-C-G Hereditary cancer-predisposing syndrome Uncertain significance (Dec 04, 2015)1768882
2-47403094-C-A Hereditary cancer-predisposing syndrome Uncertain significance (Jan 07, 2020)1768541

GnomAD

Source: gnomAD

GeneTypeBio TypeTranscript Coding Exons Length
MSH2protein_codingprotein_codingENST00000233146 16159343
pLI Probability
LOF Intolerant 		pRec Probability
LOF Recessive 		Individuals with
no LOFs 		Individuals with
Homozygous LOFs 		Individuals with
Heterozygous LOFs 		Defined p
0.8950.1051257180301257480.000119
Z-Score Observed Expected Observed/Expected Mutation Rate Total Possible in Transcript
Missense-2.456344831.310.00002326133
Missense in Polyphen188177.961.05642257
Synonymous-1.832021721.180.000008471733
Loss of Function5.13947.00.1920.00000249579

LoF frequencies by population

EthnicitySum of pLOFs p
African & African-American0.00006130.0000613
Ashkenazi Jewish0.000.00
East Asian0.0001140.000109
Finnish0.000.00
European (Non-Finnish)0.0001320.000132
Middle Eastern0.0001140.000109
South Asian0.0004010.000359
Other0.000.00

dbNSFP

Source: dbNSFP

Function
FUNCTION: Component of the post-replicative DNA mismatch repair system (MMR). Forms two different heterodimers: MutS alpha (MSH2- MSH6 heterodimer) and MutS beta (MSH2-MSH3 heterodimer) which binds to DNA mismatches thereby initiating DNA repair. When bound, heterodimers bend the DNA helix and shields approximately 20 base pairs. MutS alpha recognizes single base mismatches and dinucleotide insertion-deletion loops (IDL) in the DNA. MutS beta recognizes larger insertion-deletion loops up to 13 nucleotides long. After mismatch binding, MutS alpha or beta forms a ternary complex with the MutL alpha heterodimer, which is thought to be responsible for directing the downstream MMR events, including strand discrimination, excision, and resynthesis. Recruits DNA helicase MCM9 to chromatin which unwinds the mismatch containg DNA strand (PubMed:26300262). ATP binding and hydrolysis play a pivotal role in mismatch repair functions. The ATPase activity associated with MutS alpha regulates binding similar to a molecular switch: mismatched DNA provokes ADP-->ATP exchange, resulting in a discernible conformational transition that converts MutS alpha into a sliding clamp capable of hydrolysis-independent diffusion along the DNA backbone. This transition is crucial for mismatch repair. MutS alpha may also play a role in DNA homologous recombination repair. In melanocytes may modulate both UV-B- induced cell cycle regulation and apoptosis. {ECO:0000269|PubMed:10078208, ECO:0000269|PubMed:10660545, ECO:0000269|PubMed:15064730, ECO:0000269|PubMed:17611581, ECO:0000269|PubMed:21120944, ECO:0000269|PubMed:26300262, ECO:0000269|PubMed:9564049, ECO:0000269|PubMed:9822679, ECO:0000269|PubMed:9822680}.;
Disease
DISEASE: Hereditary non-polyposis colorectal cancer 1 (HNPCC1) [MIM:120435]: An autosomal dominant disease associated with marked increase in cancer susceptibility. It is characterized by a familial predisposition to early-onset colorectal carcinoma (CRC) and extra-colonic tumors of the gastrointestinal, urological and female reproductive tracts. HNPCC is reported to be the most common form of inherited colorectal cancer in the Western world. Clinically, HNPCC is often divided into two subgroups. Type I is characterized by hereditary predisposition to colorectal cancer, a young age of onset, and carcinoma observed in the proximal colon. Type II is characterized by increased risk for cancers in certain tissues such as the uterus, ovary, breast, stomach, small intestine, skin, and larynx in addition to the colon. Diagnosis of classical HNPCC is based on the Amsterdam criteria: 3 or more relatives affected by colorectal cancer, one a first degree relative of the other two; 2 or more generation affected; 1 or more colorectal cancers presenting before 50 years of age; exclusion of hereditary polyposis syndromes. The term 'suspected HNPCC' or 'incomplete HNPCC' can be used to describe families who do not or only partially fulfill the Amsterdam criteria, but in whom a genetic basis for colon cancer is strongly suspected. {ECO:0000269|PubMed:10375096, ECO:0000269|PubMed:10386556, ECO:0000269|PubMed:10528862, ECO:0000269|PubMed:10573010, ECO:0000269|PubMed:10612836, ECO:0000269|PubMed:10777691, ECO:0000269|PubMed:10829038, ECO:0000269|PubMed:11726306, ECO:0000269|PubMed:11870161, ECO:0000269|PubMed:11920458, ECO:0000269|PubMed:12112654, ECO:0000269|PubMed:12124176, ECO:0000269|PubMed:12132870, ECO:0000269|PubMed:12200596, ECO:0000269|PubMed:12362047, ECO:0000269|PubMed:12373605, ECO:0000269|PubMed:12655564, ECO:0000269|PubMed:12655568, ECO:0000269|PubMed:12658575, ECO:0000269|PubMed:14635101, ECO:0000269|PubMed:15046096, ECO:0000269|PubMed:15300854, ECO:0000269|PubMed:15342696, ECO:0000269|PubMed:15365995, ECO:0000269|PubMed:15613555, ECO:0000269|PubMed:15870828, ECO:0000269|PubMed:15896463, ECO:0000269|PubMed:15991316, ECO:0000269|PubMed:15996210, ECO:0000269|PubMed:16451135, ECO:0000269|PubMed:17101317, ECO:0000269|PubMed:17128465, ECO:0000269|PubMed:18561205, ECO:0000269|PubMed:18625694, ECO:0000269|PubMed:18781619, ECO:0000269|PubMed:18822302, ECO:0000269|PubMed:18951462, ECO:0000269|PubMed:21120944, ECO:0000269|PubMed:22102614, ECO:0000269|PubMed:22371642, ECO:0000269|PubMed:7874129, ECO:0000269|PubMed:8261515, ECO:0000269|PubMed:8700523, ECO:0000269|PubMed:8797773, ECO:0000269|PubMed:8872463, ECO:0000269|PubMed:9048925, ECO:0000269|PubMed:9240418, ECO:0000269|PubMed:9298827, ECO:0000269|PubMed:9311737, ECO:0000269|PubMed:9419403, ECO:0000269|PubMed:9559627, ECO:0000269|PubMed:9621522, ECO:0000269|PubMed:9718327, ECO:0000269|PubMed:9889267}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Muir-Torre syndrome (MRTES) [MIM:158320]: Rare autosomal dominant disorder characterized by sebaceous neoplasms and visceral malignancy. {ECO:0000269|PubMed:7713503}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Endometrial cancer (ENDMC) [MIM:608089]: A malignancy of endometrium, the mucous lining of the uterus. Most endometrial cancers are adenocarcinomas, cancers that begin in cells that make and release mucus and other fluids. {ECO:0000305|PubMed:11306449, ECO:0000305|PubMed:21642682}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.; DISEASE: Mismatch repair cancer syndrome (MMRCS) [MIM:276300]: An autosomal recessive, rare, childhood cancer predisposition syndrome encompassing a broad tumor spectrum. This includes hematological malignancies, central nervous system tumors, Lynch syndrome-associated malignancies such as colorectal tumors as well as multiple intestinal polyps, embryonic tumors and rhabdomyosarcoma. Multiple cafe-au-lait macules, a feature reminiscent of neurofibromatosis type 1, are often found as first manifestation of the underlying cancer. Areas of skin hypopigmentation have also been reported in MMRCS patients. {ECO:0000269|PubMed:12549480, ECO:0000269|PubMed:16372347}. Note=The disease is caused by mutations affecting the gene represented in this entry.; DISEASE: Colorectal cancer (CRC) [MIM:114500]: A complex disease characterized by malignant lesions arising from the inner wall of the large intestine (the colon) and the rectum. Genetic alterations are often associated with progression from premalignant lesion (adenoma) to invasive adenocarcinoma. Risk factors for cancer of the colon and rectum include colon polyps, long-standing ulcerative colitis, and genetic family history. {ECO:0000269|PubMed:12792735, ECO:0000269|PubMed:14504054, ECO:0000269|PubMed:15996210, ECO:0000269|PubMed:9559627}. Note=Disease susceptibility may be associated with variations affecting the gene represented in this entry.;
Pathway
Doxorubicin Pathway (Cancer Cell), Pharmacodynamics;Mismatch repair - Homo sapiens (human);Pathways in cancer - Homo sapiens (human);Busulfan Pathway, Pharmacodynamics;Colorectal cancer - Homo sapiens (human);Rac1-Pak1-p38-MMP-2 pathway;TP53 Regulates Transcription of DNA Repair Genes;Chromosomal and microsatellite instability in colorectal cancer;Mismatch repair;Mismatch repair (MMR) directed by MSH2:MSH3 (MutSbeta);Mismatch Repair;DNA Repair;Gene expression (Transcription);Generic Transcription Pathway;RNA Polymerase II Transcription;TP53 Regulates Transcription of DNA Repair Genes;Transcriptional Regulation by TP53;Direct p53 effectors;Mismatch repair (MMR) directed by MSH2:MSH6 (MutSalpha) (Consensus)

Recessive Scores

pRec
0.693

Intolerance Scores

loftool
0.00971
rvis_EVS
-2.03
rvis_percentile_EVS
1.68

Haploinsufficiency Scores

pHI
0.997
hipred
Y
hipred_score
0.746
ghis
0.703

Essentials

essential_gene_CRISPR
N
essential_gene_CRISPR2
N
essential_gene_gene_trap
N
gene_indispensability_pred
E
gene_indispensability_score
0.989

Gene Damage Prediction

AllRecessiveDominant
MendelianMediumMediumMedium
Primary ImmunodeficiencyMediumMediumMedium
CancerMediumMediumMedium

Mouse Genome Informatics

Gene name
Msh2
Phenotype
mortality/aging (the observable characteristics related to the ability of a mammalian organism to live and age that are manifested throughout development and life span); hematopoietic system phenotype; neoplasm; nervous system phenotype (the observable morphological and physiological characteristics of the extensive, intricate network of electochemical structures in the body that is comprised of the brain, spinal cord, nerves, ganglia and parts of the receptor organs that are manifested through development and lifespan); digestive/alimentary phenotype; immune system phenotype; integument phenotype (the observable morphological and physiological characteristics of the skin and its associated structures, such as the hair, nails, sweat glands, sebaceous glands and other secretory glands that are manifested through development and lifespan); cellular phenotype; homeostasis/metabolism phenotype;

Zebrafish Information Network

Gene name
msh2
Affected structure
whole organism
Phenotype tag
abnormal
Phenotype quality
neoplastic

Gene ontology

Biological process
in utero embryonic development;oxidative phosphorylation;DNA repair;mismatch repair;postreplication repair;double-strand break repair;cell cycle arrest;germ cell development;determination of adult lifespan;male gonad development;response to X-ray;response to UV-B;somatic hypermutation of immunoglobulin genes;somatic recombination of immunoglobulin gene segments;B cell mediated immunity;B cell differentiation;intra-S DNA damage checkpoint;intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator;negative regulation of neuron apoptotic process;maintenance of DNA repeat elements;isotype switching;negative regulation of DNA recombination;positive regulation of isotype switching to IgA isotypes;positive regulation of isotype switching to IgG isotypes;positive regulation of helicase activity;protein localization to chromatin
Cellular component
nuclear chromosome, telomeric region;nucleus;nucleoplasm;membrane;mismatch repair complex;MutSalpha complex;MutSbeta complex
Molecular function
magnesium ion binding;four-way junction DNA binding;DNA binding;chromatin binding;damaged DNA binding;double-stranded DNA binding;single-stranded DNA binding;protein binding;ATP binding;protein C-terminus binding;DNA-dependent ATPase activity;ATPase activity;centromeric DNA binding;enzyme binding;protein kinase binding;mismatched DNA binding;guanine/thymine mispair binding;dinucleotide insertion or deletion binding;single guanine insertion binding;single thymine insertion binding;dinucleotide repeat insertion binding;oxidized purine DNA binding;MutLalpha complex binding;protein homodimerization activity;ADP binding